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Numrering	Referens	Omslagsbild	Hitta
1.	Arndt, D. S., et al. (författare) STATE OF THE CLIMATE IN 2017 2018 Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310 Forskningsöversikt (refereegranskat)
2.	Arndt, D. S., et al. (författare) State of the Climate in 2016 2017 Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280 Tidskriftsartikel (refereegranskat)abstract In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
3.	Blunden, Jessica, et al. (författare) State of the Climate in 2012 2013 Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258 Tidskriftsartikel (refereegranskat)abstract For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
4.	Pfeffer, W. Tad, et al. (författare) The Randolph Glacier Inventory : a globally complete inventory of glaciers 2014 Ingår i: Journal of Glaciology. - 0022-1430 .- 1727-5652. ; 60:221, s. 537-552 Tidskriftsartikel (refereegranskat)abstract The Randolph Glacier Inventory (RGI) is a globally complete collection of digital outlines of glaciers, excluding the ice sheets, developed to meet the needs of the Fifth Assessment of the Intergovernmental Panel on Climate Change for estimates of past and future mass balance. The RGI was created with limited resources in a short period. Priority was given to completeness of coverage, but a limited, uniform set of attributes is attached to each of the similar to 198 000 glaciers in its latest version, 3.2. Satellite imagery from 1999-2010 provided most of the outlines. Their total extent is estimated as 726 800 +/- 34 000 km(2). The uncertainty, about +/- 5%, is derived from careful single-glacier and basin-scale uncertainty estimates and comparisons with inventories that were not sources for the RGI. The main contributors to uncertainty are probably misinterpretation of seasonal snow cover and debris cover. These errors appear not to be normally distributed, and quantifying them reliably is an unsolved problem. Combined with digital elevation models, the RGI glacier outlines yield hypsometries that can be combined with atmospheric data or model outputs for analysis of the impacts of climatic change on glaciers. The RGI has already proved its value in the generation of significantly improved aggregate estimates of glacier mass changes and total volume, and thus actual and potential contributions to sea-level rise.
5.	Zamora, Juan Carlos, et al. (författare) Considerations and consequences of allowing DNA sequence data as types of fungal taxa 2018 Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185 Tidskriftsartikel (refereegranskat)abstract Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
6.	Aaron-Morrison, Arlene P., et al. (författare) State of the climate in 2014 2015 Ingår i: Bulletin of the American Meteorological Society. - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 96 Tidskriftsartikel (refereegranskat)abstract Most of the dozens of essential climate variables monitored each year in this report continued to follow their long-term trends in 2014, with several setting new records. Carbon dioxide, methane, and nitrous oxide-the major greenhouse gases released into Earth's atmosphere-once again all reached record high average atmospheric concentrations for the year. Carbon dioxide increased by 1.9 ppm to reach a globally averaged value of 397.2 ppm for 2014. Altogether, 5 major and 15 minor greenhouse gases contributed 2.94 W m-2 of direct radiative forcing, which is 36% greater than their contributions just a quarter century ago. Accompanying the record-high greenhouse gas concentrations was nominally the highest annual global surface temperature in at least 135 years of modern record keeping, according to four independent observational analyses. The warmth was distributed widely around the globe's land areas, Europe observed its warmest year on record by a large margin, with close to two dozen countries breaking their previous national temperature records; many countries in Asia had annual temperatures among their 10 warmest on record; Africa reported above-average temperatures across most of the continent throughout 2014; Australia saw its third warmest year on record, following record heat there in 2013; Mexico had its warmest year on record; and Argentina and Uruguay each had their second warmest year on record. Eastern North America was the only major region to observe a below-average annual temperature. But it was the oceans that drove the record global surface temperature in 2014. Although 2014 was largely ENSO-neutral, the globally averaged sea surface temperature (SST) was the highest on record. The warmth was particularly notable in the North Pacific Ocean where SST anomalies signaled a transition from a negative to positive phase of the Pacific decadal oscillation. In the winter of 2013/14, unusually warm water in the northeast Pacific was associated with elevated ocean heat content anomalies and elevated sea level in the region. Globally, upper ocean heat content was record high for the year, reflecting the continued increase of thermal energy in the oceans, which absorb over 90% of Earth's excess heat from greenhouse gas forcing. Owing to both ocean warming and land ice melt contributions, global mean sea level in 2014 was also record high and 67 mm greater than the 1993 annual mean, when satellite altimetry measurements began. Sea surface salinity trends over the past decade indicate that salty regions grew saltier while fresh regions became fresher, suggestive of an increased hydrological cycle over the ocean expected with global warming. As in previous years, these patterns are reflected in 2014 subsurface salinity anomalies as well. With a now decade-long trans-basin instrument array along 26°N, the Atlantic meridional overturning circulation shows a decrease in transport of-4.2 ± 2.5 Sv decade-1. Precipitation was quite variable across the globe. On balance, precipitation over the world's oceans was above average, while below average across land surfaces. Drought continued in southeastern Brazil and the western United States. Heavy rain during April-June led to devastating floods in Canada's Eastern Prairies. Above-normal summer monsoon rainfall was observed over the southern coast of West Africa, while drier conditions prevailed over the eastern Sahel. Generally, summer monsoon rainfall over eastern Africa was above normal, except in parts of western South Sudan and Ethiopia. The south Asian summer monsoon in India was below normal, with June record dry. Across the major tropical cyclone basins, 91 named storms were observed during 2014, above the 1981-2010 global average of 82. The Eastern/Central Pacific and South Indian Ocean basins experienced significantly above-normal activity in 2014; all other basins were either at or below normal. The 22 named storms in the Eastern/Central Pacific was the basin's most since 1992. Similar to 2013, the North Atlantic season was quieter than most years of the last two decades with respect to the number of storms, despite the absence of El Niño conditions during both years. In higher latitudes and at higher elevations, increased warming continued to be visible in the decline of glacier mass balance, increasing permafrost temperatures, and a deeper thawing layer in seasonally frozen soil. In the Arctic, the 2014 temperature over land areas was the fourth highest in the 115-year period of record and snow melt occurred 20-30 days earlier than the 1998-2010 average. The Greenland Ice Sheet experienced extensive melting in summer 2014. The extent of melting was above the 1981-2010 average for 90% of the melt season, contributing to the second lowest average summer albedo over Greenland since observations began in 2000 and a record-low albedo across the ice sheet for August. On the North Slope of Alaska, new record high temperatures at 20-m depth were measured at four of five permafrost observatories. In September, Arctic minimum sea ice extent was the sixth lowest since satellite records began in 1979. The eight lowest sea ice extents during this period have occurred in the last eight years. Conversely, in the Antarctic, sea ice extent countered its declining trend and set several new records in 2014, including record high monthly mean sea ice extent each month from April to November. On 20 September, a record large daily Antarctic sea ice extent of 20.14 × 106 km2 occurred. The 2014 Antarctic stratospheric ozone hole was 20.9 million km2 when averaged from 7 September to 13 October, the sixth smallest on record and continuing a decrease, albeit statistically insignificant, in area since 1998.
7.	Leta, Tesfaye H., et al. (författare) Periprosthetic Joint Infection After Total Knee Arthroplasty With or Without Antibiotic Bone Cement 2024 Ingår i: JAMA Network Open. - 2574-3805. ; 7:5, s. 2412898-2412898 Tidskriftsartikel (refereegranskat)abstract Importance: Despite increased use of antibiotic-loaded bone cement (ALBC) in joint arthroplasty over recent decades, current evidence for prophylactic use of ALBC to reduce risk of periprosthetic joint infection (PJI) is insufficient. Objective: To compare the rate of revision attributed to PJI following primary total knee arthroplasty (TKA) using ALBC vs plain bone cement. Design, Setting, and Participants: This international cohort study used data from 14 national or regional joint arthroplasty registries in Australia, Denmark, Finland, Germany, Italy, New Zealand, Norway, Romania, Sweden, Switzerland, the Netherlands, the UK, and the US. The study included primary TKAs for osteoarthritis registered from January 1, 2010, to December 31, 2020, and followed-up until December 31, 2021. Data analysis was performed from April to September 2023. Exposure: Primary TKA with ALBC vs plain bone cement. Main Outcomes and Measures: The primary outcome was risk of 1-year revision for PJI. Using a distributed data network analysis method, data were harmonized, and a cumulative revision rate was calculated (1 - Kaplan-Meier), and Cox regression analyses were performed within the 10 registries using both cement types. A meta-analysis was then performed to combine all aggregated data and evaluate the risk of 1-year revision for PJI and all causes. Results: Among 2 168 924 TKAs included, 93% were performed with ALBC. Most TKAs were performed in female patients (59.5%) and patients aged 65 to 74 years (39.9%), fully cemented (92.2%), and in the 2015 to 2020 period (62.5%). All participating registries reported a cumulative 1-year revision rate for PJI of less than 1% following primary TKA with ALBC (range, 0.21%-0.80%) and with plain bone cement (range, 0.23%-0.70%). The meta-analyses based on adjusted Cox regression for 1 917 190 TKAs showed no statistically significant difference at 1 year in risk of revision for PJI (hazard rate ratio, 1.16; 95% CI, 0.89-1.52) or for all causes (hazard rate ratio, 1.12; 95% CI, 0.89-1.40) among TKAs performed with ALBC vs plain bone cement. Conclusions and Relevance: In this study, the risk of revision for PJI was similar between ALBC and plain bone cement following primary TKA. Any additional costs of ALBC and its relative value in reducing revision risk should be considered in the context of the overall health care delivery system.
8.	Leta, Tesfaye H., et al. (författare) The use of antibiotic-loaded bone cement and systemic antibiotic prophylactic use in 2,971,357 primary total knee arthroplasties from 2010 to 2020: an international register-based observational study among countries in Africa, Europe, North America, and Oceania 2023 Ingår i: Acta Orthopaedica. - 1745-3674 .- 1745-3682. ; 94, s. 416-425 Tidskriftsartikel (refereegranskat)abstract Background and purpose — Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA). Patients and methods — This observational study is based on 2,971,357 primary TKAs reported in 2010–2020 to national/regional joint arthroplasty registries in Australia, Den-mark, Finland, Germany, Italy, the Netherlands, New Zealand, Norway, Romania, South Africa, Sweden, Switzerland, the UK, and the USA. Aggregate-level data on trends and types of bone cement, antibiotic agents, and doses and duration of SAP used was extracted from participating registries. Results — ALBC was used in 77% of the TKAs with variation ranging from 100% in Norway to 31% in the USA. Palacos R+G was the most common (62%) ALBC type used. The primary antibiotic used in ALBC was gentamicin (94%). Use of ALBC in combination with SAP was common practice (77%). Cefazolin was the most common (32%) SAP agent. The doses and duration of SAP used varied from one single preoperative dosage as standard practice in Bolzano, Italy (98%) to 1-day 4 doses in Norway (83% of the 40,709 TKAs reported to the Norwegian arthroplasty register). Conclusion — The proportion of ALBC usage in primary TKA varies internationally, with gentamicin being the most common antibiotic. ALBC in combination with SAP was common practice, with cefazolin the most common SAP agent. The type of ALBC and type, dose, and duration of SAP varied among participating countries.
9.	Albertsen, Elena, et al. (författare) Using ecological context to interpret spatiotemporal variation in natural selection 2021 Ingår i: Evolution. - : Wiley. - 0014-3820 .- 1558-5646. ; 75:2, s. 294-309 Tidskriftsartikel (refereegranskat)abstract Spatiotemporal variation in natural selection is expected, but difficult to estimate. Pollinator-mediated selection on floral traits provides a good system for understanding and linking variation in selection to differences in ecological context. We studied pollinator-mediated selection in five populations of Dalechampia scandens (Euphorbiaceae) in Costa Rica and Mexico. Using a nonlinear path-analytical approach, we assessed several functional components of selection, and linked variation in pollinator-mediated selection across time and space to variation in pollinator assemblages. After correcting for estimation error, we detected moderate variation in net selection on two out of four blossom traits. Both the opportunity for selection and the mean strength of selection decreased with increasing reliability of cross-pollination. Selection for pollinator attraction was consistently positive and stronger on advertisement than reward traits. Selection on traits affecting pollen transfer from the pollinator to the stigmas was strong only when cross-pollination was unreliable and there was a mismatch between pollinator and blossom size. These results illustrate how consideration of trait function and ecological context can facilitate both the detection and the causal understanding of spatiotemporal variation in natural selection.
10.	Ericsson, Madelene, et al. (författare) High-intensity exercise training in mice with cardiomyocyte-specific disruption of Serca2 2010 Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 108:5, s. 1311-1320 Tidskriftsartikel (refereegranskat)abstract Several lines of evidence indicate that the sarco(endo)plasmic reticulum ATPase type 2 (SERCA2) is essential for maintaining myocardial calcium handling and cardiac pump function. Hence, a reduction in SERCA2 abundance is expected to reduce work performance and maximal oxygen uptake (VO2max) and to limit the response to exercise training. To test this hypothesis, we compared VO2max and exercise capacity in mice with cardiac disruption of Serca2 (SERCA2 KO) with control mice (SERCA2 FF). We also determined whether the effects on VO2max and exercise capacity could be modified by high-intensity aerobic exercise training. Treadmill running at 85-90% of VO2max started 2 wk after Serca2 gene disruption and continued for 4 wk. VO2max and maximal running speed were measured weekly in a metabolic chamber. Cardiac function was assessed by echocardiography during light anesthesia. In sedentary SERCA2 KO mice, the aerobic capacity was reduced by 50% and running speed by 28%, whereas trained SERCA2 KO mice were able to maintain maximal running speed despite a 36% decrease in VO2max. In SERCA2 FF mice, both VO2max and maximal running speed increased by training, while no changes occurred in the sedentary group. Left ventricle dimensions remained unchanged by training in both genotypes. In contrast, training induced right ventricle hypertrophy in SERCA2 KO mice. In conclusion, the SERCA2 protein is essential for sustaining cardiac pump function and exercise capacity. Nevertheless, SERCA2 KO mice were able to maintain maximal running speed in response to exercise training despite a large decrease in VO2max.
11.	Holstad, Agnes, et al. (författare) Evolvability predicts macroevolution under fluctuating selection 2024 Ingår i: Science (New York, N.Y.). - 1095-9203. ; 384:6696, s. 688-693 Tidskriftsartikel (refereegranskat)abstract Heritable variation is a prerequisite for evolutionary change, but the relevance of genetic constraints on macroevolutionary timescales is debated. By using two datasets on fossil and contemporary taxa, we show that evolutionary divergence among populations, and to a lesser extent among species, increases with microevolutionary evolvability. We evaluate and reject several hypotheses to explain this relationship and propose that an effect of evolvability on population and species divergence can be explained by the influence of genetic constraints on the ability of populations to track rapid, stationary environmental fluctuations.
12.	Jung, Christian, et al. (författare) A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention 2019 Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148 Tidskriftsartikel (refereegranskat)abstract Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
13.	Menkveld, Albert J., et al. (författare) Nonstandard Errors 2024 Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390 Tidskriftsartikel (refereegranskat)abstract In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
14.	Myhre, Peder L, et al. (författare) Performance of a Novel Research-Use-Only Secretoneurin ELISA in Patients with Suspected Acute Coronary Syndrome : Comparison with an Established Secretoneurin Radioimmunoassay 2021 Ingår i: Cardiology. - : S. Karger. - 0008-6312 .- 1421-9751. ; 146:5, s. 566-574 Tidskriftsartikel (refereegranskat)abstract Background: Circulating secretoneurin (SN) concentrations, as measured by established radioimmunoassay (RIA), risk stratify patients with cardiovascular disease. We now report data for a recently developed research-use-only SN enzyme-linked immunosorbent assay (ELISA) in patients with suspected acute coronary syndrome (ACS).Methods: SN ELISA was developed according to industry standards and tested in 401 unselected chest pain patients. Blood samples were drawn <24 h from admission, and we adjudicated all hospitalizations as ACS or non-ACS. The mean follow-up was 6.2 years.Results: SN ELISA with 2 monoclonal sheep anti-SN antibodies has a measuring range of 10–250 pmol/L and demonstrates excellent analytical precision and accuracy across the range of SN concentrations. SN measured by ELISA and RIA correlated in the chest pain patients: rho = 0.39, p < 0.001. SN concentrations were higher in ACS patients (n = 161 [40%]) than in non-ACS patients (n = 240) for both assays, with an area under the curve (AUC) of 0.66 (95% CI: 0.61–0.71) for ELISA and 0.59 (0.54–0.65) for RIA. SN concentrations were also higher in nonsurvivors (n = 65 [16%]) than survivors, with an AUC of 0.72 (0.65–0.79) for ELISA versus 0.64 (0.56–0.72) for RIA, p = 0.007, for difference between assays. Adjusting for age, sex, blood pressure, previous myocardial infarction, atrial fibrillation, and heart failure in multivariable analysis, SN concentrations as measured by ELISA, but not RIA, remained associated with mortality, with a hazard ratio of 1.71 (1.03–2.84), p = 0.038.Conclusions: The novel SN ELISA has excellent performance, higher AUC for diagnosis, and superior prognostic accuracy compared to the established RIA in chest pain patients.
15.	Nagel, Gabriele, et al. (författare) Air pollution and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts for Air Pollution Effects (ESCAPE) 2018 Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 143:7, s. 1632-1643 Tidskriftsartikel (refereegranskat)abstract Air pollution has been classified as carcinogenic to humans. However, to date little is known about the relevance for cancersof the stomach and upper aerodigestive tract (UADT). We investigated the association of long-term exposure to ambient airpollution with incidence of gastric and UADT cancer in 11 European cohorts. Air pollution exposure was assigned by land-useregression models for particulate matter (PM) below 10mm (PM10), below 2.5mm (PM2.5), between 2.5 and 10mm (PMcoarse),PM2.5absorbance and nitrogen oxides (NO2and NOX) as well as approximated by traffic indicators. Cox regression modelswith adjustment for potential confounders were used for cohort-specific analyses. Combined estimates were determined withrandom effects meta-analyses. During average follow-up of 14.1 years of 305,551 individuals, 744 incident cases of gastriccancer and 933 of UADT cancer occurred. The hazard ratio for an increase of 5mg/m3of PM2.5was 1.38 (95% CI 0.99; 1.92)for gastric and 1.05 (95% CI 0.62; 1.77) for UADT cancers. No associations were found for any of the other exposures consid-ered. Adjustment for additional confounders and restriction to study participants with stable addresses did not influencemarkedly the effect estimate for PM2.5and gastric cancer. Higher estimated risks of gastric cancer associated with PM2.5wasfound in men (HR 1.98 [1.30; 3.01]) as compared to women (HR 0.85 [0.5; 1.45]). This large multicentre cohort study showsan association between long-term exposure to PM2.5and gastric cancer, but not UADT cancers, suggesting that air pollutionmay contribute to gastric cancer risk.
16.	Oddsson, Asmundur, et al. (författare) Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality 2023 Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
17.	Opedal, Øystein H., et al. (författare) Evolvability and trait function predict phenotypic divergence of plant populations 2023 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 120:1 Tidskriftsartikel (refereegranskat)abstract Understanding the causes and limits of population divergence in phenotypic traits is a fundamental aim of evolutionary biology, with the potential to yield predictions of adaptation to environmental change. Reciprocal transplant experiments and the evaluation of optimality models suggest that local adaptation is common but not universal, and some studies suggest that trait divergence is highly constrained by genetic variances and covariances of complex phenotypes. We analyze a large database of population divergence in plants and evaluate whether evolutionary divergence scales positively with standing genetic variation within populations (evolvability), as expected if genetic constraints are evolutionarily important. We further evaluate differences in divergence and evolvability- divergence relationships between reproductive and vegetative traits and between selfing, mixed-mating, and outcrossing species, as these factors are expected to influence both patterns of selection and evolutionary potentials. Evolutionary divergence scaled positively with evolvability. Furthermore, trait divergence was greater for vegetative traits than for floral (reproductive) traits, but largely independent of the mating system. Jointly, these factors explained -40% of the variance in evolutionary divergence. The consistency of the evolvability-divergence relationships across diverse species suggests substantial predictability of trait divergence. The results are also consistent with genetic constraints playing a role in evolutionary divergence.
18.	Otero, Jaime, et al. (författare) Basin-scale phenology and effects of climate variability on global timing of initial seaward migration of Atlantic salmon (Salmo salar) 2014 Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 20:1, s. 61-75 Tidskriftsartikel (refereegranskat)abstract Migrations between different habitats are key events in the lives of many organisms. Such movements involve annually recurring travel over long distances usually triggered by seasonal changes in the environment. Often, the migration is associated with travel to or from reproduction areas to regions of growth. Young anadromous Atlantic salmon (Salmo salar) emigrate from freshwater nursery areas during spring and early summer to feed and grow in the North Atlantic Ocean. The transition from the freshwater ('parr') stage to the migratory stage where they descend streams and enter salt water ('smolt') is characterized by morphological, physiological and behavioural changes where the timing of this parr-smolt transition is cued by photoperiod and water temperature. Environmental conditions in the freshwater habitat control the downstream migration and contribute to within- and among-river variation in migratory timing. Moreover, the timing of the freshwater emigration has likely evolved to meet environmental conditions in the ocean as these affect growth and survival of the post-smolts. Using generalized additive mixed-effects modelling, we analysed spatio-temporal variations in the dates of downstream smolt migration in 67 rivers throughout the North Atlantic during the last five decades and found that migrations were earlier in populations in the east than the west. After accounting for this spatial effect, the initiation of the downstream migration among rivers was positively associated with freshwater temperatures, up to about 10 °C and levelling off at higher values, and with sea-surface temperatures. Earlier migration occurred when river discharge levels were low but increasing. On average, the initiation of the smolt seaward migration has occurred 2.5 days earlier per decade throughout the basin of the North Atlantic. This shift in phenology matches changes in air, river, and ocean temperatures, suggesting that Atlantic salmon emigration is responding to the current global climate changes.
19.	Pedersen, Marie, et al. (författare) Is There an Association Between Ambient Air Pollution and Bladder Cancer Incidence? Analysis of 15 European Cohorts 2018 Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 4:1, s. 113-120 Tidskriftsartikel (refereegranskat)abstract Background: Ambient air pollution contains low concentrations of carcinogens implicated in the etiology of urinary bladder cancer (BC). Little is known about whether exposure to air pollution influences BC in the general population. Objective: To evaluate the association between long-term exposure to ambient air pollution and BC incidence. Design, setting and participants: We obtained data from 15 population-based cohorts enrolled between 1985 and 2005 in eight European countries (N = 303 431; mean follow-up 14.1 yr). We estimated exposure to nitrogen oxides (NO2 and NOx), particulate matter (PM) with diameter <10 mu m (PM10), <2.5 mu m (PM2.5). between 2.5 and 10 mu m (PM2.5-10). PM2.5 absorbance (soot), elemental constituents of PM, organic carbon, and traffic density at baseline home addresses using standardized land-use regression models from the European Study of Cohorts for Air Pollution Effects project. Outcome measurements and statistical analysis: We used Cox proportional-hazards models with adjustment for potential confounders for cohort-specific analyses and meta-analyses to estimate summary hazard ratios (HRS) for BC incidence. Results and limitations: During follow-up, 943 incident BC cases were diagnosed. In the meta-analysis, none of the exposures were associated with BC risk. The summary HRs associated with a 10-mu g/m(3) increase in NO2 and 51-mu g/m(3) increase in PM2.5 were 0.98 (95% confidence interval [CI] 0.89-1.08) and 0.86 (95% CI 0.63-1.18), respectively. Limitations include the lack of information about lifetime exposure. Conclusions: There was no evidence of an association between exposure to outdoor air pollution levels at place of residence and risk of BC. Patient summary: We assessed the link between outdoor air pollution at place of residence and bladder cancer using the largest study population to date and extensive assessment of exposure and comprehensive data on personal risk factors such as smoking. We found no association between the levels of outdoor air pollution at place of residence and bladder cancer risk.
20.	Pélabon, Christophe, et al. (författare) Is There More to Within-plant Variation in Seed Size than Developmental Noise? 2021 Ingår i: Evolutionary Biology. - : Springer Science and Business Media LLC. - 0071-3260 .- 1934-2845. ; 48:3, s. 366-377 Tidskriftsartikel (refereegranskat)abstract Within-plant variation in seed size may merely reflect developmental instability, or it may be adaptive in facilitating diversifying bet-hedging, that is, production of phenotypically diverse offspring when future environments are unpredictable. To test the latter hypothesis, we analyzed patterns of variation in seed size in 11 populations of the perennial vine Dalechampia scandens grown in a common greenhouse environment. We tested whether population differences in the mean and variation of seed size covaried with environmental predictability at two different timescales. We also tested whether within-plant variation in seed size was correlated with independent measures of floral developmental instability and increased under stressful conditions. Populations differed genetically in the amount of seed-size variation occurring among plants, among infructescences within plants, and among seeds within infructescences. Within-individual variation was not detectably correlated with measures of developmental instability and did not increase under stress, but it increased weakly with short-term environmental unpredictability of precipitation at the source-population site. These results support the hypothesis that greater variation in seed size is adaptive when environmental predictability is low.
21.	Stefansson, Hreinn, et al. (författare) Homozygosity for R47H in TREM2 and the Risk of Alzheimer's Disease 2024 Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 390:23, s. 2217-2219 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
22.	Swift, Imogen J, et al. (författare) A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors. 2024 Ingår i: Alzheimer's Research & Therapy. - 1758-9193. ; 16:1 Tidskriftsartikel (refereegranskat)abstract Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations.Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data.We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p=0.007) with a trend in non-carriers (p=0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers.These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
23.	Van Steenbergen, Liza N, et al. (författare) Total hip arthroplasties in the Dutch Arthroplasty Register (LROI) and the Nordic Arthroplasty Register Association (NARA): comparison of patient and procedure characteristics in 475,685 cases. 2021 Ingår i: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 92:1, s. 15-22 Tidskriftsartikel (refereegranskat)abstract Background and purpose - Collaborations between arthroplasty registries are important in order to create the possibility of detecting inferior implants early and improve our understanding of differences between nations in terms of indications and outcomes. In this registry study we compared patient and procedure characteristics, and revision rates in the Nordic Arthroplasty Register Association (NARA) database and the Dutch Arthroplasty Register (LROI). Patients and methods - All total hip arthroplasties (THAs) performed in 2010-2016 were included from the LROI (n = 184,862) and the NARA database (n = 290,823), which contains data from Denmark, Norway, Sweden, and Finland. Descriptive statistics and Kaplan-Meier survival analyses based on all reasons for revision and stratified by fixation were performed and compared between countries. Results - In the Netherlands, the proportion of patients aged < 55 years (9%) and male patients (34%) was lower than in Nordic countries (< 55 years 11-13%; males 35-43%); the proportion of osteoarthritis (OA) (87%) was higher compared with Sweden (81%), Norway (77%), and Denmark (81%) but comparable to Finland (86%). Uncemented fixation was used in 62% of patients in the Netherlands, in 70% of patients in Denmark and Finland, and in 28% and 19% in Norway and Sweden, respectively. The 5-year revision rate for THAs for OA was lower in Sweden (2.3%, 95% CI 2.1-2.5) than in the Netherlands (3.0%, CI 2.9-3.1), Norway (3.8%, CI 3.6-4.0), Denmark (4.6%, CI 4.4-4.8), and Finland (4.4%, CI 4.3-4.5). Revision rates in Denmark, Norway, and Finland were higher for all fixation groups. Interpretation - Patient and THA procedure characteristics as well as revision rates evinced some differences between the Netherlands and the Nordic countries. The Netherlands compared best with Denmark in terms of patient and procedure characteristics, but resembled Sweden more in terms of short-term revision risk. Combining data from registries like LROI and the NARA collaboration is feasible and might possibly enable tracking of potential outlier implants.
24.	Aasebø, Kristine, et al. (författare) Prognostic role of tumour-infiltrating lymphocytes and macrophages in relation to MSI, CDX2 and BRAF status : a population-based study of metastatic colorectal cancer patients 2022 Ingår i: British Journal of Cancer. - : Springer. - 0007-0920 .- 1532-1827. ; 126:1, s. 48-56 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Tumour-infiltrating CD3, CD8 lymphocytes and CD68 macrophages are associated with favourable prognosis in localised colorectal cancer, but the effect in metastatic colorectal cancer (mCRC) is not established.METHODS: A Scandinavian population-based cohort of non-resectable mCRC patients was studied. Tissue microarrays (n = 460) were stained with CD3, CD8 and CD68 using fluorescence-based multiplex immunohistochemistry. Associations with clinicopathological variables, overall survival (OS) and progression-free survival were estimated.RESULTS: Two-thirds of microsatellite instable (MSI) and one-fourth of microsatellite stable (MSS) tumours displayed the highest quartile density of CD8. For CD3 high vs low cases, median OS was 20 vs 16 months (HR: 0.76, 95% CI: 0.59, 0.76, p = 0.025) with 3-year OS of 27 vs 13%. For CD68 high vs low cases, median OS was 23 vs 15 months (HR: 0.69, 95% CI: 0.54, 0.88, p = 0.003) with 3-year OS of 28 vs 12%. MSI, BRAF mutation and CDX2 loss were negative prognostic markers independent of tumour immune infiltration.CONCLUSIONS: In mCRC, high lymphocyte infiltration was found in proportions of MSI and MSS tumours-potential subgroups of immunotherapy response. Tumour-infiltrating CD3 lymphocytes and CD68 macrophages were associated with median and long-term survival. MSI was a significant negative prognostic marker despite high immunogenicity.
25.	Ahn, Jung-Min, et al. (författare) Prognostic value of comprehensive intracoronary physiology assessment early after heart transplantation. 2021 Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 42:48, s. 4918-4929 Tidskriftsartikel (refereegranskat)abstract We evaluated the long-term prognostic value of invasively assessing coronary physiology after heart transplantation in a large multicentre registry.Comprehensive intracoronary physiology assessment measuring fractional flow reserve (FFR), the index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) was performed in 254 patients at baseline (a median of 7.2weeks) and in 240 patients at 1year after transplantation (199 patients had both baseline and 1-year measurement). Patients were classified into those with normal physiology, reduced FFR (FFR≤0.80), and microvascular dysfunction (either IMR≥25 or CFR≤2.0 with FFR>0.80). The primary outcome was the composite of death or re-transplantation at 10years. At baseline, 5.5% had reduced FFR; 36.6% had microvascular dysfunction. Baseline reduced FFR [adjusted hazard ratio (aHR) 2.33, 95% confidence interval (CI) 0.88-6.15; P=0.088] and microvascular dysfunction (aHR 0.88, 95% CI 0.44-1.79; P=0.73) were not predictors of death and re-transplantation at 10years. At 1year, 5.0% had reduced FFR; 23.8% had microvascular dysfunction. One-year reduced FFR (aHR 2.98, 95% CI 1.13-7.87; P=0.028) and microvascular dysfunction (aHR 2.33, 95% CI 1.19-4.59; P=0.015) were associated with significantly increased risk of death or re-transplantation at 10years. Invasive measures of coronary physiology improved the prognostic performance of clinical variables (χ2 improvement: 7.41, P=0.006). However, intravascular ultrasound-derived changes in maximal intimal thickness were not predictive of outcomes.Abnormal coronary physiology 1year after heart transplantation was common and was a significant predictor of death or re-transplantation at 10years.
26.	Andersen, Zorana J., et al. (författare) Long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in 15 European cohorts within the ESCAPE project 2017 Ingår i: Journal of Environmental Health Perspectives. - Research triangle park : US department of health. - 0091-6765 .- 1552-9924. ; 125:10 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Epidemiological evidence on the association between ambient air pollution and breast cancer risk is inconsistent.OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in European women.METHODS: In 15 cohorts from nine European countries, individual estimates of air pollution levels at the residence were estimated by standardized land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE) and Transport related Air Pollution and Health impacts – Integrated Methodologies for Assessing Particulate Matter (TRANSPHORM) projects: particulate matter (PM) ≤2.5μm, ≤10μm, and 2.5–10μm in diameter (PM2.5, PM10, and PMcoarse, respectively); PM2.5 absorbance; nitrogen oxides (NO2 and NOx); traffic intensity; and elemental composition of PM. We estimated cohort-specific associations between breast cancer and air pollutants using Cox regression models, adjusting for major lifestyle risk factors, and pooled cohort-specific estimates using random-effects meta-analyses.RESULTS: Of 74,750 postmenopausal women included in the study, 3,612 developed breast cancer during 991,353 person-years of follow-up. We found positive and statistically insignificant associations between breast cancer and PM2.5 {hazard ratio (HR)=1.08 [95% confidence interval (CI): 0.77, 1.51] per 5 μg/m(3)}, PM10 [1.07 (95% CI: 0.89, 1.30) per 10 μg/m(3)], PMcoarse[1.20 (95% CI: 0.96, 1.49 per 5 μg/m(3)], and NO(2) [1.02 (95% CI: 0.98, 1.07 per 10 μg/m(3)], and a statistically significant association with NOx [1.04 (95% CI: 1.00, 1.08) per 20 μg/m(3), p=0.04].CONCLUSIONS: We found suggestive evidence of an association between ambient air pollution and incidence of postmenopausal breast cancer in European women.
27.	Bauer, Georg F., et al. (författare) Future directions for the concept of salutogenesis : A position article 2020 Ingår i: Health Promotion International. - : Oxford University Press. - 0957-4824 .- 1460-2245. ; 35:2, s. 187-195 Tidskriftsartikel (refereegranskat)abstract Aaron Antonovsky advanced the concept of salutogenesis almost four decades ago (Antonovsky, Health, Stress and Coping. Jossey-Bass, San Francisco, CA, 1979; Unravelling the Mystery of Health. Jossey-Bass,San Francisco, CA, 1987). Salutogenesis posits that life experiences shape the sense of coherence (SOC)VC that helps to mobilize resources to cope with stressors and manage tension successfully (determiningone's movement on the health Ease/Dis-ease continuum). Antonovsky considered the three-dimensionalSOC (i.e. comprehensibility, manageability, meaningfulness) as the key answer to his question about theorigin of health. The field of health promotion has adopted the concept of salutogenesis as reflected in theinternational Handbook of Salutogenesis (Mittelmark et al., The Handbook of Salutogenesis. Springer,New York, 2016). However, health promotion mostly builds on the more vague, general salutogenic orientation that implies the need to foster resources and capacities to promote health and wellbeing. Tostrengthen the knowledge base of salutogenesis, the Global Working Group on Salutogenesis (GWG-Sal)of the International Union of Health Promotion and Education produced the Handbook of Salutogenesis.During the creation of the handbook and the regular meetings of the GWG-Sal, the working group identified four key conceptual issues to be advanced: (i) the overall salutogenic model of health; (ii) the SOC concept; (iii) the design of salutogenic interventions and change processes in complex systems; (iv) the application of salutogenesis beyond health sector. For each of these areas, we first highlight Antonovsky'soriginal contribution and then present suggestions for future development. These ideas will help guideGWG-Sal's work to strengthen salutogenesis as a theory base for health promotion.
28.	Benoni, Henrik, et al. (författare) Relative and absolute cancer risks among Nordic kidney transplant recipients-a population-based study 2020 Ingår i: Transplant International. - : WILEY. - 0934-0874 .- 1432-2277. ; 33:12, s. 1700-1710 Tidskriftsartikel (refereegranskat)abstract Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2-3.4). The AER of any cancer was 1560 cases (95% CI: 1468-1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778-901), non-Hodgkin lymphoma (145, 95% CI: 119-174), lung cancer (126, 95% CI: 98.2-149), and kidney cancer (122, 95% CI: 98.0-149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6-8.6%) and 16.8% (95% CI: 16.0-17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance.
29.	Borg, Åsa A., et al. (författare) Interactions Among Female Guppies (Poecilia reticulata) Affect Growth and Reproduction 2012 Ingår i: Ethology. - : Wiley. - 0179-1613 .- 1439-0310. ; 118:8, s. 752-765 Tidskriftsartikel (refereegranskat)abstract Competition among females over resources may have consequences for their resource budgets and thereby the resource allocation between growth and reproduction. In addition, the consequences of femalefemale interactions may differ for dominant and subordinate individuals, with the dominant ones being at an advantage. In this study, we investigated the consequences of femalefemale competition in guppies by manipulating the competitive environment of females. We found that large guppy females dominated smaller females and that interactions between females likely are costly because females exposed to competition grew less. These females compensated by growing at a higher rate when no longer subjected to competition. The higher growth rate might in turn be the cause of the reduced reproductive effort in the more competitive treatments. Furthermore, interactions were more costly for females when they were in the subordinate role than in the dominant role, because the reduction in growth and reproductive effort was highest in females exposed to larger competitors. Whether there was a differential allocation of resources into growth and reproduction depending on dominance status needs further investigation. However, in general, smaller females had a higher growth rate than larger females, independent of competitive level. We also found a negative relationship between reproduction and growth in all treatments, indicating a cost of reproduction.
30.	Botteri, Edoardo, et al. (författare) Lifestyle changes in middle age and risk of cancer : evidence from the European Prospective Investigation into Cancer and Nutrition 2024 Ingår i: European Journal of Epidemiology. - 0393-2990. ; 39:2, s. 147-159 Tidskriftsartikel (refereegranskat)abstract In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers—including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others—using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95–0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07–1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65–0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.
31.	Brynildsen, Jon, et al. (författare) Circulating Secretoneurin Concentrations After Cardiac Surgery : Data From the FINNish Acute Kidney Injury Heart Study 2019 Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 47:5, s. E412-E419 Tidskriftsartikel (refereegranskat)abstract Objectives:Secretoneurin is associated with cardiomyocyte Ca2+ handling and improves risk prediction in patients with acute myocardial dysfunction. Whether secretoneurin improves risk assessment on top of established cardiac biomarkers and European System for Cardiac Operative Risk Evaluation II in patients undergoing cardiac surgery is not known.Design:Prospective, observational, single-center sub-study of a multicenter study.Setting:Prospective observational study of survival in patients undergoing cardiac surgery.Patients:A total of 619 patients undergoing cardiac surgery.Interventions:Patients underwent either isolated coronary artery bypass graft surgery, single noncoronary artery bypass graft surgery, two procedures, or three or more procedures. Procedures other than coronary artery bypass graft were valve surgery, surgery on thoracic aorta, and other cardiac surgery.Measurements and Main Results:We measured preoperative and postoperative secretoneurin concentrations and adjusted for European System for Cardiac Operative Risk Evaluation II, N-terminal pro-B-type natriuretic peptide, and cardiac troponin T concentrations in multivariate analyses. During 961 days of follow- up, 59 patients died (9.5%). Secretoneurin concentrations were higher among nonsurvivors compared with survivors, both before (168 pmol/L [quartile 1-3, 147-206 pmol/L] vs 160 pmol/L [131-193 pmol/L]; p = 0.039) and after cardiac surgery (173 pmol/L [129-217 pmol/L] vs 143 pmol/L [111-173 pmol/L]; p < 0.001). Secretoneurin concentrations decreased from preoperative to postoperative measurements in survivors, whereas we observed no significant decrease in secretoneurin concentrations among nonsurvivors. Secretoneurin concentrations were weakly correlated with established risk indices. Patients with the highest postoperative secretoneurin concentrations had worse outcome compared with patients with lower secretoneurin concentrations (p < 0.001 by the log-rank test) and postoperative secretoneurin concentrations were associated with time to death in multivariate Cox regression analysis: hazard ratio ln secretoneurin 2.96 (95% CI, 1.46-5.99; p = 0.003). Adding postoperative secretoneurin concentrations to European System for Cardiac Operative Risk Evaluation II improved patient risk stratification, as assessed by the integrated discrimination index: 0.023 (95% CI, 0.0043-0.041; p = 0.016).Conclusions:Circulating postoperative secretoneurin concentrations provide incremental prognostic information to established risk indices in patients undergoing cardiac surgery.
32.	Delanaye, Pierre, et al. (författare) Age-adapted percentiles of measured glomerular filtration in healthy individuals : extrapolation to living kidney donors over 65 years. 2022 Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 60:3, s. 401-407 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: Most data on glomerular filtration rate (GFR) originate from subjects <65 years old, complicating decision-making in elderly living kidney donors. In this retrospective multi-center study, we calculated percentiles of measured GFR (mGFR) in donors <65 years old and extrapolated these to donors ≥65 years old.METHODS: mGFR percentiles were calculated from a development cohort of French/Belgian living kidney donors <65 years (n=1,983), using quantiles modeled as cubic splines (two linear parts joining at 40 years). Percentiles were extrapolated and validated in an internal cohort of donors ≥65 years (n=147, France) and external cohort of donors and healthy subjects ≥65 years (n=329, Germany, Sweden, Norway, France, The Netherlands) by calculating percentages within the extrapolated 5th-95th percentile (P5-P95).RESULTS: Individuals in the development cohort had a higher mGFR (99.9 ± 16.4 vs. 86.4 ± 14 and 82.7 ± 15.5 mL/min/1.73 m2) compared to the individuals in the validation cohorts. In the internal validation cohort, none (0%) had mGFR below the extrapolated P5, 12 (8.2%) above P95 and 135 (91.8%) between P5-P95. In the external validation cohort, five subjects had mGFR below the extrapolated P5 (1.5%), 25 above P95 (7.6%) and 299 (90.9%) between P5-P95.CONCLUSIONS: We demonstrate that extrapolation of mGFR from younger donors is possible and might aid with decision-making in elderly donors.
33.	Elvebakken, Hege, et al. (författare) A Consensus-Developed Morphological Re-Evaluation of 196 High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms and Its Clinical Correlations 2021 Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 111:9, s. 883-894 Tidskriftsartikel (refereegranskat)abstract High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are classified according to morphology as well-differentiated neuroendocrine tumours (NETs) G3 or poorly differentiated neuroendocrine carcinomas (NECs). Little data exist concerning which morphological criteria this subdivision should be based on. Uncertainty exists if the NEC group should be further subdivided according to proliferation rate. Clinical data on NET G3 and NEC with a lower Ki-67 range are limited. A total of 213 patients with high-grade GEP-NEN (Ki-67 >20%) were included from the Nordic NEC Registries. Four experienced NET pathologists re-evaluated the cases to develop the best morphological criteria to separate NET G3 from NEC, assuming longer survival in NET G3. Organoid growth pattern, capillary network in direct contact to tumour cells, and absence of desmoplastic stroma were found to best separate NET G3 from NEC. Of 196 patients with metastatic disease, NET G3 was found in 12.3%, NEC with a Ki-67 <55% (NEC < 55) in 29.6%, and NEC with a Ki-67 >= 55% (NEC >= 55) in 56.6%. Only in 1.5%, the morphology was ambiguous. Of 164 patients receiving first-line chemotherapy, 88% received platinum/etoposide treatment. Response rate was higher for NEC >= 55 (44%) than that of NEC < 55 (25%) and NET G3 (24%) (p = 0.025 and p = 0.026). Median progression-free survival was 5 months for all groups. Median overall survival was 33 months for NET G3 compared to 11 months for both NEC < 55 and NEC >= 55 (p = 0.004 and 0.003). Specific morphological criteria can separate NET G3 from NECs and show prognostic significance. High-grade GEP-NEN patients stratified by morphology and proliferation rate demonstrate significant differences in response to chemotherapy and survival.
34.	Foss, Lene, et al. (författare) Women’s entrepreneurship policy research : a 30-year review of the evidence 2019 Ingår i: Small Business Economics. - : Springer. - 0921-898X .- 1573-0913. ; 53:2, s. 409-429 Tidskriftsartikel (refereegranskat)abstract This paper focuses on women’s entrepreneurship policy as a core component of the entrepreneurial ecosystem. We use a systematic literature review (SLR) approach to critically explore the policy implications of women’s entrepreneurship research according to gender perspective: feminist empiricism, feminist standpoint theory, and post-structuralist feminist theory. Our research question asks whether there is a link between the nature of policy implications and the different theoretical perspectives adopted, and whether scholars’ policy implications have changed as the field of women’s entrepreneurship research has developed. We concentrate on empirical studies published in the “Big Five” primary entrepreneurship research journals (SBE, ETP, JBV, JSBM, and ERD) over a period of more than 30 years (1983–2015). We find that policy implications from women’s entrepreneurship research are mostly vague, conservative, and center on identifying skills gaps in women entrepreneurs that need to be “fixed,” thus isolating and individualizing any perceived problem. Despite an increase in the number of articles offering policy implications, we find little variance in the types of policy implications being offered by scholars, regardless of the particular theoretical perspective adopted, and no notable change over our 30-year review period. Recommendations to improve the entrepreneurial ecosystem for women from a policy perspective are offered, and avenues for future research are identified.
35.	Fuerst, Johannes J., et al. (författare) The Ice-Free Topography of Svalbard 2018 Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 45:21, s. 11760-11769 Tidskriftsartikel (refereegranskat)abstract We present a first version of the Svalbard ice-free topography (SVIFT1.0) using a mass conserving approach for mapping glacier ice thickness. SVIFT1.0 is informed by more than 1 million point measurements, totalling more than 8,700 km of thickness profiles. SVIFT1.0 is publicly available and represents the geometric state around the year 2010. Our estimate for the total ice volume is 6,199 km(3), equivalent to 1.5-cm sea level rise. The thickness map suggests that 13% of the glacierized area is grounded below sea level. A complementary map of error estimates comprises uncertainties in the thickness surveys as well as in other input variables. Aggregated error estimates are used to define a likely ice-volume range of 5,200-7,300 km(3). The ice front thickness of marine-terminating glaciers is a key quantity for ice loss attribution because it controls the potential ice discharge by iceberg calving into the ocean. We find a mean ice front thickness of 135 m for the archipelago (likely range 123-158 m). Plain Language Summary Svalbard is an archipelago in the Arctic, north of Norway, which is comparable in size to the New York metropolitan area. Roughly half of it is covered by glacier ice. Yet to this day, the ice volume stored in the many glaciers on Svalbard is not well known. Many attempts have been made to infer a total volume estimate, but results differ substantially. This surprises because of the long research activity in this area. A large record of more than 1 million thickness measurements exists, making Svalbard an ideal study area for the application of a state-of-the-art mapping approach for glacier ice thickness. The mapping approach computes an ice volume that will raise global sea level by more than half an inch if instantaneously melted. If spread over the metropolitan area, New York would be buried beneath a 100-m ice cover. The asset of this approach is that it provides not only a thickness map for each glacier on the archipelago but also an error map that defines the likely local thickness range. Finally, we provide the first well-informed estimate of the ice front thickness of all marine-terminating glaciers that loose icebergs to the ocean. The archipelago-wide mean ice front cliff is 135 m.
36.	H. Britton, Thérèse, 1966- (författare) Att möta det levda : Möjligheter och hinder för förståelse av levd religion i en studiebesöksorienterad religionskunskapsundervisning 2019 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The general aim of this study is to develop knowledge about how field visit-oriented religious teaching can contribute to students’ understanding of lived religion, in terms of inner diversity, religious practice and experiential dimensions. Previous research about Religious education (RE) shows that the Swedish non-confessional school subject “Religion” mainly deals with history, dogmas and concepts. Few students are concerned with the subject-matter itself in RE. "Secular" students talk about religion as something old-fashioned that concerns "the others". On the other hand, students who identify themselves religiously do not recognize what is being taught in school about their own tradition, since they miss perspectives concerning religion as part of everyday life, i.e., lived religion. A growing interest in individuals’ lived religion has also been identified in the field of religious studies. These circumstances related to field of RE serve as motivational ground for the present doctoral thesis.This thesis investigates designed RE-teaching in lower secondary school (year nine). The teaching design draws on findings reported in the licentiate thesis (Britton 2014). Three theoretical approaches are used and integrated in a theoretical framework. The approaches applied to define and operationalize students’ understanding of lived religion are selected parts of Michail Bachtin's (1997) dialogue theory, Robert Jackson's (2002) interpretive approach of Religious education, and Meredith McGuire's (2008) religion sociology theories about lived religion.The empirical data were produced from selected parts of an enacted teaching design about Buddhism, including a field visit to a Tibetan-Buddhist congregation. The data consist of grade nine students' oral and written utterances from a lesson sequence, including lesson recordings, student journals, lesson exercises, assignments, group discussions and an examination. In addition, follow-up interviews were conducted with students, the teacher and the temple representative. Data were analysed using the integrated theoretical-analytical framework, in order to provide knowledge about what opportunities and obstacles in religious teaching that contribute to students’ understandings of lived religion.Three main results emerged. First, students' personal perspectives and values of religion in general, and of the religious tradition studied (Buddhism) in particular, are important parts of students' understanding of lived religion. From students’ responses, some perspectives that interfered with their understanding of lived (Buddhist) religion were identified: student understandings that touch upon the links between individual freedom and religion; the relation between belief and religious practice and experiences; and ‘Western Buddhism’ in relation to Buddhism outside the West. Second, three didactical tools were constructed, aiming to develop RE teaching to further facilitate students’ understanding of lived religion: individual perspective, a diversity model and self-reflection. Didactical questions about representation, safe space and self-reflexivity came up. Third, there is support for arguing that lived religion as a perspective in the Swedish school subject of religion can be a goal as well as means to create a more inclusive religious education.
37.	Hansen, Thomas F., et al. (författare) Analyzing Disparity and Rates of Morphological Evolution with Model-Based Phylogenetic Comparative Methods 2022 Ingår i: Systematic Biology. - : Oxford University Press (OUP). - 1063-5157 .- 1076-836X. ; 71:5, s. 1054-1072 Tidskriftsartikel (refereegranskat)abstract Understanding variation in rates of evolution and morphological disparity is a goal of macroevolutionary research. In a phylogenetic comparative methods framework, we present three explicit models for linking the rate of evolution of a trait to the state of another evolving trait. This allows testing hypotheses about causal influences on rates of phenotypic evolution with phylogenetic comparative data. We develop a statistical framework for fitting the models with generalized least-squares regression and use this to discuss issues and limitations in the study of rates of evolution more generally. We show that the power to detect effects on rates of evolution is low in that even strong causal effects are unlikely to explain more than a few percent of observed variance in disparity. We illustrate the models and issues by testing if rates of beak-shape evolution in birds are influenced by brain size, as may be predicted from a Baldwin effect in which presumptively more behaviorally flexible large-brained species generate more novel selection on themselves leading to higher rates of evolution. From an analysis of morphometric data for 645 species, we find evidence that both macro- and microevolution of the beak are faster in birds with larger brains, but with the caveat that there are no consistent effects of relative brain size.[Baldwin effect; beak shape; behavioral drive; bird; brain size; disparity; phylogenetic comparative method; rate of evolution.]
38.	Jansen, Iris E, et al. (författare) Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers. 2022 Ingår i: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842 Tidskriftsartikel (refereegranskat)abstract Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n=8074; replication n=5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
39.	Jespers, Willem, et al. (författare) QresFEP : An Automated Protocol for Free Energy Calculations of Protein Mutations in Q 2019 Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 15:10, s. 5461-5473 Tidskriftsartikel (refereegranskat)abstract Predicting the effect of single-point mutations on protein stability or protein-ligand binding is a major challenge in computational biology. Free energy calculations constitute the most rigorous approach to this problem, though the estimation of converged values for amino acid mutations remains challenging. To overcome this limitation, we developed tailored protocols to calculate free energy shifts associated with single-point mutations. We herein describe the QresFEP protocol, which includes an extension of our recent protocols to cover all amino acids mutations, based on the latest versions of the OPLS-AA force field. QresFEP is implemented in an application programming interface framework and the graphic interface QGui, for the molecular dynamics software Q. The complete protocol is benchmarked in several model systems, optimizing a number of sampling parameters and the implementation of Zwanzig's exponential formula and Bennet's acceptance ratio methods. QresFEP shows an excellent performance on estimating the hydration free energies of amino acid side-chain mimics, including their charged analogues. We also examined its performance on a protein-ligand binding problem of pharmaceutical relevance, the antagonism of neuropeptide Y1 G protein-coupled receptor. Here, the calculations show very good agreement with the experimental effect of 16 mutations on the binding of antagonists BIBP3226, in line with our recent applications in this field. Finally, the characterization of 43 mutations of T4-lysozyme reveals the capacity of our protocol to assess variations of the thermal stability of proteins, achieving a similar performance to alternative free energy perturbation (FEP) approaches. In summary, QresFEP is a robust, versatile, and user-friendly computational FEP protocol to examine biochemical effects of single-point mutations with high accuracy.
40.	Kliest, Tessa, et al. (författare) Clinical trials in pediatric ALS: a TRICALS feasibility study 2022 Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Taylor & Francis Group. - 2167-8421 .- 2167-9223. ; 23:7-8, s. 481-488 Tidskriftsartikel (refereegranskat)abstract Background: Pediatric investigation plans (PIPs) describe how adult drugs can be studied in children. In 2015, PIPs for Amyotrophic Lateral Sclerosis (ALS) became mandatory for European marketing-authorization of adult treatments, unless a waiver is granted by the European Medicines Agency (EMA).Objective: To assess the feasibility of clinical studies on the effect of therapy in children (<18 years) with ALS in Europe.Methods: The EMA database was searched for submitted PIPs in ALS. A questionnaire was sent to 58 European ALS centers to collect the prevalence of pediatric ALS during the past ten years, the recruitment potential for future pediatric trials, and opinions of ALS experts concerning a waiver for ALS.Results: Four PIPs were identified; two were waived and two are planned for the future. In total, 49 (84.5%) centers responded to the questionnaire. The diagnosis of 44,858 patients with ALS was reported by 46 sites; 39 of the patients had an onset < 18 years (prevalence of 0.008 cases per 100,000 or 0.087% of all diagnosed patients). The estimated recruitment potential (47 sites) was 26 pediatric patients within five years. A majority of ALS experts (75.5%) recommend a waiver should apply for ALS due to the low prevalence of pediatric ALS.Conclusions: ALS with an onset before 18 years is extremely rare and may be a distinct entity from adult ALS. Conducting studies on the effect of disease-modifying therapy in pediatric ALS may involve lengthy recruitment periods, high costs, ethical/legal implications, challenges in trial design and limited information.
41.	Knudsen, Lisa B., et al. (författare) Halogenated organic contaminants and mercury in northern fulmars (Fulmarus glacialis) : levels, relationships to dietary descriptors and blood to liver comparison 2007 Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491 .- 1873-6424. ; 146:1, s. 25-33 Tidskriftsartikel (refereegranskat)abstract The northern fulmar (Fulmarus glacialis) is an interesting candidate for the study of patterns and levels of halogenated organic contaminants (HOCs) since they accumulate high levels of certain HOCs. In the present study we characterized a suite of established and novel HOCs in northern fulmars breeding on Bjørnøya in the Norwegian Arctic. A comparison between blood and liver HOC levels was made, and the levels were related to the ratios of heavier to lighter stable isotopes of nitrogen (15)N/(14)N (delta(15)N) and carbon (13)C/(12)C (delta(13)C) in muscle. A significant difference in congener patterns between blood and liver was found. The delta(13)C was not related to HOCs, neither in liver nor in blood. Weak correlations were found between delta(15)N and liver HOC levels. The 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents (TEQs) in northern fulmars were well above thresholds for reproductive effects in seabirds.
42.	Miadlikowska, Jolanta, et al. (författare) A multigene phylogenetic synthesis for the class Lecanoromycetes (Ascomycota): 1307 fungi representing 1139 infrageneric taxa, 317 genera and 66 families. 2014 Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1095-9513 .- 1055-7903. ; 79:Online 18 April 2014, s. 132-168 Tidskriftsartikel (refereegranskat)abstract The Lecanoromycetes is the largest class of lichenized Fungi, and one of the most species-rich classes in the kingdom. Here we provide a multigene phylogenetic synthesis (using three ribosomal RNA-coding and two protein-coding genes) of the Lecanoromycetes based on 635 newly generated and 3307 publicly available sequences representing 1139 taxa, 317 genera, 66 families, 17 orders and five subclasses (four currently recognized: Acarosporomycetidae, Lecanoromycetidae, Ostropomycetidae, Umbilicariomycetidae; and one provisionarily recognized, 'Candelariomycetidae'). Maximum likelihood phylogenetic analyses on four multigene datasets assembled using a cumulative supermatrix approach with a progressively higher number of species and missing data (5-gene, 5+4-gene, 5+4+3-gene and 5+4+3+2-gene datasets) show that the current classification includes non-monophyletic taxa at various ranks, which need to be recircumscribed and require revisionary treatments based on denser taxon sampling and more loci. Two newly circumscribed orders (Arctomiales and Hymeneliales in the Ostropomycetidae) and three families (Ramboldiaceae and Psilolechiaceae in the Lecanorales, and Strangosporaceae in the Lecanoromycetes inc. sed.) are introduced. The potential resurrection of the families Eigleraceae and Lopadiaceae is considered here to alleviate phylogenetic and classification disparities. An overview of the photobionts associated with the main fungal lineages in the Lecanoromycetes based on available published records is provided. A revised schematic classification at the family level in the phylogenetic context of widely accepted and newly revealed relationships across Lecanoromycetes is included. The cumulative addition of taxa with an increasing amount of missing data (i.e., a cumulative supermatrix approach, starting with taxa for which sequences were available for all five targeted genes and ending with the addition of taxa for which only two genes have been sequenced) revealed relatively stable relationships for many families and orders. However, the increasing number of taxa without the addition of more loci also resulted in an expected substantial loss of phylogenetic resolving power and support (especially for deep phylogenetic relationships), potentially including the misplacements of several taxa. Future phylogenetic analyses should include additional single copy protein-coding markers in order to improve the tree of the Lecanoromycetes. As part of this study, a new module ("Hypha") of the freely available Mesquite software was developed to compare and display the internodal support values derived from this cumulative supermatrix approach.
43.	Myhre, Peder L., et al. (författare) Prognostic Value of Secretoneurin in Patients with Acute Respiratory Failure : Data from the FINNALI Study 2016 Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 62:10, s. 1380-1389 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: We examined whether secretoneurin (SN), a biomarker associated with cardiomyocyte Ca2+ handling, provides prognostic information in patients with acute respiratory failure (ARF).METHODS: We included 490 patients with ARF, defined as ventilatory support >6 h, with blood samples available on admission to the intensive care unit (ICU). SN concentrations were measured by RIA.RESULTS: A total of 209 patients (43%) were hospitalized with cardiovascular (CV)-related ARF, and 90-day mortality rates were comparable between CV- and non CV-related ARF (n = 281): 31% vs 24%, P = 0.11. Admission SN concentrations were higher in nonsurvivors than in survivors in both CV -related (median 148 [quartile 1-3, 117-203] vs 108 [87-143] pmol/L, P < 0.001) and non CV-related ARF (139 [115-184] vs 113 [91-139] pmol/L, P < 0.001). In patients with CV -related ARF, SN concentrations on ICU admission were associated with 90-day mortality [odds ratio (OR) 1.97 (95% CI, 1.04-3.73, P = 0.04)] after adjusting for established risk indices, including N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentrations. SN also improved patient classification in CV -related ARF as assessed by the net reclassification index: 0.32 (95% CI, 0.04-0.59), P = 0.03. The area under the curve (AUC) of SN to predict mortality in patients with CV -related ARF was 0.72 (95% CI, 0.65-0.79), and the AUC of NT-proBNP was 0.64 (0.56-0.73). In contrast, SN concentrations on ICU admission did not provide incremental prognostic value to established risk indices in patients with non CV-related ARF, and the AUC was 0.67 (0.60-0.75).CONCLUSIONS: SN concentrations measured on ICU admission provided incremental prognostic information to established risk indices in patients with CV -related ARF, but not in patients with non CV-related ARF.
44.	Myrenget, Martin Elstad, et al. (författare) The effect of a music-based caregiving intervention on pain intensity in nursing home patients with dementia : a cluster-randomized controlled study 2024 Ingår i: Pain. - : Lippincott Williams & Wilkins. - 0304-3959 .- 1872-6623. ; 165:7, s. 1550-1558 Tidskriftsartikel (refereegranskat)abstract This robust randomized controlled study did not find an effect of music-based caregiving on pain intensity in nursing home patients with dementia and chronic pain. Treatment of chronic pain in patients with dementia is challenging because they have reduced ability to report pain and are particularly vulnerable to side effects of analgesics. Different types of music-based therapy have been recommended and are used as an alternative to analgesics, but the evidence is lacking. Therefore, we performed a cluster-randomized controlled study (RCT) to reduce pain intensity using music-based caregiving (MBC) over 8 weeks in nursing home patients with dementia and chronic pain. We also investigated if the amount of MBC and different chronic pain syndromes would impact on the effect. Of the 645 patients, 498 patients from 36 wards in 12 nursing homes were screened for dementia and pain. Using the Clinical Dementia Rating Scale and the Mobilization-Observation-Behavior-Intensity-Dementia Pain Scale (range 0-10), 279 (71% females, 42% severe dementia) nursing home patients were randomized to intervention group (n = 134, 18 wards) or control group (n = 145, 18 wards). The main outcome was change in pain intensity before and after the intervention. The study did not reveal any effect of MBC on pain intensity when compared with the control group (B = -0.15, 95% CI [-0.72 to 0.43]). No significant difference was found within the intervention group analyzing the impact of intervention time (B = 0.73, 95% CI [-0.55 to 2.02]) or chronic primary vs secondary pain syndromes (B = 0.45, 95% CI [-0.05 to 0.96]). Our data from this first RCT on music and pain intensity in patients with dementia and chronic pain did not find an effect of MBC on pain.
45.	Nissen-Meyer, Lise Sofie H, et al. (författare) Paroxysmal nocturnal haemoglobinuria at Oslo University Hospital 2000-2010. 2015 Ingår i: Tidsskrift for Den Norske Lægeforening. - : Norwegian Medical Association. - 0807-7096 .- 0029-2001. ; 135:11, s. 1039-1043 Tidskriftsartikel (refereegranskat)abstract BACKGROUND Paroxysmal nocturnal haemoglobinuria (PNH) is a rare haematological disease characterised by chronic haemolysis, pancytopenia and venous thrombosis. The condition is attributable to a lack of control of complement attack on erythrocytes, thrombocytes and leukocytes, and can be diagnosed by means of flow cytometry. In this quality assurance study, we have reviewed information from the medical records of all patients tested for PNH using flow cytometry at our laboratory over a ten-year period.MATERIAL AND METHOD In the period 2000-2010 a total of 28 patients were tested for PNH using flow cytometry at the Department of Immunology and Transfusion Medicine, Oslo University Hospital. We have reviewed the results of these examinations retrospectively together with information from medical records and transfusion data for the patients concerned.RESULTS Flow cytometry identified 22 patients with PNH: four with classic disease and 18 with PNH secondary to another bone marrow disease. Five patients had atypical thrombosis. Seventeen patients received antithymocyte globulin or drug treatment; of these, six recovered from their bone marrow disease, while six died and five had a need for long-term transfusion. Five patients with life-threatening bone marrow disease underwent allogeneic stem cell transplantation, three of whom died. Six of 22 patients received eculizumab; the need for transfusion has been reduced or eliminated in three patients treated with eculizumab over a longer period.INTERPRETATION Flow cytometry identified PNH in a majority of patients from whom we obtained samples. Most patients had a PNH clone secondary to bone marrow failure. Atypical thrombosis should be borne in mind as an indication for the test. Treatment with eculizumab is relevant for selected patients with PNH.
46.	Orrem, Hilde L, et al. (författare) Acute heart failure following myocardial infarction : complement activation correlates with the severity of heart failure in patients developing cardiogenic shock. 2018 Ingår i: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822. ; 5:3, s. 292-301 Tidskriftsartikel (refereegranskat)abstract AIMS: Heart failure (HF) is an impending complication to myocardial infarction. We hypothesized that the degree of complement activation reflects severity of HF following acute myocardial infarction.METHODS AND RESULTS: The LEAF trial (LEvosimendan in Acute heart Failure following myocardial infarction) evaluating 61 patients developing HF within 48 h after percutaneous coronary intervention-treated ST-elevation myocardial infarction herein underwent a post hoc analysis. Blood samples were drawn from inclusion to Day 5 and at 42 day follow-up, and biomarkers were measured with enzyme immunoassays. Regional myocardial contractility was measured by echocardiography as wall motion score index (WMSI). The cardiogenic shock group (n = 9) was compared with the non-shock group (n = 52). Controls (n = 44) were age-matched and sex-matched healthy individuals. C4bc, C3bc, C3bBbP, and sC5b-9 were elevated in patients at inclusion compared with controls (P < 0.01). The shock group had higher levels compared with the non-shock group for all activation products except C3bBbP (P < 0.05). At Day 42, all products were higher in the shock group (P < 0.05). In the shock group, sC5b-9 correlated significantly with WMSI at baseline (r = 0.68; P = 0.045) and at Day 42 (r = 0.84; P = 0.036). Peak sC5b-9 level correlated strongly with WMSI at Day 42 (r = 0.98; P = 0.005). Circulating endothelial cell activation markers sICAM-1 and sVCAM-1 were higher in the shock group during the acute phase (P < 0.01), and their peak levels correlated with sC5b-9 peak level in the whole HF population (r = 0.32; P = 0.014 and r = 0.30; P = 0.022, respectively).CONCLUSIONS: Complement activation discriminated cardiogenic shock from non-shock in acute ST-elevation myocardial infarction complicated by HF and correlated with regional contractility and endothelial cell activation, suggesting a pathogenic role of complement in this condition.
47.	Orrem, Hilde L., et al. (författare) IL-6 Receptor Inhibition by Tocilizumab Attenuated Expression of C5a Receptor 1 and 2 in Non-ST-Elevation Myocardial Infarction 2018 Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 9 Tidskriftsartikel (refereegranskat)abstract Background: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL-6 receptor (IL-6R)-antagonist tocilizumab on the expression of the anaphylatoxin receptors in whole blood from non-ST-elevation myocardial infarction (NSTEMI) patients. Separately, anaphylatoxin receptor expression in peripheral blood mononuclear cells (PBMC) from patients with different entities of CAD was investigated. Materials and Methods: NSTEMI patients were randomized to one dose of tocilizumab (n = 28) or placebo (n = 32) and observed for 6 months. Whole blood samples drawn at inclusion, at day 2, 3 and after 6 months were used for mRNA isolation. Plasma was prepared for analysis of complement activation measured as sC5b-9 by ELISA. Furthermore, patients with different CAD entities comprising stable angina pectoris (SAP, n = 22), non-ST-elevation acute coronary syndrome (NSTE-ACS, n = 21) and ST-elevation myocardial infarction (STEMI, n = 20) were included. PBMC was isolated from blood samples obtained at admission to hospital and mRNA isolated. Anaphylatoxin-receptor-expression was analyzed with qPCR using mRNA from whole blood and PBMC, respectively. Results: Our main findings were (i) Tocilizumab decreased C5aR1 and C5aR2 mRNA expression significantly (p < 0.001) and substantially (> 50%) at day 2 and 3, whereas C3aR expression was unaffected. (ii) Tocilizumab did not affect complement activation. (iii) In analyzes of different CAD entities, C5aR1 expression was significantly increased in all CAD subgroups compared to controls with the highest level in the STEMI patients (p < 0.001). For C5aR2 and C3aR the expression compared to controls were more moderate with increased expression of C5aR2 in the STEMI group (p < 0.05) and C3aR in the NSTE-ACS group (p < 0.05). Conclusion: Expression of C5aR1 and C5aR2 in whole blood was significantly attenuated by IL-6R-inhibition in NSTEMI patients. These receptors were significantly upregulated in PBMC CAD patients with particularly high levels of C5aR1 in STEMI patients.
48.	Orrem, Hilde L., et al. (författare) Soluble IL-1 receptor 2 is associated with left ventricular remodelling in patients with ST-elevation myocardial infarction 2018 Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 268, s. 187-192 Tidskriftsartikel (refereegranskat)abstract Background: The inflammatory response following myocardial infarction (MI) is prerequisite for proper healing of infarcted tissue, but can also have detrimental effects on cardiac function. Interleukin (IL)-1 alpha and IL-1 beta are potent inflammatory mediators and their bioactivity is tightly regulated by IL-1 receptor antagonist (IL-1ra) and soluble (s) IL-1 receptors (R). We aimed to examine whether levels of soluble regulators of IL-1 signalling are changed during ST-elevation MI (STEMI) and their associations with parameters of cardiac injury and ventricular remodelling. Methods: Plasma levels of IL-1Ra, sIL-1R1, sIL-1R2 and sIL-1R accessory protein (sIL-1RAcP) were measured by immunoassays in repeated samples from patients with STEMI (n = 255) and compared to healthy controls (n=65). Results: IL-1Ra, sIL-1R1 and sIL-1R2 levels were all significantly elevated after STEMI, while levels of sIL-1RAcP were lower compared to controls. sIL-1R2 levels (at different time points) correlated positively with C-reactive protein, myocardial infarct size and change in indexed left ventricular end-diastolic and end-systolic volume (LVEDVi and LVESVi) measured by cardiac MR acutely and after 4 months, and negatively with LV ejection fraction. Patients with >median levels of sIL-1R2 in the acute phase were more likely to have increased change in LVEDVi and LVESVi. Importantly, sIL-1R2 remained significantly associated with change in LVEDVi and LVESVi also after adjustment for clinical covariates. Conclusion: Levels of sIL-1R2 are independently associated with parameters of LV adverse remodelling following STEMI. (C 18 Elsevier B.V. All rights reserved.
49.	Ottesen, Anett H., et al. (författare) Secretoneurin, a Novel Endogenous CaMKII Inhibitor, Augments Cardiomyocyte Calcium Handling and Inhibits Arrhythmogenic Calcium Release 2015 Ingår i: Biophysical Journal. - 0006-3495 .- 1542-0086. ; 108:2, s. 340A-340A Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
50.	Ottesen, Anett H., et al. (författare) Secretoneurin Is an Endogenous Calcium/Calmodulin-Dependent Protein Kinase II Inhibitor That Attenuates Ca2+-Dependent Arrhythmia 2019 Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 1941-3149 .- 1941-3084. ; 12:4 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Circulating SN (secretoneurin) concentrations are increased in patients with myocardial dysfunction and predict poor outcome. Because SN inhibits CaMKII delta (Ca2+/calmodulin-dependent protein kinase II delta) activity, we hypothesized that upregulation of SN in patients protects against cardiomyocyte mechanisms of arrhythmia. METHODS: Circulating levels of SN and other biomarkers were assessed in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT; n=8) and in resuscitated patients after ventricular arrhythmia-induced cardiac arrest (n=155). In vivo effects of SN were investigated in CPVT mice (RyR2 [ryanodine receptor 2]-R2474S) using adeno-associated virus-9-induced overexpression. Interactions between SN and CaMKII delta were mapped using pull-down experiments, mutagenesis, ELISA, and structural homology modeling. Ex vivo actions were tested in Langendorff hearts and effects on Ca2+ homeostasis examined by fluorescence (fluo-4) and patchclamp recordings in isolated cardiomyocytes. RESULTS: SN levels were elevated in patients with CPVT and following ventricular arrhythmia-induced cardiac arrest. In contrast to NT-proBNP (N-terminal proB- type natriuretic peptide) and hs-TnT (high-sensitivity troponin T), circulating SN levels declined after resuscitation, as the risk of a new arrhythmia waned. Myocardial pro-SN expression was also increased in CPVT mice, and further adeno-associated virus-9-induced overexpression of SN attenuated arrhythmic induction during stress testing with isoproterenol. Mechanistic studies mapped SN binding to the substrate binding site in the catalytic region of CaMKII delta. Accordingly, SN attenuated isoproterenol induced autophosphorylation of Thr287-CaMKII delta in Langendorff hearts and inhibited CaMKII delta-dependent RyR phosphorylation. In line with CaMKII delta and RyR inhibition, SN treatment decreased Ca2+ spark frequency and dimensions in cardiomyocytes during isoproterenol challenge, and reduced the incidence of Ca2+ waves, delayed afterdepolarizations, and spontaneous action potentials. SN treatment also lowered the incidence of early afterdepolarizations during isoproterenol; an effect paralleled by reduced magnitude of L-type Ca2+ current. CONCLUSIONS: SN production is upregulated in conditions with cardiomyocyte Ca2+ dysregulation and offers compensatory protection against cardiomyocyte mechanisms of arrhythmia, which may underlie its putative use as a biomarker in at-risk patients.

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