| 1. |
- Edgecock, T. R., et al.
(författare)
-
High intensity neutrino oscillation facilities in Europe
- 2013
-
Ingår i: Physical Review Special Topics - Accelerators and Beams. - : American Physical Society. - 1098-4402. ; 16:2, s. 021002-
-
Tidskriftsartikel (refereegranskat)abstract
- The EUROnu project has studied three possible options for future, high intensity neutrino oscillation facilities in Europe. The first is a Super Beam, in which the neutrinos come from the decay of pions created by bombarding targets with a 4 MW proton beam from the CERN High Power Superconducting Proton Linac. The far detector for this facility is the 500 kt MEMPHYS water Cherenkov, located in the Frejus tunnel. The second facility is the Neutrino Factory, in which the neutrinos come from the decay of mu(+) and mu(-) beams in a storage ring. The far detector in this case is a 100 kt magnetized iron neutrino detector at a baseline of 2000 km. The third option is a Beta Beam, in which the neutrinos come from the decay of beta emitting isotopes, in particular He-6 and Ne-18, also stored in a ring. The far detector is also the MEMPHYS detector in the Frejus tunnel. EUROnu has undertaken conceptual designs of these facilities and studied the performance of the detectors. Based on this, it has determined the physics reach of each facility, in particular for the measurement of CP violation in the lepton sector, and estimated the cost of construction. These have demonstrated that the best facility to build is the Neutrino Factory. However, if a powerful proton driver is constructed for another purpose or if the MEMPHYS detector is built for astroparticle physics, the Super Beam also becomes very attractive.
|
|
| 2. |
- Wang, Haidong, et al.
(författare)
-
Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
- 2016
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
|
|
| 3. |
- Griffith, Simon C., et al.
(författare)
-
Variation in reproductive success across captive populations: Methodological differences, potential biases and opportunities
- 2017
-
Ingår i: Ethology. - : Wiley. - 1439-0310 .- 0179-1613. ; 123:1, s. 1-29
-
Tidskriftsartikel (refereegranskat)abstract
- Our understanding of fundamental organismal biology has been disproportionately influenced by studies of a relatively small number of ‘model’ species extensively studied in captivity. Laboratory populations of model species are commonly subject to a number of forms of past and current selection that may affect experimental outcomes. Here, we examine these processes and their outcomes in one of the most widely used vertebrate species in the laboratory – the zebra finch (Taeniopygia guttata). This important model species is used for research across a broad range of fields, partly due to the ease with which it can be bred in captivity. However despite this perceived amenability, we demonstrate extensive variation in the success with which different laboratories and studies bred their subjects, and overall only 64% of all females that were given the opportunity, bred successfully in the laboratory. We identify and review several environmental, husbandry, life-history and behavioural factors that potentially contribute to this variation. The variation in reproductive success across individuals could lead to biases in experimental outcomes and drive some of the heterogeneity in research outcomes across studies. The zebra finch remains an excellent captive animal system and our aim is to sharpen the insight that future studies of this species can provide, both to our understanding of this species and also with respect to the reproduction of captive animals more widely. We hope to improve systematic reporting methods and that further investigation of the issues we raise will lead both to advances in our fundamental understanding of avian reproduction as well as to improvements in future welfare and experimental efficiency.
|
|
| 4. |
- Marshall, Helen, et al.
(författare)
-
Long-term (5-year) antibody persistence following two- and three-dose regimens of a combined hepatitis A and B vaccine in children aged 1-11 years
- 2010
-
Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 28:27, s. 4411-4415
-
Tidskriftsartikel (refereegranskat)abstract
- This study compared the long-term persistence of anti-hepatitis A (anti-HAV) and B (anti-HBs) antibodies, 5 years after vaccination of subjects aged 1-11 years with a combined hepatitis A and B vaccine either in a two-dose (0, 6 months, Adult formulation) or a three-dose (0, 1, 6 months, Paediatric formulation) schedule. At the end of the 5 years, all subjects (100%) in both groups continued to have anti-HAV antibodies >= 15 mIU/mL, while 94-97% of subjects in both groups had anti-HBs antibody concentrations >= 10 mIU/mL Subjects with anti-HBs antibody concentration <= 10 mIU/mL were administered a challenge dose of hepatitis B vaccine. All subjects mounted a vigorous immune response to the challenge indicating the presence of immunological memory to HBV.
|
|
| 5. |
- Sikkema, Lisa, et al.
(författare)
-
An integrated cell atlas of the lung in health and disease
- 2023
-
Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 29:6, s. 1563-1577
-
Tidskriftsartikel (refereegranskat)abstract
- Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1 + profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
|
|
| 6. |
- Bettegowda, Chetan, et al.
(författare)
-
Detection of circulating tumor DNA in early- and late-stage human malignancies
- 2014
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 6:224, s. 224ra24-
-
Tidskriftsartikel (refereegranskat)abstract
- The development of noninvasive methods to detect and monitor tumors continues to be a major challenge in oncology. We used digital polymerase chain reaction-based technologies to evaluate the ability of circulating tumor DNA (ctDNA) to detect tumors in 640 patients with various cancer types. We found that ctDNA was detectable in >75% of patients with advanced pancreatic, ovarian, colorectal, bladder, gastroesophageal, breast, melanoma, hepatocellular, and head and neck cancers, but in less than 50% of primary brain, renal, prostate, or thyroid cancers. In patients with localized tumors, ctDNA was detected in 73, 57, 48, and 50% of patients with colorectal cancer, gastroesophageal cancer, pancreatic cancer, and breast adenocarcinoma, respectively. ctDNA was often present in patients without detectable circulating tumor cells, suggesting that these two biomarkers are distinct entities. In a separate panel of 206 patients with metastatic colorectal cancers, we showed that the sensitivity of ctDNA for detection of clinically relevant KRAS gene mutations was 87.2% and its specificity was 99.2%. Finally, we assessed whether ctDNA could provide clues into the mechanisms underlying resistance to epidermal growth factor receptor blockade in 24 patients who objectively responded to therapy but subsequently relapsed. Twenty-three (96%) of these patients developed one or more mutations in genes involved in the mitogen-activated protein kinase pathway. Together, these data suggest that ctDNA is a broadly applicable, sensitive, and specific biomarker that can be used for a variety of clinical and research purposes in patients with multiple different types of cancer.
|
|
| 7. |
- Cadamuro, Janne, et al.
(författare)
-
Deviating glucose results in an international dual-center study. A root cause investigation
- 2022
-
Ingår i: Biochemia Medica. - : Croatian Society for Medical Biochemistry and Laboratory Medicine. - 1330-0962 .- 1846-7482. ; 32:1
-
Tidskriftsartikel (refereegranskat)abstract
- During a dual-center study on obese and normal weight children and adolescents, focusing on glucose metabolism, we observed a marked difference in glucose results (N = 16,840) between the two sites, Salzburg, Austria and Uppsala, Sweden (P < 0.001). After excluding differences in patient characteristics between the two populations as cause of this finding, we investigated other preanalytic influences. Finally, only the tubes used for blood collection at the two sites were left to evaluate. While the Vacuette FC-Mix tube (Greiner Bio-One, Kremsmunster, Austria) was used in Uppsala, in Salzburg blood collections were performed with a lithium heparin tube (LH-Monovette, Sarstedt, Germany). To prove our hypothesis, we collected two blood samples in either of these tubes from 51 children (Salzburg N = 27, Uppsala N = 24) and compared the measured glucose results. Indeed, we found the suspected bias and calculated a correction formula, which significantly diminished the differences of glucose results between the two sites (P = 0.023). Our finding is in line with those of other studies and although this issue should be widely known, we feel that it is widely neglected, especially when comparing glucose concentrations across Europe, using large databases without any information on preanalytic sample handling.
|
|
| 8. |
- Kilpi, Terhi M., et al.
(författare)
-
Immunogenicity and reactogenicity of two diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b vaccines administered at 3, 5 and 11-12 months of age
- 2009
-
Ingår i: HUM VACCINES. - : Informa UK Limited. - 1554-8619 .- 1554-8600. ; 5:1, s. 18-25
-
Tidskriftsartikel (refereegranskat)abstract
- The use of combination vaccines in the routine childhood program reduces distress to the recipients and is likely to improve uptake rates and timeliness of vaccination but requires careful evaluation and surveillance. The aim of this study was to evaluate the immunogenicity and reactogenicity of two commercial diphtheria-tetanus-acellular pertussis-hepatitis b-inactivated polio virus-Haemophilus influenzae type b (DTaP-HBV-IPV/Hib) combination vaccines when administered to infants at 3, 5 and 11-12 months of age. A total of 494 infants were randomized to receive three doses of either Infanrix hexa T (GlaxoSmithKline Biologicals; N = 246) or Hexavac (TM) (Sanofi Pasteur MSD; N = 248) in 10 centers in Italy, Finland and Sweden. After the third dose, antibodies to diphtheria, tetanus, polio and Hib were at the protective level in nearly all infants in both groups whereas the proportion of subjects who had achieved the protective concentration of = 10 mIU/ml to hepatitis B surface antigen was 99.1% (95% CI 96.7-99.9) in the Infanrix hexa T group as compared to 94.4% (95% CI 90.4-97.1) in the Hexavac T group. Antibody titers to all three polio antigens were highest in Italy and lowest in Finland. Clinically relevant general reactions (such as fever of >39.5 degrees C) were mostly reported in less than 5% of the vaccinees. Three doses of DTaP-HBV-IPV/Hib combination vaccines produced sufficient immune responses in nearly all vaccinees.
|
|
| 9. |
- Perotin-Collard, Jeanne-Marie, et al.
(författare)
-
Subtypes of eosinophilic asthma with discrete gene pathway phenotypes
- 2019
-
Ingår i: European Respiratory Journal. - : European Respiratory Society Journals. - 0903-1936 .- 1399-3003. ; 54
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Blood eosinophil counts ≥0.3x109/L are used to define Type-2, eosinophilic asthma. However, differential responses to T2 biologics of patients with eosinophilic asthma suggests that this may be a heterogeneous phenotype with subsets driven by different molecular mechanisms.Methods: Blood transcriptomic data, acquired from 99 severe asthmatics from the U-BIOPRED study (62% female, mean age 54 yr, 41% on oral steroids), were clustered by topological data analysis and cluster boundaries defined by the MORSE method. Gene pathway signatures were identified by Ingenuity Pathway Analysis.Results: Analysis revealed 3 clusters with different modulated gene pathways, i.e. molecular phenotypes. Subtype 1 had high IFN-γ, low IL5, low IL13 and low IL17 gene expression, with reduced glucocorticoid-induced gene expression. Subtype 2 had low IFNγ, high IL5, high IL13 and low IL17 gene expression. Subtype 3 had low IFNγ, high IL5, high IL13 and high IL17 gene expression. Pathway analysis suggested a strong steroid response in Subtypes 2 and 3. Clinically, the three clusters were not different in respect of age, gender, prevalence of atopy, blood or sputum eosinophil counts. Subtype 3 was characterized by high neutrophil counts in blood and bronchial epithelium, frequent sinus disease and asthma exacerbations, OCS treatment, low allergic sensitisation and low exhaled NO. Subtype 1 was characterized by high exhaled NO and more frequent IgE therapy.Conclusion: This study suggests that eosinophilic severe asthma (≥0.3x109/L) can be stratified further into 3 subtypes with distinct gene expression profiles that could be developed as molecular diagnostic biomarkers to guide treatment and thereby improve patient outcomes.
|
|
| 10. |
|
|
