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| 2. |
- Wang, Haidong, et al.
(author)
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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
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
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Journal article (peer-reviewed)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.
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| 3. |
- Cook, Michael B., et al.
(author)
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Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma : a study within the National Cancer Institute Cohort Consortium
- 2019
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In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 68:6, s. 960-968
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Cross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk.DESIGN: This nested case-control study included 296 oesophageal adenocarcinoma cases and 296 incidence density matched controls from seven prospective cohort studies. We quantitated 69 circulating inflammation markers using Luminex-based multiplex assays. Conditional logistic regression models estimated associations between inflammation markers and oesophageal adenocarcinoma, as well as direct and indirect effects of obesity and smoking on risk of malignancy.RESULTS: Soluble tumour necrosis factor receptor 2 (sTNFR2) (ORsquartile 4 vs 1=2.67, 95% CI 1.52 to 4.68) was significantly associated with oesophageal adenocarcinoma. Additional markers close to the adjusted significance threshold included C reactive protein, serum amyloid A, lipocalin-2, resistin, interleukin (IL) 3, IL17A, soluble IL-6 receptor and soluble vascular endothelial growth factor receptor 3. Adjustment for body mass index, waist circumference or smoking status slightly attenuated biomarker-cancer associations. Mediation analysis indicated that sTNFR2 may account for 33% (p=0.005) of the effect of waist circumference on oesophageal adenocarcinoma risk. Resistin, plasminogen activator inhibitor 1, C reactive protein and serum amyloid A were also identified as potential mediators of obesity-oesophageal adenocarcinoma associations. For smoking status, only plasminogen activator inhibitor 1 was a nominally statistically significant (p<0.05) mediator of cancer risk.CONCLUSION: This prospective study provides evidence of a link between systemic inflammation and oesophageal adenocarcinoma risk. In addition, this study provides the first evidence that indirect effects of excess adiposity and cigarette smoking, via systemic inflammation, increase the risk of oesophageal adenocarcinoma.
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| 5. |
- Heindel, Jerrold J., et al.
(author)
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Obesity II : Establishing causal links between chemical exposures and obesity
- 2022
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In: Biochemical Pharmacology. - : Elsevier. - 0006-2952 .- 1356-1839 .- 1873-2968. ; 199
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Research review (peer-reviewed)abstract
- Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.
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| 7. |
- Ishengoma, Deus S., et al.
(author)
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Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria and prevalence of Pfk13 and Pfmdr1 polymorphisms after a decade of using artemisinin-based combination therapy in mainland Tanzania
- 2019
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In: Malaria Journal. - : BMC. - 1475-2875. ; 18
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Journal article (peer-reviewed)abstract
- Background: The World Health Organization recommends regular therapeutic efficacy studies (TES) to monitor the performance of first and second-line anti-malarials. In 2016, efficacy and safety of artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria were assessed through a TES conducted between April and October 2016 at four sentinel sites of Kibaha, Mkuzi, Mlimba, and Ujiji in Tanzania. The study also assessed molecular markers of artemisinin and lumefantrine (partner drug) resistance.Methods: Eligible patients were enrolled at the four sites, treated with standard doses of AL, and monitored for 28 days with clinical and laboratory assessments. The main outcomes were PCR corrected cure rates, day 3 positivity rates, safety of AL, and prevalence of single nucleotide polymorphisms in Plasmodium falciparum kelch 13 (Pfk13) (codon positions: 440-600) and P. falciparum multi-drug resistance 1 (Pfmdr1) genes (codons: N86Y, Y184F and D1246Y), markers of artemisinin and lumefantrine resistance, respectively.Results: Of 344 patients enrolled, three withdrew, six were lost to follow-up; and results were analysed for 335 (97.4%) patients. Two patients had treatment failure (one early treatment failure and one recrudescent infection) after PCR correction, yielding an adequate clinical and parasitological response of > 98%. Day 3 positivity rates ranged from 0 to 5.7%. Common adverse events included cough, abdominal pain, vomiting, and diarrhoea. Two patients had serious adverse events; one died after the first dose of AL and another required hospitalization after the second dose of AL (on day 0) but recovered completely. Of 344 samples collected at enrolment (day 0), 92.7% and 100% were successfully sequenced for Pfk13 and Pfmdr1 genes, respectively. Six (1.9%) had non-synonymous mutations in Pfk13, none of which had been previously associated with artemisinin resistance. For Pfmdr1, the NFD haplotype (codons N86, 184F and D1246) was detected in 134 (39.0%) samples; ranging from 33.0% in Mlimba to 45.5% at Mkuzi. The difference among the four sites was not significant (p = 0.578). All samples had a single copy of the Pfmdr1 gene.Conclusion: The study indicated high efficacy of AL and the safety profile was consistent with previous reports. There were no known artemisinin-resistance Pfk13 mutations, but there was a high prevalence of a Pfmdr1 haplotype associated with reduced sensitivity to lumefantrine (but no reduced efficacy was observed in the subjects). Continued TES and monitoring of markers of resistance to artemisinin and partner drugs is critical for early detection of resistant parasites and to inform evidence-based malaria treatment policies.
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| 8. |
- Ishengoma, Deus S., et al.
(author)
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Microsatellites reveal high polymorphism and high potential for use in anti-malarial efficacy studies in areas with different transmission intensities in mainland Tanzania
- 2024
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In: MALARIA JOURNAL. - : Springer Nature. - 1475-2875. ; 23:1
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Journal article (peer-reviewed)abstract
- Background Tanzania is currently implementing therapeutic efficacy studies (TES) in areas of varying malaria transmission intensities as per the World Health Organization (WHO) recommendations. In TES, distinguishing reinfection from recrudescence is critical for the determination of anti-malarial efficacy. Recently, the WHO recommended genotyping polymorphic coding genes, merozoite surface proteins 1 and 2 (msp1 and msp2), and replacing the glutamate-rich protein (glurp) gene with one of the highly polymorphic microsatellites in Plasmodium falciparum to adjust the efficacy of antimalarials in TES. This study assessed the polymorphisms of six neutral microsatellite markers and their potential use in TES, which is routinely performed in Tanzania. Methods Plasmodium falciparum samples were obtained from four TES sentinel sites, Kibaha (Pwani), Mkuzi (Tanga), Mlimba (Morogoro) and Ujiji (Kigoma), between April and September 2016. Parasite genomic DNA was extracted from dried blood spots on filter papers using commercial kits. Genotyping was done using six microsatellites (Poly-alpha, PfPK2, TA1, C3M69, C2M34 and M2490) by capillary method, and the data were analysed to determine the extent of their polymorphisms and genetic diversity at the four sites. Results Overall, 83 (88.3%) of the 94 samples were successfully genotyped (with positive results for >= 50.0% of the markers), and > 50.0% of the samples (range = 47.6-59.1%) were polyclonal, with a mean multiplicity of infection (MOI) ranging from 1.68 to 1.88 among the four sites. There was high genetic diversity but limited variability among the four sites based on mean allelic richness (R-S = 7.48, range = 7.27-8.03, for an adjusted minimum sample size of 18 per site) and mean expected heterozygosity (H-e = 0.83, range = 0.80-0.85). Cluster analysis of haplotypes using STRUCTURE, principal component analysis, and pairwise genetic differentiation (F-ST) did not reveal population structure or clustering of parasites according to geographic origin. Of the six markers, Poly-alpha was the most polymorphic, followed by C2M34, TA1 and C3M69, while M2490 was the least polymorphic. Conclusion Microsatellite genotyping revealed high polyclonality and genetic diversity but no significant population structure. Poly-alpha, C2M34, TA1 and C3M69 were the most polymorphic markers, and Poly-alpha alone or with any of the other three markers could be adopted for use in TES in Tanzania.
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| 9. |
- Krämer, Martina, et al.
(author)
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A microphysics guide to cirrus – Part 2 : Climatologies of clouds and humidity from observations
- 2020
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In: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 20:21, s. 12569-12608
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Journal article (peer-reviewed)abstract
- This study presents airborne in situ and satellite remote sensing climatologies of cirrus clouds and humidity. The climatologies serve as a guide to the properties of cirrus clouds, with the new in situ database providing detailed insights into boreal midlatitudes and the tropics, while the satellite-borne data set offers a global overview.To this end, an extensive, quality-checked data archive, the Cirrus Guide II in situ database, is created from airborne in situ measurements during 150 flights in 24 campaigns. The archive contains meteorological parameters, ice water content (IWC), ice crystal number concentration (Nice), ice crystal mean mass radius (Rice), relative humidity with respect to ice (RHice), and water vapor mixing ratio (H2O) for each of the flights. Depending on the parameter, the database has been extended by about a factor of 5–10 compared to earlier studies.As one result of our investigation, we show that the medians of Nice, Rice, and RHice have distinct patterns in the IWC–T parameter space. Lookup tables of these variables as functions of IWC and T can be used to improve global model cirrus representation and remote sensing retrieval methods. Another outcome of our investigation is that across all latitudes, the thicker liquid-origin cirrus predominate at lower altitudes, while at higher altitudes the thinner in situ-origin cirrus prevail. Further, examination of the radiative characteristics of in situ-origin and liquid-origin cirrus shows that the in situ-origin cirrus only slightly warm the atmosphere, while liquid-origin cirrus have a strong cooling effect.An important step in completing the Cirrus Guide II is the provision of the global cirrus Nice climatology, derived by means of the retrieval algorithm DARDAR-Nice from 10 years of cirrus remote sensing observations from satellite. The in situ measurement database has been used to evaluate and improve the satellite observations. We found that the global median Nice from satellite observations is almost 2 times higher than the in situ median and increases slightly with decreasing temperature. Nice medians of the most frequently occurring cirrus sorted by geographical regions are highest in the tropics, followed by austral and boreal midlatitudes, Antarctica, and the Arctic. Since the satellite climatologies enclose the entire spatial and temporal Nice occurrence, we could deduce that half of the cirrus are located in the lowest, warmest (224–242 K) cirrus layer and contain a significant amount of liquid-origin cirrus.A specific highlight of the study is the in situ observations of cirrus and humidity in the Asian monsoon anticyclone and the comparison to the surrounding tropics. In the convectively very active Asian monsoon, peak values of Nice and IWC of 30 cm−3 and 1000 ppmv are detected around the cold point tropopause (CPT). Above the CPT, ice particles that are convectively injected can locally add a significant amount of water available for exchange with the stratosphere. We found IWCs of up to 8 ppmv in the Asian monsoon in comparison to only 2 ppmv in the surrounding tropics. Also, the highest RHice values (120 %–150 %) inside of clouds and in clear sky are observed around and above the CPT. We attribute this to the high H2O mixing ratios (typically 3–5 ppmv) observed in the Asian monsoon compared to 1.5 to 3 ppmv found in the tropics. Above the CPT, supersaturations of 10 %–20 % are observed in regions of weak convective activity and up to about 50 % in the Asian monsoon. This implies that the water available for transport into the stratosphere might be higher than the expected saturation value.
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| 10. |
- Ozaki, Yuto, et al.
(author)
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Globally, songs and instrumental melodies are slower and higher and use more stable pitches than speech: A Registered Report
- 2024
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In: Science Advances. - 2375-2548. ; 10:20
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Journal article (peer-reviewed)abstract
- Both music and language are found in all known human societies, yet no studies have compared similarities and differences between song, speech, and instrumental music on a global scale. In this Registered Report, we analyzed two global datasets: (i) 300 annotated audio recordings representing matched sets of traditional songs, recited lyrics, conversational speech, and instrumental melodies from our 75 coauthors speaking 55 languages; and (ii) 418 previously published adult-directed song and speech recordings from 209 individuals speaking 16 languages. Of our six preregistered predictions, five were strongly supported: Relative to speech, songs use (i) higher pitch, (ii) slower temporal rate, and (iii) more stable pitches, while both songs and speech used similar (iv) pitch interval size and (v) timbral brightness. Exploratory analyses suggest that features vary along a “musi-linguistic” continuum when including instrumental melodies and recited lyrics. Our study provides strong empirical evidence of cross-cultural regularities in music and speech.
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