| 1. |
- Aad, G, et al.
(författare)
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- 2015
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swepub:Mat__t
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| 2. |
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| 5. |
- Fullman, N., et al.
(författare)
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Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016
- 2018
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Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 391:10136, s. 2236-2271
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Tidskriftsartikel (refereegranskat)abstract
- Background A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97.1 (95% UI 95.8-98.1) in Iceland, followed by 96.6 (94.9-97.9) in Norway and 96.1 (94.5-97.3) in the Netherlands, to values as low as 18.6 (13.1-24.4) in the Central African Republic, 19.0 (14.3-23.7) in Somalia, and 23.4 (20.2-26.8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91.5 (89.1-936) in Beijing to 48.0 (43.4-53.2) in Tibet (a 43.5-point difference), while India saw a 30.8-point disparity, from 64.8 (59.6-68.8) in Goa to 34.0 (30.3-38.1) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4.8-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20.9-point to 17.0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17.2-point to 20.4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle-SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view and subsequent provision of quality health care for all populations. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 6. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 7. |
- Vos, T., et al.
(författare)
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Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016
- 2017
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Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1211-1259
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Tidskriftsartikel (refereegranskat)abstract
- Background As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57.6 million (95% uncertainty interval [UI] 40.8-75.9 million [7.2%, 6.0-8.3]), 45.1 million (29.0-62.8 million [5.6%, 4.0-7.2]), 36.3 million (25.3-50.9 million [4.5%, 3.8-5.3]), 34.7 million (23.0-49.6 million [4.3%, 3.5-5.2]), and 34.1 million (23.5-46.0 million [4.2%, 3.2-5.3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2.7% (95% UI 2.3-3.1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10.4% (95% UI 9.0-11.8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228). Interpretation The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-todate information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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| 11. |
- Fenstermacher, M.E., et al.
(författare)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Tidskriftsartikel (refereegranskat)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 12. |
- Kinyoki, DK, et al.
(författare)
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Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
- 2020
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 26:5, s. 750-759
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Tidskriftsartikel (refereegranskat)abstract
- A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic.
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| 16. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 17. |
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| 18. |
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| 19. |
- Nagaraja, Ch., et al.
(författare)
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Opening remarks
- 2016
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Konferensbidrag (refereegranskat)
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| 20. |
- Faatz, B., et al.
(författare)
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Simultaneous operation of two soft x-ray free-electron lasers driven by one linear accelerator
- 2016
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Extreme-ultraviolet to x-ray free-electron lasers (FELs) in operation for scientific applications are up to now single-user facilities. While most FELs generate around 100 photon pulses per second, FLASH at DESY can deliver almost two orders of magnitude more pulses in this time span due to its superconducting accelerator technology. This makes the facility a prime candidate to realize the next step in FELs-dividing the electron pulse trains into several FEL lines and delivering photon pulses to several users at the same time. Hence, FLASH has been extended with a second undulator line and self-amplified spontaneous emission (SASE) is demonstrated in both FELs simultaneously. FLASH can now deliver MHz pulse trains to two user experiments in parallel with individually selected photon beam characteristics. First results of the capabilities of this extension are shown with emphasis on independent variation of wavelength, repetition rate, and photon pulse length.
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| 21. |
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| 22. |
- Turkington, RC, et al.
(författare)
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Immune activation by DNA damage predicts response to chemotherapy and survival in oesophageal adenocarcinoma
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:11, s. 1918-1927
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Tidskriftsartikel (refereegranskat)abstract
- Current strategies to guide selection of neoadjuvant therapy in oesophageal adenocarcinoma (OAC) are inadequate. We assessed the ability of a DNA damage immune response (DDIR) assay to predict response following neoadjuvant chemotherapy in OAC.DesignTranscriptional profiling of 273 formalin-fixed paraffin-embedded prechemotherapy endoscopic OAC biopsies was performed. All patients were treated with platinum-based neoadjuvant chemotherapy and resection between 2003 and 2014 at four centres in the Oesophageal Cancer Clinical and Molecular Stratification consortium. CD8 and programmed death ligand 1 (PD-L1) immunohistochemical staining was assessed in matched resection specimens from 126 cases. Kaplan-Meier and Cox proportional hazards regression analysis were applied according to DDIR status for recurrence-free survival (RFS) and overall survival (OS).ResultsA total of 66 OAC samples (24%) were DDIR positive with the remaining 207 samples (76%) being DDIR negative. DDIR assay positivity was associated with improved RFS (HR: 0.61; 95% CI 0.38 to 0.98; p=0.042) and OS (HR: 0.52; 95% CI 0.31 to 0.88; p=0.015) following multivariate analysis. DDIR-positive patients had a higher pathological response rate (p=0.033), lower nodal burden (p=0.026) and reduced circumferential margin involvement (p=0.007). No difference in OS was observed according to DDIR status in an independent surgery-alone dataset.DDIR-positive OAC tumours were also associated with the presence of CD8+ lymphocytes (intratumoural: p<0.001; stromal: p=0.026) as well as PD-L1 expression (intratumoural: p=0.047; stromal: p=0.025).ConclusionThe DDIR assay is strongly predictive of benefit from DNA-damaging neoadjuvant chemotherapy followed by surgical resection and is associated with a proinflammatory microenvironment in OAC.
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| 23. |
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| 24. |
- Mourikis, TP, et al.
(författare)
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Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3101-
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Tidskriftsartikel (refereegranskat)abstract
- The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.
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| 26. |
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| 27. |
- Barnes, DR, et al.
(författare)
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Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 114:1, s. 109-122
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.Methods483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.ResultsPRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.ConclusionsPopulation-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
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| 28. |
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| 29. |
- Hakkaart, C, et al.
(författare)
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Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1061-
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09–1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
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| 30. |
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| 31. |
- Ramilowski, JA, et al.
(författare)
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Functional annotation of human long noncoding RNAs via molecular phenotyping
- 2020
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Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 30:7, s. 1060-1072
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Tidskriftsartikel (refereegranskat)abstract
- Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.
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| 32. |
- Toldo, M, et al.
(författare)
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Enhancing early detection of neurological and developmental disorders and provision of intervention in low-resource settings in Uttar Pradesh, India: study protocol of the G.A.N.E.S.H. programme
- 2020
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 10:11, s. e037335-
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Tidskriftsartikel (refereegranskat)abstract
- Around 9% of India’s children under six are diagnosed with neurodevelopmental disorders. Low-resource, rural communities often lack programmes for early identification and intervention. The Prechtl General Movement Assessment (GMA) is regarded as the best clinical tool to predict cerebral palsy in infants <5 months. In addition, children with developmental delay, intellectual disabilities, late detected genetic disorders or autism spectrum disorder show abnormal general movements (GMs) during infancy. General Movement Assessment in Neonates for Early Identification and Intervention, Social Support and Health Awareness (G.A.N.E.S.H.) aims to (1) provide evidence as to whether community health workers can support the identification of infants at high-risk for neurological and developmental disorders and disabilities, (2) monitor further development in those infants and (3) initiate early and targeted intervention procedures.MethodsThis 3-year observational cohort study will comprise at least 2000 infants born across four districts of Uttar Pradesh, India. Community health workers, certified for GMA, video record and assess the infants’ GMs twice, that is, within 2 months after birth and at 3–5 months. In case of abnormal GMs and/or reduced MOSs, infants are further examined by a paediatrician and a neurologist. If necessary, early intervention strategies (treatment as usual) are introduced. After paediatric and neurodevelopmental assessments at 12–24 months, outcomes are categorised as normal or neurological/developmental disorders. Research objective (1): to relate the GMA to the outcome at 12–24 months. Research objective (2): to investigate the impact of predefined exposures. Research objective (3): to evaluate the interscorer agreement of GMA.Ethics and disseminationG.A.N.E.S.H. received ethics approval from the Indian Government Chief Medical Officers of Varanasi and Mirzapur and from the Ramakrishna Mission Home of Service in Varanasi. GMA is a worldwide used diagnostic tool, approved by the Ethics Committee of the Medical University of Graz, Austria (27-388 ex 14/15). Apart from peer-reviewed publications, we are planning to deploy G.A.N.E.S.H. in other vulnerable settings.
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| 36. |
- Kumar, Varun, et al.
(författare)
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Highly time-resolved chemical speciation and source apportionment of organic aerosol components in Delhi, India, using extractive electrospray ionization mass spectrometry
- 2022
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 22:11, s. 7739-7761
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, the Indian capital city of Delhi has been impacted by very high levels of air pollution, especially during winter. Comprehensive knowledge of the composition and sources of the organic aerosol (OA), which constitutes a substantial fraction of total particulate mass (PM) in Delhi, is central to formulating effective public health policies. Previous source apportionment studies in Delhi identified key sources of primary OA (POA) and showed that secondary OA (SOA) played a major role but were unable to resolve specific SOA sources. We address the latter through the first field deployment of an extractive electrospray ionization time-of-flight mass spectrometer (EESI-TOF) in Delhi, together with a high-resolution aerosol mass spectrometer (AMS). Measurements were conducted during the winter of 2018/19, and positive matrix factorization (PMF) was used separately on AMS and EESI-TOF datasets to apportion the sources of OA. AMS PMF analysis yielded three primary and two secondary factors which were attributed to hydrocarbon-like OA (HOA), biomass burning OA (BBOA-1 and BBOA-2), more oxidized oxygenated OA (MO-OOA), and less oxidized oxygenated OA (LO-OOA). On average, 40 % of the total OA mass was apportioned to the secondary factors. The SOA contribution to total OA mass varied greatly between the daytime (76.8 %, 10:00–16:00 local time (LT)) and nighttime (31.0 %, 21:00–04:00 LT). The higher chemical resolution of EESI-TOF data allowed identification of individual SOA sources. The EESI-TOF PMF analysis in total yielded six factors, two of which were primary factors (primary biomass burning and cooking-related OA). The remaining four factors were predominantly of secondary origin: aromatic SOA, biogenic SOA, aged biomass burning SOA, and mixed urban SOA. Due to the uncertainties in the EESI-TOF ion sensitivities, mass concentrations of EESI-TOF SOA-dominated factors were related to the total AMS SOA (i.e. MO-OOA + LO-OOA) by multiple linear regression (MLR). Aromatic SOA was the major SOA component during the daytime, with a 55.2 % contribution to total SOA mass (42.4 % contribution to total OA). Its contribution to total SOA, however, decreased to 25.4 % (7.9 % of total OA) during the nighttime. This factor was attributed to the oxidation of light aromatic compounds emitted mostly from traffic. Biogenic SOA accounted for 18.4 % of total SOA mass (14.2 % of total OA) during the daytime and 36.1 % of total SOA mass (11.2 % of total OA) during the nighttime. Aged biomass burning and mixed urban SOA accounted for 15.2 % and 11.0 % of total SOA mass (11.7 % and 8.5 % of total OA mass), respectively, during the daytime and 15.4 % and 22.9 % of total SOA mass (4.8 % and 7.1 % of total OA mass), respectively, during the nighttime. A simple dilution–partitioning model was applied on all EESI-TOF factors to estimate the fraction of observed daytime concentrations resulting from local photochemical production (SOA) or emissions (POA). Aromatic SOA, aged biomass burning, and mixed urban SOA were all found to be dominated by local photochemical production, likely from the oxidation of locally emitted volatile organic compounds (VOCs). In contrast, biogenic SOA was related to the oxidation of diffuse regional emissions of isoprene and monoterpenes. The findings of this study show that in Delhi, the nighttime high concentrations are caused by POA emissions led by traffic and biomass burning and the daytime OA is dominated by SOA, with aromatic SOA accounting for the largest fraction. Because aromatic SOA is possibly more toxic than biogenic SOA and primary OA, its dominance during the daytime suggests an increased OA toxicity and health-related consequences for the general public.
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| 37. |
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| 38. |
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| 39. |
- Samajdar, SS, et al.
(författare)
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Association between Polypharmacy and Cardiovascular Autonomic Function among Elderly Patients in an Urban Municipality Area of Kolkata, India: A Record-Based Cross-Sectional Study
- 2022
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Ingår i: Geriatrics (Basel, Switzerland). - : MDPI AG. - 2308-3417. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the association between polypharmacy and cardiovascular autonomic function among community-dwelling elderly patients having chronic diseases. Three hundred and twenty-one patients from an urban municipality area of Kolkata, India were studied in August 2022. The anticholinergic burden and cardiac autonomic function (Valsalva ratio, orthostatic hypotension, change in diastolic blood pressure after an isometric exercise, and heart rate variability during expiration and inspiration) were evaluated. Binary logistic regression analysis was performed to find out the association of polypharmacy and total anticholinergic burden with cardiac autonomic neuropathy. A total of 305 patients (age, 68.9 ± 3.4; 65.9% male) were included. Of these patients, 81 (26.6%) were on polypharmacy. Out of these 81 patients, 42 patients were on ninety-eight potential inappropriate medications. The anticholinergic burden and the proportion of patients with cardiac autonomic neuropathy were significantly higher among patients who were on polypharmacy than those who were not (8.1 ± 2.3 vs. 2.3 ± 0.9; p = 0.03 and 56.8% vs. 44.6%; p = 0.01). The presence of polypharmacy and a total anticholinergic burden of > 3 was significantly associated with cardiac autonomic neuropathy (aOR, 2.66; 95% CI, 0.91–3.98 and aOR, 2.51; 95% CI, 0.99–3.52, respectively). Thus, polypharmacy was significantly associated with cardiac autonomic neuropathy among community-dwelling elderly patients.
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| 40. |
- Wilhelmson, Anna S K, et al.
(författare)
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Testosterone is an endogenous regulator of BAFF and splenic B cell number
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Testosterone deficiency in men is associated with increased risk for autoimmunity and increased B cell numbers through unknown mechanisms. Here we show that testosterone regulates the cytokine BAFF, an essential survival factor for B cells. Male mice lacking the androgen receptor have increased splenic B cell numbers, serum BAFF levels and splenic Baff mRNA. Testosterone deficiency by castration causes expansion of BAFF-producing fibro-blastic reticular cells (FRCs) in spleen, which may be coupled to lower splenic noradrenaline levels in castrated males, as an alpha-adrenergic agonist decreases splenic FRC number in vitro. Antibody-mediated blockade of the BAFF receptor or treatment with the neurotoxin 6-hydroxydopamine revert the increased splenic B cell numbers induced by castration. Among healthy men, serum BAFF levels are higher in men with low testosterone. Our study uncovers a previously unrecognized regulation of BAFF by testosterone and raises important questions about BAFF in testosterone-mediated protection against autoimmunity.
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| 41. |
- Wood, Jack, 1997, et al.
(författare)
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Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology
- 2022
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 41:8
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Tidskriftsartikel (refereegranskat)abstract
- Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in mi-croglia-touching plaques, neighboring plaques, and far from plaques in an aged Alzheimer's mouse model with late plaque development. In 18-month-old APPNL-F/NL-F knockin mice, with and without the Alzheimer's disease risk mutation Trem2R47H/R47H, we report that expression of 38/55 PIGs have plaque-induced micro-glial upregulation, with a subset only upregulating in microglia directly contacting plaques. For seven PIGs, including Trem2, this upregulation is prevented in APPNL-F/NL-FTrem2R47H/R47H mice. These TREM2-depen-dent genes are all involved in phagocytic and degradative processes that we show correspond to a decrease in phagocytic markers and an increase in the density of small plaques in Trem2-mutated mice. Furthermore, despite the R47H mutation preventing increased Trem2 gene expression, TREM2 protein levels and micro-glial density are still marginally increased on plaques. Hence, both microglial contact with plaques and func-tioning TREM2 are necessary for microglia to respond appropriately to amyloid pathology.
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| 42. |
- Benitez, D. P., et al.
(författare)
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Knock-in models related to Alzheimer's disease: synaptic transmission, plaques and the role of microglia
- 2021
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Ingår i: Molecular Neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Microglia are active modulators of Alzheimer's disease but their role in relation to amyloid plaques and synaptic changes due to rising amyloid beta is unclear. We add novel findings concerning these relationships and investigate which of our previously reported results from transgenic mice can be validated in knock-in mice, in which overexpression and other artefacts of transgenic technology are avoided. Methods App(NL-F) and App(NL-G-F) knock-in mice expressing humanised amyloid beta with mutations in App that cause familial Alzheimer's disease were compared to wild type mice throughout life. In vitro approaches were used to understand microglial alterations at the genetic and protein levels and synaptic function and plasticity in CA1 hippocampal neurones, each in relationship to both age and stage of amyloid beta pathology. The contribution of microglia to neuronal function was further investigated by ablating microglia with CSF1R inhibitor PLX5622. Results Both App knock-in lines showed increased glutamate release probability prior to detection of plaques. Consistent with results in transgenic mice, this persisted throughout life in App(NL-F) mice but was not evident in App(NL-G-F) with sparse plaques. Unlike transgenic mice, loss of spontaneous excitatory activity only occurred at the latest stages, while no change could be detected in spontaneous inhibitory synaptic transmission or magnitude of long-term potentiation. Also, in contrast to transgenic mice, the microglial response in both App knock-in lines was delayed until a moderate plaque load developed. Surviving PLX5266-depleted microglia tended to be CD68-positive. Partial microglial ablation led to aged but not young wild type animals mimicking the increased glutamate release probability in App knock-ins and exacerbated the App knock-in phenotype. Complete ablation was less effective in altering synaptic function, while neither treatment altered plaque load. Conclusions Increased glutamate release probability is similar across knock-in and transgenic mouse models of Alzheimer's disease, likely reflecting acute physiological effects of soluble amyloid beta. Microglia respond later to increased amyloid beta levels by proliferating and upregulating Cd68 and Trem2. Partial depletion of microglia suggests that, in wild type mice, alteration of surviving phagocytic microglia, rather than microglial loss, drives age-dependent effects on glutamate release that become exacerbated in Alzheimer's disease.
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| 43. |
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| 45. |
- Feigin, Valery L., et al.
(författare)
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Global, regional, and national burden of stroke and its risk factors, 1990-2019 : a systematic analysis for the Global Burden of Disease Study 2019
- 2021
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Tidskriftsartikel (refereegranskat)abstract
- Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% [10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% [5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million [6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million [2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million [1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million [67.7-90.8] DALYs or 55.5% [48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million [22.3-48.6] DALYs or 24.3% [15.7-33.2]), high fasting plasma glucose (28.9 million [19.8-41.5] DALYs or 20.2% [13.8-29.1]), ambient particulate matter pollution (28.7 million [23.4-33.4] DALYs or 20.1% [16.6-23.0]), and smoking (25.3 million [22.6-28.2] DALYs or 17.6% [16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.
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| 46. |
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| 47. |
- Haslett, Sophie, 1988-, et al.
(författare)
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Nighttime NO emissions strongly suppress chlorine and nitrate radical formation during the winter in Delhi
- 2023
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Ingår i: Atmospheric Chemistry And Physics. - 1680-7316 .- 1680-7324. ; 23:16, s. 9023-9036
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Tidskriftsartikel (refereegranskat)abstract
- Atmospheric pollution in urban regions is highly influenced by oxidants due to their important role in the formation of secondary organic aerosol (SOA) and smog. These include the nitrate radical (NO3), which is typically considered a nighttime oxidant, and the chlorine radical (Cl), an extremely potent oxidant that can be released in the morning in chloride-rich environments as a result of nocturnal build-up of nitryl chloride (ClNO2). Chloride makes up a higher percentage of particulate matter in Delhi than has been observed anywhere else in the world, which results in Cl having an unusually strong influence in this city. Here, we present observations and model results revealing that atmospheric chemistry in Delhi exhibits an unusual diel cycle that is controlled by high concentrations of NO during the night. As a result of this, the formation of both NO3 and dinitrogen pentoxide (N2O5), a precursor of ClNO2 and thus Cl, are suppressed at night and increase to unusually high levels during the day. Our results indicate that a substantial reduction in nighttime NO has the potential to increase both nocturnal oxidation via NO(3 )and the production of Cl during the day.
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| 48. |
- Kamra, A. K., et al.
(författare)
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Atmospheric ions and new particle formation events at a tropical location, Pune, India
- 2015
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Ingår i: Quarterly Journal of the Royal Meteorological Society. - : Wiley. - 0035-9009 .- 1477-870X. ; 141:693, s. 3140-3156
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Tidskriftsartikel (refereegranskat)abstract
- Characteristics of small, intermediate and large ions and nanometre particles, and the influences of environmental conditions and local topography on the interactions of these ions and particles in the size range of 3.85-47.8 nm diameter are studied during new particle formation (NPF) events observed at Pune, India from 20 March to 23 May 2012. During the NPF events, the formation rate of 5 nm particles ranged from 3.5 to 13.9 cm(-3) s(-1)and growth rates of both positive and negative ions were greater than those of neutral particles. Total ion concentrations in this size range were approximately double on event days than on non-event days. The NPF events were generally preceded by 2-3 h periods of enhanced concentration of ions and aerosols (PECIA) which are associated with katabatic winds from the surrounding hill-slopes at our site. During PECIA, ions 8 nm diameter grew faster and attained mode diameters greater than those of neutral particles. PECIA provided the ions of sub-8 nm diameter and dramatically reduced the condensation sinks and thus contributed to the development of conditions conducive for NPF. During PECIA, total concentrations of the ions and particles become almost equal and the Boltzmann charge distribution breaks down. During NPF events, mode diameters of the ions and particles first steeply decreased accompanied by a steep increase in condensation sink but later gradually increased at identical rates. Observations of charging ratio of 3-4 nm particles being higher than the charge equilibrium value and non-observation of charge equilibrium for >5 nm ions and particles indicate occurrence of ion nucleation and/or advection during the PECIA.
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| 49. |
- Nazir, S. U., et al.
(författare)
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Differential expression of Ets-1 in breast cancer among North Indian population
- 2019
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Ingår i: Journal of Cellular Biochemistry. - : Wiley. - 0730-2312 .- 1097-4644. ; 120:9, s. 14552-14561
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is a highly aggressive disease contributing to high mortality rate among females across the globe owing to wide geographical variations, change in lifestyle along with rapid tumor growth, drug resistance, and high metastasis rate. To understand the molecular and genetic basis of breast cancer progression; we studied the role of E26 transformation-specific-1 (Ets-1) transcription factor which is implicated to have a role in carcinogenesis like invasion, metastasis, angiogenesis, etc. Our findings revealed an overexpression of Ets-1 gene in 75 breast cancer tumors as compared with their normal adjacent tissues. The findings significantly established a co-relation between Ets-1 expression in breast cancer tissue with hormonal receptor profiles and ductal-lobular histological subtypes in Indian population. In addition, a differential expression pattern of Ets-1 was observed between high, moderate, and low grades of breast cancer patients. The present study demonstrates a crucial role of Ets-1 transcription factor which may serve as a potential biomarker for breast carcinogenesis. © 2019 Wiley Periodicals, Inc.
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