| 1. |
- Feigin, Valery L., et al.
(author)
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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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In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 20:10, s. 795-820
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Journal article (peer-reviewed)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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| 2. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 3. |
- Rando, Halie M, et al.
(author)
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Identification and Development of Therapeutics for COVID-19
- 2021
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Other publication (other academic/artistic)abstract
- After emerging in China in late 2019, the novel Severe acute respiratory syndrome-like coronavirus 2 (SARS-CoV-2) spread worldwide and as of early 2021, continues to significantly impact most countries. Only a small number of coronaviruses are known to infect humans, and only two are associated with the severe outcomes associated with SARS-CoV-2: Severe acute respiratory syndrome-related coronavirus, a closely related species of SARS-CoV-2 that emerged in 2002, and Middle East respiratory syndrome-related coronavirus, which emerged in 2012. Both of these previous epidemics were controlled fairly rapidly through public health measures, and no vaccines or robust therapeutic interventions were identified. However, previous insights into the immune response to coronaviruses gained during the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have proved beneficial to identifying approaches to the treatment and prophylaxis of novel coronavirus disease 2019 (COVID-19). A number of potential therapeutics against SARS-CoV-2 and the resultant COVID-19 illness were rapidly identified, leading to a large number of clinical trials investigating a variety of possible therapeutic approaches being initiated early on in the pandemic. As a result, a small number of therapeutics have already been authorized by regulatory agencies such as the Food and Drug Administration (FDA) in the United States, and many other therapeutics remain under investigation. Here, we describe a range of approaches for the treatment of COVID-19, along with their proposed mechanisms of action and the current status of clinical investigation into each candidate. The status of these investigations will continue to evolve, and this review will be updated as progress is made.
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| 4. |
- Rando, Halie M., et al.
(author)
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Identification and development of therapeutics for COVID-19
- 2021
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In: mSystems. - 2379-5077. ; 6:6
-
Research review (peer-reviewed)abstract
- After emerging in China in late 2019, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread worldwide, and as of mid- 2021, it remains a significant threat globally. Only a few coronaviruses are known to infect humans, and only two cause infections similar in severity to SARS-CoV-2: Severe acute respiratory syndrome-related coronavirus, a species closely related to SARS-CoV-2 that emerged in 2002, and Middle East respiratory syndrome-related coronavirus, which emerged in 2012. Unlike the current pandemic, previous epidemics were controlled rapidly through public health measures, but the body of research investigating severe acute respiratory syndrome and Middle East respiratory syndrome has proven valuable for identifying approaches to treating and preventing novel coronavirus disease 2019 (COVID-19). Building on this research, the medical and scientific communities have responded rapidly to the COVID-19 crisis and identified many candidate therapeutics. The approaches used to identify candidates fall into four main categories: adaptation of clinical approaches to diseases with related pathologies, adaptation based on virological properties, adaptation based on host response, and data-driven identification (ID) of candidates based on physical properties or on pharmacological compendia. To date, a small number of therapeutics have already been authorized by regulatory agencies such as the Food and Drug Administration (FDA), while most remain under investigation. The scale of the COVID-19 crisis offers a rare opportunity to collect data on the effects of candidate therapeutics. This information provides insight not only into the management of coronavirus diseases but also into the relative success of different approaches to identifying candidate therapeutics against an emerging disease. IMPORTANCE The COVID-19 pandemic is a rapidly evolving crisis. With the worldwide scientific community shifting focus onto the SARS-CoV-2 virus and COVID-19, a large number of possible pharmaceutical approaches for treatment and prevention have been proposed. What was known about each of these potential interventions evolved rapidly throughout 2020 and 2021. This fast-paced area of research provides important insight into how the ongoing pandemic can be managed and also demonstrates the power of interdisciplinary collaboration to rapidly understand a virus and match its characteristics with existing or novel pharmaceuticals. As illustrated by the continued threat of viral epidemics during the current millennium, a rapid and strategic response to emerging viral threats can save lives. In this review, we explore how different modes of identifying candidate therapeutics have borne out during COVID-19.
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| 5. |
- Lopes, Emily W., et al.
(author)
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Lifestyle factors for the prevention of inflammatory bowel disease
- 2022
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In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288.
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To estimate the proportion of cases of Crohn's disease (CD) and ulcerative colitis (UC) that could be prevented by modifiable lifestyle factors.DESIGN: In a prospective cohort study of US adults from the Nurses' Health Study (NHS; n=72 290), NHSII (n=93 909) and Health Professionals Follow-up Study (HPFS; n=41 871), we created modifiable risk scores (MRS; 0-6) for CD and UC based on established lifestyle risk factors, and healthy lifestyle scores (HLS; 0-9) derived from American healthy lifestyle recommendations. We calculated the population attributable risk by comparing the incidence of CD and UC between low-risk (CD-MRS≤1, UC-MRS≤2, HLS≥7) and high-risk groups. We externally validated our findings in three European cohorts: the Swedish Mammography Cohort (n=37 275), Cohort of Swedish Men (n=40 810) and European Prospective Investigation into Cancer and Nutrition (n=404 144).RESULTS: Over 5 117 021 person-years of follow-up (NHS, HPFS: 1986-2016; NHSII: 1991-2017), we documented 346 CD and 456 UC cases. Adherence to a low MRS could have prevented 42.9% (95% CI 12.2% to 66.1%) of CD and 44.4% (95% CI 9.0% to 69.8%) of UC cases. Similarly, adherence to a healthy lifestyle could have prevented 61.1% (95% CI 16.8% to 84.9%) of CD and 42.2% (95% CI 1.7% to 70.9%) of UC cases. In our validation cohorts, adherence to a low MRS and healthy lifestyle could have, respectively, prevented 43.9%-51.2% and 48.8%-60.4% of CD cases and 20.6%-27.8% and 46.8%-56.3% of UC cases.CONCLUSIONS: Across six US and European cohorts, a substantial burden of inflammatory bowel diseases risk may be preventable through lifestyle modification.
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| 6. |
- Wingenbach, T. S. H., et al.
(author)
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Incongruence between observers’ and observed facial muscle activation reduces recognition of emotional facial expressions from video stimuli
- 2018
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In: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 9:JUN
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Journal article (peer-reviewed)abstract
- According to embodied cognition accounts, viewing others’ facial emotion can elicit the respective emotion representation in observers which entails simulations of sensory, motor, and contextual experiences. In line with that, published research found viewing others’ facial emotion to elicit automatic matched facial muscle activation, which was further found to facilitate emotion recognition. Perhaps making congruent facial muscle activity explicit produces an even greater recognition advantage. If there is conflicting sensory information, i.e., incongruent facial muscle activity, this might impede recognition. The effects of actively manipulating facial muscle activity on facial emotion recognition from videos were investigated across three experimental conditions: (a) explicit imitation of viewed facial emotional expressions (stimulus-congruent condition), (b) pen-holding with the lips (stimulus-incongruent condition), and (c) passive viewing (control condition). It was hypothesised that (1) experimental condition (a) and (b) result in greater facial muscle activity than (c), (2) experimental condition (a) increases emotion recognition accuracy from others’ faces compared to (c), (3) experimental condition (b) lowers recognition accuracy for expressions with a salient facial feature in the lower, but not the upper face area, compared to (c). Participants (42 males, 42 females) underwent a facial emotion recognition experiment (ADFES-BIV) while electromyography (EMG) was recorded from five facial muscle sites. The experimental conditions’ order was counter-balanced. Pen-holding caused stimulus-incongruent facial muscle activity for expressions with facial feature saliency in the lower face region, which reduced recognition of lower face region emotions. Explicit imitation caused stimulus-congruent facial muscle activity without modulating recognition. Methodological implications are discussed.
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| 7. |
- Gõmez-Elvira, Javier, et al.
(author)
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Curiosity's rover environmental monitoring station : Overview of the first 100 sols
- 2014
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In: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:7, s. 1680-1688
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Journal article (peer-reviewed)abstract
- In the first 100 Martian solar days (sols) of the Mars Science Laboratory mission, the Rover Environmental Monitoring Station (REMS) measured the seasonally evolving diurnal cycles of ultraviolet radiation, atmospheric pressure, air temperature, ground temperature, relative humidity, and wind within Gale Crater on Mars. As an introduction to several REMS-based articles in this issue, we provide an overview of the design and performance of the REMS sensors and discuss our approach to mitigating some of the difficulties we encountered following landing, including the loss of one of the two wind sensors. We discuss the REMS data set in the context of other Mars Science Laboratory instruments and observations and describe how an enhanced observing strategy greatly increased the amount of REMS data returned in the first 100 sols, providing complete coverage of the diurnal cycle every 4 to 6 sols. Finally, we provide a brief overview of key science results from the first 100 sols. We found Gale to be very dry, never reaching saturation relative humidities, subject to larger diurnal surface pressure variations than seen by any previous lander on Mars, air temperatures consistent with model predictions and abundant short timescale variability, and surface temperatures responsive to changes in surface properties and suggestive of subsurface layering. Key Points Introduction to the REMS results on MSL mission Overiview of the sensor information Overview of operational constraints
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| 8. |
- Rando, Halie M, et al.
(author)
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Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through analysis of Viral Genomics and Structure
- 2021
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Other publication (other academic/artistic)abstract
- The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world infecting tens of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease.
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| 9. |
- Rando, Halie M, et al.
(author)
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Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure
- 2021
-
In: mSystems. - 2379-5077. ; 6:5
-
Research review (peer-reviewed)abstract
- The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).
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| 10. |
- Rivas, Manuel A., et al.
(author)
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A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis
- 2016
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In: Nature Communications. - London, United Kingdom : Nature Publishing Group. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.
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| 11. |
- Turner, Lucy M., et al.
(author)
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Pathogenic marine microbes influence the effects of climate change on a commercially important tropical bivalve
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Journal article (peer-reviewed)abstract
- There is growing evidence that climate change will increase the prevalence of toxic algae and harmful bacteria, which can accumulate in marine bivalves. However, we know little about any possible interactions between exposure to these microorganisms and the effects of climate change on bivalve health, or about how this may affect the bivalve toxin-pathogen load. In mesocosm experiments, mussels, Perna viridis, were subjected to simulated climate change (warming and/or hyposalinity) and exposed to harmful bacteria and/or toxin-producing dinoflagellates. We found significant interactions between climate change and these microbes on metabolic and/or immunobiological function and toxin-pathogen load in mussels. Surprisingly, however, these effects were virtually eliminated when mussels were exposed to both harmful microorganisms simultaneously. This study is the first to examine the effects of climate change on determining mussel toxin-pathogen load in an ecologically relevant, multi-trophic context. The results may have considerable implications for seafood safety.
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| 12. |
- Anande, Govardhan, et al.
(author)
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RNA Splicing Alterations Induce a Cellular Stress Response Associated with Poor Prognosis in Acute Myeloid Leukemia
- 2020
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 26:14, s. 3597-3607
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Journal article (peer-reviewed)abstract
- Purpose: RNA splicing is a fundamental biological process that generates protein diversity from a finite set of genes. Recurrent somatic mutations of splicing factor genes are common in some hematologic cancers but are relatively uncommon in acute myeloid leukemia (AML, < 20% of patients). We examined whether RNA splicing differences exist in AML, even in the absence of splicing factor mutations.Experimental Design: We developed a bioinformatics pipeline to study alternative RNA splicing in RNA-sequencing data from large cohorts of patients with AML.Results: We have identified recurrent differential alternative splicing between patients with poor and good prognosis. These splicing events occurred even in patients without any discernible splicing factor mutations. Alternative splicing recurrently occurred in genes with specific molecular functions, primarily related to protein translation. Developing tools to predict the functional impact of alternative splicing on the translated protein, we discovered that approximately 45% of the splicing events directly affected highly conserved protein domains. Several splicing factors were themselves misspliced and the splicing of their target transcripts were altered. Studying differential gene expression in the same patients, we identified that alternative splicing of protein translation genes in ELNAdv patients resulted in the induction of an integrated stress response and upregulation of inflammation-related genes. Finally, using machine learning techniques, we identified a splicing signature of four genes which refine the accuracy of existing risk prognosis schemes and validated it in a completely independent cohort.Conclusions: Our discoveries therefore identify aberrant alternative splicing as a molecular feature of adverse AML with clinical relevance.
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| 13. |
- Ashwin, M.J., et al.
(author)
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The bonding of CAs acceptors in InxGa1-xAs grown by chemical beam epitaxy using carbon tetrabromide as the source of carbon
- 1996
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In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 80:12, s. 6754-6760
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Journal article (peer-reviewed)abstract
- InxGa1-xAs layers (0≤x≤0.37) doped with carbon (>1020 cm-3) were grown on semi-insulating GaAs substrates by chemical beam epitaxy using carbon tetrabromide (CBr4) as the dopant source. Hall measurements imply that all of the carbon was present as CAs for values x up to 0.15. The C acceptors were passivated by exposing samples to a radio frequency hydrogen plasma for periods of up to 6 h. The nearest-neighbor bonding configurations of CAs were investigated by studying the nondegenerate antisymmetric hydrogen stretch mode (A-1 symmetry) and the symmetric XH mode (A+1 symmetry) of the H-CAs pairs using IR absorption and Raman scattering, respectively. Observed modes at 2635 and 450 cm-1 had been assigned to passivated Ga4CAs clusters. New modes at 2550 and 430 cm-1 increased in strength with increasing values of x and are assigned to passivated InGa3CAs clusters. These results were compared with ab initio local density functional theory. Modes due to AlInGaCAs clusters were detected in samples containing grown in Al and In. These results demonstrate that for InGaAs, CBr4 is an efficient C doping source since both In-CAs bonds as well as Ga-CAs bonds are formed, whereas there is no evidence for the formation of In-CAs bonds in samples doped with C derived from trimethylgallium or solid sources
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| 14. |
- Bassan, Paul, et al.
(author)
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The inherent problem of transflection-mode infrared spectroscopic microscopy and the ramifications for biomedical single point and imaging applications.
- 2013
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In: The Analyst. - : Royal Society of Chemistry (RSC). - 1364-5528 .- 0003-2654. ; 138:1, s. 144-57
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Journal article (peer-reviewed)abstract
- Transflection-mode FTIR spectroscopy has become a popular method of measuring spectra from biomedical and other samples due to the relative low cost of substrates compared to transmission windows, and a higher absorbance due to a double pass through the same sample approximately doubling the effective path length. In this publication we state an optical description of samples on multilayer low-e reflective substrates. Using this model we are able to explain in detail the so-called electric-field standing wave effect and rationalise the non-linear change in absorbance with sample thickness. The ramifications of this non-linear change, for imaging and classification systems, where a model is built from tissue sectioned at a particular thickness and compared with tissue of a different thickness are discussed. We show that spectra can be distorted such that classification fails leading to inaccurate tissue segmentation which may have subsequent implications for disease diagnostics applications.
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| 15. |
- Bayani, Amirhossein, et al.
(author)
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The influence by substrate morphology on the Rashba band splitting in graphene
- 2020
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In: Results in Physics. - : Elsevier. - 2211-3797. ; 17
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Journal article (peer-reviewed)abstract
- The influence of substrate morphology on the Rashba band splitting at the Dirac point of graphene, has been theoretically investigated. More specifically, the possibility for this splitting to be caused by spin–orbit coupling (with the heavy metal substrate) was of a special interest to study. The model system consisted of a 4H-SiC (0 0 0 1)/graphene interface, with an intercalated metal layer (Ag and Au, respectively). These intercalating metal layers were built with two different types of morphologies; either flat or buckled (with different buckling positions). The results show that depending on the position of the buckled metal atom, the size of the bandgap and band splitting (at the Dirac point of graphene) will either increase (or decrease). Moreover, the enlargement of the buckling size was also shown to affect the electronic properties of graphene (i.e., by increasing the bandgap). The sizes of the bandgaps and band splitting for the different intercalating metals (Ag and Au), were also found to be different. Spin-projected band structures was also implemented in the present study, with the purpose to show the spin-texture of graphene. It was thereby shown that the spins pined to the x and y spin components for most of the cases.
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| 16. |
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| 17. |
- Burke, Kristin E., et al.
(author)
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Identification of Menopausal and Reproductive Risk Factors for Microscopic Colitis-Results From the Nurses' Health Study
- 2018
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In: Gastroenterology. - : Saunders Elsevier. - 0016-5085 .- 1528-0012. ; 155:6, s. 1764-1775
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Microscopic colitis is a chronic inflammatory disorder of the colon primarily affecting postmenopausal women. However, the relation between hormonal determinants, including reproductive and menopausal factors, and risk of microscopic colitis has yet to be characterized.METHODS: We collected data from 227,766 women who participated in the Nurses' Health Study (NHS) and the NHSII without a baseline history of microscopic colitis. Reproductive and menopausal factors were assessed in 1988 in the NHS and 1989 in the NHSII and updated biennially. Cases of microscopic colitis were confirmed through review of pathology records. We used Cox proportional hazards modeling to estimate hazard ratios and 95% confidence intervals.RESULTS: Through 2014 in the NHS and 2015 in the NHSII, we confirmed 275 incident cases of microscopic colitis over 5,147,282 person-years. Compared with never use, current use of menopausal hormone therapy was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 2.64; 95% confidence interval 1.78-3.90). The risk increased with longer duration of use (P for trend < .0001) and decreased after discontinuation (P for trend = .002). The association did not differ according to disease subtype (P for heterogeneity = .34). Similarly, ever use of oral contraceptives was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 1.57; 95% confidence interval 1.16-2.13). There were no associations between age at menarche, parity, age at first birth, age at menopause, or menopause type and incident microscopic colitis.CONCLUSIONS: In 2 large prospective cohort studies, we observed an association between exogenous hormone use and incident microscopic colitis. Further studies are needed to determine the mechanisms underlying these associations.
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| 18. |
- Burke, Kristin E., et al.
(author)
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Smoking is Associated with an Increased Risk of Microscopic Colitis : Results From Two Large Prospective Cohort Studies of US Women
- 2018
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In: Journal of Crohn's & Colitis. - : Crohn's & Colitis Foundation of Canada. - 1873-9946 .- 1876-4479. ; 12:5, s. 559-567
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Journal article (peer-reviewed)abstract
- Introduction: Long-term data on the influence of smoking on risk of microscopic colitis are limited. We therefore sought to examine and characterize the association between smoking and risk of incident microscopic colitis in two large prospective cohorts of women.Methods: We conducted a prospective study of 231,015 women enrolled in the Nurses' Health Study (NHS) and NHSII. Information regarding smoking, other lifestyle factors, and medications were collected biennially from 1976 to 2012 in NHS and 1989 to 2013 in NHSII. Incident cases of microscopic colitis were confirmed through physician medical record review. We used Cox proportional hazards modeling to examine the association between smoking and risk of microscopic colitis.Results: We documented 166 incident cases of microscopic colitis over 6,122,779 person-years of follow up. Compared to non-smokers, the multivariable-adjusted hazard ratio (HR) for microscopic colitis was 2.52 (95% CI 1.59 - 4.00) amongst current smokers and 1.54 (95% CI 1.09 - 2.17) amongst past smokers. The risk increased with higher pack-years of smoking (Ptrend = 0.001) and diminished following smoking cessation (Ptrend = 0.017). Current smoking appeared to be more strongly associated with risk of collagenous colitis (3.68; 95% CI 1.94 - 6.97) than lymphocytic colitis (HR 1.71; 95% CI 0.83 - 3.53).Conclusion: In two large prospective cohort studies, we observed an association between current smoking and risk of microscopic colitis. Risk of microscopic colitis appeared to increase with higher pack-years and diminish following smoking cessation. Future studies focused on characterizing the biologic mechanisms underlying these associations are warranted.
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| 19. |
- Caron, Bénédicte, et al.
(author)
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IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis : the PROCTRIAL Consensus
- 2022
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In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:11, s. 2169-2627.e1
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the PROCTRIAL (Definition and endpoints for ulcerative PROCtitis in clinical TRIALs) initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults.METHODS: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters.RESULTS: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity is proposed. Secondary endpoints which should be evaluated include endoscopic remission, histological remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life.CONCLUSION: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the PROCTRIAL consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.
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| 20. |
- Carvalho, A., et al.
(author)
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Identification of the local vibrational modes of small nitrogen clusters in dilute GaAsN
- 2007
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In: Physica. B, Condensed matter. - : Elsevier BV. - 0921-4526 .- 1873-2135. ; 401-402, s. 339-342
-
Journal article (peer-reviewed)abstract
- Ultra-high-resolution infra-red local vibrational mode (IR LVM) spectroscopy measurements together with density-functional calculations have been used to identify the signatures of close substitutional nitrogen (NAs) pairs in GaAs1 - x Nx alloys with concentrations of x < 0.025. We show that the presence of sub-peaks close to the NAs absorption band can be attributed to nitrogen pairs up to fourth neighbor position. Additionally, we suggest that the nitrogen pairs which give rise to the deepest levels below the conduction band edge are the first to be removed upon annealing
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| 21. |
- Di Gravio, Chiara, et al.
(author)
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The Association of Maternal Age With Fetal Growth and Newborn Measures : The Mumbai Maternal Nutrition Project (MMNP)
- 2019
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In: Reproductive Sciences. - : SAGE PUBLICATIONS INC. - 1933-7191 .- 1933-7205. ; 26:7, s. 918-927
-
Journal article (peer-reviewed)abstract
- Background: Young maternal age is associated with poorer birth outcomes, but the mechanisms are incompletely understood. Using data from a prospective cohort of pregnant women living in Mumbai slums, India, we tested whether lower maternal age was associated with adverse fetal growth.Methods: Fetal crown-rump length (CRL) was recorded at a median (interquartile range, IQR) of 10 weeks' gestation (9-10 weeks). Head circumference (HC), biparietal diameter (BPD), femur length (FL), and abdominal circumference (AC) were recorded at 19 (19-20) and 29 (28-30) weeks. Newborns were measured at a median (IQR) of 2 days (1-3 days) from delivery. Gestation was assessed using prospectively collected menstrual period dates.Results: The sample comprised 1653 singleton fetuses without major congenital abnormalities, of whom 1360 had newborn measurements. Fetuses of younger mothers had smaller CRL (0.01 standard deviation [SD] per year of maternal age; 95% confidence interval CI: 0.00-0.02(1); P = .04), and smaller HC, FL, and AC at subsequent visits. Fetal growth of HC (0.04 cm; 95% CI: 0.02-0.05; P < .001), BPD (0.01 cm; 95% CI: 0.00-0.01; P = .009), FL (0.04 cm; 95% CI: 0.02-0.06; P < .001), and AC (0.01 cm; 95% CI: 0.00-0.01; P = .003) up to the third trimester increased with maternal age. Skinfolds, head, and mid-upper arm circumferences were smaller in newborns of younger mothers. Adjusting for maternal prepregnancy socioeconomic status, body mass index, height, and parity attenuated the associations between maternal age and newborn size but did not change those with fetal biometry.Conclusion: Fetuses of younger mothers were smaller from the first trimester onward and grew slower, independently of known confounding factors.
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| 22. |
- Erhardsson, Mikael, et al.
(author)
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Acyl ghrelin increases cardiac output while preserving right ventricular-pulmonary arterial coupling in heart failure
- 2023
-
In: ESC Heart Failure. - : John Wiley & Sons. - 2055-5822.
-
Journal article (peer-reviewed)abstract
- AIM: Acyl ghrelin increases cardiac output (CO) in heart failure with reduced ejection fraction (HFrEF). This could impair the right ventricular-pulmonary arterial coupling (RVPAC), both through an increased venous return and right ventricular afterload. We aim to investigate if acyl ghrelin increases CO with or without worsening the right-sided haemodynamics in HFrEF assessed by RVPAC.METHODS AND RESULTS: The Karolinska Acyl ghrelin Trial was a randomized double-blind placebo-controlled trial of acyl ghrelin versus placebo (120-min intravenous infusion) in HFrEF. RVPAC was assessed echocardiographically at baseline and 120 min. ANOVA was used for difference in change between acyl ghrelin versus placebo, adjusted for baseline values. Of the 30 randomized patients, 22 had available RVPAC (acyl ghrelin n = 12, placebo n = 10). Despite a 15% increase in CO in the acyl ghrelin group (from 4.0 (3.5-4.6) to 4.6 (3.9-6.1) L/min, P = 0.003), RVPAC remained unchanged; 5.9 (5.3-7.6) to 6.3 (4.8-7.5) mm·(m/s)-1 , P = 0.372, while RVPAC was reduced in the placebo group, 5.2 (4.3-6.4) to 4.8 (4.2-5.8) mm·(m/s)-1 , P = 0.035. Comparing change between groups, CO increased in the acyl ghrelin group versus placebo (P = 0.036) while RVPAC and the right ventricular pressure gradient remained unchanged.CONCLUSION: Treatment with acyl ghrelin increases CO while preserving or even improving RVPAC in HFrEF, possibly due to increased contractility, reduced PVR and/or reduced left sided filling pressures. These potential effects strengthen the role of acyl ghrelin therapy in HFrEF with right ventricular failure.
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| 23. |
- Hassler, Donald M., et al.
(author)
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Mars’ surface radiation environment measured with the Mars Science Laboratory’s Curiosity Rover
- 2014
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 343:6169
-
Journal article (peer-reviewed)abstract
- The Radiation Assessment Detector (RAD) on the Mars Science Laboratory’s Curiosity rover began making detailed measurements of the cosmic ray and energetic particle radiation environment on the surface of Mars on 7 August 2012. We report and discuss measurements of the absorbed dose and dose equivalent from galactic cosmic rays and solar energetic particles on the martian surface for ~300 days of observations during the current solar maximum. These measurements provide insight into the radiation hazards associated with a human mission to the surface of Mars and provide an anchor point with which to model the subsurface radiation environment, with implications for microbial survival times of any possible extant or past life, as well as for the preservation of potential organic biosignatures of the ancient martian environment.
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| 24. |
- Kishore, M. R. Ashwin, et al.
(author)
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Theoretical investigation on BeN2 monolayer for an efficient bifunctional water splitting catalyst
- 2020
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Journal article (peer-reviewed)abstract
- The search for an active, stable, and abundant semiconductor-based bifunctional catalysts for solar hydrogen production will make a substantial impact on the sustainable development of the society that does not rely on fossil reserves. The photocatalytic water splitting mechanism on a BeN2 monolayer has here been investigated by using state-of-the-art density functional theory calculations. For all possible reaction intermediates, the calculated changes in Gibbs free energy showed that the oxygen evolution reaction will occur at, and above, the potential of 2.06 V (against the NHE) as all elementary steps are exergonic. In the case of the hydrogen evolution reaction, a potential of 0.52 V, or above, was required to make the reaction take place spontaneously. Interestingly, the calculated valence band edge and conduction band edge positions for a BeN2 monolayer are located at the potential of 2.60 V and 0.56 V, respectively. This indicates that the photo-generated holes in the valence band can oxidize water to oxygen, and the photo-generated electrons in the conduction band can spontaneously reduce water to hydrogen. Hence, the results from the present theoretical investigation show that the BeN2 monolayer is an efficient bifunctional water-splitting catalyst, without the need for any co-catalyst.
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| 25. |
- Kishore, M. R. Ashwin, et al.
(author)
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Two-Dimensional CdX/C2N (X = S, Se) Heterostructures as Potential Photocatalysts for Water Splitting : A DFT Study
- 2020
-
In: ACS Omega. - : AMER CHEMICAL SOC. - 2470-1343. ; 5:37, s. 23762-23768
-
Journal article (peer-reviewed)abstract
- Global environmental issues, in addition to limited fossil fuel resources, are being addressed by quests in search of efficient visible-light-driven water splitting catalysts for hydrogen production. The photocatalytic water splitting activities of CdX/C2N (X = S, Se) heterostructures have been investigated here using hybrid density functional theory calculations. The calculated band gaps of CdS/C2N and CdSe/C2N heterostructures are 1.48 and 2.12 eV, respectively. These are ideal band gap values that make possible harvesting of more visible light from the solar spectrum, which will result in high solar to energy conversion efficiencies. Charge density difference analysis shows that the charge redistributions mainly occur in the interface regions and that the charges transfer from the C-2N to CdX layers. It is interesting to note that the CdX/C2N heterostructures possess a type-II band alignment, where the relative band alignment of the C2N and CdX monolayers promotes a spatial separation of the electrons (that resides in C2N) and holes (that resides in CdX). Importantly, the band edges of the heterostructures straddle the water redox potential under different pH conditions. This study demonstrates that the CdS/C2N and CdSe/C-2N heterostructures are suitable materials to split water (from various sources) in different ranges of pH values.
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| 26. |
- Li, Dalin, et al.
(author)
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A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn's Disease and Human Gut Microbiome Composition
- 2016
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In: Gastroenterology. - : Saunders Elsevier. - 0016-5085 .- 1528-0012. ; 151:4, s. 724-732
-
Journal article (peer-reviewed)abstract
- Background & Aims: Genome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA).Methods: Genotyping was performed in 10,523 IBD cases and 5726 non-IBD controls. There were 91,713 functional single-nucleotide polymorphism loci in coding regions analyzed. A novel identified association was replicated further in 2 independent cohorts. We further examined the association of the identified single-nucleotide polymorphism with microbiota from 338 mucosal lavage samples in the Mucosal Luminal Interface cohort measured using 16S sequencing.Results: We identified an association between CD and a missense variant encoding alanine or threonine at position 391 in the zinc transporter solute carrier family 39, member 8 protein (SLC39A8 alanine 391 threonine, rs13107325) and replicated the association with CD in 2 replication cohorts (combined meta-analysis P = 5.55 × 10(-13)). This variant has been associated previously with distinct phenotypes including obesity, lipid levels, blood pressure, and schizophrenia. We subsequently determined that the CD risk allele was associated with altered colonic mucosal microbiome composition in both healthy controls (P = .009) and CD cases (P = .0009). Moreover, microbes depleted in healthy carriers strongly overlap with those reduced in CD patients (P = 9.24 × 10(-16)) and overweight individuals (P = 6.73 × 10(-16)).Conclusions: Our results suggest that an SLC39A8-dependent shift in the gut microbiome could explain its pleiotropic effects on multiple complex diseases including CD.
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| 27. |
- Liu, Po-Hong, et al.
(author)
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Dietary Gluten Intake and Risk of Microscopic Colitis Among US Women without Celiac Disease : A Prospective Cohort Study
- 2019
-
In: American Journal of Gastroenterology. - : Blackwell Publishing. - 0002-9270 .- 1572-0241. ; 114:1, s. 127-134
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: Microscopic colitis is a common cause of chronic watery diarrhea among the elderly. Although the prevalence of celiac disease appears to be higher in patients with microscopic colitis, the relationship between dietary gluten intake and risk of microscopic colitis among individuals without celiac disease has not been explored.METHODS: We conducted a prospective study of 160,744 US women without celiac disease enrolled in the Nurses' Health Study (NHS) and the NHSII. Dietary gluten intake was estimated using validated food frequency questionnaires every 4 years. Microscopic colitis was confirmed through medical records review. We used Cox proportional hazard modeling to estimate the multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI).RESULTS: We documented 219 incident cases of microscopic colitis over more than 20 years of follow-up encompassing 3,716,718 person-years (crude incidence rate: 5.9/100,000 person-years) in NHS and NHSII. Dietary gluten intake was not associated with risk of microscopic colitis (Ptrend = 0.88). Compared to individuals in the lowest quintile of energy-adjusted gluten intake, the adjusted HR of microscopic colitis was 1.18 (95% CI: 0.77-1.78) for the middle quintile and 1.03 (95% CI: 0.67-1.58) for the highest quintile. Additional adjustment for primary dietary sources of gluten including refined and whole grains did not materially alter the effect estimates (All Ptrend ≥ 0.69). The null association did not differ according to lymphocytic or collagenous subtypes (Pheterogeneity = 0.72) and was not modified by age, smoking status, or body mass index (All Pinteraction ≥ 0.17).CONCLUSION: Dietary gluten intake during adulthood was not associated with risk of microscopic colitis among women without celiac disease.
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| 28. |
- Liu, Po-Hong, et al.
(author)
-
Obesity and Weight Gain Since Early Adulthood Are Associated With a Lower Risk of Microscopic Colitis
- 2019
-
In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 17:12, s. 2523-2532
-
Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Obesity promotes intestinal inflammation and might contribute to the pathogenesis of inflammatory bowel disease. We examined the association between obesity and risk of microscopic colitis in a prospective cohort study.METHODS: We collected data from 192,101 women enrolled in the Nurses' Health Study (NHS) (from 1986 through 2014) or the NHSII (from 1991 through 2015). Anthropomorphic and lifestyle information were self-reported biennially. Obesity was defined using body mass index (BMI). Microscopic colitis was confirmed by review of medical records. We used Cox proportional hazard models to estimate adjusted hazard ratios (aHRs) and 95% CIs. RESULTS: Among the participants in the NHS and NHSII, we confirmed 244 cases of microscopic colitis during 4,223,868 person-years of follow-up evaluation. Higher BMI was associated inversely with risk of microscopic colitis (Ptrend < .001). Compared with women with BMIs ranging from 18.5 to 20.9 kg/m(2), the aHRs were 0.61 (95% CI, 0.41-0.91) for overweight women (BMI, 2529.9 kg/m(2)) and 0.50 (95% CI, 0.32-0.79) for obese women (BMI >= 30 kg/m(2)). The aHR for each 5-kg/m(2) increase in BMI was 0.79 (95% CI, 0.69-0.90). Weight gain since early adulthood (age, 18 y) also was associated inversely with risk of microscopic colitis (Ptrend = .001). The aHR for each 10-kg weight gain since early adulthood was 0.85 (95% CI, 0.77-0.94). The associations were not modified by age, cohort, physical activity, or smoking status (all Pinteraction >= .26).CONCLUSIONS: Unlike many other immune- and metabolic-related disorders, obesity and weight gain since early adulthood were associated with a lower risk of microscopic colitis, based on an analysis of participants in the NHS and NHSII.
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| 29. |
- Lopes, Emily W., et al.
(author)
-
Dietary Gluten Intake Is Not Associated With Risk of Inflammatory Bowel Disease in US Adults Without Celiac Disease
- 2022
-
In: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:2, s. 303-313.e6
-
Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Diet is thought to play a role in the development of inflammatory bowel disease (IBD), though the relationship between gluten intake and risk of IBD has not been explored. The aim of this study was to determine the relationship between gluten intake and risk of incident Crohn's disease (CD) and ulcerative colitis (UC).METHODS: We performed a prospective cohort study of 208,280 US participants from the Nurses' Health Study (NHS; 1986-2016), NHSII (1991-2017), and Health Professionals Follow-up Study (1986-2016) who did not have IBD at baseline or celiac disease, and who completed semi-quantitative food frequency questionnaires. We used Cox proportional hazards modeling to estimate the risk of IBD according to quintiles of cumulative average energy-adjusted dietary gluten intake over follow-up period.RESULTS: We documented 337 CD cases and 447 UC cases over 5,115,265 person-years of follow-up evaluation. Dietary gluten intake was not associated with risk of IBD. Compared with participants in the lowest quintile of gluten intake, the adjusted hazard ratios and 95% CIs for participants in the highest quintile of gluten intake were 1.16 (95% CI, 0.82-1.64; P-trend = .41) for CD and 1.04 (95% CI, 0.75-1.44; P-trend = .64) for UC. Adjusting for primary sources of gluten intake did not materially change our estimates.CONCLUSIONS: In three large adult US prospective cohorts, gluten intake was not associated with risk of CD or UC. Our findings are reassuring at a time when consumption of gluten has been increasingly perceived as a trigger for chronic gastrointestinal diseases.
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| 30. |
- Mahidhar, G. D. P., et al.
(author)
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Understanding of Incipient discharges in Transformer Insulation by reconstruction of Digital Twins for the discharges using Generative Adversarial Networks
- 2021
-
In: 2021 Ieee Electrical Insulation Conference (Eic). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 631-634
-
Conference paper (peer-reviewed)abstract
- Partial discharge (PD) monitoring is one of the diagnostic technique adopted for identifying the variety of defects in transformer insulation. Ultra high frequency (UHF) technique is gaining importance in PD monitoring applications of transformer due to various advantages. Different type of incipient discharges arose from defects in transformer insulation that needs to be identified. In an actual test site there can be noises that can hinder data acquisition and defect identification can become difficult. By using artificially reconstructed signals of known practically occurring defect models, the loss in data can be overcome. In the present study, Deep Convolutional Generative Adversarial Networks (DCGAN) technique is adopted to reconstruct the UHF partial discharge signals with high fidelity. Time-Frequency characteristics of the signals were used to build the DCGAN network and the reconstructed UHF signals are evaluated by studying the frequency characteristics of the generated signal.
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| 31. |
- Niccum, Blake, et al.
(author)
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Alcohol Consumption is Associated With An Increased Risk of Microscopic Colitis : Results From 2 Prospective US Cohort Studies
- 2022
-
In: Inflammatory Bowel Diseases. - : Lippincott-Raven Publishers. - 1078-0998 .- 1536-4844. ; 28:8, s. 1151-1159
-
Journal article (peer-reviewed)abstract
- Background: No dietary factors have yet been shown to conclusively impact the incidence of microscopic colitis (MC). Here, we sought to examine the relationship between alcohol intake and the risk of MC.Methods: We conducted a prospective cohort study of 209,902 participants (age range, 28.5-66.7 years) enrolled in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). Validated data on alcohol consumption were collected at baseline in 1986 in the NHS and 1991 in the NHSII and updated every 4 years. Diagnoses of MC were confirmed via review of histopathology data. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).Results: Through 2016 in the NHS and 2017 in the NHSII, we confirmed 352 incident cases of MC over 4,994,324 person-years. Higher alcohol consumption was associated with an increased risk of MC (P-trend < .001). Compared to non-users, the aHRs of MC were 1.20 (95% CI, 0.86-1.67) for consumers of 0.1-4.9 g/day of alcohol, 1.90 (95% CI, 1.34-2.71) for consumers of 5-14.9 g/day, and 2.31 (95% CI, 1.54-3.46) for consumers of >= 15 g/day. The associations were consistent across the histologic subtypes of collagenous and lymphocytic colitis (P-heterogeneity = .523). When stratified by alcohol type, the risk according to every 2 servings/week appeared to be strongest with consumption of wine (aHR, 1.08; 95% CI, 1.04-1.12) as compared to beer (aHR, 1.01; 95% CI, 0.91-1.12) or liquor (aHR, 1.00; 95% CI, 0.92-1.09).Conclusions: Alcohol consumption was associated with an increased risk of MC. Further studies are needed to determine the mechanism underlying these associations, as well as the impact of reducing alcohol intake in patients with MC.
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| 32. |
- Turner, Andrew D., et al.
(author)
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Assessing the presence of marine toxins in bivalve molluscs from southwest India
- 2017
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In: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 140, s. 147-156
-
Journal article (peer-reviewed)abstract
- © 2017 Elsevier Ltd The south west coast of India has been showing a steady increase in shellfish cultivation both for local consumption and fishery export, over recent years. Perna viridis and Crassostrea madrasensis are two species of bivalve molluscs which grow in some selected regions of southern Karnataka, close to the city of Mangalore. In the early 1980s, shellfish consumers in the region were affected by intoxication from Paralytic Shellfish Poison present in local bivalves (clams and oysters) resulting in hospitalisation of many, including one fatality. Since then, there have been no further reports of serious shellfish intoxication and there is little awareness of the risks from natural toxins and no routine monitoring programme in place to protect shellfish consumers. This study presents the findings from the first ever systematic assessment of the presence of marine toxins in mussels and oysters grown in four different shellfish harvesting areas in the region. Shellfish were collected and subjected to analysis for ASP, PSP and lipophilic toxins, as well as a suite of non-EU regulated toxins such as tetrodotoxin and selected cyclic imines. Results revealed the presence of low levels of PSP toxins in oysters throughout the study period. Overall, total toxicities reached a maximum of 10% of the EU regulatory limit of 800 μg STX eq/kg. Toxin profiles were similar to those reported from the 1980 outbreak. No evidence was found for significant levels of ASP and lipophilic toxins, although some cyclic imines were detected, including gymnodimine. The results indicated that the risk to shellfish consumers during this specific study period would have been low. However, with historical evidence for extremely high levels of PSP toxins in molluscs, there is a strong need for routine surveillance of shellfish production areas for marine toxins, in order to mitigate against human health impacts resulting from unexpected harmful algal blooms, with potentially devastating socio-economic consequences.
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| 33. |
- Vimali, Jaisheela, et al.
(author)
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Chronic Viral Infection Compromises the Quality of Circulating Mucosal-Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors
- 2024
-
In: FRONTIERS IN BIOSCIENCE-LANDMARK. - : IMR PRESS. - 2768-6701. ; 29:3
-
Journal article (peer-reviewed)abstract
- Background: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. Methods: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4(+) T cells including circulating Tfh cells, CD8(+) T cells, and TCR iV alpha 7.2(+) MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-alpha, IFN-gamma) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. Results: The activation marker CD69 was significantly increased in CD4(+hi) T cells, while CD8(+) MAIT cells producing IFN-gamma were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-alpha(+)CD4(+lo) T cells, CD69(+)CD8(+) T cells, CD69(+)CD4(+) MAIT cells, PD-1(+)CD4(+hi) T cells, PD-1(+)CD8(+) T cells, and Ki67(+)CD4(+) MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-alpha levels showed a positive correlation with increase in cytokine levels and decrease in PVL. Conclusion: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.
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| 34. |
- Vimali, Jaisheela, et al.
(author)
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Plasma interleukin-7 correlation with human immunodeficiency virus RNA and CD4+T cell counts, and interleukin-5 with circulating hepatitis B virus DNA may have implications in viral control
- 2022
-
In: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 9
-
Journal article (peer-reviewed)abstract
- Chronic viral infections represent a leading cause of global morbidity and mortality. Chronic HBV, HCV, and HIV infections result in cytokine perturbations that may hold key implications in understanding the complex disease mechanisms driving virus persistence and/or resolution. Here, we determined the levels of various plasma cytokines using a commercial Bio-Plex Luminex cytokine array in chronic HBV (n = 30), HCV (n = 15), and HIV (n = 40) infections and correlated with corresponding plasma viral loads (PVLs) and liver parameters. We observed differential perturbations in cytokine profiles among the study groups. The cytokines levels positively correlated with PVL and liver transaminases. The monocyte-derived cytokines viz., MIP-1 beta, IL-8, and TNF-alpha, and Th2 cytokines like IL-4, IL-5, and IL-13 showed a better correlation with liver enzymes as compared to their corresponding PVLs. Our investigation also identified two cytokines viz., IL-5 and IL-7 that inversely correlated with HBV DNA and HIV PVLs, respectively. Regression analysis adjusted for age showed that every increase of IL-5 by one unit was associated with a reduction in HBV PVL by log(10) 0.4, whereas, every elevation by a unit of IL-7 was associated with decreased HIV PVL by log(10) 2.5. We also found that IL-7 levels correlated positively with absolute CD4+ T cell counts in HIV-infected patients. We concluded that plasma IL-5 and IL-7 may likely have a key role on viral control in HBV and HIV infections, respectively. A noteworthy increase in cytokines appears to bear protective and pathological significance, and indeed is reflective of the hosts versatile immune armory against viral persistence.
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| 35. |
- Vimali, Jaisheela, et al.
(author)
-
Surrogate Biomarkers of Disease Progression in Human Pegivirus Seropositive Human Immunodeficiency Virus-Infected Individuals
- 2023
-
In: Viral immunology. - : MARY ANN LIEBERT, INC. - 0882-8245 .- 1557-8976. ; 36:1, s. 55-62
-
Journal article (peer-reviewed)abstract
- Scientific observations indicate that an actively prevailing systemic condition could alleviate the pathology of another disease. Human pegivirus (HPgV), a highly ubiquitous flavivirus is believed to be associated with slow human immunodeficiency virus (HIV) disease progression, and has seldom been linked to hepatic pathology. In this study, we investigated whether HPgV seropositivity had any impact on surrogate markers of HIV disease progression in a cohort of HIV-infected HPgV seropositive (n = 28) and seronegative (n = 12) individuals who were prospectively evaluated for absolute CD4+ T cell counts, plasma viral load (PVL), liver enzymes, and plasma cytokine levels. The HIV PVL was relatively lower in HPgV seropositive than in HPgV seronegative HIV-infected subjects. Clinical markers of hepatic injury were significantly low among HPgV seropositive HIV-infected participants. HPgV seropositive individuals showed significantly higher levels of interleukin-7 (IL-7), and although not significant, the levels of IL-6 were lower among HPgV seropositive subjects. Spearman correlation analysis showed that the absolute CD4+T cell count was inversely correlated with HIV PVL. Exposure to HPgV appears to have a positive prognostic impact on the levels of surrogate biomarkers of HIV disease progression.
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| 36. |
- Webster, Christopher R., et al.
(author)
-
Background levels of methane in Mars' atmosphere show strong seasonal variations
- 2018
-
In: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 360:6393, s. 1093-1096
-
Journal article (peer-reviewed)abstract
- Variable levels of methane in the martian atmosphere have eluded explanation partly because the measurements are not repeatable in time or location. We report in situ measurements at Gale crater made over a 5-year period by the Tunable Laser Spectrometer on the Curiosity rover. The background levels of methane have a mean value 0.41 ± 0.16 parts per billion by volume (ppbv) (95% confidence interval) and exhibit a strong, repeatable seasonal variation (0.24 to 0.65 ppbv). This variation is greater than that predicted from either ultraviolet degradation of impact-delivered organics on the surface or from the annual surface pressure cycle. The large seasonal variation in the background and occurrences of higher temporary spikes (~7 ppbv) are consistent with small localized sources of methane released from martian surface or subsurface reservoirs.
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| 37. |
- Weickert, Martin O., et al.
(author)
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Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome
- 2018
-
In: Clinical Therapeutics. - : ELSEVIER. - 0149-2918 .- 1879-114X. ; 40:6, s. 952-962
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Journal article (peer-reviewed)abstract
- Purpose: In the placebo-controlled Phase III TELE-STAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and >= 4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m(2)) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.Methods: Assessment of the occurrence of weight change >= 3% at week 12 was prespecified in the statistical analysis plan.Findings: In 120 patients with weight data available, weight gain >= 3% was observed in 2 of 39 patients (5.1%) taking placebo [1.1), 7 of 41 (17.1%) taking telotristat ethyl 250 mg TID, and 13 of 40 (32.5%) taking telotristat ethyl 500 mg TID (P = 0.0017) at week 12. Weight loss >= 3% was observed in 5 of 39 patients (12.8%) taking placebo TID, 4 of 41 (9.8%) taking telotristat ethyl 250 mg TID, and 6 of 40 (15.0%) taking telotristat ethyl 500 mg TID (P = 0.77). Biochemical and metabolic parameters of serum albumin and cholesterol significantly increased (P = 0.02 and P = 0.001, respectively) in patients gaining weight and decreased in patients who lost weight, suggesting an improvement in overall nutritional status.
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| 39. |
- Wingenbach, T. S. H., et al.
(author)
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Perception of Discrete Emotions in Others : Evidence for Distinct Facial Mimicry Patterns
- 2020
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In: Scientific Reports. - : Nature Research. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- Covert facial mimicry involves subtle facial muscle activation in observers when they perceive the facial emotional expressions of others. It remains uncertain whether prototypical facial features in emotional expressions are being covertly mimicked and also whether covert facial mimicry involves distinct facial muscle activation patterns across muscles per emotion category, or simply distinguishes positive versus negative valence in observed facial emotions. To test whether covert facial mimicry is emotion-specific, we measured facial electromyography (EMG) from five muscle sites (corrugator supercilii, levator labii, frontalis lateralis, depressor anguli oris, zygomaticus major) whilst participants watched videos of people expressing 9 different basic and complex emotions and a neutral expression. This study builds upon previous research by including a greater number of facial muscle measures and emotional expressions. It is the first study to investigate activation patterns across muscles during facial mimicry and to provide evidence for distinct patterns of facial muscle activation when viewing individual emotion categories, suggesting that facial mimicry is emotion-specific, rather than just valence-based. © 2020, The Author(s).
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| 40. |
- Yuste, Jose, et al.
(author)
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Impaired opsonization with complement and phagocytosis of Streptococcus pyogenes in sera from subjects with inherited C2 deficiency
- 2010
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In: Microbes and Infection. - : Elsevier BV. - 1769-714X .- 1286-4579. ; 12:8-9, s. 626-634
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Journal article (peer-reviewed)abstract
- Although subjects with inherited defects of the classical complement pathway component C2 are at increased risk of infection, there are few experimental data available on which bacterial pathogens they might be susceptible to. In order to investigate whether patients with inherited C2 deficiency may have increased susceptibility to Streptococcus pyogenes infection we have analysed opsonization with C3b/iC3b and phagocytosis of three different strains of S. pyogenes in serum from 8 C2(-/-) subjects using flow cytometry assays. Sera from patients with C2 deficiency had a markedly reduced ability to opsonise S. pyogenes with C3b/iC3b. In addition, phagocytosis of all three S. pyogenes strains was impaired in sera from C2(-/-) subjects. Both the reduced opsonisation with C3b/iC3b and phagocytosis in C2(-/-) sera were markedly improved by addition of exogenous C2 protein. Neutrophil dependent killing was also reduced, confirming the functional importance of C2 deficiency for immunity to S. pyogenes. Impaired opsonisation with C3b/iC3b and phagocytosis was not related to reduced recognition of the bacteria by antibody. These data suggest that patients with C2 deficiency are at increased risk of S. pyogenes infections. (c) 2010 Elsevier Masson SAS. All rights reserved.
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