AIM： To determine the risk of malignancy and mortality in patients with a positive endomysial or anti-gliadin antibody test in Northern Ireland. METHODS： A population-based retrospective cohort study ...design was used. Laboratory test results used in the diagnosis of coeliac disease were obtained from the Regional Immunology Laboratory, cancer statistics from the Northern Ireland Cancer Registry and mortality statistics from the General Registrar Office, Northern Ireland. Age standardized incidence ratios of malignant neoplasms and standardized mortality ratios of all-cause and cause-specific mortality were calculated. RESULTS： A total of 13 338 people had an endomysial antibody and/or an anti-gliadin antibody test in Northern Ireland between 1993 and 1996. There were 490 patients who tested positive for endomysial antibodies and they were assumed to have coeliac disease. There were 1133 patients who tested positive for anti-gliadin antibodies and they were defined as gluten sensitive. Malignant neoplasms were not significantly associated with coeliac disease; however, all-cause mortality was significantly increased following diagnosis. The standardized incidence and mortality ratios for non-Hodgkin＇s lymphoma were increased in coeliac disease patients but did not reach statistical significance. Lung and breast cancer incidence were significantly lower and all-cause mortality, mortality from malignant neoplasms, non-Hodgkin＇s lymphoma and digestive system disorders were significantly higher in gluten sensitive patients compared to the Northern Ireland population. CONCLUSION： Patients with coeliac disease or gluten sensitivity had higher mortality rates than the Northern Ireland population. This association persists more than one year after diagnosis in patients testing positive for anti-gliadin antibodies. Breast cancer is significantly reduced in the cohort of patients with gluten sensitivity.
Abstract
Background
The long-term consequences of COVID-19 remain unclear. There is concern a proportion of patients will progress to develop pulmonary fibrosis. We aimed to assess the temporal ...change in CXR infiltrates in a cohort of patients following hospitalisation for COVID-19.
Methods
We conducted a single-centre prospective cohort study of patients admitted to University Hospital Southampton with confirmed SARS-CoV2 infection between 20th March and 3rd June 2020. Patients were approached for standard-of-care follow-up 12-weeks after hospitalisation. Inpatient and follow-up CXRs were scored by the assessing clinician for extent of pulmonary infiltrates; 0–4 per lung (Nil = 0, < 25% = 1, 25–50% = 2, 51–75% = 3, > 75% = 4).
Results
101 patients with paired CXRs were included. Demographics: 53% male with a median (IQR) age 53.0 (45–63) years and length of stay 9 (5–17.5) days. The median CXR follow-up interval was 82 (77–86) days with median baseline and follow-up CXR scores of 4.0 (3–5) and 0.0 (0–1) respectively. 32% of patients had persistent CXR abnormality at 12-weeks. In multivariate analysis length of stay (LOS), smoking-status and obesity were identified as independent risk factors for persistent CXR abnormality. Serum LDH was significantly higher at baseline and at follow-up in patients with CXR abnormalities compared to those with resolution. A 5-point composite risk score (1-point each; LOS ≥ 15 days, Level 2/3 admission, LDH > 750 U/L, obesity and smoking-status) strongly predicted risk of persistent radiograph abnormality (0.81).
Conclusion
Persistent CXR abnormality 12-weeks post COVID-19 was common in this cohort. LOS, obesity, increased serum LDH, and smoking-status were risk factors for radiograph abnormality. These findings require further prospective validation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Climate change is altering the rate and distribution of primary production in the world's oceans. Primary production is critical to maintaining biodiversity and supporting fishery catches, but ...predicting the response of populations to primary production change is complicated by predation and competition interactions. We simulated the effects of change in primary production on diverse marine ecosystems across a wide latitudinal range in Australia using the marine food web model Ecosim. We link models of primary production of lower trophic levels (phytoplankton and benthic producers) under climate change with Ecosim to predict changes in fishery catch, fishery value, biomass of animals of conservation interest, and indicators of community composition. Under a plausible climate change scenario, primary production will increase around Australia and generally this benefits fisheries catch and value and leads to increased biomass of threatened marine animals such as turtles and sharks. However, community composition is not strongly affected. Sensitivity analyses indicate overall positive linear responses of functional groups to primary production change. Responses are robust to the ecosystem type and the complexity of the model used. However, model formulations with more complex predation and competition interactions can reverse the expected responses for some species, resulting in catch declines for some fished species and localized declines of turtle and marine mammal populations under primary productivity increases. We conclude that climate-driven primary production change needs to be considered by marine ecosystem managers and more specifically, that production increases can simultaneously benefit fisheries and conservation. Greater focus on incorporating predation and competition interactions into models will significantly improve the ability to identify species and industries most at risk from climate change.
The nucleosome remodeling deacetylase (NuRD) complex is a highly conserved regulator of chromatin structure and transcription. Structural studies have shed light on this and other chromatin modifying ...machines, but much less is known about how they assemble and whether stable and functional sub-modules exist that retain enzymatic activity. Purification of the endogenous Drosophila NuRD complex shows that it consists of a stable core of subunits, while others, in particular the chromatin remodeler CHD4, associate transiently. To dissect the assembly and activity of NuRD, we systematically produced all possible combinations of different components using the MultiBac system, and determined their activity and biophysical properties. We carried out single-molecule imaging of CHD4 in live mouse embryonic stem cells, in the presence and absence of one of core components (MBD3), to show how the core deacetylase and chromatin-remodeling sub-modules associate in vivo. Our experiments suggest a pathway for the assembly of NuRD via preformed and active sub-modules. These retain enzymatic activity and are present in both the nucleus and the cytosol, an outcome with important implications for understanding NuRD function.
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•We have studied Drosophila nucleosome remodeling deacetylase (NuRD) assembly.•NuRD consists of a core deacetylase complex, where MTA-like acts as the scaffold.•This transiently associates with a chromatin remodeling sub-module including CHD4.•Single-molecule imaging shows that the two sub-modules associate through MBD-like.•NuRD comprises catalytically active sub-modules in both the cytosol and the nucleus.
Lake Winnipeg has experienced dramatic increases in nutrient loading and phytoplankton biomass over the last few decades, accompanied by a marked shift in community composition towards the dominance ...of cyanobacteria. Comprehensive lake-wide observations of algal blooms are critical to assessing the lake's health status, its response to nutrient management practices, and an improved understanding of the processes driving blooms. We present an analysis of the spatial and temporal variability of algal blooms on Lake Winnipeg using satellite-derived chlorophyll and indices for algal bloom intensity, spatial extent, severity, and duration over the period of ESA's MERIS mission (2002–2011). Imagery documented extensive blooms covering as much as 93% of the lake surface. Bloom conditions were analysed in the context of in-lake and watershed processes to gain further insight on the drivers of bloom events. Day to day bloom variability was driven primarily by intermittent wind mixing events, with quiescent periods leading to the formation of dense surface blooms. Seasonal bloom distribution was consistent with light limitation in the south basin and lake circulation transporting bloom material towards the north-east shore. Inter-annual variability in average bloom severity was related to both total phosphorus (TP) loadings and summer lake surface temperatures. Results provide a valuable historical time series of bloom conditions to which ongoing observations from Sentinel-3's OLCI sensor can be added for longer term monitoring and change detection.
Selective targeting of cells for intracellular delivery of therapeutics represents a major challenge for pharmaceutical intervention in disease. Here we show pH-triggered receptor-mediated ...endocytosis of nanoparticles via surface ligand exposure. Gold nanoparticles were decorated with two polymers: a 2 kDa PEG with a terminal folate targeting ligand, and a di-block copolymer including a pH-responsive and a hydrophilic block. At the normal serum pH of 7.4, the pH-responsive block (apparent pK
of 7.1) displayed a hydrophilic extended conformation, shielding the PEG-folate ligands, which inhibited cellular uptake of the nanoparticles. Under pH conditions resembling those of the extracellular matrix around solid tumours (pH 6.5), protonation of the pH-responsive polymer triggered a coil-to-globule polymer chain contraction, exposing folate residues on the PEG chains. In line with this, endocytosis of folate-decorated polymer-coated gold nanoparticles in cancer cells overexpressing folate receptor was significantly increased at pH 6.5, compared with pH 7.4. Thus, the tumour acidic environment and high folate receptor expression were effectively exploited to activate cell binding and endocytosis of these nanoparticles. These data provide proof-of-concept for strategies enabling extracellular pH stimuli to selectively enhance cellular uptake of drug delivery vectors and their associated therapeutic cargo.
The phenomenon of magical contagion – the unobserved passage of properties between entities that come into physical contact – was described by anthropologists over a century ago, yet questions remain ...about its origin, function, and universality. Contagion sensitivity, along with the emotion of disgust, has been proposed to be part of a biologically-evolved system designed to reduce exposure to pathogens by increasing the avoidance of “contaminated” objects. Yet this phenomenon has not been studied using systematic psychological comparison outside of industrialized populations. Here we document contagion sensitivity in two culturally, geographically, and economically distinct populations with little exposure to Western biomedicine and formal education: the Hadza hunter-gatherers of Tanzania and Tannese subsistence-agriculturalists of Vanuatu. In both populations, a majority of individuals rejected familiar and palatable foods when contaminating items touched the food but were subsequently removed. The Tannese children in our study showed a similar response, consistent with previous research with Western children. Our data support the proposal that contagion sensitivity is universal in human populations.
Natural and supernatural explanations are used to interpret the same events in a number of predictable and universal ways. Yet little is known about how variation in diverse cultural ecologies ...influences how people integrate natural and supernatural explanations. Here, we examine explanatory coexistence in three existentially arousing domains of human thought: illness, death, and human origins using qualitative data from interviews conducted in Tanna, Vanuatu. Vanuatu, a Melanesian archipelago, provides a cultural context ideal for examining variation in explanatory coexistence due to the lack of industrialization and the relatively recent introduction of Christianity and Western education. We argue for the integration of interdisciplinary methodologies from cognitive science and anthropology to inform research on explanatory coexistence.
Black men have higher prostate-specific antigen (PSA) levels and higher prostate cancer incidence and mortality than White men, while Asian men tend to have lower prostate cancer incidence and ...mortality than White men. Much of the evidence comes from the USA, and information from UK populations is limited.
This retrospective cohort study used data on patients registered at general practices in England contributing to the Clinical Practice Research Datalink (CPRD) Aurum dataset. Those eligible were men aged 40 and over with a record of ethnicity and a PSA test result recorded between 2010 and 2017 with no prior cancer diagnosis. The aim was to assess the incidence of prostate cancer following a raised PSA test result in men from different ethnic groups. Additionally, incidence of advanced prostate cancer was investigated. Cancer incidence was estimated from multi-level logistic regression models adjusting for potential confounding factors.
730,515 men with a PSA test were included (88.9% White). Black men and men with mixed ethnicity had higher PSA values, particularly for those aged above 60 years. In the year following a raised PSA result (using age-specific thresholds), Black men had the highest prostate cancer incidence at 24.7% (95% CI 23.3%, 26.2%); Asian men had the lowest at 13.4% (12.2%, 14.7%); incidence for White men was 19.8% (19.4%, 20.2%). The peak incidence of prostate cancer for all groups was in men aged 70-79. Incidence of prostate cancer diagnosed at an advanced stage was similar between Black and White men.
More prostate cancer was diagnosed in Black men with a raised PSA result, but rates of advanced prostate cancer were not higher in this group. In this large primary care-based cohort, the incidence of prostate cancer in men with elevated PSA levels increases with increasing age, even when using age-adjusted thresholds, with Black men significantly more likely to be diagnosed compared to White or Asian men. The incidence of advanced stage prostate cancer at diagnosis was similar for Black and White men with a raised PSA result, but lower for Asian men.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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