Cost-effectiveness of pioglitazone in type 2 diabetes patients with a history of macrovascular disease: a German perspective

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Comparative phylogeography, a tool to increase assessment efficiency of polar assemblage resilience and vulnerability

The Southern Ocean benthos is remarkably rich and diverse, and managed under a complexity of treaties and conventions, further complicated by geopolitical boundaries. Traditionally, conservation management is largely informed by species lists augmented, when data are available, by known vulnerability of the taxa. Species presence absence database resources are valuable tools with proven and positive management outcomes, however, in a vast, difficult to access and thus understudied region such as the Southern Ocean, there are large gaps in knowledge regarding the ecology, ecophysiology, life history and even species identity. Conservation biogeography identifies regions of conservation concern, rather than a species-by-species approach, but also relies on the availability of high-quality presence data from species lists and thus both approaches are undermined when species lists are inaccurate or species in general are poorly described. In addition, the data provide a snapshot of the current species diversity and have inadequate power to identify the processes underlying the patterns uncovered. Identifying historical processes common to shaping diversity (species or genetic) can be generalized across assemblages and regions, providing a more robust basis for conservation policy and decisions. In this study, largely based on consideration of Southern Ocean ophiuroids, we discuss the challenges inherent in using species lists, the power and limitations of genetic analyses, and revisit previous suggestions of building a spatial model of diversity that includes underlying evolutionary relationships transcending the simple species diversity approach, and that is applicable to assemblages, rather than just to individual taxa

A comparison of tuberculous and bacterial native joint septic arthritis infections in a retrospective cohort: presentation characteristics, outcomes and long term follow up

Objectives This retrospective observational cohort study aimed to characterise and compare the demographics, initial laboratory tests and outcomes between patients with large-joint bacterial septic arthritis (BSA) and tuberculous septic arthritis (TBSA). Methods All patients with a culture from a large, native joint growing either non-mycobacterial bacteria or Mycobacterium tuberculosis between 1 January 2012 and 1 October 2018 in our institution were included. Clinical details and admission laboratory values were obtained from patient records. Comparisons were made by Mann-Whitney U, chi-squared tests, and logistic regression analysis. Results We identified 64 BSA and 29 TBSA. On average, the BSA cases were older, had higher CRP levels and neutrophil counts and lower albumin levels. The odds ratio for having a BSA was 46 in cases with a CRP greater than 100 mg/L (95% confidence interval (CI) 8.5–850, p < 0.001) and 24 with a neutrophil count greater than 7.5x109 (95% CI 6.1–160, p < 0.001). 51% of BSA were asymptomatic at last follow up compared to 72% of TBSA. 14% of the BSA cases died during admission; there were no deaths in the TBSA group. Conclusions Significant differences exist between patients with BSA and TBSA. Whilst no test is sufficient to exclude BSA, a raised neutrophil count or a CRP greater than 100 mg/L significantly increases the odds of a bacterial aetiology. Patients with BSA had worse long-term outcomes and higher incidence of inpatient mortality

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction

Changes in undergraduate student alcohol consumption as they progress through university

BACKGROUND: Unhealthy alcohol use amongst university students is a major public health concern. Although previous studies suggest a raised level of consumption amongst the UK student population there is little consistent information available about the pattern of alcohol consumption as they progress through university. The aim of the current research was to describe drinking patterns of UK full-time undergraduate students as they progress through their degree course. METHOD: Data were collected over three years from 5895 undergraduate students who began their studies in either 2000 or 2001. Longitudinal data (i.e. Years 1–3) were available from 225 students. The remaining 5670 students all responded to at least one of the three surveys (Year 1 n = 2843; Year 2 n = 2219; Year 3 n = 1805). Results: Students reported consuming significantly more units of alcohol per week at Year 1 than at Years 2 or 3 of their degree. Male students reported a higher consumption of units of alcohol than their female peers. When alcohol intake was classified using the Royal College of Physicians guidelines [1] there was no difference between male and females students in terms of the percentage exceeding recommended limits. Compared to those who were low level consumers students who reported drinking above low levels at Year 1 had at least 10 times the odds of continuing to consume above low levels at year 3. Students who reported higher levels of drinking were more likely to report that alcohol had a negative impact on their studies, finances and physical health. Consistent with the reduction in units over time students reported lower levels of negative impact during Year 3 when compared to Year 1. CONCLUSION: The current findings suggest that student alcohol consumption declines over their undergraduate studies; however weekly levels of consumption at Year 3 remain high for a substantial number of students. The persistence of high levels of consumption in a large population of students suggests the need for effective preventative and treatment interventions for all year groups

The diverse and widespread Southern Ocean ophiuroid Amphiura belgicae should be considered a species complex

Accurate knowledge of geographic ranges of species is essential for effective conservation management. Species with large distributions and good connectivity are presumed to be resilient to adverse localised/regional conditions, whereas those with small ranges and, thus, smaller population sizes are more likely to be vulnerable. The rich benthic assemblages across the Southern Ocean are generally considered 'Antarctic' with some input from South America contributing to diversity on the sub-Antarctic island shelves. However, molecular work over the past two decades is challenging the paradigm of a general Antarctic benthic fauna, with evidence mounting for assemblages being regionally unique in terms of genetic diversity, regardless of formal taxonomic species composition. The widely distributed brittle star, Amphiura belgicae, is one element of the Southern Ocean benthic assemblage that has a complex historical taxonomic background hinting that it may in reality be a complex of species, each with small geographic range and little connectivity. Our study identified deep genetic divisions between geographically isolated populations, particularly between those on the Patagonian shelf, and elsewhere. Indeed, populations on the Patagonian shelf were more closely related to the sympatric sister species A. eugeniae than to any other Southern Ocean population. We compare our data with a study of Ophiuroglypha lymani from similar collections, highlighting that both show highly regionalized populations, particularly on Island shelves, and both share the curious phenomenon of a presumed outgroup species being an element of the ingroup. We suggest that the isolated populations of both these species are following distinct evolutionary and ecological trajectories and that both should be treated as species complexes

Use of emerging technologies to help measure fjordic biodiversity and blue carbon: mini-manned submarines and autonomous underwater vehicle swarms

Meaningful protection of global oceans lags far behind that of land and has taken little consideration of climate mitigation potential to date (such as through assessment of blue carbon stocks and change). With the new emphasis on synergistic approaches to the identification and conservation of both carbon- and species- rich habitats, we need much better knowledge of the geography and status of blue carbon habitats beyond coastal wetlands. In subpolar and polar regions, some blue carbon habitats are still emerging and work as negative (mitigating) feedback on climate change, yet remain unprotected despite strong evidence of threat overlap. Scientific research expeditions are gradually increasing our understanding, but appropriate vessels are a limiting factor due to high costs and carbon footprints. Even when available such vessels cannot access all areas (e.g., remote fjords with sills) and may struggle to measure certain aspects of habitats (e.g., steep or vertical surfaces). New technologies and opportunities have advanced to aid some of these problems, and here, two of them are considered, mini-manned submersibles and autonomous underwater vehicles. These two platforms have both become much more available and affordable (through novel partnerships) while also being much more scientifically capable. This technology has the potential to reduce the carbon footprint of science and particularly aid in assessing biology and environment status and change on steep sides, such as fjord walls

Climate change alters temporal dynamics of alpine soil microbial functioning and biogeochemical cycling via earlier snowmelt

Soil microbial communities regulate global biogeochemical cycles and respond rapidly to changing environmental conditions. However, understanding how soil microbial communities respond to climate change, and how this influences biogeochemical cycles, remains a major challenge. This is especially pertinent in alpine regions where climate change is taking place at double the rate of the global average, with large reductions in snow cover and earlier spring snowmelt expected as a consequence. Here, we show that spring snowmelt triggers an abrupt transition in the composition of soil microbial communities of alpine grassland that is closely linked to shifts in soil microbial functioning and biogeochemical pools and fluxes. Further, by experimentally manipulating snow cover we show that this abrupt seasonal transition in wide-ranging microbial and biogeochemical soil properties is advanced by earlier snowmelt. Preceding winter conditions did not change the processes that take place during snowmelt. Our findings emphasise the importance of seasonal dynamics for soil microbial communities and the biogeochemical cycles that they regulate. Moreover, our findings suggest that earlier spring snowmelt due to climate change will have far reaching consequences for microbial communities and nutrient cycling in these globally widespread alpine ecosystems

Climate change alters temporal dynamics of alpine soil microbial functioning and biogeochemical cycling via earlier snowmelt

From Springer Nature via Jisc Publications RouterHistory: received 2020-08-29, rev-recd 2021-01-26, accepted 2021-02-01, registration 2021-02-02, pub-electronic 2021-02-22, online 2021-02-22, pub-print 2021-08Publication status: PublishedFunder: RCUK | Natural Environment Research Council (NERC); doi: https://doi.org/10.13039/501100000270; Grant(s): NE/N009452/1Funder: RCUK | Biotechnology and Biological Sciences Research Council (BBSRC); doi: https://doi.org/10.13039/501100000268; Grant(s): BB/S010661/1Abstract: Soil microbial communities regulate global biogeochemical cycles and respond rapidly to changing environmental conditions. However, understanding how soil microbial communities respond to climate change, and how this influences biogeochemical cycles, remains a major challenge. This is especially pertinent in alpine regions where climate change is taking place at double the rate of the global average, with large reductions in snow cover and earlier spring snowmelt expected as a consequence. Here, we show that spring snowmelt triggers an abrupt transition in the composition of soil microbial communities of alpine grassland that is closely linked to shifts in soil microbial functioning and biogeochemical pools and fluxes. Further, by experimentally manipulating snow cover we show that this abrupt seasonal transition in wide-ranging microbial and biogeochemical soil properties is advanced by earlier snowmelt. Preceding winter conditions did not change the processes that take place during snowmelt. Our findings emphasise the importance of seasonal dynamics for soil microbial communities and the biogeochemical cycles that they regulate. Moreover, our findings suggest that earlier spring snowmelt due to climate change will have far reaching consequences for microbial communities and nutrient cycling in these globally widespread alpine ecosystems

Results of Antiretroviral Treatment Interruption and Intensification in Advanced Multi-Drug Resistant HIV Infection from the OPTIMA Trial

BACKGROUND: Guidance is needed on best medical management for advanced HIV disease with multidrug resistance (MDR) and limited retreatment options. We assessed two novel antiretroviral (ARV) treatment approaches in this setting. METHODS AND FINDINGS: We conducted a 2×2 factorial randomized open label controlled trial in patients with a CD4 count≤300 cells/µl who had ARV treatment (ART) failure requiring retreatment, to two options (a) re-treatment with either standard (≤4 ARVs) or intensive (≥5 ARVs) ART and b) either treatment starting immediately or after a 12-week monitored ART interruption. Primary outcome was time to developing a first AIDS-defining event (ADE) or death from any cause. Analysis was by intention to treat. From 2001 to 2006, 368 patients were randomized. At baseline, mean age was 48 years, 2% were women, median CD4 count was 106/µl, mean viral load was 4.74 log(10) copies/ml, and 59% had a prior AIDS diagnosis. Median follow-up was 4.0 years in 1249 person-years of observation. There were no statistically significant differences in the primary composite outcome of ADE or death between re-treatment options of standard versus intensive ART (hazard ratio 1.17; CI 0.86-1.59), or between immediate retreatment initiation versus interruption before re-treatment (hazard ratio 0.93; CI 0.68-1.30), or in the rate of non-HIV associated serious adverse events between re-treatment options. CONCLUSIONS: We did not observe clinical benefit or harm assessed by the primary outcome in this largest and longest trial exploring both ART interruption and intensification in advanced MDR HIV infection with poor retreatment options. TRIAL REGISTRATION: Clinicaltrials.gov NCT00050089