Modeling the initiation of others into injection drug use, using data from 2,500 injectors surveyed in Scotland during 2008-2009

The prevalence of injection drug use has been of especial interest for assessment of the impact of blood-borne viruses. However, the incidence of injection drug use has been underresearched. Our 2-fold aim in this study was to estimate 1) how many other persons, per annum, an injection drug user (IDU) has the equivalent of full responsibility (EFR) for initiating into injection drug use and 2) the consequences for IDUs' replacement rate. EFR initiation rates are strongly associated with incarceration history, so that our analysis of IDUs' replacement rate must incorporate when, in their injecting career, IDUs were first incarcerated. To do so, we have first to estimate piecewise constant incarceration rates in conjunction with EFR initiation rates, which are then combined with rates of cessation from injecting to model IDUs' replacement rate over their injecting career, analogous to the reproduction number of an epidemic model. We apply our approach to Scotland's IDUs, using over 2,500 anonymous injector participants who were interviewed in Scotland's Needle Exchange Surveillance Initiative during 2008-2009. Our approach was made possible by the inclusion of key questions about initiations. Finally, we extend our model to include an immediate quit rate, as a reasoned compensation for higher-than-expected replacement rates, and we estimate how high initiates' quit rate should be for IDUs' replacement rate to be 1

Can we set a global threshold age to define mature forests?

Globally, mature forests appear to be increasing in biomass density (BD). There is disagreement whether these increases are the result of increases in atmospheric CO2 concentrations or a legacy effect of previous land-use. Recently, it was suggested that a threshold of 450 years should be used to define mature forests and that many forests increasing in BD may be younger than this. However, the study making these suggestions failed to account for the interactions between forest age and climate. Here we revisit the issue to identify: (1) how climate and forest age control global forest BD and (2) whether we can set a threshold age for mature forests. Using data from previously published studies we modelled the impacts of forest age and climate on BD using linear mixed effects models. We examined the potential biases in the dataset by comparing how representative it was of global mature forests in terms of its distribution, the climate space it occupied, and the ages of the forests used. BD increased with forest age, mean annual temperature and annual precipitation. Importantly, the effect of forest age increased with increasing temperature, but the effect of precipitation decreased with increasing temperatures. The dataset was biased towards northern hemisphere forests in relatively dry, cold climates. The dataset was also clearly biased towards forests <250 years of age. Our analysis suggests that there is not a single threshold age for forest maturity. Since climate interacts with forest age to determine BD, a threshold age at which they reach equilibrium can only be determined locally. We caution against using BD as the only determinant of forest maturity since this ignores forest biodiversity and tree size structure which may take longer to recover. Future research should address the utility and cost-effectiveness of different methods for determining whether forests should be classified as mature

Robust Estimators in Generalized Pareto Models

This paper deals with optimally-robust parameter estimation in generalized Pareto distributions (GPDs). These arise naturally in many situations where one is interested in the behavior of extreme events as motivated by the Pickands-Balkema-de Haan extreme value theorem (PBHT). The application we have in mind is calculation of the regulatory capital required by Basel II for a bank to cover operational risk. In this context the tail behavior of the underlying distribution is crucial. This is where extreme value theory enters, suggesting to estimate these high quantiles parameterically using, e.g. GPDs. Robust statistics in this context offers procedures bounding the influence of single observations, so provides reliable inference in the presence of moderate deviations from the distributional model assumptions, respectively from the mechanisms underlying the PBHT.Comment: 26pages, 6 figure

High Abundances of Species in Protected Areas in Parts of their Geographic Distributions Colonized during a Recent Period of Climatic Change

It is uncertain whether Protected Areas (PAs) will conserve high abundances of species as their distributions and abundances shift in response to climate change. We analyzed large datasets for 57 butterfly and 42 odonate species (including four that have recently colonized Britain). We found that 73 of 94 species with sufficient data for analysis were more abundant inside than outside PAs in the historical parts of their British distributions, showing that PAs have retained high conservation value. A significant majority (61 of 99 species) was also more abundant inside PAs in regions they have colonized during the last 30–40 years of climate warming. Species with relatively high abundances inside PAs in long-established parts of their distributions were also disproportionately associated with PAs in recently colonized regions, revealing a set of relatively PA-reliant species. Pas, therefore, play a vital role in the conservation of biodiversity as species’ ranges become more dynamic

Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth

Background The onset of birth in humans, like other apes, differs from non-primate mammals in its endocrine physiology. We hypothesize that higher primate-specific gene evolution may lead to these differences and target genes involved in human preterm birth, an area of global health significance. Methods We performed a comparative genomics screen of highly conserved noncoding elements and identified PLA2G4C, a phospholipase A isoform involved in prostaglandin biosynthesis as human accelerated. To examine whether this gene demonstrating primate-specific evolution was associated with birth timing, we genotyped and analyzed 8 common single nucleotide polymorphisms (SNPs) in PLA2G4C in US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers. Results Detailed structural and phylogenic analysis of PLA2G4C suggested a short genomic element within the gene duplicated from a paralogous highly conserved element on chromosome 1 specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and rs11564620 in US Whites were significant after correcting for multiple tests (p < 0.006). Additionally, rs11564620 (Thr360Pro) was associated with increased metabolite levels of the prostaglandin thromboxane in healthy individuals (p = 0.02), suggesting this variant may affect PLA2G4C activity. Conclusions Our findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.Children’s Discovery InstituteMarch of Dimes Birth Defects FoundationNational Institute of General Medical Sciences (U.S.) (grant T32 GM081739)Washington University (Saint Louis, Mo.) (Mr. and Mrs. Spencer T. Olin Fellowship for Women in Graduate Study)Sigrid Jusélius FoundationSigne and Anne Gyllenberg FoundationAcademy of FinlandVanderbilt University (Turner-Hazinski grant award

The impact of early hypoglycemia and blood glucose variability on outcome in critical illness

INTRODUCTION: In critical illness, the association of hypoglycemia, blood glucose (BG) variability and outcome are not well understood. We describe the incidence, clinical factors and outcomes associated with an early hypoglycemia and BG variability in critically ill patients. METHODS: Retrospective interrogation of prospectively collected data from the Australia New Zealand Intensive Care Society Adult Patient Database on 66184 adult admissions to 24 intensive care units (ICUs) from 1 January 2000 to 31 December 2005. Primary exposure was hypoglycemia (BG or= 12.0 mmol/L) within 24 hours of admission. Primary outcome was all-cause mortality. RESULTS: The cumulative incidence of hypoglycemia and BG variability were 13.8% (95% confidence interval (CI) = 13.5 to 14.0; n = 9122) and 2.9% (95%CI = 2.8 to 3.0, n = 1913), respectively. Several clinical factors were associated with both hypoglycemia and BG variability including: co-morbid disease (P < 0.001), non-elective admissions (P < 0.001), higher illness severity (P < 0.001), and primary septic diagnosis (P < 0.001). Hypoglycemia was associated with greater odds of adjusted ICU (odds ratio (OR) = 1.41, 95% CI = 1.31 to 1.54) and hospital death (OR = 1.36, 95% CI = 1.27 to 1.46). Hypoglycemia severity was associated with 'dose-response' increases in mortality. BG variability was associated with greater odds of adjusted ICU (1.5, 95% CI = 1.4 to 1.6) and hospital (1.4, 95% CI = 1.3 to 1.5) mortality, when compared with either hypoglycemia only or neither. CONCLUSIONS: In critically ill patients, both early hypoglycemia and early variability in BG are relatively common, and independently portend an increased risk for mortality

A common missense variant of <i>LILRB₅</i> is associated with statin intolerance and myalgia

Aims A genetic variant in LILRB5 (leukocyte immunoglobulin-like receptor subfamily-B) (rs12975366: T > C: Asp247Gly) has been reported to be associated with lower creatine phosphokinase (CK) and lactate dehydrogenase (LDH) levels. Both biomarkers are released from injured muscle tissue, making this variant a potential candidate for susceptibility to muscle-related symptoms. We examined the association of this variant with statin intolerance ascertained from electronic medical records in the GoDARTS study. Methods and results In the GoDARTS cohort, the LILRB5 Asp247 variant was associated with statin intolerance (SI) phenotypes; one defined as having raised CK and being non-adherent to therapy [odds ratio (OR) 1.81; 95% confidence interval (CI): 1.34–2.45] and the other as being intolerant to the lowest approved dose of a statin before being switched to two or more other statins (OR 1.36; 95% CI: 1.07–1.73). Those homozygous for Asp247 had increased odds of developing both definitions of intolerance. Importantly the second definition did not rely on CK elevations. These results were replicated in adjudicated cases of statin-induced myopathy in the PREDICTION-ADR consortium (OR1.48; 95% CI: 1.05–2.10) and for the development of myalgia in the JUPITER randomized clinical trial of rosuvastatin (OR1.35, 95% CI: 1.10–1.68). A meta-analysis across the studies showed a consistent association between Asp247Gly and outcomes associated with SI (OR1.34; 95% CI: 1.16–1.54). Conclusion This study presents a novel immunogenetic factor associated with statin intolerance, an important risk factor for cardiovascular outcomes. The results suggest that true statin-induced myalgia and non-specific myalgia are distinct, with a potential role for the immune system in their development. We identify a genetic group that is more likely to be intolerant to their statins

The COVID guidelines India project: a rapid living evidence synthesis during a pandemic in a LMIC setting

Background: COVID-19 has had an unprecedented impact worldwide. Evidence for management interventions emerged rapidly but was difficult for clinicians and others to assess and decide how to use. Our team in India set up a national and international collaboration preparing guidance in real time to help guide clinical practice in the country during a pandemic setting. We describe our methods and the product in this paper. Methods: Specialized groups comprising core, steering, methodology, evidence synthesis, dissemination and intervention expert working groups were formed. A Cochrane Rapid Review approach was used for prioritized questions in areas of clinical equipoise in management of COVID-19. GRADE methodology was incorporated into this process and expert working groups tailored guidelines for India using the WHO Evidence to Decision framework. This was then disseminated on a widely accessible platform: indiacovidguidelines.org. A questionnaire was then used to obtain end-user feedback on the guidelines. Results: Since May 2021, a total of 20 guidelines have been developed spanning pharmacological, respiratory and other supportive interventions for management of COVID-19, with over 83,600 unique page views up to December 2023. Results from a pilot survey suggest usefulness of the guidelines, but also highlighted areas for improvement. A key output was adoption of our anticoagulation recommendation in state level COVID-19 guidelines (Kerala, India). National and institutional capacity for evidence synthesis and guidelines was strengthened. Conclusions: The COVID Guidelines India project successfully developed contextually relevant, nationally applicable, evidence-based guidelines in a timely manner, and disseminated these freely through a dedicated website while successfully building capacity amongst Indian clinicians for evidence-based guideline development. Throughout the ongoing COVID Guidelines India project, the team has maintained a 'living' approach, continuously updating and refining recommendations in response to emerging evidence during the ever-evolving pandemic landscape

Shifting Diets of Lake Trout in Northeastern Lake Michigan

Prey fish communities in Lake Michigan have been steadily changing, characterized by declines in both the quantity and quality of Alewife Alosa pseudoharengus. To evaluate concurrent changes in the diet of Lake Trout Salvelinus namaycush in northeastern Lake Michigan, we analyzed stomach contents of Lake Trout caught during gill‐net surveys and fishing tournaments from May through October 2016. We then compared the composition, on a wet‐weight basis, of 2016 diets with those previously described in a recent survey conducted in 2011. Overall, we found that Lake Trout diets in 2016 consisted mostly (94% by wet weight) of Alewives and Round Goby Neogobius melanostomus. Averaging across May through October, 61% of the Lake Trout diet consisted of Alewives. A clear seasonal shift was apparent: the diet was dominated by Round Goby (67%) during May–June, whereas Alewives dominated the diet (76%) during July–October. Seasonal dominance of Round Goby in spring Lake Trout diets has not been previously observed in northeastern Lake Michigan as Round Goby represented only 21% of the Lake Trout diet in spring of 2011. Diet composition of Lake Trout caught in gill nets did not significantly differ from diet composition of Lake Trout caught by anglers in either the May–June period or the July–October period. Although Lake Trout showed increased diet flexibility in 2016 compared with 2011, Alewives were still the predominant diet component during 2016, despite reduced Alewife biomass throughout Lake Michigan. Nonetheless, this further evidence of diet plasticity suggests that Lake Trout may be resilient to ongoing and future forage base changes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151367/1/nafm10318.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151367/2/nafm10318_am.pd