Temporal dynamics of ikaite in experimental sea ice

Ikaite (CaCO3 · 6H2O) is a metastable phase of calcium carbonate that normally forms in a cold environment and/or under high pressure. Recently, ikaite crystals have been found in sea ice, and it has been suggested that their precipitation may play an important role in air-sea CO 2 exchange in ice-covered seas. Little is known, however, of the spatial and temporal dynamics of ikaite in sea ice. Here we present evidence for highly dynamic ikaite precipitation and dissolution in sea ice grown at an outdoor pool of the Sea-ice Environmental Research Facility (SERF) in Manitoba, Canada. During the experiment, ikaite precipitated in sea ice when temperatures were below -4 °C, creating three distinct zones of ikaite concentrations: (1) a millimeter-to-centimeter-thin surface layer containing frost flowers and brine skim with bulk ikaite concentrations of >2000 μmol kg-1, (2) an internal layer with ikaite concentrations of 200-400 μmol kg -1, and (3) a bottom layer with ikaite concentrations of <100 μmol kg-1. Snowfall events caused the sea ice to warm and ikaite crystals to dissolve. Manual removal of the snow cover allowed the sea ice to cool and brine salinities to increase, resulting in rapid ikaite precipitation. The observed ikaite concentrations were on the same order of magnitude as modeled by FREZCHEM, which further supports the notion that ikaite concentration in sea ice increases with decreasing temperature. Thus, varying snow conditions may play a key role in ikaite precipitation and dissolution in sea ice. This could have a major implication for CO2 exchange with the atmosphere and ocean that has not been accounted for previously

Does directly observed therapy (DOT) reduce drug resistant tuberculosis?

<p>Abstract</p> <p>Background</p> <p>Directly observed therapy (DOT) is a widely recommended and promoted strategy to manage tuberculosis (TB), however, there is still disagreement about the role of DOT in TB control and the impact it has on reducing the acquisition and transmission of drug resistant TB. This study compares the portion of drug resistant genotype clusters, representing recent transmission, within and between communities implementing programs differing only in their directly observed therapy (DOT) practices.</p> <p>Methods</p> <p>Genotype clusters were defined as 2 or more patient members with matching IS<it>6110 </it>restriction fragment length polymorphism (RFLP) and spoligotype patterns from all culture-positive tuberculosis cases diagnosed between January 1, 1995 and December 31, 2001. Logistic regression was used to compute maximum-likelihood estimates of odds ratios (ORs) and 95% confidence intervals (CIs) comparing cluster members with and without drug resistant isolates. In the universal DOT county, all patients received doses under direct observation of health department staff; whereas in selective DOT county, the majority of received patients doses under direct observation of health department staff, while some were able to self-administer doses.</p> <p>Results</p> <p>Isolates from 1,706 persons collected during 1,721 episodes of tuberculosis were genotyped. Cluster members from the selective DOT county were more than twice as likely than cluster members from the universal DOT county to have at least one isolate resistant to isoniazid, rifampin, and/or ethambutol (OR = 2.3, 95% CI: 1.7, 3.1). Selective DOT county isolates were nearly 5 times more likely than universal DOT county isolates to belong to clusters with at least 2 resistant isolates having identical resistance patterns (OR = 4.7, 95% CI: 2.9, 7.6).</p> <p>Conclusions</p> <p>Universal DOT for tuberculosis is associated with a decrease in the acquisition and transmission of resistant tuberculosis.</p

Treatment outcome of tuberculosis patients at Gondar University Teaching Hospital, Northwest Ethiopia. A five - year retrospective study

<p>Abstract</p> <p>Background</p> <p>In Gondar University Teaching Hospital standardized tuberculosis prevention and control programme, incorporating Directly Observed Treatment, Short Course (DOTS) started in 2000. According to the proposal of World Health Organization (WHO), treatment outcome is an important indicator of tuberculosis control programs. This study investigated the outcome of tuberculosis treatment at Gondar University Teaching Hospital in Northwest Ethiopia.</p> <p>Methods</p> <p>We analyzed the records of 4000 tuberculosis patients registered at Gondar University Teaching Hospital from September 2003 to May 2008. Treatment outcome and tuberculosis type were categorized according to the national tuberculosis control program guideline. Multivariate analysis using logistic regression model was used to analyse the association between treatment outcome and potential predictor variables.</p> <p>Results</p> <p>From the total of 4000 patients, tuberculosis type was categorized as extrapulmonary in 1133 (28.3%), smear negative pulmonary tuberculosis in 2196 (54.9%) and smear positive pulmonary tuberculosis in 671 (16.8%) cases. Of all patients, treatment outcome was classified as successfully treated in 1181(29.5%), defaulted in 730 (18.3%), died in 403 (10.1%), treatment failed in six (0.2%) and transferred out in 1680 (42.0%) patients. Males had the trend to be more likely to experience death or default than females, and the elderly were more likely to die than younger. The proportion of default rate was increased across the years from 97(9.2%) to 228(42.9%). Being female, age group 15-24 years, smear positive pulmonary tuberculosis and being urban resident were associated with higher treatment success rate.</p> <p>Conclusion</p> <p>The treatment success rate of tuberculosis patients was unsatisfactorily low (29.5%). A high proportion of patients died (10.1%) or defaulted (18.3%), which is a serious public health concern that needs to be addressed urgently.</p

Study design and participant characteristics of a randomized controlled trial of directly administered antiretroviral therapy in opioid treatment programs

<p>Abstract</p> <p>Background</p> <p>HIV-infected drug users are at higher risk of non-adherence and poor treatment outcomes than HIV-infected non-drug users. Prior work from our group and others suggests that directly administered antiretroviral therapy (DAART) delivered in opioid treatment programs (OTPs) may increase rates of viral suppression.</p> <p>Methods/Design</p> <p>We are conducting a randomized trial comparing DAART to self-administered therapy (SAT) in 5 OTPs in Baltimore, Maryland. Participants and investigators are aware of treatment assignments. The DAART intervention is 12 months. The primary outcome is HIV RNA < 50 copies/mL at 3, 6, and 12 months. To assess persistence of any study arm differences that emerge during the active intervention, we are conducting an 18-month visit (6 months after the intervention concludes). We are collecting electronic adherence data for 2 months in both study arms. Of 457 individuals screened, a total of 107 participants were enrolled, with 56 and 51 randomly assigned to DAART and SAT, respectively. Participants were predominantly African American, approximately half were women, and the median age was 47 years. Active use of cocaine and other drugs was common at baseline. HIV disease stage was advanced in most participants. The median CD4 count at enrollment was 207 cells/mm³, 66 (62%) had a history of an AIDS-defining opportunistic condition, and 21 (20%) were antiretroviral naïve.</p> <p>Conclusions</p> <p>This paper describes the rationale, methods, and baseline characteristics of subjects enrolled in a randomized clinical trial comparing DAART to SAT in opioid treatment programs.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00279110">NCT00279110</a></p

Generation of Priority Research Questions to Inform Conservation Policy and Management at a National Level

Integrating knowledge from across the natural and social sciences is necessary to effectively address societal tradeoffs between human use of biological diversity and its preservation. Collaborative processes can change the ways decision makers think about scientific evidence, enhance levels of mutual trust and credibility, and advance the conservation policy discourse. Canada has responsibility for a large fraction of some major ecosystems, such as boreal forests, Arctic tundra, wetlands, and temperate and Arctic oceans. Stressors to biological diversity within these ecosystems arise from activities of the country's resource-based economy, as well as external drivers of environmental change. Effective management is complicated by incongruence between ecological and political boundaries and conflicting perspectives on social and economic goals. Many knowledge gaps about stressors and their management might be reduced through targeted, timely research. We identify 40 questions that, if addressed or answered, would advance research that has a high probability of supporting development of effective policies and management strategies for species, ecosystems, and ecological processes in Canada. A total of 396 candidate questions drawn from natural and social science disciplines were contributed by individuals with diverse organizational affiliations. These were collaboratively winnowed to 40 by our team of collaborators. The questions emphasize understanding ecosystems, the effects and mitigation of climate change, coordinating governance and management efforts across multiple jurisdictions, and examining relations between conservation policy and the social and economic well-being of Aboriginal peoples. The questions we identified provide potential links between evidence from the conservation sciences and formulation of policies for conservation and resource management. Our collaborative process of communication and engagement between scientists and decision makers for generating and prioritizing research questions at a national level could be a model for similar efforts beyond Canada

Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1

International audiencePost-transcriptional mechanisms play a predominant role in the control of microRNA (miRNA) production. Recognition of the terminal loop of precursor miRNAs by RNA-binding proteins (RBPs) influences their processing; however, the mechanistic basis for how levels of individual or subsets of miRNAs are regulated is mostly unexplored. We previously showed that hnRNP A1, an RBP implicated in many aspects of RNA processing, acts as an auxiliary factor that promotes the Microprocessor-mediated processing of pri-mir-18a. Here, by using an integrative structural biology approach, we show that hnRNP A1 forms a 1:1 complex with pri-mir-18a where both RNA recognition motifs (RRMs) bind to cognate RNA sequence motifs in the terminal loop of pri-mir-18a. Terminal loop binding induces an allosteric destabilization of base-pairing in the pri-mir-18a stem that promotes its downstream processing. Our results highlight terminal loop RNA recognition by RBPs as a potential general principle of miRNA biogenesis and regulation

Estimating the burden of antimicrobial resistance: a systematic literature review.

Background: Accurate estimates of the burden of antimicrobial resistance (AMR) are needed to establish the magnitude of this global threat in terms of both health and cost, and to paramaterise cost-effectiveness evaluations of interventions aiming to tackle the problem. This review aimed to establish the alternative methodologies used in estimating AMR burden in order to appraise the current evidence base. Methods: MEDLINE, EMBASE, Scopus, EconLit, PubMed and grey literature were searched. English language studies evaluating the impact of AMR (from any microbe) on patient, payer/provider and economic burden published between January 2013 and December 2015 were included. Independent screening of title/abstracts followed by full texts was performed using pre-specified criteria. A study quality score (from zero to one) was derived using Newcastle-Ottawa and Philips checklists. Extracted study data were used to compare study method and resulting burden estimate, according to perspective. Monetary costs were converted into 2013 USD. Results: Out of 5187 unique retrievals, 214 studies were included. One hundred eighty-seven studies estimated patient health, 75 studies estimated payer/provider and 11 studies estimated economic burden. 64% of included studies were single centre. The majority of studies estimating patient or provider/payer burden used regression techniques. 48% of studies estimating mortality burden found a significant impact from resistance, excess healthcare system costs ranged from non-significance to $1 billion per year, whilst economic burden ranged from$21,832 per case to over $3 trillion in GDP loss. Median quality scores (interquartile range) for patient, payer/provider and economic burden studies were 0.67 (0.56-0.67), 0.56 (0.46-0.67) and 0.53 (0.44-0.60) respectively. Conclusions: This study highlights what methodological assumptions and biases can occur dependent on chosen outcome and perspective. Currently, there is considerable variability in burden estimates, which can lead in-turn to inaccurate intervention evaluations and poor policy/investment decisions. Future research should utilise the recommendations presented in this review. Trial registration: This systematic review is registered with PROSPERO (PROSPERO CRD42016037510)

A Unique Radiologic Case of Optic Nerve Infarction in a Patient With Mucormycosis

This is a rare presentation of a unilateral optic nerve infarction of the left eye caused by mucormycosis in a 51-year-old man with poorly controlled Type 2 diabetes. Diffusion-weighted MRI of the orbit demonstrated extensive infarction of the left optic nerve with ipsilateral cavernous sinus thrombosis and periorbital adnexal inflammation. Left orbital exenteration and sinus debridement were performed, and mucormycosis involving the optic nerve sheath was confirmed on histopathology