Seasonal Changes in Microbial Dissolved Organic Sulfur Transformations in Coastal Waters

The marine trace gas dimethylsulfide (DMS) is the single most important biogenic source of atmospheric sulfur, accounting for up to 80% of global biogenic sulfur emissions. Approximately 300milliontonsofDMSareproducedannually,butthemajorityisdegradedbymicrobesinseawater. The DMS precursor dimethylsulfoniopropionate (DMSP) and oxidation product dimethylsulphoxide (DMSO) are also important organic sulfur reservoirs. However, the marine sinks of dissolved DMSO remain unknown. We used a novel combination of stable and radiotracers to determine seasonal changes in multiple dissolved organic sulfur transformation rates to ascertain whether microbial uptake of dissolved DMSO was a significant loss pathway. Surface concentrations of DMS ranged from 0.5 to 17.0 nM with biological consumption rates between 2.4 and 40.8 nM·d−1. DMS produced from the reduction of DMSO was not a significant process. Surface concentrations of total DMSO ranged from 2.3 to 102 nM with biological consumption of dissolved DMSO between 2.9 and 111 nM·d−1. Comparisons between 14C2-DMSO assimilation and dissimilation rates suggest that the majority of dissolved DMSO was respired (>94%). Radiotracer microbial consumption rates suggest that dissimilation of dissolved DMSO to CO2 can be a significant loss pathway in coastal waters, illustrating the significance of bacteria in controlling organic sulfur seawater concentrations

An International Study of the Ability and Cost-Effectiveness of Advertising Methods to Facilitate Study Participant Self-Enrolment Into a Pilot Pharmacovigilance Study During Early Pregnancy

Knowledge of the fetal effects of maternal medication use in pregnancy is often inadequate and current pregnancy pharmacovigilance (PV) surveillance methods have important limitations. Patient self-reporting may be able to mitigate some of these limitations, providing an adequately sized study sample can be recruited.To compare the ability and cost-effectiveness of several direct-to-participant advertising methods for the recruitment of pregnant participants into a study of self-reported gestational exposures and pregnancy outcomes.The Pharmacoepidemiological Research on Outcomes of Therapeutics by a European Consortium (PROTECT) pregnancy study is a non-interventional, prospective pilot study of self-reported medication use and obstetric outcomes provided by a cohort of pregnant women that was conducted in Denmark, the Netherlands, Poland, and the United Kingdom. Direct-to-participant advertisements were provided via websites, emails, leaflets, television, and social media platforms.Over a 70-week recruitment period direct-to-participant advertisements engaged 43,234 individuals with the study website or telephone system; 4.78% (2065/43,234) of which were successfully enrolled and provided study data. Of these 90.4% (1867/2065) were recruited via paid advertising methods, 23.0% (475/2065) of whom were in the first trimester of pregnancy. The overall costs per active recruited participant were lowest for email (€23.24) and website (€24.41) advertisements and highest for leaflet (€83.14) and television (€100.89). Website adverts were substantially superior in their ability to recruit participants during their first trimester of pregnancy (317/668, 47.5%) in comparison with other advertising methods (P<.001). However, we identified international variations in both the cost-effectiveness of the various advertisement methods used and in their ability to recruit participants in early pregnancy.Recruitment of a pregnant cohort using direct-to-participant advertisement methods is feasible, but the total costs incurred are not insubstantial. Future research is needed to identify advertising strategies capable of recruiting large numbers of demographically representative pregnant women, preferentially in early pregnancy

The antecedents and outcomes of persistent and remitting adolescent depressive symptom trajectories:a longitudinal, population-based English study

Background Depression often first emerges in adolescence and, for many, is a lifelong disorder. The long-term clinical course of depression is highly variable. We aimed to examine the adult outcomes of adolescent-onset trajectories of clinically significant depressive symptoms and to identify factors differentiating trajectories that persist and desist in adulthood. Methods We included participants from the English population-based Avon Longitudinal Study of Parents and Children with data on depressive symptoms. Self-reported depression symptoms were assessed on ten occasions when participants were age 10·5–25 years using the short Mood and Feelings Questionnaire, and major depressive disorder episodes were assessed at age 13·0 years, 15·0 years, 17·5 years, and 25·0 years. We characterised trajectories of depression symptoms using latent class growth analysis, for which we required depression data at least once from each of three key phases: ages 10·5–13·5 years; 16·5–18·5 years; and 21–25 years. We examined adult outcomes by assessing lifetime suicidal self-harm and functional impairment at age 24·0 years, and employment, education, and the self-reported Strengths and Difficulties Questionnaire at age 25·0 years. Findings We studied 4234 participants: 2651 (63%) female, 1582 (37%) male, and one individual with missing sex data. The mean age was 10·6 years (SD 0·2) at baseline and 25·8 years (SD 0·5) at the final timepoint. Data on ethnicity were not available in our data set. We identified four depression trajectory classes: adolescent-persistent depression with onset early in adolescence (7%, n≈279), adolescent-limited depression with onset later in adolescence and remittance by adult life (14%, n≈592), adult-increasing depression (25%, n≈1056), and stable-low levels of depression (54%, n≈2307). The adolescent-persistent class was associated with poor adult outcomes for functional impairment (62%), suicidal self-harm (27%), mental health difficulties (25%), and not being in education, employment, or training (16%). Adolescent-limited depression was associated with transient adolescent stress, but by early adulthood functional impairment and mental health difficulties were similar to the stable-low group. Major depressive disorder polygenic score (odds ratio [OR] 1·36, 95% CI 1·04–1·79), adolescent educational attainment (OR 0·47, 0·30–0·74), and any early childhood adversity (OR 2·60, 1·42–4·78), that persisted into adulthood (OR 1·60, 1·38–1·87) distinguished the adolescent-persistent and adolescent-limited groups. Interpretation The future course of adolescent depression can be differentiated by age at onset during adolescence, adolescent academic attainment, early and persistent adversity, and genetic loading. A detailed social and educational history could be helpful in making clinical decisions about the intensity of interventions for young people with clinically elevated depressive symptoms who seek help

Predictive use of the Maximum Entropy Production principle for Past and Present Climates

In this paper, we show how the MEP hypothesis may be used to build simple climate models without representing explicitly the energy transport by the atmosphere. The purpose is twofold. First, we assess the performance of the MEP hypothesis by comparing a simple model with minimal input data to a complex, state-of-the-art General Circulation Model. Next, we show how to improve the realism of MEP climate models by including climate feedbacks, focusing on the case of the water-vapour feedback. We also discuss the dependence of the entropy production rate and predicted surface temperature on the resolution of the model

Knockout studies reveal an important role of <i>plasmodium</i> lipoic acid protein ligase a1 for asexual blood stage parasite survival

Lipoic acid (LA) is a dithiol-containing cofactor that is essential for the function of a-keto acid dehydrogenase complexes. LA acts as a reversible acyl group acceptor and 'swinging arm' during acyl-coenzyme A formation. The cofactor is post-translationally attached to the acyl-transferase subunits of the multienzyme complexes through the action of octanoyl (lipoyl): &lt;i&gt;N&lt;/i&gt;-octanoyl (lipoyl) transferase (LipB) or lipoic acid protein ligases (LplA). Remarkably, apicomplexan parasites possess LA biosynthesis as well as scavenging pathways and the two pathways are distributed between mitochondrion and a vestigial organelle, the apicoplast. The apicoplast-specific LipB is dispensable for parasite growth due to functional redundancy of the parasite's lipoic acid/octanoic acid ligases/transferases. In this study, we show that &lt;i&gt;LplA1&lt;/i&gt; plays a pivotal role during the development of the erythrocytic stages of the malaria parasite. Gene disruptions in the human malaria parasite &lt;i&gt;P.falciparum&lt;/i&gt; consistently were unsuccessful while in the rodent malaria model parasite &lt;i&gt;P. berghei&lt;/i&gt; the &lt;i&gt;LplA1&lt;/i&gt; gene locus was targeted by knock-in and knockout constructs. However, the &lt;i&gt;LplA1&lt;/i&gt; &lt;sup&gt;(-)&lt;/sup&gt; mutant could not be cloned suggesting a critical role of LplA1 for asexual parasite growth &lt;i&gt;in vitro&lt;/i&gt; and &lt;i&gt;in vivo&lt;/i&gt;. These experimental genetics data suggest that lipoylation during expansion in red blood cells largely occurs through salvage from the host erythrocytes and subsequent ligation of LA to the target proteins of the malaria parasite

SNPLims: a data management system for genome wide association studies

<p>Abstract</p> <p>Background</p> <p>Recent progresses in genotyping technologies allow the generation high-density genetic maps using hundreds of thousands of genetic markers for each DNA sample. The availability of this large amount of genotypic data facilitates the whole genome search for genetic basis of diseases.</p> <p>We need a suitable information management system to efficiently manage the data flow produced by whole genome genotyping and to make it available for further analyses.</p> <p>Results</p> <p>We have developed an information system mainly devoted to the storage and management of SNP genotype data produced by the Illumina platform from the raw outputs of genotyping into a relational database.</p> <p>The relational database can be accessed in order to import any existing data and export user-defined formats compatible with many different genetic analysis programs.</p> <p>After calculating family-based or case-control association study data, the results can be imported in SNPLims. One of the main features is to allow the user to rapidly identify and annotate statistically relevant polymorphisms from the large volume of data analyzed. Results can be easily visualized either graphically or creating ASCII comma separated format output files, which can be used as input to further analyses.</p> <p>Conclusions</p> <p>The proposed infrastructure allows to manage a relatively large amount of genotypes for each sample and an arbitrary number of samples and phenotypes. Moreover, it enables the users to control the quality of the data and to perform the most common screening analyses and identify genes that become “candidate” for the disease under consideration.</p

Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration

Human genetic studies have suggested that polymorphisms of the GABRA2 gene encoding the GABA(A) α2-subunit are associated with ethanol dependence. Variations in this gene also convey sensitivity to the subjective effects of ethanol, indicating a role in mediating ethanol-related behaviours. We therefore investigated the consequences of deleting the α2-subunit on the ataxic and rewarding properties of ethanol in mice. Ataxic and sedative effects of ethanol were explored in GABA(A) α2-subunit wildtype (WT) and knockout (KO) mice using a Rotarod apparatus, wire hang and the duration of loss of righting reflex. Following training, KO mice showed shorter latencies to fall than WT littermates under ethanol (2 g/kg i.p.) in both Rotarod and wire hang tests. After administration of ethanol (3.5 g/kg i.p.), KO mice took longer to regain the righting reflex than WT mice. To ensure the acute effects are not due to the gabra2 deletion affecting pharmacokinetics, blood ethanol concentrations were measured at 20 minute intervals after acute administration (2 g/kg i.p.), and did not differ between genotypes. To investigate ethanol's rewarding properties, WT and KO mice were trained to lever press to receive increasing concentrations of ethanol on an FR4 schedule of reinforcement. Both WT and KO mice self-administered ethanol at similar rates, with no differences in the numbers of reinforcers earned. These data indicate a protective role for α2-subunits, against the acute sedative and ataxic effects of ethanol. However, no change was observed in ethanol self administration, suggesting the rewarding effects of ethanol remain unchange

Mining and analysis of audiology data to find significant factors associated with tinnitus masker

Objectives: The objective of this research is to find the factors associated with tinnitus masker from the literature, and by using the large amount of audiology data available from a large NHS (National Health Services, UK) hearing aid clinic. The factors evaluated were hearing impairment, age, gender, hearing aid type, mould and clinical comments. Design: The research includes literature survey for factors associated with tinnitus masker, and performs the analysis of audiology data using statistical and data mining techniques. Setting: This research uses a large audiology data but it also faced the problem of limited data for tinnitus. Participants: It uses 1,316 records for tinnitus and other diagnoses, and 10,437 records of clinical comments from a hearing aid clinic. Primary and secondary outcome measures: The research is looking for variables associated with tinnitus masker, and in future, these variables can be combined into a single model to develop a decision support system to predict about tinnitus masker for a patient. Results: The results demonstrated that tinnitus maskers are more likely to be fit to individuals with milder forms of hearing loss, and the factors age, gender, type of hearing aid and mould were all found significantly associated with tinnitus masker. In particular, those patients having Age<=55 years were more likely to wear a tinnitus masker, as well as those with milder forms of hearing loss. ITE (in the ear) hearing aids were also found associated with tinnitus masker. A feedback on the results of association of mould with tinnitus masker from a professional audiologist of a large NHS (National Health Services, UK) was also taken to better understand them. The results were obtained with different accuracy for different techniques. For example, the chi-squared test results were obtained with 95% accuracy, for Support and Confidence only those results were retained which had more than 1% Support and 80% Confidence. Conclusions: The variables audiograms, age, gender, hearing aid type and mould were found associated with the choice of tinnitus masker in the literature and by using statistical and data mining techniques. The further work in this research would lead to the development of a decision support system for tinnitus masker with an explanation that how that decision was obtained

Using interpretative phenomenological analysis to inform physiotherapy practice: An introduction with reference to the lived experience of cerebellar ataxia

The attached file is a pre-published version of the full and final paper which can be found at the link below.This article has been made available through the Brunel Open Access Publishing Fund.Qualitative research methods that focus on the lived experience of people with health conditions are relatively underutilised in physiotherapy research. This article aims to introduce interpretative phenomenological analysis (IPA), a research methodology oriented toward exploring and understanding the experience of a particular phenomenon (e.g., living with spinal cord injury or chronic pain, or being the carer of someone with a particular health condition). Researchers using IPA try to find out how people make sense of their experiences and the meanings they attach to them. The findings from IPA research are highly nuanced and offer a fine grained understanding that can be used to contextualise existing quantitative research, to inform understanding of novel or underresearched topics or, in their own right, to provoke a reappraisal of what is considered known about a specified phenomenon. We advocate IPA as a useful and accessible approach to qualitative research that can be used in the clinical setting to inform physiotherapy practice and the development of services from the perspective of individuals with particular health conditions.This article is available through the Brunel Open Access Publishing Fund

Androgen secreting steroid cell tumor of the ovary in a young lactating women with acute onset of severe hyperandrogenism: a case report and review of literature

<p>Abstract</p> <p>Introduction</p> <p>Steroid cell tumors of the ovary account for less than 0.1% of all ovarian tumors <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> and these tumours may present at any age in association with interesting presentations related to the hormonal activity and virilizing properties of tumor. Hayes and Scully <abbrgrp><abbr bid="B2">2</abbr></abbrgrp> reported 63 cases in patients ranging from 2 to 80 years of age. The subtype, not otherwise specified, is associated with androgenic changes in approximately one half of patients with this tumour <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. In a series of 63 cases from Massachusetts General Hospital, 94% of the tumors were found to be unilateral and 28.6% were malignant <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>. As most of these tumors are diagnosed at an early stage and do not recur or metastasize, little is known about their response to therapies such as chemotherapy or radiation <abbrgrp><abbr bid="B3">3</abbr></abbrgrp>.</p> <p>Case Presentation</p> <p>We present the case of a 22-year old lactating woman who presented with four months of amenorrhea associated with signs of virilization. Clinical and diagnostic evaluation revealed a right adenexal mass and elevated serum levels of testosterone and she was diagnosed as having a stage 1A androgen secreting steroid cell tumor. In view of the early stage of the disease, she underwent right salpingo-oopherectomy. Histopathological examination and immunohistochemistry confirmed the diagnosis. Two months after surgery she regained normal menses and showed regression of the androgenic changes.</p> <p>Conclusion</p> <p>Surgery remains the mainstay of the treatment of gonadotrophin receptor positive steroid cell tumors although medical therapy using Gonadotrophin Releasing Hormone [GnRH analogues has been tried recently in recurrent or inoperable cases. There is no described effective chemotherapy or radiotherapy for this condition.</p