578 research outputs found

    The diagnosis of posttraumatic stress disorder in school-aged children and adolescents following pediatric intensive care unit admission

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    Objectives: This study explored the diagnosis of posttraumatic stress disorder (PTSD) in children and adolescents following pediatric intensive care unit (PICU) admission. Specifically, the study aimed to describe the presentation and prevalence of PTSD symptoms 6 months postdischarge, explore the validity of the DSM-IV PTSD algorithm and alternative PTSD algorithm (PTSD-AA) in school-aged children and adolescents, and examine the diagnostic utility of Criterion C3 (inability to recall aspects of a trauma) in this cohort

    Fine‐scale geothermal heat flow in Antarctica can increase simulated subglacial melt estimates

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    Antarctic geothermal heat flow (GHF) affects the thermal regime of ice sheets and simulations of ice and subglacial meltwater discharge to the ocean, but remains poorly constrained. We use an ice sheet model to investigate the impact of GHF anomalies on subglacial meltwater production in the Aurora Subglacial Basin, East Antarctica. We find that spatially-variable GHF fields produce more meltwater than a constant GHF with the same background mean, and meltwater production increases as the resolution of GHF anomalies increases. Our results suggest that model simulations of this region systematically underestimate meltwater production using current GHF models. We determine the minimum basal heating required to bring the basal ice temperature to the pressure melting point, which should be taken together with the scale-length of likely local variability in targeting in-situ GHF field campaigns

    Tetrahydropyrazolo[1,5-a]Pyrimidine-3-Carboxamide and N-Benzyl-6′,7′-Dihydrospiro[Piperidine-4,4′-Thieno[3,2-c]Pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3

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    Mycobacterium tuberculosis is a major human pathogen and the causative agent for the pulmonary disease, tuberculosis (TB). Current treatment programs to combat TB are under threat due to the emergence of multi-drug and extensively-drug resistant TB. As part of our efforts towards the discovery of new anti-tubercular leads, a number of potent tetrahydropyrazolo[1,5-a]pyrimidine-3-ca​rboxamide(THPP) and N-benzyl-6′,7′-dihydrospiro[piperidine-4,​4′-thieno[3,2-c]pyran](Spiro) analogues were recently identified against Mycobacterium tuberculosis and Mycobacterium bovis BCG through a high-throughput whole-cell screening campaign. Herein, we describe the attractive in vitro and in vivo anti-tubercular profiles of both lead series. The generation of M. tuberculosis spontaneous mutants and subsequent whole genome sequencing of several resistant mutants identified single mutations in the essential mmpL3 gene. This ‘genetic phenotype’ was further confirmed by a ‘chemical phenotype’, whereby M. bovis BCG treated with both the THPP and Spiro series resulted in the accumulation of trehalose monomycolate. In vivo efficacy evaluation of two optimized THPP and Spiro leads showed how the compounds were able to reduce >2 logs bacterial cfu counts in the lungs of infected mice

    Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin

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    Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio

    A qualitative investigation of breast cancer survivors’ experiences with breastfeeding

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    This is an exploratory, qualitative investigation of breast cancer survivors’ experiences with breastfeeding. Previous studies have focused on the physiology of lactation after surgery and treatment, but have not explored factors influencing breastfeeding decisions and behavior. We used purposeful sampling to identify 11 breast cancer survivors who had a child after their diagnosis and treatment. Participants were recruited from among those in the Women’s Healthy Eating and Living (WHEL) study and a Young Survival Coalition (YSC) affiliate. We conducted semi-structured, open-ended telephone interviews lasting 45–75 min. We used social cognitive theory (SCT) to structure questions regarding influences on breastfeeding behavior. We transcribed interviews and used cross-case, inductive analysis to identify themes. Ten of 11 participants initiated breastfeeding. The following main themes emerged: 1) Cautiously hopeful, 2) Exhausting to rely on one breast, 3) Motivated despite challenges, 4) Support and lack of support, and 5) Encouraging to others. Study participants were highly motivated to breastfeed but faced considerable challenges. Participants described problems that are not unique to women with breast cancer, but experienced these to a much greater degree because they relied mostly or entirely on one lactating breast. This study revealed a need for improved access to information and support and greater sensitivity to the obstacles faced by breast cancer survivors. Results of this qualitative analysis indicate that interventions to support the efforts of breast cancer survivors who are interested in breastfeeding are warranted. Additional research would aid in the development of such interventions

    Reproductive Phase Locking of Mosquito Populations in Response to Rainfall Frequency

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    The frequency of moderate to heavy rainfall events is projected to change in response to global warming. Here we show that these hydrologic changes may have a profound effect on mosquito population dynamics and rates of mosquito-borne disease transmission. We develop a simple model, which treats the mosquito reproductive cycle as a phase oscillator that responds to rainfall frequency forcing. This model reproduces observed mosquito population dynamics and indicates that mosquito-borne disease transmission can be sensitive to rainfall frequency. These findings indicate that changes to the hydrologic cycle, in particular the frequency of moderate to heavy rainfall events, could have a profound effect on the transmission rates of some mosquito-borne diseases

    The cost of large numbers of hypothesis tests on power, effect size and sample size

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    Advances in high-throughput biology and computer science are driving an exponential increase in the number of hypothesis tests in genomics and other scientific disciplines. Studies using current genotyping platforms frequently include a million or more tests. In addition to the monetary cost, this increase imposes a statistical cost owing to the multiple testing corrections needed to avoid large numbers of false-positive results. To safeguard against the resulting loss of power, some have suggested sample sizes on the order of tens of thousands that can be impractical for many diseases or may lower the quality of phenotypic measurements. This study examines the relationship between the number of tests on the one hand and power, detectable effect size or required sample size on the other. We show that once the number of tests is large, power can be maintained at a constant level, with comparatively small increases in the effect size or sample size. For example at the 0.05 significance level, a 13% increase in sample size is needed to maintain 80% power for ten million tests compared with one million tests, whereas a 70% increase in sample size is needed for 10 tests compared with a single test. Relative costs are less when measured by increases in the detectable effect size. We provide an interactive Excel calculator to compute power, effect size or sample size when comparing study designs or genome platforms involving different numbers of hypothesis tests. The results are reassuring in an era of extreme multiple testing

    Psychosis with paranoid delusions after a therapeutic dose of mefloquine: a case report

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    BACKGROUND: Convenient once-a-week dosing has made mefloquine a popular choice as malaria prophylaxis for travel to countries with chloroquine-resistant malaria. However, the increased use of mefloquine over the past decade has resulted in reports of rare, but severe, neuropsychiatric adverse reactions, such as anxiety, depression, hallucinations and psychosis. A direct causality between mefloquine and severe reactions among travelers has been partly confounded by factors associated with foreign travel and, in the case of therapeutic doses of mefloquine, the central nervous system manifestations of Plasmodium infection itself. The present case provides a unique natural history of mefloquine-induced neuropsychiatric toxicity and revisits its dose-dependent nature. CASE PRESENTATION: This report describes an acute exacerbation of neuropsychiatric symptoms after an unwarranted therapeutic dose (1250 mg) of mefloquine in a 37-year-old male previously on a once-a-week prophylactic regimen. Neuropsychiatric symptoms began as dizziness and insomnia of several days duration, which was followed by one week of escalating anxiety and subtle alterations in behaviour. The patient's anxiety culminated into a panic episode with profound sympathetic activation. One week later, he was hospitalized after developing frank psychosis with psychomotor agitation and paranoid delusions. His psychosis remitted with low-dose quetiapine. CONCLUSION: This report suggests that an overt mefloquine-induced psychosis can be preceded by a prodromal phase of moderate symptoms such as dizziness, insomnia, and generalized anxiety. It is important that physicians advise patients taking mefloquine prophylaxis and their relatives to recognize such symptoms, especially when they are accompanied by abrupt, but subtle, changes in behaviour. Patients with a history of psychiatric illness, however minor, may be at increased risk for a mefloquine-induced neuropsychiatric toxicity. Physicians must explicitly caution patients not to self-medicate with a therapeutic course of mefloquine when a malaria diagnosis has not been confirmed

    Does Sex Trade with Violence among Genotypes in Drosophila melanogaster?

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    The evolutionary forces shaping the ability to win competitive interactions, such as aggressive encounters, are still poorly understood. Given a fitness advantage for competitive success, variance in aggressive and sexual display traits should be depleted, but a great deal of variation in these traits is consistently found. While life history tradeoffs have been commonly cited as a mechanism for the maintenance of variation, the variability of competing strategies of conspecifics may mean there is no single optimum strategy. We measured the genetically determined outcomes of aggressive interactions, and the resulting effects on mating success, in a panel of diverse inbred lines representing both natural variation and artificially selected genotypes. Males of one genotype which consistently lost territorial encounters with other genotypes were nonetheless successful against males that were artificially selected for supernormal aggression and dominated all other lines. Intransitive patterns of territorial success could maintain variation in aggressive strategies if there is a preference for territorial males. Territorial success was not always associated with male mating success however and females preferred ‘winners’ among some male genotypes, and ‘losers’ among other male genotypes. This suggests that studying behaviour from the perspective of population means may provide limited evolutionary and genetic insight. Overall patterns of competitive success among males and mating transactions between the sexes are consistent with mechanisms proposed for the maintenance of genetic variation due to nonlinear outcomes of competitive interactions
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