205 research outputs found

    Does undertaking an intercalated BSc influence first clinical year exam results at a London medical school?

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    Background: Intercalated BScs (iBScs) are an optional part of the medical school curriculum in many Universities. Does undertaking an iBSc influence subsequent student performance? Previous studies addressing this question have been flawed by iBSc students being highly selected. This study looks at data from medical students where there is a compulsory iBSc for non-graduates. Our aim was to see whether there was any difference in performance between students who took an iBSc before or after their third year (first clinical year) exams.Methods: A multivariable analysis was performed to compare the third year results of students at one London medical school who had or had not completed their iBSc by the start of this year (n = 276). A general linear model was applied to adjust for differences between the two groups in terms of potential confounders (age, sex, nationality and baseline performance).Results: The results of third year summative exams for 276 students were analysed (184 students with an iBSc and 92 without). Unadjusted analysis showed students who took an iBSc before their third year achieved significantly higher end of year marks than those who did not with a mean score difference of 4.4 (0.9 to 7.9 95% CI, p = 0.01). (overall mean score 238.4 "completed iBSc" students versus 234.0 "not completed", range 145.2 - 272.3 out of 300). There was however a significant difference between the two groups in their prior second year exam marks with those choosing to intercalate before their third year having higher marks. Adjusting for this, the difference in overall exam scores was no longer significant with a mean score difference of 1.4 (-4.9 to +7.7 95% CI, p = 0.66). (overall mean score 238.0 "completed iBSc" students versus 236.5 "not completed").Conclusions: Once possible confounders are controlled for (age, sex, previous academic performance) undertaking an iBSc does not influence third year exam results. One explanation for this confounding in unadjusted results is that students who do better in their second year exams are more likely to take an iBSc before their third year

    Dominant features in three-dimensional turbulence structure: comparison of non-uniform accelerating and decelerating flows

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    The results are presented from an experimental study to investigate three-dimensional turbulence structure profiles, including turbulence intensity and Reynolds stress, of different non-uniform open channel flows over smooth bed in subcritical flow regime. In the analysis, the uniform flow profiles have been used to compare with those of the non-uniform flows to investigate their time-averaged spatial flow turbulence structure characteristics. The measured non-uniform velocity profiles are used to verify the von Karman constant κ and to estimate sets of log-law integration constant B r and wake parameter П, where their findings are also compared with values from previous studies. From κ, B r and П findings, it has been found that the log-wake law can sufficiently represent the non-uniform flow in its non-modified form, and all κ, B r and П follow universal rules for different bed roughness conditions. The non-uniform flow experiments also show that both the turbulence intensity and Reynolds stress are governed well by exponential pressure gradient parameter β equations. Their exponential constants are described by quadratic functions in the investigated β range. Through this experimental study, it has been observed that the decelerating flow shows higher empirical constants, in both the turbulence intensity and Reynolds stress compared to the accelerating flow. The decelerating flow also has stronger dominance to determine the flow non-uniformity, because it presents higher Reynolds stress profile than uniform flow, whereas the accelerating flow does not

    The Amsterdam Studies of Acute Psychiatry I (ASAP-I); A prospective cohort study of determinants and outcome of coercive versus voluntary treatment interventions in a metropolitan area

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    Background The overall number of involuntary admissions is increasing in many European countries. Patients with severe mental illnesses more often progress to stages in which acute, coercive treatment is warranted. The number of studies that have examined this development and possible consequences in terms of optimizing health care delivery in emergency psychiatry is small and have a number of methodological shortcomings. The current study seeks to examine factors associated with compulsory admissions in the Amsterdam region, taking into account a comprehensive model with four groups of predictors: patient vulnerability, social support, responsiveness of the health care system and treatment adherence. Methods/Design This paper describes the design of the Amsterdam Study of Acute Psychiatry-I (ASAP-I). The study is a prospective cohort study, with one and two-year follow-up, comparing patients with and without forced admission by means of a selected nested case-control design. An estimated total number of 4,600 patients, aged 18 years and over, consecutively coming into contact with the Psychiatric Emergency Service Amsterdam (PESA) are included in the study. From this cohort, a randomly selected group of 125 involuntary admitted subjects and 125 subjects receiving non-coercive treatment are selected for further evaluation and comparison. First, socio-demographic, psychopathological and network characteristics, and prior use of health services will be described for all patients who come into contact with PESA. Second, the in-depth study of compulsory versus voluntary patients will examine which patient characteristics are associated with acute compulsory admission, also taking into account social network and healthcare variables. The third focus of the study is on the associations between patient vulnerability, social support, healthcare characteristics and treatment adherence in a two-year follow-up for patients with or without involuntarily admittance at the index consultation. Discussion The current study seeks to establish a picture of the determinants of acute compulsory admissions in the Netherlands and tries to gain a better understanding of the association with the course of illness and patient's perception of services and treatment adherence. The final aim is to find specific patient and health care factors that can be influenced by adjusting treatment programs in order to reduce the number of involuntary admissions

    Preliminary Investigation of the Corrosion Behavior of Proprietary Micro-alloyed Steels in Aerated and Deaerated Brine Solutions

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    The corrosion performance of fairly new generation of micro-alloyed steels was compared in different concentrations of aerated and deaerated brines. Electrochemical polarization, weight loss and surface analyses techniques were employed. The results showed a threshold of corrosion rate at 3.5 wt.% NaCl in both aerated and deaerated solutions. The average corrosion current density for steel B, for example, increased from 1.3 µA cm¯² in 1 wt.% NaCl to 1.5 µA cm¯² in 3.5 wt.% NaCl, but decreased to 1.4 µA cm¯² in 10 wt.% deaerated NaCl solutions. The aerated solutions exhibited an average of over 80% increase in corrosion current density in the respective concentrations when compared with the deaerated solution. These results can be attributed to the effects of dissolved oxygen (DO) which has a maximum solubility in 3.5 wt.% NaCl. DO as a depolarizer and electron acceptor in cathodic reactions accelerates anodic metal dissolution. The difference in carbon content and microstructures occasioned by thermo-mechanical treatment contributed to the witnessed variation in corrosion performance of the steels. Specifically, the results of the various corrosion techniques corroborated each other and showed that the corrosion rate of the micro-alloyed steels can be ranked as CR[Steel A] < CRₓ₆₅ < CR[Steel B] < CR[Steel C]

    In vivo assembly of the axon initial segment in motor neurons

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    International audienceThe axon initial segment (AIS) is responsible for both the modulation of action potentials and the maintenance of neuronal polarity. Yet, the molecular mechanisms controlling its assembly are incompletely understood. Our study in single electroporated motor neurons in mouse embryos revealed that AnkyrinG (AnkG), the AIS master organizer, is undetectable in bipolar migrating motor neurons, but is already expressed at the beginning of axonogenesis at E9.5 and initially distributed homogeneously along the entire growing axon. Then, from E11.5, a stage when AnkG is already apposed to the membrane, as observed by electron microscopy, the protein progressively becomes restricted to the proximal axon. Analysis on the global motor neurons population indicated that Neurofascin follows an identical spatio-temporal distribution, whereas sodium channels and beta 4-spectrin only appear along AnkG(+) segments at E11.5. Early patch-clamp recordings of individual motor neurons indicated that at E12.5 these nascent AISs are already able to generate spikes. Using knock-out mice, we demonstrated that neither beta 4-spectrin nor Neurofascin control the distal-to-proximal restriction of AnkG

    The Targeting of Plasmalemmal Ceramide to Mitochondria during Apoptosis

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    Ceramide is a key lipid mediator of cellular processes such as differentiation, proliferation, growth arrest and apoptosis. During apoptosis, ceramide is produced within the plasma membrane. Although recent data suggest that the generation of intracellular ceramide increases mitochondrial permeability, the source of mitochondrial ceramide remains unknown. Here, we determine whether a stress-mediated plasmalemmal pool of ceramide might become available to the mitochondria of apoptotic cells. We have previously established annexin A1—a member of a family of Ca2+ and membrane-binding proteins—to be a marker of ceramide platforms. Using fluorescently tagged annexin A1, we show that, upon its generation within the plasma membrane, ceramide self-associates into platforms that subsequently invaginate and fuse with mitochondria. An accumulation of ceramide within the mitochondria of apoptotic cells was also confirmed using a ceramide-specific antibody. Electron microscopic tomography confirmed that upon the formation of ceramide platforms, the invaginated regions of the plasma membrane extend deep into the cytoplasm forming direct physical contacts with mitochondrial outer membranes. Ceramide might thus be directly transferred from the plasma membrane to the mitochondrial outer membrane. It is conceivable that this “kiss-of-death” increases the permeability of the mitochondrial outer membrane thereby triggering apoptosis

    Weaned age variation in the Virunga mountain gorillas (Gorilla beringei beringei)

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    The final publication is available at Springer via http://dx.doi.org/10.1007/s00265-016-2066-6Weaning marks an important milestone during life history in mammals indicating nutritional independence from the mother. Age at weaning is a key measure of maternal investment and care, affecting female reproductive rates, offspring survival and ultimately the viability of a population. Factors explaining weaned age variation in the endangered mountain gorilla are not yet well understood. This study investigated the impact of group size, group type (one-male versus multi-male), offspring sex, as well as maternal age, rank, and parity on weaned age variation in the Virunga mountain gorilla population. The status of nutritional independence was established in 69 offspring using long-term suckling observations. A Cox-regression with mixed effects was applied to model weaned age and its relationship with covariates. Findings indicate that offspring in one-male groups are more likely to be weaned earlier than offspring in multi-male groups, which may reflect a female reproductive strategy to reduce higher risk of infanticide in one-male groups. Inferior milk production capacity and conflicting resource allocation between their own and offspring growth may explain later weaning in primiparous mothers compared to multiparous mothers. Sex-biased weaned age related to maternal condition defined by parity, rank, and maternal age will be discussed in the light of the Trivers-Willard hypothesis. Long-term demographic records revealed no disadvantage of early weaning for mother or offspring. Population growth and two peaks in weaned age within the Virunga population encourage future studies on the potential impact of bamboo shoots as a weaning food and other environmental factors on weaning

    Sequential Metabolism of 7-Dehydrocholesterol to Steroidal 5,7-Dienes in Adrenal Glands and Its Biological Implication in the Skin

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    Since P450scc transforms 7-dehydrocholesterol (7DHC) to 7-dehydropregnenolone (7DHP) in vitro, we investigated sequential 7DHC metabolism by adrenal glands ex vivo. There was a rapid, time- and dose-dependent metabolism of 7DHC by adrenals from rats, pigs, rabbits and dogs with production of more polar 5,7-dienes as detected by RP-HPLC. Based on retention time (RT), UV spectra and mass spectrometry, we identified the major products common to all tested species as 7DHP, 22-hydroxy-7DHC and 20,22-dihydroxy-7DHC. The involvement of P450scc in adrenal metabolic transformation was confirmed by the inhibition of this process by DL-aminoglutethimide. The metabolism of 7DHC with subsequent production of 7DHP was stimulated by forscolin indicating involvement of cAMP dependent pathways. Additional minor products of 7DHC metabolism that were more polar than 7DHP were identified as 17-hydroxy-7DHP (in pig adrenals but not those of rats) and as pregna-4,7-diene-3,20-dione (7-dehydroprogesterone). Both products represented the major identifiable products of 7DHP metabolism in adrenal glands. Studies with purified enzymes show that StAR protein likely transports 7DHC to the inner mitochondrial membrane, that 7DHC can compete effectively with cholesterol for the substrate binding site on P450scc and that the catalytic efficiency of 3βHSD for 7DHP (Vm/Km) is 40% of that for pregnenolone. Skin mitochondria are capable of transforming 7DHC to 7DHP and the 7DHP is metabolized further by skin extracts. Finally, 7DHP, its photoderivative 20-oxopregnacalciferol, and pregnenolone exhibited biological activity in skin cells including inhibition of proliferation of epidermal keratinocytes and melanocytes, and melanoma cells. These findings define a novel steroidogenic pathway: 7DHC→22(OH)7DHC→20,22(OH)27DHC→7DHP, with potential further metabolism of 7DHP mediated by 3βHSD or CYP17, depending on mammalian species. The 5–7 dienal intermediates of the pathway can be a source of biologically active vitamin D3 derivatives after delivery to or production in the skin, an organ intermittently exposed to solar radiation

    IL-1α Signaling Is Critical for Leukocyte Recruitment after Pulmonary Aspergillus fumigatus Challenge

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    Aspergillus fumigatus is a mold that causes severe pulmonary infections. Our knowledge of how A. fumigatus growth is controlled in the respiratory tract is developing, but still limited. Alveolar macrophages, lung resident macrophages, and airway epithelial cells constitute the first lines of defense against inhaled A. fumigatus conidia. Subsequently, neutrophils and inflammatory CCR2+ monocytes are recruited to the respiratory tract to prevent fungal growth. However, the mechanism of neutrophil and macrophage recruitment to the respiratory tract after A. fumigatus exposure remains an area of ongoing investigation. Here we show that A. fumigatus pulmonary challenge induces expression of the inflammasome-dependent cytokines IL-1β and IL-18 within the first 12 hours, while IL-1α expression continually increases over at least the first 48 hours. Strikingly, Il1r1-deficient mice are highly susceptible to pulmonary A. fumigatus challenge exemplified by robust fungal proliferation in the lung parenchyma. Enhanced susceptibility of Il1r1-deficient mice correlated with defects in leukocyte recruitment and anti-fungal activity. Importantly, IL-1α rather than IL-1β was crucial for optimal leukocyte recruitment. IL-1α signaling enhanced the production of CXCL1. Moreover, CCR2+ monocytes are required for optimal early IL-1α and CXCL1 expression in the lungs, as selective depletion of these cells resulted in their diminished expression, which in turn regulated the early accumulation of neutrophils in the lung after A. fumigatus challenge. Enhancement of pulmonary neutrophil recruitment and anti-fungal activity by CXCL1 treatment could limit fungal growth in the absence of IL-1α signaling. In contrast to the role of IL-1α in neutrophil recruitment, the inflammasome and IL-1β were only essential for optimal activation of anti-fungal activity of macrophages. As such, Pycard-deficient mice are mildly susceptible to A. fumigatus infection. Taken together, our data reveal central, non-redundant roles for IL-1α and IL-1β in controlling A. fumigatus infection in the murine lung
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