The specialty choices of graduates from Brighton and Sussex Medical School: a longitudinal cohort study

BACKGROUND Since 2007 junior doctors in the UK have had to make major career decisions at a point when previously many had not yet chosen a specialty. This study examined when doctors in this new system make specialty choices, which factors influence choices, and whether doctors who choose a specialty they were interested in at medical school are more confident in their choice than those doctors whose interests change post-graduation. METHODS Two cohorts of students in their penultimate year at one medical school (n = 227/239) were asked which specialty interested them as a career. Two years later, 210/227 were sent a questionnaire measuring actual specialty chosen, confidence, influence of perceptions of the specialty and experiences on choice, satisfaction with medicine, personality, self-efficacy, and demographics. Medical school and post-graduation choices in the same category were deemed 'stable'. Predictors of stability, and of not having chosen a specialty, were calculated using bootstrapped logistic regression. Differences between specialties on questionnaire factors were analysed. RESULTS 50% responded (n = 105/277; 44% of the 239 Year 4 students). 65% specialty choices were 'stable'. Factors univariately associated with stability were specialty chosen, having enjoyed the specialty at medical school or since starting work, having first considered the specialty earlier. A regression found doctors who chose psychiatry were more likely to have changed choice than those who chose general practice. Confidence in the choice was not associated with stability. Those who chose general practice valued lifestyle factors. A psychiatry choice was associated with needing a job and using one's intellect to help others. The decision to choose surgical training tended to be made early. Not having applied for specialty training was associated with being lower on agreeableness and conscientiousness. CONCLUSION Medical school experiences are important in specialty choice but experiences post-graduation remain significant, particularly in some specialties (psychiatry in our sample). Career guidance is important at medical school and should be continued post-graduation, with senior clinicians supported in advising juniors. Careers advice in the first year post-graduation may be particularly important, especially for specialties which have difficulty recruiting or are poorly represented at medical school

Natural variation in immune responses to neonatal mycobacterium bovis bacillus calmette-guerin (BCG) vaccination in a cohort of Gambian infants

Background There is a need for new vaccines for tuberculosis (TB) that protect against adult pulmonary disease in regions where BCG is not effective. However, BCG could remain integral to TB control programmes because neonatal BCG protects against disseminated forms of childhood TB and many new vaccines rely on BCG to prime immunity or are recombinant strains of BCG. Interferon-gamma (IFN-) is required for immunity to mycobacteria and used as a marker of immunity when new vaccines are tested. Although BCG is widely given to neonates IFN- responses to BCG in this age group are poorly described. Characterisation of IFN- responses to BCG is required for interpretation of vaccine immunogenicity study data where BCG is part of the vaccination strategy. Methodology/Principal Findings 236 healthy Gambian babies were vaccinated with M. bovis BCG at birth. IFN-, interleukin (IL)-5 and IL-13 responses to purified protein derivative (PPD), killed Mycobacterium tuberculosis (KMTB), M. tuberculosis short term culture filtrate (STCF) and M. bovis BCG antigen 85 complex (Ag85) were measured in a whole blood assay two months after vaccination. Cytokine responses varied up to 10 log-fold within this population. The majority of infants (89-98% depending on the antigen) made IFN- responses and there was significant correlation between IFN- responses to the different mycobacterial antigens (Spearman’s coefficient ranged from 0.340 to 0.675, p=10-6-10-22). IL-13 and IL-5 responses were generally low and there were more non-responders (33-75%) for these cytokines. Nonetheless, significant correlations were observed for IL-13 and IL-5 responses to different mycobacterial antigens Conclusions/Significance Cytokine responses to mycobacterial antigens in BCG-vaccinated infants are heterogeneous and there is significant inter-individual variation. Further studies in large populations of infants are required to identify the factors that determine variation in IFN- responses

Assessment of Chemical Inhibitor Addition to Improve the Gas Production from Biowaste

The coexistence of sulphate-reducing bacteria and methanogenic archaea in the reactors during the anaerobic digestion from sulphate-containing waste could favor the accumulation of sulfide on the biogas, and therefore reduce its quality. In this study, the effect of sulphate-reducing bacteria inhibitor (MoO−2 4 ) addition in a two phase system from sulphate-containing municipal solid waste to improve the quality of the biogas has been investigated. The results showed that although SRB and sulphide production decreased, the use of inhibitor was not effective to improve the anaerobic digestion in a two phase system from sulphate-containing waste, since a significant decrease on biogas and organic matter removal were observed. Before MoO−2 4 addition the average values of volatile solid were around 12 g/kg, after 5 days of inhibitor use, those values did exceed to 28 g/kg. Molybdate caused acidification in the reactor and it was according to decrease in the pH values. In relation to microbial consortia, the effect of inhibitor was a decrease in Bacteria (44%; 60% in sulphate-reducing bacteria) and Archaea (38%) population

Fake hands in action: embodiment and control of supernumerary limbs

Demonstrations that the brain can incorporate a fake limb into our bodily representations when stroked in synchrony with our unseen real hand [(the rubber hand illusion (RHI)] are now commonplace. Such demonstrations highlight the dynamic flexibility of the perceptual body image, but evidence for comparable RHI-sensitive changes in the body schema used for action is less common. Recent evidence from the RHI supports a distinction between bodily representations for perception (body image) and for action (body schema) (Kammers et al. in Neuropsychologia 44:2430–2436, 2006). The current study challenges and extends these findings by demonstrating that active synchronous stroking of a brush not only elicits perceptual embodiment of a fake limb (body image) but also affects subsequent reaching error (body schema). Participants were presented with two moving fake left hands. When only one was synchronous during active touch, ownership was claimed for the synchronous hand only and the accuracy of reaching was consistent with control of the synchronous hand. When both fake hands were synchronous, ownership was claimed over both, but only one was controlled. Thus, it would appear that fake limbs can be incorporated into the body schema as well as the body image, but while multiple limbs can be incorporated into the body image, the body schema can accommodate only one

Whole Blood Interferon-Gamma Responses to Mycobacterium tuberculosis Antigens in Young Household Contacts of Persons with Tuberculosis in Uganda

Due to immunologic immaturity, IFN-gamma-producing T cell responses may be decreased in young children compared to adults, thus we hypothesized that IFN-gamma responses to mycobacterial antigens in household contacts exposed to Mycobacterium tuberculosis (Mtb) would be impaired in young children relative to adults. The objective of this study was to compare whole blood IFN-gamma production in response to mycobacterial antigens between children and adults in Uganda.We studied household contacts of persons with culture-positive pulmonary tuberculosis (TB) enrolled in a cohort study conducted in Kampala, Uganda. Whole blood IFN-gamma production in response to Mtb culture-filtrate antigens was measured by ELISA and compared between infants (<2 years old, n = 80), young children (2 <5 years old, n = 216), older children (5 <15 years old, n = 443) and adults (> or =15 years old, n = 528). We evaluated the relationship between IFN-gamma responses and the tuberculin skin test (TST), and between IFN-gamma responses and epidemiologic factors that reflect exposure to Mtb, and the effect of prior BCG vaccination on IFN-gamma responses. Young household contacts demonstrated robust IFN-gamma responses comparable to those of adults that were associated with TST and known risk factors for infection. There was no effect of prior BCG immunization on the IFN-gamma response.Young children in a TB endemic setting can mount robust IFN-gamma responses generally comparable to those of adults, and as in adults, these responses correlated with the TST and known epidemiologic risk factors for Mtb infection

Dysconnectivity of the medio-dorsal thalamic nucleus in drug-naïve first episode schizophrenia: diagnosis-specific or trans-diagnostic effect?

Converging lines of evidence implicate the thalamocortical network in schizophrenia. In particular, the onset of the illness is associated with aberrant functional integration between the medio-dorsal thalamic nucleus (MDN) and widespread prefrontal, temporal and parietal cortical regions. Because the thalamus is also implicated in other psychiatric illnesses including post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), the diagnostic specificity of these alterations is unclear. Here, we determined whether aberrant functional integration between the MDN and the cortex is a specific feature of schizophrenia or a trans-diagnostic feature of psychiatric illness. Effective connectivity (EC) between the MDN and rest of the cortex was measured by applying psychophysiological interaction analysis to resting-state functional magnetic resonance imaging data of 50 patients with first episode schizophrenia (FES), 50 patients with MDD, 50 patients with PTSD and 122 healthy controls. All participants were medication-naïve. The only significant schizophrenia-specific effect was increased EC between the right MDN and the right pallidum (p < 0.05 corrected). In contrast, there were a number of significant trans-diagnostic alterations, with both right and left MDN displaying trans-diagnostic increased EC with several prefrontal and parietal regions bilaterally (p < 0.05 corrected). EC alterations between the MDN and the cortex are not specific to schizophrenia but are a trans-diagnostic feature of psychiatric disorders, consistent with emerging conceptualizations of mental illness based on a single general psychopathology factor. Therefore, dysconnectivity of the MDN could potentially be used to assess the presence of general psychopathology above and beyond traditional diagnostic boundaries

The Tuberculin Skin Test (TST) Is Affected by Recent BCG Vaccination but Not by Exposure to Non-Tuberculosis Mycobacteria (NTM) during Early Life

The tuberculin skin test (TST) is widely used in TB clinics to aid Mycobacterium tuberculosis (M.tb) diagnosis, but the definition and the significance of a positive test in very young children is still unclear. This study compared the TST in Gambian children at 4½ months of age who either received BCG vaccination at birth (Group 1) or were BCG naïve (Group 2) in order to examine the role of BCG vaccination and/or exposure to environmental mycobacteria in TST reactivity at this age. Nearly half of the BCG vaccinated children had a positive TST (≥5 mm) whereas all the BCG naïve children were non-reactive, confirming that recent BCG vaccination affects TST reactivity. The BCG naïve children demonstrated in vitro PPD responses in peripheral blood in the absence of TST reactivity, supporting exposure to and priming by environmental mycobacterial antigens. Group 2 were then vaccinated at 4½ months of age and a repeat TST was performed at 20–28 months of age. Positive reactivity (≥5 mm) was evident in 11.1% and 12.5% infants from Group 1 and Group 2 respectively suggesting that the timing of BCG vaccination had little effect by this age. We further assessed for immune correlates in peripheral blood at 4½ months of age. Mycobacterial specific IFNγ responses were greater in TST responders than in non-responders, although the size of induration did not correlate with IFNγ. However the IFNγ: IL-10 ratio positively correlated with TST induration suggesting that the relationship between PPD induced IFNγ and IL-10 in the peripheral blood may be important in controlling TST reactivity. Collectively these data provide further insights into how the TST is regulated in early life, and how a positive response might be interpreted

Polymorphic Variation in TIRAP Is Not Associated with Susceptibility to Childhood TB but May Determine Susceptibility to TBM in Some Ethnic Groups

Host recognition of mycobacterial surface molecules occurs through toll like receptors (TLR) 2 and 6. The adaptor protein TIRAP mediates down stream signalling of TLR2 and 4, and polymorphisms in the TIRAP gene (TIRAP) have been associated with susceptibility and resistance to tuberculosis (TB) in adults. In order to investigate the role of polymorphic variation in TIRAP in childhood TB in South Africa, which has one of the highest TB incidence rates in the world, we screened the entire open reading frame of TIRAP for sequence variation in two cohorts of childhood TB from different ethnic groups (Xhosa and mixed ancestry). We identified 13 SNPs, including seven previously unreported, in the two cohorts, and found significant differences in frequency of the variants between the two ethnic groups. No differences in frequency between individual SNPs or combinations were found between TB cases and controls in either cohort. However the 558C→T SNP previously associated with TB meningitis (TBM) in a Vietnamese population was found to be associated with TBM in the mixed ancestry group. Polymorphisms in TIRAP do not appear to be involved in childhood TB susceptibility in South Africa, but may play a role in determining occurrence of TBM

Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development

Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO) term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4), neurons (Neurofilament M), astrocytes (GFAP) or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals

Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function

The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies