Future career plans of Malawian medical students: a cross-sectional survey.

BACKGROUND: Malawi has one of the lowest physician densities in the world, at 1.1 doctors per 100,000 population. Undergraduate training of doctors at the national medical school has increased considerably in recent years with donor support. However, qualified doctors continue to leave the public sector in order to work or train abroad. We explored the postgraduate plans of current medical students, and the extent to which this is influenced by their background. METHODS: A self-administered questionnaire was developed after discussion with students and senior staff. This included questions on background characteristics, education before medical school, and future career plans. This was distributed to all medical and premedical students on campus over 1 week and collected by an independent researcher. One reminder visit was made to each class. Chi-squared tests were performed to investigate the relationship of student characteristics with future career plans. RESULTS: One hundred and forty-nine students completed the questionnaire out of a student body of 312, a response rate of 48%. When questioned on their plans for after graduation, 49.0% of students plan to stay in Malawi. However, 38.9% plan to leave Malawi immediately. Medical students who completed a 'premedical' foundation year at the medical school were significantly more likely to have immediate plans to stay in Malawi compared to those who completed A-levels, an advanced school-leaving qualification (P = 0.037). Current premedical students were slightly more likely to have immediate plans to work or train in Malawi compared to medical students (P = 0.049). However, a trend test across all the years was not significant. When asked about future plans, nearly half of students intend to work or train outside Malawi. CONCLUSIONS: The majority of respondents plan to leave Malawi in the future. The effectiveness of the substantial upscaling of medical education in Malawi may be diminished unless more medical students plan to work in Malawi after graduation

Isolation of 10 cyclosporine metabolites from human bile

Ten metabolites of cyclosporine were isolated from the ethyl ether extract of bile from four liver transplant patients receiving cyclosporine. Two of the metabolites were unique and previously unidentified. Liquid-liquid partitioning into diethyl ether with subsequent defatting with n-hexane was used for the initial extraction form bile. Separation of the individual metabolites (A-J) was performed using a Sephadex LH-20 column and a gradient high performance liquid chromatographic method. The molecular weights of the isolated metabolites were determined by fast atom bombardment/mass spectrometry. Gas chromatography with mass spectrometic amino acid analysis was also used to identify the amino acid composition and the hydroxylation position of metabolites A, B, C, D, and G. Proton nuclear magnetic resonance spectra were utilized to disinguish the chemical shifts of N-CH3 singlets and NH doublets of metabolites A, B, C, and D. Metabolites A, E, F, H, I, and J were reported previously in human urine and animal bile. Metabolites C and D are dihydroxylated compounds which cannot be clearly described as previously isolated compounds. Metabolites B and G are novel metabolites with a mass fragment which corresponded to a loss of 131 Da from the protonated molecular ion (MH+) in the fast atom bombardment/mass spectrometry, suggesting that the double bond in amino acid 1 has been modified. Metabolites B and G were primarily isolated from the bile of one of the liver transplant patients which contained abnormally high concentrations of these two metabolites. The method described is an efficient procedure for isolating milligram quantities of the major metabolites with greater than 95% purity

Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10.

The mechanism by which the mammalian mother accepts the implanting fetus as an allograft remains unexplained, but is likely to be the result of a combination of factors. Mononuclear cytotrophoblasts, the specialized fetal cells of the placenta that invade the uterus, play an important role. These cells express HLA-G, an unusual major histocompatibility complex class I-B molecule, and secrete cytokines and pregnancy-specific proteins that can regulate immune function. We investigated whether cytotrophoblasts secrete interleukin 10 (IL-10), a cytokine that potently inhibits alloresponses in mixed lymphocyte reactions. Cytotrophoblasts from all stages of pregnancy produced IL-10 in vitro, but neither placental fibroblasts nor choriocarcinoma (malignant trophoblast) cell lines did so. Spontaneous IL-10 production averaged 650, 853, and 992 pg/10(6) cells in the first, second, and third trimesters of pregnancy, respectively. IL-10 secretion dropped approximately 10-fold after the first 24 h of culture, and was paralleled by a decrease in messenger RNA. IL-10 messenger RNA was detected in biopsies of the placenta and the portion of the uterus that contains invasive cytotrophoblasts, suggesting that this cytokine is also produced in vivo. IL-10 secreted by cytotrophoblasts in vitro is bioactive, as determined by its ability to suppress interferon gamma production in an allogeneic mixed lymphocyte reaction. We conclude that human cytotrophoblast IL-10 may be an important factor that contributes to maternal tolerance of the allogeneic fetus

Evidence of widespread selection on standing variation in Europe at height-associated SNPs.

Strong signatures of positive selection at newly arising genetic variants are well documented in humans(1-8), but this form of selection may not be widespread in recent human evolution(9). Because many human traits are highly polygenic and partly determined by common, ancient genetic variation, an alternative model for rapid genetic adaptation has been proposed: weak selection acting on many pre-existing (standing) genetic variants, or polygenic adaptation(10-12). By studying height, a classic polygenic trait, we demonstrate the first human signature of widespread selection on standing variation. We show that frequencies of alleles associated with increased height, both at known loci and genome wide, are systematically elevated in Northern Europeans compared with Southern Europeans (P < 4.3 × 10(-4)). This pattern mirrors intra-European height differences and is not confounded by ancestry or other ascertainment biases. The systematic frequency differences are consistent with the presence of widespread weak selection (selection coefficients ∼10(-3)-10(-5) per allele) rather than genetic drift alone (P < 10(-15))

Selection of attributes for modelling Bach chorales by a genetic algorithm

A genetic algorithm selected combinations of attributes for a machine learning system. The algorithm used 90 Bach chorale melodies to train models and randomly selected sets of 10 chorales for evaluation. Compression of pitch was used as the fitness evaluation criterion. The best models were used to compress a different test set of chorales and their performance compared to human generate models. G.A. models outperformed the human models, improving compression by 10 percent

De novo human genome assemblies reveal spectrum of alternative haplotypes in diverse populations.

The human reference genome is used extensively in modern biological research. However, a single consensus representation is inadequate to provide a universal reference structure because it is a haplotype among many in the human population. Using 10× Genomics (10×G) "Linked-Read" technology, we perform whole genome sequencing (WGS) and de novo assembly on 17 individuals across five populations. We identify 1842 breakpoint-resolved non-reference unique insertions (NUIs) that, in aggregate, add up to 2.1 Mb of so far undescribed genomic content. Among these, 64% are considered ancestral to humans since they are found in non-human primate genomes. Furthermore, 37% of the NUIs can be found in the human transcriptome and 14% likely arose from Alu-recombination-mediated deletion. Our results underline the need of a set of human reference genomes that includes a comprehensive list of alternative haplotypes to depict the complete spectrum of genetic diversity across populations

Companion robots: the hallucinatory danger of human-robot interactions

The advent of the so-called Companion Robots is raising many ethical concerns among scholars and in the public opinion. Focusing mainly on robots caring for the elderly, in this paper we analyze these concerns to distinguish which are directly ascribable to robotic, and which are instead preexistent. One of these is the “deception objection”, namely the ethical unacceptability of deceiving the user about the simulated nature of the robot’s behaviors. We argue on the inconsistency of this charge, as today formulated. After that, we underline the risk, for human-robot interaction, to become a hallucinatory relation where the human would subjectify the robot in a dynamic of meaning-overload. Finally, we analyze the definition of “quasi-other” relating to the notion of “uncanny”. The goal of this paper is to argue that the main concern about Companion Robots is the simulation of a human-like interaction in the absence of an autonomous robotic horizon of meaning. In addition, that absence could lead the human to build a hallucinatory reality based on the relation with the robot

Equivalent dynamical complexity in a many-body quantum and collective human system

Proponents of Complexity Science believe that the huge variety of emergent phenomena observed throughout nature, are generated by relatively few microscopic mechanisms. Skeptics however point to the lack of concrete examples in which a single mechanistic model manages to capture relevant macroscopic and microscopic properties for two or more distinct systems operating across radically different length and time scales. Here we show how a single complexity model built around cluster coalescence and fragmentation, can cross the fundamental divide between many-body quantum physics and social science. It simultaneously (i) explains a mysterious recent finding of Fratini et al. concerning quantum many-body effects in cuprate superconductors (i.e. scale of 10^{-9} - 10^{-4} meters and 10^{-12} - 10^{-6} seconds), (ii) explains the apparent universality of the casualty distributions in distinct human insurgencies and terrorism (i.e. scale of 10^3 - 10^6 meters and 10^4 - 10^8 seconds), (iii) shows consistency with various established empirical facts for financial markets, neurons and human gangs and (iv) makes microscopic sense for each application. Our findings also suggest that a potentially productive shift can be made in Complexity research toward the identification of equivalent many-body dynamics in both classical and quantum regimes.Comment: 9 pages, 3 figures; version published in AIP Advance

Interleukin-10 containing normal human serum inhibits granzyme B release but not perforin release from alloreactive and EBV-specific T cell clones

Interleukin-10 (IL-10), also known as cytokine synthesis inhibitory factor, has pleiotropic effects in immunoregulation and inflammation. It is capable of inhibiting synthesis of pro-inflammatory cytokines like interferon γ (IFNγ), IL-2, IL-3, tumor necrosis factor α(TNFα) and granulocyte macrophage colony stimulating factor (GM-CSF) made by cells such as macrophages and T helper Type 1 cells. We observed that normal human serum, derived from a healthy individual but containing large amounts of IL-10 (arbitrarily designated as "IL-10 serum"), inhibited cytotoxic activity and interfered with granzyme B release from alloreactive cytotoxic T cell (CTL) clones _in vitro_, but did not affect perforin release. The addition of normal human serum containing high levels of anti-IL-10 IgG (arbitrarily designated as "anti-IL-10 IgG serum") neutralized the inhibitory effects of IL-10 serum. Moreover, we have identified that cytotoxic activity and granzyme B release from an Epstein-Barr virus (EBV)-specific CTL clone was similarly inhibited in the presence of IL-10 serum, while perforin release was unaffected. Anti-IL-10 IgG serum also appeared to neutralize the inhibitory effect of IL-10 serum on an EBV-specific CTL clone