Value of a UK medical degree for international students (VISION): a cross-sectional study

Objectives: It is estimated that NHS staff consist of over 200 different nationalities, with a reported 30.7% of doctors holding a nationality other than British. Despite this, international medical students represent 7.5% of all medical students studying in the UK and pay on average, 4–6 times more in tuition fees when compared with the £9250 per annum (Great British Pounds (£) in 2021) paid by home students. This study’s aim and objective are to evaluate the perception of the financial cost and value of the UK medical degree for international students and their motivations for pursuing such a degree. Methods: This is a cross-sectional observational study enquiring about international premedical, medical and medical school graduates’ perception of the value of the UK medical degree and factors influencing their decision to study in the UK. A questionnaire was developed and distributed to 24 medical schools and 64 secondary schools both internationally and across the UK. Results: A total of 352 responses from 56 nationalities were recorded. 96% of international students identified clinical and academic opportunities as the most important factors to study medicine in the UK, closely followed by quality of life (88%). The least important factor was family reasons, with 39% of individuals identifying this factor. Only 4.82% of graduates in our study considered leaving the UK after training. Overall, 54% of students felt the UK degree was value for money. This belief was significantly higher in premedical students compared with existing students and graduates (71% vs 52% and 20%, p<0.001 for all comparisons). Conclusion: The quality of medical education and international prestige are attractive factors for international students to study medicine in the UK. However, further work is needed to ascertain reasons for the differing perceptions of the value by international students at different stages in their clinical training

Hemizygous subtelomeres of an African trypanosome chromosome may account for over 75% of chromosome length

African trypanosomes are parasitic protozoa that infect a wide range of mammals, including humans. These parasites remain extracellular in the mammalian bloodstream, where antigenic variation allows them to survive the immune response. The Trypanosoma brucei nuclear genome sequence has been published recently. However, the significant chromosome size polymorphism observed among strains and subspecies of T. brucei, where total DNA content may vary up to 30%, necessitates a comparative study to determine the underlying basis and significance of such variation between parasites. In addition, the sequenced strain (Tb927) presents one of the smallest genomes analyzed among T. brucei isolates; therefore, establishing polymorphic regions will provide essential complementary information to the sequencing project. We have developed a Tb927 high-resolution DNA microarray to study DNA content variation along chromosome I, one of the most size-variable chromosomes, in different strains and subspecies of T. brucei. Results show considerable copy number polymorphism, especially at subtelomeres, but are insufficient to explain the observed size difference. Additional sequencing reveals that >50% of a larger chromosome I consists of arrays of variant surface glycoprotein genes (VSGs), involved in avoidance of acquired immunity. In total, the subtelomeres appear to be three times larger than the diploid core. These results reveal that trypanosomes can utilize subtelomeres for amplification and divergence of gene families to such a remarkable extent that they may constitute most of a chromosome, and that the VSG repertoire may be even larger than reported to date. Further experimentation is required to determine if these results are applicable to all size-variable chromosomes

Analysis of ploidy (in megabase chromosomes) in Trypanosoma brucei after genetic exchange

The megabase chromosomes of Trypanosoma brucei are normally diploid, but the extent to which this ploidy is maintained when parasites undergo genetic exchange is not known. To investigate this issue, a panel of 30 recombinant clones resulting from the co-transmission through tsetse flies of three different parental T. brucei lines in all pair-wise combinations (STIB 247, STIB 386 and TREU 927/4) were examined. These clones are products of 28 different mating events; four of them result from self-fertilisation and the others are F1 hybrids. DNA contents of the three parental lines were determined by flow cytometry and shown to differ only slightly with DNA content increasing in the order 927/4 &lt; 247 &lt; 386. Flow cytometry of the recombinant clones indicated DNA contents were similar to the parents in 28 clones and raised approximately 1.5 times the parental values in only two. The two F1 hybrid progeny with raised DNA contents were shown by marker analysis to be trisomic for seven independent loci indicating that they were probably triploid whereas progeny with DNA contents similar to parental values inherited a single allele from each parent for four independent loci indicating that they were diploid

A New, Expressed Multigene Family Containing a Hot Spot for Insertion of Retroelements Is Associated with Polymorphic Subtelomeric Regions of Trypanosoma brucei

We describe a novel gene family that forms clusters in subtelomeric regions of Trypanosoma brucei chromosomes and partially accounts for the observed clustering of retrotransposons. The ingi and ribosomal inserted mobile element (RIME) non-LTR retrotransposons share 250 bp at both extremities and are the most abundant putatively mobile elements, with about 500 copies per haploid genome. From cDNA clones and subsequently in the T. brucei genomic DNA databases, we identified 52 homologous gene and pseudogene sequences, 16 of which contain a RIME and/or ingi retrotransposon inserted at exactly the same relative position. Here these genes are called the RHS family, for retrotransposon hot spot. Comparison of the protein sequences encoded by RHS genes (21 copies) and pseudogenes (24 copies) revealed a conserved central region containing an ATP/GTP-binding motif and the RIME/ingi insertion site. The RHS proteins share between 13 and 96% identity, and six subfamilies, RHS1 to RHS6, can be defined on the basis of their divergent C-terminal domains. Immunofluorescence and Western blot analyses using RHS subfamily-specific immune sera show that RHS proteins are constitutively expressed and occur mainly in the nucleus. Analysis of Genome Survey Sequence databases indicated that the Trypanosoma brucei diploid genome contains about 280 RHS (pseudo)-genes. Among the 52 identified RHS (pseudo)genes, 48 copies are in three RHS clusters located in subtelomeric regions of chromosomes Ia and II and adjacent to the active bloodstream form expression site in T. brucei strain TREU927/4 GUTat10.1. RHS genes comprise the remaining sequence of the size-polymorphic “repetitive region” described for T. brucei chromosome I, and a homologous gene family is present in the Trypanosoma cruzi genome

Modulation of the spontaneous hemodynamic response function across levels of consciousness

Functional imaging research has already contributed with several results to the study of neural correlates of consciousness. Apart from task-related activation derived in fMRI, PET based glucose metabolism rate or cerebral blood flow account for a considerable proportion of the study of brain activity under different levels of consciousness. Resting state functional connectivity MRI is playing a crucial role to explore the consciousness related functional integration, successfully complementing PET, another widely used neuroimaging technique. Here, spontaneous hemodynamic response is introduced to characterize resting state brain activity giving information on the local metabolism (neurovascular coupling), and useful to improve the time-resolved activity and connectivity measures based on BOLD fMRI. This voxel-wise measure is then used to investigate the loss of consciousness under Propofol anesthesia and unresponsive wakefulness syndrome. Changes in the hemodynamic response in precuneus and posterior cingulate are found to be a common principle underlying loss of consciousness in both conditions. The thalamus appears to be less obviously modulated by Propofol, compared with frontoparietal regions. However, a significant increase in spontaneous thalamic hemodynamic response was found in patients in unresponsive wakefulness syndrome compared with healthy control. Our results ultimately show that anesthesia- or pathology-induced neurovascular coupling could be tracked by modulated spontaneous hemodynamic response derived from resting state fMRI

The sequence and analysis of Trypanosoma brucei chromosome II

We report here the sequence of chromosome II from Trypanosoma brucei, the causative agent of African sleeping sickness. The 1.2-Mb pairs encode about 470 predicted genes organised in 17 directional clusters on either strand, the largest cluster of which has 92 genes lined up over a 284-kb region. An analysis of the GC skew reveals strand compositional asymmetries that coincide with the distribution of protein-coding genes, suggesting these asymmetries may be the result of transcription-coupled repair on coding versus non-coding strand. A 5-cM genetic map of the chromosome reveals recombinational ‘hot’ and ‘cold’ regions, the latter of which is predicted to include the putative centromere. One end of the chromosome consists of a 250-kb region almost exclusively composed of RHS (pseudo)genes that belong to a newly characterised multigene family containing a hot spot of insertion for retroelements. Interspersed with the RHS genes are a few copies of truncated RNA polymerase pseudogenes as well as expression site associated (pseudo)genes (ESAGs) 3 and 4, and 76 bp repeats. These features are reminiscent of a vestigial variant surface glycoprotein (VSG) gene expression site. The other end of the chromosome contains a 30-kb array of VSG genes, the majority of which are pseudogenes, suggesting that this region may be a site for modular de novo construction of VSG gene diversity during transposition/gene conversion events

The DNA sequence of chromosome I of an African trypanosome: gene content, chromosome organisation, recombination and polymorphism

The African trypanosome, Trypanosoma brucei, causes sleeping sickness in humans in sub-Saharan Africa. Here we report the sequence and analysis of the 1.1 Mb chromosome I, which encodes approximately 400 predicted genes organised into directional clusters, of which more than 100 are located in the largest cluster of 250 kb. A 160-kb region consists primarily of three gene families of unknown function, one of which contains a hotspot for retroelement insertion. We also identify five novel gene families. Indeed, almost 20% of predicted genes are members of families. In some cases, tandemly arrayed genes are 99–100% identical, suggesting an active process of amplification and gene conversion. One end of the chromosome consists of a putative bloodstream-form variant surface glycoprotein (VSG) gene expression site that appears truncated and degenerate. The other chromosome end carries VSG and expression site-associated genes and pseudogenes over 50 kb of subtelomeric sequence where, unusually, the telomere-proximal VSG gene is oriented away from the telomere. Our analysis includes the cataloguing of minor genetic variations between the chromosome I homologues and an estimate of crossing-over frequency during genetic exchange. Genetic polymorphisms are exceptionally rare in sequences located within and around the strand-switches between several gene clusters