Fifth-year medical students’ perspectives on rural training in Botswana: A qualitative approach

Background. The curriculum of the Faculty of Medicine at the University of Botswana includes rural community exposure for students throughout their 5 years of training. In addition to community exposure during the first 2 years, students complete 16 weeks of family medicine and 8 weeks of public health medicine. However, as a new faculty, students’ experiences and perceptions regarding rural clinical training are not yet known.Objective. To describe the experiences and perceptions of the 5th-year medical students during their rural training and solicit their recommendations for improvement.Methods. This qualitative study used face-to-face interviews with 5th-year undergraduate medical students (N=36) at the end of their family medicine rotation in Mahalapye and Maun villages. We used a phenomenological paradigm to underpin the study. Voice-recorded interviews were transcribed and analysed using Atlas TI version 7 software (USA).Results. Three main themes were identified: (i) experiences and perceptions of the rural training environment; (ii) perceptions of the staff at rural sites; and (iii) perceptions of clinical benefits and relevance during rural training. While the majority of students perceived rural training as beneficial and valuable, a few felt that learning was compromised by limited resources and processes, such as medical equipment, internet connectivity and inadequate supervision.Conclusion. While the majority of students perceived rural training as beneficial, students identified limitations in both resources and supervision that need to be improved. Understanding students’ rural training experiences and perceptions can help the Faculty of Medicine, stakeholders and site facilitators to guide future rural training implementation

Pediatric Phantom Dosimetry of the Portable Handheld Xray2Go

Purpose: The purpose of our study was to quantify radiation dose from the XTG (Xray2Go) Handheld X-ray device for bitewing and anterior occlusal projections using a pediatric phantom. The aim was to evaluate thyroid shielding effects on effective dose (E), tissue equivalent doses (HT), and assess operator backscatter radiation. Methods: A pediatric phantom with 24 tissue site dosimeters was exposed to radiation from the Xray2Go. Projections included: Right and left bitewing (BW) without thyroid collar on phantom, BW with thyroid collar, maxillary anterior occlusal (AO) without thyroid collar, AO with thyroid collar. New dosimeters were used for each projection type, for 30 exposures. Operator wore dosimeters on forehead and right hand to quantify backscatter. Average values of HT and E were calculated. Results: Thyroid shielding produced a statistically significant difference for posterior bitewing projections at thyroid (P<.001), lymphatic nodes (P=.04), and muscle (P=.04). Operator dose from the XTG was indistinguishable from background radiation. Conclusions: Mean effective dose was less than 1 μSv for all projections. Thyroid shielding made a statistically significant difference for radiation dose with the Xray2Go for several tissue locations and for posterior bitewings effective dose. Radiation to the operator was low and indistinguishable from background radiation

The complex genetic landscape of familial MDS and AML reveals pathogenic germline variants.

The inclusion of familial myeloid malignancies as a separate disease entity in the revised WHO classification has renewed efforts to improve the recognition and management of this group of at risk individuals. Here we report a cohort of 86 acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) families with 49 harboring germline variants in 16 previously defined loci (57%). Whole exome sequencing in a further 37 uncharacterized families (43%) allowed us to rationalize 65 new candidate loci, including genes mutated in rare hematological syndromes (ADA, GP6, IL17RA, PRF1 and SEC23B), reported in prior MDS/AML or inherited bone marrow failure series (DNAH9, NAPRT1 and SH2B3) or variants at novel loci (DHX34) that appear specific to inherited forms of myeloid malignancies. Altogether, our series of MDS/AML families offer novel insights into the etiology of myeloid malignancies and provide a framework to prioritize variants for inclusion into routine diagnostics and patient management

The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature

Cutaneous squamous cell carcinoma (cSCC) has a high tumour mutational burden (50 mutations per megabase DNA pair). Here, we combine whole-exome analyses from 40 primary cSCC tumours, comprising 20 well-differentiated and 20 moderately/poorly differentiated tumours, with accompanying clinical data from a longitudinal study of immunosuppressed and immunocompetent patients and integrate this analysis with independent gene expression studies. We identify commonly mutated genes, copy number changes and altered pathways and processes. Comparisons with tumour differentiation status suggest events which may drive disease progression. Mutational signature analysis reveals the presence of a novel signature (signature 32), whose incidence correlates with chronic exposure to the immunosuppressive drug azathioprine. Characterisation of a panel of 15 cSCC tumour-derived cell lines reveals that they accurately reflect the mutational signatures and genomic alterations of primary tumours and provide a valuable resource for the validation of tumour drivers and therapeutic targets

GATA2 monoallelic expression underlies reduced penetrance in inherited GATA2-mutated MDS/AML.

Saudi Arabian Ministry of Higher Education through a doctoral scholarship awarded to A.F.A.S. and a Bloodwise Programme grant (14032) awarded to J.F., T.V., and I.D

Somatic mutational landscape of hereditary hematopoietic malignancies caused by germline variants in <i>RUNX1</i>, <i>GATA2</i>, and <i>DDX41</i>

Individuals with germ line variants associated with hereditary hematopoietic malignancies (HHMs) have a highly variable risk for leukemogenesis. Gaps in our understanding of premalignant states in HHMs have hampered efforts to design effective clinical surveillance programs, provide personalized preemptive treatments, and inform appropriate counseling for patients. We used the largest known comparative international cohort of germline RUNX1, GATA2, or DDX41 variant carriers without and with hematopoietic malignancies (HMs) to identify patterns of genetic drivers that are unique to each HHM syndrome before and after leukemogenesis. These patterns included striking heterogeneity in rates of early-onset clonal hematopoiesis (CH), with a high prevalence of CH in RUNX1 and GATA2 variant carriers who did not have malignancies (carriers-without HM). We observed a paucity of CH in DDX41 carriers-without HM. In RUNX1 carriers-without HM with CH, we detected variants in TET2, PHF6, and, most frequently, BCOR. These genes were recurrently mutated in RUNX1-driven malignancies, suggesting CH is a direct precursor to malignancy in RUNX1-driven HHMs. Leukemogenesis in RUNX1 and DDX41 carriers was often driven by second hits in RUNX1 and DDX41, respectively. This study may inform the development of HHM-specific clinical trials and gene-specific approaches to clinical monitoring. For example, trials investigating the potential benefits of monitoring DDX41 carriers-without HM for low-frequency second hits in DDX41 may now be beneficial. Similarly, trials monitoring carriers-without HM with RUNX1 germ line variants for the acquisition of somatic variants in BCOR, PHF6, and TET2 and second hits in RUNX1 are warranted