Harnessing the force of post-F2 doctors - a medical clinical fellow post that transformed locally employed doctor recruitment.

In 2018, North Bristol Trust (NBT) faced difficulties recruiting clinical fellows. In response, a new programme was introduced that includes opportunities for non-clinical time, supervision, and a study budget, as well as flexibility of contract duration and on-call commitment. This has significantly improved the application ratios, with a 94% fill rate in August 2021 and competition ratios of 2.5:1. Not only has it been successful for staffing medical rotas, but clinical fellows also report positive experiences, have gained opportunities that would not be available in a training role and feel the role will benefit their future job applications. This report outlines the new programme and analyses it from the clinical fellow and Trust perspective. We hope that by sharing this successful new programme, other organisations can take inspiration to harness the potential of the high proportion of doctors taking a break from training post-foundation programme.

Symptoms of posttraumatic stress disorder in patients with functional neurological symptom disorder.

OBJECTIVE: To describe prevalence and relevance of Post-Traumatic Stress Disorder (PTSD) symptoms in Functional Neurological Symptom Disorder (FNSD) and explore differences in PTSD symptom scores between subgroups with Psychogenic Non-Epileptic Seizures (PNES) or other FNSD. METHODS: This cross-sectional study evaluated data from 430 consecutive patients referred to a specialist psychotherapy service (69.3% female, 56% with PNES/44% with other FNSD). We analysed self-reported symptoms of Post-Traumatic Stress Disorder (PTSD Civilian Checklist, PCLC), depression (PHQ-9), anxiety (GAD-7), physical symptoms (PHQ-15), social functioning (WSAS), and health related quality of life (SF-36). Relationships between PTSD scores, diagnosis and other measures were examined. Independent associations of PTSD scores were identified using multilinear regression. RESULTS: Symptom scores likely to indicate clinical PTSD were reported by 60.7% of patients with no difference between PNES and FNSD subgroups. Those potentially symptomatic of PTSD were less likely to be living with a partner OR 2.95 (95% CI 1.83-4.04), or to be in employment OR 2.23 (95% CI 1.46-3.41) than less symptomatic patients. There were higher levels of anxiety (r = 0.62), depression (r = 0.63) and somatic symptoms (r = 0.45) and lower quality of life scores (r = 0.48) in patients with high PTSD symptom scores (p < .0001 for all comparisons). Anxiety, depression and somatic symptoms made independent contributions to the variance of PTSD symptoms. CONCLUSION: There is a high prevalence of PTSD symptoms in patient with FNSD regardless of whether they have PNES. Trauma and PTSD symptoms are negatively correlated with quality of life. Self-report instruments for anxiety, depression and somatic symptoms may predict the presence of PTSD.

Yield assessment of integument-led seed growth following targeted repair of auxin response factor 2.

SUMMARY: It is becoming increasingly vital to improve the yield of seed crops to feed an expanding population and, more recently, for biofuel production. One strategy to increase the yield is to increase the seed size, provided that there is not a concomitant decrease in seed number. In a previous study, we described a mutant in the auxin response factor 2 (ARF2) gene which produced extra cells in the seed coat and, subsequently, enlarged seeds. However, arf2 mutant plants also show severely reduced self-fertility caused, in part, by over-elongated sepals that prevent flower opening. As a low seed set increases individual seed size, a meaningful comparison of the yield in arf2 and wild-type plants could not be conducted. In this study, we show that targeted expression of wild-type ARF2 in the sepals and petals of arf2-9 mutant flowers restores flower opening and dramatically increases seed set. The restored plants retain both enlarged integuments and increased seed size, reinforcing previous evidence that arf2 mutations increase seed weight through their effect on integuments and not only via reduced fertility. We also show that the measurement of the harvest index in Arabidopsis is useful in assessing the impact of introduced traits on the yield.

Strategies for cancer gene therapy.

Gene therapy offers new opportunities for cancer treatment and prevention through the use of targeted, relatively nontoxic treatments that can identify, disable, and destroy malignant cells. This article reviews the principles behind oncogene inactivation, tumor suppressor gene replacement, inhibition of angiogenesis, immunopotentiation, molecular chemotherapy, and addition of drug resistance genes. The adcantages and limitations of viral and nonviral vectors for delivery of the therapeutic genes are presented.

HPC2/ELAC2 gene variants associated with incident prostate cancer.

The HPC2/ELAC2 gene on chromosome 17p11 was identified as a candidate gene for hereditary prostate cancer (HPC) susceptibility. Two HPC2 gene missense variants, Ser217Leu (Leu217) and Ala541Thr (Thr541) have been associated with incident prostate cancer cases in some studies, but not in others. We tested for possible associations between the two HPC2 gene variants and prostate cancer risk in incident prostate cancer cases (199) and healthy male controls (525) from the Calgary region. The Thr541 variant showed linkage disequilibrium with the Leu217 variant. The number of Leu217 homozygotes in the case and control groups (8.6 versus 8.5%) was not statistically different. Leu217 carrier status was associated with prostate cancer risk (cases 61.8% versus controls 50.3%) (OR 1.6, 95% CI 1.15-2.23). Additional analysis found that this association was not due to the co-existence of Thr541 variant (OR1.59, P=0.009). Logistic regression found that the relationship between the log odds of being a Thr541carrier and age depends on case/control status. Thr541 carriers had an increased risk for late-onset prostate cancer (P=0.028). Prostate intraepithelial neoplasia (PIN) was more common in the Leu217 allele carriers compared to non-carriers (42.3 versus 26.7%) (OR 2.05, 95% CI 1.10-3.83), and in the Thr541 carriers compared to non-carriers (50.0 versus 34.6%) (OR 1.89, 95% CI 0.75-4.78). In summary, the HPC2 gene variants Leu217 and Thr541 were associated with an increased risk for prostate cancer and for PIN in males undergoing radical prostatectomies in the Calgary region.

The Simpson-Golabi-Behmel gene, GPC3, is not involved in sporadic Wilms tumorigenesis.

Many genes have been implicated in Wilms tumor; however, only one gene, WT1, has a proven role in the development of this embryonal tumor. Wilms tumor occurs in a number of congenital syndromes including the Simpson-Golabi-Behmel syndrome (SGBS) which has phenotypic overlap with another Wilms tumor-predisposing syndrome Wiedemann-Beckwith syndrome. The putative function and expression pattern of the SGBS gene, glypican 3 (GPC3), makes it an attractive candidate Wilms tumor gene. We, therefore, hypothesized that Wilms tumors from non-SGBS patients may harbor somatic mutations of GPC3. Mutation analysis of 64 Wilms tumors was performed. One case of a tumor-specific deletion of the entire GPC3 gene and several polymorphisms were identified. GPC3 expression was evaluated in 36 Wilms tumors and 29/36 expressed GPC3. Surprisingly, we did not find evidence of functional mutations of GPC3 in sporadic Wilms tumor suggesting that GPC3 is not often directly involved in Wilms tumorigenesis.

Congenital extrarenal non-central nervous system malignant rhabdoid tumor.

Malignant rhabdoid tumor (MRT) is a rare tumor occurring mostly in kidneys and central nervous system (CNS). Its prognosis is not good. Occasionally, MRTs are diagnosed at or immediately after birth. A female neonate presented with MRT in the chest wall, axilla, right elbow, and bone marrow. Chest wall lesion was resected completely. Although the masses in axilla and bone marrow responded rapidly to chemotherapy, the elbow lesion increased in size. Despite intense treatment, the tumor relapsed in lungs and the patient died 12 months after diagnosis. Review of the literature showed twenty additional congenital MRTs arising from sites outside of the kidney and central nervous system were published in the literature. Eighteen patients had disseminated disease at diagnosis. The median overall survival time for all (n = 21) patients was 2.0 months (0-24 months). The only patient who survived had a localized tumor at initial diagnosis. Congenital, extrarenal, non-CNS MRTs are aggressive tumors with poor outcome.