Environmental Education and the Cultivation of Student Agency in the Himalaya. A case study of Dhading Besi township, Nepal

This study investigated the quality and availability of environmental education (EE) in Dhading Besi, Nepal. Focus was placed on the cultivation of students’ agency and their participation in environmental actions. Interviews were conducted jointly at two local high schools with students and teachers, and with climate science researchers and local environmental NGOs. The study found that current environmental education, although limited, was having both a positive and significant impact on students’ environmental literacy and increased their agency through active participation in environmental actions. Interview findings highlighted the need for a nationally coordinated EE framework and updated EE curriculum. This would likely result in improved environmental sustainability, climate change resilience and socio-economic development in Nepal

Preoperative cardiac risk assessment in vascular surgery: risk stratification, novel cardiac biomarkers, and their importance in abdominal aortic aneurysm surgery

Major vascular surgery is associated with a substantial risk of cardiovascular events and death. This risk is of increased importance in prophylactic elective open Abdominal Aortic Aneurysm (AAA) repair, where a balance of risk of rupture and postoperative outcome is assessed prior to management decisions. Further, the UK Small Aneurysm Trial has shown that prophylactic repair of an AAA has no survival benefit for the first three years due to the major adverse cardiac event (MACE) rate of 5-15%. There is however no ideal method of predicting this risk. Cardiac Troponin I (cTnI) is a contractile protein that is a highly sensitive and specific marker of myocardial necrosis. A few case reports have commented on the finding of preoperative asymptomatic elevated cTnI levels and poor outcome in a small number of patients undergoing major vascular surgery. There are however no studies looking at its incidence in the vascular surgical population or its utility as a preoperative marker. Several studies have noted that B-type natriuretic peptide (BNP), a diagnostic and prognostic marker of heart failure, may have a role in predicting MACE in settings including major vascular surgery. There are no studies that have investigated this role in AAA repair alone. The aim of this thesis is to investigate the incidence of, and to determine a possible role for, preoperative elevated cTnI in major vascular surgery. The further aim is to determine if a single preoperative BNP level correlated with MACE and all-cause mortality in elective open AAA repair in both the short and long-term. Comparisons to current accepted risk indices in AAA, and a possible role for BNP in EndoVascular Aneurysm Repair (EVAR) will also be investigated. Patients were recruited in two cohorts: Firstly, a prospective, 2 year observational single centre cohort study of all patients undergoing a vascular procedure, with an expected cardiac event rate >5%, recruited patients who had no clinical or ECG evidence of myocardial ischaemia. Preoperative cTnI was performed in all and postoperative screening (clinical assessment, ECG and cTnI) for cardiac events was performed at days 2, 5 and 30. 213 patient were recruited, of whom 11 (5.2%) had an asymptomatic elevated preoperative cTnI (>0.02 ng/ml). Eight of these patients proceeded directly to theatre, and 2 were delayed but later underwent surgery with a persistently elevated cTnI. Of these 10 patients, 5 (50%) died and 4 (40%) suffered MACE. The remaining patient was delayed due to the poor outcome of the preceding patients, and later underwent an uncomplicated aortic bifurcation graft with a normal cTnI level which had been preceded by coronary intervention. Secondly, a prospective, 2 year observational multi-centre cohort study in the 3 largest vascular units in Glasgow (Gartnavel General Hospital, Glasgow Royal Infirmary and Southern General Hospital) was performed between August 2005 and August 2007, recruiting all patients who were admitted for both elective open AAA repair and EVAR. Preoperative BNP levels were performed and batch analysed at the end of the study. Postoperative screening for cardiac events was performed as described above. Data was collected to allow calculation of risk indices associated with outcome in AAA repair (Glasgow Aneurysm Score [GAS], Vascular physiology only Physiological and Operative Severity Score for enUmeration of Mortality [V{p}-POSSUM], Vascular Biochemical and Haematological Outcome Model [VBHOM], Revised Cardiac Risk Index [RCRI] and Preoperative Risk Score of the Estimation of Physiological Ability and Surgical Stress Score [PRS of E-PASS]). Follow-up was continued to a minimum of 3 years, where possible, with cause of death recorded. 106 of 111 patients were recruited. The median [interquartile range] BNP concentrations in the 16 patients (15%) who suffered immediate postoperative MACE was 206 [118-454] vs 35 [17-61] pg/ml in the remainder (p=0.001). ROC analysis indicated a BNP concentration of 99.5 pg/ml best predicted MACE (area under the curve 0.927), with sensitivity of 88% and specificity of 89%. The BNP in patients who suffered cardiac death was significantly higher than in those that did not (median BNP 496 [280-881] vs 38 [18-84] pg/ml, p=0.043). ROC analysis revealed a cut-off of 448 pg/ml (AUC 0.963), with sensitivity 80%, specificity 100%, positive predictive value 100% and negative predictive value 99%. Not only did higher values of BNP predict MACE, but it was also found to predict all-cause mortality in the immediate (median BNP 100 [84-521] vs 35 [17-81], p=0.028), intermediate (median BNP 201 [97-496] vs 35 [17-73], p60.5 pg/ml (AUC 0.761) found to best predict death at 3 years. Whilst BNP was found to predict outcome, most risk indices performed poorly. The GAS, VBHOM and RCRI performed poorly and did not predict any outcome measure. V(p)-POSSUM was, however, found to predict all outcome measures (p=0.028, p=0.030, p=0.038 for MACE, cardiac death and all-cause mortality respectively). The PRS component of E-PASS was found to predict MACE (p=0.019) and cardiac death (p=0.017). BNP performed better than any risk index. During the study period only 40 of 42 patients admitted for elective EVAR were recruited. Of these 40, only 3 suffered a non-fatal MI and 1 died of respiratory failure. BNP was not found to predict MACE or death in this cohort, and due to the small number of patients, and events, no strong conclusions could be drawn. Whilst preoperative elevated cTnI was found to identify patients that were at an increased risk of both postoperative MACE and death following their major vascular surgical procedure, its use in elective open AAA repair is limited due to infrequent occurrence. Preoperative serum BNP concentration, however, predicted postoperative MACE, cardiac death and all-cause mortality in patients undergoing elective open AAA repair on immediate, intermediate and long term follow-up. Further, BNP performed better than any current risk index for elective open AAA surgery. This simple blood test, therefore, offers valuable information regarding risk stratification of prospective surgical patients and should be considered a part of routine preoperative assessment in this prophylactic procedure

Are patients with HHV-8 associated Castleman disease successfully treated with rituximab at risk of subsequently developing HHV-8 negative (idiopathic) Castleman disease?

Introduction: Multicentric Castleman disease (MCD) is a lymphoproliferative disorder characterized by lymph node histopathology and systemic symptoms. To our knowledge, there are no descriptions in the literature of long-term outcomes of human herpesvirus-8 (HHV-8)-associated MCD. Case Description: We report a case of a 70-year-old male living with human immunodeficiency virus and a history of human herpesvirus-8 (HHV-8)-associated MCD. The patient reported having had low-grade fever for two weeks. Extensive workup revealed systemic lymphadenopathy without evidence of autoimmune disease or malignancy. Lymph node biopsy was consistent with HHV-8-negative idiopathic MCD (iMCD). The patient was subsequently scheduled for anti-interleukin-6 therapy. Discussion: The present case is the first report of probable development of iMCD after long-term follow-up for HHV-8-associated MCD. The case illustrates the possible long-term consequences of MCD, suggesting the necessity of further research on the pathogenesis of CD. Conclusion: Given the uncertainty in the long-term outcomes of HHV-8-associated MCD, periodic surveillance of patients with a history of HHV-8-associated MCD is warranted. Prospective nationwide cohort studies comparing characteristics of HHV-8-associated MCD and iMCD would bring further insights

A systematic literature review of the career choice of helping professionals who have experienced cumulative harm as a result of adverse childhood experiences

The pervasive effects of cumulative harm resulting from adverse childhood experiences influence all aspects of an individual’s life course. Research highlights a relationship between early trauma and career choice; however, there is a dearth of research pertaining specifically to cumulative harm and the influence on career choice in the helping professions. A systematic literature review was conducted to explore the associations of cumulative harm and childhood trauma on career decision making in people in the helping professions. A search was conducted across databases between February 1990 and February 2019 relevant to searches combining three areas of interest: (a) 'childhood trauma', (b) 'career choice', and (c) 'helping professionals'. Database searches and further manual searches yielded a total of 208 articles, and 28 studies satisfied all inclusion criteria. Only studies that were peer-reviewed and published between February 1990 and February 2019 were included. The evidence from the review indicated that family of origin dysfunction, parentification, individual characteristics, and traits developed through adversity, and experiential motivations were associated with the career choice in the helping professions. Further research is required to explore different professional cohorts and the utility of life themes as both a source of data for research and reflexive practice in helping professionals

Diagnosis, treatment, and outcome of patients with oesophagogastric cancer during the COVID-19 pandemic:national study

Background: The national response to COVID-19 has had a significant impact on cancer services. This study investigated the effect of national lockdown on diagnosis, management, and outcomes of patients with oesophagogastric cancers in Scotland. Methods: This retrospective cohort study included consecutive new patients presenting to regional oesophagogastric cancer multidisciplinary teams in National Health Service Scotland between October 2019 and September 2020. The study interval was divided into before and after lockdown, based on the first UK national lockdown. Electronic health records were reviewed and results compared. Results: Some 958 patients with biopsy-proven oesophagogastric cancer in 3 cancer networks were included: 506 (52.8 per cent) before and 452 (47.2 per cent) after lockdown. Median age was 72 (range 25–95) years and 630 patients (65.7 per cent) were men. There were 693 oesophageal (72.3 per cent) and 265 gastric (27.7 per cent) cancers. Median time to gastroscopy was 15 (range 0–337) days before versus 19 (0–261) days after lockdown (P < 0.001). Patients were more likely to present as an emergency after lockdown (8.5 per cent before versus 12.4 per cent after lockdown; P = 0.005), had poorer Eastern Cooperative Oncology group performance status, were more symptomatic, and presented with a higher stage of disease (stage IV: 49.8 per cent before versus 58.8 per cent after lockdown; P = 0.04). There was a shift to treatment with non-curative intent (64.6 per cent before versus 77.4 per cent after lockdown; P < 0.001). Median overall survival was 9.9 (95 per cent c.i. 8.7 to 11.4) months before and 6.9 (5.9 to 8.3) months after lockdown (HR 1.26, 95 per cent c.i. 1.09 to 1.46; P = 0.002). Conclusion: This national study has highlighted the adverse impact of COVID-19 on oesophagogastric cancer outcomes in Scotland. Patients presented with more advanced disease and a shift towards treatment with non-curative intent was observed, with a subsequent negative impact on overall survival

Recommended Patient-Reported Core Set of Symptoms to Measure in Head and Neck Cancer Treatment Trials

We identified a standard core set of patient-reported symptoms and health-related quality-of-life (HRQOL) domains to be assessed in head and neck (H&N) cancer clinical trials. The core symptom and HRQOL domain scores were used to guide recommendations by a working group of experts as part of a National Cancer Institute Symptom Management and HRQOL Clinical Trials Planning Meeting. A PubMed search was conducted using the search terms of “health-related quality of life” and “head & neck cancer,” limited to publications from January 1, 2000, to December 31, 2010. Fifty-four articles were used to guide the choice of recommendations. Twenty-nine symptoms and nine domains were identified, from which 12 H&N-specific core symptoms and HRQOL domains were recommended: swallowing, oral pain, skin changes, dry mouth, dental health, opening mouth/trismus, taste, excess/thick mucous/saliva, shoulder disability/motion, voice/hoarseness, social domain, and functional domain. This core set of 12 H&N-specific, patient-reported symptoms and HRQOL domains should be assessed in future H&N cancer clinical trials

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts