Examining medical student volunteering during the COVID-19 pandemic as a prosocial behaviour during an emergency.

PURPOSE: Understanding the factors that influence prosocial behaviour during the COVID-19 pandemic is essential due to the disruption to healthcare provision. METHODS: We conducted an in-depth, mixed-methods cross-sectional survey, from 2 May 2020 to 15 June 2020, of medical students at medical schools in the United Kingdom. Data analysis was informed by Latané and Darley's theory of prosocial behaviour during an emergency. RESULTS: A total of 1145 medical students from 36 medical schools responded. Although 947 (82.7%) of students were willing to volunteer, only 391 (34.3%) had volunteered. Of the students, 92.7% understood they may be asked to volunteer; however, we found deciding one's responsibility to volunteer was mitigated by a complex interaction between the interests of others and self-interest. Further, concerns revolving around professional role boundaries influenced students' decisions over whether they had the required skills and knowledge. CONCLUSION: We propose two additional domains to Latané and Darley's theory that medical students consider before making their final decision to volunteer: 'logistics' and 'safety'. We highlight modifiable barriers to prosocial behaviour and provide suggestions regarding how the conceptual framework can be operationalized within educational strategies to address these barriers. Optimizing the process of volunteering can aid healthcare provision and may facilitate a safer volunteering process. Key messages  What is already known on this topic: There is a discrepancy between the number of students willing to volunteer during pandemics and disasters, and those who actually volunteer. Understanding the factors that influence prosocial behaviour during the current COVID-19 pandemic and future pandemics and disasters is essential. What this study adds: We expanded on Latané and Darley's theory of prosocial behaviour in an emergency and used this to conceptualize students' motivations to volunteer, highlighting a number of modifiable barriers to prosocial behaviour during the COVID-19 pandemic. How this study might affect research, practice, or policy: We provide suggestions regarding how the conceptual framework can be operationalized to support prosocial behaviours during emergencies for the ongoing COVID-19 pandemic and future crises.

Clinical support during COVID-19: An opportunity for service and learning? A cross-sectional survey of UK medical students.

PURPOSE: Medical students providing support to clinical teams during Covid-19 may have been an opportunity for service and learning. We aimed to understand why the reported educational impact has been mixed to inform future placements. METHODS: We conducted a cross-sectional survey of medical students at UK medical schools during the first Covid-19 'lockdown' period in the UK (March-July 2020). Analysis was informed by the conceptual framework of service and learning. RESULTS: 1245 medical students from 37 UK medical schools responded. 57% of respondents provided clinical support across a variety of roles and reported benefits including increased preparedness for foundation year one compared to those who did not (p < 0.0001). However, not every individual's experience was equal. For some, roles complemented the curriculum and provided opportunities for clinical skill development, reflection, and meaningful contribution to the health service. For others, the relevance of their role to their education was limited; these roles typically focused on service provision, with few opportunities to develop. CONCLUSION: The conceptual framework of service and learning can help explain why student experiences have been heterogeneous. We highlight how this conceptual framework can be used to inform clinical placements in the future, in particular the risks, benefits, and structures.[Box: see text].

COVIDReady2 study protocol: cross-sectional survey of medical student volunteering and education during the COVID-19 pandemic in the United Kingdom.

BACKGROUND: The coronavirus disease 2019 pandemic has led to global disruption of healthcare. Many students volunteered to provide clinical support. Volunteering to work in a clinical capacity was a unique medical education opportunity; however, it is unknown whether this was a positive learning experience or which volunteering roles were of most benefit to students. METHODS: The COVIDReady2 study is a national cross-sectional study of all medical students at medical schools in the United Kingdom. The primary outcome is to explore the experiences of medical students who volunteered during the pandemic in comparison to those who did not. We will compare responses to determine the educational benefit and issues they faced. In addition to quantitative analysis, thematic analysis will be used to identify themes in qualitative responses. DISCUSSION: There is a growing body of evidence to suggest that service roles have potential to enhance medical education; yet, there is a shortage of studies able to offer practical advice for how these roles may be incorporated in future medical education. We anticipate that this study will help to identify volunteer structures that have been beneficial for students, so that similar infrastructures can be used in the future, and help inform medical education in a non-pandemic setting. TRIAL REGISTRATION: Not Applicable.

Systematic review of medical student willingness to volunteer and preparedness for pandemics and disasters.

OBJECTIVE: This systematic review aimed to estimate the willingness of students to volunteer during a disaster, and how well-prepared medical students are for volunteering by assessing their knowledge and medical school curriculum of disaster and pandemic medicine. RESULTS: A total of 37 studies met inclusion criteria including 11 168 medical students and 91 medical schools. 24 studies evaluated knowledge (64.9%), 16 evaluated volunteering (43.2%) and 5 evaluated medical school curricula (13.5%). Weighted mean willingness to volunteer during a disaster was 68.4% (SD=21.7%, range=26.7%-87.8%, n=2911), and there was a significant difference between those planning to volunteer and those who actually volunteered (p<0.0001). We identified a number of modifiable barriers which may contribute to this heterogeneity. Overall, knowledge of disasters was poor with a weighted mean of 48.9% (SD=15.1%, range=37.1%-87.0%, n=2985). 36.8% of 76 medical schools curricula included teaching on disasters. However, students only received minimal teaching (2-6 hours). CONCLUSIONS: This study demonstrates that there is a large number of students who are willing to volunteer during pandemics. However, they are unlikely to be prepared for these roles as overall knowledge is poor, and this is likely due to minimal teaching on disasters at medical school. During the current COVID-19 pandemic and in future disasters, medical students may be required to volunteer as auxiliary staff. There is a need to develop infrastructure to facilitate this process as well as providing education and training to ensure students are adequately prepared to perform these roles safely.

Identification of a gene regulatory network associated with prion replication.

Prions consist of aggregates of abnormal conformers of the cellular prion protein (PrP(C)). They propagate by recruiting host-encoded PrP(C) although the critical interacting proteins and the reasons for the differences in susceptibility of distinct cell lines and populations are unknown. We derived a lineage of cell lines with markedly differing susceptibilities, unexplained by PrP(C) expression differences, to identify such factors. Transcriptome analysis of prion-resistant revertants, isolated from highly susceptible cells, revealed a gene expression signature associated with susceptibility and modulated by differentiation. Several of these genes encode proteins with a role in extracellular matrix (ECM) remodelling, a compartment in which disease-related PrP is deposited. Silencing nine of these genes significantly increased susceptibility. Silencing of Papss2 led to undersulphated heparan sulphate and increased PrP(C) deposition at the ECM, concomitantly with increased prion propagation. Moreover, inhibition of fibronectin 1 binding to integrin α8 by RGD peptide inhibited metalloproteinases (MMP)-2/9 whilst increasing prion propagation. In summary, we have identified a gene regulatory network associated with prion propagation at the ECM and governed by the cellular differentiation state.

DINO (Diet In Nutrients Out) - an integrated dietary assessment system.

OBJECTIVE: The current paper describes Diet In Nutrients Out (DINO), an integrated dietary assessment system incorporating dietary data entry and nutritional analysis within one platform for use in dietary assessment in small-scale intervention studies to national surveys. DESIGN: DINO contains >6000 food items, mostly aggregated composites of branded foods, across thirty-one main food groups divided into 151 subsidiary groups for detailed reporting requirements, with fifty-three core nutrient fields. SETTING: MRC Human Nutrition Research (HNR), Cambridge, UK and MRC Keneba, Gambia. SUBJECTS: DINO is used across dietary assessment projects at HNR and MRC Keneba. RESULTS: DINO contains macro- and micronutrients as well as additional variables of current research and policy interest, such as caffeine, whole grains, vitamin K and added sugars. Disaggregated data are available for fruit, vegetables, meat, fish and cheese in composite foods, enabling greater accuracy when reporting food consumption or assessing adherence to dietary recommendations. Portion sizes are categorised in metric and imperial weights, with standardised portion sizes for each age group. Regular reviews are undertaken for portion sizes and food composition to ensure contemporary relevance. A training programme and a checking schedule are adhered to for quality assurance purposes, covering users and data. Eating context questions are integrated to record where and with whom the respondent is eating, allowing examination between these factors and the foods consumed. CONCLUSIONS: An up-to-date quality-assured system for dietary assessment is crucial for nutritional surveillance and research, but needs to have the flexibility to be tailored to address specific research questions.

Cognitive outcomes from the randomised, active-controlled Ketamine for Adult Depression Study (KADS).

BACKGROUND: Due to its rapid antidepressant effect, ketamine has recently been clinically translated for people with treatment-resistant depression. However, its cognitive profile remains unclear, particularly with repeated and higher doses. In the present study, we report the cognitive results from a recent large multicentre randomised controlled trial, the Ketamine for Adult Depression Study (KADS). METHODS: In this randomised, double-blind, active-controlled, parallel group, multicentre phase 3 trial study we investigated potential cognitive changes following repeated treatment of subcutaneous racemic ketamine compared to an active comparator, midazolam, over 4 weeks, which involved two cohorts; Cohort 1 involved a fixed dose treatment protocol (0.5 mg/kg ketamine), Cohort 2 involved a dose escalation protocol (0.5-0.9 mg/kg) based on mood outcomes. Participants with treatment-resistant Major Depressive Disorder (MDD) were recruited from 7 mood disorder centres and were randomly assigned to receive ketamine (Cohort 1 n = 33; Cohort 2 n = 53) or midazolam (Cohort 1 n = 35; Cohort 2 n = 53) in a 1:1 ratio. Cognitive measurements were assessed at baseline and at the end of randomised treatment. RESULTS: Results showed that in Cohort 1, there were no differences between ketamine and midazolam in cognitive outcomes. For Cohort 2, there was similarly no difference between conditions for cognitive outcomes. LIMITATIONS: The study included two Cohorts with different dosing regimes. CONCLUSIONS: The findings support the cognitive safety of repeated fixed and escalating doses at least in the short-term in people with treatment resistant MDD.

Randomised controlled trial of neurostimulation for symptoms of anorexia nervosa (TRENA study): study protocol.

BACKGROUND: Anorexia nervosa (AN) has amongst the highest mortality rates and the highest treatment costs of any psychiatric disorder. Recently, interest in non-invasive brain stimulation as a novel treatment for AN has grown. These include repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). METHODS: This double-blind, randomised sham-controlled trial will compare the relative acceptability and efficacy of tDCS and rTMS in people with AN. 70 participants will be randomised to active or sham tDCS, or active or sham rTMS treatment (2:1:2:1 ratio) over an 8-week treatment period. Participants will receive treatment as usual across the study duration. The primary outcomes are change on the Eating Disorder Examination Questionnaire and treatment acceptability. Secondary outcomes will include change in weight, cognition, mood, interpersonal functioning, and quality of life. Following the 8-week assessment, all participants will have the option of receiving an additional 12 weeks of at-home tDCS. A follow-up assessment will be conducted at 20 weeks post treatment. DISCUSSION: Research into non-invasive brain stimulation as treatments for AN has potential to improve clinical outcomes for patients by comparing the relative efficacy and acceptability of both treatment modalities in the inpatient and at-home setting (i.e., for at-home tDCS) results from this study will provide important information for informing future larger clinical trials of these treatments for AN. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05788042.

The association between temperature, heart rate, and respiratory rate in children aged under 16 years attending urgent and emergency care settings.

BACKGROUND AND IMPORTANCE: Body temperature is considered an independent determinant of respiratory rate and heart rate; however, there is limited scientific evidence regarding the association. This study aimed to assess the association between temperature, and heart rate and respiratory rate in children. OBJECTIVE: The objective of this study was to validate earlier findings that body temperature causes an increase of approximately 10 bpm rise in heart rate per 1 °C rise in temperature, in children aged under 16 years old. DESIGN: A prospective study using anonymised prospectively collected patient data of 188 635 attendances, retrospectively extracted from electronic patient records. SETTINGS AND PARTICIPANTS: Four Emergency or Urgent Care Departments in the North West of England. Participants were children and young people aged 0-16 years old who attended one of the four sites over a period of 3 years. OUTCOME MEASURES AND ANALYSIS: Multiple linear regression models, adjusted for prespecified confounders (including oxygen saturation, heart rate, respiratory rate, site of attendance, age), were used to examine the influence of various variables on heart rate and respiratory rate. MAIN RESULTS: Among the 235 909 patient visits (median age 5) included, the mean temperature was 37.0 (SD, 0.8). Mean heart rate and respiratory rate were 115.6 (SD, 29.0) and 26.9 (SD, 8.3), respectively. For every 1 °C increase in temperature, heart rate will on average be 12.3 bpm higher (95% CI, 12.2-12.4), after accounting for oxygen saturation, location of attendance, and age. For every 1 °C increase in temperature, there is on average a 0.3% decrease (95% CI, 0.2-0.4%) in respiratory rate. CONCLUSION: In this study on children attending urgent and emergency care settings, there was an independent association between temperature and heart rate but not between temperature and respiratory rate.

The narrative coherence of witness transcripts in children on the autism spectrum.

BACKGROUND AND AIMS: Autistic children often recall fewer details about witnessed events than typically developing children (of comparable age and ability), although the information they recall is generally no less accurate. Previous research has not examined the narrative coherence of such accounts, despite higher quality narratives potentially being perceived more favourably by criminal justice professionals and juries. This study compared the narrative coherence of witness transcripts produced by autistic and typically developing (TD) children (ages 6-11 years, IQs 70+). METHODS AND PROCEDURES: Secondary analysis was carried out on interview transcripts from a subset of 104 participants (autism = 52, TD = 52) who had taken part in a larger study of eyewitness skills in autistic and TD children. Groups were matched on chronological age, IQ and receptive language ability. Coding frameworks were adopted from existing narrative research, featuring elements of 'story grammar'. OUTCOMES AND RESULTS: Whilst fewer event details were reported by autistic children, there were no group differences in narrative coherence (number and diversity of 'story grammar' elements used), narrative length or semantic diversity. CONCLUSIONS AND IMPLICATIONS: These findings suggest that the narrative coherence of autistic children's witness accounts is equivalent to TD peers of comparable age and ability.

Epigenetic mechanisms silence a disintegrin and metalloprotease 33 expression in bronchial epithelial cells.

BACKGROUND: A disintegrin and metalloprotease 33 (ADAM33) polymorphism is strongly associated with asthma and bronchial hyperresponsiveness. Although considered to be a mesenchymal cell-specific gene, recent reports have suggested epithelial expression of ADAM33 in patients with severe asthma. OBJECTIVES: Because dysregulated expression of ADAM33 can contribute to disease pathogenesis, we characterized the mechanism or mechanisms that control its transcription and investigated ADAM33 expression in bronchial biopsy specimens and brushings from healthy and asthmatic subjects. METHODS: The ADAM33 promoter and CpG island methylation were analyzed by using bioinformatics, luciferase reporters, and bisulfite sequencing of genomic DNA. Epithelial-mesenchymal transition was induced by using TGF-beta1. ADAM33 mRNA was scrutinized in bronchial biopsy specimens and brushings by using reverse transcriptase-quantitative polymerase chain reaction, melt-curve analysis, and direct sequencing. RESULTS: The predicted ADAM33 promoter (-550 to +87) had promoter transcriptional activity. Bisulfite sequencing showed that the predicted promoter CpG island (-362 to +80) was hypermethylated in epithelial cells but hypomethylated in ADAM33-expressing fibroblasts. Treatment of epithelial cells with 5-aza-deoxycytidine caused demethylation of the CpG island and induced ADAM33 expression. In contrast, phenotypic transformation of epithelial cells through a TGF-beta-induced epithelial-mesenchymal transition was insufficient to induce ADAM33 expression. ADAM33 mRNA was confirmed in bronchial biopsy specimens, but no validated signal was detected in bronchial brushings from healthy or asthmatic subjects. CONCLUSION: The ADAM33 gene contains a regulatory CpG island within its promoter, the methylation status of which tightly controls its expression in a cell type-specific manner. ADAM33 repression is a stable feature of airway epithelial cells, irrespective of disease.

The soluble form of a disintegrin and metalloprotease 33 promotes angiogenesis: implications for airway remodeling in asthma.

BACKGROUND: A disintegrin and metalloprotease (ADAM)-33 is a susceptibility gene for asthma and chronic obstructive pulmonary disease whose function remains unknown. OBJECTIVE: Because asthmatic bronchoalveolar lavage fluid contains high levels of soluble ADAM33 (sADAM33), which includes the catalytic domain, we postulated that its release from cell membranes might play functional roles in airway remodeling by promoting angiogenesis. METHODS: The proangiogenic activity of the highly purified catalytic domain of ADAM33 or a catalytically inactive mutant was studied in vitro (Matrigel assay), ex vivo (human embryonic/fetal lung explants) and in vivo (chorioallantoic membrane assay). The regulation of sADAM33 release from cells overexpressing full-length ADAM33 and its biological activity were characterized. RESULTS: We show that the purified catalytic domain of ADAM33, but not its inactive mutant, causes rapid induction of endothelial cell differentiation in vitro, and neovascularization ex vivo and in vivo. We also show that TGF-beta(2) enhances sADAM33 release from cells overexpressing full-length ADAM33 and that this truncated form is biologically active. CONCLUSION: The discovery that sADAM33 promotes angiogenesis defines it as a tissue remodeling gene with potential to affect airflow obstruction and lung function independently of inflammation. As TGF-beta(2) enhances sADAM33 release, environmental factors that cause epithelial damage may synergize with ADAM33 in asthma pathogenesis, resulting in a disease-related gain of function. This highlights the potential for interplay between genetic and environmental factors in this complex disease.

Sorption of chlorhexidine on cellulose: mechanism of binding and molecular recognition.

Chlorhexidine (CH) is an effective antimicrobial agent. There has been very little work published concerning the interactions of CH with, and its adsorption mechanism on, cellulose. In this paper, such physical chemistry parameters are examined and related to computational chemistry studies. Adsorption isotherms were constructed following application of CH to cellulose. These were typical of a Langmuir adsorption isotherm, but at higher concentrations displayed good correlation also with a Freundlich isotherm. Sorption was attributed to a combination of electrostatic (major contribution) and hydrogen bonding forces, which endorsed computational chemistry proposals: electrostatic interactions between CH and carboxylic acid groups in the cellulose dominate with a contribution to binding through hydrogen bonding of the biguanide residues and the p-chlorophenol moieties (Yoshida H-bonding) with the cellulose hydroxyl groups. At high CH concentrations, there is evidence of monolayer and bilayer aggregation. Differences in sorption between CH and another antimicrobial agent previously studied, poly(hexamethylenebiguanide) (PHMB), are attributed to higher molecular weight of PHMB and higher charge density of biguanide residues in CH (due to the relative electron withdrawing effect of the p-chlorophenol moiety).

Validity of retrospective measures of early maltreatment and depressive episodes using the Childhood Experience of Care and Abuse (CECA) instrument -- A life-course study of adult chronic depression - 2.

BACKGROUND: A previous paper, using data collected retrospectively from sister pairs, reported substantial associations of adult depressive episodes lasting at least 12 months with childhood maltreatment [Brown, G.W., Craig, T.K.J., Harris, T.O. Handley, R.V. & Harvey, A.L. 2007a-this issue. Development of a retrospective interview measure of parental maltreatment using the Childhood Experience of Care & Abuse (CECA) instrument - a life-course study of adult chronic depression - 1. J. Affect. Disord. doi:10.1016/j.jad.2007.05.022]. Risk was far less when depressive episodes of any duration were considered. This paper considers how much scientific weight can be placed on these findings in the light of doubt often expressed about retrospective collection of childhood and adult data. METHODS: The retrospectively gathered material was obtained from adult sister pairs within 5 years of age, comprising a high-risk series (n = 118) where the first sister was selected as likely to have experienced childhood abuse or neglect, and a comparison series (n = 80) where she was selected at random. Current age ranged between early 20s and 50s. Data was collected by semi-structured interviews, using investigator-based ratings covering a wide range of parental behaviour and childhood behaviour. RESULTS: A series of analyses failed to reveal evidence of significant bias in the collection of material about adult depression or parental maltreatment. There was, however, some evidence of under reporting. LIMITATIONS: Conclusions from such analyses can only be judged in terms of degree of plausibility. CONCLUSIONS: Nothing emerged to suggest the presence of significant bias in the aetiological findings of our earlier paper. There is evidence of some underreporting of both early adverse experience and adult depressive episodes, but this is unlikely to threaten the conclusions drawn about the link of parental maltreatment with adult chronic depressive episodes.

Development of a retrospective interview measure of parental maltreatment using the Childhood Experience of Care and Abuse (CECA) instrument -- A life-course study of adult chronic depression - 1.

BACKGROUND: Childhood maltreatment among women is related to risk of adult depression and particularly an episode taking a chronic course. This paper explores the aspects of parental behaviour involved. METHODS: An expanded version of CECA (Childhood Experiences of Care and Abuse), a retrospective interview-based instrument covering neglect as well as various forms of abuse is used to develop a new index of parental maltreatment. Data are derived from an enquiry of sister pairs between early 20s and 50s, comprising a high-risk series (n=118) where the first sister was selected as likely to have experienced childhood abuse or neglect, and a comparison series (n=80) where she was selected at random. RESULTS: Adverse maternal behaviour emerges as of critical importance for the link with adult chronic depression. Maternal lack of affection ('neglect') and maternal rejection ('emotional abuse') form the core of an index of parental maltreatment, and it is concluded that persistent rejection, particularly from a mother, appears to be the core experience of importance. The findings of behavioural genetics that the experience of siblings of parents in ordinary families often differs have been found to hold for the more extreme behaviour involved in maltreatment. Difference between siblings in risk of later chronic depression is entirely related to such experience. LIMITATIONS: The study is based on retrospective questioning of adult women. Our next paper considers the possible threats to validity involved [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007a. Validity of retrospective measures of early maltreatment and depressive episodes using CECA (Childhood Experience of Care and Abuse) - a life-course study of adult chronic depression - 2. J. Affect. Disord. doi:10.1016/j.jad.2007.06.003]. CONCLUSIONS: Parental maltreatment emerges as a critical determinant of later chronic depressive episodes among adult women.

Child-specific and family-wide risk factors using the retrospective Childhood Experience of Care & Abuse (CECA) instrument: a life-course study of adult chronic depression - 3.

BACKGROUND: An earlier paper [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007a-this issue. Development of a retrospective interview measure of parental maltreatment using the Childhood Experience of Care & Abuse (CECA) instrument - a life-course study of adult chronic depression - 1. J. Affect. Disord. doi:10.1016/j.jad.2007.05.022] documented an association between parental maltreatment and risk of adult chronic depression. This paper explores the contribution of other child-specific factors (e.g. conduct problems) and family-wide factors (e.g. parental discord). METHODS: Data are derived from an enquiry of 198 women largely comprising of adult sister pairs. Data was collected by semi-structured interviews covering a wide range of parental behaviour and childhood behaviour. RESULTS: Parental maltreatment emerged as channelling the effect of family-wide factors on risk of adult chronic depression, but with a child's conduct problems and shame-withdrawal partly mediating this link. A child's depression before 17, although correlated with parental maltreatment, did not appear to play a significant role in adult depression. This core model is supplemented by analyses exploring the mechanisms involved. A mother's rejection/physical abuse and her depression via her lax control, for example, account for the link of parental maltreatment with conduct problems. Also 'rebelliousness' of a child relates to the chances of her low affection moving to rejection. "Rebelliousness" also appears to play a role in why the paired sisters so often had a different experience of maltreatment. LIMITATIONS: The data is collected retrospectively - but see [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L., 2007b-this issue. Validity of retrospective measures of early maltreatment and depressive episodes using the Childhood Experience of Care and Abuse (CECA) instrument - A life-course study of adult chronic depression - 2. J. Affect. Disord. doi:10.1016/j.jad.2007.06.003]. CONCLUSIONS: Child-specific factors play a major role in the origins of adult chronic depressive episodes. This, however, is fully consistent with an equally significant contribution from family-wide factors. The crucial point is that the link of the latter with such depression appears to be indirect and mediated very largely by parental maltreatment.