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This clinical manual provides a CBT-based psychosocial intervention for use with individuals distressed about their appearance due to a disfigurement from birth, accident or illness, or those coping with another visible difference.   * Contains a wealth of case material with specific relevance to physical health conditions that affect appearance, practical advice on assessment, and session-by-session guidance for addressing common issues * Written by leading academics and clinicians working in the management of disfigurement and rational appearance anxiety * Uses a flexible stepped-care model that allows for use by experienced CBT practitioners as well those wishing to deliver a more basic psychological intervention * Identifies the psychological factors involved in appearance anxiety while also addressing the practical concerns of living with a visible difference, such as managing the reactions of others

Background Before COVID-19, people with rare diseases (RD) experienced numerous disparities in quality of life and healthcare access and quality, yet little is known about the experiences of this underserved group during the pandemic. Results During the first wave of the COVID-19 pandemic in the United States, spring and summer of 2020, 759 participants representing 231 unique RDs responded to open-ended questions about the impact of the pandemic on life with a RD, healthcare access, and coping. Qualitative conventional content analysis was used to analyze responses. Identified themes represented positive and negative dimensions of change, including a shock to the (health) system , coping with uncertainty , and the value of social support while isolated . Conclusions Limitations in healthcare access and quality were the most frequently described as impacts of COVID-19. Other major negative impacts included exacerbation of symptoms, psychological distress, and a lack of usual social support and reliable information. However, participants also noted silver linings, especially in healthcare. For some, expanded telehealth enhanced their ability to access medical and mental health providers and RD specialists. Finally, many participants hoped that, by highlighting social and health inequities faced by people with RDs and other minorities, the pandemic would prompt greater understanding and policies that could improve the quality of life of the RD community.

BackgroundIndividual behaviour changes, such as hand hygiene and physical distancing, are required on a population scale to reduce transmission of infectious diseases such as COVID-19. However, little is known about effective methods of communicating risk reducing information, and how populations might respond.ObjectiveTo synthesise evidence relating to what (1) characterises effective public health messages for managing risk and preventing infectious disease and (2) influences people’s responses to messages.DesignA rapid systematic review was conducted. Protocol is published on Prospero CRD42020188704.Data sourcesElectronic databases were searched: Ovid Medline, Ovid PsycINFO and Healthevidence.org, and grey literature (PsyarXiv, OSF Preprints) up to May 2020.Study selectionAll study designs that (1) evaluated public health messaging interventions targeted at adults and (2) concerned a communicable disease spread via primary route of transmission of respiratory and/or touch were included. Outcomes included preventative behaviours, perceptions/awareness and intentions. Non-English language papers were excluded.SynthesisDue to high heterogeneity studies were synthesised narratively focusing on determinants of intentions in the absence of measured adherence/preventative behaviours. Themes were developed independently by two researchers and discussed within team to reach consensus. Recommendations were translated from narrative synthesis to provide evidence-based methods in providing effective messaging.ResultsSixty-eight eligible papers were identified. Characteristics of effective messaging include delivery by credible sources, community engagement, increasing awareness/knowledge, mapping to stage of epidemic/pandemic. To influence intent effectively, public health messages need to be acceptable, increase understanding/perceptions of health threat and perceived susceptibility.DiscussionThere are four key recommendations: (1) engage communities in development of messaging, (2) address uncertainty immediately and with transparency, (3) focus on unifying messages from sources and (4) frame messages aimed at increasing understanding, social responsibility and personal control. Embedding principles of behavioural science into public health messaging is an important step towards more effective health-risk communication during epidemics/pandemics.

The solventogenic clostridia have long been known for their ability to convert sugars from complex feedstocks into commercially important solvents. Although the acetone-butanol-ethanol process fell out of favour decades ago, renewed interest in sustainability and ‘green’ chemistry has re-established our appetite for reviving technologies such as these, albeit with 21st century improvements. As CRISPR-Cas genome editing tools are being developed and applied to the solventogenic clostridia, their industrial potential is growing. Through integration of new pathways, the beneficial traits and historical track record of clostridial fermentation can be exploited to generate a much wider range of industrially relevant products. Here we show the application of genome editing using the endogenous CRISPR-Cas mechanism of Clostridium saccharoperbutylacetonicum N1-4(HMT), to generate a deletion, SNP and to integrate new DNA into the genome. These technological advancements pave the way for application of clostridial species to the production of an array of products.

Summary The development and advent of mutagenesis tools for solventogenic clostridial species in recent years has allowed for the increased refinement of industrially relevant strains. In this study we have utilised CLEAVE™, a CRISPR/Cas genome editing system developed by Green Biologics Ltd., to engineer a strain of Clostridium saccharoperbutylacetonicum N1‐4(HMT) with potentially useful solvents titres and energy metabolism. As one of two enzymes responsible for the conversion of glyceraldehyde‐3‐phosphate (GAP) to 3‐phosphoglyceric acid in glycolysis, it was hypothesised that deletion of gapN would increase ATP and NADH production that could in turn improve solvent production. Herein, whole genome sequencing has been used to evaluate CLEAVE™ and the successful knockout of gapN, demonstrating a clean knockout with no other detectable variations from the wild type sequence. Elevated solvent levels were detected during the first 24 h of batch fermentation, indicating an earlier shift to solventogenesis. A 2.4‐fold increase in ATP concentration was observed, and quantitation of NAD(P)H derivatives revealed a more reducing cytoplasm for the gapN strain. These findings expand our understanding of clostridium carbon metabolism and report a new approach to optimising biofuel production. This article employs a combination of genetic, genomic and microbiological techniques to demonstrate that manipulation of glyceraldehyde‐3‐phosphate activity in a solventogenic clostridium species can enhance butanol and acetone titres. These findings expand our understanding of clostridium carbon metabolism and report a new approach to optimising biofuel production.

Public health teams need to understand how the public responds to vaccination messages in a pandemic or epidemic to inform successful campaigns encouraging the uptake of new vaccines as they become available. A rapid systematic review was performed by searching PsycINFO, MEDLINE, healthevidence.org, OSF Preprints and PsyArXiv Preprints in May 2020 for studies including at least one health message promoting vaccine uptake of airborne-, droplet- and fomite-spread viruses. Included studies were assessed for quality using the Mixed Methods Appraisal Tool (MMAT) or the Assessment of Multiple Systematic Reviews (AMSTAR), and for patient and public involvement (PPI) in the research. Thirty-five articles were included. Most reported messages for seasonal influenza (n = 11; 31%) or H1N1 (n = 11; 31%). Evidence from moderate to high quality studies for improving vaccine uptake included providing information about virus risks and vaccination safety, as well as addressing vaccine misunderstandings, offering vaccination reminders, including vaccination clinic details, and delivering mixed media campaigns across hospitals or communities. Behavioural influences (beliefs and intentions) were improved when: shorter, risk-reducing or relative risk framing messages were used; the benefits of vaccination to society were emphasised; and beliefs about capability and concerns among target populations (e.g., vaccine safety) were addressed. Clear, credible, messages in a language target groups can understand were associated with higher acceptability. Two studies (6%) described PPI in the research process. Future campaigns should consider the beliefs and information needs of target populations in their design, including ensuring that vaccine eligibility and availability is clear, and messages are accessible. More high quality research is needed to demonstrate the effects of messaging interventions on actual vaccine uptake.

Despite cigarette-like adverse health outcomes associated with waterpipe tobacco smoking and increase in its use among youth, it is a much underexplored research area. We aimed to measure the prevalence and patterns of waterpipe tobacco use and evaluate tobacco control policy with respect to waterpipe tobacco, in several universities across the UK. We also aimed to measure stop smoking practitioners' encounter of waterpipe tobacco smoking. We distributed an online survey to six UK universities, asking detailed questions on waterpipe tobacco. Multivariable logistic regression models, adjusted for age, gender, ethnicity, graduate status, university and socioeconomic status (SES) assessed associations between waterpipe tobacco smoking (single use and dual use with cigarettes) and sociodemographic variables. SES was ascertained by average weekly self-spend on non-essentials. We also descriptively analysed data from a 2012 survey of stop smoking practitioners to assess the proportion of clients that used waterpipe regularly. f 2217 student responses, 66.0% (95% CI 63.9-68.0%) had tried waterpipe tobacco smoking; 14.3% (95% CI 12.8-15.8%) reported past-30 day use, and 8.7% (95% CI 7.6-9.9%) reported at least monthly users. Past-30 day waterpipe-only use was associated with being younger (AOR 0.95, 95% CI 0.91-0.99), male (AOR 1.44, 95% CI 1.08-1.94), higher SES (AOR 1.16, 95% CI 1.06-1.28) and belonging to non-white ethnicities (vs. white, AOR 2.24, 95% CI 1.66-3.04). Compared to less than monthly users, monthly users were significantly more likely to have urges to smoke waterpipe (28.1% vs. 3.1%, p<0.001) report difficulty in quitting (15.5% vs. 0.8%, p<0.001), report feeling guilty, and annoyed when criticised about waterpipe smoking (19.2% vs. 9.2%, p<0.001). Nearly a third (32.5%) of respondents who had tried waterpipe had violated the UK smokefree law and a quarter (24.5%) reporting seeing health warnings on waterpipe tobacco packaging or apparatuses. Of 1,282 smoking cessation practitioners, a quarter (23.4%, 95% CI 21.5-26.1%) reported having some clients who regularly use waterpipes, but 69.5% (95% CI 67.0-72.0%) never ask clients about waterpipe use. Three quarters (74.8%, 95% CI 72.4-77.1%) want more information about waterpipe tobacco smoking. While two thirds of university students have ever tried waterpipe tobacco, at least monthly use is less common. Regular users display features of waterpipe tobacco dependence, and a substantial minority of SSS practitioners encounter clients who regularly use waterpipe. The lack of training on waterpipe for SSS practitioners and reported violations of smokefree laws for waterpipe highlight the need for regular surveillance of and a coordinated tobacco control strategy for waterpipe use.

The minichromosome maintenance (MCM) proteins are essential conserved proteins required for DNA replication in archaea and eukaryotes. MCM proteins are believed to provide the replicative helicase activity that unwinds template DNA ahead of the replication fork. Consistent with this hypothesis, MCM proteins can form hexameric complexes that possess ATP-dependent DNA unwinding activity. The molecular mechanism by which the energy of ATP hydrolysis is harnessed to DNA unwinding is unknown, although the ATPase activity has been attributed to a highly conserved AAA+ family ATPase domain. Here we show that changes to Nand C-terminal motifs in the single MCM protein from the archaeon Methanothermobacter thermautotrophicus (MthMCM) can modulate ATP hydrolysis, DNA binding, and duplex unwinding. Furthermore, these motifs appear to influence the movement of the β-α-β insert in helix-2 of the MCM ATPase domain. Removal of this motif from MthMCM increased dsDNA-stimulated ATP hydrolysis and increased the affinity of the mutant complex for ssDNA and dsDNA. Deletion of the helix-2 insert additionally resulted in the abrogation of DNA unwinding. Our results provide significant insight into the molecular mechanisms used by the MCM helicase to both regulate and execute DNA unwinding.

BackgroundStaff retention in Emergency Medicine (EM) is at crisis level and could be attributed in some part to adverse working conditions. This study aimed to better understand current concerns relating to working conditions and working practices in Emergency Departments (EDs).MethodsA qualitative approach was taken, using focus groups with ED staff (doctors, nurses, advanced care practitioners) of all grades, seniority and professional backgrounds from across the UK. Snowball recruitment was undertaken using social media and Royal College of Emergency Medicine communication channels. Focus group interviews were conducted online and organised by profession. A semi-structured topic guide was used to explore difficulties in the work environment, impact of these difficulties, barriers and priorities for change. Data were analysed using a directive content analysis to identify common themes.ResultsOf the 116 clinical staff who completed the eligibility and consent forms, 46 met criteria and consented, of those, 33 participants took part. Participants were predominantly white British (85%), females (73%) and doctors (61%). Four key themes were generated: ‘culture of blame and negativity’, ‘untenable working environments’, ‘compromised leadership’ and ‘striving for support’. Data pertaining to barriers and opportunities for change were identified as sub-themes. In particular, strong leadership emerged as a key driver of change across all aspects of working practices.ConclusionThis study identified four key themes related to workplace concerns and their associated barriers and opportunities for change. Culture, working environment and need for support echoed current narratives across healthcare settings. Leadership emerged more prominently than in prior studies as both a barrier and opportunity for well-being and retention in the EM workplace. Further work is needed to develop leadership skills early on in clinical training, ensure protected time to deliver the role, ongoing opportunities to refine leadership skills and a clear pathway to address higher levels of management.

The manufacture of bio-chemicals through the use of microbial fermentation and renewable feedstock has a number of well-known advantages linked to sustainability and reduced impacts on the environment. Markets for molecules produced with greener credentials are growing as consumers become more aware of what is in the formulated products they use every day. The use of solventogenic clostridia has now been re-commercialised for the production of bio-acetone and bio-n-butanol. The different impurity profiles of these bio-based molecules compared with petro-versions results in performance advantages in downstream derivatisation chemistry, giving an added benefit alongside sustainability advantages. Advances in genome editing now enable us to take the benefits observed with clostridial fermentation and apply them to the production of the next generation of bio-molecules.