'A true partner around the table?' Perceptions of how to strengthen public health's contributions to the alcohol licensing process

Introduction: There are increased opportunities for public health practitioners (PHPs) in England to shape alcohol availability and reduce harms through a statutory role in licensing processes in local government. However, how public health can effectively influence alcohol licence decision-making is little understood. Methods: A mixed methods study was conducted to identify challenges faced by PHPs and mechanisms to strengthen their role. This involved a survey of practitioners across London local authorities (n = 18) and four focus group discussions with a range of licensing stakeholders (n = 36). Results: Survey results indicated a varied picture of workload, capacity to respond to licence applications and levels of influence over decision-making among PHPs in London. Practitioners described a felt lack of status within the licence process, and difficulties using and communicating public health evidence effectively, without a health licensing objective. Strategies considered supportive included engaging with other responsible authorities and developing understanding and relationships over time. Conclusions: Against political and resource constraints at local and national government levels, pragmatic approaches for strengthening public health influence over alcohol licensing are required, including promoting relationships between stakeholders and offering opportunities for PHPs to share best practice about making effective contributions to licensing

Multinational Experiences in Reducing and Preventing the Use of Restraint and Seclusion

Restraint and seclusion (R/S) have been used in many countries and across service sectors for centuries. With the recent and increasing recognition of the harm associated with these procedures, efforts have been made to reduce and prevent R/S. Following a scathing media exposé in 1998 and congressional scrutiny, the United States began a national effort to reduce and prevent R/S use. With federal impetus and funding, an evidence-based practice, the Six Core Strategies1 to Prevent Conflict, Violence and the Use of Seclusion and Restraint, was developed. This model was widely and successfully implemented in a number of U.S. states and is being adopted by other countries, including Finland, Australia, and the United Kingdom. Recently, the first cluster randomized controlled study of the Six Core Strategies in Finland provided the first evidence-based data of the safety and effectiveness of a coercion prevention methodology. Preliminary findings of some of the international efforts are discussed. Reduction in R/S use and other positive outcomes are also reported

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p<0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p<0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p<0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

Making the diagnosis of Chronic Fatigue Syndrome/Myalgic Encephalitis in primary care: a qualitative study

<p>Abstract</p> <p>Background</p> <p>NICE guidelines emphasise the role of the primary care team in the management of patients with Chronic Fatigue Syndrome/Myalgic Encephalitis (CFS/ME). A key stage in effective management is making an accurate early diagnosis, supported by appropriate referral.</p> <p>Methods</p> <p>A nested qualitative study within a multi-centre randomised controlled trial which aimed to explore GPs' views on their role in making the diagnosis of CFS/ME and subsequent management of patients in primary care. Semi-structured interviews with 22 GPs. Interviews were transcribed verbatim and an iterative approach used to develop themes from the dataset.</p> <p>Results</p> <p>GPs described difficulties in defining CFS/ME and suggested that their role in making a diagnosis was to exclude physical causes for the patient's symptoms, but they reported little confidence in positively attributing the label of CFS/ME to a patient and their symptoms. GPs suggested that the label of CFS/ME could be potentially harmful for the patient. The role of referral to secondary care was debated and GPs struggled defining their own role in management of this group of patients.</p> <p>Conclusions</p> <p>Until GPs feel comfortable making the diagnosis of CFS/ME and facilitating initial management, and have appropriate services to refer patients to, there will continue to be delays in confirming the diagnosis and patients presenting in primary care with fatigue may not receive appropriate care.</p> <p>Trial Registration</p> <p>ISRCTN 74156610</p

Practice Nurses' views of their role in the management of Chronic Fatigue Syndrome/Myalagic Encephalitis: a qualitative study

<p>Abstract</p> <p>Background</p> <p>NICE guidelines suggest that patients with Chronic Fatigue Syndrome/Myalgic Encephalitis (CFS/ME) should be managed in Primary Care. Practice Nurses are increasingly being involved in the management of long-term conditions, so are likely to also have a growing role in managing CFS/ME. However their attitudes to, and experiences of patients with CFS/ME and its management must be explored to understand what barriers may exist in developing their role for this group of patients. The aim of this study was to explore Practice Nurses' understanding and beliefs about CFS/ME and its management.</p> <p>Methods</p> <p>Semi-structured interviews with 29 Practice Nurses. Interviews were transcribed verbatim and an iterative approach used to develop themes from the dataset.</p> <p>Results</p> <p>Practice nurses had limited understanding about CFS/ME which had been largely gained through contact with patients, friends, personal experiences and the media rather than formal training. They had difficulty seeing CFS/ME as a long term condition. They did identify a potential role they could have in management of CFS/ME but devalued their own skills in psychological intervention, and suggested counselling would be an appropriate therapeutic option. They recognised a need for further training and on going supervision from both medical and psychological colleagues. Some viewed the condition as contentious and held pejorative views about CFS/ME. Such scepticism and negative attitudes will be a significant barrier to the management of patients with CFS/ME in primary care.</p> <p>Conclusion</p> <p>The current role of Practice Nurses in the ongoing management of patients with CFS/ME is limited. Practice Nurses have little understanding of the evidence-base for treatment of CFS/ME, particularly psychological therapies, describing management options in terms of advice giving, self-help or counselling. Practice Nurses largely welcomed the potential development of their role in this area, but identified barriers and training needs which must be addressed to enable them to feel confident managing of patients with this condition. Training must begin by addressing negative attitudes to patients with CFS/ME.</p

A Single Polar Residue and Distinct Membrane Topologies Impact the Function of the Infectious Bronchitis Coronavirus E Protein

The coronavirus E protein is a small membrane protein with a single predicted hydrophobic domain (HD), and has a poorly defined role in infection. The E protein is thought to promote virion assembly, which occurs in the Golgi region of infected cells. It has also been implicated in the release of infectious particles after budding. The E protein has ion channel activity in vitro, although a role for channel activity in infection has not been established. Furthermore, the membrane topology of the E protein is of considerable debate, and the protein may adopt more than one topology during infection. We previously showed that the HD of the infectious bronchitis virus (IBV) E protein is required for the efficient release of infectious virus, an activity that correlated with disruption of the secretory pathway. Here we report that a single residue within the hydrophobic domain, Thr16, is required for secretory pathway disruption. Substitutions of other residues for Thr16 were not tolerated. Mutations of Thr16 did not impact virus assembly as judged by virus-like particle production, suggesting that alteration of secretory pathway and assembly are independent activities. We also examined how the membrane topology of IBV E affected its function by generating mutant versions that adopted either a transmembrane or membrane hairpin topology. We found that a transmembrane topology was required for disrupting the secretory pathway, but was less efficient for virus-like particle production. The hairpin version of E was unable to disrupt the secretory pathway or produce particles. The findings reported here identify properties of the E protein that are important for its function, and provide insight into how the E protein may perform multiple roles during infection

Dual Functions of ASCIZ in the DNA Base Damage Response and Pulmonary Organogenesis

Zn2+-finger proteins comprise one of the largest protein superfamilies with diverse biological functions. The ATM substrate Chk2-interacting Zn2+-finger protein (ASCIZ; also known as ATMIN and ZNF822) was originally linked to functions in the DNA base damage response and has also been proposed to be an essential cofactor of the ATM kinase. Here we show that absence of ASCIZ leads to p53-independent late-embryonic lethality in mice. Asciz-deficient primary fibroblasts exhibit increased sensitivity to DNA base damaging agents MMS and H2O2, but Asciz deletion or knock-down does not affect ATM levels and activation in mouse, chicken, or human cells. Unexpectedly, Asciz-deficient embryos also exhibit severe respiratory tract defects with complete pulmonary agenesis and severe tracheal atresia. Nkx2.1-expressing respiratory precursors are still specified in the absence of ASCIZ, but fail to segregate properly within the ventral foregut, and as a consequence lung buds never form and separation of the trachea from the oesophagus stalls early. Comparison of phenotypes suggests that ASCIZ functions between Wnt2-2b/ß-catenin and FGF10/FGF-receptor 2b signaling pathways in the mesodermal/endodermal crosstalk regulating early respiratory development. We also find that ASCIZ can activate expression of reporter genes via its SQ/TQ-cluster domain in vitro, suggesting that it may exert its developmental functions as a transcription factor. Altogether, the data indicate that, in addition to its role in the DNA base damage response, ASCIZ has separate developmental functions as an essential regulator of respiratory organogenesis

Longer-term efficiency and safety of increasing the frequency of whole blood donation (INTERVAL): extension study of a randomised trial of 20 757 blood donors

Background: The INTERVAL trial showed that, over a 2-year period, inter-donation intervals for whole blood donation can be safely reduced to meet blood shortages. We extended the INTERVAL trial for a further 2 years to evaluate the longer-term risks and benefits of varying inter-donation intervals, and to compare routine versus more intensive reminders to help donors keep appointments. Methods: The INTERVAL trial was a parallel group, pragmatic, randomised trial that recruited blood donors aged 18 years or older from 25 static donor centres of NHS Blood and Transplant across England, UK. Here we report on the prespecified analyses after 4 years of follow-up. Participants were whole blood donors who agreed to continue trial participation on their originally allocated inter-donation intervals (men: 12, 10, and 8 weeks; women: 16, 14, and 12 weeks). They were further block-randomised (1:1) to routine versus more intensive reminders using computer-generated random sequences. The prespecified primary outcome was units of blood collected per year analysed in the intention-to-treat population. Secondary outcomes related to safety were quality of life, self-reported symptoms potentially related to donation, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin and other factors. This trial is registered with ISRCTN, number ISRCTN24760606, and has completed. Findings: Between Oct 19, 2014, and May 3, 2016, 20 757 of the 38 035 invited blood donors (10 843 [58%] men, 9914 [51%] women) participated in the extension study. 10 378 (50%) were randomly assigned to routine reminders and 10 379 (50%) were randomly assigned to more intensive reminders. Median follow-up was 1·1 years (IQR 0·7–1·3). Compared with routine reminders, more intensive reminders increased blood collection by a mean of 0·11 units per year (95% CI 0·04–0·17; p=0·0003) in men and 0·06 units per year (0·01–0·11; p=0·0094) in women. During the extension study, each week shorter inter-donation interval increased blood collection by a mean of 0·23 units per year (0·21–0·25) in men and 0·14 units per year (0·12–0·15) in women (both p&lt;0·0001). More frequent donation resulted in more deferrals for low haemoglobin (odds ratio per week shorter inter-donation interval 1·19 [95% CI 1·15–1·22] in men and 1·10 [1·06–1·14] in women), and lower mean haemoglobin (difference per week shorter inter-donation interval −0·84 g/L [95% CI −0·99 to −0·70] in men and −0·45 g/L [–0·59 to −0·31] in women) and ferritin concentrations (percentage difference per week shorter inter-donation interval −6·5% [95% CI −7·6 to −5·5] in men and −5·3% [–6·5 to −4·2] in women; all p&lt;0·0001). No differences were observed in quality of life, serious adverse events, or self-reported symptoms (p&gt;0.0001 for tests of linear trend by inter-donation intervals) other than a higher reported frequency of doctor-diagnosed low iron concentrations and prescription of iron supplements in men (p&lt;0·0001). Interpretation: During a period of up to 4 years, shorter inter-donation intervals and more intensive reminders resulted in more blood being collected without a detectable effect on donors' mental and physical wellbeing. However, donors had decreased haemoglobin concentrations and more self-reported symptoms compared with the initial 2 years of the trial. Our findings suggest that blood collection services could safely use shorter donation intervals and more intensive reminders to meet shortages, for donors who maintain adequate haemoglobin concentrations and iron stores. Funding: NHS Blood and Transplant, UK National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives