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The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science., To help meet the ensuing demand for COVID-19 reagents, this article presents an openly available ‘coronavirus toolkit’ (https://mrcppu-covid.bio) and describes the generation and validation of these tools, including a simple SARS-CoV-2 reverse genetics system and a near-comprehensive panel of SARS-CoV-2 antibodies.

Indwelling pleural catheters (IPCs) are commonly used in the management of malignant pleural effusion (MPE). There is little data on their use in non-malignant conditions. All IPC insertions for non-malignant cases from five large UK centres were found using prospectively maintained databases. Data were collected on 57 IPC insertions. The commonest indications were hepatic hydrothorax (33%) and inflammatory pleuritis (26%). The mean weekly fluid output was 2.8 L (SD 2.52). 48/57 (84%) patients had no complications. Suspected pleural infection was documented in 2 (3.5%) cases. 33% (19/57) of patients underwent 'spontaneous' pleurodesis at a median time of 71 days. Patients with hepatic disease achieved pleurodesis significantly less often than those with non-hepatic disease (p=0.03). These data support the use of IPCs in select cases of non-malignant disease when maximal medical therapy has failed.

The ‘NEET’ population has recently become a national focus for concern. The term refers to young people, aged 16 to 19, who are ‘not in education, employment or training’. The nature of the NEET population is recognised as very diverse, and the size is estimated as between 13.2 per cent to 14.5 per cent of all 16- to 19-year-olds. Routes into the population can be explained through psychological theories such as developmental contextualism, the focal model and resiliency theory. Several interventions and preventative strategies are already in place, with varying degrees of success. It is proposed that EPs can play an important role in reducing the NEET population through application of their five core functions.

While local residents are widely recognised to play a pivotal role in the development and management of destinations, their role in the context of visitor attractions has largely been overlooked. This paper seeks to explore the purposes and processes of local-resident engagement by attractions. A web-based survey of paid-entry attractions in Scotland was used to investigate the perceived salience of local residents in managers’ decision making. In-depth interviews with managers of three Scottish attractions then sought to specify the forms in which such engagement is undertaken. Despite evidence that attraction managers increasingly recognise the salience of local residents in their decision making, evidence from the interviews suggests that they tend not to favour deep engagement with local residents. Instead, local resident engagement by attraction managers tends to be “informative” in style. Where there is evidence of more substantial participation, it tends to be partial, reactive and ad hoc.

Background Recurrent symptomatic non-infectious pleural effusions can be effectively treated with MT and TP with pleurodesis rates approaching 85% in variety of malignant and benign aetiologies. When TL is likely at MT, management is uncertain. Aim We report on a single centre experience of inserting an IPC at MT with or without talc poudrage for suspected trapped lung. TL was suspected if any of the following were observed (a) failure of lung to inflate on voluntary coughing at MT, (b) visceral involvement of more than 25%, (c) radiological evidence of endobronchial compromise and (d) hydropneumothorax following previous thoracocentesis. Method A review of all IPC insertions at MT performed at our institution between March 2009 and Feb 2013 assessing indications, length of stay (LoS) after procedure, use of concurrent TP, IPC removal rates and recorded complications. All cases had been performed using rigid thoracoscopy. TP was performed with 4g sterile graded talc. Rocket 16F IPC were used in all cases. Results All IPCs were inserted during MT for likely or possible TL. N = 36cases. 14 male. Diagnoses–10 benign recurrent effusions; 26 malignant. See table 1 for details. Median age 73yrs (45–92). Median LoS post procedure–non-elective 7 days (1–23); elective 2.5 days (0–6). 22 (56%) had concurrent TP (18 for malignancy). 14 (36%) had their IPC removed with median time to removal 40 days (28–119) and of these, 11 had received TP during MT. 20 patients have died during follow up (none procedure-related) of which 11 still had their IPC in situ . Complications–2 blocked drains (not talc group, 1 case needing additional thoracocentesis), 2 leaking caps (replaced). Discussion IPC insertion at MT with or without TP for cases of suspected TL appears to be safe, effective and obviates the need for further pleural intervention at a later date. This potentially has significant benefits to the patient as well as a reduction in overall healthcare costs to the NHS. Using the above criteria predicted TL in 78% of patients. This single centre observation needs to be investigated by a larger multi-centre study in patients with suspected TL at MT.

Although indwelling pleural catheters (IPC) are commonly used to allow the outpatient management of malignant pleural effusions, an increasing number if IPCs are being inserted to control effusions caused by non-malignant processes. This is the first UK-based series to analyse the use of IPCs in this setting. Methods We analysed data from 3 UK hospitals with large pleural services. IPCs inserted between 2007 and June 2012 were identified retrospectively. Information was obtained from hospital records and from patients’ primary physicians. Bilateral or non-sequential IPCs in a single patient were treated as separate data points. Results 30 IPCs were inserted, with a year-on-year rise in the number of drains seen over the analysis period. The mean age of patients was 64 (range 37–92 years). 57% were male. IPCs stayed in place for a median of 95 days (IQR 41–211) before death or removal. 6 patients died with their IPC in situ. The majority of drains (47%, n=14) were inserted for the management of hepatic hydrothorax of varying aetiology (see table 1). 10 of these patients were given human albumin solution (HAS) intermittently with drainage. 87% of patients began with a drainage frequency of 3 times per week or greater. At final analysis only 37% of patients remained in this group, with 50% overall experiencing a reduction in drainage needs. Drainages were most often performed by community nurses (30%) or family members (30%). Complications included drain site leak (n=1), equipment failure (n=1), pleural infection (n=2) and skin infection (n=1). IPCs were removed in 54% (n=16), with 6 patients achieving successful pleurodesis. Other reasons for removal included fluid loculation (n=2), or transplant operation(n=3). 83% of patients needed no additional pleural intervention following IPC insertion. In only 1 case did the primary physician feel the insertion of the IPC was not of value. Conclusions These data suggest the use of IPCs in the non-malignant setting is increasing. Complications were rare and most patients could be managed for extended periods in the community alone. This series would suggest that IPCs are a viable option for the management of recurrent pleural effusions of non-malignant aetiology. Dr Maskell has received an unrestricted research grant from Care Fusion, not related to this study. Dr Rahman acts as a consultant to Rocket Medical UK, not related to this study.

Although familial clustering has been described, few studies have quantified the risk of airflow obstruction in siblings of patients with chronic obstructive pulmonary disease (COPD). One hundred fifty-two subjects with airflow obstruction and a low gas transfer factor (but without PiZ alpha(1)-antitrypsin deficiency) were identified and 150 were enrolled in the study. Complete data were obtained from 173 of 221 siblings of these subjects. Forty-four of 126 current or ex-smoking siblings had airflow obstruction (FEV(1)/FVC < 0.7) and 36 also had a FEV(1) < 80% predicted, in keeping with COPD. One hundred eleven current or ex-smoking siblings were matched for age, sex, and smoking history with 419 subjects, without a known family history of COPD, from the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort. The prevalence of COPD was much lower in the EPIC group (9.3%) when compared with the siblings (31.5%; odds ratio, 4.70; 95% confidence interval, 2.63 to 8.41). The odds ratio for COPD in siblings with less than a 30 pack-year smoking history was 5.39 (95% confidence interval, 2.49 to 11.67) when compared with matched control subjects. Taken together these results demonstrate a significant familial risk of airflow obstruction in smoking siblings of patients with severe COPD.

Deoxygenation of 2,5-di-tert-butylnitrosobenzene (1) by triethylphosphite gave a complex mixture containing 2,5-di-tert-butylaniline, 2,5,2′,5′-tetra-tert-butylazobenzene, N-(2,5-di-tert-butylphenyl)-α-tert-butyl-α-2-(5-tert-butylpyridyl)nitrone, and diethyl N-(2,5-di-tert-butylphenyl)phosphoramidate. In contrast deoxygenation of 2,4,6-tri-tert-butylnitrosobenzene (2) yielded mainly 3,3-dimethyl-5,7-di-tert-butyl-2,3-dihydroindole (80%), together with small amounts of 2,4,6-tri-tert-butylaniline and a product of side chain rearrangement, 2-(2-methyl-3-propenyl)-4,6-di-tert-butylaniline. Reaction pathways involving nitrenoid intermediates account for the various products. The different types of products from 1 and 2 are explained in terms of differential steric and conformational effects.