'Give us the real tools to do our jobs': views of UK stakeholders on the role of a public health objective for alcohol licensing.

OBJECTIVES: This study ascertains the views of UK stakeholders on the actual, and possible, impact of a public health licensing objective in their day-to-day work. STUDY DESIGN AND METHODS: Twenty-eight interviews were conducted with members of public health teams who were actively engaged in alcohol licensing in their local area between 2017 and 2019. Six teams were based in Scotland (where there is a public health licensing objective) and 14 in England (where there is no similar objective). RESULTS: Scottish participants reported that while challenges remained in applying the public health licensing objective, progress had been made and the objective was beneficial to their work. Participants in England felt that an objective would increase the legitimacy, value and impact of their contributions. In both Scotland and England, constructive relationships between PHTs, licensing authorities and other key stakeholders were developing suggesting that PHTs could have a sustainable and positive role in licensing. CONCLUSIONS: In many Scottish areas, the alcohol licensing system is evolving to take constructive account of its public health objective. In England, PHTs that have invested resources in engaging in this area have demonstrated an ability to work effectively within licensing systems. Strong support for the adoption of a public health licensing objective among these PHTs adds weights to calls for the UK Government to reconsider its previous decision not to introduce such an objective.

Training in colorectal surgery in Europe and 20 years of the European Board of Surgical Qualification coloproctology examination.

AIM: Training in colorectal surgery across Europe is not yet standardized. The European Board of Surgical Qualification (EBSQ) coloproctology examination has been held annually since 1998. The aims of this study were to illustrate the current situation of coloproctology specialization in Europe and to analyse the EBSQ examinations held over the last 20 years. METHOD: A survey, focused on current training and education in colorectal surgery in Europe, was conducted among all national representatives of the European Society of Coloproctology (ESCP) in 2018. Candidate demographics (1998-2018) and the results of the EBSQ examination (2007-2018) were analysed. RESULTS: In Europe, there are currently 26 national colorectal societies, 27 national annual colorectal meetings, 16 national specialized training programmes and 13 national colorectal fellowships. Six countries have board certification in colorectal surgery and five a dedicated examination. During the last 20 years, 475 candidates from 29 countries, of whom 88 (19%) were women, passed the EBSQ examination. The pass rate was higher in younger applicants (< 42 years, P = 0.01). The success rate was higher for candidates with academic experience (more than five publications or presentations) and with an academic title (thesis) (P = 0.01). CONCLUSION: Colorectal surgical training is still not standardized in Europe, although efforts have been made to recognize colorectal surgery as an independent speciality. The number of holders of the EBSQ Diploma has increased over the years, demonstrating the acceptance of the examination among European surgeons. Young candidates with an academic profile are the most successful.

Tropism of influenza B viruses in human respiratory tract explants and airway organoids.

Despite causing regular seasonal epidemics with substantial morbidity, mortality and socioeconomic burden, there is still a lack of research into influenza B viruses (IBVs). In this study, we provide for the first time a systematic investigation on the tropism, replication kinetics and pathogenesis of IBVs in the human respiratory tract.Physiologically relevant ex vivo explant cultures of human bronchus and lung, human airway organoids, and in vitro cultures of differentiated primary human bronchial epithelial cells and type-I-like alveolar epithelial cells were used to study the cellular and tissue tropism, replication competence and induced innate immune response of 16 IBV strains isolated from 1940 to 2012 in comparison with human seasonal influenza A viruses (IAVs), H1N1 and H3N2. IBVs from the diverged Yamagata- and Victoria-like lineages and the earlier undiverged period were included.The majority of IBVs replicated productively in human bronchus and lung with similar competence to seasonal IAVs. IBVs infected a variety of cell types, including ciliated cells, club cells, goblet cells and basal cells, in human airway organoids. Like seasonal IAVs, IBVs are low inducers of pro-inflammatory cytokines and chemokines. Most results suggested a higher preference for the conducting airway than the lower lung and strain-specific rather than lineage-specific pathogenicity of IBVs.Our results highlighted the non-negligible virulence of IBVs which require more attention and further investigation to alleviate the disease burden, especially when treatment options are limited.

Dual therapy with renally adjusted lamivudine and dolutegravir: a switch strategy to manage comorbidity and toxicity in older, suppressed patients?

OBJECTIVES: The aim of the study was to evaluate the efficacy of dual therapy with lamivudine (3TC), with dose adjustment for renal function, and dolutegravir (DTG) in a subgroup of patients fully suppressed on treatment who were switched because of concerns about comorbidity and toxicity on their current triple drug regimen. METHODS: A retrospective evaluation of clinical and pathological parameters from an electronic patient record from a single centre was carried out. RESULTS: There were no virological failures in 52 patients with a median age of 60.5 years. The median duration of follow-on dual therapy was 2.29 years (28 months; range 1.10-3.34 years). In 25 of 52 (48%) cases, the dose of 3TC was adjusted taking into account reduced renal function, and none of these patients experienced virological failure. Four additional patients discontinued early, because of side effects of the switch, with no failure. CONCLUSIONS: This retrospective review suggests that 3TC and DTG may be effective in controlling viral load in older patients with comorbidities. This regimen appears to be a useful option in the context of comorbidities (including renal impairment) and polypharmacy in older patients. However, this review has been conducted in one centre and in a small population of patients. Therefore, further multicentre trials involving larger populations of patients are needed.

Session 3: Beyond TME and radiotherapy MRI evaluation of rectal cancer treatment response.

Magnetic resonance imaging plays an increasingly important role in evaluating the effect of cancer treatment. Imaging alone cannot predict pathological complete response and imaging interpretation should be combined with clinical information and endoscopy findings to predict complete response. Professor Blomqvist reviews current and future imaging techniques and whether the quantitative can add significant or important prognostic information over the current qualitative techniques.

Session 3: Beyond the boundaries of Total Mesorectal Excision - where surgeons fear to tread.

Approximately 10-15% of patients present with an advanced rectal cancer that extends beyond the conventional total mesorectal excision (TME) planes. In such cases extending the surgery to ensure resection with clear margins (R0 resection) is essential in order to achieve long-term cure. Professor Holm describes the techniques of beyond-TME exenterative surgery, the methods of patient selection and outcomes.

Session 3: Many ways to organ preserve the rectum but which is correct?

From the patient's perspective, cancer cure with full preservation of function is a crucial goal. There are many advances that have emerged which may make this possible in a greater proportion of patients without compromising oncological outcomes. Professor Tekkis reviews the options and evidence to date for 'organ preservation' and the expert panel discuss the implications for current and future patient care.

Session 3: Intra-operative radiotherapy - creating new surgical boundaries.

In patients with advanced and recurrent colorectal cancer, surgical resection with clear margins is the greatest challenge and is limited by known anatomical constraints. Preoperative or intra-operative assessment of the limits of surgical dissection may help to explore the possibility of improving resectability through either targeted external beam radiotherapy or intra-operative radiotherapy. Professor Chang reviews the evidence base and potential advantages and disadvantages of this approach, whilst the expert panel agree a consensus on the evidence for assessment and therapy of such patients.

Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract.

Poor human-to-human transmission of influenza A H5N1 virus has been attributed to the paucity of putative sialic acid alpha2-3 virus receptors in the epithelium of the human upper respiratory tract, and thus to the presumed inability of the virus to replicate efficiently at this site. We now demonstrate that ex vivo cultures of human nasopharyngeal, adenoid and tonsillar tissues can be infected with H5N1 viruses in spite of an apparent lack of these receptors.

Restorative proctocolectomy in patients with ulcerative colitis: a cross-sectional Danish population study on function and quality of life.

AIM: The study evaluated function and quality of life (QoL) in all patients having restorative proctocolectomy (RPC) in Denmark for ulcerative colitis (UC) from 1980 to 2010. Inclusion of all patients in one country has never previously been achieved. METHOD: All patients who had had a RPC in Denmark, from the first case in 1980 to the last case in 2010, were studied. A cross-sectional questionnaire survey was performed, and function and QoL were assessed using a standardized questionnaire - the Short-Form 36 (SF36) - and the inflammatory bowel disease questionnaire (IBDQ). RESULTS: The median duration of follow up was 11 (range, 1-30) years. Apart from deaths, pouch failures and research protection, data on function and QoL were obtained from 1047 (85%) of 1229 patients who had a functioning pouch at the time of the investigation. More female patients than male patients experienced urgency (56% vs 44%, P = 0.0021). The median number of bowel movements per 24 h was 7 (range, 1-23) in female patients and 6 (range, 1-20) in male patients (P < 0.001). Pad usage was more frequent among female patients than among male patients (62% vs 38%, P < 0.001). A higher incidence of major incontinence (P = 0.009) and use of pads (P = 0.01) was found among patients who had been operated on 21-30 years previously compared with those operated on 11-20 years previously. The prevalence of urgency was higher in patients who received surgery 0-10 years previously compared with 11-20 years previously (P = 0.009). The total IBDQ score was higher in male patients than in female patients (P < 0.001). Male patients scored higher in five of eight SF36 domains (P < 0.001). CONCLUSION: Female patients had more urgency, a higher frequency of defaecation and higher pad usage. This was associated with a reduced QoL. Nevertheless, RPC resulted in good function and a high degree of satisfaction in most patients.

Temperature changes of CoolSticks during simulated use.

INTRODUCTION: Cold sensation is often used to check neuraxial anaesthesia and analgesia. One opportunity to reduce the carbon footprint of anaesthesia is to replace vapo-coolant sprays such as ethyl chloride with a reusable device called the CoolStick, which is cooled in a refrigerator between uses. We designed a study to investigate how long the CoolStick remains at its working temperature, which we defined as <15 °C. METHOD: Experiments were undertaken using a thermocouple and digital temperature sensor attached to the CoolStick. We conducted two experiments to assess temperature changes following removal from the refrigerator for 10 min; the first investigated passive re-warming in the ambient theatre environment and the second investigated re-warming in simulated use. In our third experiment, we investigated the time taken to cool the device in the refrigerator, following use. Each experiment was repeated three times. RESULTS: In the passive re-warming experiment, the mean CoolStick temperature was 7.3 °C at the start, and 14.3 °C after 10 min. In the simulated use experiment, the mean CoolStick temperature was 7.3 °C at the start, and 18.9 °C at 10 min. In the cooling experiment, the mean CoolStick temperature was 15 °C at the start and 7.6 °C at 40 min. CONCLUSION: Our study indicates that it is feasible to use the CoolStick for providing cold sensation in clinical practice. Further study would be required to directly compare the effectiveness of the device to existing methods such as coolant sprays or ice in the clinical setting.

Proceed with reasonable care: When legal principles inform training to prevent harm during childbirth.

Maternity claims represent the highest value and second highest number of clinical negligence claims reported to the NHS Litigation Authority (NHSLA). Most obstetric litigation is brought under the law of negligence which requires the claimant to show three things: that a duty of care was owed, that the duty was breached and that the breach caused loss. Training to prevent litigation should focus on 'Clinical' - multidisciplinary, simulation-training and 'Non-Clinical' (starting all discussions with women and their families timely, informing them about 'material' risks and addressing their particular concern, treating decision-making as a team process, using translation services early in the process, even before the emergency occur). Therefore, maternity claims are one of the most frequent and most expensive ones. Each unexpected pregnancy outcome can possibly trigger litigation. Effective training should address both 'clinical' and 'non-clinical' situations.

Thyroid hormones and bone development.

Thyroid hormones are critical determinants of postnatal skeletal development. Thyroid hormone deficiency or excess in children results in severe abnormalities of linear growth and bone maturation. These clinical observations have been recapitulated in mutant mice and these models have facilitated studies of the mechanisms of thyroid hormone action in the developing skeleton. In this review, we consider in detail the direct and indirect effects of thyroid hormone on bone and the molecular mechanisms involved.

Central nervous system regeneration: from leech to opossum.

A major problem of neurobiology concerns the failure of injured mammalian spinal cord to repair itself. This review summarizes work done on two preparations in which regeneration can occur: the central nervous system of an invertebrate, the leech, and the spinal cord of an immature mammal, the opossum. The aim is to understand cellular and molecular mechanisms that promote and prevent regeneration. In the leech, an individual axon regrows successfully to re-establish connections with its synaptic target, while avoiding other neurons. Functions that were lost are thereby restored. Moreover, pairs of identified neurons become re-connected with appropriate synapses in culture. It has been shown that microglial cells and nitric oxide play key roles in leech CNS regeneration. In the opossum, the neonatal brain and spinal cord are so tiny that they survive well in culture. Fibres grow across spinal cord lesions in neonatal animals and in vitro, but axon regeneration stops abruptly between postnatal days 9 and 12. A comprehensive search has been made in spinal cords that can and cannot regenerate to identify genes and establish their locations. At 9 days, growth-promoting genes, their receptors and key transcription molecules are up-regulated. By contrast at 12 days, growth-inhibitory molecules associated with myelin are prominent. The complete sequence of the opossum genome and new methods for transfecting genes offer ways to determine which molecules promote and which inhibit spinal cord regeneration. These results lead to questions about how basic research on mechanisms of regeneration could be 'translated' into effective therapies for patients with spinal cord injuries.

The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles.

The production of virus-like particles (VLPs) constitutes a relevant and safe model to study molecular determinants of virion egress. The minimal requirement for the assembly of VLPs for the coronavirus responsible for severe acute respiratory syndrome in humans (SARS-CoV) is still controversial. Recent studies have shown that SARS-CoV VLP formation depends on either M and E proteins or M and N proteins. Here we show that both E and N proteins must be coexpressed with M protein for the efficient production and release of VLPs by transfected Vero E6 cells. This suggests that the mechanism of SARS-CoV assembly differs from that of other studied coronaviruses, which only require M and E proteins for VLP formation. When coexpressed, the native envelope trimeric S glycoprotein is incorporated onto VLPs. Interestingly, when a fluorescent protein tag is added to the C-terminal end of N or S protein, but not M protein, the chimeric viral proteins can be assembled within VLPs and allow visualization of VLP production and trafficking in living cells by state-of-the-art imaging technologies. Fluorescent VLPs will be used further to investigate the role of cellular machineries during SARS-CoV egress.

Laparoscopic subtotal cholecystectomy: initial experience with laparoscopic management of difficult cholecystitis.

AIM: Laparoscopic cholecystectomy (LC) is now accepted as the 'gold standard' procedure for cholecystectomy. However, a significant proportion of patients with complicated cholecystitis are still converted to 'open' to complete the procedure. Laparoscopic subtotal cholecystectomy (LSC) is an option, which is still too infrequently used. METHODS: A single surgeon in our NHS trust has performed 1150 LCs since September 1999. The procedure was converted to LSC in 52 cases (4.52%) due to complicated cholecystitis. The data were collected and prospectively analysed for any morbidity or complications in the peri-operative period. RESULTS: At the initial presentation, 21 patients (40.38%) were diagnosed with recurrent biliary colic, 24 patients (46.15%) had acute cholecystitis, 6 patients (11.53%) had jaundice, and 1 patient (1.92%) had peritonitis due to gallbladder (GB) perforation. Twenty-six cases (50%) were performed as emergencies, i.e. within one week of symptoms, and 26 (50%) were planned for surgery within four weeks after symptoms started. The cystic duct or Hartmann's pouch stump was closed using endo-loop application in 34 (65.38%), intracorporeal suturing of stump of Hartmann's pouch in 13 (25%), and closure of cystic duct opening in the Hartmann's pouch by purse-string suturing in 5 cases (9.62%). CONCLUSION: LSC is a safe option in treating gallstone disease when inflammation or fibrosis precludes conventional dissection of Calot's triangle. LSC can clearly help reduce morbidity associated with open laparotomy.