Comparing extraction method efficiency for high-throughput palaeoproteomic bone species identification.

High-throughput proteomic analysis of archaeological skeletal remains provides information about past fauna community compositions and species dispersals in time and space. Archaeological skeletal remains are a finite resource, however, and therefore it becomes relevant to optimize methods of skeletal proteome extraction. Ancient proteins in bone specimens can be highly degraded and consequently, extraction methods for well-preserved or modern bone might be unsuitable for the processing of highly degraded skeletal proteomes. In this study, we compared six proteomic extraction methods on Late Pleistocene remains with variable levels of proteome preservation. We tested the accuracy of species identification, protein sequence coverage, deamidation, and the number of post-translational modifications per method. We find striking differences in obtained proteome complexity and sequence coverage, highlighting that simple acid-insoluble proteome extraction methods perform better in highly degraded contexts. For well-preserved specimens, the approach using EDTA demineralization and protease-mix proteolysis yielded a higher number of identified peptides. The protocols presented here allowed protein extraction from ancient bone with a minimum number of working steps and equipment and yielded protein extracts within three working days. We expect further development along this route to benefit large-scale screening applications of relevance to archaeological and human evolution research.

Plating vs Closed Reduction for Fractures in the Distal Radius in Older Patients: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Distal radius fractures are common and are managed with or without surgery. Current evidence indicates surgical treatment is not superior to nonsurgical treatment at 12 months. Objective: Does surgical treatment for displaced distal radius fractures in patients 60 years or older provide better patient-reported wrist pain and function outcomes than nonsurgical treatment at 24 months? Design, Setting, and Participants: In this secondary analysis of a combined multicenter randomized clinical trial (RCT) and a parallel observational study, 300 patients were screened from 19 centers in Australia and New Zealand. Of these, 166 participants were randomized to surgical or nonsurgical treatment. Participants who declined randomization (n = 134) were included in the parallel observational group with the same treatment options and follow-up. Participants were followed up at 3, 12, and 24 months by a blinded assessor. The 24-month outcomes are reported herein. Data were collected from December 1, 2016, to December 31, 2020, and analyzed from February 4 to October 21, 2021. Interventions: Surgical treatment consisting of open reduction and internal fixation using a volar-locking plate (VLP group) and nonsurgical treatment consisting of closed reduction and cast immobilization (CR group). Main Outcomes and Measures: The primary outcome was patient-reported function using the Patient-Rated Wrist Evaluation (PRWE) questionnaire. Secondary outcomes included health-related quality of life, wrist pain, patient-reported treatment success, patient-rated bother with appearance, and posttreatment complications. Results: Among the 166 randomized and 134 observational participants (300 participants; mean [SD] age, 71.2 [7.5] years; 269 women [89.7%]), 151 (91.0%) randomized and 118 (88.1%) observational participants were followed up at 24 months. In the RCT, no clinically important difference occurred in mean PRWE scores at 24 months (13.6 [95% CI, 9.1-18.1] points for VLP fixation vs 15.8 [95% CI, 11.3-20.2] points for CR; mean difference, 2.1 [95% CI, -4.2 to 8.5]; P = .50). There were no between-group differences in all other outcomes except for patient-reported treatment success, which favored VLP fixation (33 of 74 [44.6%] in the CR group vs 54 of 72 [75.0%] in the VLP fixation group reported very successful treatment; P = .002). Rates of posttreatment complications were generally low and similar between treatment groups, including deep infection (1 of 76 [1.3%] in the CR group vs 0 of 75 in the VLP fixation group) and complex regional pain syndrome (2 of 76 [2.6%] in the CR group vs 1 of 75 [1.3%] in the VLP fixation group). The 24-month trial outcomes were consistent with 12-month outcomes and with outcomes from the observational group. Conclusions and Relevance: Consistent with previous reports, these findings suggest that VLP fixation may not be superior to CR for displaced distal radius fractures for patient-rated wrist function in persons 60 years or older during a 2-year period. Significantly higher patient-reported treatment success at 2 years in the VLP group may be attributable to other treatment outcomes not captured in this study. Trial Registration: ANZCTR.org Identifier: ACTRN12616000969460.

How gender, education and nutrition knowledge contribute to food insecurity among adults in Australia.

Food and nutrition insecurity occurs when healthy and safe food cannot be obtained by socially acceptable means and arises as a result of complex interactions between socioeconomic and demographic determinants. These factors contribute to discrepancies in health and well-being between men and women and may also explain differential rates of food insecurity. The objectives of this cross-sectional study were to investigate the intersection between gender, education, nutrition knowledge and food security status within a high-income country context. Australian adults over 16 years of age who identified as having primary responsibility for food in their household were recruited via social media and a panel. Respondents completed a self-administered survey that included sociodemographic data, nutrition-related knowledge and food security status. Food security was measured using the Australian Household Food and Nutrition Security Scale an adapted version of the United States Department of Agriculture Household Food Security Survey. Among the 1010 survey respondents, household food insecurity (HFI) was highly prevalent (43% were food insecure, with 26% of these severely food insecure). Gender may affect associations between education, nutrition knowledge and HFI. Education was significantly associated with HFI among women but not among men. Conversely, nutrition knowledge was significantly inversely associated with food security among men but not among women. Differences in determinants of HFI exist between men and women, and programs aimed at addressing food insecurity may be more effective if tailored accordingly to account for the social and demographic factors associated with HFI.

Endoscopy training in the UK pre-COVID-19 environment: a multidisciplinary survey of endoscopy training and the experience of reciprocal feedback.

OBJECTIVE: Training in gastrointestinal endoscopy in the UK occurs predominantly in a real world one-to-one trainer to trainee interaction. Previous surveys have shown surgical and gastroenterology trainees have had mixed experiences of supervision and training, and no surveys have explored specifically the role of trainee to trainer feedback. This study aimed to explore the experience of training and of providing trainer feedback for all disciplines of endoscopy trainees. DESIGN/METHOD: An online survey designed in collaboration with Joint Advisory Committee training committee and trainee representatives was distributed from January 2020 but was interrupted by the COVID-19 pandemic and hence terminated early. RESULTS: There were 129 responses, including trainees from all disciplines and regions, of which 86/129 (66.7%) rated the culture in their endoscopy units favourably-either good or excellent. 65/129 (50.4%) trainees reported having one or more training lists allocated per week, with 41/129 (31.8%) reporting only ad hoc lists. 100/129 (77.5%) respondents were given feedback and 97/129 (75.2%) were provided with learning points from the list. 65/129 (50.4%) respondents reported their trainer completed a direct observation of procedure or direct observation of polypectomies. 73/129 (56.6%) respondents reported that they felt able to give feedback to their trainer, with 88/129 (68.2%) feeling they could do this accurately. Barriers to trainer feedback cited included time constraints, lack of anonymity and concerns about affecting the trainer-trainee relationship. CONCLUSION: Overall, the training environment has improved since previous surveys. There are still issues around interdisciplinary differences with some surgical trainees finding the training environment less welcoming, and trainee perceptions of hierarchical barriers and trainer responsiveness to feedback limiting the accuracy of their feedback.

Surgical Plating vs Closed Reduction for Fractures in the Distal Radius in Older Patients: A Randomized Clinical Trial.

Importance: The burden of injury and costs of wrist fractures are substantial. Surgical treatment became popular without strong supporting evidence. Objective: To assess whether current surgical treatment for displaced distal radius fractures provided better patient-reported wrist pain and function than nonsurgical treatment in patients 60 years and older. Design, Setting, and Participants: In this multicenter randomized clinical trial and parallel observational study, 300 eligible patients were screened from 19 centers in Australia and New Zealand from December 1, 2016, until December 31, 2018. A total of 166 participants were randomized to surgical or nonsurgical treatment and followed up at 3 and 12 months by blinded assessors. Those 134 individuals who declined randomization were included in a parallel observational cohort with the same treatment options and follow-up. The primary analysis was intention to treat; sensitivity analyses included as-treated and per-protocol analyses. Intervention: Surgical treatment was open reduction and internal fixation using a volar-locking plate (VLP). Nonsurgical treatment was closed reduction and cast immobilization (CR). Main Outcomes and Measures: The primary outcome was the Patient-Rated Wrist Evaluation score at 12 months. Secondary outcomes were Disabilities of Arm, Shoulder, and Hand questionnaire score, health-related quality of life, pain, major complications, patient-reported treatment success, bother with appearance, and therapy use. Results: In the 300 study participants (mean [SD] age, 71.2 [7.5] years; 269 [90%] female; 166 [81 VLP and 85 CR] in the randomized clinical trial sample and 134 [32 VLP and 102 CR] in the observational sample), no clinically important between-group difference in 12-month Patient-Rated Wrist Evaluation scores (mean [SD] score of 19.8 [21.1] for VLP and 21.5 [24.3] for CR; mean difference, 1.7 points; 95% CI -5.4 to 8.8) was observed. No clinically important differences were found in quality of life, wrist pain, or bother at 3 and 12 months. No significant difference was found in total complications between groups (12 of 84 [14%] for the CR group vs 6 of 80 [8%] for the VLP group; risk ratio [RR], 0.53; 95% CI, 0.21-1.33). Patient-reported treatment success favored the VLP group at 12 months (very successful or successful: 70 [89%] vs 57 [70%]; RR, 1.26; 95% CI, 1.07-1.48; P = .005). There was greater use of postoperative physical therapy in the VLP group (56 [72%] vs 44 [54%]; RR, 1.32; 95% CI, 1.04-1.69; P = 0.02). Conclusions and Relevance: This randomized clinical trial found no between-group differences in improvement in wrist pain or function at 12 months from VLP fixation over CR for displaced distal radius fractures in older people. Trial Registration: http://anzctr.org.au identifier: ACTRN12616000969460.

Impact of a national basic skills in colonoscopy course on trainee performance: An interrupted time series analysis.

BACKGROUND: The Joint Advisory Group on Gastrointestinal Endoscopy basic skills in colonoscopy (BSC) course was introduced in 2009 to improve colonoscopy training within the United Kingdom, but its impact on trainee performance is unknown. AIM: To assess whether attendance of the BSC could improve colonoscopy performance. METHODS: Trainees awarded colonoscopy certification between 2011-2016 were stratified into 3 groups according to pre-course procedure count (< 70, 70-140 and > 140). Study outcomes, comprising the unassisted caecal intubation rate (CIR) and the performance indicator of colonic intubation (PICI), were studied over the 50 procedures pre and post- course. Interrupted time series analyses were performed to detect step-change changes attributable to the course. RESULTS: A total of 369 trainees with pre-course procedure counts of < 70 (n = 118), 70-140 (n = 121) and > 140 (n = 130) were included. Over the 50 pre-course procedures, significant linear improvements in CIR were found, with average increases of 4.2, 3.6 and 1.7 percentage points (pp) per 10 procedures performed in the < 70, 70-140 and > 140 groups respectively (all P < 0.001). The < 70 procedures group saw a significant step-change improvement in CIR, increasing from 46% in the last pre-course procedure, to 51% in the first procedure post-course (P = 0.005). The CIR step-change was not significant in the 70-140 (68% to 71%; P = 0.239) or > 140 (86% to 87%; P = 0.354) groups. For PICI, significant step-change improvements were seen in all three groups, with average increases of 5.6 pp (P < 0.001), 5.4 pp (P = 0.003) and 3.9 pp (P = 0.014) respectively. CONCLUSION: Attendance of the BSC was associated with a significant step-change improvement in PICI, regardless of prior procedural experience. However, CIR data suggest that the optimal timing of course attendance appears to be at earlier stages of training (< 70 procedures).

A Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly (CROSSFIRE): a statistical analyses plan.

BACKGROUND: We are performing a combined randomised and observational study comparing internal fixation to non-surgical management for common wrist fractures in older patients. This paper describes the statistical analysis plan. METHODS/DESIGN: A Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly (CROSSFIRE) is a randomised controlled trial comparing two types of usual care for treating wrist fractures in older patients, surgical fixation using volar locking plates and non-surgical treatment using closed reduction and plaster immobilisation. The primary aim of this comparative-effectiveness study is to determine whether surgery is superior to non-surgical treatment with respect to patient-reported wrist function at 12 months post treatment. The secondary outcomes include radiographic outcomes, complication rates and patient-reported outcomes including quality of life, pain, treatment success and cosmesis. Primary analysis will use a two-sample t test and an intention-to-treat analysis using the randomised arm of the study. Statistical analyses will be two-tailed and significance will be determined by p < 0.05. Sensitivity analyses will be conducted to assess for differences in intention-to-treat, per-protocol and as-treated analyses. Sensitivity analyses will also be conducted to assess selection bias by evaluating differences in participants between the randomised and observational study arms, and for bias relating to any missing data. An economic analysis will be conducted separately if surgery is shown to provide superior outcomes to a level of clinical significance. DISCUSSION: This statistical analysis plan describes the analysis of the CROSSFIRE study which aims to provide evidence to aid clinical decision-making in the treatment of distal radius fractures in older patients. TRIAL REGISTRATION: CROSSFIRE was approved by The Hunter New England Human Research Ethics Committee (HNEHREC Reference No: 16/02/17/3.04). Registered on 22 July 2016 with The Australian and New Zealand Clinical Trials Registry (ANZCTR Number; ACTRN12616000969460 ). This manuscript is based on v.11 of the statistical analysis plan. A copy of v.11, signed by the chief investigator and the senior statistician is kept at the administering institution.

Determination of ice interface temperature, sublimation rate and the dried product resistance, and its application in the assessment of microcollapse using through-vial impedance spectroscopy.

Through-vial impedance spectroscopy (TVIS) is a new approach for characterizing product attributes during freeze-drying process development. In this study, a pair of copper foil electrodes was attached to the external surface of a Type I glass tubing vial, of nominal capacity 10 mL and containing 3.5 g of an aqueous solution of 5%w/v lactose, and the impedance spectrum of the vial and contents recorded during a lyophilization cycle. The cycle included a temperature ramp in the primary drying stage in order to induce a collapse event in the dry layer. Using the peak in the dielectric loss spectrum, associated with the dielectric relaxation of ice, methods were developed to predict the sublimation rate and the ice interface temperature at the sublimation front, from which the dry layer resistance was then calculated. A four-fold increase in sublimation rate and a reduction in the dry layer resistance wereobserved once the ice interface temperature reached -33 °C, which coincides with the onset of the glass transition (as determined by DSC) and the time point at which micro-collapse occurred (as evidenced by SEM images at the end of the cycle). This work suggests a prospective application of impedance measurements in driving process efficiencies by operating the dryer at the highest achievable temperature (i.e. the collapse temperature) whilst avoiding macro-collapse.

An evaluation of SecondBite® 's FoodMate® , a nutrition education and skill-building program aimed at reducing food insecurity.

ISSUE ADDRESSED: Enhancing food skills and nutrition knowledge may help promote healthy eating among people who are food insecure. FoodMate® by SecondBite® , an 8-week nutrition education and food hamper program, focuses on developing food skills and independence among Australians at risk of/experiencing food insecurity. This study aimed to explore participants' perceptions of and experiences with FoodMate® over a long-term (up to 2 years) follow-up. METHODS: For evaluation purposes, SecondBite® previously collected data from participants prior to (T1) and following completion (T2) of FoodMate® . This paper reports results from semi-structured telephone interviews conducted in a follow-up study (2016/2017, T3) among 19 adults enrolled in FoodMate® programs delivered in Victoria and New South Wales within the previous two years. Data were analysed using inductive thematic analysis of responses to T3 open-ended questions, and descriptive analysis of closed-ended question responses (T1 vs T2 vs T3). RESULTS: Major qualitative themes included program enjoyment; perceived positive long-term program impact on participants' eating and related attitudes and skills; barriers to cooking; suggested program modifications; and impact on others. In descriptive quantitative analyses, participants' diet; confidence to cook using basic ingredients, follow simple recipes and try new foods; cooking and food-related skills; social engagement and life satisfaction all improved between T1 and T3. CONCLUSIONS: Overall, FoodMate® was well-received and associated with long-term positive changes in a range of outcomes. Wider implementation among vulnerable groups should be considered. SO WHAT?: Future health promotion initiatives could adopt FoodMate® to increase food skills and knowledge among adults experiencing food insecurity.

Deep sedation and anaesthesia in complex gastrointestinal endoscopy: a joint position statement endorsed by the British Society of Gastroenterology (BSG), Joint Advisory Group (JAG) and Royal College of Anaesthetists (RCoA).

In the UK, more than 2.5 million endoscopic procedures are carried out each year. Most are performed under conscious sedation with benzodiazepines and opioids administered by the endoscopist. However, in prolonged and complex procedures, this form of sedation may provide inadequate patient comfort or result in oversedation. As a result, this may have a negative impact on procedural success and patient outcome. In addition, there have been safety concerns on the high doses of benzodiazepines and opioids used particularly in prolonged and complex procedures such as endoscopic retrograde cholangiopancreatography. Diagnostic and therapeutic endoscopy has evolved rapidly over the past 5 years with advances in technical skills and equipment allowing interventions and procedural capabilities that are moving closer to minimally invasive endoscopic surgery. It is vital that safe and appropriate sedation practices follow the inevitable expansion of this portfolio to accommodate safe and high-quality clinical outcomes. This position statement outlines the current use of sedation in the UK and highlights the role for anaesthetist-led deep sedation practice with a focus on propofol sedation although the choice of sedative or anaesthetic agent is ultimately the choice of the anaesthetist. It outlines the indication for deep sedation and anaesthesia, patient selection and assessment and procedural details. It considers the setup for a deep sedation and anaesthesia list, including the equipment required, the environment, staffing and monitoring requirements. Considerations for different endoscopic procedures in both emergency and elective setting are also detailed. The role for training, audit, compliance and future developments are discussed.

Lamotrigine for people with borderline personality disorder: a RCT.

BACKGROUND: No drug treatments are currently licensed for the treatment of borderline personality disorder (BPD). Despite this, people with this condition are frequently prescribed psychotropic medications and often with considerable polypharmacy. Preliminary studies have indicated that mood stabilisers may be of benefit to people with BPD. OBJECTIVE: To examine the clinical effectiveness and cost-effectiveness of lamotrigine for people with BPD. DESIGN: A two-arm, double-blind, placebo-controlled individually randomised trial of lamotrigine versus placebo. Participants were randomised via an independent and remote web-based service using permuted blocks and stratified by study centre, the severity of personality disorder and the extent of hypomanic symptoms. SETTING: Secondary care NHS mental health services in six centres in England. PARTICIPANTS: Potential participants had to be aged ≥ 18 years, meet diagnostic criteria for BPD and provide written informed consent. We excluded people with coexisting psychosis or bipolar affective disorder, those already taking a mood stabiliser, those who spoke insufficient English to complete the baseline assessment and women who were pregnant or contemplating becoming pregnant. INTERVENTIONS: Up to 200 mg of lamotrigine per day or an inert placebo. Women taking combined oral contraceptives were prescribed up to 400 mg of trial medication per day. MAIN OUTCOME MEASURES: Outcomes were assessed at 12, 24 and 52 weeks after randomisation. The primary outcome was the total score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. The secondary outcomes were depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment and adverse events. Higher scores on all measures indicate poorer outcomes. RESULTS: Between July 2013 and October 2015 we randomised 276 participants, of whom 195 (70.6%) were followed up 52 weeks later. At 52 weeks, 49 (36%) of those participants prescribed lamotrigine and 58 (42%) of those prescribed placebo were taking it. At 52 weeks, the mean total ZAN-BPD score was 11.3 [standard deviation (SD) 6.6] among those participants randomised to lamotrigine and 11.5 (SD 7.7) among those participants randomised to placebo (adjusted mean difference 0.1, 95% CI -1.8 to 2.0; p = 0.91). No statistically significant differences in secondary outcomes were seen at any time. Adjusted costs of direct care for those prescribed lamotrigine were similar to those prescribed placebo. LIMITATIONS: Levels of adherence in this pragmatic trial were low, but greater adherence was not associated with better mental health. CONCLUSIONS: The addition of lamotrigine to the usual care of people with BPD was not found to be clinically effective or provide a cost-effective use of resources. FUTURE WORK: Future research into the treatment of BPD should focus on improving the evidence base for the clinical effectiveness and cost-effectiveness of non-pharmacological treatments to help policy-makers make better decisions about investing in specialist treatment services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN90916365. FUNDING: Funding for this trial was provided by the Health Technology Assessment programme of the National Institute for Health Research (NIHR) and will be published in full in Health Technology Assessment; Vol. 22, No. 17. See the NIHR Journals Library website for further project information. The Imperial Biomedical Research Centre Facility, which is funded by NIHR, also provided support that has contributed to the research results reported within this paper. Part of Richard Morriss' salary during the project was paid by NIHR Collaboration for Leadership in Applied Health Research and Care East Midlands.

A combined randomised and observational study of surgery for fractures in the distal radius in the elderly (CROSSFIRE)-a study protocol.

Fractures of the distal radius are common and occur in all age groups. The incidence is high in older populations due to osteoporosis and increased falls risk. Considerable practice variation exists in the management of distal radius fractures in older patients ranging from closed reduction with cast immobilisation to open reduction with plate fixation. Plating is currently the most common surgical treatment. While there is evidence showing no significant advantage for some forms of surgical fixation over conservative treatment, and no difference between different surgical techniques, there is a lack of evidence comparing two of the most common treatments used: closed reduction and casting versus plating. Surgical management involves significant costs and risks compared with conservative management. High-level evidence is required to address practice variation, justify costs and to provide the best clinical outcomes for patients. METHODS AND ANALYSIS: This pragmatic, multicentre randomised comparative effectiveness trial aims to determine whether plating leads to better pain and function and is more cost-effective than closed reduction and casting of displaced distal radius fractures in adults aged 60 years and older. The trial will compare the two techniques but will also follow consenting patients who are unwilling to be randomised in a separate, observational cohort. Inclusion of non-randomised patients addresses selection bias, provides practice and outcome insights about standard care, and improves the generalisability of the results from the randomised trial. ETHICS AND DISSEMINATION: CROSSFIRE(Combined Randomised and Observational Study of Surgery for Fractures In the distal Radius in the Elderly) was reviewed and approved by The Hunter New England HREC (HNEHREC Reference No: 16/02/17/3.04). The results of the trial will be published in a peer-reviewed journal and will be disseminated via various forms of media. Results will be incorporated in clinical recommendations and practice guidelines produced by professional bodies. REGISTRATION: CROSSFIRE has been registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR: ACTRN12616000969460).

Translation strategies, contradiction, and the theory of social representations: Why discussing needles may improve blood donor retention.

Retaining blood donors is a cost-effective way of ensuring a safe blood supply, yet despite the plethora of research, only 5.1% of the eligible population in Australia donate blood and 40% of these do not make a second donation. We offer an alternative to traditional approaches by conceptualizing blood donation within social representations theory as socially derived symbolic knowledge with a specific focus on cognitive polyphasia and Guimelli's (1998) normative and functional dimensions. An online survey, completed by 703 residents from NSW Australia, comprised a blood donation word association task, Likert-style questions constructed from previous word association data and contextualized blood donation statements. Individual difference scaling analysis revealed all donor groups (including non-donors) associated blood donation with a few central, albeit contradictory ideas/beliefs. Exploratory factor analysis and confirmatory factor analysis performed on a split data set of the Likert-style items reiterated this finding. Interpreted through Guimelli's dichotomy, all donor groups were aware of these contradictory normative and functional ideas/beliefs but when explicitly asked, it was the functional aspect that differentiated the groups. We argue the key to retaining donors is understanding the interdependence between how blood donation is socially understood at the societal level of discourse and donor behaviour. Translational strategies for recruitment and retention are discussed.

Proximity of the axillary nerve during bicortical drilling for biceps tenodesis.

PURPOSE: Pathology of the biceps tendon can contribute to significant shoulder pain and dysfunction for which biceps tenodesis may be indicated. A variety of techniques tenodesing the biceps tendon have been described. Recently, tenodesis using a uni- or bicortical button has been advocated. This cadaveric study investigates the proximity of the axillary nerve to the position of bicortical drill passages during biceps tenodesis. METHODS: Twelve cadaveric shoulder specimens were used. The axillary nerve was marked during a preparatory dissection using wire. Drills were passed through the humerus at the proximal and distal ends of the bicipital groove, and at the superior insertion point of pectoralis major (PM). These were left in situ. The distances between these drills and the axillary nerves were measured using computed tomography imaging. RESULTS: The drill bits placed at the superior insertion of PM were in closest proximity to the axillary nerve (3D distance mean 10.7 mm, 95 % confidence interval 7.2-14.2 mm). A drill placed at the distal end of the bicipital groove was a mean distance of 18.2 mm from the nerve. CONCLUSIONS: This study highlights the need for caution when drilling the posterior humeral cortex during biceps tenodesis, particularly during drilling at the superior insertion of PM as this is the location that poses the highest risk to the axillary nerve. To our knowledge, this is the first cadaveric study to radiologically assess the proximity of the axillary nerve to the positions of biceps tenodesis. Surgeons should therefore be cautious when performing bicortical drilling for biceps tenodesis, and a supero-lateral drill trajectory would pose a smaller risk to the axillary nerve.

Evaluation of an air-liquid interface cell culture model for studies on the inflammatory and cytotoxic responses to tobacco smoke aerosols.

In vitro toxicological studies for tobacco product assessment have traditionally been undertaken using the particulate phase of tobacco smoke. However, this does not truly reflect exposure conditions that occur in smokers. Thus in vitro cell culture systems are required in which cells are exposed to tobacco whole smoke (WS) at the air-liquid interface (ALI). In this study bronchial epithelial cells were cultured on semi-permeable membranes, transitioned to the ALI and the robustness and sensitivity of the cells to tobacco WS and vapour phase (VP) assessed. Although no effect of air exposure was observed on cell viability, IL-6 and IL-8 release was increased. Exposure to WS resulted in a significant dose dependent decrease in cell viability and a significant non-dose dependent increase in inflammatory mediator secretion. The VP was found to contribute approximately 90% of the total cytotoxicity derived from WS. The cell culture system was also able to differentiate between two smoking regimens and was sensitive to passage number with increased inflammatory mediator secretion and lower cell viability observed in cell cultures of low passage number following WS exposure. This simple cell culture system may facilitate studies on the toxicological impact of future tobacco products and nicotine delivery devices.

Capsule endoscopy to detect primary tumour site in metastatic neuroendocrine tumours.

BACKGROUND: In patients with metastatic neuroendocrine tumours, primary tumour localisation is often difficult with morphological and/or functional imaging. Although utilised in investigating various small bowel pathologies, evidence for using video capsule endoscopy to identify suspected small bowel primaries in patients exhibiting metastatic neuroendocrine tumours is limited. AIMS: To assess the role of video capsule endoscopy in locating primary small bowel neuroendocrine tumours when conventional imaging fails to identify the origin of metastatic disease. METHODS: We retrospectively compared our institutional database of patients presenting with metastatic neuroendocrine tumours between January 2010 and December 2013 with an analogous database of patients undergoing video capsule endoscopy for various indications. Patients whose primary tumours were not located radiologically and also underwent capsule endoscopy were identified. RESULTS: 390 patients with metastasised neuroendocrine tumours presented within the study period. In 11 (2.8%) the primary tumour was not located radiologically. Video capsule endoscopy identified lesions suggestive of small bowel primary in 8/10 patients in whom it was successful. Small bowel primary was confirmed by histological analysis of surgical specimens. CONCLUSIONS: Our study supports the use of video capsule endoscopy as part of the diagnostic work-up in selected patients presenting with metastatic neuroendocrine tumours of unknown primary. The clinical utility of this technology requires clearer definition.

Subclinical miliary Mycobacterium bovis following BCG immunotherapy for transitional cell carcinoma of the bladder.

The authors present an unusual case of a 51-year-old man who developed relatively mild non-specific symptoms following intravesical BCG instillation for superficial transitional cell carcinoma of the bladder, with radiological investigations demonstrating typical features of miliary tuberculosis (TB). Transbronchial biopsy showed small foci of poorly formed granuloma suggestive of Mycobacterium infection. The patient's respiratory symptoms only became apparent 7 days after discharge having had 4 weeks of unremarkable inpatient stay where he remained clinically well. Prompt anti-TB treatment resulted in a remarkable improvement in his symptoms and radiological appearance, supporting the diagnosis of disseminated Mycobacterium bovis infection. This case highlights the importance of recognising miliary M bovis as a potential complication in patients receiving BCG immunotherapy, and that the disease course can be subclinical with delayed onset of symptoms.

Factors affecting the use of impedance spectroscopy in the characterisation of the freezing stage of the lyophilisation process: the impact of liquid fill height in relation to electrode geometry.

This study aims to investigate the application of impedance spectroscopy using fixed electrode geometries on a standard glass vial in the characterisation of the freezing process of solutions at different fill liquid volumes. Impedance spectra (between 10 and 10(6) Hz) were recorded every 3 min, during the freezing cycle on a solution of 30 mg/mL sucrose contained within 10 mL glass vials having an electrode system (two thin copper foils: w, 18 mm; h, 5 mm) affixed to the external surface of the vial. A fill factor (Φ) was defined in terms of the relative height of the solution volume to the height of the electrodes from the base of the vial. Solution volumes of 1.5 to 5 mL (corresponding to Φ= 0.5-1.6) were investigated to establish the applicability of having a fixed electrode geometry for a range of solution volumes. A linear relationship between the time duration of the ice formation/solidification phase and the fill factor suggests that fixed electrode geometries may be used to investigate a range of fill volumes. The benefit of this approach is that it does not invade the solution and hence records the freezing process without providing additional nucleation sites and in a manner which is representative of the entire fill volume.