Laparoscopic cholecystectomy performed by a surgical care practitioner: a review of outcomes.

INTRODUCTION: Surgical care practitioners (SCPs) are non-medical workers involved in various aspects of the management of surgical patients. The role includes assisting and performing surgical procedures. More than 60,000 laparoscopic cholecystectomies (LC) are performed annually in the UK. With ever-increasing pressure on waiting lists, it is important to look at fully utilising the skills of our entire workforce. We report what we believe is the first published series of LC performed by an SCP. METHODS: A retrospective review of a prospectively collected database was performed. The primary outcome was any complication requiring intervention. Secondary outcomes were minor complications, operative time, length of stay, conversion and readmission. RESULTS: In total, 170 patients were operated on. Indications were biliary colic in 127 (74.7%), cholecystitis in 30 (17.6%) and pancreatitis in 13 (7.6%). Mean operating time was 65min (range 35-152min). Fifty-three operations were assisted by a consultant, 110 by a specialist or associate specialist grade (SAS) doctor and 7 by a core trainee (CT2). Some 139 (81.7%) patients were discharged on the day of surgery and 24 (14.1%) stayed one night in hospital. There were no major complications. Five patients required readmission, three with pain and two with port site infections. There were no conversions or transfusions required. CONCLUSIONS: There is a paucity of published data on surgical outcomes of procedures performed by SCPs. With a structured, supervised approach, SCPs could be trained to take on more complex procedures and further strengthen the surgical workforce. This study demonstrates that elective LC can be safely performed by an appropriately trained and supervised SCP.

Posterior stabilised total knee arthroplasty is associated with improved post-operative knee specific function, health related quality of life and greater satisfaction when compared to cruciate retaining protheses.

PURPOSE: To assess whether there were differences in knee specific function, health related quality of life (HRQoL), and satisfaction between patients with a cruciate retaining (CR) or a posterior stabilised (PS) total knee arthroplasty (TKA) at 1 and 2 years postoperatively. METHODS: A retrospective review of TKA (CR and PS) patients from a prospectively collected arthroplasty database. Patient demographics, body mass index and ASA grade, Oxford knee score (OKS) and EuroQol 5-dimension (EQ-5D) 3-level, which was used to assess HRQoL, were collected preoperatively and 1 year and 2 years postoperatively. Regression was used to adjust for confounding factors. RESULTS: The sample included 3122 TKA, of which 1009 (32.3%) were CR and 2112 (67.7%) were PS. The PS group were more likely to be female (odd ratio (OR) 1.26, p = 0.003) and undergo resurfacing of the patella (OR 6.63, p < 0.001). There was a significantly greater improvement in the 1 year OKS in the PS group (mean difference (MD) 0.9, p = 0.016). The PS TKA was independently associated with a greater 1 year (MD 1.1, 95% CI 0.4 to 1.9, p = 0.001) and 2 years (MD 0.8, p = 0.037) post-operative improvements in OKS. PS TKA was also independently associated with a greater 1 year (MD 0.021, p = 0.024) and 2 years (MD 0.022, p = 0.025) post-operative and change in EQ-5D utility compared to the CR group. The PS group was more likely to be satisfied with their outcome at 1 year (OR 1.75, p < 0.001) and at 2 years (OR 1.38, p = 0.001) when adjusting for confounders. CONCLUSION: PS TKA was associated with a better knee specific function and HRQoL when compared to CR, but the clinical significance of this is not clear. However, the PS group was more likely to be satisfied with their outcome compared to the CR group.

Emotional eating among adults with healthy weight, overweight and obesity: a systematic review and meta-analysis.

BACKGROUND: Emotional eating (EE) is a disordered eating behaviour which may lead to overeating. It is not clear whether EE presents to an equal degree among adults, regardless of their body mass index (BMI) status. The aim of this study was to assess whether there is a difference in degree of EE between adults with healthy weight, overweight and obesity. METHODS: MEDLINE and APA PsycINFO databases were searched from inception up to January 2022 for studies that reported EE scores from validated questionnaires. The quality of all included studies was assessed using the AXIS tool. Meta-analysis used random effects and standardised mean difference (SMD). Heterogeneity was investigated using I2 statistics and sensitivity analyses. RESULTS: A total of 11 studies with 7207 participants were included in the meta-analysis. Degree of EE was greater in adults with a BMI above the healthy range, compared to adults with a healthy BMI (SMD 0.31, 95% CI 0.17 to 0.45; I2 = 85%). However, subgroup analysis found that degree of EE was greater only in adults with obesity (SMD 0.61, 95% CI 0.41 to 0.81; I2 = 62%), and there was no difference in degree of EE between adults with overweight and those with a healthy BMI. CONCLUSIONS: Degree of EE is greater among adults living with obesity, compared to adults with a healthy BMI, indicating a need for behavioural support to support EE among people living with obesity seeking weight management. Future research should examine the long-term effectiveness of interventions for EE.

"Is it time to throw out the weighing scales?" Implicit weight bias among healthcare professionals working in bariatric surgery services and their attitude towards non-weight focused approaches.

Background: People living with overweight or obesity (PLwO) can be stigmatised by healthcare professionals (HCPs). Reducing focus on weight is a proposed strategy to provide less threatening healthcare experiences. Given the lack of research on weight bias within obesity services, this study aimed to explore implicit bias among obesity specialist HCPs and explore views on non-weight focused approaches. Methods: Obesity specialist HCPs were invited to a webinar, "An exploration of non-weight focused approaches within bariatric services", held in October 2021. Implicit weight bias was examined using the BiasProof mobile device test, based on the Implicit Association Test. Poll data was analysed descriptively, and qualitative data was analysed using framework analysis. Findings: 82 of the 113 HCPs who attended the webinar consented to contribute data to the study. Over half (51%) had an implicit weight bias against PLwO. Most (90%) agreed/strongly agreed that obesity services are too weight focused and that patients should not be weighed at every appointment (86%). Perceived benefits of taking a non-weight focused approach included patient-led care, reducing stigma and supporting patient wellbeing, while perceived barriers included loss of objectivity, inducing risk and difficulty demonstrating effectiveness. Interpretation: Our findings indicate that half of obesity specialists HCPs in our sample of 82 providers, who are primarily dieticians and psychologists, have an implicit weight bias against PLwO. HCPs feel that a weight-focused approach within services was a barrier to patient care, but that there is a lack of alternative non-weight focused measures. Further research is needed into substitute outcome measures for clinical practice, also seeking the views of PLwO, and into interventions to address implicit weight bias. Funding: Johnson & Johnson funded the BiasProof licence and publication open access charge.

A pre-registered short-term forecasting study of COVID-19 in Germany and Poland during the second wave.

Disease modelling has had considerable policy impact during the ongoing COVID-19 pandemic, and it is increasingly acknowledged that combining multiple models can improve the reliability of outputs. Here we report insights from ten weeks of collaborative short-term forecasting of COVID-19 in Germany and Poland (12 October-19 December 2020). The study period covers the onset of the second wave in both countries, with tightening non-pharmaceutical interventions (NPIs) and subsequently a decay (Poland) or plateau and renewed increase (Germany) in reported cases. Thirteen independent teams provided probabilistic real-time forecasts of COVID-19 cases and deaths. These were reported for lead times of one to four weeks, with evaluation focused on one- and two-week horizons, which are less affected by changing NPIs. Heterogeneity between forecasts was considerable both in terms of point predictions and forecast spread. Ensemble forecasts showed good relative performance, in particular in terms of coverage, but did not clearly dominate single-model predictions. The study was preregistered and will be followed up in future phases of the pandemic.

Experiences and perceptions of dietitians for obesity management: a general practice qualitative study.

BACKGROUND: Multi-component lifestyle interventions are the first line treatment for obesity. Dietitians are ideally placed healthcare professionals to deliver such interventions. However, only a small proportion of patients with obesity are referred by general practice to dietitians, and the reasons for this are not clear. The present study aimed to explore general practice healthcare professionals' (GPHCPs) experiences and perceptions of dietitians in the context of obesity management. METHODS: A convenience sample of GPHCPs practicing in the UK was recruited via a targeted social media strategy, using virtual snowball sampling. Data were collected using semi-structured interviews and analysed using framework analysis. RESULTS: In total, 20 participants were interviewed (11 general practice nurses and nine general practitioners). Experiences of referring patients with obesity for dietetic intervention resulted in two main themes: (i) access barriers and (ii) the dietetic consult experience. Three themes emerged from participants' perceptions of a role for general practice dietitians: (i) utilising dietetic expertise; (ii) access to dietitian; and (iii) time. Participants experienced barriers to accessing dietitians for obesity management and felt that having a dietitian working within their general practice team would help address this. Having a dietitian embedded within their general practice team was perceived to have the potential to alleviate GPHCPs' clinical time pressures, offer opportunities for upskilling, and may improve patient engagement with obesity management. CONCLUSIONS: GPHCPs perceived that embedding a dietitian within their general practice team would be valuable and beneficial for obesity management. Our findings provide support for the funding of general practice dietitian roles in the UK.

Group versus one-to-one multi-component lifestyle interventions for weight management: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Multi-component lifestyle interventions that incorporate diet, physical activity and behaviour change are effective for weight management. However, it is not clear whether delivery in a group or one-to-one format influences weight loss efficacy. The present study aimed to systematically review the evidence of the effectiveness of group compared to one-to-one multi-component lifestyle interventions for weight management. METHODS: MEDLINE, EMBASE, CINAHL, CENTRAL and ISRCTN databases were searched from inception up to February 2020 for randomised controlled trials comparing group versus one-to-one multi-component lifestyle interventions for weight loss in adults with a body mass index ≥ 25 kg m-2 . The primary outcome was weight loss (kg) at 12 months and the secondary outcome was attainment of ≥5% weight loss at 12 months. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta-analysis used random effects and estimated risk ratios and continuous inverse variance methods. Heterogeneity was investigated using I2 statistics and sensitivity analyses. RESULTS: Seven randomised controlled trials with 2576 participants were included. Group interventions were favoured over one-to-one interventions for weight loss at 12 months (-1.9 kg, 95% confidence interval = -1.3 to -2.6; I2  = 99%). Participants of group interventions were more likely to attain ≥5% weight loss at 12 months relative to one-to-one interventions (relative risk = 1.58, 95% confidence interval = 1.25-2.00; I2  = 60%). CONCLUSIONS: Group multi-component lifestyle interventions are superior for weight loss compared to one-to-one interventions with respect to adult weight management. Further research is required to determine whether specific components of group interventions can explain the superiority of weight loss outcomes in group interventions.

An assessment of an Australasian pathway for the introduction of transanal total mesorectal excision (taTME).

AIM: To evaluate the use of a pathway for the introduction of transanal total mesorectal excision (taTME) into Australia and New Zealand. METHOD: A pathway for surgeons with an appropriate level of specialist training and baseline skill set was initiated amongst colorectal surgeons; it includes an intensive course, a series of proctored cases and ongoing contribution to audit. Data were collected for patients who had taTME, for benign and malignant conditions, undertaken by the initial adopters of the technique. RESULTS: A total of 133 taTME procedures were performed following the introduction of a training pathway in March 2015. The indication was rectal cancer in 84% of cases. There was one technique-specific visceral injury, which occurred prior to that surgeon completing the pathway. There were no cases of postoperative mortality; morbidity occurred in 27.1%. The distal resection margin was clear in all cases of rectal cancer, and the circumferential resection margin was positive in two cases. An intact or nearly intact total mesorectal excision was obtained in more than 98% of cases. CONCLUSION: This study demonstrates the safe and controlled introduction of a new surgical technique in a defined surgeon population with the use of a pathway for training. The authors recommend a similar pathway to facilitate the introduction of taTME to colorectal surgical practice.

A systematic review and meta-analysis on the incubation period of Campylobacteriosis.

Accurate knowledge of pathogen incubation period is essential to inform public health policies and implement interventions that contribute to the reduction of burden of disease. The incubation period distribution of campylobacteriosis is currently unknown with several sources reporting different times. Variation in the distribution could be expected due to host, transmission vehicle, and organism characteristics, however, the extent of this variation and influencing factors are unclear. The authors have undertaken a systematic review of published literature of outbreak studies with well-defined point source exposures and human experimental studies to estimate the distribution of incubation period and also identify and explain the variation in the distribution between studies. We tested for heterogeneity using I 2 and Kolmogorov-Smirnov tests, regressed incubation period against possible explanatory factors, and used hierarchical clustering analysis to define subgroups of studies without evidence of heterogeneity. The mean incubation period of subgroups ranged from 2·5 to 4·3 days. We observed variation in the distribution of incubation period between studies that was not due to chance. A significant association between the mean incubation period and age distribution was observed with outbreaks involving only children reporting an incubation of 1·29 days longer when compared with outbreaks involving other age groups.

Phylogeny and taxonomic revision of Microascaceae with emphasis on synnematous fungi.

The taxonomy of the synnematous genera Cephalotrichum, Doratomyces and Trichurus, and other related genera Gamsia, Wardomyces and Wardomycopsis, has been controversial and relies mainly on morphological criteria. These are microascaceous saprobic fungi mostly found in air and soil and with a worldwide distribution. In order to clarify their taxonomy and to delineate generic boundaries within the Microascaceae, we studied 57 isolates that include clinical, environmental and all the available ex-type strains of a large set of species by means of morphological, physiological and molecular phylogenetic analyses using DNA sequence data of four loci (the ITS region, and fragments of rDNA LSU, translation elongation factor 1α and ß-tubulin). The results demonstrate that Cephalotrichum, Doratomyces and Trichurus are congeneric and the genus Cephalotrichum is accepted here with Echinobotryum as a further synonym. The genera Acaulium and Fairmania, typified by A. albonigrescens and F. singularis, respectively, are distinct from Microascus and Scopulariopsis, Gamsia is distinct from Wardomyces, and Wardomycopsis is confirmed as a separate genus in the Microascaceae. Two new species of Cephalotrichum are described as C. brevistipitatum and C. hinnuleum. Nine new combinations are proposed, i.e. Acaulium acremonium, A. caviariforme, Cephalotrichum asperulum, C. columnare, C. cylindricum, C. dendrocephalum, C. gorgonifer, Gamsia columbina and Wardomyces giganteus. A neotype is designed for C. stemonitis. Lectotypes and epitypes are designated for A. acremonium, A. albonigrescens, C. gorgonifer, C. nanum and W. anomalus. Cephalotrichum cylindricum, C. microsporum, F. singularis and Gamsia columbina are also epitypified with new specimens. Descriptions of the phenotypic features and dichotomous keys for identification are provided for accepted species in the different genera.

Intestinal lymphoma--a review of the management of emergency presentations to the general surgeon.

INTRODUCTION: Intestinal non-Hodgkin's lymphoma (NHL) is uncommon but not rare. This paper aims to review the recent evidence for the management of perforated NHL of the intestine, consider when chemotherapy should be commenced and examine the likely outcomes and prognosis for patients presenting as surgical emergencies with this condition. METHODS: MEDLINE and Cochrane databases were searched using intestinal lymphoma, clinical presentation, perforation, management and prognosis. The full text of relevant articles was retrieved and reference lists checked for additional articles. FINDINGS: Emergency surgery was required at disease presentation for between 11 and 64% of intestinal NHL cases. Perforation occurs in 1-25% of cases, and also occurs whilst on chemotherapy for NHL. Intestinal bleeding occurs in 2-22% of cases. Obstruction occurs more commonly in small bowel (5-39%) than large bowel NHL and intussusceptions occur in up to 46%. Prognosis is generally poor, especially for T cell lymphomas. CONCLUSIONS: There is a lack of quality evidence for the elective and emergency treatment of NHL involving the small and large intestine. There is a lack of information regarding the impact an emergency presentation has on the timing of postoperative chemotherapy and overall prognosis. It is proposed that in order to develop evidence-based treatment protocols, there should be an intestinal NHL registry.

Predictors of outcome in palliative colonic stent placement for malignant obstruction.

BACKGROUND: Emergency surgery for large bowel obstruction carries significant morbidity and mortality. After initially promising results, concerns have been raised over complication rates for self-expandable metal stents (SEMS) in both the palliative and bridge-to-surgery settings. This article documents the technique used at the authors' institution, and reports on success and complication rates, as well as identifying predictors of endoscopic reintervention or surgical treatment. METHODS: Data were collected for a prospective cohort of consecutive patients undergoing attempted colonoscopic SEMS insertion at a single institution between 1998 and 2013. Multivariable logistic models were fitted to assess possible predictors of endoscopic reintervention and surgical treatment. RESULTS: Palliative SEMS insertion was attempted in 146 patients. Primary colorectal cancer was the most common cause of obstruction (95.2 per cent). The majority of patients (77.4 per cent) were treated in an acute setting, with a high technical success rate of 97.3 per cent. The perforation rate was 4.8 per cent and the 30-day procedural mortality rate 2.7 per cent. No predictors of early complications were identified, although patients with metastases and those who received chemotherapy were more likely to have late complications. Some 30.8 per cent of patients required at least one further intervention, with 11.0 per cent of the cohort requiring a stoma. Endoscopic reintervention was largely successful. CONCLUSION: SEMS offer a valid alternative to operative intervention in the palliative management of malignant large bowel obstruction. Patients receiving chemotherapy are more likely to receive endoscopic reintervention, which is largely successful.

Outcomes following treatment for pelvic floor mesh complications.

INTRODUCTION AND HYPOTHESIS: Our aim was to determine symptoms and degree of improvement in a cohort of women who presented following treatment for vaginal mesh complications. METHODS: This study was a follow-up to a multicenter, retrospective study of women who presented to four tertiary referral centers for management of vaginal-mesh-related complications. Study participants completed a one-time follow-up survey regarding any additional treatment, current symptoms, and degree of improvement from initial presentation. RESULTS: Two hundred and sixty women received surveys; we had a response rate of 41.1 % (107/260). Complete data were available for 101 respondents. Survey respondents were more likely to be postmenopausal (p = 0.006), but otherwise did not differ from nonrespondents. Fifty-one percent (52/101) of women underwent surgery as the primary intervention for their mesh complication; 8 % (4/52) underwent a second surgery; 34 % (17/52) required a second nonsurgical intervention. Three patients required three or more surgeries. Of the 30 % (30/101) of respondents who reported pelvic pain prior to intervention, 63 % (19/30) reported improvement, 30 % (9/30) were worse, and 7 % (2/30) reported no change. Of the 33 % (33/101) who reported voiding dysfunction prior to intervention, 61 % (20/33) reported being at least somewhat bothered by these symptoms. CONCLUSIONS: About 50 % of women with mesh complications in this study underwent surgical management as treatment, and <10 % required a second surgery. Most patients with pain preintervention reported significant improvement after treatment; however, almost a third reported worsening pain or no change after surgical management. Less than half of patients with voiding dysfunction improved after intervention.

Implementation of the INTERGROWTH-21st Project in the United States.

The North American site in the INTERGROWTH-21(st) Project was North Seattle, Washington State, USA. The majority of the data were collected from within Seattle City, which has approximately 12 300 births per year. The sample for the Newborn Cross-Sectional Study (NCSS) was drawn from two hospitals (Swedish Medical Center and the University of Washington) covering almost 80% of deliveries within the target population. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from several antenatal clinics serving the University of Washington Medical Center and Providence Everett Medical Center. Special activities to encourage participation and raise awareness of the studies included furnishing the recruitment sites with fliers designed by the Project Coordinating Unit, and presenting the studies to clinical staff to encourage providers to refer appropriate patients. One of the major challenges at this site was the low recruitment rate in the early phase of the FGLS because of the high rates of smoking, maternal age >35 years and body mass index >30 years. This was remedied by the inclusion of other ancillary clinics, as well as increased advertising among the general public.

A case for revising the strength of the relationship between childhood asthma and atopy in the developing world.

INTRODUCTION: Asthma is the commonest chronic condition of children. Diagnosis remains difficult and many surrogate markers are used, such as documenting evidence of atopy. METHOD: Two studies investigated the role of atopy in childhood asthma. The first documented the prevalence and nature of allergy sensitivities in a group of asthmatic children compared with non-asthmatic children in Pretoria, South Africa. The second enrolled a random sample of asthmatic children and their mothers attending the Children's Chest and Allergy Clinic at Steve Biko Academic Hospital, Pretoria. Children were classified as having atopic or non-atopic asthma. Mothers completed a questionnaire to reveal atopic features. RESULTS: In the first study, only 45.0% of asthmatic children had a positive skin-prick test (SPT), as opposed to 16.2% of control children. This is a lower proportion than in many reported international studies. In the second study, 64 children with atopic asthma and 36 with non-atopic asthma were studied, along with their mothers. The proportion of children with atopic asthma did not differ for mothers with and without a positive SPT (p=0.836), a history of asthma (p=0.045) or symptoms suggestive of an allergic disease (p=1.000), or who were considered to be allergic (p=0.806). The odds ratio (OR) of a child having atopic asthma when he or she had a mother with a doctor-diagnosed history of asthma was 4.76, but the sensitivity was low (21.9%). CONCLUSION: The data demonstrate that fewer asthmatic children in South Africa are atopic than was previously thought. Also, all maternal allergic or asthmatic associations are poor predictors of childhood atopic asthma. Despite the increased risk of atopic asthma in a child of a mother who has a doctor diagnosis of asthma (OR 4.76; p=0.045), this is a poor predictor of atopic asthma (sensitivity 21.9%).

A methodological study to compare survey-based and observation-based evaluations of organisational and safety cultures and then compare both approaches with markers of the quality of care.

BACKGROUND: Patient safety concerns have focused attention on organisational and safety cultures, in turn directing attention to the measurement of organisational and safety climates. OBJECTIVES: First, to compare levels of agreement between survey- and observation-based measures of organisational and safety climates/cultures and to compare both measures with criterion-based audits of the quality of care, using evidence-based markers drawn from national care standards relating to six common clinical conditions. (This required development of an observation-based instrument.) Second, to examine whether observation-based evaluations could replace or augment survey measurements to mitigate concerns about declining response rates and increasing social desirability bias. Third, to examine mediating factors in safety and organisational climate scores. DESIGN: The study had three strands: (A) a postal questionnaire survey to elicit staff perceptions of organisational and safety climates, using six prevalidated scales; (B) semistructured non-participant observation of clinical teams; and (C) a retrospective criterion-based audit carried out by non-clinical auditors to minimise hindsight bias. Standardised summary scores were created for each strand, and pairs of measurements were compared (strand A with strand B, strand A with strand C, and strand B with strand C) using Bland-Altman plots to evaluate agreement. Correlations were also examined. Multilevel modelling of Strand A scores explored mediating factors. SETTING AND PARTICIPANTS: Eight emergency departments and eight maternity units in England, UK. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Examination of feasibility, correlation and agreement. RESULTS: Strand A: the overall response rate was 27.6%, whereas site-specific rates ranged from 9% to 47%. We identified more mediating factors than previous studies; variable response rates had little effect on the results. Organisational and safety climate scores were strongly correlated (r = 0.845) and exhibited good agreement [standard deviation (SD) differences 0.449; 14 (88%) within ± 0.5; one large difference]. Two commonly used scales had high levels of positive responses, suggesting positive climates or social desirability bias. Strand B: scoring on a four-point scale was feasible. Observational evaluation of teamwork culture was good but too limited for evaluating organisational culture. Strand C: a total of 359-399 cases were audited per condition. The results varied widely between different markers for the same condition, so selection matters. Each site performed well on some markers but not others, with few consistent patterns. Some national guidelines were contested. Comparisons: the comparison of safety climate (survey) and teamwork culture (observation) revealed a moderately low correlation (r = 0.316) and good agreement [SD differences 1.082; 7 (44%) within ±0.5; one large difference]. The comparison of safety climate (survey) and performance (audit) revealed lower correlation (r = 0.150, i.e. relationship not linear) but reasonably good agreement [SD differences 0.992; 9 (56%) within ± 0.5; two large differences]. Comparisons between performance (audit) and both organisational climate (survey) and teamwork culture (observation) showed negligible correlations (< 0.1) but moderately good agreement [SD differences 1.058 and 1.241; 6 (38%) and 7 (44%) within ± 0.5; each with two large differences (at different sites)]. Field notes illuminated large differences. CONCLUSIONS: Climate scores from staff surveys are not unduly affected by survey response rates, but increasing use risks social desirability bias. Safety climate provides a partial indicator of performance, but qualitative data are needed to understand discrepant results. Safety climate (surveys) and, to a lesser degree, teamwork culture (observations) are better indicators of performance than organisational climate (surveys) or attempts to evaluate organisational culture from time-limited observations. Scoring unobtrusive, time-limited observations to evaluate teamwork culture is feasible, but the instrument developed for this study needs further testing. A refined observation-based measure would be useful to augment or replace surveys. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

C1 neurons excite locus coeruleus and A5 noradrenergic neurons along with sympathetic outflow in rats.

C1 neurons activate sympathetic tone and stimulate the hypothalamic­pituitary­adrenal axis in circumstances such as pain, hypoxia or hypotension. They also innervate pontine noradrenergic cell groups, including the locus coeruleus (LC) and A5. Activation of C1 neurons reportedly inhibits LC neurons; however, because these neurons are glutamatergic and have excitatory effects elsewhere, we re-examined the effect of C1 activation on pontine noradrenergic neurons (LC and A5) using a more selective method. Using a lentivirus that expresses channelrhodopsin2 (ChR2) under the control of the artificial promoter PRSx8, we restricted ChR2 expression to C1 neurons (67%), retrotrapezoid nucleus neurons (20%) and cholinergic neurons (13%). The LC contained ChR2-positive terminals that formed asymmetric synapses and were immunoreactive for vesicular glutamate transporter type 2. Low-frequency photostimulation of ChR2-expressing neurons activated LC (38 of 65; 58%) and A5 neurons (11 of 16; 69%) and sympathetic nerve discharge. Locus coeruleus and A5 inhibition was not seen unless preceded by excitation. Locus coeruleus activation was eliminated by intracerebroventricular kynurenic acid. Stimulation of ChR2-expressing neurons at 20 Hz produced modest increases in LC and A5 neuronal discharge. In additional rats, the retrotrapezoid nucleus region was destroyed with substance P­saporin prior to lentivirus injection into the rostral ventrolateral medulla, increasing the proportion of C1 ChR2-expressing neurons (83%). Photostimulation in these rats activated the same proportion of LC and A5 neurons as in control rats but produced no effect on sympathetic nerve discharge owing to the destruction of bulbospinal C1 neurons. In conclusion, low-frequency stimulation of C1 neurons activates pontine noradrenergic neurons and sympathetic nerve discharge, possibly via the release of glutamate from monosynaptic C1 inputs.

An integrated approach to optimizing skin delivery of cosmetic and pharmaceutical actives.

The academic literature on skin delivery provides countless examples of scientific insights into specific aspects of the overall process. For the practical formulator, however, it is difficult to know how to combine such insights in a way that fits into the realities of commercial formulations. In this study, five key principles are combined into an integrated approach that can be applied to real-world formulations. Given the complexities of skin science, the integrated approach cannot be expected to be highly precise. Instead, it is intended as a way for a formulation team to balance the many conflicting issues. The predictions are sufficiently specific to be examined by those with the appropriate analytical resources and data on formulation efficacy. It is hoped that such challenges will allow the approach to be refined for the future.

The third generation superconducting 28 GHz electron cyclotron resonance ion source VENUS (invited).

VENUS is a third generation electron cyclotron resonance (ECR) ion source, which incorporates a high field superconducting NbTi magnet structure, a 28 GHz gryotron microwave source and a state of the art closed cycle cryosystem. During the decade from initial concept to regular operation, it has demonstrated both the feasibility and the performance levels of this new generation of ECR ion sources and required innovation on magnet construction, plasma chamber design, and beam transport. In this paper, the development, performance, and major innovations are described as well as a look to the potential to construct a fourth generation ECR ion source.