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The role of the neuropeptide cholecystokinin in schizophrenia has been widely explored because of its modulating action on midbrain dopamine neurons. The recent discovery of more specific receptor subtype cholecystokinin antagonists should be considered as potential treatment for schizophrenia with fewer side effects. This paper reviews cholecystokinin/dopamine interactions in animal and human studies. Clinical trials with cholecystokinin agonists and antagonists in schizophrenia are updated.
Total laryngectomy is often utilised to manage squamous cell carcinoma of the larynx or hypopharynx. This study reports on surgical trends and outcomes over a 10-year period.
A retrospective review of patients undergoing total laryngectomy for squamous cell carcinoma was performed (n = 173), dividing patients into primary and salvage total laryngectomy cohorts.
A shift towards organ-sparing management was observed. Primary total laryngectomy was performed for locoregionally advanced disease and utilised reconstruction less than salvage total laryngectomy. Overall, 11 per cent of patients developed pharyngocutaneous fistulae (primary: 6 per cent; salvage: 20 per cent) and 11 per cent neopharyngeal stenosis (primary: 9 per cent; salvage: 15 per cent). Pharyngocutaneous fistulae rates were higher in the reconstructed primary total laryngectomy group (24 per cent; 4 of 17), compared with primary closure (3 per cent; 3 of 90) (p = 0.02). Patients were significantly more likely to develop neopharyngeal stenosis following pharyngocutaneous fistulae in salvage total laryngectomy (p = 0.01) and reconstruction in primary total laryngectomy (p = 0.02). Pre-operative haemoglobin level and adjuvant treatment failed to predict pharyngocutaneous fistulae development.
Complications remain hard to predict and there are continuing causes of morbidity. Additionally, prior treatment continues to affect surgical outcomes.
Animal studies have suggested that exposure of the middle ear to topical local anaesthesia may be ototoxic. This study aimed to report sensorineural hearing outcomes and patients’ satisfaction in those who underwent myringotomy and ventilation tube insertion using topical local anaesthesia.
Twenty-nine patients (32 ears) were operated on. Pre- and post-operative audiology findings were compared. A Likert-type questionnaire on treatment satisfaction was completed at the end of the procedure.
Median patient age was 55 years (range, 27–88 years). Pre- and post-operative bone conduction pure tone averages were 26.76 dB and 25.26 dB respectively (mean reduction of −1.22 dB, 95 per cent confidence interval of −5.91 to 8.13 dB; p = 0.7538). One ear (3 per cent) had a reduction in pure tone average of 10 dB.
The results suggest that sensorineural hearing loss is not a complication of ear exposure to topical local anaesthesia during myringotomy and ventilation tube insertion. The procedure was well perceived.
We present Phantom, a fast, parallel, modular, and low-memory smoothed particle hydrodynamics and magnetohydrodynamics code developed over the last decade for astrophysical applications in three dimensions. The code has been developed with a focus on stellar, galactic, planetary, and high energy astrophysics, and has already been used widely for studies of accretion discs and turbulence, from the birth of planets to how black holes accrete. Here we describe and test the core algorithms as well as modules for magnetohydrodynamics, self-gravity, sink particles, dust–gas mixtures, H2 chemistry, physical viscosity, external forces including numerous galactic potentials, Lense–Thirring precession, Poynting–Robertson drag, and stochastic turbulent driving. Phantom is hereby made publicly available.
This review aimed to critically analyse data pertaining to the clinical presentation and treatment of neuroendocrine carcinomas of the larynx.
A PubMed search was performed using the term ‘neuroendocrine carcinoma’. English-language articles on neuroendocrine carcinoma of the larynx were reviewed in detail.
Results and conclusion
While many historical classifications have been proposed, in contemporary practice these tumours are sub-classified into four subtypes: carcinoid, atypical carcinoid, small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma. These tumours exhibit a wide range of biological behaviour, ranging from the extremely aggressive nature of small and large cell neuroendocrine carcinomas, which usually have a fatal prognosis, to the less aggressive course of carcinoid tumours. In small and large cell neuroendocrine carcinomas, a combination of irradiation and chemotherapy is indicated, while carcinoid and atypical carcinoid tumour management entails conservation surgery.
Taking J. A. Baker's celebrated book The Peregrine as its focus, the article seeks to locate Baker's writing within a broader, less elevated field of postwar observation and publication that worked to shape new ways of understanding, apprehending and taking pleasure from the natural environment. This included the recording practices and publications of the national and county naturalist and birdwatching societies that flourished in these years. The article shows how Baker's book was as much the product of this world of organised amateur natural history as it was of the world of high literature. Baker's book also sheds light on the reconfiguring of bird-human relations within competing postwar cultures of nature and the article uses it to explore the relationship between birdwatching and the bird-centred field sport of falconry. As organised birdwatching sought to establish moral authority over other bird-centred countryside pursuits in its understanding of natural relations, it cast field sports and other countryside practices as atavistic and archaic relics of older cultures of nature. Baker's The Peregrine allows us to see the convergences between the close attention to birds of prey and an intimacy with them that was shared by birdwatchers like Baker and falconers, even as Baker's narrative also sheds light on the differences between the two practices.
Results are presented from our ongoing studies of Titan using ALMA during the period 2012-2015, including a confirmation of the previous detection of vinyl cyanide (C2H3CN), as well as the first spatial map for this species on Titan. Simultaneous mapping of HC3N, CH3CN and C2H5CN reveal characteristic abundance patterns for each species that provide insight into their individual photochemical lifetimes, and help inform our understanding of Titan’s unique, time-variable atmospheric chemistry and global circulation. A time-sequence of HC3N maps covering 38 months reveals a dramatic change in the distribution of this gas consistent with high-altitude photochemical production followed by advection towards the southern (winter) pole, combined with rapid loss in the north after Titan’s 2009 seasonal equinox. The 2015 C2H3CN and C2H5CN maps show abundance peaks in Titan’s southern hemisphere, similar to those observed for the short-lived HC3N molecule. The longer-lived CH3CN, on the other hand, remains more concentrated in the north.
The effectiveness of individually administered cognitive processing therapy (CPT) when compared with treatment as usual (TAU) in a community sexual assault centre was tested. Trauma survivors with acute stress disorder (ASD) following sexual assault were randomised to either CPT (n = 25) or TAU (n = 22), and assessed at pretreatment, posttreatment, and 3-, 6- and 12-month follow-up. Both groups demonstrated large reductions in PTSD and depression symptoms following treatment, and these gains were maintained over the course of follow-ups (Cohen's ds for PTSD symptom reductions ranging between 0.76 to 1.45). Although smaller and not always consistent, between-group effect sizes typically favoured CPT. Effect sizes (d) ranged between 0.13–0.50 for posttraumatic stress and 0.13–0.41 for depression over the course of follow-ups. Independent assessment of PTSD severity indicated more CPT participants reached good end-state functioning at 12-month follow-up (50%) than TAU (31%). Although both treatments were effective, there were some indications that CPT led to better outcomes relative to therapists delivering their usual therapy. The present study demonstrates that evidence-based, trauma-focused therapy such as CPT can be effective when delivered as an early intervention in a routine mental health setting.
Despite aggressive multimodal therapy, human glioblastoma (hGBM), a highly malignant grade IV astrocytic tumour, remains incurable and inevitably relapses. Recent data has implicated intratumoral heterogeneity as the driver of therapy resistance and tumour relapse in hGBM. Thus models that capture the evolving hGBM biology in response to chemoradiotherapy will allow for the identification of cellular pathways that govern GBM therapy failure. In this study, we have developed a novel model to profile the clonal evolution of treatment naïve brain tumour initiating cell (BTIC) enriched hGBMs through chemoradiotherapy using: stem cell assays, BTIC marker expression and transcriptome analysis, immunohistochemistry, and cellular DNA barcoding technology. We report that treatment of hGBM BTICs leads to increased self-renewal capacity and higher transcript expression of stem cell genes Bmi1 and Sox2. Based on global transcriptome analysis of the in vitro treated hGBM, we also identify a hyper-aggressive form of glioma. Using our therapy-adapted hGBM-mouse xenograft model, we discover that despite tumour regression and increased mouse survival post-therapy, tumour relapse remains inevitable. The treatment-refractory cells again have increased self-renewal capacity and higher expression of Bmi1 and Sox2. Furthermore, by combining cellular DNA barcoding technology, which barcodes hGBM at single cell resolution, with our novel in vitro and in vivo therapy models, we are able to determine whether a pre-existing or a therapy driven subpopulation(s) seeds hGBM tumour relapse. Profiling the dynamic nature of heterogeneous hGBM subpopulations through disease progression and treatment may lead to the identification of novel therapeutic targets for the treatment of recurrent hGBM.
Sarcoma of the head and neck is a rare condition that poses significant challenges in management and often requires radical multimodality treatment.
This study aimed to analyse current clinical presentation, evaluation, management dilemmas and oncological outcomes.
Computer records and case notes were analysed, and 39 patients were identified. Variables were compared using Pearson's chi-square test and the log-rank test, while survival outcomes were calculated using the Kaplan–Meier method.
The histopathological diagnosis was Kaposi sarcoma in 20.5 per cent of cases, chondrosarcoma in 15.3 per cent and osteosarcoma in 10.2 per cent. A range of other sarcomas were diagnosed in the remaining patients. The site of disease was most commonly sinonasal, followed by the oral cavity and larynx.
Wide local excision with clear resection margins is essential to achieve local control and long-term survival. There is a need for cross-specialty collaboration in order to accrue the evidence which will be necessary to improve long-term outcomes.
Inadvertent (or incidental) parathyroidectomy can occur during thyroidectomy. However, the factors associated with inadvertent parathyroidectomy remain unclear. This study aimed to report the rate of inadvertent parathyroidectomy during thyroidectomy and associated risk factors.
Variables including fine needle aspiration cytology findings, age, sex, thyroid weight, concurrent neck dissection, extent of thyroidectomy, and the presence of cancer and parathyroid tissue within the specimen were recorded for 266 patients. The incidence of post-operative hypocalcaemia was also recorded. Univariate and multivariate analysis were performed to identify factors associated with inadvertent parathyroidectomy.
The inadvertent parathyroidectomy rate was 16 per cent. Univariate analysis revealed that cancer and concurrent neck dissection predicted inadvertent parathyroidectomy. On multivariate analysis, only concurrent neck dissection remained an independent predictor of inadvertent parathyroidectomy: it was associated with a fourfold increase in inadvertent parathyroidectomy.
The inadvertent parathyroidectomy rate was 16 per cent and concurrent neck dissection was identified as an independent predictor of inadvertent parathyroidectomy.
Despite national guidance recommending testing and vaccination of household contacts of hepatitis B-infected pregnant women, provision and uptake of this is sub-optimal. The aim of this study was to evaluate the use of in-home dried blood spot (DBS) testing to increase testing and vaccination of household contacts of hepatitis B-infected pregnant women as an alternative approach to conventional primary-care follow-up. The study was conducted across two London maternity trusts (North Middlesex and Newham). All hepatitis B surface antigen-positive pregnant women identified through these trusts were eligible for inclusion. The intervention of in-home DBS testing for household contacts was introduced at North Middlesex Trust from November 2010 to December 2011. Data on testing and vaccination uptake from GP records across the two trusts were compared between baseline (2009) and intervention (2010–2011) periods. In-home DBS service increased testing uptake for all ages (P < 0·001) with the biggest impact seen in partners, where testing increased from 30·3% during the baseline period to 96·6% during the intervention period in North Middlesex Trust. Although impact on vaccine uptake was less marked, improvements were observed for adults. The provision of nurse-led home-based DBS may be useful in areas of high prevalence.
Provision of non-pharmacological interventions is a common policy objective for people with dementia, and support groups are an increasingly common intervention. However, there have been few attempts to synthesize evidence on the effectiveness of support groups for people with dementia. This review investigated the outcomes of support groups for people with dementia, explored participant characteristics and reviewed group formats.
A systematic review was undertaken and a narrative synthesis of data from 29 papers (reporting on 26 groups and a survey of a range of groups) was conducted.
Support groups seem acceptable to people with dementia. Qualitative studies report subjective benefits for participants but there is limited evidence of positive outcomes based on quantitative data. Samples have tended to be homogenous and this may limit the generalizability of findings.
Although qualitative studies will remain important in this area, further mixed-methods randomized controlled trials (RCTs)or comparison group studies with longer follow-up periods are needed to strengthen the evidence base.
With the increasing use of chemoradiotherapy protocols, total laryngectomy carries increasing risks such as pharyngocutaneous fistula. There is little reference to the use of antibiotic prophylaxis in salvage surgery. This study aimed to determine the current practice in antibiotic prophylaxis for total laryngectomy in the UK.
A questionnaire was designed using SurveyMonkey software, and distributed to all ENT-UK registered head and neck surgeons.
The survey revealed that 19 surgeons (51 per cent) follow a protocol for antibiotic prophylaxis in primary total laryngectomy and 17 (46 per cent) follow a protocol in salvage total laryngectomy. Only 11 (30 per cent) use anti-methicillin-resistant Staphylococcus aureus agents in their antibiotic prophylaxis. The duration of prophylaxis varies considerably. Nineteen surgeons (51 per cent) revealed that their choice of antibiotic prophylaxis reflected non-evidence-based practices.
There appears to be little evidence-based guidance on antibiotic prophylaxis in primary and salvage total laryngectomy. The survey highlights the need for more research in order to inform national guidance on antibiotic prophylaxis in primary and salvage total laryngectomy.
The prevalence of occult neck metastasis in patients undergoing salvage total laryngectomy remains unclear, and there is controversy regarding whether elective neck dissection should routinely be performed.
A retrospective case note review of 32 consecutive patients undergoing salvage total laryngectomy in a tertiary centre was performed, in order to correlate pre-operative radiological staging with histopathological staging.
The median patient age was 61 years (range, 43–84 years). With regard to lymph node metastasis, 28 patients were pre-operatively clinically staged (following primary radiotherapy or chemoradiotherapy) as node-negative, 1 patient was staged as N1, two patients as N2c and one patient as N3. Fifty-two elective and seven therapeutic neck dissections were performed. Pathological analysis up-staged two patients from clinically node-negative (following primary radiotherapy or chemoradiotherapy) to pathologically node-positive (post-surgery). No clinically node-positive patients were down-staged. More than half of the patients suffered a post-operative fistula.
Pre-operative neck staging had a negative predictive value of 96 per cent. Given the increased complications associated with neck dissection in the salvage setting, consideration should be given to conservative management of the neck in clinically node-negative patients (staged following primary radiotherapy or chemoradiotherapy).
Direct skin involvement of nodal metastasis from mucosal head and neck squamous cell carcinoma has traditionally been considered a poor prognostic indicator.
This retrospective review identified eight patients (five with mucosal upper aerodigestive and three with occult primary squamous cell carcinoma) who presented between 2000 and 2007 with direct skin involvement of nodal metastasis.
Five patients were treated with extended radical and three with extended modified radical neck dissection. Closure was achieved directly (four cases), with local (two) or pedicled (two) flaps. Surgery was always followed by radiotherapy (pan-mucosal or to the primary site). The five-year recurrence-free and disease-specific survival rates were 100 per cent.
It is exceptionally rare to encounter direct skin involvement of metastatic lymph nodes from mucosal head and neck squamous cell carcinoma without evidence of involvement of other anatomical structures. Surgical intervention is possible and combined modality treatment with curative intent is essential, as most patients can have a favourable outcome.
To assess the nutritional quality of lunchtime food consumption among elementary-school children on Prince Edward Island according to the source of food consumed (home v. school).
Students completed a lunchtime food record during an in-class survey. Dietary adequacy was assessed by comparing median micronutrient intakes with one-third of the Estimated Average Requirement; median macronutrient intakes were compared with the Acceptable Macronutrient Distribution Ranges. The Wilcoxon signed rank test was used to assess differences in nutrient intakes according to source of food consumed.
Elementary schools in Prince Edward Island, Canada.
Grade 5 and 6 students (n 1980).
Foods purchased at school were higher in nutrient density for ten micronutrients (Ca, Mg, K, Zn, vitamin A, vitamin D, riboflavin, niacin, vitamin B6 and vitamin B12) compared with packed lunch foods from home, which were higher in three micronutrients (Fe, vitamin C and folate). School lunches provided sufficient protein but were higher in sugar and fat than home lunches. Foods brought from home were higher in carbohydrates, fibre and Na than foods purchased at school.
The overall nutritional quality of lunches was poor, regardless of source. A significant proportion of foods consumed by the students came from home sources; these were lower nutritional quality and were higher in Na than foods offered at school. Findings suggest that improving the dietary habits of school-aged children will require a collaborative effort from multiple stakeholders, including parents.