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Objective: We previously reported that participants with atypical anorexia nervosa (atypical AN) had higher historical and admission weights, greater eating disorder psychopathology, but similar rates of amenorrhea and weight suppression at baseline as compared to anorexia nervosa (AN); here, we compare 1‐year outcomes. Method: Weight, % median body mass index (%mBMI), Eating Disorder Examination Questionnaire (EDE‐Q) scores, resumption of menses, and rehospitalizations were examined at 3, 6, and 12 months post‐discharge. Analyses (N = 111) compared changes in %mBMI, weight suppression, and EDE‐Q scores over time between atypical AN and AN. Results: Among the participants (48 atypical AN, 63 AN), both groups gained weight but those with atypical AN had lower gains than those with AN in %mBMI (p =.02) and greater weight suppression (p =.002) over time. EDE‐Q scores improved over time, independent of weight suppression, with no significant difference between atypical AN and AN. Groups did not differ by rates of resumption of menses (80% atypical AN, 76.9% AN) or rehospitalization (29.2% atypical AN, 37.9% AN). Greater weight suppression predicted longer time to restore menses and more days of rehospitalization. Discussion: Individuals with atypical AN regained a smaller proportion of body mass and were more weight suppressed over time. Change in eating disorder cognitions, resumption of menses, and rehospitalization rates at 1‐year follow‐up did not differ between groups. There was no significant difference in weight suppression between groups for those who were psychologically improved at 12 months. Findings highlight limitations in our understanding of weight recovery in atypical AN. New metrics for recovery are urgently needed. Public Significance: Little is known about outcome in atypical anorexia nervosa (atypical AN). We examined recovery metrics in young people with atypical AN and anorexia nervosa (AN) 1 year after medical hospitalization. Individuals with atypical AN showed slower weight gain and remained further from their pre‐illness weight. There were no differences in the rates of psychological recovery, resumption of menses, or rehospitalization. New metrics are needed to assess recovery in atypical AN. [ABSTRACT FROM AUTHOR]

Introduction: The importance of primary health care (PHC) to Aboriginal Australians is widely acknowledged, as is the underservicing of the Aboriginal Australian population. Aboriginal People continue to face significant obstacles when accessing and using health care services. Objective: This study identifies environmental factors (beyond personal and service delivery) that functioned as barriers and enablers to Aboriginal Australians' experiences accessing PHC during crises and recommends approaches during future events. Design: This research utilised a case study approach. Data were collected through in‐depth interviews and analysed using thematic analysis. The study was set in Lakes Entrance, a regional Victorian locality with a sizable Aboriginal community, which was affected by bushfires during 2019/2020 and COVID‐19 restrictions during 2020‐2021. Participants were 18 Aboriginal People over the age of 18 living in the locality during either bushfires or COVID‐19. Findings: The barriers identified included the impact on PHC access of priorities other than health, including housing; financial constraints; difficulties with transport; medical bureaucracy and the physical environment of the health care setting, including appointment‐making processes; interactions with medical reception staff; and waiting room environments. Enablers identified included the supportive role of the local Aboriginal Community Controlled Health Organisations (ACCHO) and their staff, which was highlighted in participant responses. Discussion: The preference of many Aboriginal people to access PHC via their local ACCHO, rather than mainstream health care services, appears even more salient during crises than in normal times. This research identified that ACCHOs are ideally placed to promote and protect the health of Aboriginal communities during crises. Conclusion: Results may help direct interventions to improve PHC access and experiences for regional Aboriginal communities both during and outside periods of crisis. [ABSTRACT FROM AUTHOR]

Objective: To determine sex differences in cholesterol and triglyceride levels among adolescents and young adults hospitalized for medical complications of eating disorders. Methods: A retrospective electronic medical record review of patients aged 9–25 years admitted to the University of California, San Francisco Eating Disorders Program for medical stabilization, between 2012 and 2020, was conducted. Non‐fasting total cholesterol and triglycerides were collected; however, LDL and HDL levels were not available. Results: Among 83 males and 441 females, mean ± SD age was 15.5 ± 2.8 years, 64.1% had anorexia nervosa, and admission percent median body mass index was 87.3 ± 13.9. The proportion of males and females with high total cholesterol (13.3% vs. 18.1%, Cramer's V = 0.05, p =.28) and high triglyceride levels (9.6% vs. 8.1%, Cramer's V = 0.02, p =.63) did not differ. Mean total cholesterol levels were higher in females compared to males (F 169.6 ± 41.1 mg/dL vs. M 154.5 ± 45.1 mg/dL, Cohen's d = 0.36, p =.003), although a majority were within the normal range. In adjusted linear regression models, male (compared to female) sex (B = −14.40, 95% CI −24.54, −4.27) and higher percent median body mass index (B = −0.33, 95% CI −0.60, −0.06) were associated with lower total cholesterol levels in adjusted models (R2 = 0.04). Discussion: Building on prior work showing equally severe complications of eating disorders in males compared to females, we did not find sex differences in those presenting with high total cholesterol or triglycerides. Future research is needed to understand the pathophysiology and role of dyslipidemia in acute malnutrition, and the impact of nutritional rehabilitation and weight restoration. Public Significance: We found that the proportion of male and female adolescents and young adults hospitalized for medical complications of an eating disorder with high total cholesterol did not significantly differ. Although average total cholesterol levels were higher in female compared to male patients with eating disorders, a majority of these levels remained within the normal range. Patients with more severe malnutrition had a higher risk of elevated total cholesterol levels. Clinicians should consider monitoring cholesterol levels in young people hospitalized for restrictive eating disorders. [ABSTRACT FROM AUTHOR]

Objective: This study invited providers who care for patients with eating disorders to inform engagement, communication, and collaboration with psilocybin‐assisted psychotherapy interventions. Method: Medical and mental health providers who treat patients with eating disorders were recruited via professional referral networks and participant driven sampling from across California to participate in one of five focus groups. Discussion topics included prior knowledge of psychedelic therapy, interest/concerns related to psilocybin therapy, and opportunities for collaboration. Study team members completed iterative rounds of coding with a grounded theory approach. Results: A total of 32 participants reported a range of familiarity with psychedelics. Some raised concerns about the risks of administering psilocybin to malnourished patients and to those with psychological comorbidities. Despite these concerns, participants were hopeful to see psilocybin therapy as a treatment for patients with eating disorders. In anticipating challenges, providers had concerns about equity in access to care among publicly insured and non‐English speaking patients. They requested opportunities for continuing education about psilocybin therapy. Discussion: Our findings demonstrate provider interest in psilocybin therapy for the treatment of patients with eating disorders. As psilocybin therapy interventions are developed, providers caring for patients with eating disorders value collaboration to improve longitudinal patient outcomes. Public Significance: This study invited healthcare providers of patients with eating disorders to discuss their thoughts around the use of psilocybin‐assisted psychotherapy in this population. Findings will help inform emerging psilocybin therapy clinical trials with the goal of successful translation and adoption in real world clinical settings. [ABSTRACT FROM AUTHOR]

Objective: Hypophosphatasia (HPP) is a rare disease characterized by incomplete or defective bone mineralization due to a mutation in the alkaline phosphatase (ALP) gene causing low levels of ALP. Disease presentation is heterogeneous and can present as a chronic pain syndrome like fibromyalgia (FM). Our objective was to determine if there are any potential patients with HPP in the group of patients who were diagnosed with FM. Antiresorptive therapy use can trigger atypical femur fractures in patients with HPP. Methods: We performed a retrospective chart review of all patients 18 years or older at a single academic center who were diagnosed with FM and had either a low or a normal ALP level. The following characteristics were reviewed: biological sex; age; history of fractures; diagnosis of osteoporosis, osteopenia, osteoarthritis, and chondrocalcinosis; genetic testing; vitamin B6 level testing; and medications. Results: Six hundred eleven patients with FM were identified. Two hundred had at least one low ALP level, and 57 had at least three consecutively low measurements of ALP, 44% of which had a history of fractures. No patients had vitamin B6 levels checked. None of the patients had previous genetic testing for HPP or underwent testing for zinc or magnesium levels. Conclusion: The percentage of patients with FM who were found to have consistently low ALP levels was 9.3%. None had vitamin B6 level or genetic testing, suggesting that the diagnosis was not suspected. It is important to diagnose HPP given the availability of enzyme replacement therapy to prevent complications from HPP such as fractures. Our data support screening for this condition as a part of the initial workup of FM. [ABSTRACT FROM AUTHOR]

Cognitive-motor dual-tasking is a complex activity that predicts falls risk and cognitive impairment in older adults. Cognitive and physical training can both lead to improvements in dual-tasking; however, less is known about what mechanisms underlie these changes. To investigate this, 33 healthy older adults were randomized to one of three training arms: Executive function (EF; n = 10), Aerobic Exercise (AE; n = 10), Gross Motor Abilities (GMA; n = 13) over 12 weeks (1 h, 3×/week). Single and dual-task performance (gait speed, m/s; cognitive accuracy, %) was evaluated before and after training, using the 2-back as concurrent cognitive load. Training arms were designed to improve cognitive and motor functioning, through different mechanisms (i.e., executive functioning - EF, cardiorespiratory fitness - CRF, and energy cost of walking - ECW). Compared to baseline, we observed few changes in dualtask gait speed following training (small effect). However, dual-task cognitive accuracy improved significantly, becoming facilitated by walking (large effect). There were no differences in the magnitude of improvements across training arms. We also found that older adults with lower cognitive ability (i.e., MoCA score < 26; n = 14) improved more on the dual-task cognitive accuracy following training, compared to older adults with higher cognitive ability (i.e., MoCA =26; n = 18). Taken together, the results suggest that regardless of the type of intervention, training appears to strengthen cognitive efficiency during dualtasking, particularly for older adults with lower baseline cognitive status. These gains appear to occur via different mechanisms depending on the form of intervention. Implications of this research are paramount, as we demonstrate multiple routes for improving cognitive-motor dual-tasking in older adults, which may help reduce risk of cognitive impairment. [ABSTRACT FROM AUTHOR]

Traditionally, the assessment of endometrial receptivity at transvaginal ultrasound scan has been based on the thickness and the morphological appearance of the endometrium. The objective of this study was to prospectively evaluate endometrial thickness (ET), endometrial morphology and uterine artery Doppler parameters prior to assisted reproduction treatment (ART) in the prediction of pregnancy outcome. This was a prospective cohort study. ET, morphology and uterine artery Doppler (UtAD) pulsatility index (PI) and resistance index (RI) were measured in the mid-luteal stage of the menstrual cycle ultrasonographically, timed with urinary luteinizing hormone testing. A total of 50 women were included in the analysis. The clinical pregnancy rate (CPR) per embryo transfer was 42.0% (n = 21/50). Twenty nine women (58.0%) had an unsuccessful outcome. There were no differences in mean ± SD endometrial thickness (ET) (10.0 ± 1.8 mm vs. 10.5 ± 2.4; p = 0.43), or endometrial morphology (100% (n = 21) vs 100% (n = 29); p = 1.00) between the pregnant and not pregnant groups. Similarly, there were no differences in mean ± SD UtAD PI (2.17 ± 0.83 vs. 2.07 ± 0.81; p = 0.67 or mean ± SD UtAD RI (0.84 ± 0.10 vs. 0.81 ± 0.10; p = 0.30). Ultrasonographic endometrial assessment did not differentiate between those who would have a subsequent clinical pregnancy. [ABSTRACT FROM AUTHOR]

Context: Interventions to promote serious illness conversations have shown promise in promoting high-quality care. However, in randomized trials, some participants may benefit more from the intervention than others.Objectives: To examine heterogeneity of treatment effect and identify subgroups of patients with serious illness who might benefit most from interventions to enhance communication about goals of care.Methods: We used data from a multi-center cluster-randomized trial evaluating a communication intervention to increase goals-of-care discussions in the outpatient setting. Patients (n = 249 intervention, n = 288 usual care) had serious illness with an expected median survival of two years. Using model-based recursive partitioning, we tested heterogeneity of the intervention's effect on the occurrence of patient-reported goals-of-care discussions, electronic health record documentation of goals-of-care discussions, patients' ratings of quality of communication, and patients' symptoms of psychological distress at three and six months.Results: We found two significant interactions. For patients' overall rating of clinician communication (n = 251), the intervention effect was positive for patients with higher household income, but not those with lower income (P < 0.001). For patients' symptoms of depression at six months (n = 288), the intervention was associated with fewer symptoms of depression among those whose self-assessed health was poor, but not among those with fair to excellent health (P < 0.001).Conclusions: Identifying heterogeneity of treatment effect can be a valuable exercise following completion of a randomized trial. Interactions between the intervention and patient income and self-assessed health suggest these factors could be used to design more effective interventions to enhance communication about goals of care. [ABSTRACT FROM AUTHOR]

Evidence for acute amphetamine effects on behavioural impulsivity in healthy populations remains elusive and, at times, mixed. This review collates and reviews the clinical literature on the acute effects of amphetamines on measures of behavioural impulsivity in healthy adults. Randomised and placebo-controlled clinical trials that assessed behavioural impulsivity following the administration of an acute dose of amphetamine or a related psychostimulant (including amphetamine analogues and methylphenidate) were eligible for inclusion. The EBSCOHost, SCOPUS, PsychNet, Web of Science and ProQuest databases were searched from inception to 26 April 2021. Study selection, data extraction and the Cochrane risk of bias assessments were conducted by two independent reviewers. Reporting follows PRISMA guidelines, and the review was registered a priori on the PROSPERO database (Registration No: CRD42021249861). A total of 20 studies were included, comprising a total of 737 participants. Overall, results indicate that low-moderate doses of amphetamine and related psychostimulants may improve (i.e., reduce) impulsive responding without compromising performance, reflecting enhanced inhibitory control of behaviour. These effects are mild and appear most pronounced in individuals with high baseline impulsivity. This review highlights the need for greater consistency in behavioural task selection and future high-quality and well-designed studies to address current concerns around growing prescription psychostimulant use and misuse. [ABSTRACT FROM AUTHOR]

Background: As uncertainty remains about whether clinical response influences cognitive function after electroconvulsive therapy (ECT) for depression, we examined the effect of remission status on cognitive function in depressed patients 4 months after a course of ECT. Method: A secondary analysis was undertaken on participants completing a randomised controlled trial of ketamine augmentation of ECT for depression who were categorised by remission status (MADRS ⩽10 v. >10) 4 months after ECT. Cognition was assessed with self-rated memory and neuropsychological tests of anterograde verbal and visual memory, autobiographical memory, verbal fluency and working memory. Patients were assessed through the study, healthy controls on a single occasion, and compared using analysis of variance. Results: At 4-month follow-up, remitted patients (N = 18) had a mean MADRS depression score of 3.8 (95% CI 2.2–5.4) compared with 27.2 (23.0–31.5) in non-remitted patients (N = 19), with no significant baseline differences between the two groups. Patients were impaired on all cognitive measures at baseline. There was no deterioration, with some measures improving, 4-months after ECT, at which time remitted patients had significantly improved self-rated memory, anterograde verbal memory and category verbal fluency compared with those remaining depressed. Self-rated memory correlated with category fluency and autobiographical memory at follow-up. Conclusions: We found no evidence of persistent impairment of cognition after ECT. Achieving remission improved subjective memory and verbal memory recall, but other aspects of cognitive function were not influenced by remission status. Self-rated memory may be useful to monitor the effects of ECT on longer-term memory. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether prophylactic administration of oxytocin plus ergonovine or oxytocin plus carboprost is more effective than oxytocin alone in reducing the need for additional uterotonics among women undergoing cesarean delivery for labor arrest.Methods: In this double-blind, three-arm randomized controlled trial, participants were assigned to receive either oxytocin 5 units intravenous alone, or with ergonovine 0.25 mg intravenous or carboprost 0.25 mg intramuscular immediately after delivery, followed with maintenance infusion of oxytocin 40 milliunits/minute in all groups. Uterine tone was assessed at 3, 5, and 10 minutes after delivery, and additional uterotonics were administered if deemed necessary. The primary outcome was intraoperative need for additional uterotonics. Secondary outcomes included uterine tone, calculated blood loss, and side effects. A sample size of 34 per group (n=102), based on the null hypothesis that there is no association between treatment assignment and the need for additional uterotonics, permitted independent post hoc pairwise comparisons between oxytocin plus ergonovine, oxytocin plus carboprost, and oxytocin alone using an adjusted P-value of .025. The association between the need for additional uterotonics and treatment group was assessed using the χ2 test.Results: From June 2013 through July 2019, 105 participants were randomized (35 per group) and data from 100 participants were analyzed: oxytocin (n=35), oxytocin plus ergonovine (n=33), and oxytocin plus carboprost (n=32). There was no difference in the requirement of additional intraoperative uterotonics across groups (oxytocin [37%] vs oxytocin plus ergonovine [33%] vs oxytocin plus carboprost [34%], P=.932). Uterine tone and calculated blood loss were similar across groups. Incidence of nausea or vomiting was higher in oxytocin plus ergonovine (85%; odds ratio [OR] 5.3, 95% CI 1.7-16.9, P=.003) and oxytocin plus carboprost (72%; OR 2.4, 95% CI 0.9-6.7, P=.086) compared with the oxytocin (51%) group.Conclusion: Compared with oxytocin alone, prophylactic use of a combination of uterotonic drugs did not reduce the need for additional uterotonics at cesarean delivery for labor arrest.Clinical Trial Registration: ClinicalTrials.gov, NCT01869556. [ABSTRACT FROM AUTHOR]

Despite decades of improvement in the quality and outcomes of cardiovascular care, significant gaps remain. Existing quality improvement strategies are often limited in scope to specific clinical conditions and episodic care. Health services and outcomes research is essential to inform gaps in care but rarely results in the development and implementation of care delivery solutions. Although individual health systems are engaged in projects to improve the quality of care delivery, these efforts often lack a robust study design or implementation evaluation that can inform generalizability and further dissemination. Aligning the work of health care systems and health services and outcomes researchers could serve as a strategy to overcome persisting gaps in cardiovascular quality and outcomes. We describe the inception of the Cardiovascular Quality Improvement and Care Innovation Consortium that seeks to rapidly improve cardiovascular care by (1) developing, implementing, and evaluating multicenter quality improvement projects using innovative care designs; (2) serving as a resource for quality improvement and care innovation partners; and (3) establishing a presence within existing quality improvement and care innovation structures. Success of the collaborative will be defined by projects that result in changes to care delivery with demonstrable impacts on the quality and outcomes of care across multiple health systems. Furthermore, insights gained from implementation of these projects across sites in Cardiovascular Quality Improvement and Care Innovation Consortium will inform and promote broad dissemination for greater impact. [ABSTRACT FROM AUTHOR]

Background: Acute flaccid myelitis is characterized by acute-onset flaccid limb weakness with predominantly gray matter lesions in the spinal cord spanning one or more segments. Rates of full recovery are poor, and there is no standard treatment or definitive cause.Methods: This is a retrospective review of children diagnosed with acute flaccid myelitis in Texas during 2016. Patients were identified through a Texas collaborative of six hospitals in four major metropolitan areas. Data abstraction included health history, illness presentation, medical treatments, laboratory studies, imaging data, recovery, and ability to perform activities of daily living up to approximately two years from illness onset.Results: Among all sites, 21 patients met inclusion criteria. Treatments varied with the most common being intravenous immunoglobulin, high-dose methylprednisolone, and plasmapheresis. No differences were seen in response to medical treatments. A potential etiology was found in 12 (57%) cases, including four with enterovirus D68. Five cases recovered fully. Of the 16 patients without full recovery, abilities ranged from (1) able to perform all activities of daily living for age independently (n = 5), (2) mild deficits (n = 5), and (3) substantial reliance on caregivers for activities of daily living (n = 6).Conclusion: Many reports describe symptoms and outcomes of acute flaccid myelitis, but limited data are available on long-term functional outcomes. We were unable to make a strong case for any single cause or treatment modality. Fortunately, the majority of patients (15, 71%) were able to perform activities of daily living with complete independence or only mild deficits. [ABSTRACT FROM AUTHOR]

To characterize and compare two intramuscular drug protocols using alfaxalone and alfaxalone–medetomidine combination for the field immobilization of free-ranging koalas. Blinded, randomized, comparative field study. A total of 66 free-ranging koalas from the Mount Lofty Ranges, South Australia. Koalas were randomly allocated into two groups. Group A animals were given alfaxalone alone at 3.5 mg kg–1. Group AM animals were given alfaxalone 2 mg kg–1 and medetomidine 40 μg kg–1, reversed with atipamezole at 0.16 mg kg–1. Blinded operators recorded heart rate (HR), respiratory rate (f R), cloacal temperature, depth of sedation and times to: first effect, sedation suitable for clinical interventions, first arousal and full recovery. Data were analysed using independent t test, Mann–Whitney U test, chi-square analysis and log-rank test at 5% level of significance. Suitable immobilization for clinical examination and sample collection was achieved in all animals. In groups A and AM, median time to working depth was 6.5 minutes (range: 3.4–15) and 8.1 minutes (range: 4.3–24) and time to complete recovery was 66 minutes (range: 12–138) and 34 minutes (range: 4–84), respectively, following reversal. Time to first effect was significantly shorter in group A (p = 0.013), whereas time to full arousal was significantly shorter in group AM (p = 0.007) probably due to the administration of atipamezole. Maximum HR was 117 ± 28 beats minute–1 in group A, which was a significant increase from baseline values (p < 0.0001), whereas group AM showed a significant tachypnoea of 67 ± 25 (normal f R 10–15; p < 0.0001). Both the protocols produced immobilization, enabling clinical examination and sample collection; however, protocol AM was more suitable for field work due to shorter recovery times. [ABSTRACT FROM AUTHOR]

Objective: Although Indigenous women are exposed to high rates of risk factors for perinatal mental health problems, the magnitude of their risk is not known. This lack of data impedes the development of appropriate screening and treatment protocols, as well as the proper allocation of resources for Indigenous women. The objective of this systematic review and meta-analysis was to compare rates of perinatal mental health problems among Indigenous and non-Indigenous women.Methods: We searched Medline, EMBASE, PsycINFO, CINAHL, and Web of Science from their inceptions until February 2019. Studies were included if they assessed mental health in Indigenous women during pregnancy and/or up to 12 months postpartum.Results: Twenty-six articles met study inclusion criteria and 21 were eligible for meta-analysis. Indigenous identity was associated with higher odds of mental health problems (odds ratio [OR] 1.62; 95% confidence interval [CI], 1.25 to 2.11). Odds were higher still when analyses were restricted to problems of greater severity (OR 1.95; 95% CI, 1.21 to 3.16) and young Indigenous women (OR 1.86; 95% CI, 1.51 to 2.28).Conclusion: Indigenous women are at increased risk of mental health problems during the perinatal period, particularly depression, anxiety, and substance misuse. However, resiliency among Indigenous women, cultural teachings, and methodological issues may be affecting estimates. Future research should utilize more representative samples, adapt and validate diagnostic and symptom measures for Indigenous groups, and engage Indigenous actors, leaders, and related allies to help improve the accuracy of estimates, as well as the well-being of Indigenous mothers, their families, and future generations.Trial Registration: PROSPERO-CRD42018108638. [ABSTRACT FROM AUTHOR]

The comparative study of communication and media has made significant progress in the past 15 years or so, at least if we judge progress by the sheer quantity of comparative research now published. Methodologically speaking, comparative communication research has, however, developed largely in a quantitative direction over this time period. Qualitative methods of comparative communication research, of how best to design and conduct such research, have yet to receive sustained attention and lag behind some other fields and disciplines in the social sciences, both in terms of making comparisons over time and across space. In this feature article, I briefly make the argument that a greater engagement with qualitative methodological issues would help to make both quantitative and qualitative comparative communication research generally across its breadth and depth become more innovative, robust, and systematic. [ABSTRACT FROM AUTHOR]

Introduction: Talimogene laherparepvec is a first-in-class oncolytic immunotherapy for intratumoral injection with proven efficacy and tolerability in patients with unresectable early metastatic melanoma (stage IIIB-IVM1a) in the pivotal phase III OPTiM study. The objective was to characterize melanoma patients treated with talimogene laherparepvec in routine clinical practice in Germany.Methods: A retrospective chart review was conducted in unresectable stage IIIB-IVM1a melanoma patients. Data on demographics, disease and medical history, and use of talimogene laherparepvec were collected. A survey was also conducted to understand physician treatment decisions.Results: Data for 27 patients who initiated talimogene laherparepvec between June 2016 and July 2017 were analyzed (median age 68; stage IIIB/C disease 56%). All patients had prior surgery, and over half had repeated resections for recurrent disease (median 3). Overall, 48% of patients received at least one prior local treatment, mainly radiation therapy or electrochemotherapy. Talimogene laherparepvec was first-line systemic therapy in 63% of patients. The most frequent prior systemic treatment was immunotherapy (7/27 patients). At end of follow-up, 13 patients were still on talimogene laherparepvec and 14 patients had discontinued treatment. Among those who discontinued, 8 (57%) did not receive subsequent systemic therapy. Only one patient receiving first-line talimogene laherparepvec received a subsequent systemic therapy. Three patients stopped treatment because of no remaining injectable lesions. Median treatment duration was 22.1 weeks overall and 27.9 weeks in stage IIIB/C disease patients. Nearly all cutaneous lesions (93%) were injected with talimogene laherparepvec compared to subcutaneous (83%) and nodal lesions (77%). No new safety signals were reported. The main reasons given in the physician survey for treating with talimogene laherparepvec were good tolerability, overall efficacy, and lack of contraindications.Conclusion: Talimogene laherparepvec is now included as a routine treatment option for unresectable early metastatic melanoma in Germany. This study characterizes the first patients treated with talimogene laherparepvec in Europe and confirms the good tolerability observed in clinical trials.Trial Registration: EUPAS registry, EUPAS17410.Funding: Amgen Inc. [ABSTRACT FROM AUTHOR]

Background: Cystic Fibrosis (CF) management requires complex treatment regimens but adherence to treatment is poor and has negative health implications. There are various methods of measuring adherence, but little is known regarding the extent of adherence measurement in CF centres throughout the UK and Ireland.Objective: To determine the adherence monitoring practices in CF centres throughout the UK and Ireland, and to establish CF pharmacists' views on these practices.Setting: UK and Ireland Cystic Fibrosis Pharmacists' Group's annual meeting (2014).Methods: A questionnaire was designed, piloted and distributed to pharmacists attending the UK and Ireland Cystic Fibrosis Pharmacists' Group's annual meeting (2014). The main outcome measures were the methods of inhaled/nebulised antibiotic supply and the methods used to measure treatment adherence in CF centres. The questionnaire also ascertained the demographic information of participating pharmacists. Closed question responses were analysed using descriptive statistics. Open questions were analysed using content analysis.Results: Twenty-one respondents (84 % response) were included in the analysis and were mostly from English centres (66.7 %). Detailed records of patients receiving their inhaled/nebulised antibiotics were lacking. Adherence was most commonly described to be measured at 'every clinic visit' (28.6 %) and 'occasionally' (28.6 %). Patient self-reported adherence was the most commonly used method of measuring adherence in practice (90.5 %). The availability of electronic adherence monitoring in CF centres did not guarantee its use. Pharmacists attributed an equal professional responsibility for adherence monitoring in CF to Consultants, Nurses and Pharmacists. Seventy-six percent of pharmacists felt that the current adherence monitoring practices within their own unit were inadequate and associated with the absence of sufficient specialist CF pharmacist involvement. Many suggested that greater specialist pharmacist involvement could facilitate improved adherence monitoring.Conclusion: Current adherence knowledge is largely based on self-report. Further work is required to establish the most appropriate method of adherence monitoring in CF centres, to improve the recording of adherence and to understand the impact of increased specialist pharmacist involvement on that adherence. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies suggest that pulmonary function is associated with fruit and vegetable consumption and plasma concentrations of antioxidant vitamins. Also, expiratory flow limitation (EFL) has been reported to limit ventilation during exercise in healthy individuals. We hypothesized antioxidant vitamin supplementation (AVS) would increase resting expiratory flow rates in healthy subjects and reduce EFL during exercise.Methods: Ten healthy, nonsmoking subjects (5 M/5 W), consuming <5 servings of fruit and vegetables per day, participated in a randomized, single-blinded crossover design study with subjects receiving a placebo (PLA) or AVS [vitamins C (500 mg), E (400 IU), beta-carotene (15,000 IU), zinc (7.5 mg), selenium (50 mg), copper (1 mg), and manganese (2.5 mg)] for 4 weeks. After a minimum 4-week washout period, subjects received the alternate supplementation. Pulmonary function tests and total antioxidant status (TAS) from plasma were measured pre- and post-supplement period. Subjects completed a pre- and post-supplement treadmill test for 20 min at 70% [Formula: see text] followed by increasing workload until exhaustion.Results: AVS increased (p < 0.05) TAS by ~21% and resting expiratory flow rates (FEF25-75, FEF50) by ~9%. Following AVS, %EFL was significantly reduced by ~15% at minute 15, 20, and end-exercise with no change (p > 0.05) in end-expiratory lung volumes. Breathing frequency and ratings of perceived exertion and dyspnea were also lower (p < 0.05) at min 20 of exercise. No changes (p > 0.05) were evident at rest or during exercise with PLA.Conclusions: These results suggest that AVS can increase TAS, improve resting expiratory flow rates and reduce EFL during exercise in healthy subjects who are not meeting fruit and vegetable recommendations. [ABSTRACT FROM AUTHOR]

Background: Magnetic seizure therapy (MST) is a novel brain stimulation technique that uses a high-powered transcranial magnetic stimulation device to produce therapeutic seizures. Preliminary MST studies have found antidepressant effects in the absence of cognitive side effects but its efficacy compared to electroconvulsive therapy (ECT) remains unclear. The aim of this study was to investigate the therapeutic efficacy and cognitive profile of MST compared to standard right unilateral ECT treatment.Methods: Thirty-seven patients completed a course of at least nine ECT or MST treatments in a randomized double-blind protocol. Assessments of depression severity and cognition were performed before and after treatment.Results: No difference in the antidepressant effectiveness between the treatments was seen across any of the clinical outcome measures, although the overall response rates in both groups were quite low. In regards to cognition, following MST there were significant improvements in tests of psychomotor speed, verbal memory, and cognitive inhibition, with no reductions in cognitive performance. Following ECT there was significant improvement in only one of the cognitive inhibition tasks. With respect to the between-group comparisons, the MST group showed a significantly greater improvement on psychomotor speed than ECT.Conclusions: MST showed similar efficacy to right unilateral ECT in patients with treatment-resistant depression without cognitive side effects but in a sample that was only of sufficient size to demonstrate relatively large differences in response between the two groups. Future research should aim to optimize the methods of MST administration and compare its efficacy to ECT in large randomized controlled trials. [ABSTRACT FROM AUTHOR]

The optimum time interval for 10 ml boluses of bupivacaine 0.0625% + fentanyl 2 μg.ml-1 as part of a programmed intermittent epidural bolus regimen has been found to be 40 min. This regimen was shown to be effective without the use of supplementary patient-controlled epidural analgesia boluses in 90% of women during the first stage of labour, although with a rate of sensory block to ice above T6 in 34% of women. We aimed to determine the optimum programmed intermittent epidural bolus volume at a 40 min interval to provide effective analgesia in 90% of women (EV90 ) during the first stage of labour, without the use of patient-controlled epidural analgesia. We performed a prospective double-blind dose-finding study using the biased coin up-and-down sequential allocation method in 40 women. The estimated EV90 was 11.0 (95%CI 10.0-11.7) ml with the isotonic regression method and 10.7 (95%CI 10.3-11.0) ml with the truncated Dixon and Mood method. Overall, 18 women had a sensory block above T6, and 37 women exhibited no motor block. No women required treatment for hypotension. In conclusion, it is not possible to reduce the programmed intermittent epidural bolus volume from 10 ml, used in our current regimen, without compromising the quality of analgesia. Using this regimen, a high proportion of women will develop a sensory block above T6. [ABSTRACT FROM AUTHOR]

Hemp-derivative (Cannabis sativa L.) food products containing trace levels of Δ-9-tetrahydrocannabinol (THC) are proposed for consumption in Australia and New Zealand; however, it is unclear whether use of these products will negatively affect existing drug screening protocols. This double-blind, within-subjects, cross-over trial assessed 35 adults (17 male; 18 female), aged 22-52 years [Mean=30.7, Standard Deviation (S.D)±7.6]. Low dose THC oil [5mL bearer sesame oil containing 10mg/kg THC (0.046mg THC per 5mL dose)]; high dose THC oil [5mL bearer sesame oil containing 20mg/kg THC (0.092mg THC per 5mL dose)]; and a placebo oil (THC negative) was consumed during a three-week protocol. The Securetec Drugwipe® II Twin device assessed THC presence (cut-off 20ng/mL) in oral fluid at baseline, at 5, 30, 60, 120 and 240min post-treatment. Blood was drawn at baseline, 30, 120 and 240min post-treatment, and urine at baseline and 240min post-treatment. No THC was detected in oral fluid, blood or urine samples at any time-point following consumption of the low or high THC dose. Trace concentrations of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THCa) were detected in blood 4-h after consumption of the high THC treatment (M=0.0001mg/L) and in urine at 4-h post consumption of both low and high THC treatments (M=0.0001mg/L and 0.0004mg/L, respectively). Consumption of low-content THC oil does not result in positive biological assessments. It is therefore highly unlikely that ingestion of products containing these levels of THC will negatively impact existing region-specific drug driving enforcement protocols. [ABSTRACT FROM AUTHOR]

Bedside gastric ultrasonography can be performed reliably by anaesthetists to assess gastric content in the peri-operative period. We aimed to study the relationship between gastric cross-sectional area, assessed by ultrasound, and volumes of clear fluids ingested by pregnant women. We recruited 60 non-labouring third-trimester pregnant women in a randomised controlled and assessor-blinded study. A standardised scanning protocol of the gastric antrum was performed in the 45° semirecumbent and 45° semirecumbent-right lateral positions. Subjects were randomly allocated to drink one out of six predetermined volumes of apple juice (0 ml, 50 ml, 100 ml, 200 ml, 300 ml, 400 ml). Qualitative and quantitative assessments at a baseline period after an 8-h fast, and immediately after the drink, were used to establish the correlation between antral cross-sectional area and volume ingested. A predictive model to estimate gastric volume was developed. Antral cross-sectional area in the semirecumbent right lateral position significantly correlated with the ingested volume (Spearman rank correlation = 0.7; p < 0.0001). A cut-off value of 9.6 cm2 discriminated ingested volumes ≥ 1.5 ml.kg-1 with a sensitivity of 80%, a specificity of 66.7%, and an area under the curve of 0.82. A linear predictive model was developed for gastric volume based only on antral cross-sectional area (Volume (ml) = -327.1 + 215.2 × log (cross-sectional area) (cm2 )). We conclude that in pregnant women in the third trimester of gestation, the antral cross-sectional area correlates well with volumes ingested, and this cut-off value in the semirecumbent right lateral position discriminates high gastric volumes. [ABSTRACT FROM AUTHOR]

Streptococcus mutans is recognized as one of the key contributors to the dysbiotic state that results in dental caries. Existing treatment strategies reduce the incidence of tooth decay, but they also eliminate both the cariogenic and beneficial microbes. Here we introduce a novel treatment alternative using Sephadex, cross-linked dextranomer microspheres (DMs), typically used for gel filtration chromatography. In addition DM beads can be used for affinity purification of glucosyltransferases (GTFs) from S. mutans. In this study we take advantage of the native pathogenic mechanisms used by S. mutans to adhere, form a biofilm and induce dental caries through the expression of surface-associated GTFs. We demonstrate that planktonic and biofilm-grown (adhered to hydroxyapatite-coated pegs to mimic the tooth surface) S. mutans, specifically and competitively attach to DMs. Further investigation demonstrated that DMs are a specific affinity resin for S. mutans and other cariogenic/pathogenic oral streptococci, whereas other commensal and probiotic strains failed to readily adhere to DMs. Using antimicrobial cargo loaded into the DM lumen, we demonstrate that when in co-culture with non-binding to even modestly binding commensal species, S. mutans was selectively killed. This proof of concept study introduces a novel means to safely and effectively reduce the pool of S. mutans and other pathogenic streptococci in the oral cavity with limited disturbance of the necessary commensal (healthy) microbiota when compared with current oral healthcare products. [ABSTRACT FROM AUTHOR]

The recreational use of various stimulant drugs has been implicated in the development of movement disorders through dysregulation of the dopaminergic and serotoninergic neurotransmitter systems. The present study investigated psychomotor differences in current and former recreational stimulant drug users compared with nonusing controls. Sixty participants comprised 3 groups: 20 current stimulant drug users (CSUs; 11 men, aged 31.4 ± 9.1 years), 20 former stimulant drug users (FSUs; 5 men, aged 39.1 ± 8.5 years), and 20 nonuser controls (NUCs; 5 men, aged 35.7 ± 6.4 years). Psychomotor arm steadiness for each participant was assessed with a wrist-attached accelerometer during 5 arm positions with eyes open and then eyes closed. Arm-drop of arm position was indicated by the arm longitudinal rotation axis (ALoRA), and tremor was indicated by the overall vector of dynamic body acceleration (VeDBA). Overall, CSUs performed the most poorly on ALoRA ( P < .05) and VeDBA indices ( P < .05), and FSUs perform almost as poorly on VeDBA indices ( P < .05) compared with NUCs. It was concluded that stimulant drug use, primarily MDMA and amphetamines, may result in acute stimulant-induced tremor as well as long-term proprioceptive deficits in terms of arm-droop. [ABSTRACT FROM AUTHOR]

In this longitudinal study, attributional and social processes involved in symptoms of mental health problems (depressive symptoms and aggressive behavior) were identified by investigating anxious and angry rejection sensitivity (RS), causal attributions of self-blame and peer-blame, and responses to rejection threat of withdrawal and retribution. Young adolescents (N = 713, grades 5-7) completed questionnaires three times in their regular classrooms over 14 months. Participants who reported more self-blame for rejection were more likely to withdraw in response to rejection threat, and withdrawal and anxious RS were associated with increased depressive symptoms at T3 relative to T1. In contrast, adolescents higher in the angry form of RS and who reported more peer-blame for rejection were more likely to seek retribution, which in turn was associated with more overt/relational aggressive behavior at T3 relative to T1. Depressive symptom level measured at T1 also was associated with later RS and coping with withdrawal, and aggressive behavior at T1 was associated with later retribution. Sex of the participants did not moderate any longitudinal associations, and only one prospective path, from T1 depressive symptoms to T2 RS anxious, was moderated by age. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic sensitivity of computed diffusion-weighted (DW)-MR imaging for the detection of breast cancer.Materials and Methods: Local research ethics approval was obtained. A total of 61 women (median 48 years) underwent dynamic contrast enhanced (DCE)- and DW-MR between January 2011 and March 2012, including 27 with breast cancer on core biopsy and 34 normal cases. Standard ADC maps using all four b values (0, 350, 700, 1150) were used to generate computed DW-MR images at b = 1500 s/mm(2) and b = 2000 s/mm(2) . Four image sets were read sequentially by two readers: acquired b = 1150 s/mm(2) , computed b = 1500 s/mm(2) and b = 2000 s/mm(2) , and DCE-MR at an early time point. Cancer detection was rated using a five-point scale; image quality and background suppression were rated using a four-point scale. The diagnostic sensitivity for breast cancer detection was compared using the McNemar test and inter-reader agreement with a Kappa value.Results: Computed DW-MR resulted in higher overall diagnostic sensitivity with b = 2000 s/mm(2) having a mean diagnostic sensitivity of 76% (range 49.8-93.7%) and b = 1500 s/mm(2) having a mean diagnostic sensitivity of 70.3% (range 32-97.7%) compared with 44.4% (range 25.5-64.7%) for acquired b = 1150 s/mm(2) (both p = 0.0001). Computed DW-MR images produced better image quality and background suppression (mean scores for both readers: 2.55 and 2.9 for b 1500 s/mm(2) ; 2.55 and 3.15 for b 2000 s/mm(2) , respectively) than the acquired b value 1150 s/mm(2) images (mean scores for both readers: 2.4 and 2.45, respectively).Conclusion: Computed DW-MR imaging has the potential to improve the diagnostic sensitivity of breast cancer detection compared to acquired DW-MR. J. Magn. Reson. Imaging 2016;44:130-137. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical utility of the reverse gradient algorithm in correcting distortions in diffusion-weighted images of the cervix and for increasing diagnostic performance.Materials and Methods: Forty-one patients ages 25-72 years (mean 40 ± 11 years) with suspected or early stage cervical cancer were imaged at 3T using an endovaginal coil. T2 -weighted (W) and diffusion-weighted images with right and left phase-encode gradient directions were obtained coronal to the cervix (b = 0, 100, 300, 500, 800 s mm(-2) ). Differences in angle of the endocervical canal to the x-axis between T2 W and right-gradient, left-gradient, and corrected images were measured. Uncorrected and corrected images were assessed for diagnostic performance when viewed together with T2 W images by two independent observers against subsequent histology.Results: The angles of the endocervical canal relative to the x-axis were significantly different between the T2 W images and the right-gradient images (P = 0.007), approached significance for left-gradient images (P = 0.055), and were not significantly different after correction (P = 0.95). Corrected images enabled a definitive diagnosis in 34% (n = 14) of patients classified as equivocal on uncorrected images. Tumor volume in this subset was 0.18 ± 0.44 cm(3) (mean ± SD; sensitivity of detection 100% [8/8], specificity 50% [3/6] for an experienced observer). Correction did not improve diagnostic performance for the less-experienced observer.Conclusion: Distortion-corrected diffusion-weighted images improved correspondence with T2 W images and diagnostic performance in a third of cases. [ABSTRACT FROM AUTHOR]

Findings from confederate paradigms predict that mimicry is an adaptive route to social connection for rejection-sensitive individuals (Lakin, Chartrand, & Arkin, 2008). However, dyadic perspectives predict that whether mimicry leads to perceived connection depends on the rejection sensitivity (RS) of both partners in an interaction. We investigated these predictions in 50 college women who completed a dyadic cooperative task in which members were matched or mismatched in being dispositionally high or low in RS. We used a psycholinguistics paradigm to assess, through independent listeners' judgments (N = 162), how much interacting individuals accommodate phonetic aspects of their speech toward each other. Results confirmed predictions from confederate paradigms in matched RS dyads. However, mismatched dyads showed an asymmetry in levels of accommodation and perceived connection: Those high in RS accommodated more than their low-RS partner but emerged feeling less connected. Mediational analyses indicated that low-RS individuals' nonaccommodation in mismatched dyads helped explain their high-RS partners' relatively low perceived connection to them. Establishing whether mimicry is an adaptive route to social connection requires analyzing mimicry as a dyadic process influenced by the needs of each dyad member. [ABSTRACT FROM AUTHOR]

Objective: To compare sensitivity and specificity of endovaginal versus external-array coil T2-W and T2-W + DWI for detecting and staging small cervical tumours.Methods: Optimised endovaginal and external array coil MRI at 3.0-T was done prospectively in 48 consecutive patients with stage Ia/Ib1 cervical cancer. Sensitivity/specificity for detecting tumour and parametrial extension against histopathology for a reading radiologist were determined on coronal T2-W and T2W + DW images. An independent radiologist also scored T2-W images without and with addition of DWI for the external-array and endovaginal coils on separate occasions >2 weeks apart. Cohen's kappa assessed inter- and intra-observer agreement.Results: Median tumour volume in 19/38 cases positive on subsequent histology was 1.75 cm(3). Sensitivity, specificity, PPV, NPV were: reading radiologist 91.3 %, 89.5 %, 91.3 %, 89.5 %, respectively; independent radiologist T2-W 82.6 %, 73.7 %, 79.1 %, 77.8 % for endovaginal, 73.9 %, 89.5 %, 89.5 %, 73.9 % for external-array coil. Adding DWI improved sensitivity and specificity of endovaginal imaging (78.2 %, 89.5 %); adding DWI to external-array imaging improved specificity (94.7 %) but reduced sensitivity (66.7 %). Inter- and intra-observer agreement on T2-W + DWI was good (kappa = 0.67 and 0.62, respectively).Conclusion: Endovaginal coil T2-W MRI is more sensitive than external-array coil for detecting tumours <2 cm(3); adding DWI improves specificity of endovaginal imaging but reduces sensitivity of external-array imaging.Key Points: • Endovaginal more accurate than external-array T2-W MRI for detecting small cervical cancers. • Addition of DWI improves sensitivity and specificity of endovaginal T2-W imaging. • Addition of DWI substantially reduces sensitivity of external-array T2-W imaging. [ABSTRACT FROM AUTHOR]

Background: The language profile of behavioral variant frontotemporal dementia (bvFTD) remains to be fully defined.Objective: We aimed to quantify the extent of language deficits in this patient group.Methods: We assessed a cohort of patients with bvFTD (n = 24) in relation to patients with semantic variant primary progressive aphasia (svPPA; n = 14), nonfluent variant primary progressive aphasia (nfvPPA; n = 18), and healthy age-matched individuals (n = 24) cross-sectionally and longitudinally using a comprehensive battery of language and general neuropsychological tests. Neuroanatomical associations of language performance were assessed using voxel-based morphometry of patients' brain magnetic resonance images.Results: Relative to healthy controls, and after accounting for nonverbal executive performance, patients with bvFTD showed deficits of noun and verb naming and single word comprehension, diminished spontaneous propositional speech, and deterioration in naming performance over time. Within the bvFTD group, patients with MAPT mutations had more severe impairments of noun naming and single word comprehension than patients with C9orf72 mutations. Overall the bvFTD group had less severe language deficits than patients with PPA, but showed a language profile that was qualitatively similar to svPPA. Neuroanatomical correlates of naming and word comprehension performance in bvFTD were identified predominantly in inferior frontal and antero-inferior temporal cortices within the dominant hemispheric language network.Conclusions: bvFTD is associated with a language profile including verbal semantic impairment that warrants further evaluation as a novel biomarker. [ABSTRACT FROM AUTHOR]

Objective The Standardized Field Sobriety Tests (SFST) are utilised widely to assess fitness to drive when law enforcement suspects a driver's ability to drive is impaired, whether by drugs or alcohol. The SFST ostensibly achieve this through assessment of the level of drivers’ cognitive and psychomotor impairment, although no studies have explicitly assessed the relatedness of cognitive ability and performance on the SFST. The current study aimed to assess the relationship between the three components of the SFST with a well validated computerised cognitive battery. Method A sub-set of 61 placebo condition participants comprised the sample, with 33 females and 28 males (mean age 25.45 years). Correlations between the individual SFST subscales ‘Horizontal Gaze Nystagmus’ (HGN), the ‘One Leg Stand’ (OLS) and the ‘Walk and Turn’ test (WAT) and Cognitive Drug Research (CDR) sub-scales of ‘Quality of Working Memory’, ‘Power of Attention’ and ‘Continuity of Attention’ were analysed using point-biserial correlation. Results Sixty participants were included for analyses. A weak–moderate positive (five subscales) and a moderate–strong negative (two subscales) association was noted between seven of the nine individual CDR subscales and the SFST subscale of the WAT test (all p < 0.05). Individually, a moderate positive association was noted between the sub-scale ‘Nystagmus lack of smooth pursuit’ and ‘digit vigilance reaction time’ and ‘choice reaction time; reaction time’ (both p < 0.05) and ‘Nystagmus head move and/or jerk’ and ‘simple reaction time’ ( p < 0.001). When assessed as a partially composite factor, a comparable association was also noted between the composite score of the SFST subscale ‘Nystagmus head move and/or jerk’ and both (a) simple and (b) digit vigilance reaction time (both p < 0.05). No association was noted between any of the individual cognitive variables and the SFST subscale ‘OLS’, or between composite cognitive scores ‘Quality of Working Memory’, ‘Power of Attention’ and ‘Continuity of Attention’ and total SFST scores. Discussion Variation in some aspects of cognitive performance was found to be moderately and positively correlated with some individual aspects of the SFST; particularly among tasks which assess reaction time. Impairment of these cognitive processes can also contribute to the completion of complex tasks such as driving or the SFST. Complex behavioural tasks such as driving are often severely impaired due to intoxication, and thus in a practical sense, the SFST can still be considered a useful screening tool to identify drug or alcohol impaired drivers. [ABSTRACT FROM AUTHOR]

Symptoms suggesting altered processing of pain and temperature have been described in dementia diseases and may contribute importantly to clinical phenotypes, particularly in the frontotemporal lobar degeneration spectrum, but the basis for these symptoms has not been characterized in detail. Here we analysed pain and temperature symptoms using a semi-structured caregiver questionnaire recording altered behavioural responsiveness to pain or temperature for a cohort of patients with frontotemporal lobar degeneration (n = 58, 25 female, aged 52-84 years, representing the major clinical syndromes and representative pathogenic mutations in the C9orf72 and MAPT genes) and a comparison cohort of patients with amnestic Alzheimer's disease (n = 20, eight female, aged 53-74 years). Neuroanatomical associations were assessed using blinded visual rating and voxel-based morphometry of patients' brain magnetic resonance images. Certain syndromic signatures were identified: pain and temperature symptoms were particularly prevalent in behavioural variant frontotemporal dementia (71% of cases) and semantic dementia (65% of cases) and in association with C9orf72 mutations (6/6 cases), but also developed in Alzheimer's disease (45% of cases) and progressive non-fluent aphasia (25% of cases). While altered temperature responsiveness was more common than altered pain responsiveness across syndromes, blunted responsiveness to pain and temperature was particularly associated with behavioural variant frontotemporal dementia (40% of symptomatic cases) and heightened responsiveness with semantic dementia (73% of symptomatic cases) and Alzheimer's disease (78% of symptomatic cases). In the voxel-based morphometry analysis of the frontotemporal lobar degeneration cohort, pain and temperature symptoms were associated with grey matter loss in a right-lateralized network including insula (P < 0.05 corrected for multiple voxel-wise comparisons within the prespecified anatomical region of interest) and anterior temporal cortex (P < 0.001 uncorrected over whole brain) previously implicated in processing homeostatic signals. Pain and temperature symptoms accompanying C9orf72 mutations were specifically associated with posterior thalamic atrophy (P < 0.05 corrected for multiple voxel-wise comparisons within the prespecified anatomical region of interest). Together the findings suggest candidate cognitive and neuroanatomical bases for these salient but under-appreciated phenotypic features of the dementias, with wider implications for the homeostatic pathophysiology and clinical management of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Archaeometry is the application of scientific techniques used to analyze archaeological materials. The Cretan Bronze Age Minoan Kernos, has hitherto, been regarded as a gaming board or for religious purposes. Here, it is shown, that, it was designed, specifically, to predict the occurrence of the 9th. January 1860 BCE Total Solar Eclipse. A prototype magnetic compass was centrally facilitated in a non-magnetic marble structure, whose geomagnetic declination angle, appears to coincide with the Kernos" eclipse prediction-axis orientation. Comparisons of eclipse constructions taken from Kernos measurements, with those of Hipparchus (2nd. c. BCE), appear to be similar, suggesting a common origin. Evidence obtained using a multidisciplinary approach, is testament to the sophistication of Middle Bronze Age science and technology and the ability to create a mathematically-based eclipse predictor and magnetic compass, 3800 years ago and 1700 years before the advent of the Antikythera Mechanism. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that mothers show a different pattern of brain responses when viewing their own compared to other infants. However, there is inconsistency across functional imaging studies regarding the key areas involved, and none have examined relationships between brain and behavioural responses to infants. We examined the brain regions activated when mothers viewed videos of their own infant contrasted with an unknown infant, and whether these are associated with behavioural and self-reported measures of mother-infant relations. Method: Twenty right-handed mothers viewed alternating 30-sec blocks of video of own 4–9 month infant and an unfamiliar matched infant, interspersed with neutral video. Whole brain functional magnetic resonance images (fMRI) were acquired on a 1.5T Philips Intera scanner using a TR of 2.55 s. Videotaped mother-infant interactions were systematically evaluated blind to family information to generate behavioural measures for correlational analysis. Results: Enhanced blood oxygenation functional imaging responses were found in the own versus unknown infant contrast in the bilateral precuneus, right superior temporal gyrus, right medial and left middle frontal gyri and left amygdala. Positive mother-infant interaction (less directive parent behaviour; more positive/attentive infant behaviour) was significantly associated with greater activation in several regions on viewing own versus unknown infant, particularly the middle frontal gyrus. Mothers' perceived warmth of her infant was correlated with activations in the same contrast, particularly in sensory and visual areas. Conclusion: This study partially replicates previous reports of the brain regions activated in mothers in response to the visual presentation of their own infant. It is the first to report associations between mothers' unique neural responses to viewing their own infant with the quality of her concurrent behaviour when interacting with her infant and with her perceptions of infant warmth. These findings provide support for developing fMRI as a potential biomarker of parenting risk and change. [ABSTRACT FROM AUTHOR]

Archaeointensity results were obtained from ceramic sherds incorporated in the 'mortar' of two Rhodian Byzantine churches. Samples were analysed using a modified Thellier method with samples orientated so that the Natural Remanent Magnetization is at right angles to the applied laboratory field. Only a few samples showed high magnetic stability and an archaeointensity result was obtained from ceramic sherds (tilebrick) from the lower interior walls of the church (Afandou Katholiki). Comparison with the Geomagnetic Field Variation plot indicated the probability density of possible dates between ~1000 to ~1500 AD. a date, broadly consistent with historical records. [ABSTRACT FROM AUTHOR]

Political sex scandals are largely absent in some democracies but proliferate in others. However, there have so far been few if any comprehensive attempts to document the actual number of sex scandals that have occurred and to explain their presence (and, indeed, absence), and the one study that has (Barker's 1994 study) ended in the early 1990s and had numerous problems in relation to defining and documenting such scandals. Based on extensive research, this article documents the number of sex scandals in eight advanced industrial democracies and tries to explain their occurrence using Charles Ragin's fuzzy set qualitative comparative analysis. The article has three goals: to determine the number of sex scandals in different democracies, explain why this might be, and demonstrate the utility of fuzzy set qualitative case analysis for small- and medium-N comparative research. [ABSTRACT FROM PUBLISHER]

Most contemporary work on public spheres tends to adopt, either explicitly or implicitly, Habermas’s idea of a deliberative public sphere as a normative model. There are, however, a number of other normative models available that are rarely the subject of empirical scrutiny: republican, liberal and multicultural. This article poses the empirical question of whether actually existing public spheres more closely resemble one model rather than another. To answer this question, the authors develop ways to measure public spheres, at both national and transnational level. They ground this attempt to move comparative media analysis forward conceptually and empirically via a case study comparing media content about the EU Constitution in six countries. [ABSTRACT FROM AUTHOR]

Abstract: Background: Mental illness affects 8% of the population. The early identification and treatment of mental illness can reduce the progression and complications of the illness. Objective: The objective of this study was to identify unsuspected psychiatric illness in patients presenting to the emergency department (ED) with non-psychiatric-related complaints. A comparison of the test results and the emergency physician assessments were then compared. Methods: All consenting and stable patients who presented to the ED with non-psychiatric complaints were given the Mini-International Neuropsychiatric Interview (MINI). It was administered to the patient by a trained research fellow before the patient was seen by the physician. Before the patient''s departure from the ED, the research fellow notified the emergency physician of the results of the MINI interview. After the emergency physician was notified of the diagnosis of the MINI, any change in the treatment was reviewed. Results: A total of 211 patients were enrolled in the study. The majority of patients (55%) tested negative for all undiagnosed mental illnesses. The top diagnoses were as follows: major depression (24%), general anxiety (9%), and drug abuse (8%). Of all those patients who tested positive for an undiagnosed mental illness, only 2% were diagnosed by the ED attending. Conclusions: The idea that the ED is a good place to identify undiagnosed mental health illnesses was confirmed. The use of an independent test such as the MINI was also shown to be useful to aid the emergency physician in identifying undetected mental illnesses. [Copyright &y& Elsevier]

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Copyright of Revista Española de Cirugía Ortopédica y Traumatologia (English Edition) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Scutellaria is a geographically widespread and diverse genus of the Lamiaceae family of herbaceous plants commonly known as skullcaps. Scutellaria is used widely as an ethnobotanical herb for the treatment of various ailments ranging from cancers, cirrhosis, jaundice, hepatitis, anxiety and nervous disorders. We used (1) reverse-phase liquid chromatography coupled to a diode array detector (LC-DAD), and (2) multiple reaction monitoring (MRM) using mass spectrometry (LC-MS/MS) to quantify the levels of acteoside, scutellarin, scetellarein, baicalin, baicalein, wogonin, wogonoside, apigenin, chrysin, and oroxylin A in aqueous methanolic extracts of roots, shoots and leaves of S. baicalensis, S. lateriflora, S. racemosa, S. tomentosa and S. wrightii. Our results indicate that both methods (LC-DAD and LC-MS/MS) were robust for the detection of the 10 analytes from Scutellaria extracts although greater sensitivities were achieved using LC-MS/MS in MRM mode. MRM enabled the detection of low levels of analytes which were otherwise undetected using LC-DAD. The baicalin content of S. wrightii roots were 5-fold higher than the commonly used S. baicalensis. Additionally, we also showed that leaves of both S. wrightii and S. tomentosa are good sources of scutellarin compared to S. baicalensis. Our data clearly demonstrated that previously uncharacterized species, S. wrightii and S. tomentosa are both good sources of flavonoids, particularly scutellarin, baicalin, wogonin and baicalein. [ABSTRACT FROM AUTHOR]

BackgroundBoth past depressive episodes and the personality trait of depressive rumination are strong risk factors for future depression. Depression is associated with abnormal emotional processing, which may be a neurobiological marker for vulnerability to depression. A consistent picture has yet to emerge as to how a history of depression and the tendency to ruminate influence emotional processing. The aim of this study was to investigate the relationship between rumination, past depression and neural responses when processing face emotions.MethodThe Ruminative Responses Scale (RRS) was completed by 30 remitted depressives and 37 controls who underwent functional magnetic resonance imaging (fMRI) scanning while viewing happy, sad, fearful and neutral faces.ResultsThe remitted depressives showed overall reductions in neural responses to negative emotions relative to the controls. However, in the remitted depressives, but not the controls, RRS scores were correlated with increased neural responses to negative emotions and decreased responses to happiness in limbic regions.ConclusionsAutomatic emotion processing biases and rumination seem to be correlated to aspects of vulnerability to depression. However, remission from depression may be maintained by a general suppression of limbic responsiveness to negative emotion. [ABSTRACT FROM PUBLISHER]

Background: Transcription factors often play important roles in tumourigenesis. Members of the PEA3 subfamily of ETS-domain transcription factors fulfil such a role and have been associated with tumour metastasis in several different cancers. Moreover, the activity of the PEA3 subfamily transcription factors is potentiated by Ras-ERK pathway signalling, which is itself often deregulated in tumour cells.Methods: Immunohistochemical patterns of PEA3 expression and active ERK signalling were analysed and mRNA expression levels of PEA3, ER81, MMP-1 and MMP-7 were determined in gastric adenocarcinoma samples.Results: Here, we have studied the expression of the PEA3 subfamily members PEA3/ETV4 and ER81/ETV1 in gastric adenocarcinomas. PEA3 is upregulated at the protein level in gastric adenocarcinomas and both PEA3/ETV4 and ER81/ETV1 are upregulated at the mRNA level in gastric adenocarcinoma tissues. This increased expression correlates with the expression of a target gene associated with metastasis, MMP-1. Enhanced ERK signalling is also more prevalent in late-stage gastric adenocarcinomas, and the co-association of ERK signalling and PEA3 expression also occurs in late-stage gastric adenocarcinomas. Furthermore, the co-association of ERK signalling and PEA3 expression correlates with decreased survival rates.Conclusions: This study shows that members of the PEA3 subfamily of transcription factors are upregulated in gastric adenocarcinomas and that the simultaneous upregulation of PEA3 expression and ERK pathway signalling is indicative of late-stage disease and a poor survival prognosis. [ABSTRACT FROM AUTHOR]

Objectives: The timely recruitment of study participants is a critical component of successful trials. Benign prostatic hyperplasia (BPH), a common nonmalignant urologic condition among older men, is characterized by lower urinary tract symptoms (LUTS). Successful recruitment methods for a trial of medical therapy for BPH, Medical Therapy of Prostate Symptoms (MTOPS), were mass mailing and advertising. The Complementary and Alternative Medicines Trial for Urological Symptoms (CAMUS) was designed to evaluate a botanical therapy, saw palmetto, for the treatment of BPH. The objective of this study was to evaluate recruitment strategies for CAMUS and to contrast the baseline characteristics of CAMUS participants with those recruited to a similar trial using conventional medical therapy. Design: CAMUS is a randomized, double-blind, placebo-controlled trial designed to evaluate the effects of saw palmetto given at escalating doses over an 18-month period on relief from LUTS. Subjects: The target enrollment goal was 350 men with LUTS from 11 clinical centers over a 12-month period. The recruitment techniques used and participants contacted, screened, and randomized through each technique were obtained from the clinical centers. Baseline characteristics of the CAMUS participants were compared with participants in the MTOPS trial who met the CAMUS eligibility criteria for LUTS. Results: The target enrollment goal was achieved in 11 months. The overall monthly recruitment rate per site was 3.7 and ranged from 2.4 to 8.0. The most successful recruitment methods were mass mailing and advertising, which accounted for 39% and 35% of the study participants, respectively. In comparison to MTOPS participants, CAMUS participants were younger, more highly educated, more diverse, and had less severe urinary symptoms. Conclusions: Successful recruitment methods for CAMUS were similar to those in MTOPS. The use of botanical therapy attracted a less symptomatic and more educated study population. [ABSTRACT FROM AUTHOR]

Background: Endoscopy (esophagogastroduodenoscopy, EGD) to screen for esophageal varices (EV) is recommended in patients with portal hypertension. Reports indicate that capsule endoscopy (CE) is capable of identifying large/medium varices (L/MV) when the varix comprises more than 25% of the circumference of the field of view.Aims: We evaluated the ability of CE to discriminate the size of EV using this grading scale.Methods: Patients underwent CE and EGD on the same day. A blinded investigator interpreted capsule findings. CE labeled EV as L/MV if ≥25% of the lumen circumference was occupied, and small/none for <25%.Results: A total of 37 patients were enrolled in this prospective, observational study at a single tertiary-care academic center. Three CE were excluded due to rapid esophageal transit time or technical malfunction. Using a 25% threshold, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for EC to discriminate L/MV were 23.5%, 88.2%, 66.7%, and 53.6%, respectively (κ=0.12). Reducing the threshold to 12.5% resulted in sensitivity, specificity, PPV, and NPV of 88.2%, 64.7%, 71.4%, and 84.6%, respectively (κ=0.53). A receiver-operator characteristic (ROC) curve showed a 15% threshold to be optimal in discriminating EV size using CE, resulting in sensitivity, specificity, PPV, and NPV of 76.5%, 82.4%, 81.3%, and 77.8%, respectively (κ=0.59).Conclusions: This study indicates that discriminating EV size by the current capsule scale is unreliable. Lowering the grading threshold improved the ability to discriminate EV size by CE. In the proper context, CE is an alternative to EGD to screen for EV. [ABSTRACT FROM AUTHOR]

Introduction: Roux-en-Y gastric bypass (RNYGB) surgery offers an effective and enduring treatment for morbid obesity. Gastric bypass may alter gastrointestinal (GI) flora possibly resulting in bacterial overgrowth and dysmotility. Our hypothesis was that daily use of probiotics would improve GI outcomes after RNYGB.Methods: Forty-four patients undergoing RNYGB were randomized to either a probiotic or control group; 2.4 billion colonies of Lactobacillus were administered daily postoperatively to the probiotic group. The outcomes of H(2) levels indicative of bacterial overgrowth, GI-related quality of life (GIQoL), serologies, and weight loss were measured preoperatively and at 3 and 6 months postoperatively. Categorical variables were analyzed by chi(2) test and continuous variables were analyzed by t test with a p < 0.05 for significance.Results: At 6 months, a statistically significant reduction in bacterial overgrowth was achieved in the probiotic group with a preoperative to postoperative change of sum H(2) part per million (probiotics = -32.13, controls = 0.80). Surprisingly, the probiotic group attained significantly greater percent excess weight loss than that of control group at 6 weeks (controls = 25.5%, probiotic = 29.9%) and 3 months (38.55%, 47.68%). This trend also continued but was not significant at 6 months (60.78%, 67.15%). The probiotic group had significantly higher postoperative vitamin B12 levels than the control group. Both probiotic and control groups significantly improved their GIQoL.Conclusion: In this novel study, probiotic administration improves bacterial overgrowth, vitamin B12 availability, and weight loss after RNYGB. These data may provide further evidence that altering the GI microbiota can influence weight loss. [ABSTRACT FROM AUTHOR]

Background: The authors believe it would be useful to have surgical robots capable of some degree of autonomous action in cooperation with the human members of a surgical team. They believe that a starting point for such development would be a system for delivering and retrieving instruments during a surgical procedure.Methods: The described robot delivers instruments to the surgeon and retrieves the instruments when they are no longer being used. Voice recognition software takes in requests from the surgeon. A mechanical arm with a gripper is used to handle the instruments. Machine-vision cameras locate the instruments after the surgeon puts them down. Artificial intelligence software makes decisions about the best response to the surgeon's requests.Results: A robot was successfully used in surgery for the first time June 16, 2005. The operation involved excision of a benign lipoma. The procedure lasted 31 min, during which time the robot performed 16 instrument deliveries and 13 instrument returns with no significant errors. The average time between verbal request and delivery of an instrument was 12.4 s.Conclusions: The described robot is capable of delivering instruments to a surgeon at command and can retrieve them independently using machine vision. This robot, termed a "surgical instrument server," represents a new class of information-processing machines that will relieve the operating room team of repetitive tasks and allow the members to focus more attention on the patient. [ABSTRACT FROM AUTHOR]

Background: Telomerase is detectable in 85% of cancers, but is largely repressed in normal tissues. Human telomerase RNA (hTR) inhibition is a promising anti-cancer strategy, but requires differential expression between malignant and normal tissue.Method: Archival paraffin sections from 48 oral squamous cell carcinomas (SCC) (23 floor of mouth, 25 tongue) and 56 oesophageal carcinomas (41 SCC, 15 adenocarcinomas) were evaluated for hTR expression using a radiolabelled riboprobe. Results were compared with expression in controls and adjacent histologically normal tissue. Statistical analysis was by the chi2 test.Results: hTR was detectable in 76% of oral SCC overall (floor of mouth 65%, tongue 88%, P=0.61), and in 54% of oesophageal cancers (SCC 51%, adenocarcinoma 60%, P=0.56). Detectable hTR expression was significantly more frequent in oral SCC than oesophageal SCC (P=0.01). hTR expression was only detected in normal tissue at low levels in basal squamous epithelium. There was agreement of hTR expression between 8/9 surgically excised carcinomas and their initial diagnostic biopsies.Conclusion: Tumour-specific hTR expression confirms hTR inhibition as a possible therapeutic strategy in some if not all oesophageal and oral cancers. Generally concordant hTR status between biopsy and resection suggest that biopsy may have a role in selecting candidates for telomerase inhibition therapy. [ABSTRACT FROM AUTHOR]

To determine if the risk of hip fracture difference between persons receiving benzodiazepines with long (greater than or equal to 24 hours) or short (less than 24 hours) elimination half-lives, we conducted a nested case-control study among residents of the Canadian province of Saskatchewan who were 65 years of age and older. We identified 4501 cases occurring between 1977 and 1985 from computerized hospital records and 24,041 population controls. Current benzodiazepine use, defined as having filled a prescription in the past 30 days, was ascertained from computerized pharmacy records. The relative risk of hip fracture was 1.7 (95% confidence interval, 1.5 to 2.0) for current users of long half-life benzodiazepines, in contrast to that of 1.1 (95% confidence interval, 0.9 to 1.3) for current users of short half-life drugs. This finding was not altered by sex, age, calendar year, nursing home residence, or history of hospitalization. Medical record review for a sample of 189 cases suggested that this finding was not due to confounding by dementia, ambulatory status, functional status, or body mass. [ABSTRACT FROM AUTHOR]