Anticancer potential of myricetin bulk and nano forms in vitro in lymphocytes from myeloma patients.

Evading apoptosis and chemo-resistance are considered as very important factors which help tumour progression and metastasis. Hence, to overcome chemo-resistance, there is an urgent requirement for emergence of more effective treatment options. Myricetin, a naturally occurring flavonoid, is present in various plant-derived foods and shows antitumour potential in different cancers. In the present in vitro study, results from the comet assay demonstrated that myricetin bulk (10 µM) and nano (20 µM) forms exhibited a non-significant level of genotoxicity in lymphocytes from multiple myeloma patients when compared to those from healthy individuals. Western blot results showed a decrease in Bcl-2/Bax ratio and an increase in P53 protein levels in lymphocytes from myeloma patients, but not in lymphocytes from healthy individuals. A significant increase in intracellular reactive oxygen species level was also observed, suggesting that regulation of apoptotic proteins triggered by myricetin exposure in lymphocytes from myeloma patients occurred through P53 and oxidative stress-dependent pathways. The potency of myricetin against lymphocytes from myeloma patients marks it a potential candidate to be considered as an alternative to overcome chemo-resistance in cancer therapies.

Outcome of autoimmune cytopenia after hematopoietic cell transplantation in primary immunodeficiency.

BACKGROUND: Post hematopoietic cell transplantation (HCT) autoimmune cytopenia (AIC) is a potentially life-threatening complication, but studies focusing on large cohorts of patients transplanted for primary immunodeficiency are lacking. OBJECTIVES: This study sought to determine the incidence, risk factors, and outcomes of post-HCT AIC and B-lymphocyte function following rituximab. METHODS: We retrospectively studied 502 children with primary immunodeficiency who were transplanted at our center between 1987 and 2018. RESULTS: Thirty-six patients (9%) developed post-HCT AIC, with a median onset of 6.5 months post-HCT. On univariate analysis, pre-HCT AIC, mismatched donor, alemtuzumab, anti-thymocyte antiglobulin, and acute and chronic graft versus host disease were significantly associated with post-HCT AIC. After multivariate analysis, alemtuzumab (subdistribution hazard ratio, 9.0; 95% CI, 1.50-54.0; P = .02) was independently associated with post-HCT AIC. Corticosteroid and high-dose intravenous immunoglobulin achieved remission in 50% (n = 18), additional rituximab led to remission in 25% (n = 9), and the remaining 25% were treated with a combination of various modalities including sirolimus (n = 5), bortezomib (n = 3), mycophenolate mofetil (n = 2), splenectomy (n = 2), and second HCT (n = 3). The mortality of post-HCT AIC reduced from 25% (4 of 16) prior to 2011 to 5% (1 of 20) after 2011. The median follow-up of 5.8 years (range, 0.4 to 29.1 years) showed that 26 of 30 survivors (87%) were in complete remission, and 4 were in remission with ongoing sirolimus and low-dose steroids. Of the 17 who received rituximab, 7 had B-lymphocyte recovery, 5 had persistent low B-lymphocyte count and remained on intravenous immunoglobulin replacement, 2 had second HCT, and 3 died. CONCLUSIONS: The frequency of post HCT AIC in our cohort was 9%, and the most significant risk factors for its occurrence were the presence of graft versus host disease and the use of alemtuzumab.

Leadership, Engineering and Ethical Clashes at Boeing.

When there are disasters in our society, whether on an individual, organizational or systemic level, individuals or groups of individuals are often singled out for blame, and commonly it is assumed that the alleged culprits engaged in deliberate misdeeds. But sometimes, at least, these disasters occur not because of deliberate malfeasance, but rather because of complex organizational and systemic circumstances that result in these negative outcomes. Using the Boeing Corporation and its 737 MAX aircraft crashes as an example, this ethical analysis will examine some of the organizational problems that led to changes in management in Boeing and ultimately resulted in the fatal accidents. We will examine ethical blind spots within the company that led to the deadly accidents, and we will study the kinds of circumstances that are particularly acute in organizations such as Boeing, and which contributed to the malfunctions in the 737 MAX and the two resulting crashes. The Boeing 737 MAX example is not a singular case, but rather shares similarities with other engineering disasters such as the Challenger and Columbia explosions, and the ignition switch failures at General Motors each of which seem to have been at least partly the result of organizational shortcomings involving a compromise in commitment to safety. These parallels lead us to conclude that organizational malfeasance poses a serious ethical challenge for engineers and their organizations. We will conclude with some tentative suggestions for avoiding such tragic incidents in the future.

ROS-induced oxidative damage in lymphocytes ex vivo/in vitro from healthy individuals and MGUS patients: protection by myricetin bulk and nanoforms.

We investigated the protective role of myricetin bulk and nanoforms, against reactive oxygen species (ROS)-induced oxidative stress caused by hydrogen peroxide and tertiary-butyl hydro peroxide in lymphocytes in vitro from healthy individuals and those from pre-cancerous patients suffering with monoclonal gammopathy of undetermined significance (MGUS). The change in intracellular reactive oxygen species was measured once cells were treated with myricetin bulk forms and nanoforms with and without either hydrogen peroxide or tertiary-butyl hydro peroxide co-supplementation. The direct and indirect antioxidant activity of myricetin was spectrofluometrically measured using the fluorescent dye 2',7'-dichlorofluorescin diacetate and using the Comet assay, respectively. Hydrogen peroxide (50 µM) and tertiary-butyl hydro peroxide (300 µM) induced a higher level of reactive oxygen species-related DNA damage and strand breaks. Addition of myricetin nanoform (20 µM) and bulk (10 µM) form could, however, significantly prevent hydrogen peroxide- and tertiary-butyl hydro peroxide-induced oxidative imbalances and the nanoform was more effective. Glutathione levels were also quantified using a non-fluorescent dye. Results suggest that myricetin treatment had no significant effect on the cellular antioxidant enzyme, glutathione. The current study also investigates the effect of myricetin on the induction of double-strand breaks by staining the gamma-H2AX foci immunocytochemically. It was observed that myricetin does not induce double-strand breaks at basal levels rather demonstrated a protective effect.

Ex vivo/in vitro protective effect of myricetin bulk and nano-forms on PhIP-induced DNA damage in lymphocytes from healthy individuals and pre-cancerous MGUS patients.

2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) is a central dietary mutagen, produced when proteinaceous food is heated at very high temperatures potentially causing DNA strand breaks. This study investigates the protective potential of a well-researched flavonoid, myricetin in its bulk and nano-forms against oxidative stress induced ex vivo/in vitro by PhIP in lymphocytes from pre-cancerous monoclonal gammopathy of undetermined significance (MGUS) patients and those from healthy individuals. The results from the Comet assay revealed that in the presence of myricetin bulk (10 µM) and myricetin nano (20 µM), the DNA damage caused by a high dose of PhIP (100 µM) was significantly (P < 0.001) reduced in both groups. However, nano has shown better protection in lymphocytes from pre-cancerous patients. Consistent results were obtained from the micronucleus assay where micronuclei frequency in binucleated cells significantly decreased upon supplementing PhIP with myricetin bulk (P < 0.01) and myricetin nano (P < 0.001), compared to the PhIP treatment alone. To briefly determine the cellular pathways involved in the protective role of myricetin against PhIP, we studied gene expression of P53 and ATR kinase (ATM- and Rad3-related), using the real-time PCR technique.

Later school start times for supporting the education, health, and well-being of high school students.

BACKGROUND: A number of school systems worldwide have proposed and implemented later school start times as a means of avoiding the potentially negative impacts that early morning schedules can have on adolescent students. Even mild sleep deprivation has been associated with significant health and educational concerns: increased risk for accidents and injuries, impaired learning, aggression, memory loss, poor self-esteem, and changes in metabolism. Although researchers have begun to explore the effects of delayed school start time, no one has conducted a rigorous review of evidence to determine whether later school start times support adolescent health, education, and well-being. OBJECTIVES: We aimed to assess the effects of a later school start time for supporting health, education, and well-being in high school students.Secondary objectives were to explore possible differential effects of later school start times in student subgroups and in different types of schools; to identify implementation practices, contextual factors, and delivery modes associated with positive and negative effects of later start times; and to assess the effects of later school start times on the broader community (high school faculty and staff, neighborhood, and families). SEARCH METHODS: We conducted the main search for this review on 28 October 2014 and updated it on 8 February 2016. We searched CENTRAL as well as 17 key electronic databases (including MEDLINE, Embase, ERIC, PsycINFO, and Sociological Abstracts), current editions of relevant journals and organizational websites, trial registries, and Google Scholar. SELECTION CRITERIA: We included any randomized controlled trials, controlled before-and-after studies, and interrupted time series studies with sufficient data points that pertained to students aged 13 to 19 years and that compared different school start times. Studies that reported either primary outcomes of interest (academic outcomes, amount or quality of sleep, mental health indicators, attendance, or alertness) or secondary outcomes (health behaviors, health and safety indicators, social outcomes, family outcomes, school outcomes, or community outcomes) were eligible. DATA COLLECTION AND ANALYSIS: At least two review authors independently determined inclusion and exclusion decisions through screening titles, abstracts, and full-text reports. Two review authors independently extracted data for all eligible studies. We presented findings through a narrative synthesis across all studies. When two or more study samples provided sufficient information to permit effect size calculations, we conducted random-effects meta-analyses to synthesize effects across studies. MAIN RESULTS: Our search located 17 eligible records reporting on 11 unique studies with 297,994 participants; the studies examined academic outcomes, amount and quality of sleep, mental health indicators, attendance, and student alertness. Overall, the quality of the body of evidence was very low, as we rated most studies as being at high or unclear risk of bias with respect to allocation, attrition, absence of randomization, and the collection of baseline data. Therefore, we cannot be confident about the effects of later school start times.Preliminary evidence from the included studies indicated a potential association between later school start times and academic and psychosocial outcomes, but quality and comparability of these data were low and often precluded quantitative synthesis. Four studies examined the association between later school start times and academic outcomes, reporting mixed results. Six studies examined effects on total amount of sleep and reported significant, positive relationships between later school start times and amount of sleep. One study provided information concerning mental health outcomes, reporting an association between decreased depressive symptoms and later school start times. There were mixed results for the association between later school start times and absenteeism. Three studies reported mixed results concerning the association between later school start times and student alertness. There was limited indication of potential adverse effects on logistics, as the qualitative portions of one study reported less interaction between parents and children, and another reported staffing and scheduling difficulties. Because of the insufficient evidence, we cannot draw firm conclusions concerning adverse effects at this time.It is important to note the limitations of this evidence, especially as randomized controlled trials and high-quality primary studies are difficult to conduct; school systems are often unwilling or unable to allow researchers the necessary control over scheduling and data collection. Moreover, this evidence does not speak to the process of implementing later school starts, as the included studies focused on reporting the effects rather than exploring the process. AUTHORS' CONCLUSIONS: This systematic review on later school start times suggests several potential benefits for this intervention and points to the need for higher quality primary studies. However, as a result of the limited evidence base, we could not determine the effects of later school start times with any confidence.

Simplifying medication regimens for residents of aged care facilities: Pharmacist and physician use of a structured five-step medication simplification tool.

BACKGROUND: Pharmacist-led medication regimen simplification using a structured approach can reduce unnecessary medication regimen complexity in residential aged care facilities (RACFs), but no studies have investigated simplification by different health professionals, nor the extent to which simplification is recommended during comprehensive medication reviews. OBJECTIVES: To compare medication regimen simplification opportunities identified by pharmacists, general medical practitioners (GPs), and geriatricians and to determine if pharmacists identified simplification opportunities during routinely conducted comprehensive medication reviews in RACFs for these same residents. METHODS: Three pharmacists, three GPs and three geriatricians independently applied the Medication Regimen Simplification Guide for Residential Aged CarE (MRS GRACE) to medication data for 83 residents taking medications at least twice daily. Interrater agreement was calculated using Fleiss's kappa. Pharmacist medication review reports for the same 83 residents were then examined to identify if the pharmacists conducting these reviews had recommended any of the simplification strategies. RESULTS: Overall, 77 residents (92.8 %) taking medications at least twice daily could have their medication regimen simplified by at least one health professional. Pharmacists independently simplified 53.0-77.1 % of medication regimens (Κ = 0.60, 95%CI 0.46-0.75, indicating substantial agreement), while GPs simplified 74.7-89.2 % (Κ = 0.44, 95%CI 0.24-0.64, moderate agreement) and geriatricians simplified 41.0-66.3 % (Κ = 0.30, 95%CI 0.16-0.44, fair agreement). No simplification recommendations were included in the reports previously prepared by pharmacists as part of the comprehensive medication reviews undertaken for these residents. CONCLUSION: Pharmacists, GPs, and geriatricians can all identify medication regimen simplification opportunities, although these opportunities differ within and between professional groups. Although opportunities to simplify medication regimens during comprehensive medication reviews exist, simplification is not currently routinely recommended by pharmacists performing these reviews in Australian RACFs.

Engineering ethics: looking back, looking forward.

The eight pieces constituting this Meeting Report are summaries of presentations made during a panel session at the 2011 Association for Practical and Professional Ethics (APPE) annual meeting held between March 3rd and 6th in Cincinnati. Lisa Newton organized the session and served as chair. The panel of eight consisted both of pioneers in the field and more recent arrivals. It covered a range of topics from how the field has developed to where it should be going, from identification of issues needing further study to problems of training the next generation of engineers and engineering-ethics scholars.

A comparison of maternal and perinatal outcomes with vaginal delivery: indicated induction versus spontaneous labor.

OBJECTIVE: To determine if there is a difference in the maternal and perinatal characteristics and outcomes of women undergoing a medically indicated labor induction and delivering vaginally compared to women in spontaneous labor delivering vaginally. METHODS: This is a planned secondary analysis of previously published data with additional data collected for a case-control design. Maternal and perinatal characteristics and outcomes of women undergoing a medically indicated labor induction of labor and delivering vaginally were compared with the next woman who went into labor spontaneously and delivered vaginally. RESULTS: There were 1097 women in the medically indicated labor group and 1096 women in the spontaneous labor group. The medically indicated induction group was younger (p < .0001), had less women of "other" race (p = .004), were of a lower gravidity and parity (p < .0001), had a lower Bishops' score on admission (p < .0001), had a greater proportion of umbilical arterial cord pH values <7.1 and <7.0 (p < .0001). Additionally, the induction group had longer first and second stages of labor (p < .0001). While the unadjusted rates of post-partum complications and NICU admission were higher in the medically indicated labor induction group, only cord gas pH <7.1 remained statistically significant after adjustment. CONCLUSION: Even with successful vaginal delivery of a medically indicated induction of labor, the risk for adverse outcomes remains elevated.

Program foundations and beginning of concerns (part 1 of 3). When residents shouldn't become clinicians: getting a grip on fair and defensible processes for termination of training.

Training programs have the dual responsibility of providing excellent training for their learners and ensuring their graduates are competent practitioners. Despite everyone's best efforts a small minority of learners will be unable to achieve competence and cannot graduate. Unfortunately, program decisions for training termination are often overturned, not because the academic decision was wrong, but because fair assessment processes were not implemented or followed. This series of three articles, intended for those setting residency program assessment policies and procedures, outlines recommendations, from establishing robust assessment foundations and the beginning of concerns (Part One), to established concerns and formal remediation (Part Two) to participating in formal appeals and after (Part Three). With these 14 recommendations on how to get a grip on fair and defensible processes for termination of training, career-impacting decisions that are both fair for the learner and defensible for programs are indeed possible. They are offered to minimize the chances of academic decisions being overturned, an outcome which wastes program resources, poses patient safety risks, and delays the resident finding a more appropriate career path. This article (part one in the series of three) will focus on the foundational aspects of residency training and the emergence of concerns.

Les programmes de formation ont la double responsabilité de fournir une excellente formation aux apprenants et de s'assurer qu'à l'issue de celle-ci les diplômés sont des praticiens compétents. Malgré tous les efforts déployés, une petite minorité d'apprenants ne parviendra pas à atteindre le niveau de compétence requis pour obtenir son diplôme. Malheureusement, la décision de la direction du programme de mettre fin à la formation d'un étudiant est souvent annulée, non pas parce qu'elle n'était pas académiquement fondée, mais parce qu'on a omis d'appliquer ou de suivre un processus d'évaluation juste. Cette série de trois articles, destinée aux responsables des politiques et procédures d'évaluation des programmes de résidence, présente des recommandations concernant l'établissement de bases d'évaluation solides et l'émergence de préoccupations quant à la progression d'un résident dans le programme (première partie), les préoccupations confirmées et la remédiation formelle (deuxième partie), et enfin le processus d'appel formel et ses suites (troisième partie). La mise en œuvre de ces 14 recommandations sur la définition de processus justes et légitimes pour mettre fin à la formation d'un apprenant devrait permettre de prendre des décisions aux répercussions importantes pour la carrière qui sont néanmoins à la fois justes envers la personne et justifiées du point de vue du programme. Elles sont proposées pour éviter la révision des décisions de nature académique, qui entraîne un gaspillage de ressources pour le programme, pose des risques pour la sécurité des patients et retarde la recherche d'un cheminement de carrière plus approprié pour le résident. Cette première partie de la série de trois articles se concentre sur les aspects fondamentaux de la formation en résidence et sur l'émergence de préoccupations.

Formal remediation and probation (part 2 of 3). When residents shouldn't become clinicians: getting a grip on fair and defensible processes for termination of training.

Training programs have the dual responsibility of providing excellent training for their learners and ensuring their graduates are competent practitioners. Despite everyone's best efforts a small minority of learners will be unable to achieve competence and cannot graduate. Unfortunately, program decisions for training termination are often overturned, not because the academic decision was wrong, but because fair assessment processes were not implemented or followed. This series of three articles, intended for those setting residency program assessment policies and procedures, outlines recommendations, from establishing robust assessment foundations and the beginning of concerns (Part One), to established concerns and formal remediation (Part Two) to participating in formal appeals and after (Part Three). With these 14 recommendations on how to get a grip on fair and defensible processes for termination of training, career-impacting decisions that are both fair for the learner and defensible for programs are indeed possible. They are offered to minimize the chances of academic decisions being overturned, an outcome which wastes program resources, poses patient safety risks, and delays the resident finding a more appropriate career path. This article (Part Two in the series of three) will focus on what to do when concerns become established, and a formal remediation or probation is necessary.

Les programmes de formation ont la double responsabilité de fournir une excellente formation aux apprenants et de s'assurer qu'à l'issue de celle-ci les diplômés sont des praticiens compétents. Malgré tous les efforts déployés, une petite minorité d'apprenants ne parviendra pas à atteindre le niveau de compétence requis pour obtenir son diplôme. Malheureusement, la décision de la direction du programme de mettre fin à la formation d'un étudiant est souvent annulée, non pas parce qu'elle n'était pas académiquement fondée, mais parce qu'on a omis d'appliquer ou de suivre un processus d'évaluation juste. Cette série de trois articles, destinée aux responsables des politiques et procédures d'évaluation des programmes de résidence, présente des recommandations concernant l'établissement de bases d'évaluation solides et l'émergence de préoccupations quant à la progression d'un résident dans le programme (première partie), les préoccupations confirmées et la remédiation formelle (deuxième partie), et enfin le processus d'appel formel et ses suites (troisième partie). La mise en œuvre de ces 14 recommandations sur la définition de processus justes et légitimes pour mettre fin à la formation d'un apprenant devrait permettre de prendre des décisions aux répercussions importantes pour la carrière qui sont néanmoins à la fois justes envers la personne et justifiées du point de vue du programme. Elles sont proposées pour éviter la révision des décisions de nature académique, qui entraîne un gaspillage de ressources pour le programme, pose des risques pour la sécurité des patients et retarde la recherche d'un cheminement de carrière plus approprié pour le résident. Cet article (le deuxième d'une série en trois parties) traite de ce qu'il faut faire lorsque les préoccupations sont établies et qu'une remédiation formelle ou une probation est nécessaire.

The appeal process and beyond (part 3 of 3). When residents shouldn't become clinicians: getting a grip on fair and defensible processes for termination of training.

Training programs have the dual responsibility of providing excellent training for their learners and ensuring their graduates are competent practitioners. Despite everyone's best efforts a small minority of learners will be unable to achieve competence and cannot graduate. Unfortunately, program decisions for training termination are often overturned, not because the academic decision was wrong, but because fair assessment processes were not implemented or followed. This series of three articles, intended for those setting residency program assessment policies and procedures, outlines recommendations, from establishing robust assessment foundations and the beginning of concerns (Part One), to established concerns and formal remediation (Part Two) to participating in formal appeals and after (Part Three). With these 14 recommendations on how to get a grip on fair and defensible processes for termination of training, career-impacting decisions that are both fair for the learner and defensible for programs are indeed possible. They are offered to minimize the chances of academic decisions being overturned, an outcome which wastes program resources, poses patient safety risks, and delays the resident finding a more appropriate career path. This article (Part Three in the series of three) will focus on the formal appeals and what to do after the appeal.

Les programmes de formation ont la double responsabilité de fournir une excellente formation aux apprenants et de s'assurer qu'à l'issue de celle-ci les diplômés sont des praticiens compétents. Malgré tous les efforts déployés, une petite minorité d'apprenants ne parviendra pas à atteindre le niveau de compétence requis pour obtenir son diplôme. Malheureusement, la décision de la direction du programme de mettre fin à la formation d'un étudiant est souvent annulée, non pas parce qu'elle n'était pas académiquement fondée, mais parce qu'on a omis d'appliquer ou de suivre un processus d'évaluation juste. Cette série de trois articles, destinée aux responsables des politiques et procédures d'évaluation des programmes de résidence, présente des recommandations concernant l'établissement de bases d'évaluation solides et l'émergence de préoccupations quant à la progression d'un résident dans le programme (première partie), les préoccupations confirmées et la remédiation formelle (deuxième partie), et enfin le processus d'appel formel et ses suites (troisième partie). La mise en œuvre de ces 14 recommandations sur la définition de processus justes et légitimes pour mettre fin à la formation d'un apprenant devrait permettre de prendre des décisions aux répercussions importantes pour la carrière qui sont néanmoins à la fois justes envers la personne et justifiées du point de vue du programme. Elles sont proposées pour éviter la révision des décisions de nature académique, qui entraîne un gaspillage de ressources pour le programme, pose des risques pour la sécurité des patients et retarde la recherche d'un cheminement de carrière plus approprié pour le résident. Cet article (le troisième d'une série en trois parties) portera sur les appels formels et sur ce qu'il conviendrait de faire à la suite de l'appel.

An in vitro investigation into the protective and genotoxic effects of myricetin bulk and nano forms in lymphocytes of MGUS patients and healthy individuals.

The present study investigated the genoprotective and genotoxic effects of myricetin bulk (10 µM) and nano forms (20 µM) in the lymphocytes from pre-cancerous, monoclonal gammopathy of unknown significance (MGUS) patients and healthy individuals using the Comet and micronucleus assays. The study also evaluated the effect of myricetin on P53 expression levels, using the Western blot technique. Results showed that throughout the in-vitro treatment, lymphocytes from the patients group had higher levels of baseline DNA damage compared to the healthy group. Myricetin in both forms induced significant DNA damage, only at higher concentrations (>40 µM). The micronucleus assay showed a significant reduction (P < 0.01) in the frequency of micronuclei in mono-nucleated cells in the patient group treated with the nano form of myricetin at the non-toxic dose of 20 µM. There was a significant increase in both gene and protein P53 levels in lymphocytes isolated from healthy individuals and pre-cancerous patients. These results suggested a protective effect of myricetin and indicated its nutritional supplement potential for protection against cancer development among patients suffering from MGUS.

Proactive approaches to identifying dementia and dementia risk; a qualitative study of public attitudes and preferences.

OBJECTIVES: The aim of this study was to critically explore the views of the public about the acceptability and feasibility of proactive approaches to earlier dementia diagnosis and also identification of people at high risk of dementia. DESIGN: Qualitative study using task group methodology and thematic data analysis. SETTING: Task groups were held either at the university (n=5) or at a carers' centre (n=1). PARTICIPANTS: A convenience sample of 31 of 54 participants identified by local non-statutory agencies took part in a task group. All were aged between 40 years and 80 years, 21 were women and 10men participated. RESULTS: Despite the use of task group methodology, participants expressed limited understandings of dementia and confusion between proactive approaches. Nevertheless, they highlighted a range of potential benefits and limitations of proactive approaches and the ethical issues raised. There was a preference to embed risk assessment within routine health checks, which focused on achieving a healthier lifestyle, rather than specifically on dementia. Participants emphasised the need to ensure informed consent prior to use of proactive approaches and to provide appropriate support. They also suggested alternative approaches that could potentially facilitate the early detection of dementia or reduce risk at a population level. CONCLUSIONS: As international policy on dementia shifts towards a prevention agenda there is growing interest in identifying those at risk of developing dementia. This study provides useful insights into the acceptability of the use of such proactive approaches among the public. The introduction of proactive approaches to dementia identification raises complex practical and ethical issues, particularly in the context of low public understanding of dementia. The importance of better quality information about dementia (and the likelihood of developing dementia) and provision of psychological support for those undergoing risk assessment were highlighted.

Increased cerebellar vermis white-matter volume in men with schizophrenia.

We aimed to investigate cerebellar structural abnormalities and their functional significance in patients with schizophrenia. Forty right-handed men with schizophrenia and 40 sex, age and handedness matched controls underwent a volumetric magnetic resonance scan with 1 mm3 isotropic spatial resolution. Cerebellar grey- and white-matter volumes were analysed using voxel-based morphometry. Patients with schizophrenia completed a battery of neuropsychological tests assessing sustained attention (continuous performance test), memory (Hopkins memory test) and executive function (verbal fluency and Wisconsin card sorting tests). Patients with schizophrenia exhibited significantly increased cerebellar vermis white-matter volume compared with controls. By contrast, total cerebellar volume, and grey- and white-matter volumes of cerebellar hemispheres were not significantly different between groups. Increased vermis white-matter volume in patients was associated with poor verbal fluency performance. We concluded that increased white-matter in the cerebellar vermis, possibly suggesting anomalous connectivity, may be associated with verbal executive dysfunction in men with chronic schizophrenia.

Urethral Diverticulum Presenting as a Large Vaginal Mass Complicating Pregnancy and Delivery.

BACKGROUND A case report of urethral diverticulum complicating pregnancy is presented. The diagnosis and management are challenging because of the rare nature of this condition, the varied presentations and differential diagnoses, and the possibility of misdiagnosis. CASE REPORT A 25-year-old primigravida with scheduled induction of labor at 39 weeks gestation due to gestational diabetes mellitus presented for a routine antenatal appointment at 38 weeks and four days. On digital cervical examination, she was found to have a large semi-solid anterior vaginal mass, shown by trans-vaginal ultrasound to have a nearly solid appearance of a 5×7 cm mass with septation. Maternal Fetal Medicine and Gynecologic Oncology consultations were obtained primary cesarean section with vaginal biopsy in the Operating Room were recommended. Following an uncomplicated cesarean delivery and with the patient still under spinal anesthesia, the anterior vaginal mass was examined and found to contain 200 ml of purulent material. Because a diagnosis of urethral diverticulum was made, a biopsy was not performed. The patient was placed on antibiotic prophylaxis for the remainder of her hospital course. Follow-up CT scan confirmed a large urethral diverticulum, and she was referred to the Fetal Pelvic Medicine and Reconstructive Surgery (FPMRS) and Urogynecology units for treatment. CONCLUSIONS Early identification of urethral diverticulum during the pregnancy may allow for treatment and a trial of labor with vaginal delivery. MRI is the recommended imaging modality in identifying urethral diverticulum.

A new dissimilarity measure for finding semantic structure in category fluency data with implications for understanding memory organization in schizophrenia.

The ordering of words in category fluency lists is indicative of the semantic distance between items in conceptual memory. Several studies have concluded from structural analyses of such data, using cluster analysis or multidimensional scaling, that the semantic memory of patients with schizophrenia is more disorganized than that of controls. Previous studies have based their analyses on a measure of average interitem dissimilarity devised by A. S. Chan et al. (1993). Here the authors derive a new and improved method of determining dissimilarity and show that when this measure is applied to the fluency lists of patients with schizophrenia, the average pattern of organization for the animal category has similar structure to that of controls, but with greater variability between individuals.

The provision of assistive technology products and services for people with dementia in the United Kingdom.

In this review we explore the provision of assistive technology products and services currently available for people with dementia within the United Kingdom. A scoping review of assistive technology products and services currently available highlighted 171 products or product types and 331 services. In addition, we assimilated data on the amount and quality of information provided by assistive technology services alongside assistive technology costs. We identify a range of products available across three areas: assistive technology used 'by', 'with' and 'on' people with dementia. Assistive technology provision is dominated by 'telecare' provided by local authorities, with services being subject to major variations in pricing and information provision; few currently used available resources for assistive technology in dementia. We argue that greater attention should be paid to information provision about assistive technology services across an increasingly mixed economy of dementia care providers, including primary care, local authorities, private companies and local/national assistive technology resources.

Exploring the views of GPs, people with dementia and their carers on assistive technology: a qualitative study.

OBJECTIVES: To explore the views and experiences of people with dementia, their family carers and general practitioners (GPs) on their knowledge and experience of accessing information about, and use of, assistive technology (AT) in dementia care. DESIGN: Qualitative methods with semistructured interviews and thematic analysis. PARTICIPANTS: 56 participants comprising 17 GPs, 13 people with dementia and 26 family carers. SETTING: Community care settings in the North East of England. RESULTS: 4 main themes emerged: awareness and experience of AT; accessing information on AT; roles and responsibilities in the current care system and the future commissioning of AT services. All participants had practical experience of witnessing AT being used in practice. For people with dementia and their families, knowledge was usually gained from personal experience rather than from health and social care professionals. For GPs, knowledge was largely gained through experiential, patient-led learning. All groups acknowledged the important role of the voluntary sector but agreed a need for clear information pathways for AT; such pathways were perceived to be essential to both service providers and service commissioners. CONCLUSIONS: People with dementia and their family carers appear to be mainly responsible for driving a gradual increase in both awareness and the use of AT in dementia care. GPs should be equipped with the relevant knowledge to ensure families living with dementia receive appropriate information and support to enable them to live independently for as long as possible. There is an urgent need to simplify current complex community care pathways; as demonstrated in other chronic health conditions, a single point of access and a named lead professional may improve future care.

The turn to the local: the possibility of returning health care to the community.

It is not too early to suggest that the attempts to place medical cae in private hands (through group insurance arrangements) has not fulfilled its promise--or better, the promises that were made for it. Yet history has not been kind to plans to make government the single payer, and the laudable progress in medical technology has placed high-technology medical care beyond the reach of most private budgets. In this paper I suggest that the major problem of the U.S. health care system as presently conceived is a failure of legitimacy, and I put forward a proposal that purports to solve that problem. The proposal is to localize health care, on the model of a public school system, on the argument that such localization will answer most of the questions of legitimacy at the core of the private insurance imbroglio, provide a brake for medical costs, while preserving our ability to take advantage of the most advanced medical interventions. I present some initial arguments for the proposal, but await its proof in the dialogue emerging as the present insurance system collapses.