Detection of cognitive impairment with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in adolescents with psychotic symptomatology.

Cognitive impairment has been identified in the early phase of schizophrenia spectrum disorders, and is a major contributor to disease-related disability. While screening tools assessing cognitive impairment have been validated for adult schizophrenic populations, there is a need for brief, easily administered, standardized instruments that provide clinically relevant information for adolescents. This study examines the utility of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in identifying and quantifying neurocognitive impairment in adolescents with schizophrenia spectrum disorders and other serious psychiatric illnesses. 112 adolescents, including 32 healthy subjects and 80 patients, were administered the RBANS. Patients with psychotic disorders demonstrated significant impairment on the RBANS total score compared to patients with other disorders and healthy controls, but this impairment appeared somewhat less severe than is typically reported for in adult patients with schizophrenia on this measure. The RBANS appears to be sensitive in the detection of neurocognitive impairment in a psychiatric population of adolescents with psychotic symptomatology, and may therefore have utility as a clinical screening instrument and/or neurocognitive outcome measure in this population.

Therapeutic Drug Monitoring of the new targeted anticancer agents imatinib, nilotinib, dasatinib, sunitinib, sorafenib and lapatinib by LC tandem mass spectrometry.

The treatment of some cancer patients has shifted from traditional, non-specific cytotoxic chemotherapy to chronic treatment with molecular targeted therapies. Imatinib mesylate, a selective inhibitor of tyrosine kinases (TKIs) is the most prominent example of this new era and has opened the way to the development of several additional TKIs, including sunitinib, nilotinib, dasatinib, sorafenib and lapatinib, in the treatment of various hematological malignancies and solid tumors. All these agents are characterized by an important inter-individual pharmacokinetic variability, are at risk for drug interactions, and are not devoid of toxicity. Additionally, they are administered for prolonged periods, anticipating the careful monitoring of their plasma exposure via Therapeutic Drug Monitoring (TDM) to be an important component of patients' follow-up. We have developed a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) requiring 100 microL of plasma for the simultaneous determination of the six major TKIs currently in use. Plasma is purified by protein precipitation and the supernatant is diluted in ammonium formate 20 mM (pH 4.0) 1:2. Reverse-phase chromatographic separation of TKIs is obtained using a gradient elution of 20 mM ammonium formate pH 2.2 and acetonitrile containing 1% formic acid, followed by rinsing and re-equilibration to the initial solvent composition up to 20 min. Analyte quantification, using matrix-matched calibration samples, is performed by electro-spray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effects variability (<9.6%), overall process efficiency (87.1-104.2%), as well as TKIs short- and long-term stability in plasma. The method is precise (inter-day CV%: 1.3-9.4%), accurate (-9.2 to +9.9%) and sensitive (lower limits of quantification comprised between 1 and 10 ng/mL). This is the first broad-range LC-MS/MS assay covering the major currently in-use TKIs. It is an improvement over previous methods in terms of convenience (a single extraction procedure for six major TKIs, reducing significantly the analytical time), sensitivity, selectivity and throughput. It may contribute to filling the current knowledge gaps in the pharmacokinetics/pharmacodynamics relationships of the latest TKIs developed after imatinib and better define their therapeutic ranges in different patient populations in order to evaluate whether a systematic TDM-guided dose adjustment of these anticancer drugs could contribute to minimize the risk of major adverse reactions and to increase the probability of efficient, long lasting, therapeutic response.

An empirical hierarchical Bayesian unification of occupational exposure assessment methods.

In occupational exposure assessment of airborne contaminants, exposure levels can either be estimated through repeated measurements of the pollutant concentration in air, expert judgment or through exposure models that use information on the conditions of exposure as input. In this report, we propose an empirical hierarchical Bayesian model to unify these approaches. Prior to any measurement, the hygienist conducts an assessment to generate prior distributions of exposure determinants. Monte-Carlo samples from these distributions feed two level-2 models: a physical, two-compartment model, and a non-parametric, neural network model trained with existing exposure data. The outputs of these two models are weighted according to the expert's assessment of their relevance to yield predictive distributions of the long-term geometric mean and geometric standard deviation of the worker's exposure profile (level-1 model). Bayesian inferences are then drawn iteratively from subsequent measurements of worker exposure. Any traditional decision strategy based on a comparison with occupational exposure limits (e.g. mean exposure, exceedance strategies) can then be applied. Data on 82 workers exposed to 18 contaminants in 14 companies were used to validate the model with cross-validation techniques. A user-friendly program running the model is available upon request.

Evaluation of organ-specific peripheral doses after 2-dimensional, 3-dimensional and hybrid intensity modulated radiation therapy for breast cancer based on Monte Carlo and convolution/superposition algorithms: implications for secondary cancer risk assessment.

To make a comprehensive evaluation of organ-specific out-of-field doses using Monte Carlo (MC) simulations for different breast cancer irradiation techniques and to compare results with a commercial treatment planning system (TPS). Three breast radiotherapy techniques using 6MV tangential photon beams were compared: (a) 2DRT (open rectangular fields), (b) 3DCRT (conformal wedged fields), and (c) hybrid IMRT (open conformal+modulated fields). Over 35 organs were contoured in a whole-body CT scan and organ-specific dose distributions were determined with MC and the TPS. Large differences in out-of-field doses were observed between MC and TPS calculations, even for organs close to the target volume such as the heart, the lungs and the contralateral breast (up to 70% difference). MC simulations showed that a large fraction of the out-of-field dose comes from the out-of-field head scatter fluence (>40%) which is not adequately modeled by the TPS. Based on MC simulations, the 3DCRT technique using external wedges yielded significantly higher doses (up to a factor 4-5 in the pelvis) than the 2DRT and the hybrid IMRT techniques which yielded similar out-of-field doses. In sharp contrast to popular belief, the IMRT technique investigated here does not increase the out-of-field dose compared to conventional techniques and may offer the most optimal plan. The 3DCRT technique with external wedges yields the largest out-of-field doses. For accurate out-of-field dose assessment, a commercial TPS should not be used, even for organs near the target volume (contralateral breast, lungs, heart).

An Assessment of the Microbiology of Hand Contact Surfaces in the Retail Environment

This study aimed to assess the microbiology of food and hand contact surfaces in the retail environment and the potential for these surfaces to act as vehicles for the spread of foodborne pathogens. During the survey, 10 stores in the Republic of Ireland (ROI) were visited by student Environmental Health Officers (EHOs) who took swab samples from four surfaces: conveyor belts, long-life shopping bags, shopping trolley handles and keypads on card payment units. The swab samples were examined for the presence of the pathogens Salmonella, Campylobacter and Listeria. The Aerobic Colony Counts, as well as the levels of E. coli and Enterobacteriaceae, were also determined. In addition, structured questionnaires were used with retailers to establish the stores’ regimes for the cleaning of conveyor belts. Similarly, shoppers donating their long-life shopping bags for sampling were questioned about how they normally use these bags, and the results were compared with those from the microbiological survey. The results indicated that the hygiene of the surfaces sampled was good, with Salmonella, Campylobacter and Listeria not detected in any of the samples, and levels of both Enterobacteriaceae and E. coli were below the limits of detection in all but one sample. Aerobic Colony Counts varied but none of the results obtained would be deemed ‘unacceptable’ or ‘unsatisfactory’ under guidelines for ready-to-eat foods

Engineering, conjugation, and immunogenicity assessment of Escherichia coli O121 O antigen for its potential use as a typhoid vaccine component.

State-of-the-art production technologies for conjugate vaccines are complex, multi-step processes. An alternative approach to produce glycoconjugates is based on the bacterial N-linked protein glycosylation system first described in Campylobacter jejuni. The C. jejuni N-glycosylation system has been successfully transferred into Escherichia coli, enabling in vivo production of customized recombinant glycoproteins. However, some antigenic bacterial cell surface polysaccharides, like the Vi antigen of Salmonella enterica serovar Typhi, have not been reported to be accessible to the bacterial oligosaccharyltransferase PglB, hence hamper development of novel conjugate vaccines against typhoid fever. In this report, Vi-like polysaccharide structures that can be transferred by PglB were evaluated as typhoid vaccine components. A polysaccharide fulfilling these requirements was found in Escherichia coli serovar O121. Inactivation of the E. coli O121 O antigen cluster encoded gene wbqG resulted in expression of O polysaccharides reactive with antibodies raised against the Vi antigen. The structure of the recombinantly expressed mutant O polysaccharide was elucidated using a novel HPLC and mass spectrometry based method for purified undecaprenyl pyrophosphate (Und-PP) linked glycans, and the presence of epitopes also found in the Vi antigen was confirmed. The mutant O antigen structure was transferred to acceptor proteins using the bacterial N-glycosylation system, and immunogenicity of the resulting conjugates was evaluated in mice. The conjugate-induced antibodies reacted in an enzyme-linked immunosorbent assay with E. coli O121 LPS. One animal developed a significant rise in serum immunoglobulin anti-Vi titer upon immunization.

Accident & Emergency Nursing Assessment of Deliberate Self Harm. Exploring the Impact of Introducing a Suicide Education Programme and a Suicide Intent Scale into A&E/MAU Nursing Practice: A Pilot Study

A proposal to pilot nursing assessment of self harm in Accident and Emergency Departments (A&E) was developed by key stakeholders in nurse education and suicide prevention in the South East and submitted to the National Council for the Professional Development of Nursing and Midwifery in April 2002.The proposal included the introduction of a suicide intent scale. Following an initial training programme, a suicide intent scale was utilised by nursing staff in A&E and the Medical Assessment Unit (MAU),Wexford General Hospital and evaluated over a period of nine months. Four months into the study the National Suicide Research Foundation (NSRF) was invited to collaboratively prepare a successful submission to the Health Research Board (HRB) as part of ‘Building Partnerships for a Healthier Future Research Awards 2004’. The NSRF undertook independent scientific evaluation of the outcomes of the suicide awareness programme. The study is in line with priorities determined by Reach Out, the National Strategy for Action on Suicide Prevention 2005-2014 (HSE, 2005) and the HSE-South East Suicide Prevention Programme through raising nursing staff awareness of the public health issue of suicide/deliberate self harm and by improving the efficiency and quality of nursing services offered to persons who present to acute hospitals with deliberate self harm. The study findings indicate evidence to positively support nursing assessment of DSH using a suicide intent scale in terms of assessing behavioural characteristics of individual clients and their suicide risk. Enhanced confidence levels of nursing personnel in caring for suicidal clients was demonstrated by staff who participated in an education programme related to risk assessment and specifically the use of a suicide intent scale.This resource was contributed by The National Documentation Centre on Drug Use.

Psychosis with coexisting substance misuse: assessment and management in adults and young people.

This guideline offers best practice advice on the assessment and management of people with psychosis and coexisting substance misuse. Psychosis is a condition that affects a person’s mental state, including their thoughts, mood and behaviour. The symptoms of psychosis are:• hallucinations – hearing voices and sometimes seeing things that are not really there• delusions – having fixed beliefs that are false but which the person believes in completely. Substance misuse is a broad term encompassing, in this guideline, the harmful use of any psychotropic substance, including alcohol and either legal or illicit drugs. Use of such substances is harmful when it has a negative effect on a person’s life, including their physical and mental health, relationships, work, education and finances or leads to offending behaviour.This resource was contributed by The National Documentation Centre on Drug Use.

Functional assessment of chest wall integrity after methylmethacrylate reconstruction.

BACKGROUND: All patients with extensive resection of the anterolateral chest wall and the sternum followed by reconstruction with methylmethacrylate substitutes were assessed prospectively 6 months after the operation to delineate chest wall integrity with pulmonary function and cine-magnetic resonance imaging. METHODS: Twenty-six patients underwent chest wall reconstruction by use of methylmethacrylate between 1994 and 1998 due to primary tumors in 35%, metastases in 27%, T3 lung cancer in 19%, and debridement for radionecrosis and osteomyelitis in 19% of patients. Three to eight ribs were resected and additional sternum resection was performed in 39% of patients. RESULTS: There was no 30-day mortality. All patients were extubated after the operation without need for reintubation. Prosthesis dislocation occurred in 1 patient and infection in 2 patients during follow-up. Nineteen patients (73%) suffered no restrictions of daily activities. Clinical examination revealed normal shoulder girdle function in 77% of patients. There was no significant difference between preoperative and postoperative FEV1 (forced expiratory volume in 1 second) measurements in patients with lobectomy or wedge resections. Cinemagnetic resonance imaging revealed concordant chest wall movements during respiration in 92% of patients without paradoxical movements or implant dislocations being observed. CONCLUSIONS: Large defects of the anterolateral chest wall and sternum can be reconstructed efficiently with methylmethacrylate substitutes with minimal morbidity and excellent cosmetic and functional outcome.

Critical evaluation of outcome scales assessment of lateral ankle ligament reconstruction

Introduction: Les résultats d'une chirurgie du pied et de la cheville peuvent être évalués par des scores spécifiques à la région anatomique ainsi que par des scores spécifiques à la pathologie. Beaucoup de scores existent rendant la comparaison entre les études difficile. La présente étude se focalise sur une pathologie fréquente du pied et de la cheville et compare les résultats obtenu par deux scores spécifiques à la région et deux scores spécifiques à la pathologie. Méthode: Nous avons revu 41 patients ayant bénéficié d'une plastie ligamentaire externe de la cheville. Quatre scores ont été administrés simultanément: the Cumberland Ankle Instability Tool (CAIT) et the Chronic Ankle Instability Scale (CAIS), spécifiques à la pathologie, the American Orthopedic Foot & Ankle Society (AOFAS) hindfoot scale et the Foot and Ankle Ability Measure comprenant deux parties (FAAM1 et FAAM2), spécifiques à la région anatomique. Le degré de corrélation entre les scores a été évalué par le coefficient de corrélation de Pearson. L'analyse graphique des variances a été utilisée pour le choix de tests paramétriques versus non paramétriques. Des tests non paramétriques, le Kruskal-Wallis pour éliminer l'hypothèse nulle et le Mann-Whitney pour la comparaison entre les scores deux à deux, ont été utilisés. Résultats: Une différence significative (p<.005) a été démontrée entre le CAIS et l'AOFAS (p=.0002), entre le CAIS et le FAAM1 (p=.0001) et entre le CAIT et l'AOFAS (p=.0003) Conclusions: Cette étude compare les performances de quatre scores dont deux spécifiques à la région anatomique et deux spécifiques à la pathologie. Nous avons démontré une bonne corrélation entre les scores ainsi que des différences significatives entre les résultats obtenus par chacun d'eux. Les résultats obtenus par les scores spécifiques à la pathologie semblent être plus précis que ceux obtenus par les scores spécifiques à la région anatomique. De plus, nous avons mis en évidence une forte corrélation entre l'AOFAS et les autres scores. Le FAAM semble être un bon compromis car il offre la possibilité, du fait de ses deux parties, d'évaluer le résultat en fonction de la demande fonctionnelle du patient. Perspectives: Un algorithme est proposé qui permet d'évaluer la littérature spécifique de manière plus critique et peut s'adapter également à la recherche et à la clinique relative à d'autres pathologies du pied et de la cheville

Will climate change drive alien invasive plants into areas of high protection value? An improved model-based regional assessment to prioritise the management of invasions.

Species distribution models (SDMs) studies suggest that, without control measures, the distribution of many alien invasive plant species (AIS) will increase under climate and land-use changes. Due to limited resources and large areas colonised by invaders, management and monitoring resources must be prioritised. Choices depend on the conservation value of the invaded areas and can be guided by SDM predictions. Here, we use a hierarchical SDM framework, complemented by connectivity analysis of AIS distributions, to evaluate current and future conflicts between AIS and high conservation value areas. We illustrate the framework with three Australian wattle (Acacia) species and patterns of conservation value in Northern Portugal. Results show that protected areas will likely suffer higher pressure from all three Acacia species under future climatic conditions. Due to this higher predicted conflict in protected areas, management might be prioritised for Acacia dealbata and Acacia melanoxylon. Connectivity of AIS suitable areas inside protected areas is currently lower than across the full study area, but this would change under future environmental conditions. Coupled SDM and connectivity analysis can support resource prioritisation for anticipation and monitoring of AIS impacts. However, further tests of this framework over a wide range of regions and organisms are still required before wide application.

In-depth assessment delivers the verdict on the Government�۪s promise of a more equal society

An independent and detailed expert analysis of a decade of reforms (published 25 February) takes up the challenge made by Peter Mandelson in 1997 to “judge us after ten years of success in office. For one of the fruits of that success will be that Britain has become a more equal society.����”Commissioned by the Joseph Rowntree Foundation, the study, by a team led by LSE’s Centre for Analysis of Social Exclusion, shows sharp contrasts between different policy areas. Notable success stories include reductions in child and pensioner poverty, improved education outcomes for the poorest children and schools, and narrowing economic and other divides between deprived and other areas.But health inequalities continued to widen, gaps in incomes between the very top and very bottom grew, and poverty increased for working-age people without children.����In several policy areas there was a marked contrast between the first half of the New Labour period and the second half, when progress has slowed or even stalled.John Hills, one of the leaders of study, said, “Whether Britain has moved towards becoming a ‘more equal society’ depends on what you look at, and when. Where clear initiatives were taken, results followed. But as the growth of living standards slowed, even well before the recession, and public finances tightened, momentum seems to have been lost in several key areas.”Kitty Stewart added, “The government can take heart from achievements such as the reduction in child poverty up to 2004.����Recent data show that by then, child well-being in the UK had begun to move up the European league table from its dismal showing at the start of the decade that formed the basis of UNICEF’s damning 2007 report. But even with improved figures, Britain was still left with one of the highest rates of child poverty out of the 15 original EU members, and the latest figures show it had increased again by 2006/7.”����The study concludes that the decade from 1997 was favourable to an egalitarian agenda in several ways: the economy grew continuously; the government had large majorities and aspired to create more equality; and public attitudes surveys suggested pent-up demand for more public expenditure. But that environment now looks very uncertain, not just in the near future, but also in the longer term.����Fiscal pressures from an ageing society could further constrain resources available for redistribution, and public attitudes towards the benefit system have hardened while support for redistribution has declined.Hills added, “The 1980s and 1990s showed that hoping that rapid growth in living standards at the top would ‘trickle down’ to those at the bottom did not work.����The period since 1997 has shown that gains are possible through determined interventions, but they require intensive and continuous effort to be sustained.”JRF Chief Executive Julia Unwin added, “We know the potential impact the deepening recession will have on those already living in poverty. This book provides an important, timely and comprehensive assessment of where we are and what remains to be done.”

Impact of a smoking ban in public places: a rapid assessment in the Seychelles.

Background We assessed the impact of a smoking ban in hospitality venues in the Seychelles 9 months after legislation was implemented. Methods Survey officers observed compliance with the smoking ban in 38 most popular hospitality venues and administered a structured questionnaire to two customers, two workers and one manager in each venue. Results Virtually no customers or workers were seen smoking in the indoor premises. Patrons, workers and managers largely supported the ban. The personnel of the hospitality venues reported that most smokers had no difficulty refraining from smoking. However, a third of workers did not systematically request customers to stop smoking and half of them did not report adequate training. Workers reported improved health. No substantial change in the number of customers was noted. Conclusion A ban on public smoking was generally well implemented in hospitality venues but some less than optimal findings suggest the need for adequate training of workers and strengthened enforcement measures. The simple and inexpensive methodology used in this rapid survey may be a useful approach to evaluate the implementation and impact of clean air policy in low and middle-income countries.

Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue.

Background: The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE) tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months. Methods: RNA from fresh frozen (FF) and FFPE tumor samples of 82 patients were used for quality control, and independent FFPE tissues of 342 postmenopausal participants of BIG 1-98 with ER-positive cancer were analyzed by measuring prospectively selected genes and computing scores representing the functions of the estrogen receptor (eight genes, ER_8), the progesterone receptor (five genes, PGR_5), Her2 (two genes, HER2_2), and proliferation (ten genes, PRO_10) by quantitative reverse transcription PCR (qRT-PCR) on TaqMan Low Density Arrays. Molecular scores were computed for each category and ER_8, PGR_5, HER2_2, and PRO_10 scores were combined into a RISK_25 score. Results: Pearson correlation coefficients between FF- and FFPE-derived scores were at least 0.94 and high concordance was observed between molecular scores and immunohistochemical data. The HER2_2, PGR_ 5, PRO_10 and RISK_25 scores were significant predictors of disease free-survival (DFS) in univariate Cox proportional hazard regression. PRO_10 and RISK_25 scores predicted DFS in patients with histological grade II breast cancer and in lymph node positive disease. The PRO_10 and PGR_ 5 scores were independent predictors of DFS in multivariate Cox regression models incorporating clinical risk indicators; PRO_10 outperformed Ki-67 labeling index in multivariate Cox proportional hazard analyses. Conclusions: Scores representing the endocrine responsiveness and proliferation status of breast cancers were developed from gene expression analyses based on RNA derived from FFPE tissues. The validation of the molecular scores with tumor samples of participants of the BIG 1-98 trial demonstrates that such scores can serve as independent prognostic factors to estimate disease free survival (DFS) in postmenopausal patients with estrogen receptor positive breast cancer.