Optimizing detection of RDX vapors using designed experiments for remote sensing.
This paper presents results of designed experiments performed to study the effect of four factors on the detection of RDX vapors from desorption into an atmospheric flow tube mass spectrometer (AFT-MS). The experiments initially included four independent factors: gas flow rate, desorption current, solvent evaporation time and RDX mass. The values of three detection responses, peak height, peak width, and peak area were recorded but only the peak height response was analyzed. Results from the first block of experiments indicated that solvent evaporation time was not statistically significant at the 95% confidence level. A second round of experiments was designed and executed using flow rate, current, and RDX mass as factors and the results were used to create a model to predict conditions resulting in maximum peak height. Those conditions were confirmed experimentally and used to obtain data for a calibration model. The calibration model represented RDX amounts ranging from 1 to 25 pg desorbed into an air flow of 7 L min(-1). Air samples from a shipping container that held 2 closed explosive storage magazines were collected on metal filaments for varying amounts for time ranging from 5 to 90 minutes. RDX was detected from all of the filaments sampled by desorption into the AFT-MS. From the calibration model, RDX vapor concentrations within the shipping container were calculated to be in the range of 1 to 50 parts-per-quadrillion (ppqv) from data collected on 2 separate days.


The presence and accessibility of firearms in the homes of adolescent suicides. A case-control study.
The presence of guns in the home, the type of gun, and the method of storage were all hypothesized to be associated with risk for adolescent suicide. Case-control study. The case group consisted of 47 adolescent suicide victims. The two psychiatric inpatient control groups were 47 suicide attempters and 47 never-suicidal psychiatric controls, frequency-matched to the suicide victims on age, gender, and county of origin. The cases were a consecutive community sample, whereas the inpatients were drawn from a university psychiatric hospital. Odds of the presence of guns in the home of suicide victims (cases) relative to controls. Guns were twice as likely to be found in the homes of suicide victims as in the homes of attempters (adjusted odds ratio, 2.1; 95% confidence interval, 1.2 to 3.7) or psychiatric controls (adjusted odds ratio, 2.2; 95% confidence interval, 1.4 to 3.5). Handguns were not associated with suicide to any statistically significantly greater extent than long guns. There was no difference in the methods of storage of firearms among the three groups, so that even guns stored locked, or separate from ammunition, were associated with suicide by firearms. The availability of guns in the home, independent of firearms type or method of storage, appears to increase the risk for suicide among adolescents. Physicians should make a clear and firm recommendation that firearms be removed from the homes of adolescents judged to be at suicidal risk.


QT interval duration in 24-hour Holter monitoring after different interventional treatment of coronary artery disease in patients after the myocardial infarction.
QT interval prolongation is discussed as a possible risk factor of dangerous arrhythmias. The aim of this study was to evaluate the influence of different interventional treatment of coronary artery disease in patients after myocardial infarction on QT interval duration. Two groups of patients were analyzed. The first group (G1) consisted of 37 patients in whom PTCA was performed; the second group (G2)--42 pts after surgical myocardial revascularisation (CABG). The 24-hour electrocardiography monitoring was performed in all the patients. Results were analyzed especially considering the average daily values of QT, QTp, QTc and RR duration. In patients after CABG we observed statistically significant prolongation of QTc interval duration what was not noticeable in patients after PTCA. The cardiosurgical procedure of coronary by-pass grafting in patients with coronary artery disease after the myocardial infarction in contrary of PTCA may lead to significant prolongation of QTc interval duration. This problem needs further investigation.


Accurate pan-specific prediction of peptide-MHC class II binding affinity with improved binding core identification.
A key event in the generation of a cellular response against malicious organisms through the endocytic pathway is binding of peptidic antigens by major histocompatibility complex class II (MHC class II) molecules. The bound peptide is then presented on the cell surface where it can be recognized by T helper lymphocytes. NetMHCIIpan is a state-of-the-art method for the quantitative prediction of peptide binding to any human or mouse MHC class II molecule of known sequence. In this paper, we describe an updated version of the method with improved peptide binding register identification. Binding register prediction is concerned with determining the minimal core region of nine residues directly in contact with the MHC binding cleft, a crucial piece of information both for the identification and design of CD4(+) T cell antigens. When applied to a set of 51 crystal structures of peptide-MHC complexes with known binding registers, the new method NetMHCIIpan-3.1 significantly outperformed the earlier 3.0 version. We illustrate the impact of accurate binding core identification for the interpretation of T cell cross-reactivity using tetramer double staining with a CMV epitope and its variants mapped to the epitope binding core. NetMHCIIpan is publicly available at http://www.cbs.dtu.dk/services/NetMHCIIpan-3.1 .


Group-level and functional-region analysis of electric-field shape during cerebellar transcranial direct current stimulation with different electrode montages.
Cerebellar transcranial direct current stimulation (ctDCS) is a neuromodulation scheme that delivers a small current to the cerebellum. In this work, we computationally investigate the distributions and strength of the stimulation dosage during ctDCS with the aim of determining the targeted cerebellar regions of a group of subjects with different electrode montages. We used a new inter-individual registration method that permitted the projection of computed electric fields (EFs) from individual realistic head models (n = 18) to standard cerebellar template for the first time. Variations of the EF on the cerebellar surface were found to have standard deviations of up to 55% of the mean. The dominant factor that accounted for 62% of the variability of the maximum EFs was the skin-cerebellum distance, whereas the cerebrospinal fluid volume explained 53% of the average EF distribution. Despite the inter-individual variations, a systematic tendency of the EF hotspot emerges beneath the active electrode in group-level analysis. The hotspot can be adjusted by the electrode position so that the most effective stimulation is delivered to a group of subjects. Targeting specific cerebellar structures with ctDCS is not straightforward, as neuromodulation depends not only on the placement/design of the electrodes configuration but also on inter-individual variability due to anatomical differences. The proposed method permitted generalizing the EFs to a cerebellum atlas. The atlas is useful for studying the mechanisms of ctDCS, planning ctDCS and explaining findings of experimental studies.


Alternative splicing: global insights.
Following the original reports of pre-mRNA splicing in 1977, it was quickly realized that splicing together of different combinations of splice sites--alternative splicing--allows individual genes to generate more than one mRNA isoform. The full extent of alternative splicing only began to be revealed once large-scale genome and transcriptome sequencing projects began, rapidly revealing that alternative splicing is the rule rather than the exception. Recent technical innovations have facilitated the investigation of alternative splicing at a global scale. Splice-sensitive microarray platforms and deep sequencing allow quantitative profiling of very large numbers of alternative splicing events, whereas global analysis of the targets of RNA binding proteins reveals the regulatory networks involved in post-transcriptional gene control. Combined with sophisticated computational analysis, these new approaches are beginning to reveal the so-called 'RNA code' that underlies tissue and developmentally regulated alternative splicing, and that can be disrupted by disease-causing mutations.


Quality of Life of Sardinian Immigrants in Buenos Aires and of People Living in Italy and Sardinia: Does the Kind of Care have a Role for People with Depression?
The aim of the study was to compare the Quality of Life (QoL) of Sardinian immigrants to Argentina with Sardinians residing in Sardinia. The hypothesis was that a different availability of effective treatments for mood disorders may impact the well being of persons with these disorders. One out of five families of Sardinian origin was randomly selected. An Italian study (including Sardinia) was adopted as the control. The Mood Disorder Questionnaire was used for screening mania/hypomania; the diagnosis of Current Major Depressive Disorder was conducted by means of the Patient Health Questionnaire in immigrants and by means of a clinical interview in the control study and in an immigrant subsample (to verify comparability); the Short-Form Health Survey-12 was applied to measure QoL. The Sardinian immigrants showed a higher QoL than Italians in Italy (but not with Sardinians residing in Sardinia). On the contrary, the attributable burden worsening QoL due to lifetime manic/hypomanic episodes, as well as to current depressive episodes, was found higher among Sardinian immigrants with respect to both Sardinian residents in Sardinia and the total Italian sample. The use of effective treatment for mood disorder was higher in Italy. The study found that in a sample of Sardinian immigrants in Buenos Aires the impact of a mood disorder affects QoL more incisively than in Sardinians residing in Sardinia. The suggested hypothesis of a possible role of beliefs guiding the search for treatments will be verified in future studies.


Identification and validation of a gene expression signature that predicts outcome in adult men with germ cell tumors.
Germ cell tumor (GCT) is the most common malignancy in young adult men. Currently, patients are risk-stratified on the basis of clinical presentation and serum tumor markers. The introduction of molecular markers could improve outcome prediction. Expression profiling was performed on 74 nonseminomatous GCTs (NSGCTs) from cisplatin-treated patients (ie, training set) and on 34 similarly treated patients with NSGCTs (ie, validation set). A gene classifier was developed by using prediction analysis for microarrays (PAM) for the binary end point of 5-year overall survival (OS). A predictive score was developed for OS by using the univariate Cox model. In the training set, PAM identified 140 genes that predicted 5-year OS (cross-validated classification rate, 60%). The PAM model correctly classified 90% of patients in the validation set. Patients predicted to have good outcome had significantly longer survival than those with poor predicted outcome (P < .001). For the OS end point, a 10-gene model had a predictive accuracy (ie, concordance index) of 0.66 in the training set and a concordance index of 0.83 in the validation set. Dichotomization of the samples on the basis of the median score resulted in significant differences in survival (P = .002). For both end points, the gene-based predictor was an independent prognostic factor in a multivariate model that included clinical risk stratification (P < .01 for both). We have identified gene expression signatures that accurately predict outcome in patients with GCTs. These predictive genes should be useful for the prediction of patient outcome and could provide novel targets for therapeutic intervention.


The significance of opportunistic predators for the sympatric carnivorous plant species Drosera intermedia and Drosera rotundifolia.
Earlier feeding experiments with Drosera in the field using adult Drosophila melanogaster as prey had shown that D. intermedia reacts three times as strong with respect to biomass production as the sympatric species D. rotundifolia. The present study shows that in D. rotundifolia only 29% of added flies remain on the leaves for more than 24 h, but 95% in D. intermedia. Opportunistic predators, mostly ants, are likely to be responsible for this difference. Ants were often observed robbing food from the leaves of D. rotundifolia, and showed a much higher activity in the microhabitat of this species. In both species of Drosera larger individuals were better than smaller ones in retaining added flies. The activity of ants significantly increased with air temperature and the duration of sunshine. The advantage of plundering seems to be more important for the ants than the danger of being caught. The prey collected from Drosera may be an important source of food for bog-dwelling ants.


Correlates of eating disorder in middle-aged and older adults: evidence from 2007 British National Psychiatric Morbidity Survey.
This study aims to investigate: (a) the association of eating disorders with childhood sexual abuse and recent stressful life events; (b) the coexistence of eating disorders and other common psychiatric disorders; and (c) the impact of eating disorders on obesity, medical conditions, and health service utilization. We conducted secondary data analyses based on population-based study, which consists of a nationally representative sample of 2,870 community-dwelling adults aged 50 and above, interviewed in 2006 to 2007. The 12-month prevalence of eating disorders was 2.61%. Multivariate analyses revealed that eating disorders were more common among younger age groups, women, and those who reported stressful life events. In addition, eating disorders were significantly related to anxiety disorders, agoraphobia, panic disorder, obesity, and cancer. This study supports the notion that eating disorders in older adults are associated with a number of psychosocial, psychiatric, and medical conditions.


Neuroimage evidence and the insanity defense.
The introduction of neuroscientific evidence in criminal trials has given rise to fears that neuroimagery presented by an expert witness might inordinately influence jurors' evaluations of the defendant. In this experiment, a diverse sample of 1,170 community members from throughout the U.S. evaluated a written mock trial in which psychological, neuropsychological, neuroscientific, and neuroimage-based expert evidence was presented in support of a not guilty by reason of insanity (NGRI) defense. No evidence of an independent influence of neuroimagery was found. Overall, neuroscience-based evidence was found to be more persuasive than psychological and anecdotal family history evidence. These effects were consistent across different insanity standards. Despite the non-influence of neuroimagery, however, jurors who were not provided with a neuroimage indicated that they believed neuroimagery would have been the most helpful kind of evidence in their evaluations of the defendant.


An accelerated failure time regression model for illness-death data: A frailty approach.
This work presents a new model and estimation procedure for the illness-death survival data where the hazard functions follow accelerated failure time (AFT) models. A shared frailty variate induces positive dependence among failure times of a subject for handling the unobserved dependency between the nonterminal and the terminal failure times given the observed covariates. The motivation behind the proposed modeling approach is to leverage the well-known interpretability advantage of AFT models with respect to the observed covariates, while also benefiting from the simple and intuitive interpretation of the hazard functions. A semiparametric maximum likelihood estimation procedure is developed via a kernel smoothed-aided expectation-maximization algorithm, and variances are estimated by weighted bootstrap. We consider existing frailty-based illness-death models and place particular emphasis on highlighting the contribution of our current research. The breast cancer data of the Rotterdam tumor bank are analyzed using the proposed as well as existing illness-death models. The results are contrasted and evaluated based on a new graphical goodness-of-fit procedure. Simulation results and data analysis nicely demonstrate the practical utility of the shared frailty variate with the AFT regression model under the illness-death framework.


Protocol for a pragmatic randomised controlled trial of Body Brain Life-General Practice and a Lifestyle Modification Programme to decrease dementia risk exposure in a primary care setting.
It has been estimated that a 10%-25% reduction in seven key risk factors could potentially prevent 1.1-3.0 million Alzheimer's disease cases globally. In addition, as dementia is preceded by more subtle cognitive deficits which have substantial social and economic impact, effective preventative interventions would likely have more extensive benefits. The current study evaluates in primary care a multidomain risk-reduction intervention targeting adults with high risk of developing dementia. A randomised controlled trial (RCT) is being conducted to evaluate three intervention programmes using a pragmatic approach suitable to the clinic: (1) a 12-week online and face-to-face dementia risk-reduction intervention (Body Brain Life-General Practice (BBL-GP)); (2) a 6-week face-to-face group lifestyle modification programme (LMP); and (3) a 12-week email-only programme providing general health information. We aim to recruit 240 participants, aged 18 and over, to undergo a comprehensive cognitive and physical assessment at baseline and follow-ups (postintervention, 18, 36 and 62 weeks). The primary outcome is dementia risk measured with the modified version of the Australian National University-Alzheimer's Disease Risk Index Short Form. Secondary outcomes are cognitive function measured with Trails A and B, and the Digit Symbol Modalities Test; physical activity with moderate-vigorous physical activity and the International Physical Activity Questionnaire; depression with the Centre for Epidemiological Studies Depression; cost evaluation with the 12-item Short Form Health Survey, Framingham Coronary Heart Disease Risk Score and Australian Type 2 Diabetes Risk Assessment Tool; diet quality with the Australian Recommended Food Score; and sleep quality with the Pittsburgh Sleep Quality Index. This RCT is a novel pragmatic intervention applied in a primary care setting to reduce the dementia risk exposure in adults at high risk. If successful, BBL-GP and LMP will provide a versatile, evidence-based package that can be easily and quickly rolled out to other primary care settings and which can be scaled up at relatively low cost compared with other strategies involving intensive interventions. ACTRN12616000868482.


In situ preparation of powder and the sorption behaviors of molecularly imprinted polymers through the complexation between polymer ion of methyl methacrylate/acrylic acid and Ca++ ion.
Molecularly imprinted polymer (MIP) powders were prepared using a simple complexation strategy between the polymer carboxylate groups and template molecule followed by metal cation cross-linking of residual polymer carboxylates. Polymer powders were formed in situ by templating carboxylic acid containing polymers with 4-ethylaniline (4-EA), followed by addition of an aqueous CaCl2 solution. The solution remained homogeneous. The powders were prepared by precipitation by slowly adding a non-solvent, H2O, to the mixture. The resulting particles were very porous with uptake capacity that approached the theoretical value. We suggest two types of complexes are formed between the template, 4-EA, and polymer. The isolated entry type forms well defined cavities for the template with high specific selectivity, while the adjacent entry type forms wider binding sites without specific sorption for isomeric molecules. To evaluate conditions for forming materials with high affinity and selectivity, three MIPs were prepared containing 0.5, 1.0, and 1.5 equivalents of template to the base polymer. The MIP containing 0.5 eq showed higher specific selectivity to 4-EA, but the MIP containing 1.5 eq had noticeably lower selectivity. The lower selectivity is attributed to poorly formed binding sites with little selective sorption to any isomer when the higher ratio of template was used. However at the lower ratio of template the isolated entry is preferably formed to produce well defined binding cavities with higher selectivity to template.


Consultation liaison in primary care for people with mental disorders.
Approximately 25% of people will be affected by a mental disorder at some stage in their life. Despite the prevalence and negative impacts of mental disorders, many people are not diagnosed or do not receive adequate treatment. Therefore primary health care has been identified as essential to improving the delivery of mental health care. Consultation liaison is a model of mental health care where the primary care provider maintains the central role in the delivery of mental health care with a mental health specialist providing consultative support. Consultation liaison has the potential to enhance the delivery of mental health care in the primary care setting and in turn improve outcomes for people with a mental disorder. To identify whether consultation liaison can have beneficial effects for people with a mental disorder by improving the ability of primary care providers to provide mental health care. We searched the EPOC Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), and bibliographic databases: MEDLINE, EMBASE, CINAHL and PsycINFO, in March 2014. We also searched reference lists of relevant studies and reviews to identify any potentially relevant studies. We included randomised controlled trials (RCTs) which compared consultation liaison to standard care or other service models of mental health care in the primary setting. Included participants were people attending primary care practices who required mental health care or had a mental disorder, and primary care providers who had direct contact with people in need of mental health care. Two review authors independently screened the titles and abstracts of identified studies against the inclusion criteria and extracted details including the study design, participants and setting, intervention, outcomes and any risk of bias. We resolved any disagreements by discussion or referral to a third author. We contacted trial authors to obtain any missing information.We collected and analysed data for all follow-up periods: up to and including three months following the start of treatment; between three and 12 months; and more than 12 months following the start of therapy.We used a random-effects model to calculate the risk difference (RD) for binary data and number needed to treat for an additional beneficial outcome (NNTB), if differences between groups were significant. The mean difference (MD) or standardised mean difference (SMD) was calculated for continuous data. There were 8203 citations identified from database searches and reference lists. We included 12 trials with 2605 consumer participants and more than 905 primary care practitioner participants. Eleven trials compared consultation liaison to standard care and one compared consultation liaison to collaborative care, with a case manager co-ordinating mental health care. People with depression were included in eight trials; and one trial each included people with a variety of disorders: depression, anxiety and somatoform disorders; medically unexplained symptoms; and drinking problems. None of the included trials reported separate data for children or older people.There was some evidence that consultation liaison improved mental health up to three months following the start of treatment (two trials, n = 445, NNTB 8, 95% CI 5 to 25) but there was no evidence of its effectiveness between three and 12 months. Consultation liaison also appeared to improve consumer satisfaction (up to three months: one trial, n = 228, NNTB 3, 95% CI 3 to 5; 3 to 12 months: two trials, n = 445, NNTB 8, 95% CI 5 to 17) and adherence (3 to 12 months: seven trials, n = 1251, NNTB 6, 95% CI 4 to 13) up to 12 months. There was also an improvement in the primary care provider outcomes of providing adequate treatment between three to 12 months (three trials, n = 797, NNTB 7, 95% CI 4 to 17) and prescribing pharmacological treatment up to 12 months (four trials, n = 796, NNTB 13, 95% CI 7 to 50). There was also some evidence that consultation liaison may not be as effective as collaborative care in regards to symptoms of mental disorder, disability, general health status, and provision of treatment.The quality of these findings were low for all outcomes however, apart from consumer adherence from three to 12 months, which was of moderate quality. Eight trials were rated a high risk of performance bias because consumer participants were likely to have known whether or not they were allocated to the intervention group and most outcomes were self reported. Bias due to attrition was rated high in eight trials and reporting bias was rated high in six. There is evidence that consultation liaison improves mental health for up to three months; and satisfaction and adherence for up to 12 months in people with mental disorders, particularly those who are depressed. Primary care providers were also more likely to provide adequate treatment and prescribe pharmacological therapy for up to 12 months. There was also some evidence that consultation liaison may not be as effective as collaborative care in terms of mental disorder symptoms, disability, general health status, and provision of treatment. However, the overall quality of trials was low particularly in regards to performance and attrition bias and may have resulted in an overestimation of effectiveness. More evidence is needed to determine the effectiveness of consultation liaison for people with mental disorders particularly for those with mental disorders other than depression.


Predictors of exercise in individuals with schizophrenia: A test of the transtheoretical model of behavior change.
Mortality in individuals with schizophrenia, including deaths not attributable to accidents and suicide, is at least twice that of the general population. While increasing physical exercise could promote positive mental and physical health outcomes in individuals with schizophrenia, only one other study of the determinants of exercise within this population has been reported. Our study attempts to resolve this void in knowledge by testing the applicability of the transtheoretical model (TTM) of behavior change to predicting exercise behavior in those with schizophrenia. Forty-nine participants (42 with schizophrenia and 7 with schizoaffective disorder) from three community mental health centers in Melbourne, Australia, completed a series of questionnaires, an interview, physical health measures, and had their medical records examined. These measures were used: TTM exercise stage, TTM mediators of change, health status, health-risk behaviors, use of antipsychotic medications, psychopathology, psychiatric history, and demographic information. Variables found to be significantly correlated with exercise stage were then included in a series of regression analyses to determine their relative predictive power for exercise stage. The results demonstrated that the TTM and its associated measures may be valid for integration into interventions for promoting exercise in individuals with schizophrenia, despite high levels of psychopathology symptoms. Routine clinical practice should promote exercise in people with schizophrenia and the TTM may be of benefit to this end. Strategies that promote exercise when self-perceived poor health is seen as a significant barrier are particularly important, as is the reduction of caffeine consumption and other health-adverse behaviors.


Theory of chromatic noise masking applied to testing linearity of S-cone detection mechanisms.
A method for testing the linearity of cone combination of chromatic detection mechanisms is applied to S-cone detection. This approach uses the concept of mechanism noise, the noise as seen by a postreceptoral neural mechanism, to represent the effects of superposing chromatic noise components in elevating thresholds and leads to a parameter-free prediction for a linear mechanism. The method also provides a test for the presence of multiple linear detectors and off-axis looking. No evidence for multiple linear mechanisms was found when using either S-cone increment or decrement tests. The results for both S-cone test polarities demonstrate that these mechanisms combine their cone inputs nonlinearly.


Detection of major capsid protein of infectious myonecrosis virus in shrimps using monoclonal antibodies.
Infectious myonecrosis virus (IMNV) has been causing a progressive disease in farm-reared shrimps in Brazil and Indonesia. Immunodiagnostic methods for IMNV detection, although reliable, are not employed currently because monoclonal antibodies (MAbs) against this virus are not available. In this study, a fragment of the IMNV major capsid protein gene, comprising amino acids 300-527 (IMNV(300-527)), was cloned and expressed in Escherichia coli. The nucleotide sequence of the recombinant IMNV(300-527) fragment displayed a high degree of identity to the major capsid protein of IMNV isolates from Brazil (99%) and Indonesia (98%). Ten MAbs were generated against the expressed fragment, and eight of these, mostly IgG(2a) or IgG(2b), were able to bind to IMNV in tissue extracts from shrimps infected naturally in immunodot-blot assays. Six of these MAbs recognized a approximately 100 kDa protein in a Western-blot, which is the predicted mass of IMNV major capsid protein, and also bound to viral inclusions present in muscle fibroses and in coagulative myonecrosis, as demonstrated by immunohistochemistry. Among all those MAbs created, four did not cross-react with non-infected shrimp tissues; this observation supports their applicability as a sensitive and specific immunodiagnosis of IMNV infection in shrimps.


Effects of changes in diagnosis and registration on time trends in recorded childhood cancer incidence in Great Britain.
Increases in recorded childhood cancer incidence are widely reported, but do not necessarily represent real increases in risk. Time trends might conceal underlying steps caused by changes in diagnosis and registration procedures. Using records from the National Registry of Childhood Tumours 1966-2005 (N=54650), the age-sex-standardised rate for residents of Great Britain aged under 15 years was calculated by individual year of diagnosis for each cancer subtype, and the average annual percentage change (trend) was assessed. The timing of assumed step changes in rate was estimated by iterative Poisson regression, and compared graphically with the approximate timing of innovations previously identified from published sources. Estimated timing of underlying steps approximately coincided with the following relevant innovations: biochemical assays, mid-1980s (hepatic and germ-cell cancer); diagnostic imaging, mid-1980s to early 1990s (intracranial/intraspinal tumours, neuroblastoma, soft-tissue sarcoma); revised cancer registration scheme, 1971 (leukaemia, bone and soft-tissue sarcoma); mandatory registration, 1993 (intracranial/intraspinal tumours, retinoblastoma, melanoma/carcinoma); cancer registration improvements, 2001 (leukaemia, renal and hepatic cancer). While the possibility of some real change in risk cannot be excluded, for many cancer subtypes the estimated timing of underlying step changes in rate appeared to correspond with changes in diagnosis or registration procedures. Childhood cancer may have been considerably under-recorded in the past.


Development of key performance indicators for prehospital emergency care.
Key performance indicators (KPIs) are used to monitor and evaluate critical areas of clinical and support functions that influence patient outcome. Traditional prehospital emergency care performance monitoring has focused solely on response time metrics. The landscape of emergency care delivery in Ireland is in the process of significant national reconfiguration. The development of KPIs is therefore considered one of the key priorities in prehospital research. The aim of this study was to develop a suite of KPIs for prehospital emergency care in Ireland. A systematic literature review of prehospital care performance measurement was undertaken followed by a three-round Delphi consensus process facilitated by a broad-based multidisciplinary group of panellists. The consensus process was conducted between June 2012 and October 2013. Each candidate indicator on the Delphi survey questionnaire was rated using a 5-point Likert-type rating scale. Agreement was defined as at least 70% of responders rating an indicator as 'agree' or 'strongly agree' on the rating scale. Data were analysed using descriptive statistics. Sensitivity of the ratings was examined for robustness by bootstrapping the original sample. Of the 78 citations identified by the systematic review, 5 relevant publications were used to select candidate indicators for the Delphi round 1 questionnaire. Response rates in Delphi rounds 1 and 2 were 89% and 83%, respectively. Following the consensus development conference, 101 KPIs reached consensus. Based on the Donabedian framework for quality-of-care indicators, 7 of the KPIs which reached agreement were structure KPIs, 74 were process KPIs and 20 were outcome KPIs. The highest ranked indicator was a process KPI ('Direct transport of ST-elevation myocardial infarction patients to a primary percutaneous intervention (PCI)-capable facility for ECG to PCI time <90 min'). Improving the quality of prehospital care requires the development and implementation of performance measurement using scientifically valid and reliable KPIs. Employing a Delphi panel of key multidisciplinary Emergency Medical Service stakeholders, it was feasible to develop a suite of 101 KPIs for performance monitoring of prehospital emergency care in Ireland. This suite of KPIs may contribute to a framework for achieving safer, better care in the prehospital environment.


Dynamics of material modifications following laser-breakdown in bulk fused silica.
We report on the material response during the cooling phase in bulk fused silica following localized energy deposition via laser-induced breakdown.We use a time-resolved microscope system to acquire images of the region of energy deposition at delay times covering the entire timeline of events. In addition, this system is configured to perform pump-and-probe damage testing measurements to investigate the evolution of the transient absorption of the modified material. The main features of a damage site are established at approximately 30 ns after the pump pulse, i.e. cracks reach their final size within this time frame. The results reveal that the cracks and melted core exhibit a transient absorption up until about 300 ns and 200 micros delay times, respectively, and suggest that the melted region returns to solid phase at approximately 70 ms delay.


Genome Analyses of the Microalga Picochlorum Provide Insights into the Evolution of Thermotolerance in the Green Lineage.
While the molecular events involved in cell responses to heat stress have been extensively studied, our understanding of the genetic basis of basal thermotolerance, and particularly its evolution within the green lineage, remains limited. Here, we present the 13.3-Mb haploid genome and transcriptomes of a halotolerant and thermotolerant unicellular green alga, Picochlorum costavermella (Trebouxiophyceae) to investigate the evolution of the genomic basis of thermotolerance. Differential gene expression at high and standard temperatures revealed that more of the gene families containing up-regulated genes at high temperature were recently evolved, and less originated at the ancestor of green plants. Inversely, there was an excess of ancient gene families containing transcriptionally repressed genes. Interestingly, there is a striking overlap between the thermotolerance and halotolerance transcriptional rewiring, as more than one-third of the gene families up-regulated at 35 °C were also up-regulated under variable salt concentrations in Picochlorum SE3. Moreover, phylogenetic analysis of the 9,304 protein coding genes revealed 26 genes of horizontally transferred origin in P. costavermella, of which five were differentially expressed at higher temperature. Altogether, these results provide new insights about how the genomic basis of adaptation to halo- and thermotolerance evolved in the green lineage.


Proteomics of cypress pollen allergens using double and triple one-dimensional electrophoresis.
Italian cypress (Cupressus sempervirens, Cups) pollen causes allergic diseases in inhabitants of many of the cities surrounding the Mediterranean basin. However, allergens of Cups pollen are still poorly known. We introduce here a novel proteomic approach based on double one-dimensional gel electrophoresis (D1-DE) as an alternative to the 2-DE immunoblot, for the specific IgE screening of allergenic proteins from pollen extracts. The sequential one-dimensional combination of IEF and SDS-PAGE associated with IgE immunoblotting allows a versatile multiplexed immunochemical analysis of selected groups of allergens by converting a single protein spot into an extended protein band. Moreover, the method appears to be valuable for MS/MS identification, without protein purification, of a new Cups pollen allergen at 43 kDa. D1-DE immunoblotting revealed that the prevalence of IgE sensitization to this allergen belonging to the polygalacturonase (PG) family was 70% in tested French allergic patients. In subsequent triple one-dimensional gel electrophoresis, the Cups pollen PG was shown to promote lectin-based protein-protein interactions. Therefore, D1-DE could be used in routine work as a convenient alternative to 2-DE immunoblotting for the simultaneous screening of allergenic components under identical experimental conditions, thereby saving considerable amounts of sera and allergen extracts.


Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks.
Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress.


Checkpoint signaling and error correction require regulation of the MPS1 T-loop by PP2A-B56.
During mitosis, the formation of microtubule-kinetochore attachments is monitored by the serine/threonine kinase monopolar spindle 1 (MPS1). MPS1 is recruited to unattached kinetochores where it phosphorylates KNL1, BUB1, and MAD1 to initiate the spindle assembly checkpoint. This arrests the cell cycle until all kinetochores have been stably captured by microtubules. MPS1 also contributes to the error correction process rectifying incorrect kinetochore attachments. MPS1 activity at kinetochores requires autophosphorylation at multiple sites including threonine 676 in the activation segment or "T-loop." We now demonstrate that the BUBR1-bound pool of PP2A-B56 regulates MPS1 T-loop autophosphorylation and hence activation status in mammalian cells. Overriding this regulation using phosphomimetic mutations in the MPS1 T-loop to generate a constitutively active kinase results in a prolonged mitotic arrest with continuous turnover of microtubule-kinetochore attachments. Dynamic regulation of MPS1 catalytic activity by kinetochore-localized PP2A-B56 is thus critical for controlled MPS1 activity and timely cell cycle progression.


Optimization and Standardization of Human Saliva Collection for MALDI-TOF MS.
SARS-CoV-2 outbreak led to unprecedented innovative scientific research to preclude the virus dissemination and limit its impact on life expectancy. Waiting for the collective immunity by vaccination, mass-testing, and isolation of positive cases remain essential. The development of a diagnosis method requiring a simple and non-invasive sampling with a quick and low-cost approach is on demand. We hypothesized that the combination of saliva specimens with MALDI-TOF MS profiling analyses could be the winning duo. Before characterizing MS saliva signatures associated with SARS-CoV-2 infection, optimization and standardization of sample collection, preparation and storage up to MS analyses appeared compulsory. In this view, successive experiments were performed on saliva from healthy healthcare workers. Specimen sampling with a roll cotton of Salivette® devices appeared the most appropriate collection mode. Saliva protein precipitation with organic buffers did not improved MS spectra profiles compared to a direct loading of samples mixed with acetonitrile/formic acid buffer onto MS plate. The assessment of sample storage conditions and duration revealed that saliva should be stored on ice until MS analysis, which should occur on the day of sampling. Kinetic collection of saliva highlighted reproducibility of saliva MS profiles over four successive days and also at two-week intervals. The intra-individual stability of saliva MS profiles should be a key factor in the future investigation for biomarkers associated with SARS-CoV-2 infection. However, the singularity of MS profiles between individuals will require the development of sophisticated bio-statistical analyses such as machine learning approaches. MALDI-TOF MS profiling of saliva could be a promising PCR-free tool for SARS-CoV-2 screening.


Measurements of skeletal muscle mass and power are positively related to a Mediterranean dietary pattern in women.
The age-related loss of skeletal muscle and function are risk factors for osteoporosis and fractures. We found that higher adherence to the Mediterranean diet score was significantly associated with greater fat-free mass and leg explosive power suggesting a role for the Mediterranean Diet in prevention of loss of muscle outcomes. The loss of skeletal muscle mass, strength, and function with age are contributing risk factors for the onset of sarcopenia, frailty, osteoporosis, fractures, and mortality. Nutrition may affect the progression and trajectory of these changes in skeletal muscle but the role of the micronutrient-rich Mediterranean diet (MD) has hardly been investigated in relation to these muscle outcomes. We examined associations between the MD score (MDS) and FFM% (fat-free mass / weight × 100), FFMI (fat-free mass/height2), hand grip strength, and leg explosive power (LEP, watts/kg) in a cross-sectional study in 2570 women aged 18-79 years from the TwinsUK study. Measurements of body composition were made using dual-energy X-ray absorptiometry and dietary intake assessed by a food frequency questionnaire. FFM%, FFMI, grip strength, and LEP were compared across quartiles of the MDS after adjustment for covariates, with CRP measured in a subgroup (n = 1658). Higher adherence to the MDS was positively associated with measurements of muscle outcomes, with significant differences of 1.7 % for FFM% and 9.6 % for LEP (P trend <0.001), comparing extreme quartiles of intake, but not with grip strength or CRP concentrations. For the first time in a northern European population, we have observed significant positive associations between the MDS and FFM% and LEP in healthy women that are potentially clinically relevant, independent of the factors known to influence muscle outcomes. Our findings emphasize the potential role for overall diet quality based on the MD in the prevention of age-related loss of skeletal muscle outcomes.


Caustics due to complex water menisci.
Shadows of leaves and other objects that can float on the surface of still or slowly flowing water such as a pond or a gently flowing stream have shapes that frequently look nothing like their boundaries because of meniscus effects. Menisci can either refract light into the shadow region making it brighter, or away from it extending the area of darkness. Generally speaking one will find both effects in the shadows of leaves with complicated outlines. In this paper we present an approximate theoretical model for the light intensity in these shadow regions with results of laboratory experiments and computer simulations matching our calculations. The calculations indicate a minimum depth for the water of ∼10 cm for typical floating leaves at which caustic structures form in the shadows. For depths significantly less than this, the shadows will more or less match the outline of the leaf. But for depths much greater the shadows will be significantly different, often not looking anything like the leaf itself.


Neurosarcoidosis: guidance for the general neurologist.
Neurosarcoidosis (NS) more commonly occurs in the setting of systemic disease. The diagnosis is based on a clinical history suggestive of NS, presence of noncaseating granulomas, and supportive evidence of sarcoid pathology, laboratory, and imaging studies. NS could involve any part of the nervous system and often demands high doses of steroids for symptom control. It presents low response to isolated steroids administration and frequently requires immunosuppressive agents. In NS, lymphocytes are polarized toward an excessive Th1 response, leading to overproduction of TNF-alpha and INF-gama, as well as lL-2 and IL-15. Infliximab, a chimeric monoclonal antibody that neutralizes the biological activity of TNF-alpha, is a new option in the NS treatment. We revised pathophysiology, clinical manifestations, diagnostic work up, and treatment of NS as guidance for the general neurologist.


Causal Inference on Discrete Data Using Additive Noise Models.
Inferring the causal structure of a set of random variables from a finite sample of the joint distribution is an important problem in science. The case of two random variables is particularly challenging since no (conditional) independences can be exploited. Recent methods that are based on additive noise models suggest the following principle: Whenever the joint distribution P((X,Y)) admits such a model in one direction, e.g., Y = f(X)+N, N ⊥ X, but does not admit the reversed model X=g(Y)+Ñ, Ñ ⊥ Y, one infers the former direction to be causal (i.e., X → Y). Up to now, these approaches only dealt with continuous variables. In many situations, however, the variables of interest are discrete or even have only finitely many states. In this work, we extend the notion of additive noise models to these cases. We prove that it almost never occurs that additive noise models can be fit in both directions. We further propose an efficient algorithm that is able to perform this way of causal inference on finite samples of discrete variables. We show that the algorithm works on both synthetic and real data sets.


Chloroplast Genome of Novel Rice Germplasm Identified in Northern Australia.
Rice (Oryza sativa L.) was probably domesticated from O. rufipogon in Asia in the last 10,000 years. Relatives of cultivated rice (A genome species of Oryza) are found in South America, Africa, Australia and Asia. These A genome species are the close relatives of cultivated rice and represent the effective gene pool for rice improvement. Members of this group in Northern Australia include, an annual species, O. meridionalis, and two recently distinguished perennial taxa, to one of which the name O. rufipogon has been applied and the other a perennial form of O. meridionalis. Comparison of whole chloroplast genome sequences of these taxa has now been used to determine the relationships between the wild taxa and cultivated rice. The chloroplast genomes of the perennials were both found to be distinguished from O. rufipogon from Asia by 124 or 125 variations and were distinguished from each other by 53 variations. These populations have remained isolated from the overwhelming genetic impact of the large domesticated rice populations in Asia and may be unique descendants of the gene pool from which domesticated rice arose. The conservation of this wild genetic resource may be critical for global food security.


The role of transdermal buprenorphine in the treatment of cancer pain: an expert panel consensus.
The semi-synthetic opioid, buprenorphine, has the general structure of morphine but differs from it in significant ways, both pharmacologically and clinically. A number of long-term studies have shown effective, long-lasting analgesia in moderate to severe cancer and non-cancer pain, including neuropathic pain, with a low incidence of constipation, nausea, dizziness and tiredness. The treatment of moderate to severe chronic pain has improved as a result of the development of new methods of administration of this substance, particularly the introduction of the transdermal drug delivery system, which offers a number of advantages over the usual oral and parenteral routes. A panel of experts specialising in palliative care and pain treatment was convened in November 2007 to discuss their clinical experiences with transdermal buprenorphine and other analgesics. The aim was to provide practical guidance on the treatment of cancer pain with transdermal buprenorphine, particularly when there is a need for increasing pain relief leading to high and increasing doses. A literature search on the use of transdermal buprenorphine was carried out for the panel meeting (based on a search of PubMed to November 2007 - since updated by an additional search for the period to February 2009) and a number of case histories were presented and discussed. This commentary article presents this evidence and the consensus findings of the expert panel. The Panel reached consensus that transdermal buprenorphine was a valuable treatment for chronic cancer pain, including its neuropathic components. A number of general recommendations were made. Large-scale, randomised clinical studies are needed to provide product comparisons on the use of analgesics in the treatment of neuropathic pain although it was recognised that such studies may not be practicable. Data on the treatment of acute and chronic pain should be kept separate in general. Physicians should be made more aware of the problem of hyperalgesic effects of some opioids in long term use. Buprenorphine in contrast has been described to exert an antihyperalgesic effect. The development of analgesic tolerance with some opioids in long term use and the lack of it with buprenorphine requires further studies. The registered dose range of 35-140 microg/h was considered adequate to achieve sufficient pain relief in most patients although some members of the panel presented data showing that increases beyond this dose range provided improved pain relief if slow titration is used. However, it was generally felt that more evidence was needed before this could become generally acceptable. The consensus was that transdermal buprenorphine has a valuable role to play in the treatment of chronic cancer pain because of its efficacy and good safety and tolerability profile, including a low risk of respiratory depression, a lack of immunosuppression and a lack of accumulation in patients with impaired renal function.


Systemic β-Adrenergic Receptor Activation Augments the ex vivo Expansion and Anti-Tumor Activity of Vγ9Vδ2 T-Cells.
TCR-gamma delta (γδ) T-cells are considered important players in the graft-vs.-tumor effect following allogeneic hematopoietic cell transplantation (alloHCT) and have emerged as candidates for adoptive transfer immunotherapy in the treatment of both solid and hematological tumors. Systemic β-adrenergic receptor (β-AR) activation has been shown to mobilize TCR-γδ T-cells to the blood, potentially serving as an adjuvant for alloHCT and TCR-γδ T-cell therapy. We investigated if systemic β-AR activation, using acute dynamic exercise as an experimental model, can increase the mobilization, ex vivo expansion, and anti-tumor activity of TCR-γδ T-cells isolated from the blood of healthy humans. We also sought to investigate the β-AR subtypes involved, by administering a preferential β1-AR antagonist (bisoprolol) and a non-preferential β1 + β2-AR antagonist (nadolol) prior to exercise as part of a randomized placebo controlled cross-over experiment. We found that exercise mobilized TCR-γδ cells to blood and augmented their ex vivo expansion by ~182% compared to resting blood when stimulated with IL-2 and ZOL for 14-days. Exercise also increased the proportion of CD56+, NKG2D+/CD62L-, CD158a/b/e+ and NKG2A- cells among the expanded TCR-γδ cells, and increased their cytotoxic activity against several tumor target cells (K562, U266, 221.AEH) in vitro by 40-60%. Blocking NKG2D on TCR-γδ cells in vitro eliminated the augmented cytotoxic effects of exercise against U266 target cells. Furthermore, administering a β1 + β2-AR (nadolol), but not a β1-AR (bisoprolol) antagonist prior to exercise abrogated the exercise-induced enhancement in TCR-γδ T-cell mobilization and ex vivo expansion. Furthermore, nadolol completely abrogated while bisoprolol partially inhibited the exercise-induced increase in the cytotoxic activity of the expanded TCR-γδ T-cells. We conclude that acute systemic β-AR activation in healthy donors markedly augments the mobilization, ex vivo expansion, and anti-tumor activity of TCR-γδ T-cells and that some of these effects are due to β2-AR signaling and phenotypic shifts that promote a dominant activating signal via NKG2D. These findings highlight β-ARs as potential targets to favorably alter the composition of allogeneic peripheral blood stem cell grafts and improve the potency of TCR-γδ T-cell immune cell therapeutics.


RASSF1A disrupts the NOTCH signaling axis via SNURF/RNF4-mediated ubiquitination of HES1.
RASSF1A promoter methylation has been correlated with tumor dedifferentiation and aggressive oncogenic behavior. Nevertheless, the underlying mechanism of RASSF1A-dependent tumor dedifferentiation remains elusive. Here, we show that RASSF1A directly uncouples the NOTCH-HES1 axis, a key suppressor of differentiation. Interestingly, the crosstalk of RASSF1A with HES1 occurs independently from the signaling route connecting RASSF1A with the Hippo pathway. At the molecular level, we demonstrate that RASSF1A acts as a scaffold essential for the SUMO-targeted E3 ligase SNURF/RNF4 to target HES1 for degradation. The reciprocal relationship between RASSF1A and HES1 is evident across a wide range of human tumors, highlighting the clinical significance of the identified pathway. We show that HES1 upregulation in a RASSF1A-depleted environment renders cells non-responsive to the downstream effects of γ-secretase inhibitors (GSIs) which restrict signaling at the level of the NOTCH receptor. Taken together, we report a mechanism through which RASSF1A exerts autonomous regulation of the critical Notch effector HES1, thus classifying RASSF1A expression as an integral determinant of the clinical effectiveness of Notch inhibitors.


Immersion in water during labor and delivery.
Immersion in water has been suggested as a beneficial alternative for labor, delivery, or both and over the past decades has gained popularity in many parts of the world. Immersion in water during the first stage of labor may be associated with decreased pain or use of anesthesia and decreased duration of labor. However, there is no evidence that immersion in water during the first stage of labor otherwise improves perinatal outcomes, and it should not prevent or inhibit other elements of care. The safety and efficacy of immersion in water during the second stage of labor have not been established, and immersion in water during the second stage of labor has not been associated with maternal or fetal benefit. Given these facts and case reports of rare but serious adverse effects in the newborn, the practice of immersion in the second stage of labor (underwater delivery) should be considered an experimental procedure that only should be performed within the context of an appropriately designed clinical trial with informed consent. Facilities that plan to offer immersion in the first stage of labor need to establish rigorous protocols for candidate selection, maintenance and cleaning of tubs and immersion pools, infection control procedures, monitoring of mothers and fetuses at appropriate intervals while immersed, and immediately and safely moving women out of the tubs if maternal or fetal concerns develop.


Bone metastases, general and clinical issues.
The skeleton is the most common organ for metastasis from solid tumours. Bone metastases pose significant diagnostic and clinical challenges and represent an important cause of cancer-related morbidity. Without appropriate bone-directed therapy, many patients will be at high risk for potentially debilitating skeletal-related events (SREs), such as pain, bone fractures, neurologic deficits and hypercalcemia, severely impacting on the patient's quality of life. Because of their high incidence, bone metastases impose significant demands on health care resources. The optimal management of skeletal metastases depends on the underlying biology of the disease, the extent of bone involvement, the presence and severity of symptoms, the availability of effective systemic therapies and life expectancy of the patient. This article discusses clinical issues concerning diagnosis and available treatment approaches based on the presentation of skeletal involvement. Emphasis is placed on the role of external beam-radiotherapy as a local mode of treatment for palliation of bone pain, decompression of epidural compression and as potential ablative approach through high-dose image-guided irradiation (IGRT) in patients presenting with oligometastatic disease.


Examining the associations of perceived community racism with self-reported physical activity levels and health among older racial minority adults.
Racial health disparities are more pronounced among older adults. Few studies have examined how racism influences health behaviors. This study's purpose was to examine how opportunities for physical activity (PA) and community racism are associated with older racial minorities' reported engagement in PA. We also investigated how PA levels influenced health. We analyzed survey data obtained from a health assessment conducted in 3360 households in Texas, USA, which included items pertaining to PA, community characteristics, and health. Our sample contained 195 women and 85 men (mean age 70.16), most of whom were African American. We found no direct relationship between opportunities and PA. Results suggested that perceived community racism moderated this association. When community racism was low, respondents found ways to be active whether they perceived opportunities or not. When community racism was high, perceived lack of opportunities significantly impeded PA engagement. We found the expected association between PA and health. Results suggested that negative effects of community racism were counteracted through increased opportunities for PA.


Effects of a hybrid maternal environment on brain growth and corpus callosum defects of inbred BALB/c mice: a study using ovarian grafting.
The corpus callosum of many but not all BALB/c mice is either abnormally small or absent. The basis for the defect is hereditary, but the proportion of mice expressing the anomaly can be modified by changing the early environment. The present study investigated the effects of an F1 hybrid maternal environment, which is known to promote better fetal development than an inbred environment, on body and brain growth in BALB/c and on the incidence of the corpus callosal defect. Ovarian follicle cells from BALB/cWah (albino) mice were grafted into pigmented F1 hybrid, BALB/cWah, and pigmented BALB female hosts of comparable age which were subsequently mated to BALB/cWah males. Groups of unoperated BALB/cWah and pigmented BALB dams were included as controls. Data from 111 litters were analyzed. Results showed that BALB mice with F1 mothers had heavier bodies at birth, weaning, and 100 days of age and heavier brains at 100 days than those with either grafted or ungrafted BALB mothers. The effects at birth were evident across all litter sizes (2 to 11), but those at weaning and 100 days were seen only in litters of more than 5 or 6. Neither the F1 hybrid maternal environment nor the grafting procedure itself appeared to influence the incidence or expression of the corpus callosal defect. About 22% of the offspring from each of the three groups (ungrafted BALB, grafted BALB, and grafted F1) showed a defective corpus callosum.


Prevalence of malaria infection in Butajira area, south-central Ethiopia.
In 2005, the Ethiopian government launched a massive expansion of the malaria prevention and control programme. The programme was aimed mainly at the reduction of malaria in populations living below 2,000 m above sea level. Global warming has been implicated in the increase in the prevalence of malaria in the highlands. However, there is still a paucity of information on the occurrence of malaria at higher altitudes. The objective of this study was to estimate malaria prevalence in highland areas of south-central Ethiopia, designated as the Butajira area. Using a multi-stage sampling technique, 750 households were selected. All consenting family members were examined for malaria parasites in thick and thin blood smears. The assessment was repeated six times for two years (October 2008 to June 2010). In total, 19,207 persons were examined in the six surveys. From those tested, 178 slides were positive for malaria, of which 154 (86.5%) were positive for Plasmodium vivax and 22 (12.4%) for Plasmodium falciparum; the remaining two (1.1%) showed mixed infections of Plasmodium falciparum and Plasmodium vivax. The incidence of malaria was higher after the main rainy season, both in lower lying and in highland areas. The incidence in the highlands was low and similar for all age groups, whereas in the lowlands, malaria occurred mostly in those of one to nine years of age. This study documented a low prevalence of malaria that varied with season and altitudinal zone in a highland-fringe area of Ethiopia. Most of the malaria infections were attributable to Plasmodium vivax.


The metal-ionic liquid interface as characterized by impedance spectroscopy and in situ scanning tunneling microscopy.
We summarize our results of electrochemical measurements carried out on inert or close-to-inert metals in ionic liquids, with the aim to explore the metal|ionic liquid interface structure. To this we used electrochemical methods: cyclic voltammetry, impedance spectroscopy, potential of zero total charge measurements and structure-sensitive techniques, such as in situ scanning tunneling spectroscopy. The studied systems were mostly single crystals of noble metals in imidazolium-based ionic liquids. The two main findings are: (i) in the potential window where no Faradaic reactions occur, the interfacial capacitance exhibits a frequency dependence due to double-layer rearrangement processes and (ii) in certain cases ordered anion and cation structures exist at the interface.


SAGE analysis of cell types involved in tolerance induction.
Investigations into the mechanisms of immunological tolerance are currently hindered by a paucity of convenient markers, both for the identification and isolation of tolerant cell types and for monitoring the establishment of tolerance in in vivo models. Although high-affinity autoreactive T cells are deleted in the thymus during the establishment of central tolerance, escaping autoreactive cells require modulation in the periphery. Dendritic cells (DC) and regulatory T cells (Treg) are both implicated in the establishment and maintenance of peripheral tolerance, although specific interactions and mechanisms remain to be established. The serial analysis of gene expression (SAGE) approach to transcript profiling offers potential, not only for new insight into tolerogenic mechanisms, unbiased by current dogma, but also for the identification of novel molecular markers of tolerance. SAGE provides both quantitative and qualitative information on transcripts sampled on the basis of frequency of occurrence in the initial mRNA pool. This information is generated in the form of electronic databases that accumulate as a permanent resource and confer on SAGE the ability to readily compare across wide datasets. This offers particular potential when attempting to correlate gene expression with functional phenotype. By comparing variously generated functionally distinct/related immune populations, such as effector T cells and either natural, CD4+CD25+, or adaptive, Tr1, Tregs and/or immune and tolerance prone DC, it should be possible, using SAGE, to identify both individual genes and also signatures of genes associated with protolerogenic rather than immunogenic phenotypes.


Variational Bayes inference of spatial mixture models for segmentation.
Mixture models are commonly used in the statistical segmentation of images. For example, they can be used for the segmentation of structural medical images into different matter types, or of statistical parametric maps into activating and nonactivating brain regions in functional imaging. Spatial mixture models have been developed to augment histogram information with spatial regularization using Markov random fields (MRFs). In previous work, an approximate model was developed to allow adaptive determination of the parameter controlling the strength of spatial regularization. Inference was performed using Markov Chain Monte Carlo (MCMC) sampling. However, this approach is prohibitively slow for large datasets. In this work, a more efficient inference approach is presented. This combines a variational Bayes approximation with a second-order Taylor expansion of the components of the posterior distribution, which would otherwise be intractable to Variational Bayes. This provides inference on fully adaptive spatial mixture models an order of magnitude faster than MCMC. We examine the behavior of this approach when applied to artificial data with different spatial characteristics, and to functional magnetic resonance imaging statistical parametric maps.


LTR-retrotransposons in R. exoculata and other crustaceans: the outstanding success of GalEa-like copia elements.
Transposable elements are major constituents of eukaryote genomes and have a great impact on genome structure and stability. They can contribute to the genetic diversity and evolution of organisms. Knowledge of their distribution among several genomes is an essential condition to study their dynamics and to better understand their role in species evolution. LTR-retrotransposons have been reported in many diverse eukaryote species, describing a ubiquitous distribution. Given their abundance, diversity and their extended ranges in C-values, environment and life styles, crustaceans are a great taxon to investigate the genomic component of adaptation and its possible relationships with TEs. However, crustaceans have been greatly underrepresented in transposable element studies. Using both degenerate PCR and in silico approaches, we have identified 35 Copia and 46 Gypsy families in 15 and 18 crustacean species, respectively. In particular, we characterized several full-length elements from the shrimp Rimicaris exoculata that is listed as a model organism from hydrothermal vents. Phylogenic analyses show that Copia and Gypsy retrotransposons likely present two opposite dynamics within crustaceans. The Gypsy elements appear relatively frequent and diverse whereas Copia are much more homogeneous, as 29 of them belong to the single GalEa clade, and species- or lineage-dependent. Our results also support the hypothesis of the Copia retrotransposon scarcity in metazoans compared to Gypsy elements. In such a context, the GalEa-like elements present an outstanding wide distribution among eukaryotes, from fishes to red algae, and can be even highly predominant within a large taxon, such as Malacostraca. Their distribution among crustaceans suggests a dynamics that follows a "domino days spreading" branching process in which successive amplifications may interact positively.


Clinical score to detect congenital heart defects: Concept of second screening.
Neonatal screening for congenital heart defects at birth can miss some heart defects, sometimes few critical ones, and the scenario is even worse in those neonates who had never undergone a neonatal checkup (home deliveries). Immunization clinic can serve as a unique opportunity as the second checkpoint for the screening of the children. A history- and examination-based test can serve as an effective tool to screen out children with heart defects. The aim of this study was to establish the sensitivity and specificity of a clinical screening tool for the identification of congenital heart defects at the first visit of an infant after birth for immunization. This is a cross-sectional observational study which the consecutive children presenting at 6 weeks of age for immunization or any child presenting for the first time (outborn delivery) till 6 months of age in the immunization clinic were subjected to detailed history and examination and findings were recorded on a predesigned pro forma and a clinical score was calculated. All these children were then subjected to echocardiography for confirmation of the diagnosis of congenital heart disease (CHD), and the sensitivity and specificity of the test were recorded. A total of 970 babies were screened, out of them 31 were diagnosed with CHD and 18 had undergone neonatal screening at birth. A clinical score of 3 or more had more chances of detecting CHD. The sensitivity of the cutoff score as 3 was 96.77% and specificity was 98.72, with a positive predictive value of 71.43%, a negative predictive value of 99.89%, and an accuracy of 98.66%. The history- and examination-based tool is an effective method for early identification of CHD and can easily be used by peripheral workers working in remote places with poor resources enabling prompt referral.


Effects of injectable dexmedetomidine-ketamine-midazolam and isoflurane inhalation anesthetic protocols on ocular variables in captive black-tailed prairie dogs (Cynomys ludovicianus).
To evaluate the effects of injectable dexmedetomidine-ketamine-midazolam (DKM) and isoflurane inhalation (ISO) anesthetic protocols on selected ocular variables in captive black-tailed prairie dogs (Cynomys ludovicianus; BTPDs). 9 zoo-kept BTPDs. The BTPDs received dexmedetomidine hydrochloride (0.25 mg/kg, IM), ketamine hydrochloride (40 mg/kg, IM), and midazolam hydrochloride (1.5 mg/kg, IM) or inhalation of isoflurane and oxygen in a randomized complete crossover design (2-day interval between anesthetic episodes). Pupil size, globe position, tear production, and intraocular pressure measurements were recorded at 5, 30, and 45 minutes after induction of anesthesia. For each BTPD, a phenol red thread test was performed in one randomly selected eye and a modified Schirmer tear test I was performed in the other eye. Intraocular pressure was measured by rebound tonometry. Compared with findings for the DKM protocol, pupil size was smaller at all time points when the BTPDs underwent the ISO protocol. Globe position remained central during anesthesia with the DKM protocol, whereas it varied among central, ventromedial, and ventrolateral positions during anesthesia with the ISO protocol. Tear production and intraocular pressure decreased significantly over time when the BTPDs underwent either protocol. Results indicated that ophthalmic examination findings for anesthetized BTPDs can be influenced by the anesthetic protocol used. The DKM protocol may result in more consistent pupil size and globe position, compared with that achieved by use of the ISO protocol. Tear production and intraocular pressure measurements should be conducted promptly after induction of anesthesia to avoid the effect of anesthetic episode duration on these variables.


Using patient serum to epitope map soybean glycinins reveals common epitopes shared with many legumes and tree nuts.
Soybean consumption is increasing in many Western diets; however, recent reviews suggest that the prevalence of soy allergy can be as high as 0.5% for the general population and up to 13% for children. The immunoglobulin-E (IgE) binding of sera from six soy-sensitive adult human subjects to soybean proteins separated by 2D gel electrophoresis was studied. Synthetic peptide sets spanning the mature glycinin subunit A2 and A3 primary sequences were used to map the IgE-binding regions. Putative epitopes identified in this study were also localized on glycinin hexamer models using bioinformatics software. We identified linear IgE-binding epitopes of the major storage protein Gly m 6 by screening individual soy-sensitive patient sera. These epitopes were then further analysed by 3D in silico model localization and compared to other plant storage protein epitopes. Web-based software applications were also used to study the ability to accurately predict epitopes with mixed results. A total of nine putative IgE-binding epitopes were identified in the glycinin A3 (A3.1-A3.3) and A2 (A2.1-A2.6) subunits. Most patients' sera IgE bound to only one or two epitopes, except for one patient's serum which bound to four different A2 epitopes. Two epitopes (A3.2 and A2.4) overlapped with a previously identified epitope hot spot of 11S globulins from other plant species. Most epitopes were predicted to be exposed on the surface of the 3D model of the glycinin hexamer. Amino acid sequence alignments of soybean acidic glycinins and other plant globulins revealed one dominant epitope hot spot among the four reported hot spots. This study may be helpful for future development of soy allergy immunotherapy and diagnosis.


Refugees, asylum-seekers and undocumented migrants and the experience of parenthood: a synthesis of the qualitative literature.
To synthesize the recent qualitative literature and identify the integrative themes describing the parenthood experiences of refugees, asylum-seekers and undocumented migrants. We searched seven online databases for the period January 2006 to February 2017. We included English and French published peer-reviewed articles and graduate-level dissertations, which qualitatively examined the parenthood experiences of refugees, asylum-seekers and undocumented migrants. We summarized study characteristics and performed a thematic analysis across the studies. One hundred thirty eight studies met inclusion criteria. All but three were conducted in high-income countries, mainly in the US. Migrants studied were mostly undocumented from Latin America and refugees from Sub-Saharan Africa. Almost all studies (93%) included mothers; about half (47%) included fathers; very few (5%) included extended family members. We identified three integrative themes: 1) experiencing hardship and/or loss in the context of precarious migration and past traumas; 2) building resilience and strength by bridging language, norms and expectations; and 3) living transnationally: obligations, challenges and resources. Each theme contributed to shaping the parenthood experience; the transnationalism theme intersected with the themes on hardship and loss and resilience and strength. More research is needed with fathers, extended family members, asylum-seekers and in the LMIC context. A transnational lens needs to be applied to programs, policies and future research for refugee, asylum-seeker and undocumented migrant parents. Addressing transnational concerns (family separation and reunification), acknowledging transnational resources, fostering a transnational family identity and conducting transnational and longitudinal studies are potentially pivotal approaches for this sub-population of parents.


2-(5,6-Diphenyl-1,2,4-triazin-3-yl)aniline.
The title compound, C21H16N4, obtained under standard Suzuki cross-coupling conditions, is a model compound in the synthesis and biological activity evaluation of new aza-analogues of sildenafil containing a pyrazolo-[4,3-e][1,2,4]triazine system. An N-H⋯N intra-molecular hydrogen bond involving the amino-benzene system and the 1,2,4-triazine moiety helps to establish a near coplanar orientation of the rings with a dihedral angle of 12.04 (4)°, which is believed to be necessary for the biological activity of sildenafil analogues. The 1,2,4-triazine ring is slightly distorted from planarity [r.m.s deviation = 0.0299 (11) Å] and forms dihedral angles of 58.60 (4) and 36.35 (3)° with the pendant phenyl rings. The crystal packing features bifurcated N-H⋯(N,N) hydrogen bonds linking screw-axis-related mol-ecules into chains parallel to the [010] direction and π-π inter-actions, with a centroid-centroid separation of 3.8722 (7) Å and a slippage of 1.412 (3) Å. The crystal studied was a nonmerohedral twin with a ratio of 0.707 (2):0293 (2).


High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial.
The optimum duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains undefined. We aimed to determine whether long-term androgen deprivation was superior to short-term androgen deprivation when combined with high-dose radiotherapy. In this open-label, multicentre, phase 3 randomised controlled trial, patients were recruited from ten university hospitals throughout Spain. Eligible patients had clinical stage T1c-T3b N0M0 prostate adenocarcinoma with intermediate-risk and high-risk factors according to 2005 National Comprehensive Cancer Network criteria. Patients were randomly assigned (1:1) using a computer-generated randomisation schedule to receive either 4 months of androgen deprivation combined with three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range 76-82 Gy; short-term androgen deprivation group) or the same treatment followed by 24 months of adjuvant androgen deprivation (long-term androgen deprivation group), stratified by prostate cancer risk group (intermediate risk vs high risk) and participating centre. Patients assigned to the short-term androgen deprivation group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy (flutamide 750 mg per day or bicalutamide 50 mg per day) was added during the first 2 months of treatment. Patients assigned to long-term suppression continued with the same luteinising hormone-releasing hormone analogue every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175212. Between Nov 7, 2005, and Dec 20, 2010, 178 patients were randomly assigned to receive short-term androgen deprivation and 177 to receive long-term androgen deprivation. After a median follow-up of 63 months (IQR 50-82), 5-year biochemical disease-free survival was significantly better among patients receiving long-term androgen deprivation than among those receiving short-term treatment (90% [95% CI 87-92] vs 81% [78-85]; hazard ratio [HR] 1·88 [95% CI 1·12-3·15]; p=0·01). 5-year overall survival (95% [95% CI 93-97] vs 86% [83-89]; HR 2·48 [95% CI 1·31-4·68]; p=0·009) and 5-year metastasis-free survival (94% [95% CI 92-96] vs 83% [80-86]; HR 2·31 [95% CI 1·23-3·85]; p=0·01) were also significantly better in the long-term androgen deprivation group than in the short-term androgen deprivation group. The effect of long-term androgen deprivation on biochemical disease-free survival, metastasis-free survival, and overall survival was more evident in patients with high-risk disease than in those with low-risk disease. Grade 3 late rectal toxicity was noted in three (2%) of 177 patients in the long-term androgen deprivation group and two (1%) of 178 in the short-term androgen deprivation group; grade 3-4 late urinary toxicity was noted in five (3%) patients in each group. No deaths related to treatment were reported. Compared with short-term androgen deprivation, 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical control and overall survival in patients with prostate cancer, particularly those with high-risk disease, with no increase in late radiation toxicity. Longer follow-up is needed to determine whether men with intermediate-risk disease benefit from more than 4 months of androgen deprivation. Spanish National Health Investigation Fund, AstraZeneca.


Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy, and systemic chemotherapy in patients with malignant pleural mesothelioma: a 10-year experience.
We evaluated the long-term results of pleurectomy/decortication (P/D), hyperthermic pleural lavage with povidone-iodine, prophylactic chest wall radiotherapy (21 Gy), and systemic chemotherapy in patients with malignant pleural mesothelioma. A cohort of patients having surgery between January 2004 and December 2013 were retrospectively studied. All patients received prophylactic radiotherapy postoperatively and all were supposed to receive systemic chemotherapy, either preoperatively or as adjuvant therapy. Patients were reviewed at 30 days, then followed up 6-monthly. (18)F-FDG-PET-CT was used routinely to diagnose disease recurrence. Second-line therapies were administered when appropriate. Survival and prognostic factors were analyzed by the Kaplan-Meier method, log-rank test, and Cox regression analysis. One hundred two patients had P/D followed by prophylactic radiotherapy and were referred for adjuvant chemotherapy. Median age at operation was 64 years. Eighty-one patients (79.4%) were male; 57 patients (55.9%) had complete macroscopic resection. Thirty-day mortality was nil and 30 patients (29.4%) experienced postoperative complications. Seventy-three patients had epithelioid mesothelioma (71.5%). Sixty-eight patients (66.6%) had N0 disease. Ninety-six patients (94.1%) received the planned 4 to 6 chemotherapy cycles. At last follow-up, 49 patients were alive. Univariate analysis showed no significant difference when sex, age >70 years, nodal status, or prior chemotherapy were considered. The overall median survival was 32 months and 5-year survival rate was 23.1%. Median survival and 5-year survival rates were 35.0 months and 30.7% for epithelioid mesothelioma and 15 months and 7% for nonepithelioid mesothelioma, respectively (P = .0001). Median survival was 45.0 months for R0-R1 resection versus 17.4 months for R2 resection (P = .0001). P/D, hyperthermic pleural lavage with povidone-iodine, prophylactic chest wall radiotherapy, and systemic chemotherapy is a safe and well-tolerated multimodality therapy.


The Comparative Analysis of Antiviral Activity of Native and Modified Fucoidans from Brown Algae Fucus evanescens In Vitro and In Vivo.
The enzymatic depolymerization of fucoidans from brown algae allowed the production of their standardized derivatives with different biological activities. This work aimed to compare the antiviral activities of native (FeF) and modified with enzyme (FeHMP) fucoidans from F. evanescens. The cytotoxicity and antiviral activities of the FeF and FeHMP against herpes viruses (HSV-1, HSV-2), enterovirus (ECHO-1), and human immunodeficiency virus (HIV-1) in Vero and human MT-4 cell lines were examined by methylthiazolyltetrazolium bromide (MTT) and cytopathic effect (CPE) reduction assays, respectively. The efficacy of fucoidans in vivo was evaluated in the outbred mice model of vaginitis caused by HSV-2. We have shown that both FeF and FeHMP significantly inhibited virus-induced CPE in vitro and were more effective against HSV. FeF exhibited antiviral activity against HSV-2 with a selective index (SI) > 40, and FeHMP with SI ˃ 20, when they were added before virus infection or at the early stages of the HSV-2 lifecycle. Furthermore, in vivo studies showed that after intraperitoneal administration (10 mg/kg), both FeF and FeHMP protected mice from lethal intravaginal HSV-2 infection to approximately the same degree (44-56%). Thus, FeF and FeHMP have comparable potency against several DNA and RNA viruses, allowing us to consider the studied fucoidans as promising broad-spectrum antivirals.


Menopause-Associated Lipid Metabolic Disorders and Foods Beneficial for Postmenopausal Women.
Menopause is clinically diagnosed as a condition when a woman has not menstruated for one year. During the menopausal transition period, there is an emergence of various lipid metabolic disorders due to hormonal changes, such as decreased levels of estrogens and increased levels of circulating androgens; these may lead to the development of metabolic syndromes including cardiovascular diseases and type 2 diabetes. Dysregulation of lipid metabolism affects the body fat mass, fat-free mass, fatty acid metabolism, and various aspects of energy metabolism, such as basal metabolic ratio, adiposity, and obesity. Moreover, menopause is also associated with alterations in the levels of various lipids circulating in the blood, such as lipoproteins, apolipoproteins, low-density lipoproteins (LDLs), high-density lipoproteins (HDL) and triacylglycerol (TG). Alterations in lipid metabolism and excessive adipose tissue play a key role in the synthesis of excess fatty acids, adipocytokines, proinflammatory cytokines, and reactive oxygen species, which cause lipid peroxidation and result in the development of insulin resistance, abdominal adiposity, and dyslipidemia. This review discusses dietary recommendations and beneficial compounds, such as vitamin D, omega-3 fatty acids, antioxidants, phytochemicals-and their food sources-to aid the management of abnormal lipid metabolism in postmenopausal women.


Early growth response proteins (EGR) and nuclear factors of activated T cells (NFAT) form heterodimers and regulate proinflammatory cytokine gene expression.
Activation of transcription factors by receptor mediated signaling is an essential step for T lymphocyte effector function. Following antigenic stimulation of T cells the two central cytokines IL-2 and TNFalpha are co-expressed and co-regulated. Two important transcription factors, i.e., early growth response (EGR) protein EGR-1 and nuclear factors of activated T cells (NFAT) protein NFATc, regulate transcription of the human IL-2 cytokine and the same combination of EGR and NFAT proteins seems relevant for coordinated cytokine expression. Here we demonstrate that the zinc finger protein EGR-1 and two members of the NFAT protein family bind simultaneously to adjacent elements position -168 to -150 within the TNFalpha promoter. Both promoter sites are important for TNFalpha gene transcription as shown by transfection assays having the IL-2 and TNFalpha promoters linked to a luciferase reporter. The use of promoter deletion constructs with the zinc finger protein (ZIP), the NFAT binding element or a combination of both deleted show a functional cooperation of these elements and of their binding factors. These experiments demonstrate that EGR-1 as well as EGR-4 functionally cooperate with NFAT proteins and induce expression of both cytokine genes. Using tagged NFATc and NFATp in glutathione S-transferase pull down assays showed interaction and physical complex formation of each NFAT protein with recombinant, as well as native, EGR-1 and EGR-4 proteins. Thus EGR-NFAT interaction and complex formation seems essential for human cytokine expression as adjacent ZIP and NFAT elements are conserved in the IL-2 and TNFalpha gene promoters. Binding of regulatory EGR and NFAT factors to these sites and the functional interaction and formation of stable heterodimeric complexes indicate an important role of these factors for gene transcription.


Ethyl acetate extract of Chinese medicinal herb Sarcandra glabra induces growth inhibition on human leukemic HL-60 cells, associated with cell cycle arrest and up-regulation of pro-apoptotic Bax/Bcl-2 ratio.
Sarcandra glabra (Thunb.) Nakai, colloquially known as Caoshanhu, is a Chinese medicinal herb with reported anti-tumor, anti-inflammatory, anti-viral and non-specific immunoenhancing properties. Although the plant has been clinically used for treating a variety of diseases, its bioactive ingredients are largely unknown and its mode of action has never been investigated. In this study, the anti-tumor property of ethyl acetate (EA) extract of S. glabra was investigated by determining its in vitro growth-inhibitory effects on a panel of human cancer cell lines of different histotypes. Growth inhibition of the EA extract on the cancer cells seemed to be selective, and the leukemic HL-60 was found to be the most responsive after 48 h of treatment (IC50=58 microg/ml). Flow cytometric studies further illustrated that the extract might interfere with DNA replication and thus arrested the cell cycle at S phase in the leukemic cells, followed by DNA fragmentation and loss of phospholipid asymmetry in the plasma membrane after 72 h of treatment. Concurrently, the pro-apoptotic Bax/Bcl-2 ratio was also up-regulated by more than 178% of the control level. All these findings suggested that the extract had initiated apoptosis to kill the leukemic cells. Results from this pioneer study help to establish a scientific foundation for future research and development of the bioactive ingredients in EA extract of S. glabra as efficacious anti-cancer agents.


Mental health correlates of drug treatment among women who use methamphetamine.
Women comprise over one-third of people who use methamphetamine in the United States and have a higher prevalence of negative mental health consequences of methamphetamine use than men. Yet, few studies have investigated the mental health correlates of drug treatment among this population. We examined the relationship between mental disorders, mental health treatment, and drug treatment among women who use methamphetamine. We used respondent-driven sampling to recruit women who use methamphetamine (N = 322) for a survey about mental disorders, mental health treatment, drug use and treatment, and sociodemographic factors. Bivariate and multivariable logistic regression analyses were conducted. Bivariate analyses indicated that race/ethnicity, mental health treatment, and presence and number of mental disorders were associated with drug treatment. Multivariable analyses revealed that women who reported mental health treatment during a 6-month period had almost twice the odds of also reporting drug treatment than other women (AOR = 1.90; 95% CI = 1.11, 3.25), after controlling for mental disorders and race/ethnicity. Among women who use methamphetamine, participation in one service system (mental health treatment) is a key factor in increasing the odds of participation in another service system (drug treatment). Further research should establish the temporal association between mental health and drug treatment. The present study demonstrates the association between mental health treatment and drug treatment, above and beyond presence or number of mental disorders, and provides direction for drug treatment providers seeking to improve treatment entry and participation among women who use methamphetamine.


Are alcohol expectancies associations? Comment on Moss and Albery (2009).
Moss and Albery presented a dual-process model of the alcohol-behavior link, integrating alcohol expectancy and alcohol myopia theory. Their integrative theory rests on a number of assumptions including, first, that alcohol expectancies are associations that can be activated automatically by an alcohol-relevant context, and second, that alcohol selectively reduces propositional reasoning. As a result, behavior comes under the control of associative processes after alcohol consumption. We agree with the second but not with the first assumption, based on theoretical and empirical arguments. Although in some cases expectancies may involve a simple association, they are propositional in nature. We demonstrate that this assertion is supported by existing literature cited in Moss and Albery. Moreover, 6 recent studies consistently demonstrated that under circumstances in which executive control is impaired (either as a stable individual difference or under the acute influence of alcohol), associative processes, over and above expectancies, predict alcohol-related behavior. Taken together, the evidence strongly suggests a fundamental distinction between expectancies and associations in memory: Effects of propositional expectancies and executive functions are impaired under the acute influence of alcohol, but memory associations are not. This difference in perspective not only has theoretical implications but also leads to different predictions regarding acute alcohol effects in society.


Simultaneous activity and surface area measurements on single mesoporous nanoparticle aggregates.
The underpotential deposition of hydrogen and the hydrogen evolution reaction is studied at individual mesoporous nanoparticles. This work shows how the electroactive surface area and catalytic activity of these individual particles can be simultaneously measured.


Towards a sustainable system of drug development.
Drug development has become the exclusive activity of large pharmaceutical companies. However, the output of new drugs has been decreasing for the past decade and the prices of new drugs have risen steadily, leading to access problems for many patients. By analyzing the history of drug development and the pharmaceutical industry, we identified the main factors causing this system failure. Although many solutions have been suggested to fix the drug development system, we believe that a combination of reforms of the regulatory and patent systems is necessary to make drug development sustainable. These reforms must be combined with a larger, open-access role for public research institutes in the discovery, clinical evaluation and safety evaluation of new drugs.


Circulating vitamin D metabolites, polymorphism in vitamin D receptor, and colorectal adenoma risk.
Vitamin D is a potential agent for the prevention of colorectal cancer possibly through mechanisms mediated by the vitamin D receptor (VDR). We investigated the association of circulating vitamin D metabolites and a genetic variant of the VDR gene with advanced colorectal adenoma, a precursor lesion of colorectal cancer. Cases with advanced adenoma of the distal large bowel and gender- and ethnicity-matched controls with a negative sigmoidoscopy were randomly selected from participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. Genotype analysis of the VDR TaqI polymorphism was completed on 763 cases and 774 controls. Serum levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured in a subset of 394 cases and 397 controls. Serum levels of 25(OH)D were inversely associated with advanced adenoma risk in women but not in men. Comparing those in the highest quintile with those in the lowest quintile, the risk for advanced adenoma decreased by 73% in women [odds ratio (OR) = 0.27, 95% confidence interval (95% CI) = 0.11-0.69; P for trend = 0.0002], while the risk did not decrease in men (OR = 1.10, 95% CI = 0.60-2.05; P for trend = 0.85). In women, 25(OH)D levels were significantly higher in current users of hormone replacement therapy (HRT) than in former or never HRT users. Neither serum 1,25(OH)(2)D nor VDR TaqI genotype was associated with advanced adenoma risk. Higher serum 25(OH)D levels were associated with decreased adenoma risk. Serum 1,25(OH)(2)D and VDR TaqI genotype were not associated with adenoma risk.


Enhancement of the humoral immune response by Echinacea purpurea in female Swiss mice.
Various preparations of the plant Echinacea purpurea have been investigated for their potential to enhance immune function, primarily through activation of innate immune responses. Few studies have examined the potential for enhancement of humoral immunity. Using female Swiss mice we administered a volumetric dose of a glycerine extract of E. purpurea by oral gavage, to evaluate effects on the IgM specific antibody forming cell (AFC) response. Four days of treatment following immunization with sheep red blood cells (SRBC) produced a significant enhancement over naive controls at doses of 0.4 and 0.8 mL/kg/day. A few clinical trials and anecdotal reports have suggested that the greatest efficacy for E. purpurea occurs in acute use following onset of illness. A time course study, using the time of SRBC immunization to mimic the onset of illness, examined the effects of 8 and 4 days of E. purpurea treatment at 0.6 mL/kg/day. Only in the 4-day administration, with dosing beginning 1 hour after SRBC immunization, was there an observed enhancement of the antibody forming cell response. This supports the acute use of E. purpurea as suggested by anecdotal reports, and demonstrates the potential for enhancement of humoral immune responses as well as innate immune responses.