Search

We present Visbrain, a Python open-source package that offers a comprehensive visualization suite for neuroimaging and electrophysiological brain data. Visbrain consists of two levels of abstraction: (1) objects which represent highly configurable neuro-oriented visual primitives (3D brain, sources connectivity, etc.) and (2) graphical user interfaces for higher level interactions. The object level offers flexible and modular tools to produce and automate the production of figures using an approach similar to that of Matplotlib with subplots. The second level visually connects these objects by controlling properties and interactions through graphical interfaces. The current release of Visbrain (version 0.4.2) contains 14 different objects and three responsive graphical user interfaces, built with PyQt: Signal , for the inspection of time-series and spectral properties, Brain for any type of visualization involving a 3D brain and Sleep for polysomnographic data visualization and sleep analysis. Each module has been developed in tight collaboration with end-users, i.e., primarily neuroscientists and domain experts, who bring their experience to make Visbrain as transparent as possible to the recording modalities (e.g., intracranial EEG, scalp-EEG, MEG, anatomical and functional MRI). Visbrain is developed on top of VisPy, a Python package providing high-performance 2D and 3D visualization by leveraging the computational power of the graphics card. Visbrain is available on Github and comes with a documentation, examples, and datasets (http://visbrain.org).

Purpose: To explore Canadian and Australian community pharmacists' practice experiences in caring for people at risk of suicide., Methods: We conducted a thematic analysis of 176 responses to an open-ended extension question in an online survey., Results: Four themes were identified and include referrals and triage, accessibility for confiding, emotional toll, and stigma. Subthemes included gatekeeping the medication supply, sole disclosure, planning for end of life, concerns of support people, assessing the validity of suicidality, gaps in the system, not directly asking, ill-equipped, resources in the pharmacy, relying on others to continue care, and attention seeking., Conclusions: Community pharmacists are caring for patients at risk of suicide frequently, and often with patients seeking the help of pharmacists directly. Pharmacists engage in activities and actions that would be considered outside of the traditional dispensing roles and provide support and intervention to people at risk of suicide through collaboration and other mechanisms. Further research to determine appropriate education and training and postvention supports is required.

Background: The incidence of labour induction has risen worldwide over the past decade, and this may contribute to the rising caesarean delivery rate. The mechanisms for induction of labour are generally divided into two categories: mechanical and pharmacological., Aims: The objective of this study was to determine if mechanical induction with Dilapan-S is an acceptable, safe method of induction of labour in post-dates uncomplicated nulliparous pregnancy., Methods: This was a single-centre prospective observational pilot study trial. Fifty-two low-risk nulliparous women with an unfavourable cervix, scheduled for induction of labour for post-dates ≥ 41 weeks gestation, were offered induction of labour with Dilapan-S or Propess from May 2016 until November 2016. The primary outcomes measured were compliance to study protocol and maternal (infection, hyperstimulation) and neonatal outcomes (Apgar score at birth). The secondary outcome measures included change in Bishop's score and caesarean delivery rate., Results: Compliance to study protocol was 25/26 (96%); it was possible to insert Dilapan-S in all but one woman. There were no differences in maternal and neonatal primary outcomes between the groups. There were no cases in either arm of hyperstimulation with either induction method. No difference between the groups was noted in the caesarean delivery rate nor in the mean change in Bishop's score., Conclusions: Dilapan-S is an acceptable, safe form of induction of labour in post-dates uncomplicated nulliparous pregnancy. No cases of hyperstimulation were found, and therefore, Dilapan-S may be a suitable option for outpatient induction of labour in low-risk post-dates nulliparas.

Invariant natural killer T (iNKT) cells recognize glycolipid antigens bound to CD1d molecules on antigen-presenting cells. Therapeutic activation of iNKT cells with the xenogeneic glycolipid α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in murine models, but clinical trials using α-GalCer-stimulated human iNKT cells have shown limited efficacy. We synthesized a series of thioglycoside analogs of α-GalCer with different substituents to the galactose residue and found that two of these compounds, XZ7 and XZ11, bound to CD1d-transfected HeLa cells and activated lines of expanded human iNKT cells. Both compounds stimulated cytolytic degranulation by iNKT cells and while XZ7 preferentially stimulated the production of the antitumor cytokine interferon-γ (IFN-γ), XZ11 preferentially stimulated interleukin-4 (IL-4) production. This biased T helper type 1 effector profile of XZ7 was also evident when iNKT were stimulated with dendritic cells presenting this glycolipid. Separate analysis of the responses of CD4+, CD8α+ and CD4-CD8- iNKT cells indicated that XZ7 preferentially activated CD8α+ iNKT cells, and to a lesser degree, CD4-CD8- iNKT cells. The partial agonist effect of glycolipid XZ7, inducing cytotoxicity and IFN-γ production but not IL-4 production, indicates that specific protumour activities of iNKT cells can be abolished, while preserving their antitumor activities, by introducing structural modifications to α-GalCer. Since XZ7 was much less potent than α-GalCer as an iNKT cell agonist, it is unlikely to be superior to α-GalCer as a therapeutic agent for cancer, but may serve as a parent compound for developing more potent structural analogs.

Background: From December 2014 to September 2016, a cholera outbreak in Kenya, the largest since 2010, caused 16,840 reported cases and 256 deaths. The outbreak affected 30 of Kenya's 47 counties and occurred shortly after the decentralization of many healthcare services to the county level. This mixed-methods study, conducted June-July 2015, assessed cholera preparedness in Homa Bay, Nairobi, and Mombasa counties and explored clinic- and community-based health care workers' (HCW) experiences during outbreak response., Methods: Counties were selected based on cumulative cholera burden and geographic characteristics. We conducted 44 health facility cholera preparedness checklists (according to national guidelines) and 8 focus group discussions (FGDs). Frequencies from preparedness checklists were generated. To determine key themes from FGDs, inductive and deductive codes were applied; MAX software for qualitative data analysis (MAXQDA) was used to identify patterns., Results: Some facilities lacked key materials for treating cholera patients, diagnosing cases, and maintaining infection control. Overall, 82% (36/44) of health facilities had oral rehydration salts, 65% (28/43) had IV fluids, 27% (12/44) had rectal swabs, 11% (5/44) had Cary-Blair transport media, and 86% (38/44) had gloves. A considerable number of facilities lacked disease reporting forms (34%, 14/41) and cholera treatment guidelines (37%, 16/43). In FDGs, HCWs described confusion regarding roles and reporting during the outbreak, which highlighted issues in coordination and management structures within the health system. Similar to checklist findings, FGD participants described supply challenges affecting laboratory preparedness and infection prevention and control. Perceived successes included community engagement, health education, strong collaboration between clinic and community HCWs, and HCWs' personal passion to help others., Conclusions: The confusion over roles, reporting, and management found in this evaluation highlights a need to adapt, implement, and communicate health strategies at the county level, in order to inform and train HCWs during health system transformations. International, national, and county stakeholders could strengthen preparedness and response for cholera and other public health emergencies in Kenya, and thereby strengthen global health security, through further investment in the existing Integrated Disease Surveillance and Response structure and national cholera prevention and control plan, and the adoption of county-specific cholera control plans.

Background/introduction: Sarcoidosis is a multi-systemic disorder of unknown etiology, characterized by the presence of non-caseating granulomas in target organs. In 90% of cases, there is thoracic involvement. Fifty to seventy percent of pulmonary sarcoidosis patients will experience acute, self-limiting disease. For the subgroup of patients who develop persistent disease, no targeted therapy is currently available., Aim: To investigate the potential of the single nucleotide polymorphism (SNP), Toll-like receptor 3 Leu412Phe (TLR3 L412F; rs3775291), as a causative factor in the development of and in disease persistence in pulmonary sarcoidosis. To investigate the functionality of TLR3 L412F in vitro in primary human lung fibroblasts from pulmonary sarcoidosis patients., Design: SNP-genotyping and cellular assays, respectively, were used to investigate the role of TLR3 L412F in the development of persistent pulmonary sarcoidosis., Methods: Cohorts of Irish sarcoidosis patients (n = 228), healthy Irish controls (n = 263) and a secondary cohort of American sarcoidosis patients (n = 123) were genotyped for TLR3 L412F. Additionally, the effect of TLR3 L412F in primary lung fibroblasts from pulmonary sarcoidosis patients was quantitated following TLR3 activation in the context of cytokine and type I interferon production, TLR3 expression and apoptotic- and fibroproliferative-responses., Results: We report a significant association between TLR3 L412F and persistent clinical disease in two cohorts of Irish and American Caucasians with pulmonary sarcoidosis. Furthermore, activation of TLR3 in primary lung fibroblasts from 412 F-homozygous pulmonary sarcoidosis patients resulted in reduced IFN-β and TLR3 expression, reduced apoptosis- and dysregulated fibroproliferative-responses compared with TLR3 wild-type patients., Discussion/conclusion: This study identifies defective TLR3 function as a previously unidentified factor in persistent clinical disease in pulmonary sarcoidosis and reveals TLR3 L412F as a candidate biomarker.

Shared enemies may instigate or modify competitive interactions between species. The dis-equilibrium caused by non-native species introductions has revealed that the outcome of such indirect interactions can often be dramatic. However, studies of enemy-mediated competition mostly consider the impact of a single enemy, despite species being embedded in complex networks of interactions. Here, we demonstrate that native red and invasive grey squirrels in Britain, two terrestrial species linked by resource and disease-mediated apparent competition, are also now linked by a second enemy-mediated relationship involving a shared native predator recovering from historical persecution, the European pine marten. Through combining spatial capture-recapture techniques to estimate pine marten density, and squirrel site-occupancy data, we find that the impact of exposure to predation is highly asymmetrical, with non-native grey squirrel occupancy strongly negatively affected by exposure to pine martens. By contrast, exposure to pine marten predation has an indirect positive effect on red squirrel populations. Pine marten predation thus reverses the well-documented outcome of resource and apparent competition between red and grey squirrels., (© 2018 The Authors.)

Objective. To evaluate mental health first aid (MHFA) skills using simulated patients and to compare self-reported confidence in providing MHFA with performance during simulated patient roleplays. Methods. Pharmacy students self-evaluated their confidence in providing MHFA post-training. Two mental health vignettes and an assessment rubric based on the MHFA Action Plan were developed to assess students' observed MHFA skills during audio-recorded simulated patient roleplays. Results. There were 163 students who completed the MHFA training, of which 88% completed self-evaluations. There were 84% to 98% of students who self-reported that they agreed or strongly agreed they were confident providing MHFA. Postnatal depression (PND) and suicide vignettes were randomly assigned to 36 students. More students participating in the PND roleplay took appropriate actions, compared to those participating in the suicide role-play. However, more students participating in the suicide role play assessed alcohol and/or drug use. Ten (71%) participants in the PND roleplay and six (40%) in the suicide roleplay either avoided using suicide-specific terminology completely or used multiple terms rendering their inquiry unclear. Conclusion. Self-evaluated confidence levels in providing MHFA did not always reflect observed performance. Students had difficulty addressing suicide with only half passing the suicide vignette and many avoiding suicide-specific terminology. This indicates that both self-reported and observed behaviors should be used for post-training assessments.

Over time, a bird population's acoustic and morphological features can diverge from the parent species. A quantitative measure of difference between two populations of species/subspecies is extremely useful to zoologists. Work in this paper takes a dialect difference system first developed for speech and refines it to automatically measure vocalisation difference between bird populations by extracting pitch contours. The pitch contours are transposed into pitch codes. A variety of codebook schemes are proposed to represent the contour structure, including a vector quantization approach. The measure, called Bird Vocalisation Difference, is applied to bird populations with calls that are considered very similar, very different, and between these two extremes. Initial results are very promising, with the behaviour of the metric consistent with accepted levels of similarity for the populations tested to date. The influence of data size on the measure is investigated by using reduced datasets. Results of species pair classification using Gaussian mixture models with Mel-frequency cepstral coefficients is also given as a baseline indicator of class confusability.

Background: While pharmacists are among the most accessible primary health professionals within a mother's healthcare team to identify potential cases of perinatal depression (PND), very little in the literature suggests that this role has been explored., Aim: The aim of this study was to explore community pharmacists' perspectives on their potential roles in perinatal mental health promotion (recognition and health education) and the factors affecting these roles., Methods: In total, 20 semi-structured, in-depth interviews were conducted with community pharmacists., Results: Most pharmacists highlighted their significant roles in recognising PND symptoms and providing medication-related support to perinatal mothers. Barriers to service provision included inter-professional role boundaries, the lack of established referral systems and service remuneration and the lack of adequate training in mental health., Conclusion: Pharmacists could potentially reinforce their involvement in mental health promotion activities.

Competing Interests: Declaration of Conflicting Interests:The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

In an environment of constrained resources, policymakers must identify solutions for financing and delivering health services that are efficient and sustainable. However, such solutions require that policymakers understand the complex interaction between household utilization patterns, factors influencing household medical decisions, and provider performance. This study examined whether and under what conditions out-of-pocket, transportation, and time costs influenced Kenyan households' choice of medical provider for childhood diarrhoeal illnesses. It compared these decisions with the actual cost and quality of those providers to assess strategies for increasing the utilization of high quality, low-cost primary care. This study analyzed nationally-representative survey data through several multinomial nested logit models. On average, time costs accounted for the greatest share of total costs. Households spent the most time and transportation costs utilizing public care, yet were more likely to incur catastrophic time and out-of-pocket costs seeking private care for their child's diarrhoeal illness. Out-of-pocket, transportation, and time costs influenced households' choice of provider, though demand was cost inelastic and households were most responsive to transportation costs. Poorer households were the most responsive to changes in all cost types and most likely to self-treat or utilize informal care. Many households utilized informal care that, relative to formal care, cost the same but was of worse quality-suggesting that such households were making poor medical decisions for their children. To achieve public policy objectives, such as financial risk protection for childhood illnesses and equitable access to primary care, policymakers could focus on three areas: (1) refine financing strategies for further reducing household out-of-pocket costs; (2) reduce or subsidize time and transportation costs for households seeking public and private care; and (3) increase transparency of costs and quality to improve household decisions., (© The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Macrophage migration inhibitory factor (MIF) is a key proinflammatory mediator that we have previously shown to be associated with an aggressive clinical phenotype in cystic fibrosis. It possesses unique tautomerase enzymatic activity. However, to date, no human-derived substrate has been identified that has the capacity to interact with this cytokine's unique tautomerase activity. This led us to hypothesize that MIF may have the capacity to interact with external substrates. We describe for the first time how Pseudomonas aeruginosa can utilize human recombinant MIF (rMIF) to significantly ( P < 0.01) enhance its endogenous biofilm formation. Our in vivo studies demonstrate that utilizing a small-molecular-weight inhibitor targeting MIF's tautomerase activity (SCD-19) significantly reduces the inflammatory response in a murine pulmonary chronic P. aeruginosa model. In addition, we show that in in vitro experiments, pretreatment of P. aeruginosa with rMIF is associated with reduced bacterial killing by tobramycin. Our novel findings support the concept of an anti-MIF strategy that targets this enzymatic activity as a potential future antibacterial therapeutic approach.-Tynan, A., Mawhinney, L., Armstrong, M. E., O'Reilly, C., Kennedy, S., Caraher, E., Jülicher, K., O'Dwyer, D., Maher, L., Schaffer, K., Fabre, A., McKone, E. F., Leng, L., Bucala, R., Bernhagen, J., Cooke, G., Donnelly, S. C. Macrophage migration inhibitory factor enhances Pseudomonas aeruginosa biofilm formation, potentially contributing to cystic fibrosis pathogenesis., (© FASEB.)

Induced pluripotent stem cells (iPSCs) technology is a method for generating pluripotent stem cells in vitro from fully differentiated cells such as fibroblast cells. The potential applications of iPSC technology in cell therapy and disease modeling could influence current medical practices. Despite current advances in iPSC technology, many patient-derived reprogrammed cells are not suitable for clinical trial because most protocols rely on virus-based techniques, which pose the risk of integration of the viral genome into the chromosomes. Therefore, non-viral methods such as mRNA and protein-based reprogramming are promising alternatives when generating clinically safe iPSCs. In a previous study, we generated human iPSCs using cell extracts with cell penetration peptide (CPP) for the delivery of reprogramming proteins [Kim et al. Cell Stem Cells, 2009]. In here, we show that the expression of reprogramming factors in mammalian cells and subsequent purification of these factors by FLAG-Tag could reprogram fibroblasts into iPSCs., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Medications are commonly used in suicide attempts. Pharmacists are inextricably linked to medications and may have roles in helping those at risk of suicide. We conducted a scoping review to characterize the existing literature and make recommendations about future research., Methods: We used a 6-step approach based on an existing scoping review methodological framework, including identifying the research question; identifying relevant studies and other literature; study and literature selection; data charting; collating, summarizing and reporting results; and dissemination of results. We searched electronic databases, various grey literature sources and mobile app stores., Results: Thirty-five articles were included following screening of 1013 database citations. Of 1085 results from grey literature searches, we included 12. Most publications were opinion pieces ( n = 22), followed by survey studies ( n = 9), primarily assessing pharmacists' knowledge and attitudes. Themes included education and training to impact knowledge and attitudes, gatekeeping of medication supply, collaboration and integration, and role perception. Public perspectives on pharmacists' roles were limited., Conclusions: Research regarding pharmacists' roles in the care of people at risk for suicide is limited. The areas that have dominated the literature include legal liability, especially with respect to gatekeeping medications, ethical decision making and education and training. Research is needed to determine what methods, outcomes and measures are required to best serve in building the evidence base for policy and practice decisions in this area., Competing Interests: Declaration of Conflicting Interests:The authors have no financial or other conflicts of interest related to this work.

We introduce Sleep, a new Python open-source graphical user interface (GUI) dedicated to visualization, scoring and analyses of sleep data. Among its most prominent features are: (1) Dynamic display of polysomnographic data, spectrogram, hypnogram and topographic maps with several customizable parameters, (2) Implementation of several automatic detection of sleep features such as spindles, K-complexes, slow waves, and rapid eye movements (REM), (3) Implementation of practical signal processing tools such as re-referencing or filtering, and (4) Display of main descriptive statistics including publication-ready tables and figures. The software package supports loading and reading raw EEG data from standard file formats such as European Data Format, in addition to a range of commercial data formats. Most importantly, Sleep is built on top of the VisPy library, which provides GPU-based fast and high-level visualization. As a result, it is capable of efficiently handling and displaying large sleep datasets. Sleep is freely available (http://visbrain.org/sleep) and comes with sample datasets and an extensive documentation. Novel functionalities will continue to be added and open-science community efforts are expected to enhance the capacities of this module.

Face recognition is a highly specialized capability that has implicit and explicit memory components. Studies show that learning tasks with facial components are dependent on rapid eye movement and non-rapid eye movement sleep features, including rapid eye movement sleep density and fast sleep spindles. This study aimed to investigate the relationship between sleep-dependent consolidation of memory for faces and partial rapid eye movement sleep deprivation, rapid eye movement density, and fast and slow non-rapid eye movement sleep spindles. Fourteen healthy participants spent 1 night each in the laboratory. Prior to bed they completed a virtual reality task in which they interacted with computer-generated characters. Half of the participants (REMD group) underwent a partial rapid eye movement sleep deprivation protocol and half (CTL group) had a normal amount of rapid eye movement sleep. Upon awakening, they completed a face recognition task that contained a mixture of previously encountered faces from the task and new faces. Rapid eye movement density and fast and slow sleep spindles were detected using in-house software. The REMD group performed worse than the CTL group on the face recognition task; however, rapid eye movement duration and rapid eye movement density were not related to task performance. Fast and slow sleep spindles showed differential relationships to task performance, with fast spindles being positively and slow spindles negatively correlated with face recognition. The results support the notion that rapid eye movement and non-rapid eye movement sleep characteristics play complementary roles in face memory consolidation. This study also raises the possibility that fast and slow spindles contribute in opposite ways to sleep-dependent memory consolidation., (© 2017 European Sleep Research Society.)

Background: Although it is well recognized that autism is associated with altered patterns of over- and under-connectivity, specifics are still a matter of debate. Little has been done so far to synthesize available literature using whole-brain electroencephalography (EEG) and magnetoencephalography (MEG) recordings., Objectives: 1) To systematically review the literature on EEG/MEG functional and effective connectivity in autism spectrum disorder (ASD), 2) to synthesize and critically appraise findings related with the hypothesis that ASD is characterized by long-range underconnectivity and local overconnectivity, and 3) to provide, based on the literature, an analysis of tentative factors that are likely to mediate association between ASD and atypical connectivity (e.g., development, topography, lateralization)., Methods: Literature reviews were done using PubMed and PsychInfo databases. Abstracts were screened, and only relevant articles were analyzed based on the objectives of this paper. Special attention was paid to the methodological characteristics that could have created variability in outcomes reported between studies., Results: Our synthesis provides relatively strong support for long-range underconnectivity in ASD, whereas the status of local connectivity remains unclear. This observation was also mirrored by a similar relationship with lower frequencies being often associated with underconnectivity and higher frequencies being associated with both under- and over-connectivity. Putting together these observations, we propose that ASD is characterized by a general trend toward an under-expression of lower-band wide-spread integrative processes compensated by more focal, higher-frequency, locally specialized, and segregated processes. Further investigation is, however, needed to corroborate the conclusion and its generalizability across different tasks. Of note, abnormal lateralization in ASD, specifically an elevated left-over-right EEG and MEG functional connectivity ratio, has been also reported consistently across studies., Conclusions: The large variability in study samples and methodology makes a systematic quantitative analysis (i.e. meta-analysis) of this body of research impossible. Nevertheless, a general trend supporting the hypothesis of long-range functional underconnectivity can be observed. Further research is necessary to more confidently determine the status of the hypothesis of short-range overconnectivity. Frequency-band specific patterns and their relationships with known symptoms of autism also need to be further clarified.

Large models of complex neuronal circuits require specifying numerous parameters, with values that often need to be extracted from the literature, a tedious and error-prone process. To help establishing shareable curated corpora of annotations, we have developed a literature curation framework comprising an annotation format, a Python API (NeuroAnnotation Toolbox; NAT), and a user-friendly graphical interface (NeuroCurator). This framework allows the systematic annotation of relevant statements and model parameters. The context of the annotated content is made explicit in a standard way by associating it with ontological terms (e.g., species, cell types, brain regions). The exact position of the annotated content within a document is specified by the starting character of the annotated text, or the number of the figure, the equation, or the table, depending on the context. Alternatively, the provenance of parameters can also be specified by bounding boxes. Parameter types are linked to curated experimental values so that they can be systematically integrated into models. We demonstrate the use of this approach by releasing a corpus describing different modeling parameters associated with thalamo-cortical circuitry. The proposed framework supports a rigorous management of large sets of parameters, solving common difficulties in their traceability. Further, it allows easier classification of literature information and more efficient and systematic integration of such information into models and analyses.

Future limited water availability may reduce the potential of tree improvement to increase timber yields. We investigated ecophysiological variation between full-sibling families of Sitka spruce (Picea sitchensis (Bong.) Carr.) growing under contrasting water availability conditions: control (optimal) water availability and limited water availability. One-year-old seedlings of nine improved families plus an unimproved seed lot were grown in pots in a greenhouse and the two water availability treatments imposed via drip irrigation. Whole-plant water use varied between families. Stomatal conductance and the light-saturated quantum yield of photosystem II at times differed between families, but not consistently. Certain families showed considerably greater increases in electron transport rate with increasing photosynthetically active radiation. Limited water availability resulted in reduced branch water potential, leaf stomatal conductance and transpiration per unit leaf area, and increased whole-plant water-use efficiency, in all genetic material. The responses of plant water use and leaf carbon isotope composition to water limitation, were, however, initially influenced by variation in vigour between families-with conservative growth in some material slowing the decline in substrate moisture content. As the duration of water deficit extended, these variables showed a more uniform response across families. Between-family variation in physiological mechanisms of drought tolerance was not detected. Thus, for Sitka spruce, assessing juvenile material may not allow selection to prevent reductions in productivity associated with long-term sub-optimal growing conditions, but screening for conservative growth (within families as well as between families) may be beneficial where survival of relatively short-term water limitation is the primary concern., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sleep spindles and K-complexes are among the most prominent micro-events observed in electroencephalographic (EEG) recordings during sleep. These EEG microstructures are thought to be hallmarks of sleep-related cognitive processes. Although tedious and time-consuming, their identification and quantification is important for sleep studies in both healthy subjects and patients with sleep disorders. Therefore, procedures for automatic detection of spindles and K-complexes could provide valuable assistance to researchers and clinicians in the field. Recently, we proposed a framework for joint spindle and K-complex detection (Lajnef et al., 2015a) based on a Tunable Q-factor Wavelet Transform (TQWT; Selesnick, 2011a) and morphological component analysis (MCA). Using a wide range of performance metrics, the present article provides critical validation and benchmarking of the proposed approach by applying it to open-access EEG data from the Montreal Archive of Sleep Studies (MASS; O'Reilly et al., 2014). Importantly, the obtained scores were compared to alternative methods that were previously tested on the same database. With respect to spindle detection, our method achieved higher performance than most of the alternative methods. This was corroborated with statistic tests that took into account both sensitivity and precision (i.e., Matthew's coefficient of correlation (MCC), F1, Cohen κ). Our proposed method has been made available to the community via an open-source tool named Spinky (for spindle and K-complex detection). Thanks to a GUI implementation and access to Matlab and Python resources, Spinky is expected to contribute to an open-science approach that will enhance replicability and reliable comparisons of classifier performances for the detection of sleep EEG microstructure in both healthy and patient populations.

Aldoxime dehydratase catalyses the conversion of aldoximes to their corresponding nitriles. Utilization of the aldoxime-nitrile metabolising enzyme pathway can facilitate the move towards a greener chemistry. In this work, a real-time PCR assay was developed for the detection of aldoxime dehydratase genes in aldoxime/nitrile metabolising microorganisms which have been purified from environmental sources. A conventional PCR assay was also designed allowing gene confirmation via sequencing. Aldoxime dehydratase genes were identified in 30 microorganisms across 11 genera including some not previously shown to harbour the gene. The assay displayed a limit of detection of 1 pg/μL DNA or 7 CFU/reaction. This real-time PCR assay should prove valuable in the high-throughput screening of micro-organisms for novel aldoxime dehydratase genes towards pharmaceutical and industrial applications.

The scope and purpose of this work is 2-fold: to synthesize the available evidence and to translate it into recommendations. This document provides recommendations only when there is evidence to support them. As such, they do not constitute a complete protocol for clinical use. Our intention is that these recommendations be used by others to develop treatment protocols, which necessarily need to incorporate consensus and clinical judgment in areas where current evidence is lacking or insufficient. We think it is important to have evidence-based recommendations to clarify what aspects of practice currently can and cannot be supported by evidence, to encourage use of evidence-based treatments that exist, and to encourage creativity in treatment and research in areas where evidence does not exist. The communities of neurosurgery and neuro-intensive care have been early pioneers and supporters of evidence-based medicine and plan to continue in this endeavor. The complete guideline document, which summarizes and evaluates the literature for each topic, and supplemental appendices (A-I) are available online at https://www.braintrauma.org/coma/guidelines., (Copyright © 2016 Brain Trauma Foundation.)

Automatic phrase detection systems of bird sounds are useful in several applications as they reduce the need for manual annotations. However, birdphrase detection is challenging due to limited training data and background noise. Limited data occur because of limited recordings or the existence of rare phrases. Background noise interference occurs because of the intrinsic nature of the recording environment such as wind or other animals. This paper presents a different approach to birdsong phrase classification using template-based techniques suitable even for limited training data and noisy environments. The algorithm utilizes dynamic time-warping (DTW) and prominent (high-energy) time-frequency regions of training spectrograms to derive templates. The performance of the proposed algorithm is compared with the traditional DTW and hidden Markov models (HMMs) methods under several training and test conditions. DTW works well when the data are limited, while HMMs do better when more data are available, yet they both suffer when the background noise is severe. The proposed algorithm outperforms DTW and HMMs in most training and testing conditions, usually with a high margin when the background noise level is high. The innovation of this work is that the proposed algorithm is robust to both limited training data and background noise.

Introduction: Physician health programs (PHPs) generate high rates of sustained abstinence in addicted physicians, through a combination of formal treatment, self-help involvement, regular monitoring via random urine toxicology tests, and powerful incentives generated by the threat of losing one's medical license. Recently, Caron Treatment Centers developed a new continuing care intervention, "My First Year of Recovery" (MyFYR), which is modeled after PHPs but provides extended recovery support to a broader segment of those with substance use disorders. This paper presents initial outcome data from MyFYR., Methods: MyFYR features frequent outcomes monitoring via urine toxicology tests, and also includes a web-based social platform to coordinate efforts of recovery coaches, family members, and others (e.g., employers, probation officers). Participants were the first 198 clients who enrolled in MyFYR after participating in residential treatment at Caron. Substance use outcomes were determined by a combination of urine toxicology tests, client self-report, and information from family members obtained during a 12-month period following entry into MyFYR., Results: Clients in MyFYR provided 70% of scheduled urine samples, for an average of 16.4 urine samples per client. Only 4.1% of the samples tested positive for alcohol or any drug. As determined by urine toxicology and client and family reports, 54% of the participants had some use of alcohol or drugs during the follow-up. Of these relapsed clients, 70.1% were retained or re-engaged in MyFYR, and of these, half were able to re-establish abstinence of two months duration or more, as documented by urine toxicology., Discussion: These initial results are extremely promising, as they document high rates of sustained participation in urine drug test monitoring and positive outcome in clients not under the threat of losing a professional license or incarceration., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Strong evidence has been presented linking chronic inflammation to the onset and pathogenesis of cancer. The multifunctional pro-inflammatory protein macrophage migration inhibitory factor (MIF) occupies a central role in the inflammatory pathway and has been implicated in the tumorigenesis, angiogenesis, and metastasis of many cancer phenotypes. This review highlights the current state of the art, which presents MIF, and the second member of the MIF structural superfamily, D-DT (MIF2), as significant mediators in the inflammatory-cancer axis. Although the mechanism by which MIF asserts its biological activity has yet to be fully understood, it has become clear in recent years that for certain phenotypes of cancer, MIF represents a valid therapeutic target. Current research efforts have focused on small molecule approaches that target MIF's unique tautomerase active site and neutralization of MIF with anti-MIF antibodies. These approaches have yielded promising results in a number of preclinical murine cancer models and have helped to increase our understanding of MIF biological activity. More recently, MIF's involvement in a number of key protein-protein interactions, such as with CD74 and HSP90, has been highlighted and provides a novel platform for the development of anti-MIF chemotherapeutic strategies in the future., (© 2016 Wiley Periodicals, Inc.)

Stigma and discrimination in relation to mental illnesses have been described as having worse consequences than the conditions themselves. Most medical literature in this area of research has been descriptive and has focused on attitudes towards people with mental illness rather than on interventions to reduce stigma. In this narrative Review, we summarise what is known globally from published systematic reviews and primary data on effective interventions intended to reduce mental-illness-related stigma or discrimination. The main findings emerging from this narrative overview are that: (1) at the population level there is a fairly consistent pattern of short-term benefits for positive attitude change, and some lesser evidence for knowledge improvement; (2) for people with mental illness, some group-level anti-stigma inventions show promise and merit further assessment; (3) for specific target groups, such as students, social-contact-based interventions usually achieve short-term (but less clearly long-term) attitudinal improvements, and less often produce knowledge gains; (4) this is a heterogeneous field of study with few strong study designs with large sample sizes; (5) research from low-income and middle-income countries is conspicuous by its relative absence; (6) caution needs to be exercised in not overgeneralising lessons from one target group to another; (7) there is a clear need for studies with longer-term follow-up to assess whether initial gains are sustained or attenuated, and whether booster doses of the intervention are needed to maintain progress; (8) few studies in any part of the world have focused on either the service user's perspective of stigma and discrimination or on the behaviour domain of behavioural change, either by people with or without mental illness in the complex processes of stigmatisation. We found that social contact is the most effective type of intervention to improve stigma-related knowledge and attitudes in the short term. However, the evidence for longer-term benefit of such social contact to reduce stigma is weak. In view of the magnitude of challenges that result from mental health stigma and discrimination, a concerted effort is needed to fund methodologically strong research that will provide robust evidence to support decisions on investment in interventions to reduce stigma., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

To investigate differences in sleep spindle properties and scalp topography between patients with rapid eye movement sleep behaviour disorder (RBD) and healthy controls, whole-night polysomnograms of 35 patients diagnosed with RBD and 35 healthy control subjects matched for age and sex were compared. Recordings included a 19-lead 10-20 electroencephalogram montage and standard electromyogram, electrooculogram, electrocardiogram and respiratory leads. Sleep spindles were automatically detected using a standard algorithm, and their characteristics (amplitude, duration, density, frequency and frequency slope) compared between groups. Topological analyses of group-discriminative features were conducted. Sleep spindles occurred at a significantly (e.g. t34 = -4.49; P = 0.00008 for C3) lower density (spindles ∙ min(-1) ) for RBD (mean ± SD: 1.61 ± 0.56 for C3) than for control (2.19 ± 0.61 for C3) participants. However, when distinguishing slow and fast spindles using thresholds individually adapted to the electroencephalogram spectrum of each participant, densities smaller (31-96%) for fast but larger (20-120%) for slow spindles were observed in RBD in all derivations. Maximal differences were in more posterior regions for slow spindles, but over the entire scalp for fast spindles. Results suggest that the density of sleep spindles is altered in patients with RBD and should therefore be investigated as a potential marker of future neurodegeneration in these patients., (© 2015 European Sleep Research Society.)

Since the 1990s, concerns about a global obesity epidemic have flourished. These concerns regarding obesity are expressed in popular culture and scientific literature and emphasize both weight and weight loss when defining health and well-being. As a result scholars are now calling attention to a "shadow epidemic" of weight stigma that is shown to have harmful physiological and psychological impacts in youth. In tandem with "globesity" concerns, there has been a similar concern expressed over the epidemic of type 2 diabetes, which some have termed "diabesity." Although there is less known about diabetes stigma, the topic has much overlap with obesity stigma. In this narrative review we discuss the related problems of obesity and type 2 diabetes stigma, with an emphasis on issues specific to youth, as relevant. Drawing from literature on weight bias, critical weight studies, and Health at Every Size (HAES), we highlight pedagogical approaches to address obesity stigma and their implications to redress the problem of type 2 diabetes-related stigma in health care.

This paper investigates the advantage of using the kinematic theory of rapid human movements as a complementary approach to those based on classical dynamical features to characterize and analyze kindergarten children's ability to engage in graphomotor activities as a preparation for handwriting learning. This study analyzes nine different movements taken from 48 children evenly distributed among three different school grades corresponding to pupils aged 3, 4, and 5 years. On the one hand, our results show that the ability to perform graphomotor activities depends on kindergarten grades. More importantly, this study shows which performance criteria, from sophisticated neuromotor modeling as well as more classical kinematic parameters, can differentiate children of different school grades. These criteria provide a valuable tool for studying children's graphomotor control learning strategies. On the other hand, from a practical point of view, it is observed that school grades do not clearly reflect pupils' graphomotor performances. This calls for a large-scale investigation, using a more efficient experimental design based on the various observations made throughout this study regarding the choice of the graphic shapes, the number of repetitions and the features to analyze., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Populations living in informal settlements with inadequate water and sanitation infrastructure are at risk of epidemic disease. In 2010, we conducted 398 household surveys in two informal settlements in Nairobi, Kenya with isolated cholera cases. We tested source and household water for free chlorine residual (FCR) and Escherichia coli in approximately 200 households. International guidelines are ≥0.5 mg/L FCR at source, ≥0.2 mg/L at household, and <1 E. coli/100 mL. In these two settlements, 82% and 38% of water sources met FCR guidelines; and 7% and 8% were contaminated with E. coli, respectively. In household stored water, 82% and 35% met FCR guidelines and 11% and 32% were contaminated with E. coli, respectively. Source water FCR≥0.5 mg/L (p=0.003) and reported purchase of a household water treatment product (p=0.002) were associated with increases in likelihood that household stored water had ≥0.2 mg/L FCR, which was associated with a lower likelihood of E. coli contamination (p<0.001). These results challenge the assumption that water quality in informal settlements is universally poor and the route of disease transmission, and highlight that providing centralized water with ≥0.5 mg/L FCR or (if not feasible) household water treatment technologies reduces the risk of waterborne cholera transmission in informal settlements.

Background: Prescribing of antidepressants varies widely between European countries despite no evidence of difference in the prevalence of affective disorders., Aims: To investigate associations between the use of antidepressants, country-level spending on healthcare and country-level attitudes towards mental health problems., Method: We used Eurobarometer 2010, a large general population survey from 27 European countries, to measure antidepressant use and regularity of use. We then analysed the associations with country-level spending on healthcare and country-level attitudes towards mental health problems., Results: Higher country spending on healthcare was strongly associated with regular use of antidepressants. Beliefs that mentally ill people are 'dangerous' were associated with higher use, and beliefs that they 'never recover' or 'have themselves to blame' were associated with lower and less regular use of antidepressants., Conclusions: Contextual factors, such as healthcare spending and public attitudes towards mental illness, may partly explain variations in antidepressant use and regular use of these medications., (© The Royal College of Psychiatrists 2015.)

Memory consolidation is associated with sleep physiology but the contribution of specific sleep stages remains controversial. To clarify the contribution of REM sleep, participants were administered two REM sleep-sensitive tasks to determine if associated changes occurred only in REM sleep. Twenty-two participants (7 men) were administered the Corsi Block Tapping and Tower of Hanoi tasks prior to and again after a night of sleep. Task improvers and non-improvers were compared for sleep structure, sleep spindles, and dream recall. Control participants (N = 15) completed the tasks twice during the day without intervening sleep. Overnight Corsi Block improvement was associated with more REM sleep whereas Tower of Hanoi improvement was associated with more N2 sleep. Corsi Block improvement correlated positively with %REM sleep and Tower of Hanoi improvement with %N2 sleep. Post-hoc analyses suggest Tower of Hanoi effects-but not Corsi Block effects-are due to trait differences. Sleep spindle density was associated with Tower of Hanoi improvement whereas spindle amplitude correlated with Corsi Block improvement. Number of REM awakenings for dream reporting (but not dream recall per se) was associated with Corsi Block, but not Tower of Hanoi, improvement but was confounded with REM sleep time. This non-replication of one of 2 REM-sensitive task effects challenges both 'dual-process' and 'sequential' or 'sleep organization' models of sleep-dependent learning and points rather to capacity limitations on REM sleep. Experimental awakenings for sampling dream mentation may not perturb sleep-dependent learning effects; they may even enhance them., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Sleep spindle properties index cognitive faculties such as memory consolidation and diseases such as major depression. For this reason, scoring sleep spindle properties in polysomnographic recordings has become an important activity in both research and clinical settings. The tediousness of this manual task has motivated efforts for its automation. Although some progress has been made, increasing the temporal accuracy of spindle scoring and improving the performance assessment methodology are two aspects needing more attention. In this paper, four open-access automated spindle detectors with fine temporal resolution are proposed and tested against expert scoring of two proprietary and two open-access databases. Results highlight several findings: (1) that expert scoring and polysomnographic databases are important confounders when comparing the performance of spindle detectors tested using different databases or scorings; (2) because spindles are sparse events, specificity estimates are potentially misleading for assessing automated detector performance; (3) reporting the performance of spindle detectors exclusively with sensitivity and specificity estimates, as is often seen in the literature, is insufficient; including sensitivity, precision and a more comprehensive statistic such as Matthew's correlation coefficient, F1-score, or Cohen's κ is necessary for adequate evaluation; (4) reporting statistics for some reasonable range of decision thresholds provides a much more complete and useful benchmarking; (5) performance differences between tested automated detectors were found to be similar to those between available expert scorings; (6) much more development is needed to effectively compare the performance of spindle detectors developed by different research teams. Finally, this work clarifies a long-standing but only seldomly posed question regarding whether expert scoring truly is a reliable gold standard for sleep spindle assessment.

We present a complete framework for time-frequency parametrization of EEG transients, based upon matching pursuit (MP) decomposition, applied to the detection of sleep spindles. Ranges of spindles duration (>0.5 s) and frequency (11-16 Hz) are taken directly from their standard definitions. Minimal amplitude is computed from the distribution of the root mean square (RMS) amplitude of the signal within the frequency band of sleep spindles. Detection algorithm depends on the choice of just one free parameter, which is a percentile of this distribution. Performance of detection is assessed on the first cohort/second subset of the Montreal Archive of Sleep Studies (MASS-C1/SS2). Cross-validation performed on the 19 available overnight recordings returned the optimal percentile of the RMS distribution close to 97 in most cases, and the following overall performance measures: sensitivity 0.63 ± 0.06, positive predictive value 0.47 ± 0.08, and Matthews coefficient of correlation 0.51 ± 0.04. These concordances are similar to the results achieved on this database by other automatic methods. Proposed detailed parametrization of sleep spindles within a universal framework, encompassing also other EEG transients, opens new possibilities of high resolution investigation of their relations and detailed characteristics. MP decomposition, selection of relevant structures, and simple creation of EEG profiles used previously for assessment of brain activity of patients in disorders of consciousness are implemented in a freely available software package Svarog (Signal Viewer, Analyzer and Recorder On GPL) with user-friendly, mouse-driven interface for review and analysis of EEG. Svarog can be downloaded from http://braintech.pl/svarog.

The identification of specific genetic alterations as key oncogenic drivers and the development of targeted therapies are together transforming clinical oncology and creating a pressing need for increased breadth and throughput of clinical genotyping. Next-generation sequencing assays allow the efficient and unbiased detection of clinically actionable mutations. To enable precision oncology in patients with solid tumors, we developed Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), a hybridization capture-based next-generation sequencing assay for targeted deep sequencing of all exons and selected introns of 341 key cancer genes in formalin-fixed, paraffin-embedded tumors. Barcoded libraries from patient-matched tumor and normal samples were captured, sequenced, and subjected to a custom analysis pipeline to identify somatic mutations. Sensitivity, specificity, reproducibility of MSK-IMPACT were assessed through extensive analytical validation. We tested 284 tumor samples with previously known point mutations and insertions/deletions in 47 exons of 19 cancer genes. All known variants were accurately detected, and there was high reproducibility of inter- and intrarun replicates. The detection limit for low-frequency variants was approximately 2% for hotspot mutations and 5% for nonhotspot mutations. Copy number alterations and structural rearrangements were also reliably detected. MSK-IMPACT profiles oncogenic DNA alterations in clinical solid tumor samples with high accuracy and sensitivity. Paired analysis of tumors and patient-matched normal samples enables unambiguous detection of somatic mutations to guide treatment decisions., (Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

A build-couple-pair strategy, including double-reductive amination macrocyclization, has been used to generate decorated macrocycles (eannaphanes) with an embedded triazole and monosaccharide. Biological screening led to the identification of an inducer of apoptosis in leukemic cells, which acts at least partially as a 5-HT2 antagonist.

EEG sleep spindles are short (0.5-2.0 s) bursts of activity in the 11-16 Hz band occurring during non-rapid eye movement (NREM) sleep. This sporadic activity is thought to play a role in memory consolidation, brain plasticity, and protection of sleep integrity. Many automatic detectors have been proposed to assist or replace experts for sleep spindle scoring. However, these algorithms usually detect too many events making it difficult to achieve a good tradeoff between sensitivity (Se) and false detection rate (FDr). In this work, we propose a semi-automatic detector comprising a sensitivity phase based on well-established criteria followed by a specificity phase using spatial and spectral criteria. In the sensitivity phase, selected events are those which amplitude in the 10-16 Hz band and spectral ratio characteristics both reject a null hypothesis (p < 0.1) stating that the considered event is not a spindle. This null hypothesis is constructed from events occurring during rapid eye movement (REM) sleep epochs. In the specificity phase, a hierarchical clustering of the selected candidates is done based on events' frequency and spatial position along the anterior-posterior axis. Only events from the classes grouping most (at least 80%) spindles scored by an expert are kept. We obtain Se = 93.2% and FDr = 93.0% in the first phase and Se = 85.4% and FDr = 86.2% in the second phase. For these two phases, Matthew's correlation coefficients are respectively 0.228 and 0.324. Results suggest that spindles are defined by specific spatio-spectral properties and that automatic detection methods can be improved by considering these features.

Manual processing of sleep recordings is extremely time-consuming. Efforts to automate this process have shown promising results, but automatic systems are generally evaluated on private databases, not allowing accurate cross-validation with other systems. In lacking a common benchmark, the relative performances of different systems are not compared easily and advances are compromised. To address this fundamental methodological impediment to sleep study, we propose an open-access database of polysomnographic biosignals. To build this database, whole-night recordings from 200 participants [97 males (aged 42.9 ± 19.8 years) and 103 females (aged 38.3 ± 18.9 years); age range: 18-76 years] were pooled from eight different research protocols performed in three different hospital-based sleep laboratories. All recordings feature a sampling frequency of 256 Hz and an electroencephalography (EEG) montage of 4-20 channels plus standard electro-oculography (EOG), electromyography (EMG), electrocardiography (ECG) and respiratory signals. Access to the database can be obtained through the Montreal Archive of Sleep Studies (MASS) website (http://www.ceams-carsm.ca/en/MASS), and requires only affiliation with a research institution and prior approval by the applicant's local ethical review board. Providing the research community with access to this free and open sleep database is expected to facilitate the development and cross-validation of sleep analysis automation systems. It is also expected that such a shared resource will be a catalyst for cross-centre collaborations on difficult topics such as improving inter-rater agreement on sleep stage scoring., (© 2014 European Sleep Research Society.)

Purpose: The aim of this study was to compare the frequency of ERG rearrangement, PTEN deletion, SPINK1 overexpression, and SPOP mutation in prostate cancer in African American and Caucasian men., Experimental Design: Dominant tumor nodules from radical prostatectomy specimens of 105 African American men (AAM) were compared with 113 dominant nodules from Caucasian men (CaM). Clinical and pathologic characteristics of the two groups were similar. SPINK1 overexpression was evaluated by immunohistochemistry, ERG rearrangement and PTEN deletion by FISH, and SPOP mutation by Sanger sequencing., Results: ERG rearrangement was identified in 48 of 113 tumors (42.5%) in CaM and 29 of 105 tumors (27.6%) in AAM (P = 0.024). PTEN deletion was seen in 19 of 96 tumors (19.8%) in CaM and 7 of 101 tumors (6.9%) in AAM (P = 0.011). SPINK1 overexpression was present in 9 of 110 tumors (8.2%) in CaM and 25 of 105 tumors (23.4%) in AAM (P = 0.002). SPOP mutation was identified in 8 of 78 (10.3%) tumors in CaM and 4 of 88 (4.5%) tumors in AAM (P = 0.230). When adjusted for age, body mass index, Gleason score, and pathologic stage, ERG rearrangement and SPINK1 overexpression remain significantly different (P = 0.018 and P = 0.008, respectively), and differences in PTEN deletion and SPOP mutation approach significance (P = 0.061 and P = 0.087, respectively)., Conclusions: Significant molecular differences exist between prostate cancers in AAM and CaM. SPINK1 overexpression, an alteration associated with more aggressive prostate cancers, was more frequent in AAM, whereas ERG rearrangement and PTEN deletion were less frequent in this cohort. Further investigation is warranted to determine whether these molecular differences explain some of the disparity in incidence and mortality between these two ethnic groups., (©2014 American Association for Cancer Research.)

Background: During the aerosol delivery device design and optimization process, in vitro lung dose (LD) measurements are often performed using soft face models, which may provide a more clinically relevant representation of face mask dead volume (MDV) and face mask seal (FMS) than hard face models. However, a comparison of MDV, FMS, and LD for hard and soft face models is lacking., Methods: Metal, silicone, and polyurethane represented hard, soft, and very soft facial materials, respectively. MDV was measured using a water displacement technique. FMS was measured using a valved holding chamber (VHC) flow rate technique. The LD of beclomethasone dipropionate (BDP) delivered via a 100-μg Qvar® pressurized metered dose inhaler with AeroChamber Plus® Flow-Vu® VHC and Small Mask, defined as that which passes through the nasal airways of the idealized infant geometry, was measured using a bias tidal flow system with a filter. MDV, FMS, and LD were measured at 1.5 lb and 3.5 lb of applied force. A mathematical model was used to predict LD based on experimental measurements of MDV and FMS., Results: Experimental BDP LD measurements for ABS, silicone, and polyurethane at 1.5 lb were 0.9 (0.6) μg, 2.4 (1.9) μg, and 19.3 (0.9) μg, respectively. At 3.5 lb, the respective LD was 10.0 (1.5) μg, 13.8 (1.4) μg, and 14.2 (0.9) μg. Parametric analysis with the mathematical model showed that differences in FMS between face models had a greater impact on LD than differences in MDV., Conclusions: The use of soft face models resulted in higher LD than hard face models, with a greater difference at 1.5 lb than at 3.5 lb. A lack of a FMS led to decreased dose consistency; therefore, a sealant should be used when measuring LD with a hard ABS or soft silicone face model at 1.5 lb of applied force or less.

This paper uses human movement analyses to assess the susceptibility of brain stroke, one of the most important causes of disability in elders. To that end, a computerized battery of nine neuromuscular tests has been designed and evaluated with a sample of 120 subjects with or without stoke risk factors. The kinematics of the movements produced was analyzed using a computational neuromuscular model and predictive characteristics were extracted. Logistic regression and linear discriminant analysis with leave-one-out cross-validation was used to infer the probability of presence of brain stroke risk factors. The clinical potential value of movement information for stroke prevention was assessed by computing area under the receiver operating characteristic curve (AUC) for the diagnostic of risk factors based on motion analysis. AUC mostly varying between 0.6 and 0.9 were obtained, depending on the neuromuscular test and the risk factor investigated (obesity, diabetes, hypertension, hypercholesterolemia, cigarette smoking, and cardiac disease). Our results support the feasibility of the proposed methodology and its potential application for the development of brain stroke prevention tools. Although further research is needed to improve this methodology and its outcome, results are promising and the proposed approach should be of great interest for many experimenters open to novel approaches in preventive medicine and in gerontology. It should also be valuable for engineers, psychologists, and researchers using human movements for the development of diagnostic and neuromuscular assessment tools.

Rationale: Poor adherence to inhaler use can be due to poor temporal and/or technique adherence. Up until now there has been no way of reliably tracking both these factors in everyday inhaler use., Objectives: This paper introduces a device developed to create time stamped acoustic recordings of an individual's inhaler use, in which empirical evidence of temporal and technique adherence in inhaler use can be monitored over time. The correlation between clinical outcomes and adherence, as determined by this device, was compared for temporal adherence alone and combined temporal and technique adherence., Findings: The technology was validated by showing that the doses taken matched the number of audio recordings (r2 = 0.94, p<0.01). To demonstrate that audio analysis of inhaler use gives objective information, in vitro studies were performed. These showed that acoustic profiles of inhalations correlated with the peak inspiratory flow rate (r2 = 0.97, p<0.01), and that the acoustic energy of exhalations into the inhaler was related to the amount of drug removed. Despite training, 16% of participants exhaled into the mouthpiece after priming, in >20% of their inhaler events. Repeated training reduced this to 7% of participants (p = 0.03). When time of use was considered, there was no evidence of a relationship between adherence and changes in AQLQ (r2 = 0.2) or PEFR (r2 = 0.2). Combining time and technique the rate of adherence was related to changes in AQLQ (r2 = 0.53, p = 0.01) and PEFR (r2 = 0.29, p = 0.01)., Conclusions: This study presents a novel method to objectively assess how errors in both time and technique of inhaler use impact on clinical outcomes., Trial Registration: EudraCT 2011-004149-42.

Background: Several tests have been suggested to assess the isometric endurance of the cervical flexor (NFME) and extensors (NEE) muscles. This study proposes to determine whether neck flexors endurance is related to extensor endurance, and whether cervical muscle endurance is related to disability, pain amount and pain stage in subjects with neck pain., Methods: Thirty subjects (18 women, 12 men, mean ± SD age: 43 ± 12 years) complaining of neck pain filled out the Visual Analogue Scale (VAS) and the Neck Pain and Disability Scale-Italian version (NPDS-I). They also completed the timed endurance tests for the cervical muscles., Results: The mean endurance was 246.7 ± 150 seconds for the NEE test, and 44.9 ± 25.3 seconds for the NMFE test. A significant correlation was found between the results of these two tests (r = 0.52, p = 0.003). A positive relationship was also found between VAS and NPDS-I (r = 0.549, p = 0.002). The endurance rates were similar for acute/subacute and chronic subjects, whereas males demonstrated significantly higher values compared to females in NFME test., Conclusions: These findings suggest that neck flexors and extensors endurance are correlated and that the cervical endurance is not significantly altered by the duration of symptoms in subjects with neck pain.

Background: A convergence of studies has revealed sleep spindles to be associated with sleep-related cognitive processing and even with fundamental waking state capacities such as intelligence. However, some spindle characteristics, such as propagation direction and delay, may play a decisive role but are only infrequently investigated because of technical complexities., New Method: A new methodology for assessing sleep spindle propagation over the human scalp using noninvasive electroencephalography (EEG) is described. This approach is based on the alignment of time-frequency representations of spindle activity across recording channels., Results: This first of a two-part series concentrates on framing theoretical considerations related to EEG spindle propagation and on detailing the methodology. A short example application is provided that illustrates the repeatability of results obtained with the new propagation measure in a sample of 32 night recordings. A more comprehensive experimental investigation is presented in part two of the series., Comparison With Existing Method(s): Compared to existing methods, this approach is particularly well adapted for studying the propagation of sleep spindles because it estimates time delays rather than phase synchrony and it computes propagation properties for every individual spindle with windows adjusted to the specific spindle duration., Conclusions: The proposed methodology is effective in tracking the propagation of spindles across the scalp and may thus help in elucidating the temporal aspects of sleep spindle dynamics, as well as other transient EEG and MEG events. A software implementation (the Spyndle Python package) is provided as open source software., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: This communication is the second of a two-part series that describes and tests a new methodology for assessing the propagation of EEG sleep spindles. Whereas the first part describes the methodology in detail, this part proposes a thorough evaluation of the approach by applying it to a sample of laboratory sleep recordings., New Method: The tested methodology is based on the alignment of time-frequency representations of spindle activity across recording channels and is used for assessing sleep spindle propagation over the human scalp using noninvasive EEG., Results: Spindle propagation displays features that suggest wave displacements of global synaptic potential fields. Propagation patterns that are coherent (as opposed to random), laterally symmetrical, and highly repeatable within and between subjects were observed. Propagation was slower from posterior to anterior and from central to lateral brain regions than in the opposite directions. Propagation speeds varying between 2.3 and 7.0m/s were obtained. A distinct grouping of propagation properties was noted for a small cluster of frontal electrodes. No propagation between distantly separated scalp locations was observed. The values of spindle characteristics such as average frequency, RMS amplitude, frequency slope, and duration, depend largely on propagation direction but are only mildly correlated with propagation delay., Comparison With Existing Method(s): Results obtained are in line with many results published in the literature and offer new measures for describing sleep spindle behavior., Conclusions: Propagation properties provide new information about sleep spindle behavior and thus allow more precise automated assessments of spindle-related functions., (Copyright © 2013 Elsevier B.V. All rights reserved.)