The second physical therapy summit on global health: developing an action plan to promote health in daily practice and reduce the burden of non-communicable diseases

Based on indicators that emerged from The First Physical Therapy Summit on Global Health (2007), the Second Summit (2011) identified themes to inform a global physical therapy action plan to integrate health promotion into practice across the World Confederation for Physical Therapy (WCPT) regions. Working questions were: (1) how well is health promotion implemented within physical therapy practice; and (2) how might this be improved across five target audiences (i.e. physical therapist practitioners, educators, researchers, professional body representatives, and government liaisons/consultants). In structured facilitated sessions, Summit representatives (n=32) discussed: (1) within WCPT regions, what is working and the challenges; and (2) across WCPT regions, what are potential directions using World CaféTM methodology. Commonalities outweighed differences with respect to strategies to advance health-focused physical therapy as a clinical competency across regions and within target audiences. Participants agreed that health-focused practice is a professional priority, and a strategic action plan was needed to develop it as a clinical competency. The action plan and recommendations largely paralleled the principles and objectives of the World Health Organization's non-communicable diseases action plan. A third Summit planned for 2015 will provide a mechanism for follow-up to evaluate progress in integrating health-focused physical therapy within the profession.info:eu-repo/semantics/acceptedVersio

Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data

BACKGROUND: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated. METHODS: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility. RESULTS: Antimicrobial susceptibility category agreement in each year was ≥91%. Discrepancies in susceptibility categories were generally because the MICs for EQA panel isolates were on or very close to the susceptibility or resistance breakpoints. A high proportion of isolates tested over the 10 years were within one (≥90%) or two (≥97%) MIC log2 dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods. CONCLUSIONS: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.The study was funded by the European Centre for Disease Prevention and Control (Framework Contract No. ECDC/2013/015). The funding body contributed to the design of the study, the interpretation of the data and to the writing of the manuscript.S

Foxp2 Regulates Gene Networks Implicated in Neurite Outgrowth in the Developing Brain

Forkhead-box protein P2 is a transcription factor that has been associated with intriguing aspects of cognitive function in humans, non-human mammals, and song-learning birds. Heterozygous mutations of the human FOXP2 gene cause a monogenic speech and language disorder. Reduced functional dosage of the mouse version (Foxp2) causes deficient cortico-striatal synaptic plasticity and impairs motor-skill learning. Moreover, the songbird orthologue appears critically important for vocal learning. Across diverse vertebrate species, this well-conserved transcription factor is highly expressed in the developing and adult central nervous system. Very little is known about the mechanisms regulated by Foxp2 during brain development. We used an integrated functional genomics strategy to robustly define Foxp2-dependent pathways, both direct and indirect targets, in the embryonic brain. Specifically, we performed genome-wide in vivo ChIP–chip screens for Foxp2-binding and thereby identified a set of 264 high-confidence neural targets under strict, empirically derived significance thresholds. The findings, coupled to expression profiling and in situ hybridization of brain tissue from wild-type and mutant mouse embryos, strongly highlighted gene networks linked to neurite development. We followed up our genomics data with functional experiments, showing that Foxp2 impacts on neurite outgrowth in primary neurons and in neuronal cell models. Our data indicate that Foxp2 modulates neuronal network formation, by directly and indirectly regulating mRNAs involved in the development and plasticity of neuronal connections

Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation

Correction: Exome Sequencing in an Admixed Isolated Population IndicatesNFXL1 Variants Confer a Risk for Specific Language Impairment

Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10–4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model

Non-Psychotic Outcomes and Personality Disorders in Young People at Ultra-High Risk of Developing a Psychotic Disorder: A Long-Term Follow-Up Study

© 2019 Anneliese Elizabeth Spiteri-StainesBackground: Despite there being a large body of research available on the precursors of psychosis (the “prodromal” phase), there is a paucity of literature available on pre or comorbid mental and personality disorders in the ultra-high risk (UHR) for psychosis population. Most research thus far has been cross-sectional, with only a few long-term follow-ups, limiting the ability to investigate the long-term pattern and outcomes of comorbidity. Aims: The current study investigated comorbidity of non-psychotic mental and personality disorders in the UHR population - specifically, the prevalence of these disorders at entry and follow-up and their association with clinical and functional outcomes over the long-term (6 to 12 years). In addition, this study investigated the issue of whether UHR status is specific to psychosis outcomes or for a range of non-psychotic mental disorders, including major depressive disorder, anxiety disorder and personality disorders. The current study also aimed to identify baseline clinical predictors of the long-term trajectories of mental disorder. Method: The sample comprised 172 young people from the Personal Assessment & Crisis Evaluation (PACE) Clinic considered to be at UHR of developing a psychotic disorder. The majority of the original sample (n=125, 72.7%) presented for follow-up assessment (mean=8.8 years, range = 6.8 to 12.1 years since baseline assessment). Comorbid non-psychotic mental and personality disorders were assessed using the Structured Clinical Interview for DSM-IV (SCID I and II). Global functioning was assessed using the global assessment of functioning (GAF) scale, the Social and Occupational Functioning Assessment Scale (SOFAS) and the Quality of Life Scale (QLS). Results: Only 13% of participants did not meet criteria for a non-psychotic mental disorder diagnosis at baseline. The remaining 87% of participants were diagnosed with mental disorders, the majority of which were mood disorders (79%), followed by anxiety disorders (48%) and substance use disorders (18%). The pattern of disorder prevalence present at baseline continued at follow-up, though at a reduced rate, with 48.8% not meeting criteria for non-psychotic mental disorder. The disorder that proved to be most persistent for participants over time was mood disorder, with 45% of the sample experiencing this continuously. Baseline clinical predictor variables were unable to predict remission of a non-psychotic mental disorder. However, meeting Trait Vulnerability UHR criteria predicted incidence of a non-psychotic disorder and high scores on baseline psychopathology predicted continuous non-psychotic disorder over time. Presence of a continuous non-psychotic mental disorder was also associated with lower functional outcomes on multiple measures at follow-up. Baseline mental disorder was not significantly associated with transition to psychosis. Persistence of attenuated psychotic symptoms was experienced by 30% of the sample at follow up assessment and this was significantly associated with impairment in social and occupational functioning. Personality disorders were reported by 19% of the sample at follow-up. The most prevalent disorder was borderline personality disorder (11%). Personality disorders were associated with poorer clinical and functional outcomes: presence of personality disorders (compared to no personality disorder) was associated with an increased rate of transition to psychosis, and was associated with presence of comorbid non-psychotic mental disorder and poorer social and functional outcomes. Conclusions: Most (84%) participants meeting UHR criteria at baseline did not go on to develop psychosis. The majority did, however, present with persisting non-psychotic mental disorders that were associated with poorer functional outcomes at follow-up. The course of non-psychotic mental disorders in UHR participants over time was able to be predicted for continuous and incident disorders using baseline clinical variables, though the strength of the predictions was modest. Therefore, the link between baseline clinical predictors and long-term mental health outcomes would benefit from further investigation. Almost one-third of UHR participants continued to experience attenuated psychotic symptoms over the longer term. Those who also met criteria for personality disorders at follow-up were also more likely to be experiencing comorbid non-psychotic mental disorders, poorer functional outcomes and an increased risk of transition to psychosis than those who did not have a personality disorder. This research indicates that people meeting criteria for UHR are at risk of experiencing a range of other non-psychotic psychiatric problems over time

Impact of Relative Permeability Hysteresis on the Numerical Simulation

Abstract Pore-scale physics, laboratory investigations, and field experience, dictate that three-phase relative permeabilities exhibit strong dependence on the saturation path and the saturation history. Such dependence is especially relevant in immiscible wateralternating-gas (WAG) processes, which are characterized by a sequence of three-phase drainage and imbibition cycles. In this paper, we study the influence of relative permeability hysteresis on the field-scale predictions of WAG injection. Because their measurement is difficult and time-consuming, three-phase relative permeabilities are usually interpolated from two-phase data. The errors associated with this procedure have been investigated by Oak (SPE 20183), who reported that interpolated values might differ significantly from experimental ones. The effect of using different interpolation models in field-scale simulations has been illustrated by a number of authors, who found that recovery predictions could be significantly different depending on the three-phase relative permeability model. Here, we study the impact of using history-dependent saturation functions in reservoir simulations. First, we investigate the degree of accuracy with which different hysteretic models reproduce Oak's three-phase relative permeability data. In doing so, we assess the validity of existing models, and we identify the model parameters subject to most uncertainty. Our analysis suggests that current models account for some of the hysteretic behavior observed experimentally, but do not reproduce experimental measurements adequately during cyclic water/gas injection. Second, we illustrate how the use of a hysteretic relative permeability model affects reservoir simulations. We use a synthetic model of a quarter five-spot pattern in a homogenous reservoir, and a more realistic heterogeneous reservoir modified from the PUNQ-S3 model. We find that there is striking disparity in the simulation results depending on whether a hysteretic or a nonhysteretic model is employed. Therefore, we conclude that (1) it is essential to incorporate hysteresis in the relative permeabilities in order to obtain accurate predictions of realistic immiscible WAG processes; and (2) enhancements are needed to improve the predictive capabilities of current relative permeability hysteresis models.