Study of user-experience of an objective test (QbTest) to aid ADHD assessment and medication management: a multi-methods approach

Background The diagnosis and monitoring of Attention deficit hyperactivity disorder (ADHD) typically relies on subjective reports and observations. Objective continuous performance tests (CPTs) have been incorporated into some services to support clinical decision making. However, the feasibility and acceptability of adding such a test into routine practice is unknown. The study aimed to investigate the feasibility and acceptability of adding an objective computerised test to the routine assessment and monitoring of attention deficit hyperactivity disorder (ADHD). Methods Semi-structured interviews were conducted with clinicians (n = 10) and families (parents/young people, n = 20) who participated in a randomised controlled trial. Additionally, the same clinicians (n = 10) and families (n = 76) completed a survey assessing their experience of the QbTest. The study took place in child and adolescent mental health and community paediatric clinics across the UK. Interview transcripts were thematically analysed. Results Interviewed clinicians and families valued the QbTest for providing an objective, valid assessment of symptoms. The QbTest was noted to facilitate communication between clinicians, families and schools. However, whereas clinicians were more unanimous on the usefulness of the QbTest, survey findings showed that, although the majority of families found the test useful, less than half felt the QbTest helped them understand the clinician’s decision making around diagnosis and medication. The QbTest was seen as a potentially valuable tool to use early in the assessment process to streamline the care pathway. Although clinicians were conscious of the additional costs, these could be offset by reductions in time to diagnosis and the delivery of the test by a Healthcare Assistant. Conclusions The findings indicate the QbTest is an acceptable and feasible tool to implement in routine clinical settings. Clinicians should be mindful to discuss the QbTest results with families to enable their understanding and engagement with the process. Further findings from definitive trials are required to understand the cost/benefit; however, the findings from this study support the feasibility and acceptability of integrating QbTest in the ADHD care pathway

Neutrino Mass, Sneutrino Dark Matter and Signals of Lepton Flavor Violation in the MRSSM

We study the phenomenology of mixed-sneutrino dark matter in the Minimal R-Symmetric Supersymmetric Standard Model (MRSSM). Mixed sneutrinos fit naturally within the MRSSM, as the smallness (or absence) of neutrino Yukawa couplings singles out sneutrino A-terms as the only ones not automatically forbidden by R-symmetry. We perform a study of randomly generated sneutrino mass matrices and find that (i) the measured value of $\Omega_{DM}$ is well within the range of typical values obtained for the relic abundance of the lightest sneutrino, (ii) with small lepton-number-violating mass terms $m_{nn}^{2} {\tilde n} {\tilde n}$ for the right-handed sneutrinos, random matrices satisfying the $\Omega_{DM}$ constraint have a decent probability of satisfying direct detection constraints, and much of the remaining parameter space will be probed by upcoming experiments, (iii) the $m_{nn}^{2} {\tilde n} {\tilde n}$ terms radiatively generate appropriately small Majorana neutrino masses, with neutrino oscillation data favoring a mostly sterile lightest sneutrino with a dominantly mu/tau-flavored active component, and (iv) a sneutrino LSP with a significant mu component can lead to striking signals of e-mu flavor violation in dilepton invariant-mass distributions at the LHC.Comment: Revised collider analysis in Sec. 5 after fixing error in particle spectrum, References adde

Who Watches the Watchmen? An Appraisal of Benchmarks for Multiple Sequence Alignment

Multiple sequence alignment (MSA) is a fundamental and ubiquitous technique in bioinformatics used to infer related residues among biological sequences. Thus alignment accuracy is crucial to a vast range of analyses, often in ways difficult to assess in those analyses. To compare the performance of different aligners and help detect systematic errors in alignments, a number of benchmarking strategies have been pursued. Here we present an overview of the main strategies--based on simulation, consistency, protein structure, and phylogeny--and discuss their different advantages and associated risks. We outline a set of desirable characteristics for effective benchmarking, and evaluate each strategy in light of them. We conclude that there is currently no universally applicable means of benchmarking MSA, and that developers and users of alignment tools should base their choice of benchmark depending on the context of application--with a keen awareness of the assumptions underlying each benchmarking strategy.Comment: Revie

Evaluating the effects of bilingual traffic signs on driver performance and safety

Variable Message Signs (VMS) can provide immediate and relevant information to road users and bilingual VMS can provide great flexibility in countries where a significant proportion of the population speak an alternative language to the majority. The study reported here evaluates the effect of various bilingual VMS configurations on driver behaviour and safety. The aim of the study was to determine whether or not the visual distraction associated with bilingual VMS signs of different configurations (length, complexity) impacted on driving performance. A driving simulator was used to allow full control over the scenarios, road environment and sign configuration and both longitudinal and lateral driver performance was assessed. Drivers were able to read one and two-line monolingual signs and two-line bilingual signs without disruption to their driving behaviour. However, drivers significantly reduced their speed in order to read four-line monolingual and four-line bilingual signs, accompanied by an increase in headway to the vehicle in front. This implies that drivers are possibly reading the irrelevant text on the bilingual sign and various methods for reducing this effect are discussed

Is palliative care support associated with better quality end-of-life care indicators for patients with advanced cancer? A retrospective cohort study.

OBJECTIVES: This study aimed to establish the association between timing and provision of palliative care (PC) and quality of end-of-life care indicators in a population of patients dying of cancer. SETTING: This study uses linked cancer patient data from the National Cancer Registry, the electronic medical record system used in primary care (SystmOne) and the electronic medical record system used within a specialist regional cancer centre. The population resided in a single city in Northern England. PARTICIPANTS: Retrospective data from 2479 adult cancer decedents who died between January 2010 and February 2012 were registered with a primary care provider using the SystmOne electronic health record system, and cancer was certified as a cause of death, were included in the study. RESULTS: Linkage yielded data on 2479 cancer decedents, with 64.5% who received at least one PC event. Decedents who received PC were significantly more likely to die in a hospice (39.4% vs 14.5%, P<0.005) and less likely to die in hospital (23.3% vs 40.1%, P<0.05), and were more likely to receive an opioid (53% vs 25.2%, P<0.001). PC initiated more than 2 weeks before death was associated with avoiding a hospital death (≥2 weeks, P<0.001), more than 4 weeks before death was associated with avoiding emergency hospital admissions and increased access to an opioid (≥4 weeks, P<0.001), and more than 33 weeks before death was associated with avoiding late chemotherapy (≥33 weeks, no chemotherapy P=0.019, chemotherapy over 4 weeks P=0.007). CONCLUSION: For decedents with advanced cancer, access to PC and longer duration of PC were significantly associated with better end-of-life quality indicators

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Accurate detection of Neisseria gonorrhoeae ciprofloxacin susceptibility directly from genital and extragenital clinical samples: towards genotype-guided antimicrobial therapy.

INTRODUCTION: Increasing use of nucleic acid amplification tests (NAATs) as the primary means of diagnosing gonococcal infection has resulted in diminished availability of Neisseria gonorrhoeae antimicrobial susceptibility data. We conducted a prospective diagnostic assessment of a real-time PCR assay (NGSNP) enabling direct detection of gonococcal ciprofloxacin susceptibility from a range of clinical sample types. METHODS: NGSNP, designed to discriminate an SNP associated with ciprofloxacin resistance within the N. gonorrhoeae genome, was validated using a characterized panel of geographically diverse isolates (n = 90) and evaluated to predict ciprofloxacin susceptibility directly on N. gonorrhoeae-positive NAAT lysates derived from genital (n = 174) and non-genital (n = 116) samples (n = 290), from 222 culture-confirmed clinical episodes of gonococcal infection. RESULTS: NGSNP correctly genotyped all phenotypically susceptible (n = 49) and resistant (n = 41) panel isolates. Ciprofloxacin-resistant N. gonorrhoeae was responsible for infection in 29.7% (n = 66) of clinical episodes evaluated. Compared with phenotypic susceptibility testing, NGSNP demonstrated sensitivity and specificity of 95.8% (95% CI 91.5%-98.3%) and 100% (95% CI 94.7%-100%), respectively, for detecting ciprofloxacin-susceptible N. gonorrhoeae, with a positive predictive value of 100% (95% CI 97.7%-100%). Applied to urogenital (n = 164), rectal (n = 40) and pharyngeal samples alone (n = 30), positive predictive values were 100% (95% CI 96.8%-100%), 100% (95% CI 87.2%-100%) and 100% (95% CI 82.4%-100%), respectively. CONCLUSIONS: Genotypic prediction of N. gonorrhoeae ciprofloxacin susceptibility directly from clinical samples was highly accurate and, in the absence of culture, will facilitate use of tailored therapy for gonococcal infection, sparing use of current empirical treatment regimens and enhancing acquisition of susceptibility data for surveillance

Low Scale Flavor Gauge Symmetries

We study the possibility of gauging the Standard Model flavor group. Anomaly cancellation leads to the addition of fermions whose mass is inversely proportional to the known fermion masses. In this case all flavor violating effects turn out to be controlled roughly by the Standard Model Yukawa, suppressing transitions for the light generations. Due to the inverted hierarchy the scale of new gauge flavor bosons could be as low as the electroweak scale without violating any existing bound but accessible at the Tevatron and the LHC. The mechanism of flavor protection potentially provides an alternative to Minimal Flavor Violation, with flavor violating effects suppressed by hierarchy of scales rather than couplings.Comment: 24 pages + appendices; v2) Refs. added and numerical examples improved. Results unchanged; v3) small typos in appendix B correcte

A pilot study comparing the metabolic profiles of elite-level athletes from different sporting disciplines

Background: The outstanding performance of an elite athlete might be associated with changes in their blood metabolic profile. The aims of this study were to compare the blood metabolic profiles between moderate- and high-power and endurance elite athletes and to identify the potential metabolic pathways underlying these differences. Methods: Metabolic profiling of serum samples from 191 elite athletes from different sports disciplines (121 high- and 70 moderate-endurance athletes, including 44 high- and 144 moderate-power athletes), who participated in national or international sports events and tested negative for doping abuse at anti-doping laboratories, was performed using non-targeted metabolomics-based mass spectroscopy combined with ultrahigh-performance liquid chromatography. Multivariate analysis was conducted using orthogonal partial least squares discriminant analysis. Differences in metabolic levels between high- and moderate-power and endurance sports were assessed by univariate linear models. Results: Out of 743 analyzed metabolites, gamma-glutamyl amino acids were significantly reduced in both high-power and high-endurance athletes compared to moderate counterparts, indicating active glutathione cycle. High-endurance athletes exhibited significant increases in the levels of several sex hormone steroids involved in testosterone and progesterone synthesis, but decreases in diacylglycerols and ecosanoids. High-power athletes had increased levels of phospholipids and xanthine metabolites compared to moderate-power counterparts. Conclusions: This pilot data provides evidence that high-power and high-endurance athletes exhibit a distinct metabolic profile that reflects steroid biosynthesis, fatty acid metabolism, oxidative stress, and energy-related metabolites. Replication studies are warranted to confirm differences in the metabolic profiles associated with athletes’ elite performance in independent data sets, aiming ultimately for deeper understanding of the underlying biochemical processes that could be utilized as biomarkers with potential therapeutic implications

Do psychosocial interventions have an impact on maternal perception of perinatal depression?

YesPoor perinatal mental health, in particular depression, affects at least 10% of new mothers in the UK. Current best practice recommends the use of talking therapies or medication, however, many women choose not to use medication or are deterred from accessing NHS services for example due to immigration status. Those who can access NHS treatment often face a long waiting list to see a clinician or therapist. Untreated perinatal depression impacts on the health and wellbeing of mothers and babies, consequently it is essential that alternative psychosocial interventions delivered by non-clinicians are considered. A systematic review was conducted on seven quantitative studies examining the effect of psychosocial interventions in reducing maternal symptoms of depression. Interventions focused either on physical activity or peer support, measuring depression scores on a validated screening tool. The review concludes that antenatal group peer support may benefit women in the antenatal period and that postnatal peer telephone support may be helpful for primiparous women but further large scale research is required