Smartphone-based pathogen diagnosis in urinary sepsis patients.

BackgroundThere is an urgent need for rapid, sensitive, and affordable diagnostics for microbial infections at the point-of-care. Although a number of innovative systems have been reported that transform mobile phones into potential diagnostic tools, the translational challenge to clinical diagnostics remains a significant hurdle to overcome.MethodsA smartphone-based real-time loop-mediated isothermal amplification (smaRT-LAMP) system was developed for pathogen ID in urinary sepsis patients. The free, custom-built mobile phone app allows the phone to serve as a stand-alone device for quantitative diagnostics, allowing the determination of genome copy-number of bacterial pathogens in real time.FindingsA head-to-head comparative bacterial analysis of urine from sepsis patients revealed that the performance of smaRT-LAMP matched that of clinical diagnostics at the admitting hospital in a fraction of the time (~1 h vs. 18-28 h). Among patients with bacteremic complications of their urinary sepsis, pathogen ID from the urine matched that from the blood - potentially allowing pathogen diagnosis shortly after hospital admission. Additionally, smaRT-LAMP did not exhibit false positives in sepsis patients with clinically negative urine cultures.InterpretationThe smaRT-LAMP system is effective against diverse Gram-negative and -positive pathogens and biological specimens, costs less than $100 US to fabricate (in addition to the smartphone), and is configurable for the simultaneous detection of multiple pathogens. SmaRT-LAMP thus offers the potential to deliver rapid diagnosis and treatment of urinary tract infections and urinary sepsis with a simple test that can be performed at low cost at the point-of-care. FUND: National Institutes of Health, Chan-Zuckerberg Biohub, Bill and Melinda Gates Foundation

Day surgery in a teaching hospital: identifying barriers to productivity.

Introduction: Ambulatory surgery is a standard of care for many surgical procedures due to cost-effectiveness and benefits to patients including the reduced risk of contracting hospital infection by reducing the hospital stay. However, late cancellations can be costly. We examined the utilisation of the surgical day ward in our institution over a four-year period. Methods: A retrospective study of surgical day ward records from September 2007 to September 2011 in one institution. Parameters investigated included the number of planned admissions. Reasons for cancellations were also collected. Results: A total of 17,461 procedures were intended as a day ward admission during the study interval. There were 3,539 procedures that were cancelled (20.3%). The prevalent proportion of cancellations (n = 1,367) (38.6%) were due to patients not showing up for their procedures (7.8% of planned admissions); 1,188 (33.6%) patients were cancelled by the admissions office due to bed shortages, accounting for 6.8 % of planned admissions and 650 (18.4%) of cases were due to last minute cancellations by patients, accounting for 3.7% of all planned admission. The remaining 334 (9.4%) of cases were cancelled on medical grounds including patients who were considered unfit for the intended procedure, or anti-coagulations not appropriately ceased prior to surgery, accounting for 1.9% of all planned admissions. Conclusion: The cancellation rate in this study was high, mainly due to failure of patients to attend or signal their intentions, inadequate bed capacity and bed closure strategies. The ring fencing and protection of day beds and a more active patient management interaction would have had the greatest impact on increased efficiency

Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer's disease: a case series.

BACKGROUND: The causes of phenotypic heterogeneity in familial Alzheimer's disease with autosomal dominant inheritance are not well understood. We aimed to characterise clinical phenotypes and genetic associations with APP and PSEN1 mutations in symptomatic autosomal dominant familial Alzheimer's disease (ADAD). METHODS: We retrospectively analysed genotypic and phenotypic data (age at symptom onset, initial cognitive or behavioural symptoms, and presence of myoclonus, seizures, pyramidal signs, extrapyramidal signs, and cerebellar signs) from all individuals with ADAD due to APP or PSEN1 mutations seen at the Dementia Research Centre in London, UK. We examined the frequency of presenting symptoms and additional neurological features, investigated associations with age at symptom onset, APOE genotype, and mutation position, and explored phenotypic differences between APP and PSEN1 mutation carriers. The proportion of individuals presenting with various symptoms was analysed with descriptive statistics, stratified by mutation type. FINDINGS: Between July 1, 1987, and Oct 31, 2015, age at onset was recorded for 213 patients (168 with PSEN1 mutations and 45 with APP mutations), with detailed history and neurological examination findings available for 121 (85 with PSEN1 mutations and 36 with APP mutations). We identified 38 different PSEN1 mutations (four novel) and six APP mutations (one novel). Age at onset differed by mutation, with a younger onset for individuals with PSEN1 mutations than for those with APP mutations (mean age 43·6 years [SD 7·2] vs 50·4 years [SD 5·2], respectively, p<0·0001); within the PSEN1 group, 72% of age at onset variance was explained by the specific mutation. A cluster of five mutations with particularly early onset (mean age at onset <40 years) involving PSEN1's first hydrophilic loop suggests critical functional importance of this region. 71 (84%) individuals with PSEN1 mutations and 35 (97%) with APP mutations presented with amnestic symptoms, making atypical cognitive presentations significantly more common in PSEN1 mutation carriers (n=14; p=0·037). Myoclonus and seizures were the most common additional neurological features; individuals with myoclonus (40 [47%] with PSEN1 mutations and 12 [33%] with APP mutations) were significantly more likely to develop seizures (p=0·001 for PSEN1; p=0·036 for APP), which affected around a quarter of the patients in each group (20 [24%] and nine [25%], respectively). A number of patients with PSEN1 mutations had pyramidal (21 [25%]), extrapyramidal (12 [14%]), or cerebellar (three [4%]) signs. INTERPRETATION: ADAD phenotypes are heterogeneous, with both age at onset and clinical features being influenced by mutation position as well as causative gene. This highlights the importance of considering genetic testing in young patients with dementia and additional neurological features in order to appropriately diagnose and treat their symptoms, and of examining different mutation types separately in future research. FUNDING: Medical Research Council and National Institute for Health Research

Generation and characterization of carbonyl ylides from pyrazolinone spirooxiranes

Laser flash photolyses of 1-oxa-5,6-diazaspiro[2.4]hept-6-ene-4-ones I (Ar [triple bond] Ph, p-NO2Ph, p-CH3OPh; R1 [tripe bond] CH3, Ph; R2, R3 [triple bond] CH3; R2 [triple bond] Ph, p-NO2Ph, p-ClPh, 2-naphthyl; R3 [triple bond] H) and of the symmetrical oxirane II give rise to transients with absorption spectra in the visible region and lifetimes of the order of 0.3 - 10 [mu]s in benzene at room temperature. Sensitization experiments in some cases indicate that the intermediate may arise from a triplet as well as a singlet excited state. Transients from I are quenched by alcohols and 2,3-dimethyl-2-butene whereas that from II is not. Steady state photolyses of I in methanol give products consistent with the assignment of the structure of the transient as a carbonyl ylide incorporating the pyrazolinone ring.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31041/1/0000718.pd

The Change Up Project : using social norming theory with young people to address domestic abuse and promote healthy relationships

This paper presents the findings of a secondary analysis of data collected during a pilot project, Change Up, which used a social norming approach (SNA) to address domestic violence and abuse (DVA) with young people aged 13–14. A SNA is based upon a well-articulated theory of behavior and evidence-based methodology for addressing social justice issues. This reflects a paradigm shift focusing upon strengths and positives, rather than pathologizing behaviours. Adopting a SNA, the Change Up project comprised a baseline survey followed by the intervention (workshop and peer-to-peer campaign), ending with a post-intervention survey. It was delivered in two high schools in a UK city between 2015 and 16. A secondary analysis of the survey data collected during the surveys and qualitative data collected at the end of each workshop was undertaken and this is reported here. Change Up data illustrates that most young people in the sample thought that DVA is unacceptable. There was, however, a gender difference in the norms held about the social acceptability of girls using physical violence against boys (and vice versa). The analysis of Change Up data indicates that a social norming approach to DVA programs aimed at young people can be successful in promoting attitude and behaviour change. It also highlights a continuing need for young people’s education about relationships and gender equality

Assessing the Factorial Validity of the Attitudes and Belief Scale 2-Abbreviated Version: A Call for the Development a Gold Standard Method of Measuring Rational and Irrational Beliefs

Rational Emotive Behaviour Therapy (REBT) does not possess a measure of rational and irrational beliefs that meets internationally recognised standards for acceptable psychometric properties. Without such a measure the theory/practice of REBT cannot be rigorously evaluated, thus undermining its scientific veracity. The current study investigates the validity and reliability of a recently developed measure of rational and irrational beliefs: the Attitudes and Belief Scale 2-Abbreviated Version (ABS-2-AV). University students from three countries completed the ABS-2-AV (N = 397). An alternative models framework using confirmatory factor analysis indicated that a theoretically consistent eight-factor model of the ABS-2-AV provided the best fit of the data. A number of post-hoc modifications were required in order to achieve acceptable model fit results, and these modifications revealed important methodological limitations with the ABS-2-AV. Results indicated that the validity of the ABS-2-AV was undermined due to items measuring both the psychological process of interest (rational and irrational beliefs) and the context in which these beliefs processes are presented. This is a serious methodological limitation of the ABS-2 and all questionnaires derived from it, including the ABS-2-AV. This methodological limitation resulted in the ABS-2-AV possessing poor internal reliability. These limitations are discussed in relation to the broader REBT literature and the impact such problems have on research and practice. A call is made for REBT researchers to come together to develop a “gold standard” method of assessing rational and irrational beliefs that meets international standard for psychometric excellence

Measurement of the Branching Fraction for B- --> D0 K*-

We present a measurement of the branching fraction for the decay B- --> D0 K*- using a sample of approximately 86 million BBbar pairs collected by the BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the K*- through its decay to K0S pi-. We measure the branching fraction to be B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}.Comment: 7 pages, 1 postscript figure, submitted to Phys. Rev. D (Rapid Communications

Time-integrated luminosity recorded by the BABAR detector at the PEP-II e+e- collider

This article is the Preprint version of the final published artcile which can be accessed at the link below.We describe a measurement of the time-integrated luminosity of the data collected by the BABAR experiment at the PEP-II asymmetric-energy e+e- collider at the ϒ(4S), ϒ(3S), and ϒ(2S) resonances and in a continuum region below each resonance. We measure the time-integrated luminosity by counting e+e-→e+e- and (for the ϒ(4S) only) e+e-→μ+μ- candidate events, allowing additional photons in the final state. We use data-corrected simulation to determine the cross-sections and reconstruction efficiencies for these processes, as well as the major backgrounds. Due to the large cross-sections of e+e-→e+e- and e+e-→μ+μ-, the statistical uncertainties of the measurement are substantially smaller than the systematic uncertainties. The dominant systematic uncertainties are due to observed differences between data and simulation, as well as uncertainties on the cross-sections. For data collected on the ϒ(3S) and ϒ(2S) resonances, an additional uncertainty arises due to ϒ→e+e-X background. For data collected off the ϒ resonances, we estimate an additional uncertainty due to time dependent efficiency variations, which can affect the short off-resonance runs. The relative uncertainties on the luminosities of the on-resonance (off-resonance) samples are 0.43% (0.43%) for the ϒ(4S), 0.58% (0.72%) for the ϒ(3S), and 0.68% (0.88%) for the ϒ(2S).This work is supported by the US Department of Energy and National Science Foundation, the Natural Sciences and Engineering Research Council (Canada), the Commissariat à l’Energie Atomique and Institut National de Physique Nucléaire et de Physiquedes Particules (France), the Bundesministerium für Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany), the Istituto Nazionale di Fisica Nucleare (Italy), the Foundation for Fundamental Research on Matter (The Netherlands), the Research Council of Norway, the Ministry of Education and Science of the Russian Federation, Ministerio de Ciencia e Innovación (Spain), and the Science and Technology Facilities Council (United Kingdom). Individuals have received support from the Marie-Curie IEF program (European Union) and the A.P. Sloan Foundation (USA)

Does Environmental Enrichment Reduce Stress? An Integrated Measure of Corticosterone from Feathers Provides a Novel Perspective

Enrichment is widely used as tool for managing fearfulness, undesirable behaviors, and stress in captive animals, and for studying exploration and personality. Inconsistencies in previous studies of physiological and behavioral responses to enrichment led us to hypothesize that enrichment and its removal are stressful environmental changes to which the hormone corticosterone and fearfulness, activity, and exploration behaviors ought to be sensitive. We conducted two experiments with a captive population of wild-caught Clark's nutcrackers (Nucifraga columbiana) to assess responses to short- (10-d) and long-term (3-mo) enrichment, their removal, and the influence of novelty, within the same animal. Variation in an integrated measure of corticosterone from feathers, combined with video recordings of behaviors, suggests that how individuals perceive enrichment and its removal depends on the duration of exposure. Short- and long-term enrichment elicited different physiological responses, with the former acting as a stressor and birds exhibiting acclimation to the latter. Non-novel enrichment evoked the strongest corticosterone responses of all the treatments, suggesting that the second exposure to the same objects acted as a physiological cue, and that acclimation was overridden by negative past experience. Birds showed weak behavioral responses that were not related to corticosterone. By demonstrating that an integrated measure of glucocorticoid physiology varies significantly with changes to enrichment in the absence of agonistic interactions, our study sheds light on potential mechanisms driving physiological and behavioral responses to environmental change