A starting point in the evaluation of the outcome of care: an example using cancer registry information

Many health services worldwide are paying increasing attention to the evaluation of care. However, most studies in the past have concentrated on structure and process instead of outcome. The objective of this paper is to show how a fairly simple technique can provide a possible feedback loop to a health service system. A study on patients with lung cancer in East Anglia, UK is used as an example. Using information which was more or less routinely collected in cancer registration, the study showed that there was no significant difference between the survival of patients seen in the eight districts in East Anglia. Adjustment by the use proportional hazard modelling for prognostic factors including age, sex, histological type, stage and whether active treatment was given did not alter the outcome. This finding was slightly unexpected in view of the presumed (yet not documented) variation in enthusiasm and expertise among the districts. Such a result should be seen as a starting point for studies designed to examine the effects of the level of care provided and resource use on the length and quality of survival. While the methodology requires refinement and substantial local difficulties may arise, development of similar researches on the outcome of care should be encouraged in Hong Kong.published_or_final_versio

Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders.

Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P<0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability

Probabilistic Map-matching using Particle Filters

Increasing availability of vehicle GPS data has created potentially transformative opportunities for trac management, route planning and other location-based services. Critical to the utility of the data is their accuracy. Map-matching is the process of improving the accuracy by aligning GPS data with the road network. In this paper, we propose a purely probabilistic approach to map-matching based on a sequential Monte Carlo algorithm known as particle filters. The approach performs map-matching by producing a range of candidate solutions, each with an associated probability score. We outline implementation details and thoroughly validate the technique on GPS data of varied quality

Probabilistic Map-matching using Particle Filters

Increasing availability of vehicle GPS data has created potentially transformative opportunities for trac management, route planning and other location-based services. Critical to the utility of the data is their accuracy. Map-matching is the process of improving the accuracy by aligning GPS data with the road network. In this paper, we propose a purely probabilistic approach to map-matching based on a sequential Monte Carlo algorithm known as particle filters. The approach performs map-matching by producing a range of candidate solutions, each with an associated probability score. We outline implementation details and thoroughly validate the technique on GPS data of varied quality

Hypothermia protects brain mitochondrial function from hypoxemia in a murine model of sepsis

Sepsis is commonly associated with brain dysfunction, but the underlying mechanisms remain unclear, although mitochondrial dysfunction and microvascular abnormalities have been implicated. We therefore assessed whether cerebral mitochondrial dysfunction during systemic endotoxemia in mice increased mitochondrial sensitivity to a further bioenergetic insult (hyoxemia), and whether hypothermia could improve outcome. Mice (C57bl/6) were injected intraperitoneally with lipopolysaccharide (LPS) (5 mg/kg; n = 85) or saline (0.01 ml/g; n = 47). Six, 24 and 48h later, we used confocal imaging in vivo to assess cerebral mitochondrial redox potential and cortical oxygenation in response to changes in inspired oxygen. The fraction of inspired oxygen (FiO2) at which the cortical redox potential changed was compared between groups. In a subset of animals, spontaneous hypothermia was maintained or controlled hypothermia induced during imaging. Decreasing FiO2 resulted in a more reduced cerebral redox state around veins but preserved oxidation around arteries. This pattern appeared at a higher FiO2 in LPS-injected animals, suggesting an increased sensitivity of cortical mitochondria to hypoxemia. This increased sensitivity was accompanied by a decrease in cortical oxygenation, but was attenuated by hypothermia. These results suggest that systemic endotoxemia influences cortical oxygenation and mitochondrial function, and that therapeutic hypothermia can be protective

Decreased mass specific respiration under experimental warming is robust to the microbial biomass method employed

Hartley et al. question whether reduction in Rmass, under experimental warming, arises because of the biomass method. We show the method they treat as independent yields the same result. We describe why the substrate-depletion hypothesis may not solely explain observed responses, and urge caution in interpretation of the seasonal data. © 2009 Blackwell Publishing Ltd/CNRS

Structural basis for hemoglobin capture by Staphylococcus aureus cell-surface protein, IsdH

Pathogens must steal iron from their hosts to establish infection. In mammals, hemoglobin (Hb) represents the largest reservoir of iron, and pathogens express Hb-binding proteins to access this source. Here, we show how one of the commonest and most significant human pathogens, Staphylococcus aureus, captures Hb as the first step of an iron-scavenging pathway. The x-ray crystal structure of Hb bound to a domain from the Isd (iron-regulated surface determinant) protein, IsdH, is the first structure of a Hb capture complex to be determined. Surface mutations in Hb that reduce binding to the Hb-receptor limit the capacity of S. aureus to utilize Hb as an iron source, suggesting that Hb sequence is a factor in host susceptibility to infection. The demonstration that pathogens make highly specific recognition complexes with Hb raises the possibility of developing inhibitors of Hb binding as antibacterial agents. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc

Edge Detection in Landing Budgerigars (Melopsittacus undulatus)

Background: While considerable scientific effort has been devoted to studying how birds navigate over long distances, relatively little is known about how targets are detected, obstacles are avoided and smooth landings are orchestrated. Here we examine how visual features in the environment, such as contrasting edges, determine where a bird will land. Methodology/Principal Findings: Landing in budgerigars (Melopsittacus undulatus) was investigated by training them to fly from a perch to a feeder, and video-filming their landings. The feeder was placed on a grey disc that produced a contrasting edge against a uniformly blue background. We found that the birds tended to land primarily at the edge of the disc and walk to the feeder, even though the feeder was in the middle of the disc. This suggests that the birds were using the visual contrast at the boundary of the disc to target their landings. When the grey level of the disc was varied systematically, whilst keeping the blue background constant, there was one intermediate grey level at which the budgerigar's preference for the disc boundary disappeared. The budgerigars then landed randomly all over the test surface. Even though this disc is (for humans) clearly distinguishable from the blue background, it offers very little contrast against the background, in the red and green regions of the spectrum. Conclusions: We conclude that budgerigars use visual edges to target and guide landings. Calculations of photoreceptor excitation reveal that edge detection in landing budgerigars is performed by a color-blind luminance channel that sums the signals from the red and green photoreceptors, or, alternatively, receives input from the red double-cones. This finding has close parallels to vision in honeybees and primates, where edge detection and motion perception are also largely color-blind

An in vitro analysis of medial structures and a medial soft tissue reconstruction in a constrained condylar total knee arthroplasty

Purpose: The aim of this study was to quantify the medial soft tissue contributions to stability following constrained condylar (CC) total knee arthroplasty (TKA) and determine whether a medial reconstruction could restore stability to a soft tissue-deficient, CC-TKA knee. Methods: Eight cadaveric knees were mounted in a robotic system and tested at 0°, 30°, 60°, and 90° of flexion with ±50 N anterior–posterior force, ±8 Nm varus–valgus, and ±5 Nm internal–external torque. The deep and superficial medial collateral ligaments (dMCL, sMCL) and posteromedial capsule (PMC) were transected and their relative contributions to stabilising the applied loads were quantified. After complete medial soft tissue transection, a reconstruction using a semitendinosus tendon graft was performed, and the effect on kinematic behaviour under equivocal conditions was measured. Results: In the CC-TKA knee, the sMCL was the major medial restraint in anterior drawer, internal–external, and valgus rotation. No significant differences were found between the rotational laxities of the reconstructed knee to the pre-deficient state for the arc of motion examined. The relative contribution of the reconstruction was higher in valgus rotation at 60° than the sMCL; otherwise, the contribution of the reconstruction was similar to that of the sMCL. Conclusion: There is contention whether a CC-TKA can function with medial deficiency or more constraint is required. This work has shown that a CC-TKA may not provide enough stability with an absent sMCL. However, in such cases, combining the CC-TKA with a medial soft tissue reconstruction may be considered as an alternative to a hinged implant

Ethnic inequalities and pathways to care in psychosis in England: a systematic review and meta-analysis

© The Author(s). 2018Background: As part of a national programme to tackle ethnic inequalities, we conducted a systematic review and meta-analysis of research on ethnic inequalities in pathways to care for adults with psychosis living in England and/or Wales. Methods: Nine databases were searched from inception to 03.07.17 for previous systematic reviews, including forward and backward citation tracking and a PROSPERO search to identify ongoing reviews. We then carried forward relevant primary studies from included reviews (with the latest meta-analyses reporting on research up to 2012), supplemented by a search on 18.10.17 in MEDLINE, Embase, PsycINFO and CINAHL for primary studies between 2012 and 2017 that had not been covered by previous meta-analyses. Results: Forty studies, all conducted in England, were included for our updated meta-analyses on pathways to care. Relative to the White reference group, elevated rates of civil detentions were found for Black Caribbean (OR = 3.43, 95% CI = 2.68 to 4.40, n = 18), Black African (OR = 3.11, 95% CI = 2.40 to 4.02, n = 6), and South Asian patients (OR = 1.50, 95% CI 1.07 to 2.12, n = 10). Analyses of each Mental Health Act section revealed significantly higher rates for Black people under (civil) Section 2 (OR = 1.53, 95% CI = 1.11 to 2.11, n = 3). Rates in repeat admissions were significantly higher than in first admission for South Asian patients (between-group difference p < 0.01). Some ethnic groups had more police contact (Black African OR = 3.60, 95% CI = 2.15 to 6.05, n = 2; Black Caribbean OR = 2.64, 95% CI = 1.88 to 3.72, n = 8) and criminal justice system involvement (Black Caribbean OR = 2.76, 95% CI = 2.02 to 3.78, n = 5; Black African OR = 1.92, 95% CI = 1.32 to 2.78, n = 3). The White Other patients also showed greater police and criminal justice system involvement than White British patients (OR = 1.49, 95% CI = 1.03 to 2.15, n = 4). General practitioner involvement was less likely for Black than the White reference group. No significant variations over time were found across all the main outcomes. Conclusions: Our updated meta-analyses reveal persisting but not significantly worsening patterns of ethnic inequalities in pathways to psychiatric care, particularly affecting Black groups. This provides a comprehensive evidence base from which to inform policy and practice amidst a prospective Mental Health Act reform. Trial registration: CRD42017071663Peer reviewedFinal Published versio