Challenges of Replicating Success

Khrishnamurti used to tell a story about Man walking along the shore of the sea of life looking for the shell of truth. God and the Devil are watching from atop the cliffs rising far above the sand and water. Man finds the shell of truth in the roaring surf and picks it up. God turns to the Devil and says, I\u27ve got you now, for Man has discovered truth. I\u27m not worried, replies the Devil. Just wait until he organizes it. Although we hope no one would ever presume to have found the truth, most of us in the service field tend to cherish the bit of knowledge we have found in our own program-especially if it has met with success. This summer, the government gave funding to sixteen projects promoting youth service, New Orleans Summerbridge among them, and asked us all to organize our respective truths ... and in some cases, to replicate them. As participants in the Summerbridge project, we\u27re here to say that, yes, truths are out there - programs that are working. However, we must report also that the Devil is no fool-organizing programs to expand can be extremely difficult. As the national service program is gradually phased in, a large number of existing local projects will be faced with the same issues we dealt with this summer: how do you take a program that is working, add to it an infusion of federal money, and expand it to a much larger scale

Actions Speak Louder Than Goals: Valuing Player Actions in Soccer

Assessing the impact of the individual actions performed by soccer players during games is a crucial aspect of the player recruitment process. Unfortunately, most traditional metrics fall short in addressing this task as they either focus on rare actions like shots and goals alone or fail to account for the context in which the actions occurred. This paper introduces (1) a new language for describing individual player actions on the pitch and (2) a framework for valuing any type of player action based on its impact on the game outcome while accounting for the context in which the action happened. By aggregating soccer players' action values, their total offensive and defensive contributions to their team can be quantified. We show how our approach considers relevant contextual information that traditional player evaluation metrics ignore and present a number of use cases related to scouting and playing style characterization in the 2016/2017 and 2017/2018 seasons in Europe's top competitions.Comment: Significant update of the paper. The same core idea, but with a clearer methodology, applied on a different data set, and more extensive experiments. 9 pages + 2 pages appendix. To be published at SIGKDD 201

The inter-observer agreement of examining pre-school children with acute cough: a nested study

BACKGROUND: The presence of clinical signs have implications for diagnosis, prognosis and treatment. Therefore, the aim of this study was to examine the inter-observer agreement of clinical signs in pre-school children presenting to primary care. METHODS: A nested study comparing two clinical assessments within a prospective cohort of 256 pre-school children with acute cough recruited from eight general practices in Leicestershire, UK. We examined agreement (using kappa statistics) between unstandardised and standardised clinical assessments of tachypnoea, chest signs and fever. RESULTS: Kappa values were poor or fair for all clinical signs (range 0.12 to 0.39) with chest signs the most reliable. CONCLUSIONS: Primary care clinicians should be aware that clinical signs may be unreliable when making diagnosis, prognosis and treatment decisions in pre-school children with cough. Future research should aim to further our understanding of how best to identify abnormal clinical signs

Retinal and choroidal thickness in early age-related macular degeneration

Purpose: To compare retinal thickness and choroidal thickness at increasing retinal eccentricity in individuals with early age-related macular degeneration (AMD) and in healthy controls using enhanced choroidal penetration, 3-dimensional optical coherence tomography at 1060 nm. Design: Cross-sectional study. Methods: Individuals with early AMD (n = 16; mean age, 71.6 ± 8.5 years) and a comparison group of healthy controls (n = 16; 67.6 ± 5.4 years) were recruited. Three-dimensional (20 degrees × 20 degrees) long-wavelength optical coherence tomography (1060 nm) images (approximately 8-μm axial resolution; 47 000 A scans/second, centered on the fovea) were obtained from all participants after pupil dilation. Retinal thickness was measured between the inner limiting membrane and the retinal pigment epithelium. Choroidal thickness was measured between the retinal pigment epithelium and the choroid–scleral interface. Thickness measurements were obtained subfoveally and at 0.5-mm intervals to a maximum of 2.0 mm nasally, temporally, superiorly, and inferiorly. The main outcome measures were retinal and choroidal thickness (measured in micrometers) at different eccentricities on vertical and horizontal meridians. Results: Mean retinal thickness was reduced significantly in the group of participants with early AMD compared with the control group at multiple locations within 2.0 mm of the fovea. This difference was most significant at the fovea, where the mean retinal thickness of the early AMD group was 179 ± 27 μm and that of the control group was 202 ± 18 μm (P = .008). There was no significant difference in choroidal thickness between groups at any location. Conclusions: Retinal thickness is reduced in early AMD, but choroidal thickness seems to be unaffected by the early disease process

Validity and Reproducibility of a Self-Administered Semi-Quantitative Food-Frequency Questionnaire for Estimating Usual Daily Fat, Fibre, Alcohol, Caffeine and Theobromine Intakes among Belgian Post-Menopausal Women

A novel food-frequency questionnaire (FFQ) was developed and validated to assess the usual daily fat, saturated, mono-unsaturated and poly-unsaturated fatty acid, fibre, alcohol, caffeine, and theobromine intakes among Belgian post-menopausal women participating in dietary intervention trials with phyto-oestrogens. The relative validity of the FFQ was estimated by comparison with 7 day (d) estimated diet records (EDR, n 64) and its reproducibility was evaluated by repeated administrations 6 weeks apart (n 79). Although the questionnaire underestimated significantly all intakes compared to the 7 d EDR, it had a good ranking ability (r 0.47–0.94; weighted κ 0.25–0.66) and it could reliably distinguish extreme intakes for all the estimated nutrients, except for saturated fatty acids. Furthermore, the correlation between repeated administrations was high (r 0.71–0.87) with a maximal misclassification of 7% (weighted κ 0.33–0.80). In conclusion, these results compare favourably with those reported by others and indicate that the FFQ is a satisfactorily reliable and valid instrument for ranking individuals within this study population

The effectiveness of pulsed electrical stimulation (E-PES) in the management of osteoarthritis of the knee: a protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) of the knee is one of the main causes of musculoskeletal disability in the western world. Current available management options provide symptomatic relief (exercise and self-management, medication and surgery) but do not, in general, address the disease process itself. Moreover, adverse effects and complications with some of these interventions (medication and surgery) and the presence of co-morbidities commonly restrict their use. There is clearly a need to investigate treatments that are more widely applicable for symptom management and which may also directly address the disease process itself.</p> <p>In two randomised controlled trials of four and 12 weeks duration, pulsed electrical stimulation was shown to be effective in managing the symptoms of OA of the knee. Laboratory and animal studies demonstrate the capacity of externally applied electric and electromagnetic fields to positively affect chondrocyte proliferation and extracellular matrix protein production. This latter evidence provides strong theoretical support for the use of electrical stimulation to maintain and repair cartilage in the clinical setting and highlights its potential as a disease-modifying modality.</p> <p>Methods/Design</p> <p>A double-blind, randomised, placebo-controlled, repeated measures trial to examine the effectiveness of pulsed electrical stimulation in providing symptomatic relief for people with OA of the knee over 26 weeks.</p> <p>Seventy people will be recruited and information regarding age, gender, body mass index and medication use will be recorded. The population will be stratified for age, gender and baseline pain levels.</p> <p>Outcome measures will include pain (100 mm VAS and WOMAC 3.1), function (WOMAC 3.1), stiffness (WOMAC 3.1), patient global assessment (100 mm VAS) and quality of life (SF-36). These outcomes will be measured at baseline, four, 16 and 26 weeks. Activity levels will be measured at baseline and 16 weeks using accelerometers and the Human Activity Profile questionnaire. A patient global perceived effect scale (11-point Likert) will be completed at 16 and 26 weeks.</p> <p>Discussion</p> <p>This paper describes the protocol for a randomised, double-blind, placebo-controlled trial that will contribute to the evidence regarding the use of sub-sensory pulsed electrical stimulation in the management of OA of the knee.</p> <p>Trial registration</p> <p>Australian Clinical Trials Registry ACTRN12607000492459.</p

A partial form of inherited human USP18 deficiency underlies infection and inflammation

International audienceHuman USP18 is an interferon (IFN)-stimulated gene product and a negative regulator of type I IFN (IFN-I) signaling. It also removes covalently linked ISG15 from proteins, in a process called deISGylation. In turn, ISG15 prevents USP18 from being degraded by the proteasome. Autosomal recessive complete USP18 deficiency is life-threatening in infancy owing to uncontrolled IFN-I–mediated autoinflammation. We report three Moroccan siblings with autoinflammation and mycobacterial disease who are homozygous for a new USP18 variant. We demonstrate that the mutant USP18 (p.I60N) is normally stabilized by ISG15 and efficient for deISGylation but interacts poorly with the receptor-anchoring STAT2 and is impaired in negative regulation of IFN-I signaling. We also show that IFN-γ–dependent induction of IL-12 and IL-23 is reduced owing to IFN-I–mediated impairment of myeloid cells to produce both cytokines. Thus, insufficient negative regulation of IFN-I signaling by USP18-I60N underlies a specific type I interferonopathy, which impairs IL-12 and IL-23 production by myeloid cells, thereby explaining predisposition to mycobacterial disease