329 research outputs found

    The Sugar Daddy's Game: How Wealthy Investors Change Competition in Professional Team Sports

    Get PDF
    Professional sports leagues have witnessed the appearance of so-called "sugar daddies" - people who invest enormous amounts of money into clubs and become their owners. This paper presents a contest model of a professional sports league that incorporates this phenomenon. We analyze how the appearance of a sugar daddy alters competitive balance and social welfare compared to a league with purely profit-maximizing club owners. We further show that the welfare effect of revenue sharing in a sugar daddy league is ambiguous and depends on the degree of redistribution and on whether the sugar daddy invests in a small or large club.Competitive balance, contest model, social welfare, sports leagues, sugar daddy

    Frequency and Clinical Presentation of Mucocutaneous Disease Due to Mycoplasma pneumoniae Infection in Children With Community-Acquired Pneumonia

    Full text link
    Importance The diagnosis of Mycoplasma pneumoniae infection as the cause of mucocutaneous disease is challenging because current diagnostic tests are not able to differentiate M pneumoniae infection from carriage. Objective To examine the frequency and clinical presentation of M pneumoniae-induced mucocutaneous disease in children with community-acquired pneumonia (CAP) using improved diagnostics. Design, Setting, and Participants This prospective, longitudinal cohort study included 152 children aged 3 to 18 years with CAP enrolled in a CAP study from May 1, 2016, to April 30, 2017, at the University Children's Hospital Zurich. Children were inpatients or outpatients with clinically defined CAP according to the British Thoracic Society guidelines. Data analysis was performed from July 10, 2017, to June 29, 2018. Main Outcomes and Measures Frequency and clinical presentation of M pneumoniae-induced mucocutaneous disease in childhood CAP. Mycoplasma pneumoniae infection was diagnosed by polymerase chain reaction (PCR) of oropharyngeal samples and confirmed with the measurement of specific peripheral blood IgM antibody-secreting cells by enzyme-linked immunospot assay to differentiate M pneumoniae-infected patients from carriers with CAP caused by other pathogens. Mucocutaneous disease was defined as any eruptive lesion that involved skin and/or mucous membranes occurring during the CAP episode. Results Among 152 enrolled children with CAP (median [interquartile range] age, 5.7 [4.3-8.9] years; 84 [55.3%] male), 44 (28.9%) tested positive for M pneumoniae by PCR; of these, 10 children (22.7%) developed mucocutaneous lesions. All 10 patients with mucocutaneous eruptions tested positive for specific IgM antibody-secreting cells. Skin manifestations were found in 3 cases (2.8%) of M pneumoniae PCR-negative CAP (P < .001). The spectrum of M pneumoniae-induced mucocutaneous disease included M pneumoniae-induced rash and mucositis (3 cases [6.8%]), urticaria (2 cases [4.5%]), and maculopapular skin eruptions (5 cases [11.4%]). Two patients had ocular involvement as the sole mucosal manifestation (bilateral anterior uveitis and nonpurulent conjunctivitis). Patients with M pneumoniae-induced mucocutaneous disease had longer duration of prodromal fever (median [interquartile range], 10.5 [8.3-11.8] vs 7.0 [5.5-9.5] days; P = .02) and higher C-reactive protein levels (median [interquartile range], 31 [22-59] vs 16 [7-23] mg/L; P = .04) than patients with CAP due to M pneumoniae without mucocutaneous manifestations. They were also more likely to require oxygen (5 [50%] vs 1 [5%]; P = .007), to require hospitalization (7 [70%] vs 4 [19%]; P = .01), and to develop long-term sequelae (3 [30%] vs 0; P = .03). Conclusions and Relevance Mucocutaneous disease occurred significantly more frequently in children with CAP due to M pneumoniae than in children with CAP of other origins. Mycoplasma pneumoniae-induced mucocutaneous disease was associated with increased systemic inflammation, morbidity, and a higher risk of long-term sequelae

    Understanding efficacy-safety balance of biologics in moderate-to-severe pediatric psoriasis

    Full text link
    BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease affecting both adults and children. To better understand the efficacy-safety profile of biologics in children with moderate-to-severe psoriasis, this study aimed to analyze efficacy and safety data of randomized controlled trials (RCTs) performed in pediatric psoriasis and to compare efficacy outcomes in children with those in adults. METHODS: RCTs investigating biologics in children with moderate-to-severe psoriasis were identified in a systematic literature review. PASI75/90 treatment responses at weeks 11/12 were analyzed comparing biologics with control arms. Serious adverse events (SAEs) were analyzed at the end of each study. Efficacy data from RCTs in adults with psoriasis were selected for the same biologics. Risk ratios (RR) of selected RCTs were pooled together in a statistical random effects model using the inverse variance method. RESULTS: For children, there were 1 etanercept, 2 secukinumab, 1 ixekizumab and 1 ustekinumab placebo-controlled RCTs and 1 adalimumab RCT using methotrexate as reference arm at weeks 11/12. For adults, out of 263 RCTs, 7 adalimumab and 15 etanercept (TNF inhibitors) and 4 ixekizumab and 12 ustekinumab (IL-17 and IL-12/23 inhibitors) RCTs reported PASI75/90 efficacy responses at weeks 11/12. Regarding efficacy, all biologics showed improved PASI responses over control arms. RRs ranges were 2.02-7.45 in PASI75 and 4.10-14.50 in PASI90. The highest PASI75 responses were seen for ustekinumab 0.375 mg/kg (RR = 7.25, 95% CI 2.83-18.58) and ustekinumab 0.75 mg/kg (RR = 7.45, 95% CI 2.91-19.06) in the CADMUS study. The highest PASI90 response was seen for ixekizumab (RR = 14.50, 95% CI 4.82-43.58) in the IXORA-PEDS study. SAE incidences in pediatric and adult arms with biologics were 0 to 3% except for a pediatric arm with adalimumab 0.40 mg/kg (8%). For adults, pooled RR also showed improved PASI responses over placebo for all biologics, with highest PASI75 response observed for ixekizumab (pooled RR = 16.18, 95% CI 11.83-22.14). CONCLUSION: Both adults and children with psoriasis show superior efficacy with biologics compared to control arms after 3 months of treatment with SAE incidences in the low percentages. Additional longer-term clinical studies are warranted to fully understand the overall efficacy-safety profile of biologics in children with moderate-to-severe psoriasis

    Разработка технологического процесса изготовления штока 2М138И.01.06.030 СБ

    Get PDF
    Раздел "Объект и методы исследования" содержит служебное назначение изделия, расчет годовой программы выпуска изделия. Раздел "Расчеты и аналитика" содержит выбор баз, разработку маршрута технологического процесса, выбор оборудования и средств технологического оснащения, расчёт припусков на обработку. В разделе "Результаты проведённого исследования" приведено описание конструкции и расчёт приспособления. Раздел "Социальная ответственность" посвящён вопросам безопасной работы на участке и пожарной безопасности. В разделе "Финансовый менеджмент, ресурсоэффективность и ресурсосбережение" рассчитана себестоимость изготовления детали.The section "Object and methods of research" contains the service purpose of the product, the calculation of the annual production program of the product. The section "Calculations and Analytics" contains the selection of bases, development of the route of the process. In the Section "Results of the research contains" the description of design and calculation of the adaptation. The section "Social responsibility" is devoted to the issues of safe work on the site and fire safety. In the section "Financial management, resource efficiency and resource saving" calculated the cost of manufacturing parts

    Identifying a cut‐off point for normal mobility: a comparison of the timed ‘up and go' test in community‐dwelling and institutionalised elderly women

    Get PDF
    Background: physical mobility testing is an essential component of the geriatric assessment. The timed up and go test measures basic mobility skills including a sequence of functional manoeuvres used in everyday life. Objectives: to create a practical cut‐off value to indicate normal versus below normal timed up and go test performance by comparing test performance of community‐dwelling and institutionalised elderly women. Setting and participants: 413 community‐dwelling and 78 institutionalised mobile elderly women (age range 65-85 years) were enrolled in a cross‐sectional study. Measurements: timed up and go test duration, residential and mobility status, age, height, weight and body mass index were documented. Results: 92% of community‐dwelling elderly women performed the timed up and go test in less than 12 seconds and all community‐dwelling women had times below 20 seconds. In contrast only 9% of institutionalised elderly women performed the timed up and go test in less than 12 seconds, 42% were below 20 seconds, 32% had results between 20 and 30 seconds and 26% were above 30 seconds. The 10th-90th percentiles for timed up and go test performance were 6.0-11.2 seconds for community‐dwelling and 12.7-50.1 seconds for institutionalised elderly women. When stratifying participants according to mobility status, the timed up and go test duration increased significantly with decreasing mobility (Kruskall‐Wallis‐test: p<0.0001). Linear regression modelling identified residential status (p<0.0001) and physical mobility status (p<0.0001) as significant predictors of timed up and go performance. This model predicted 54% of total variation of timed up and go test performance. Conclusion: residential and mobility status were identified as the strongest predictors of timed up and go test performance. We recommend the timed up and go test as a screening tool to determine whether an in‐depth mobility assessment and early intervention, such as prescription of a walking aid, home visit or physiotherapy, is necessary. Community‐dwelling elderly women between 65 and 85 years of age should be able to perform the timed up and go test in 12 seconds or les

    The Tribological Behaviour of Carbon Fibre Reinforced Polyaryletherketones (PAEKs) through their Glass Transitions.

    Get PDF
    yesAdvanced engineering polymers of the Polyaryletherketone (PAEK) family with carbon fibre reinforcement are finding application in engineering systems as tribological bearing surfaces under severe operating conditions that cyclically move the polymer into and beyond the glass transition temperature region. To support such an application, the friction in high speed and low load PAEK-steel sliding contacts was investigated both unlubricated and lubricated with a trinonyl trimellitate ester, a base fluid for high temperature industrial lubricants. Four polymers in the PAEK family, PEEK, PEK, PEKEKK and PEKK, with 30%wt of carbon fibre whiskers were tested against an AISI 4140 steel disc. When unlubricated, low friction depended upon the formation of a PAEK transfer film on the steel disc and when this became unstable in the glass transition region the friction increased to much higher levels with associated polymer surface damage. Frictional heating due to the high sliding speed dominated the differences in glass transition behaviour between the four PAEKs. When lubricated, the lubricant film controlled friction and there was no significant effect of the glass transition of any of the PAEKs. The irreversible nature of the glass transition in PAEKs in such tribological applications, due to high surface damage at high temperature, means that it is essential to ensure effective lubrication in both fluid film and boundary lubrication.Innovate UK, Knowledge Transfer Partnershi

    Congenital syphilis in Switzerland: a retrospective cohort study, 2010 to 2019

    Get PDF
    AIMS OF THE STUDY We previously reported a re-emergence of syphilis from 2006 to 2009 with detection of congenital syphilis in Switzerland. This study aimed to reassess the incidence of children exposed to maternal syphilis during pregnancy and congenital syphilis in a following 10-year period in the canton of Zurich, the most populous canton in Switzerland with the highest incidences of syphilis. METHODS Children were identified both by reviewing medical records at the four major neonatal and paediatric hospitals providing acute care in the canton of Zurich and by the serological database of the syphilis reference laboratory. Inclusion criteria for children were (a) date of birth in the period 2010-2019, (b) place of birth in the canton of Zurich, (c) evaluation for syphilis due to positive syphilis pregnancy screening and (d) age <1 year at diagnosis. Results were compared with epidemiological data provided by the Federal Office of Public Health (FOPH). RESULTS We identified and evaluated 17 children after potential exposure to maternal syphilis. Residual antibodies of a past infection were found in 11 mothers. Six children were identified as having had real exposure to asymptomatic maternal syphilis. From an epidemiological perspective, the distribution of the cases followed a similar pattern as confirmed syphilis cases in women of childbearing age reported to the FOPH. No cases of congenital syphilis were observed. CONCLUSIONS In contrast to the rise in syphilis infections, this study identified no cases of congenital syphilis in the canton of Zurich, Switzerland, in the period 2010-2019. Syphilis pregnancy screening may have prevented congenital syphilis by diagnosing and allowing adequate treatment of asymptomatic maternal syphilis

    Life-Threatening Primary Varicella Zoster Virus Infection With Hemophagocytic Lymphohistiocytosis-Like Disease in GATA2 Haploinsufficiency Accompanied by Expansion of Double Negative T-Lymphocytes

    Get PDF
    Two unrelated patients with GATA2-haploinsufficiency developed a hemophagocytic lymphohistiocytosis (HLH)-like disease during a varicella zoster virus (VZV) infection. High copy numbers of VZV were detected in the blood, and the patients were successfully treated with acyclovir and intravenous immunoglobulins. After treatment with corticosteroids for the HLH, both patients made a full recovery. Although the mechanisms leading to this disease constellation have yet to be characterized, we hypothesize that impairment of the immunoregulatory role of NK cells in GATA2-haploinsufficiency may have accentuated the patients' susceptibility to HLH. Expansion of a double negative T-lymphocytic population identified with CyTOF could be a further factor contributing to HLH in these patients. This is the first report of VZV-triggered HLH-like disease in a primary immunodeficiency and the third report of HLH in GATA2-haploinsufficiency. Since HLH was part of the presentation in one of our patients, GATA2-haploinsufficiency represents a potential differential diagnosis in patients presenting with the clinical features of HLH—especially in cases of persisting cytopenia after recovery from HLH

    Vitamin D testing and treatment: a narrative review of current evidence

    Get PDF
    Vitamin D testing and treatment is a subject of controversial scientific discussions, and it is challenging to navigate through the expanding vitamin D literature with heterogeneous and partially opposed opinions and recommendations. In this narrative review, we aim to provide an update on vitamin D guidelines and the current evidence on the role of vitamin D for human health with its subsequent implications for patient care and public health issues. Vitamin D is critical for bone and mineral metabolism, and it is established that vitamin D deficiency can cause rickets and osteomalacia. While many guidelines recommend target serum 25-hydroxyvitamin D (25[OH]D) concentrations of ≥50 nmol/L (20 ng/mL), the minimum consensus in the scientific community is that serum 25(OH)D concentrations below 25–30 nmol/L (10–12 ng/mL) must be prevented and treated. Using this latter threshold of serum 25(OH)D concentrations, it has been documented that there is a high worldwide prevalence of vitamin D deficiency that may require public health actions such as vitamin D food fortification. On the other hand, there is also reason for concern that an exploding rate of vitamin D testing and supplementation increases costs and might potentially be harmful. In the scientific debate on vitamin D, we should consider that nutrient trials differ from drug trials and that apart from the opposed positions regarding indications for vitamin D treatment we still have to better characterize the precise role of vitamin D for human health

    Monoallelic Mutations in the Translation Initiation Codon of KLHL24 Cause Skin Fragility

    Get PDF
    The genetic basis of epidermolysis bullosa, a group of genetic disorders characterized by the mechanically induced formation of skin blisters, is largely known, but a number of cases still remain genetically unsolved. Here, we used whole-exome and targeted sequencing to identify monoallelic mutations, c.1A>G and c.2T>C, in the translation initiation codon of the gene encoding kelch-like protein 24 (KLHL24) in 14 individuals with a distinct skin-fragility phenotype and skin cleavage within basal keratinocytes. Remarkably, mutation c.1A>G occurred de novo and was recurrent in families originating from different countries. The striking similarities of the clinical features of the affected individuals point to a unique and very specific pathomechanism. We showed that mutations in the translation initiation codon of KLHL24 lead to the usage of a downstreamtranslation initiation site with the same reading frame and formation of a truncated polypeptide. The pathobiology was examined in keratinocytes and fibroblasts of the affected individuals and via expression of mutant KLHL24, and we found mutant KLHL24 to be associated with abnormalities of intermediate filaments in keratinocytes and fibroblasts. In particular, KLHL24 mutations were associated with irregular and fragmented keratin 14. Recombinant overexpression of normal KLHL24 promoted keratin 14 degradation, whereas mutant KLHL24 showed less activity than the normal molecule. These findings identify KLHL24 mutations as a cause of skin fragility and identify a role for KLHL24 in maintaining the balance between intermediate filament stability and degradation required for skin integrity.Peer reviewe
    corecore