Quadratic distances on probabilities: A unified foundation

This work builds a unified framework for the study of quadratic form distance measures as they are used in assessing the goodness of fit of models. Many important procedures have this structure, but the theory for these methods is dispersed and incomplete. Central to the statistical analysis of these distances is the spectral decomposition of the kernel that generates the distance. We show how this determines the limiting distribution of natural goodness-of-fit tests. Additionally, we develop a new notion, the spectral degrees of freedom of the test, based on this decomposition. The degrees of freedom are easy to compute and estimate, and can be used as a guide in the construction of useful procedures in this class.Comment: Published in at http://dx.doi.org/10.1214/009053607000000956 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Sputtered NiO_x Films for Stabilization of p^+n-lnP Photoanodes for Solar-Driven Water Oxidation

A photoanode protection strategy using a multifunctional NiO_x coating is presented. The ransparency/antireflectivity, low electrochromism, conduction of holes, corrosion protection, and active electrocatalysis for water-oxidation half-reaction are described

A study on the safety and efficacy of reveglucosidase alfa in patients with late-onset Pompe disease.

BackgroundLate-onset Pompe disease is a rare genetic neuromuscular disorder caused by lysosomal acid alpha-glucosidase (GAA) deficiency that ultimately results in mobility loss and respiratory failure. Current enzyme replacement therapy with recombinant human (rh)GAA has demonstrated efficacy in subjects with late-onset Pompe disease. However, long-term effects of rhGAA on pulmonary function have not been observed, likely related to inefficient delivery of rhGAA to skeletal muscle lysosomes and associated deficits in the central nervous system. To address this limitation, reveglucosidase alfa, a novel insulin-like growth factor 2 (IGF2)-tagged GAA analogue with improved lysosomal uptake, was developed. This study evaluated the pharmacokinetics, safety, and exploratory efficacy of reveglucosidase alfa in 22 subjects with late-onset Pompe disease who were previously untreated with rhGAA.ResultsReveglucosidase alfa plasma concentrations increased linearly with dose, and the elimination half-life was <1.2 h. Eighteen of 22 subjects completed 72 weeks of treatment. The most common adverse events were hypoglycemia (63%), dizziness, fall, headache, and nausea (55% for each). Serious adverse events included hypersensitivity (n = 1), symptomatic hypoglycemia (n = 2), presyncope (n = 1), and acute cardiac failure (n = 1). In the dose-escalation study, all treated subjects tested positive for anti-reveglucosidase alfa, anti-rhGAA, anti-IGF1, and anti-IGF2 antibodies at least once. Subjects receiving 20 mg/kg of reveglucosidase alfa demonstrated increases in predicted maximum inspiratory pressure (13.9%), predicted maximum expiratory pressure (8.0%), forced vital capacity (-0.4%), maximum voluntary ventilation (7.4 L/min), and mean absolute walking distance (22.3 m on the 6-min walk test) at 72 weeks.ConclusionsAdditional studies are needed to further assess the safety and efficacy of this approach. Improvements in respiratory muscle strength, lung function, and walking endurance in subjects with LOPD may make up for the risk of hypersensitivity reactions and hypoglycemia. Reveglucosidase alfa may provide a new treatment option for patients with late-onset Pompe disease.Trial registrationISRCTN01435772 and ISRCTN01230801 , registered 27 October 2011

The Effect of Supplemental Medical and Prescription Drug Coverage on Health Care Spending for Medicare Beneficiaries with Cancer

AbstractObjectivesTo examine whether patients with newly diagnosed cancer respond differently to supplemental coverage than the general Medicare population.MethodsA cohort of newly diagnosed cancer patients (n = 1,799) from the 1997-2007 Medicare Current Beneficiary Survey and a noncancer cohort (n = 9,726) were identified and matched by panel year. Two-year total medical care spending was estimated by using generalized linear models with gamma distribution and log link—including endogeneity-corrected models. Interactions between cancer and type of insurance allowed testing for differential effects of a cancer diagnosis.ResultsThe cancer cohort spent an adjusted $15,605 more over 2 years than did the noncancer comparison group. Relative to those without supplemental coverage, beneficiaries with employer-sponsored insurance, other private with prescription drug coverage, and public coverage had significantly higher total spending ($3,510, $2,823, and$4,065, respectively, for main models). For beneficiaries with cancer, supplemental insurance effects were similar in magnitude yet negative, suggesting little net effect of supplemental insurance for cancer patients. The endogeneity-corrected models produced implausibly large main effects of supplemental insurance, but the Cancer × Insurance interactions were similar in both models.ConclusionsMedicare beneficiaries with cancer are less responsive to the presence and type of supplemental insurance than are beneficiaries without cancer. Proposed restrictions on the availability of supplemental insurance intended to reduce Medicare spending would be unlikely to limit expenditures by beneficiaries with cancer, but would shift the financial burden to those beneficiaries. Policymakers should consider welfare effects associated with coverage restrictions

Methods for identifying surgical wound infection after discharge from hospital: a systematic review.

Background: Wound infections are a common complication of surgery that add significantly to the morbidity of patients and costs of treatment. The global trend towards reducing length of hospital stay post-surgery and the increase in day case surgery means that surgical site infections (SSI) will increasingly occur after hospital discharge. Surveillance of SSIs is important because rates of SSI are viewed as a measure of hospital performance, however accurate detection of SSIs post-hospital discharge is not straightforward. Methods: We conducted a systematic review of methods of post discharge surveillance for surgical wound infection and undertook a national audit of methods of post-discharge surveillance for surgical site infection currently used within United Kingdom NHS Trusts. Results: Seven reports of six comparative studies which examined the validity of post-discharge surveillance methods were located; these involved different comparisons and some had methodological limitations, making it difficult to identify an optimal method. Several studies evaluated automated screening of electronic records and found this to be a useful strategy for the identification of SSIs that occurred post discharge. The audit identified a wide range of relevant post-discharge surveillance programmes in England, Scotland and Wales and Northern Ireland; however, these programmes used varying approaches for which there is little supporting evidence of validity and/or reliability. Conclusion: In order to establish robust methods of surveillance for those surgical site infections that occur post discharge, there is a need to develop a method of case ascertainment that is valid and reliable post discharge. Existing research has not identified a valid and reliable method. A standardised definition of wound infection ( e. g. that of the Centres for Disease Control) should be used as a basis for developing a feasible, valid and reliable approach to defining post discharge SSI. At a local level, the method used to ascertain post discharge SSI will depend upon the purpose of the surveillance, the nature of available routine data and the resources available

ANALYSIS AND DESIGN OF THERMOELECTRIC INFRARED MICROSENSOR

ABSTRACT In this study, a novel thermoelectric infrared microsensor (TIMS) is designed by using commercial CMOS IC processes with subsequent bulk-micromachining process. This microsensor has the advantages of high fill factor, low noise equivalent temperature difference (NETD), and simple fabrication process. The key feature is that thermocouple cantilever beams with low solid thermal conductance have been placed under the membrane of thermoelectric infrared microsensor. In order to improve the performance of the infrared sensor, the basic physical characteristics of this sensor have been analyzed. Finite element analysis is used to simulate the electro-thermo-mechanical behavior of the device and to demonstrate the feasibility of our design. Besides, a method for manufacturing the infrared microsensor is also provided and the performance of the presented design has been examined. The analytical results concluded that lowering down the number of the thermocouples does not affect the responsivity but do reduce the total resistance. Also, the detectivity and responsivity are obviously increased for the proposed TIMS. Finally, the deviation between the theoretical and the simulated results is discussed

Potential effects of phytoestrogen genistein in modulating acute methotrexate chemotherapy-induced osteoclastogenesis and bone damage in rats

Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage