Steroid Therapy for Bacterial Meningitis

Routine dexamethasone therapy for bacterial meningitis in pediatric patients is controversial. Two experts debated this topic at the 1993 meeting of the Infectious Diseases Society of America. Both experts agreed that for management of Haemophilus influenzae meningitis, dexamethasone significantly reduced sensorineural hearing loss and probably reduced other long-term sequelae. Because relatively few patients with pneumococcal and meningococcal meningitis have been studied, no conclusions could be reached regarding the effectiveness of dexamethasone. Dr. Urs Schaad emphasized the impressive anti-inflammatory effects of dexamethasone in experimental pneumococcal meningitis and the lack of any adverse events when given to children for 2 or 4 days. He recommended routine use of dexamethasone in treating pediatric patients with bacterial meningitis. Dr. Sheldon Kaplan expressed concern regarding the effectiveness of steroids in treating pneumococcal meningitis, especially when penicillin-resistant and cephalosporin-resistant isolates are present, and he addressed the question of the long-term effects of administration of dexamethasone in children with viral meningitis. He advised against the routine use of dexamethasone for non-H. influenzae meningiti

The Control, Development and Utilization of the Missouri River and its Tributaries

The speakers at this conference were Professors Condra, Caldwell, Stout, Phillips, Bengtson, and Gov. George L. Sheldon, with Dean Charles E. Bessey presiding. The principal object of the meeting was to make known reliable information in regard to the Missouri river, concerning which there is widespread interest and in some instances a tendency to magnify the future possibilities of the river. This paper is an account of the conference. It gives some of the thoughts that were emphasized at the symposium, reciting the facts as they were given by those who have investigated the respective phases of the theme. GEOGRAPHIC CONDITIONS IN THE MISSOURI RIVER BASIN. BY G. E. CONDRA EARLY NAVIGATION ON THE MISSOURI RIVER. BY H. W. CALDWELL THE RELATIONS OF POWER AND IRRIGATION AT THE HEADWATERS OF THE MISSOURI TO FLOODS IN THE LOWER COURSES OF THE RIVER BY O. V. P. STOUT THE RELATIONS OF FORES\u27fS TO RUN-OFF WATER. BY F. J. PHILLIPS MEANDERS OF THE MISSOURI RIVER AND THEIR EFFECTS. BY. N. A. BENGTSON WAYS AND MEANS. GOV. GEO. L, SHELDON

Baseline characteristics and enrichment results from the SONAR trial

Aim: The SONAR trial uses an enrichment design based on the individual response to the selective endothelin receptor antagonist atrasentan on efficacy (the degree of the individual response in the urinary albumin‐to‐creatinine ratio [UACR]) and safety/tolerability (signs of sodium retention and acute increases in serum creatinine) to assess the effects of this agent on major renal outcomes. The patient population and enrichment results are described here. Methods: Patients with type 2 diabetes with an estimated glomerular filtration rate (eGFR) within 25 to 75 mL/min/1.73 m2 and UACR between 300 and 5000 mg/g were enrolled. After a run‐in period, eligible patients received 0.75 mg/d of atrasentan for 6 weeks. A total of 2648 responder patients in whom UACR decreased by ≥30% compared to baseline were enrolled, as were 1020 non‐responders with a UACR decrease of <30%. Patients who experienced a weight gain of >3 kg and in whom brain natriuretic peptide exceeded ≥300 pg/mL, or who experienced an increase in serum creatinine >20% (0.5 mg/dL), were not randomized. Results: Baseline characteristics were similar for atrasentan responders and non‐responders. Upon entry to the study, median UACR was 802 mg/g in responders and 920 mg/g in non‐responders. After 6 weeks of treatment with atrasentan, the UACR change in responders was −48.8% (95% CI, −49.8% to −47.9%) and in non‐responders was −1.2% (95% CI, −6.4% to 3.9%). Changes in other renal risk markers were similar between responders and non‐responders except for a marginally greater reduction in systolic blood pressure and eGFR in responders. Conclusions: The enrichment period has successfully identified a population with a profound UACR reduction without clinical signs of sodium retention in whom a large atrasentan effect on clinically important renal outcomes is possible. The SONAR trial aims to establish whether atrasentan confers renal protection

Cosmological Constraints from the Large Scale Weak Lensing of SDSS MaxBCG Clusters

We derive constraints on the matter density \Om and the amplitude of matter clustering \sig8 from measurements of large scale weak lensing (projected separation R=5-30\hmpc) by clusters in the Sloan Digital Sky Survey MaxBCG catalog. The weak lensing signal is proportional to the product of \Om and the cluster-mass correlation function \xicm. With the relation between optical richness and cluster mass constrained by the observed cluster number counts, the predicted lensing signal increases with increasing \Om or \sig8, with mild additional dependence on the assumed scatter between richness and mass. The dependence of the signal on scale and richness partly breaks the degeneracies among these parameters. We incorporate external priors on the richness-mass scatter from comparisons to X-ray data and on the shape of the matter power spectrum from galaxy clustering, and we test our adopted model for \xicm against N-body simulations. Using a Bayesian approach with minimal restrictive priors, we find \sig8(\Om/0.325)^{0.501}=0.828 +/- 0.049, with marginalized constraints of \Om=0.325_{-0.067}^{+0.086} and \sig8=0.828_{-0.097}^{+0.111}, consistent with constraints from other MaxBCG studies that use weak lensing measurements on small scales (R<=2\hmpc). The (\Om,\sig8) constraint is consistent with and orthogonal to the one inferred from WMAP CMB data, reflecting agreement with the structure growth predicted by GR for an LCDM cosmological model. A joint constraint assuming LCDM yields \Om=0.298 +/- 0.020 and \sig8=0.831 +/- 0.020. Our cosmological parameter errors are dominated by the statistical uncertainties of the large scale weak lensing measurements, which should shrink sharply with current and future imaging surveys.Comment: 20 pages, 12 figures, MNRAS Submitted. For a brief video explaining the key result of this paper, see http://www.youtube.com/user/OSUAstronomy, or http://v.youku.com/v_show/id_XNDI3ODA3NzY4.html in countries where YouTube is not accessibl

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

Individual atrasentan exposure is associated with long-term kidney and heart failure outcomes in patients with type 2 diabetes and chronic kidney disease

Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase 2 trials. We evaluated whether plasma exposure was associated with long-term outcomes for kidney protection and heart failure in the phase 3 SONAR trial (n=3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time-to-event models were used to quantify the association between plasma exposure and long-term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared to placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% CI: 0.28-0.85) for kidney events and 1.13 (95% CI: 1.03-2.20) for heart failure events. At the mean atrasentan exposure the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population

Conducting Molecular Epidemiological Research in the Age of HIPAA: A Multi-Institutional Case-Control Study of Breast Cancer in African-American and European-American Women

Breast cancer in African-American (AA) women occurs at an earlier age than in European-American (EA) women and is more likely to have aggressive features associated with poorer prognosis, such as high-grade and negative estrogen receptor (ER) status. The mechanisms underlying these differences are unknown. To address this, we conducted a case-control study to evaluate risk factors for high-grade ER- disease in both AA and EA women. With the onset of the Health Insurance Portability and Accountability Act of 1996, creative measures were needed to adapt case ascertainment and contact procedures to this new environment of patient privacy. In this paper, we report on our approach to establishing a multicenter study of breast cancer in New York and New Jersey, provide preliminary distributions of demographic and pathologic characteristics among case and control participants by race, and contrast participation rates by approaches to case ascertainment, with discussion of strengths and weaknesses

The Seventh Data Release of the Sloan Digital Sky Survey

This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most of the roughly 2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry over 250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A coaddition of these data goes roughly two magnitudes fainter than the main survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2 in the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog (UCAC-2), reducing the rms statistical errors at the bright end to 45 milli-arcseconds per coordinate. A systematic error in bright galaxy photometr is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat-fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor correction

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

Rationale and protocol of the Study Of diabetic Nephropathy with AtRasentan (SONAR) trial:A clinical trial design novel to diabetic nephropathy

Aims Individuals with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin‐to‐creatinine ratio (UACR), with a large variability between patients. We are assessing its effect on renal outcomes in the Study Of diabetic Nephropathy with AtRasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit. Materials and Methods SONAR is a randomized, double‐blind, placebo‐controlled trial with approximately 3500 participants who have stage 2–4 CKD and macroalbuminuria and are receiving a maximum tolerated dose of a renin‐angiotensin system inhibitor. Results After 6 weeks of exposure to atrasentan 0.75 mg once daily (enrichment period), participants with ≥30% UACR decrease and no tolerability issues (responders) were randomly assigned to placebo or atrasentan 0.75 mg/day. The responder group will be used for primary efficacy and safety analyses. Approximately 1000 participants with <30% UACR reduction (non‐responders) were also randomized to placebo or atrasentan. The primary endpoint is a composite of a sustained doubling of serum creatinine or end‐stage renal disease. The original power calculation indicated that a total of 425 primary renal events in the responder group provides 90% power to detect a 27% reduction in relative risk (alpha level of .05). Conclusion SONAR aims to determine whether atrasentan added to guideline‐recommended therapies safely reduces the risk of CKD progression and delays the onset of end‐stage renal disease in patients with type 2 diabetes and nephropathy. SONAR also aims to establish whether the enrichment of patients based on their initial “surrogate” response to atrasentan will deliver a trial design in accord with personalized treatment of diabetic kidney disease