Background Previous randomized controlled trials evaluating the efficacy of mycophenolate mofetil (MMF) in patients with immunoglobulin A nephropathy (IgAN) have produced varying results. Study ...Design Double-blind placebo-controlled randomized controlled trial. Setting & Participants 52 children, adolescents, and adults with biopsy-proven IgAN in 30 centers in the United States and Canada. Entry criteria: age older than 7 to younger than 70 years; urine protein-creatinine ratio (UPCR), ≥0.6 g/g (males) or ≥0.8 g/g (females); and estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2 (≥40 mL/min/1.73 m2 if receiving angiotensin-converting enzyme inhibitor). Mean age, 32 ± 12 (SD) years; 62% men; and 73% white. Intervention Lisinopril (or losartan) plus a highly purified omega-3 fatty acid (Omacor Pronova Biocare) was given to 94 patients for 3 months; 52 of the patients with persistent UPCR ≥ 0.6 g/g (males) and ≥0.8 g/g (females) were randomly assigned to MMF or placebo (target dose, 25-36 mg/kg/d) in addition to lisinopril/losartan plus Omacor. Outcomes Change in UPCR after 6 and 12 months treatment with MMF/placebo and 12 months after the end of treatment. Measurements UPCR measured on 24-hour urine samples. Glomerular filtration rate estimated with the Schwartz (age < 18 years) or Cockcroft-Gault (age ≥ 18 years) formula. Results 44 patients completed 6 months of treatment with MMF (n = 22) or placebo (n = 22). The trial was terminated early at the recommendation of the Data Monitoring Committee because of the lack of benefit. No patient achieved a complete remission (UPCR < 0.2 g/g). Mean UPCRs at randomization and after 6 months were 1.45 (95% CI, 1.16-1.75) and 1.40 (95% CI, 1.09-1.70) for MMF and 1.41 (95% CI, 1.17-1.65) and 1.58 (95% CI, 1.13-2.04) for placebo, respectively. The mean difference in UPCR change between these groups (MMF minus placebo) was −0.22 (95% CI, −0.75 to 0.31; P = 0.4). Adverse events were rare apart from nausea (MMF, 8.7%; placebo, 3.7%); one of these MMF patients withdrew. Limitations Low patient enrollment and short follow-up. Conclusions MMF did not reduce proteinuria significantly in patients with IgAN who had persistent proteinuria after lisinopril/losartan plus Omacor.
Abstract Objectives Osteoarthritis (OA) is a leading cause of disability, but the relationship with premature mortality remains uncertain. We aimed to investigate the relationship between OA and ...mortality from any cause and from cardiovascular disease (CVD). Methods Electronic literature databases searches were conducted to identify prospective studies comparing mortality in a sample of people with and without OA. Risk of all-cause and CVD mortality were summarized using adjusted hazard ratios (HRs) for joint specific (hand, hip, and knee) and joint non-specific OA. New data from the Progetto Veneto Anziani (PRO.V.A.) study were also included. Results From the PRO.V.A. study ( N = 2927), there was no significant increase in mortality risk for participants with any joint OA ( N = 1858) compared to non-OA (all-cause, HR = 0.95, 95% CI: 0.77–1.15 and CVD, HR = 1.12, 95% CI: 0.82–1.54). On meta-analysis, seven studies (OA = 10,018/non-OA = 18,541), with a median 12-year follow-up, reported no increased risk of any-cause mortality in those with OA (HR = 1.10, 95% CI: 0.97–1.25). After removing data on hand OA, a significant association between OA and mortality was observed (HR = 1.18, 95% CI: 1.08–1.28). There was a significant higher risk of overall mortality for (1) studies conducted in Europe, (2) patients with multi-joint OA; and (3) a radiological diagnosis of OA. OA was associated with significantly higher CVD mortality (HR = 1.21, 95% CI: 1.10–1.34). Conclusions People with OA are at increased risk of death due to CVD. The relationship with overall mortality is less clear and may be moderated by the presence of hand OA.
The Lunar Reconnaissance Orbiter/Lyman Alpha Mapping Project (LAMP) ultraviolet instrument detected a 0.5–2% icy regolith mix on the floor of some of the southern pole permanently shadowed craters of ...the Moon. We present calculations indicating that most or all of this icy regolith detected by LAMP (sensed to a depth of <1 μm) has to be relatively young—less than 2,000 years old—due to the surface erosional loss by plasma sputtering (external ionized gas‐surface interactions), meteoric impact vaporization, and meteoric impact ejection. These processes, especially meteoric impact ejection, will disperse water along the crater floor, even onto warm regions where it will then undergo desorption. We have determined that there should be a water exosphere over polar craters (e.g., like Haworth crater) and calculated that a model 40‐km‐diameter crater should emit ~10(exp 19) H2O per second into the exosphere in the form of free molecules and ice‐embedded particulates.
Recent evidence for the nonskeletal effects of vitamin D, coupled with recognition that vitamin D deficiency is common, has revived interest in this hormone. Vitamin D is produced by skin exposed to ...ultraviolet B radiation or obtained from dietary sources, including supplements. Persons commonly at risk for vitamin D deficiency include those with inadequate sun exposure, limited oral intake, or impaired intestinal absorption. Vitamin D adequacy is best determined by measurement of the 25-hydroxyvitamin D concentration in the blood. Average daily vitamin D intake in the population at large and current dietary reference intake values are often inadequate to maintain optimal vitamin D levels. Clinicians may recommend supplementation but be unsure how to choose the optimal dose and type of vitamin D and how to use testing to monitor therapy. This review outlines strategies to prevent, diagnose, and treat vitamin D deficiency in adults.
Calculations using a three-dimensional global atmospheric chemistry model (IMPACT) indicate that n-C8F17CH2CH2OH (widely used in industrial and consumer products) degrades in the atmosphere to give ...perfluorooctanoic acid (PFOA) and other perfluorocarboxylic acids (PFCAs). PFOA is persistent, bioaccumulative, and potentially toxic. Molar yields of PFOA depend on location and season, are in the range of 1−10%, and are of the correct order of magnitude to explain the observed levels in Arctic fauna. Fluorotelomer alcohols such as n-C8F17CH2CH2OH appear to be a significant global source of persistent bioaccumulative perfluorocarboxylic acid pollution. This is the first modeling study of the atmospheric chemistry of a fluorotelomer alcohol.
ABSTRACT
We report observations and analysis of the nearby gamma-ray burst GRB 161219B (redshift z = 0.1475) and the associated Type Ic supernova (SN) 2016jca. GRB 161219B had an isotropic gamma-ray ...energy of ∼1.6 × 1050 erg. Its afterglow is likely refreshed at an epoch preceding the first photometric points (0.6 d), which slows down the decay rates. Combined analysis of the SN light curve and multiwavelength observations of the afterglow suggest that the GRB jet was broad during the afterglow phase (full opening angle ∼42° ± 3°). Our spectral series shows broad absorption lines typical of GRB supernovae (SNe), which testify to the presence of material with velocities up to ∼0.25c. The spectrum at 3.73 d allows for the very early identification of an SN associated with a GRB. Reproducing it requires a large photospheric velocity ($35\, 000 \pm 7000$ km s−1). The kinetic energy of the SN is estimated through models to be Ekin≈4 × 1052 erg in spherical symmetry. The ejected mass in the explosion was Mej≈6.5 ± 1.5 M⊙, much less than that of other GRB-SNe, demonstrating diversity among these events. The total amount of 56Ni in the explosion was 0.27 ± 0.05 M⊙. The observed spectra require the presence of freshly synthesized 56Ni at the highest velocities, at least three times more than a standard GRB-SN. We also find evidence for a decreasing 56Ni abundance as a function of decreasing velocity. This suggests that SN 2016jca was a highly aspherical explosion viewed close to on-axis, powered by a compact remnant. Applying a typical correction for asymmetry, the energy of SN 2016jca was ∼(1–3) × 1052 erg, confirming that most of the energy produced by GRB-SNe goes into the kinetic energy of the SN ejecta.
Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty ...in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation.
Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a 'high' and a 'low' tumour microarray, respectively.
Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error.
Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness.
Soft γ-ray repeaters exhibit bursting emission in hard X-rays and soft γ-rays. During the active phase, they emit random short (milliseconds to several seconds long), hard-X-ray bursts, with peak ...luminosities
of 10
to 10
erg per second. Occasionally, a giant flare with an energy of around 10
to 10
erg is emitted
. These phenomena are thought to arise from neutron stars with extremely high magnetic fields (10
to 10
gauss), called magnetars
. A portion of the second-long initial pulse of a giant flare in some respects mimics short γ-ray bursts
, which have recently been identified as resulting from the merger of two neutron stars accompanied by gravitational-wave emission
. Two γ-ray bursts, GRB 051103 and GRB 070201, have been associated with giant flares
. Here we report observations of the γ-ray burst GRB 200415A, which we localized to a 20-square-arcmin region of the starburst galaxy NGC 253, located about 3.5 million parsecs away. The burst had a sharp, millisecond-scale hard spectrum in the initial pulse, which was followed by steady fading and softening over 0.2 seconds. The energy released (roughly 1.3 × 10
erg) is similar to that of the superflare
from the Galactic soft γ-ray repeater SGR 1806-20 (roughly 2.3 × 10
erg). We argue that GRB 200415A is a giant flare from a magnetar in NGC 253.
We present comprehensive observations and analysis of the energetic H-stripped SN 2016coi (a.k.a. ASASSN-16fp), spanning the γ-ray through optical and radio wavelengths, acquired within the first ...hours to ∼420 days post explosion. Our observational campaign confirms the identification of He in the supernova (SN) ejecta, which we interpret to be caused by a larger mixing of Ni into the outer ejecta layers. By modeling the broad bolometric light curve, we derive a large ejecta-mass-to-kinetic-energy ratio (Mej ∼ 4-7 M , Ek ∼ (7-8) × 1051 erg). The small Ca ii λλ7291,7324 to O i λλ6300,6364 ratio (∼0.2) observed in our late-time optical spectra is suggestive of a large progenitor core mass at the time of collapse. We find that SN 2016coi is a luminous source of X-rays (LX > 1039 erg s−1 in the first ∼100 days post explosion) and radio emission (L8.5 GHz ∼ 7 × 1027 erg s−1 Hz−1 at peak). These values are in line with those of relativistic SNe (2009bb, 2012ap). However, for SN 2016coi, we infer substantial pre-explosion progenitor mass loss with a rate ∼ (1-2) × and a sub-relativistic shock velocity vsh ∼ 0.15c, which is in stark contrast with relativistic SNe and similar to normal SNe. Finally, we find no evidence for a SN-associated shock breakout γ-ray pulse with energy Eγ > 2 × 1046 erg. While we cannot exclude the presence of a companion in a binary system, taken together, our findings are consistent with a massive single-star progenitor that experienced large mass loss in the years leading up to core collapse, but was unable to achieve complete stripping of its outer layers before explosion.
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