Corticosteroid use after kidney transplantation results in severe bone loss and high fracture risk. Although corticosteroid withdrawal in the early posttransplant period has been associated with bone ...mass preservation, there are no published data regarding corticosteroid withdrawal and risk of fracture. We hypothesized lower fracture incidence in patients discharged from the hospital without than with corticosteroids after transplantation. From the United States Renal Data System (USRDS), 77 430 patients were identified who received their first kidney transplant from 2000 to 2006. Fracture incidence leading to hospitalization was determined from 2000 to 2007; discharge immunosuppression was determined from United Networks for Organ Sharing forms. Time‐to‐event analyses were used to evaluate fracture risk. Median (interquartile range) follow‐up was 1448 (808–2061) days. There were 2395 fractures during follow‐up; fracture incidence rates were 0.008 and 0.0058 per patient‐year for recipients discharged with and without corticosteroid, respectively. Corticosteroid withdrawal was associated with a 31% fracture risk reduction (HR 0.69; 95% CI 0.59–0.81). Fractures associated with hospitalization are significantly lower with regimens that withdraw corticosteroid. As this study likely underestimates overall fracture incidence, prospective studies are needed to determine differences in overall fracture risk in patients managed with and without corticosteroids after kidney transplantation.
In this analysis of the United States Renal Data System, discharge from the hospital after kidney transplantation without maintenance corticosteroids is associated with a 31% reduction in fractures leading to hospitalizations.
Project 8 Phase III Design Concept Esfahani, A Ashtari; Böser, S; Claessens, C ...
Journal of physics. Conference series,
09/2017, Letnik:
888, Številka:
1
Journal Article
Recenzirano
Odprti dostop
We present a working concept for Phase III of the Project 8 experiment, aiming to achieve a neutrino mass sensitivity of 2 eV (90 % C.L.) using a large volume of molecular tritium and a phased ...antenna array. The detection system is discussed in detail.
Background: Chronic prenatal alcohol exposure causes a spectrum of deleterious effects in offspring, collectively termed fetal alcohol spectrum disorders (FASD), and deficits in executive function ...are prevalent in FASD. The goal of this research was to test the hypothesis that children with FASD exhibit performance deficits in tasks that assess attention, planning and spatial working memory.
Methods: Subjects (8–15 years male and female children) with a diagnosis of fetal alcohol syndrome (FAS), partial FAS (pFAS), or alcohol‐related neurodevelopmental disorder (ARND), and age‐ and sex‐matched controls, completed four tasks selected from the Cambridge Neuropsychological Tests Automated Battery (CANTAB®).
Results: Compared with age‐matched control children (n = 92), subjects with FASD (n = 89) exhibited longer reaction and decision times (effect size range; Cohen's d = .51 to .73), suggesting deficits in attention. Children with FASD demonstrated deficits in planning and spatial working memory that became more pronounced when task difficulty increased. The largest effect size in this study population (Cohen’s d = 1.1) occurred in the spatial working memory task. Only one outcome measure revealed differences across the diagnostic subgroups, although all groups were different from control.
Conclusion: This study demonstrates that deficits in multiple executive function domains, including set shifting, planning and strategy use, attention and spatial working memory, can be assessed in children with FASD using an easy to administer, brief battery of computer‐based neuropsychological tasks. The tasks appear to be equally sensitive for brain injury resulting from prenatal exposure to alcohol, regardless of the presence of facial dysmorphology.
The Project 8 collaboration seeks to measure the absolute neutrino mass scale by means of precision spectroscopy of the beta decay of tritium. Our technique, cyclotron radiation emission ...spectroscopy, measures the frequency of the radiation emitted by electrons produced by decays in an ambient magnetic field. Because the cyclotron frequency is inversely proportional to the electron's Lorentz factor, this is also a measurement of the electron's energy. In order to demonstrate the viability of this technique, we have assembled and successfully operated a prototype system, which uses a rectangular waveguide to collect the cyclotron radiation from internal conversion electrons emitted from a gaseous 83mKr source. Here we present the main design aspects of the first phase prototype, which was operated during parts of 2014 and 2015. We will also discuss the procedures used to analyze these data, along with the features which have been observed and the performance achieved to date.
Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The ...vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3′ terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3′-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3′ end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment.
Reactive oxygen species damage DNA and result in health issues. The major damage product, 8-oxo-7,8-dihydroguanine (8oG), is repaired by human adenine DNA glycosylase homologue (MUTYH). Although ...MUTYH misfunction is associated with a genetic disorder called MUTYH-associated polyposis (MAP) and MUTYH is a potential target for cancer drugs, the catalytic mechanism required to develop disease treatments is debated in the literature. This study uses molecular dynamics simulations and quantum mechanics/molecular mechanics techniques initiated from DNA–protein complexes that represent different stages of the repair pathway to map the catalytic mechanism of the wild-type MUTYH bacterial homologue (MutY). This multipronged computational approach characterizes a DNA–protein cross-linking mechanism that is consistent with all previous experimental data and is a distinct pathway across the broad class of monofunctional glycosylase repair enzymes. In addition to clarifying how the cross-link is formed, accommodated by the enzyme, and hydrolyzed for product release, our calculations rationalize why cross-link formation is favored over immediate glycosidic bond hydrolysis, the accepted mechanism for all other monofunctional DNA glycosylases to date. Calculations on the Y126F mutant MutY highlight critical roles for active site residues throughout the reaction, while investigation of the N146S mutant rationalizes the connection between the analogous N224S MUTYH mutation and MAP. In addition to furthering our knowledge of the chemistry associated with a devastating disorder, the structural information gained about the distinctive MutY mechanism compared to other repair enzymes represents an important step for the development of specific and potent small-molecule inhibitors as cancer therapeutics.
The recently developed technique of Cyclotron Radiation Emission Spectroscopy (CRES) uses frequency information from the cyclotron motion of an electron in a magnetic bottle to infer its kinetic ...energy. Here we derive the expected radio-frequency signal from an electron in a waveguide CRES apparatus from first principles. We demonstrate that the frequency-domain signal is rich in information about the electron's kinematic parameters and extract a set of measurables that in a suitably designed system are sufficient for disentangling the electron's kinetic energy from the rest of its kinematic features. This lays the groundwork for high-resolution energy measurements in future CRES experiments, such as the Project 8 neutrino mass measurement.
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