The Radar Echo Telescope for Cosmic Rays (RET-CR) is a recently funded experiment designed to detect the englacial cascade of a cosmic ray-initiated air shower via in-ice radar, toward the goal of a ...full-scale, next-generation experiment to detect ultrahigh energy neutrinos in polar ice. For cosmic rays with a primary energy greater than 10 PeV, roughly 10% of an air shower’s energy reaches the surface of a high elevation ice sheet (≳2 ˙km) concentrated into a radius of roughly 10 cm. This penetrating shower core creates an in-ice cascade orders of magnitude more dense than the preceding in-air cascade. Additionally, this dense cascade can be detected via the radar echo technique, where transmitted radio waves are reflected from the ionization deposit left in the wake of the cascade. RET-CR will test the radar echo method in nature, with the in-ice cascade of a cosmic ray-initiated air shower serving as a test beam. In this work, we present the projected event rate and sensitivity based upon a three part simulation using corsika, geant4, and radioscatter. RET-CR expects ~1 radar echo event per day.
Summary
This paper provides a framework for the development of national guidelines for the management of glucocorticoid-induced osteoporosis in men and women aged 18 years and over in whom oral ...glucocorticoid therapy is considered for 3 months or longer.
Introduction
The need for updated guidelines for Europe and other parts of the world was recognised by the International Osteoporosis Foundation and the European Calcified Tissue Society, which set up a joint Guideline Working Group at the end of 2010.
Methods and results
The epidemiology of GIO is reviewed. Assessment of risk used a fracture probability-based approach, and intervention thresholds were based on 10-year probabilities using FRAX. The efficacy of intervention was assessed by a systematic review.
Conclusions
Guidance for glucocorticoid-induced osteoporosis is updated in the light of new treatments and methods of assessment. National guidelines derived from this resource need to be tailored within the national healthcare framework of each country.
Large-scale DNA sequencing identifies incidental rare variants in established Mendelian disease genes, but the frequency of related clinical phenotypes in unselected patient populations is not well ...established. Phenotype data from electronic medical records (EMRs) may provide a resource to assess the clinical relevance of rare variants.
To determine the clinical phenotypes from EMRs for individuals with variants designated as pathogenic by expert review in arrhythmia susceptibility genes.
This prospective cohort study included 2022 individuals recruited for nonantiarrhythmic drug exposure phenotypes from October 5, 2012, to September 30, 2013, for the Electronic Medical Records and Genomics Network Pharmacogenomics project from 7 US academic medical centers. Variants in SCN5A and KCNH2, disease genes for long QT and Brugada syndromes, were assessed for potential pathogenicity by 3 laboratories with ion channel expertise and by comparison with the ClinVar database. Relevant phenotypes were determined from EMRs, with data available from 2002 (or earlier for some sites) through September 10, 2014.
One or more variants designated as pathogenic in SCN5A or KCNH2.
Arrhythmia or electrocardiographic (ECG) phenotypes defined by International Classification of Diseases, Ninth Revision (ICD-9) codes, ECG data, and manual EMR review.
Among 2022 study participants (median age, 61 years interquartile range, 56-65 years; 1118 55% female; 1491 74% white), a total of 122 rare (minor allele frequency <0.5%) nonsynonymous and splice-site variants in 2 arrhythmia susceptibility genes were identified in 223 individuals (11% of the study cohort). Forty-two variants in 63 participants were designated potentially pathogenic by at least 1 laboratory or ClinVar, with low concordance across laboratories (Cohen κ = 0.26). An ICD-9 code for arrhythmia was found in 11 of 63 (17%) variant carriers vs 264 of 1959 (13%) of those without variants (difference, +4%; 95% CI, -5% to +13%; P = .35). In the 1270 (63%) with ECGs, corrected QT intervals were not different in variant carriers vs those without (median, 429 vs 439 milliseconds; difference, -10 milliseconds; 95% CI, -16 to +3 milliseconds; P = .17). After manual review, 22 of 63 participants (35%) with designated variants had any ECG or arrhythmia phenotype, and only 2 had corrected QT interval longer than 500 milliseconds.
Among laboratories experienced in genetic testing for cardiac arrhythmia disorders, there was low concordance in designating SCN5A and KCNH2 variants as pathogenic. In an unselected population, the putatively pathogenic genetic variants were not associated with an abnormal phenotype. These findings raise questions about the implications of notifying patients of incidental genetic findings.
Yet, more people die each year of CVD than from any other single cause: CVD causes 30% of deaths any given year, more than all infectious and parasitic diseases combined (2). ...CVD is a significant ...cause of premature death and the primary driver of morbidity for all NCDs, the largest burden of which occurs in low- and middle-income countries. ...we want to ensure that the World Health Organization's "25x25" targets regarding risk factors are included in all national plans, an area around which the World Heart Federation and its members are focusing resources and attention. ...we support the proposed SDG health goal as the overarching goal to achieve these results: "Ensure healthy lives and promote wellbeing for all at all ages."
Summary Objective Cannabinoid receptors and their ligands have been implicated in the regulation of various physiological processes but their role in osteoarthritis has not been investigated. The aim ...of this study was to evaluate the role of the type 2 cannabinoid receptor ( Cnr2 ) in regulating susceptibility to osteoarthritis in mice. Methods We analysed the severity of knee osteoarthritis as assessed by the Osteoarthritis Research Society International (OARSI) scoring system in mice with targeted deletion of Cnr2 ( Cnr2 −/− ) and wild type (WT) littermates. Studies were conducted in mice subjected to surgical destabilisation of the medial meniscus (DMM) and in those with spontaneous age-related osteoarthritis (OA). Results Osteoarthritis was more severe following DMM in the medial compartment of the knee in Cnr2 −/− compared with WT mice (mean ± sem score = 4.9 ± 0.5 vs 3.6 ± 0.3; P = 0.017). Treatment of WT mice with the CB2-selective agonist HU308 following DMM reduced the severity of OA in the whole joint (HU308 = 8.4 ± 0.2 vs vehicle = 10.4 ± 0.6; P = 0.007). Spontaneous age related osteoarthritis was also more severe in the medial compartment of the knee in 12-month old Cnr2 −/− mice compared with WT (5.6 ± 0.5 vs 3.5 ± 0.3, P = 0.008). Cultured articular chondrocytes from Cnr2 −/− mice produced less proteoglycans in vitro than wild type chondrocytes. Conclusion These studies demonstrate that the Cnr2 pathway plays a role in the pathophysiology of osteoarthritis in mice and shows that pharmacological activation of CB2 has a protective effect. Further studies of the role of cannabinoid receptors in the pathogenesis of osteoarthritis in man are warranted.
A resolution to the difficulties faced by parents, physicians, and pediatric patients in treating DSDs will only come with better communication and improved research methodologies. Advocacy groups ...and the Internet have allowed the intersex community to have a larger role in guiding the research and the ethical frameworks that are used in treating these disorders. These disorders are unusual and collaboration across medical centers should be the rule rather than the exception. When possible, treatments that are innovative or experimental should be subjected to rigorous research oversight 29,30. Defined periods of family crisis in which counseling and education become important are at the time of diagnosis 30,31, at the time of any surgical procedure, and at the beginning of major developmental stages. Historically, children were often left uninformed until someone judged them old and mature enough to comprehend how they were different. These attempts to protect individual children from their condition may have left them vulnerable to a personal crisis at an age when sexual identity and identity with a peer group are important. Both the needs of the child and the adult the child will become should be considered in making treatment decisions for children and adolescents with DSDs. It is best to counsel parents and educate developing children in a way that parallels chronologic and conceptual growth. When possible, the child should be involved in an age-appropriate fashion in the decision-making process and accurate information about the child's history and body should be made available. In addition, parents and families need as much information as possible and support systems that will help them navigate these challenging situations.
The incidence and associated costs of neonatal abstinence syndrome (NAS) have recently risen sharply; newborns with NAS occupy 4% of NICU beds. We implemented a coordinated program for NAS including ...standardized protocols for scoring, medications and weaning, and a calm rooming-in environment, to improve family-centered care and to decrease both length of stay (LOS) and hospital costs.
In early 2013, a multidisciplinary quality improvement team began consecutive plan-do-study-act (PDSA) cycles. We trained nurses in modified Finnegan scoring, ensured scoring only after on-demand feeds during skin-to-skin care, and standardized physician score interpretation. We provided prenatal family education, increased family involvement in symptom monitoring and nonpharmacologic treatment, and treated otherwise healthy infants on the inpatient pediatric unit instead of in the NICU. We measured outcomes using statistical process control methods.
At baseline, 46% of inborn infants at-risk for NAS were treated with morphine; by 2015, this decreased to 27%. Adjunctive use of phenobarbital decreased from 13% to 2% in the same period. Average LOS for morphine-treated newborns decreased from 16.9 to 12.3 days, average hospital costs per treated infant decreased from $19 737 to $8755, and costs per at-risk infant dropped from $11 000 to $5300. Cumulative morphine dose decreased from 13.7 to 6.6 mg per treated newborn. There were no adverse events, and 30-day readmission rates remained stable.
A coordinated, standardized NAS program safely reduced pharmacologic therapy, LOS, and hospital costs. Rooming-in with family and decreased use of NICU beds were central to achieved outcomes.
Little information exists about what primary care physicians (PCPs) and patients experience if patients are invited to read their doctors' office notes.
To evaluate the effect on doctors and patients ...of facilitating patient access to visit notes over secure Internet portals.
Quasi-experimental trial of PCPs and patient volunteers in a year-long program that provided patients with electronic links to their doctors' notes.
Primary care practices at Beth Israel Deaconess Medical Center (BIDMC) in Massachusetts, Geisinger Health System (GHS) in Pennsylvania, and Harborview Medical Center (HMC) in Washington.
105 PCPs and 13,564 of their patients who had at least 1 completed note available during the intervention period.
Portal use and electronic messaging by patients and surveys focusing on participants' perceptions of behaviors, benefits, and negative consequences.
11,155 corrected of 13,564 patients with visit notes available opened at least 1 note (84% at BIDMC, 82% corrected at GHS, and 47% at HMC). Of 5219 corrected patients who opened at least 1 note and completed a postintervention survey, 77% to 59% corrected across the 3 sites reported that open notes helped them feel more in control of their care; 60% to 78% of those taking medications reported increased medication adherence; 26% to 36% had privacy concerns; 1% to 8% reported that the notes caused confusion, worry, or offense; and 20% to 42% reported sharing notes with others. The volume of electronic messages from patients did not change. After the intervention, few doctors reported longer visits (0% to 5%) or more time addressing patients' questions outside of visits (0% to 8%), with practice size having little effect; 3% to 36% of doctors reported changing documentation content; and 0% to 21% reported taking more time writing notes. Looking ahead, 59% to 62% of patients believed that they should be able to add comments to a doctor's note. One out of 3 patients believed that they should be able to approve the notes' contents, but 85% to 96% of doctors did not agree. At the end of the experimental period, 99% of patients wanted open notes to continue and no doctor elected to stop.
Only 3 geographic areas were represented, and most participants were experienced in using portals. Doctors volunteering to participate and patients using portals and completing surveys may tend to offer favorable feedback, and the response rate of the patient surveys (41%) may further limit generalizability.
Patients accessed visit notes frequently, a large majority reported clinically relevant benefits and minimal concerns, and virtually all patients wanted the practice to continue. With doctors experiencing no more than a modest effect on their work lives, open notes seem worthy of widespread adoption.
The Robert Wood Johnson Foundation, the Drane Family Fund, the Richard and Florence Koplow Charitable Foundation, and the National Cancer Institute.
We describe here the design and initial implementation of the eMERGE‐PGx project. eMERGE‐PGx, a partnership of the Electronic Medical Records and Genomics Network and the Pharmacogenomics Research ...Network, has three objectives: (i) to deploy PGRNseq, a next‐generation sequencing platform assessing sequence variation in 84 proposed pharmacogenes, in nearly 9,000 patients likely to be prescribed drugs of interest in a 1‐ to 3‐year time frame across several clinical sites; (ii) to integrate well‐established clinically validated pharmacogenetic genotypes into the electronic health record with associated clinical decision support and to assess process and clinical outcomes of implementation; and (iii) to develop a repository of pharmacogenetic variants of unknown significance linked to a repository of electronic health record–based clinical phenotype data for ongoing pharmacogenomics discovery. We describe site‐specific project implementation and anticipated products, including genetic variant and phenotype data repositories, novel variant association studies, clinical decision support modules, clinical and process outcomes, approaches to managing incidental findings, and patient and clinician education methods.
Clinical Pharmacology & Therapeutics (2014); 96 4, 482–489. doi:10.1038/clpt.2014.137
PDF
