Bone Involvement in Hyperphosphatemic Familial Tumoral Calcinosis: A New Phenotypic Presentation

Mutations in FGF23, KL, and GALNT3 have been identified as the cause for the development of hyperphosphatemic familial tumoral calcinosis (HFTC). Patients with HFTC typically present in childhood or adolescence with periarticular soft tissue deposits that eventually progress to disrupt normal joint articulation. Mutations in the GALNT3 gene were shown to account for the hyperphosphatemic state in both HFTC and hyperostosis-hyperphosphatemia syndrome (HHS), the latter characterized by bone involvement. We present the case of a patient of a Druze ethnic origin with known HFTC that presented to our department with the first documented case of pathologic fracture occurring secondary to the disease. Our report introduces this new phenotypic presentation, suggests a potential role for prophylactic bone screening, and highlights the need for preconception genetic screening in selected populations

The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function

The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is ubiquitously expressed in both the central nervous system and in the periphery. CHRNA7 is genetically linked to multiple disorders with cognitive deficits, including schizophrenia, bipolar disorder, ADHD, epilepsy, Alzheimer's disease, and Rett syndrome. The regulation of CHRNA7 is complex; more than a dozen mechanisms are known, one of which is a partial duplication of the parent gene. Exons 5–10 of CHRNA7 on chromosome 15 were duplicated and inserted 1.6 Mb upstream of CHRNA7, interrupting an earlier partial duplication of two other genes. The chimeric CHRFAM7A gene product, dupα7, assembles with α7 subunits, resulting in a dominant negative regulation of function. The duplication is human specific, occurring neither in primates nor in rodents. The duplicated α7 sequence in exons 5–10 of CHRFAM7A is almost identical to CHRNA7, and thus is not completely queried in high throughput genetic studies (GWAS). Further, pre-clinical animal models of the α7nAChR utilized in drug development research do not have CHRFAM7A (dupα7) and cannot fully model human drug responses. The wide expression of CHRNA7, its multiple functions and modes of regulation present challenges for study of this gene in disease

Statistical issues related to dietary intake as the response variable in intervention trials.

The focus of this paper is dietary intervention trials. We explore the statistical issues involved when the response variable, intake of a food or nutrient, is based on self-report data that are subject to inherent measurement error. There has been little work on handling error in this context. A particular feature of self-reported dietary intake data is that the error may be differential by intervention group. Measurement error methods require information on the nature of the errors in the self-report data. We assume that there is a calibration sub-study in which unbiased biomarker data are available. We outline methods for handling measurement error in this setting and use theory and simulations to investigate how self-report and biomarker data may be combined to estimate the intervention effect. Methods are illustrated using data from the Trial of Nonpharmacologic Intervention in the Elderly, in which the intervention was a sodium-lowering diet and the response was sodium intake. Simulations are used to investigate the methods under differential error, differing reliability of self-reports relative to biomarkers and different proportions of individuals in the calibration sub-study. When the reliability of self-report measurements is comparable with that of the biomarker, it is advantageous to use the self-report data in addition to the biomarker to estimate the intervention effect. If, however, the reliability of the self-report data is low compared with that in the biomarker, then, there is little to be gained by using the self-report data. Our findings have important implications for the design of dietary intervention trials. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd

Postoperative infection following strabismus surgery: case series and increased incidence in a single large referral center

Purpose To identify and analyze cases of postoperative infection following strabismus surgery at a large referral center and to report the incidence, risk factors, and outcomes. Methods An electronic database search identified strabismus procedures at Duke Eye Center from July 1996 to October 2017. Diagnosis codes for periocular infections were used to further identify patients with possible infections following strabismus surgery. Results Of 9,111 strabismus surgeries, 13 (0.14%) met criteria for probable infection, all occurring since October 2012 (0/6580 before vs 13/2531 [0.51%] after; P < 0.0001). Mean age of infection cases was 11.4 years; 11 patients (85%) were under 18 years of age. Associated previous diagnoses were genetic abnormalities with associated developmental delay (n = 5 [38%]), previous skin or ear infection (n = 4 [31%]), and acute or chronic rhinitis (n = 3 [23%]). Infection site cultures revealed methicillin-resistant Staphylococcus aureus (n = 3 [23%]), methicillin-sensitive S. aureus (n = 3 [23%]), and Streptococcus pyogenes/group-A Streptococcus (n = 2 [15%]). Only 1 case had bilateral infection. Infection remained extraocular in all cases, but one eye lost light perception secondary to optic atrophy. No common surgeon/procedure/preparation-related risks were identified. Conclusions A unifying explanation for the increase in post–strabismus surgery infections at Duke Eye Center was not identified. Potential risk factors include age <18 years, developmental delay, immune compromise, preceding nonocular infection, and bacterial colonization

Converting From 3.6 and 4.5 Micron Fluxes to Stellar Mass

We use high spatial resolution maps of stellar mass and infrared flux of the Large Magellanic Cloud (LMC) to calibrate a conversion between 3.6 and 4.5 micron fluxes and stellar mass, M_* = 10^{5.65} * F_{3.6}^{2.85} * F_{4.5}^{-1.85} * (D/0.05)^2 M_solar, where fluxes are in Jy and D is the luminosity distance to the source in Mpc, and to provide an approximate empirical estimate of the fractional internal uncertainty in M_* of 0.3*sqrt{N/10^6}, where N is the number of stars in the region. We find evidence that young stars and hot dust contaminate the measurements, but attempts to remove this contamination using data that is far superior than what is generally available for unresolved galaxies resulted in marginal gains in accuracy. The scatter among mass estimates for regions in the LMC is comparable to that found by previous investigators when modeling composite populations, and so we conclude that our simple conversion is as precise as possible for the data and models currently available. Our results allow for a reasonably bottom-heavy initial mass function, such as Salpeter or heavier, and moderately disfavor lighter versions such as a diet-Salpeter or Chabrier initial mass function.Comment: 7 pages, 6 figures, to be published in the Astronomical Journa

Translating research into practice: Protocol for a community-engaged, stepped wedge randomized trial to reduce disparities in breast cancer treatment through a regional patient navigation collaborative

BACKGROUND: Racial and socioeconomic disparities in breast cancer mortality persist. In Boston, MA, Black, Non-Hispanic women and Medicaid-insured individuals are 2-3 times more likely to have delays in treatment compared to White or privately insured women. While evidence-based care coordination strategies for reducing delays exist, they are not systematically implemented across healthcare settings. METHODS: Translating Research Into Practice (TRIP) utilizes community engaged research methods to address breast cancer care delivery disparities. Four Massachusetts Clinical and Translational Science Institute (CTSI) hubs collaborated with the Boston Breast Cancer Equity Coalition (The Coalition) to implement an evidence-based care coordination intervention for Boston residents at risk for delays in breast cancer care. The Coalition used a community-driven process to define the problem of care delivery disparities, identify the target population, and develop a rigorous pragmatic approach. We chose a cluster-randomized, stepped-wedge hybrid type I effectiveness-implementation study design. The intervention implements three evidence-based strategies: patient navigation services, a shared patient registry for use across academic medical centers, and a web-based social determinants of health platform to identify and address barriers to care. Primary clinical outcomes include time to first treatment and receipt of guideline-concordant treatment, which are captured through electronic health records abstraction. We will use mixed methods to collect the secondary implementation outcomes of acceptability, adoption/penetration, fidelity, sustainability and cost. CONCLUSION: TRIP utilizes an innovative community-driven research strategy, focused on interdisciplinary collaborations, to design and implement a translational science study that aims to more efficiently integrate proven health services interventions into clinical practice

The Extragalactic Distance Scale without Cepheids IV

The Cepheid period-luminosity relation is the primary distance indicator used in most determinations of the Hubble constant. The tip of the red giant branch (TRGB) is an alternative basis. Using the new ANU SkyMapper Telescope, we calibrate the Tully Fisher relation in the I band. We find that the TRGB and Cepheid distance scales are consistent.Comment: ApJ in press 201

Genetic Divergence of Influenza A(H3N2) Amino Acid Substitutions Mark the Beginning of the 2016-2017 Winter Season in Israel

BACKGROUND: Influenza vaccine composition is reevaluated each year due to the frequency and accumulation of genetic changes that influenza viruses undergo. The beginning of the 2016-2017 influenza surveillance period in Israel has been marked by the dominance of influenza A(H3N2). OBJECTIVES: To evaluate the type, subtype, genetic evolution and amino acid substitutions of influenza A(H3N2) viruses detected among community patients with influenza-like illness (ILI) and hospitalized patients with respiratory illness in the first weeks of the 2016-2017 influenza season. STUDY DESIGN: Respiratory samples from community patients with influenza-like illness and from hospitalized patients underwent identification, subtyping and molecular characterization. Hemagglutinin sequences were compared to the vaccine strain, phylogenetic tree was created, and amino acid substitutions were determined. RESULTS: Influenza A(H3N2) predominated during the early stages of the 2016-2017 influenza season. Noticeably, approximately 20% of community patients and 36% of hospitalized patients, positive for influenza CONCLUSIONS: Characterization of the 2016-2017 A(H3N2) influenza viruses is imperative for determining the future influenza vaccine composition