Characteristics of undiagnosed diseases network applicants: implications for referring providers

Abstract Background The majority of undiagnosed diseases manifest with objective findings that warrant further investigation. The Undiagnosed Diseases Network (UDN) receives applications from patients whose symptoms and signs have been intractable to diagnosis; however, many UDN applicants are affected primarily by subjective symptoms such as pain and fatigue. We sought to characterize presenting symptoms, referral sources, and demographic factors of applicants to the UDN to identify factors that may determine application outcome and potentially differentiate between those with undiagnosed diseases (with more objective findings) and those who are less likely to have an undiagnosed disease (more subjective symptoms). Methods We used a systematic retrospective review of 151 consecutive Not Accepted and 50 randomly selected Accepted UDN applications. The primary outcome was whether an applicant was Accepted, or Not Accepted, and, if accepted, whether or not a diagnosis was made. Objective and subjective symptoms and information on prior specialty consultations were collected from provider referral letters. Demographic data and decision data on network acceptance were gathered from the UDN online portal. Results Fewer objective findings and more subjective symptoms were found in the Not Accepted applications. Not Accepted referrals also were from older individuals, reported a shorter period of illness, and were referred to the UDN by their primary care physicians. All of these differences reached statistical significance in comparison with Accepted applications. The frequency of subspecialty consults for diagnostic purposes prior to UDN application was similar in both groups. Conclusions The preponderance of subjective and lack of objective findings in the Not Accepted applications distinguish these from applicants that are accepted for evaluation and diagnostic efforts through the UDN. Not Accepted applicants are referred primarily by their primary care providers after multiple specialist consultations fail to yield answers. Distinguishing between patients with undiagnosed diseases with objective findings and those with primarily subjective findings can delineate patients who would benefit from further diagnostic processes from those who may have functional disorders and need alternative pathways for management of their symptoms. Trial registration clinicaltrials.gov NCT02450851 , posted May 21st 2015

Constraining the Oceanic Uptake and Fluxes of Greenhouse Gases by Building an Ocean Network of Certified Stations: The Ocean Component of the Integrated Carbon Observation System, ICOS-Oceans

The European Research Infrastructure Consortium “Integrated Carbon Observation System” (ICOS) aims at delivering high quality greenhouse gas (GHG) observations and derived data products (e.g., regional GHG-flux maps) for constraining the GHG balance on a European level, on a sustained long-term basis. The marine domain (ICOS-Oceans) currently consists of 11 Ship of Opportunity lines (SOOP – Ship of Opportunity Program) and 10 Fixed Ocean Stations (FOSs) spread across European waters, including the North Atlantic and Arctic Oceans and the Barents, North, Baltic, and Mediterranean Seas. The stations operate in a harmonized and standardized way based on community-proven protocols and methods for ocean GHG observations, improving operational conformity as well as quality control and assurance of the data. This enables the network to focus on long term research into the marine carbon cycle and the anthropogenic carbon sink, while preparing the network to include other GHG fluxes. ICOS data are processed on a near real-time basis and will be published on the ICOS Carbon Portal (CP), allowing monthly estimates of CO2 air-sea exchange to be quantified for European waters. ICOS establishes transparent operational data management routines following the FAIR (Findable, Accessible, Interoperable, and Reusable) guiding principles allowing amongst others reproducibility, interoperability, and traceability. The ICOS-Oceans network is actively integrating with the atmospheric (e.g., improved atmospheric measurements onboard SOOP lines) and ecosystem (e.g., oceanic direct gas flux measurements) domains of ICOS, and utilizes techniques developed by the ICOS Central Facilities and the CP. There is a strong interaction with the international ocean carbon cycle community to enhance interoperability and harmonize data flow. The future vision of ICOS-Oceans includes ship-based ocean survey sections to obtain a three-dimensional understanding of marine carbon cycle processes and optimize the existing network design

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Measurement of the dependence of transverse energy production at large pseudorapidity on the hard-scattering kinematics of proton-proton collisions at √s=2.76 TeV with ATLAS

The relationship between jet production in the central region and the underlying-event activity in a pseudorapidity-separated region is studied in 4.0 pb-1 of s=2.76 TeV pp collision data recorded with the ATLAS detector at the LHC. The underlying event is characterised through measurements of the average value of the sum of the transverse energy at large pseudorapidity downstream of one of the protons, which are reported here as a function of hard-scattering kinematic variables. The hard scattering is characterised by the average transverse momentum and pseudorapidity of the two highest transverse momentum jets in the event. The dijet kinematics are used to estimate, on an event-by-event basis, the scaled longitudinal momenta of the hard-scattered partons in the target and projectile beam-protons moving toward and away from the region measuring transverse energy, respectively. Transverse energy production at large pseudorapidity is observed to decrease with a linear dependence on the longitudinal momentum fraction in the target proton and to depend only weakly on that in the projectile proton. The results are compared to the predictions of various Monte Carlo event generators, which qualitatively reproduce the trends observed in data but generally underpredict the overall level of transverse energy at forward pseudorapidity

Search for high-mass diphoton resonances in pp collisions at √s = 8 TeV with the ATLAS detector

This article describes a search for high-mass resonances decaying to a pair of photons using a sample of 20.3  fb−¹ of pp collisions at √s = 8 TeV recorded with the ATLAS detector at the Large Hadron Collider. The data are found to be in agreement with the Standard Model prediction, and limits are reported in the framework of the Randall-Sundrum model. This theory leads to the prediction of graviton states, the lightest of which could be observed at the Large Hadron Collider. A lower limit of 2.66 (1.41) TeV at 95% confidence level is set on the mass of the lightest graviton for couplings of k/M̄Pl=0.1(0.01)

Measurements of the charge asymmetry in top-quark pair production in the dilepton final state at s √ =8 TeV with the ATLAS detector

Measurements of the top-antitop quark pair production charge asymmetry in the dilepton channel, characterized by two high-pT leptons (electrons or muons), are presented using data corresponding to an integrated luminosity of 20.3  fb−1 from pp collisions at a center-of-mass energy s√=8  TeV collected with the ATLAS detector at the Large Hadron Collider at CERN. Inclusive and differential measurements as a function of the invariant mass, transverse momentum, and longitudinal boost of the tt¯ system are performed both in the full phase space and in a fiducial phase space closely matching the detector acceptance. Two observables are studied: AℓℓC based on the selected leptons and Att¯C based on the reconstructed tt¯ final state. The inclusive asymmetries are measured in the full phase space to be AℓℓC=0.008±0.006 and Att¯C=0.021±0.016, which are in agreement with the Standard Model predictions of AℓℓC=0.0064±0.0003 and Att¯C=0.0111±0.0004

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure