Transition into adult healthcare services in Scotland –findings from a study concerning service users at the Scottish Spina Bifida Association

Background and Aims: Literature on interventions that enable young people with spina bifida and/or hydrocephalus to have smooth transition, into adult healthcare services, stress the need for the process to start early and to include all family members. The study reported here was set to quantify and articulate the experiences of service users who are or due to be going through the transition process in Scotland today. Methods and Results: Focus group sessions, in the North of Scotland and in the ‘Central Belt’, captured rich qualitative data. A survey, sent to eligible participants on the Spina Bifida National database, offered complimentary data source. Despite the fact that the number of returned questionnaires was low (n = 20), data analysis identified a number of core recurring themes. These include issues concerning Communications, Respect, Choice and Control. Findings suggest that there is a significant chasm between the political rhetoric and the reality faced by young people with spina bifida moving to adult healthcare services. Conclusion: A possible way to facilitate successful transition of young people is using personal healthcare information as the locus for needed change. More research is needed to ascertain whether a ‘Person-Centred Record’, which is set to empower young people on their transition pathway, is an appropriate transition tool

Implications of Electronics Constraints for Solid-State Quantum Error Correction and Quantum Circuit Failure Probability

In this paper we present the impact of classical electronics constraints on a solid-state quantum dot logical qubit architecture. Constraints due to routing density, bandwidth allocation, signal timing, and thermally aware placement of classical supporting electronics significantly affect the quantum error correction circuit's error rate. We analyze one level of a quantum error correction circuit using nine data qubits in a Bacon-Shor code configured as a quantum memory. A hypothetical silicon double quantum dot quantum bit (qubit) is used as the fundamental element. A pessimistic estimate of the error probability of the quantum circuit is calculated using the total number of gates and idle time using a provably optimal schedule for the circuit operations obtained with an integer program methodology. The micro-architecture analysis provides insight about the different ways the electronics impact the circuit performance (e.g., extra idle time in the schedule), which can significantly limit the ultimate performance of any quantum circuit and therefore is a critical foundation for any future larger scale architecture analysis.Comment: 10 pages, 7 figures, 3 table

Development and Application of a Functional Human Esophageal Mucosa Explant Platform to Eosinophilic Esophagitis.

There is an increasing prevalence of esophageal diseases but intact human tissue platforms to study esophageal function, disease mechanisms, and the interactions between cell types in situ are lacking. To address this, we utilized full thickness human donor esophagi to create and validate the ex vivo function of mucosa and smooth muscle (n = 25). Explanted tissue was tested for contractile responses to carbachol and histamine. We then treated ex vivo human esophageal mucosa with a cytokine cocktail to closely mimic the Th2 and inflammatory milieu of eosinophilic esophagitis (EoE) and assessed alterations in smooth muscle and extracellular matrix function and stiffening. We found that full thickness human esophagus as well as the individual layers of circular and longitudinal muscularis propria developed tension in response to carbachol ex vivo and that mucosa demonstrated squamous cell differentiation. Treatment of mucosa with Th2 and fibrotic cytokines recapitulated the majority of the clinical Eosinophilic Esophagitis Diagnostic Profile (EDP) on fluidic transcriptional microarray. Transforming growth factor-beta-1 (TGFβ1) increased gene expression of fibronectin, smooth muscle actin, and phospholamban (p < 0.001). The EoE cocktail also increased stiffness and decreased mucosal compliance, akin to the functional alterations in EoE (p = 0.001). This work establishes a new, transcriptionally intact and physiologically functional human platform to model esophageal tissue responses in EoE

Classification of Dust Days by Satellite Remotely Sensed Aerosol Products

Considerable progress in satellite remote sensing (SRS) of dust particles has been seen in the last decade. From an environmental health perspective, such an event detection, after linking it to ground particulate matter (PM) concentrations, can proxy acute exposure to respirable particles of certain properties (i.e. size, composition, and toxicity). Being affected considerably by atmospheric dust, previous studies in the Eastern Mediterranean, and in Israel in particular, have focused on mechanistic and synoptic prediction, classification, and characterization of dust events. In particular, a scheme for identifying dust days (DD) in Israel based on ground PM10 (particulate matter of size smaller than 10 nm) measurements has been suggested, which has been validated by compositional analysis. This scheme requires information regarding ground PM10 levels, which is naturally limited in places with sparse ground-monitoring coverage. In such cases, SRS may be an efficient and cost-effective alternative to ground measurements. This work demonstrates a new model for identifying DD and non-DD (NDD) over Israel based on an integration of aerosol products from different satellite platforms (Moderate Resolution Imaging Spectroradiometer (MODIS) and Ozone Monitoring Instrument (OMI)). Analysis of ground-monitoring data from 2007 to 2008 in southern Israel revealed 67 DD, with more than 88 percent occurring during winter and spring. A Classification and Regression Tree (CART) model that was applied to a database containing ground monitoring (the dependent variable) and SRS aerosol product (the independent variables) records revealed an optimal set of binary variables for the identification of DD. These variables are combinations of the following primary variables: the calendar month, ground-level relative humidity (RH), the aerosol optical depth (AOD) from MODIS, and the aerosol absorbing index (AAI) from OMI. A logistic regression that uses these variables, coded as binary variables, demonstrated 93.2 percent correct classifications of DD and NDD. Evaluation of the combined CART-logistic regression scheme in an adjacent geographical region (Gush Dan) demonstrated good results. Using SRS aerosol products for DD and NDD, identification may enable us to distinguish between health, ecological, and environmental effects that result from exposure to these distinct particle populations

Predictors and outcomes of crossover to surgery from physical therapy for meniscal tear and osteoarthritis a randomized trial comparing physical therapy and surgery

BACKGROUND: Arthroscopic partial meniscectomy (APM) combined with physical therapy (PT) have yielded pain relief similar to that provided by PT alone in randomized trials of subjects with a degenerative meniscal tear. However, many patients randomized to PT received APM before assessment of the primary outcome. We sought to identify factors associated with crossing over to APM and to compare pain relief between patients who had crossed over to APM and those who had been randomized to APM. METHODS: We used data from the MeTeOR (Meniscal Tear in Osteoarthritis Research) Trial of APM with PT versus PT alone in subjects ≥45 years old who had mild-to-moderate osteoarthritis and a degenerative meniscal tear. We assessed independent predictors of crossover to APM among those randomized to PT. We also compared pain relief at 6 months among those randomized to PT who crossed over to APM, those who did not cross over, and those originally randomized to APM. RESULTS: One hundred and sixty-four subjects were randomized to and received APM and 177 were randomized to PT, of whom 48 (27%) crossed over to receive APM in the first 140 days after randomization. In multivariate analyses, factors associated with a higher likelihood of crossing over to APM among those who had originally been randomized to PT included a baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score of ≥40 (risk ratio [RR] = 1.99; 95% confidence interval [CI] = 1.00, 3.93) and symptom duration of <1 year (RR = 1.74; 95% CI = 0.98, 3.08). Eighty-one percent of subjects who crossed over to APM and 82% of those randomized to APM had an improvement of ≥10 points in their pain score at 6 months, as did 73% of those who were randomized to and received only PT. CONCLUSIONS: Subjects who crossed over to APM had presented with a shorter symptom duration and greater baseline pain than those who did not cross over from PT. Subjects who crossed over had rates of surgical success similar to those of the patients who had been randomized to surgery. Our findings also suggest that an initial course of rigorous PT prior to APM may not compromise surgical outcome. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence

N-Terminal Pro–B-Type Natriuretic Peptide in the Emergency Department: The ICON-RELOADED Study

Background Contemporary reconsideration of diagnostic N-terminal pro–B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed. Objectives This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting. Methods Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (−) likelihood ratios (LRs) for acute HF. Results Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR− was 0.09 (95% CI: 0.05 to 0.13). Conclusions In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF

Ionic and electronic properties of the topological insulator Bi2_2Te2_2Se investigated using β\beta-detected nuclear magnetic relaxation and resonance of 8^8Li

We report measurements on the high temperature ionic and low temperature electronic properties of the 3D topological insulator Bi$_2$Te$_2$Se using ion-implanted $^8$Li $\beta$-detected nuclear magnetic relaxation and resonance. With implantation energies in the range 5-28 keV, the probes penetrate beyond the expected range of the topological surface state, but are still within 250 nm of the surface. At temperatures above ~150 K, spin-lattice relaxation measurements reveal isolated $^8$Li$^{+}$ diffusion with an activation energy $E_{A} = 0.185(8)$ eV and attempt frequency $\tau_{0}^{-1} = 8(3) \times 10^{11}$ s$^{-1}$ for atomic site-to-site hopping. At lower temperature, we find a linear Korringa-like relaxation mechanism with a field dependent slope and intercept, which is accompanied by an anomalous field dependence to the resonance shift. We suggest that these may be related to a strong contribution from orbital currents or the magnetic freezeout of charge carriers in this heavily compensated semiconductor, but that conventional theories are unable to account for the extent of the field dependence. Conventional NMR of the stable host nuclei may help elucidate their origin.Comment: 17 pages, 12 figures, submitted to Phys. Rev.

Using Satellite Aerosol Retrievals to Monitor Surface Particulate Air Quality

The MODIS and MISR aerosol products were designed nearly two decades ago for the purpose of climate applications. Since launch of Terra in 1999, these two sensors have provided global, quantitative information about column-integrated aerosol properties, including aerosol optical depth (AOD) and relative aerosol type parameters (such as Angstrom exponent). Although primarily designed for climate, the air quality (AQ) community quickly recognized that passive satellite products could be used for particulate air quality monitoring and forecasting. However, AOD and particulate matter (PM) concentrations have different units, and represent aerosol conditions in different layers of the atmosphere. Also, due to low visible contrast over brighter surface conditions, satellite-derived aerosol retrievals tend to have larger uncertainty in urban or populated regions. Nonetheless, the AQ community has made significant progress in relating column-integrated AOD at ambient relative humidity (RH) to surface PM concentrations at dried RH. Knowledge of aerosol optical and microphysical properties, ambient meteorological conditions, and especially vertical profile, are critical for physically relating AOD and PM. To make urban-scale maps of PM, we also must account for spatial variability. Since surface PM may vary on a finer spatial scale than the resolution of standard MODIS (10 km) and MISR (17km) products, we test higher-resolution versions of MODIS (3km) and MISR (1km research mode) retrievals. The recent (July 2011) DISCOVER-AQ campaign in the mid-Atlantic offers a comprehensive network of sun photometers (DRAGON) and other data that we use for validating the higher resolution satellite data. In the future, we expect that the wealth of aircraft and ground-based measurements, collected during DISCOVER-AQ, will help us quantitatively link remote sensed and ground-based measurements in the urban region

Evaluating the Patient-Reported Outcomes Measurement Information System scales in acute intermittent porphyria.

PurposeAcute intermittent porphyria (AIP) is a rare inborn error of heme biosynthesis characterized by life-threatening acute attacks. Few studies have assessed quality of life (QoL) in AIP and those that have had small sample sizes and used tools that may not have captured important domains.MethodsBaseline data from the Porphyrias Consortium's Longitudinal Study were obtained for 259 patients, including detailed disease and medical history data, and the following Patient-Reported Outcomes Measurement Information System (PROMIS) scales: anxiety, depression, pain interference, fatigue, sleep disturbance, physical function, and satisfaction with social roles. Relationships between PROMIS scores and clinical and biochemical AIP features were explored.ResultsPROMIS scores were significantly worse than the general population across all domains, except depression. Each domain discriminated well between asymptomatic and symptomatic patients with symptomatic patients having worse scores. Many important clinical variables like symptom frequency were significantly associated with domain scores in univariate analyses, showing responsiveness of the scales, specifically pain interference and fatigue. However, most regression models only explained ~20% of the variability observed in domain scores.ConclusionPain interference and fatigue were the most responsive scales in measuring QoL in this AIP cohort. Future studies should assess whether these scales capture longitudinal disease progression and treatment response

The Ultra-Potent and Selective TLR8 Agonist VTX-294 Activates Human Newborn and Adult Leukocytes

Background: Newborns display distinct immune responses that contribute to susceptibility to infection and reduced vaccine responses. Toll-like receptor (TLR) agonists may serve as vaccine adjuvants, when given individually or in combination, but responses of neonatal leukocytes to many TLR agonists are diminished. TLR8 agonists are more effective than other TLR agonists in activating human neonatal leukocytes in vitro, but little is known about whether different TLR8 agonists may distinctly activate neonatal leukocytes. We characterized the in vitro immuno-stimulatory activities of a novel benzazepine TLR8 agonist, VTX-294, in comparison to imidazoquinolines that activate TLR8 (R-848; (TLR7/8) CL075; (TLR8/7)), with respect to activation of human newborn and adult leukocytes. Effects of VTX-294 and R-848 in combination with monophosphoryl lipid A (MPLA; TLR4) were also assessed. Methods: TLR agonist specificity was assessed using TLR-transfected HEK293 cells expressing a NF-κB reporter gene. TLR agonist-induced cytokine production was measured in human newborn cord and adult peripheral blood using ELISA and multiplex assays. Newborn and adult monocytes were differentiated into monocyte-derived dendritic cells (MoDCs) and TLR agonist-induced activation assessed by cytokine production (ELISA) and co-stimulatory molecule expression (flow cytometry). Results: VTX-294 was ∼100x more active on TLR8- than TLR7-transfected HEK cells (EC50, ∼50 nM vs. ∼5700 nM). VTX-294-induced TNF and IL-1β production were comparable in newborn cord and adult peripheral blood, while VTX-294 was ∼ 1 log more potent in inducing TNF and IL-1β production than MPLA, R848 or CL075. Combination of VTX-294 and MPLA induced greater blood TNF and IL-1β responses than combination of R-848 and MPLA. VTX-294 also potently induced expression of cytokines and co-stimulatory molecules HLA-DR and CD86 in human newborn MoDCs. Conclusions: VTX-294 is a novel ultra-potent TLR8 agonist that activates newborn and adult leukocytes and is a candidate vaccine adjuvant in both early life and adulthood