Parental height in relation to offspring coronary heart disease: examining transgenerational influences on health using the west of Scotland Midspan Family Study

<b>Background </b>Adult height is known to be inversely related to coronary heart disease (CHD) risk. We sought to investigate transgenerational influence of parental height on offspring’s CHD risk. <p></p> <b>Methods </b>Parents took part in a cardiorespiratory disease survey in two Scottish towns during the 1970s, in which their physical stature was measured. In 1996, their offspring were invited to participate in a similar survey, which included an electrocardiogram recording and risk factor assessment.<p></p> <b>Results </b>A total of 2306 natural offspring aged 30–59 years from 1456 couples were subsequently flagged for notification of mortality and followed for CHD-related hospitalizations. Taller paternal and/or maternal height was associated with socio-economic advantage, heavier birthweight and increased high-density lipoprotein cholesterol in offspring. Increased height in fathers, but more strongly in mothers (risk ratio for 1 SD change in maternal height = 0.85; 95% confidence interval: 0.76 to 0.95), was associated with a lower risk of offspring CHD, adjusting for age, sex, other parental height and CHD risk factors. <p></p> <b>Conclusion </b>There is evidence of an association between taller parental, particularly maternal, height and lower offspring CHD risk. This may reflect an influence of early maternal growth on the intrauterine environment provided for her offspring

Treatment regimens and outcomes in severe and moderate haemophilia A in the UK: The THUNDER study

Introduction: The THUNDER study provides an analysis of treatment patterns and outcomes in UK patients with severe or moderate haemophilia A (SHA/MHA) in 2015. Methods: Patients with SHA or MHA registered with the UK National Haemophilia Database (NHD) were segregated by severity, inhibitor status and age. Haemophilia joint health score (HJHS) was derived from NHD records and treatment regimen and annualized bleed/joint‐bleed rate (ABR/AJBR) from Haemtrack (HT) in HT‐compliant patients. Results: We report 1810 patients with SHA and 864 with MHA. Prophylaxis was used in 94.9% (n = 130/137) of HT‐compliant children <12 years with SHA, falling to 74.1% (n = 123/166) aged ≥40 years. Median ABR increased with age (1.0, IQR 0.0‐5.0, <12 years; 3.0 IQR, 1.0‐8.0, ≥40 years). Inhibitors were present in 159 (8.8%) SHA and 34 (3.9%) MHA. Median ABR increased from 2.0 (<12 years) to 21.(≥40 years) in SHA inhibitor patients using prophylaxis. Prophylaxis was used by 68.8% of HT‐compliant MHA patients (n = 106) (median FVIII baseline 0.01 IU/mL) associated with a median (IQR) ABR of 3.0 (1.0‐7.0). Median HJHS (n = 453) increased with age in SHA and MHA. Median (IQR) HJHS was higher in SHA inhibitor (17.0, 0.0‐64.5) than non‐ or past inhibitor patients (7.0, 0.0‐23.0). Conclusions: Increasing ABR with age persists despite current prophylaxis regimens.SHA and MHA had similar ABR/AJBR and HJHS, leading to a suspicion that a subgroup of MHA may be relatively undertreated. More intensive prophylaxis may improve outcomes, but this requires further study

Structural Refinement for the Modal nu-Calculus

We introduce a new notion of structural refinement, a sound abstraction of logical implication, for the modal nu-calculus. Using new translations between the modal nu-calculus and disjunctive modal transition systems, we show that these two specification formalisms are structurally equivalent. Using our translations, we also transfer the structural operations of composition and quotient from disjunctive modal transition systems to the modal nu-calculus. This shows that the modal nu-calculus supports composition and decomposition of specifications.Comment: Accepted at ICTAC 201

UK export performance research - review and implications

Previous research on export performance has been criticized for being a mosaic of autonomous endeavours and for a lack of theoretical development. Building upon extant models of export performance, and a review and analysis of research on export performance in the UK for the period 1990-2005, an integrated model of export performance is developed and theoretical explanations of export performance are put forward. It is suggested that a multi-theory approach to explaining export performance is viable. Management and policy implications for the UK emerging from the review and synthesis of the literature and the integrated model are discussed

A 750 mW, continuous-wave, solid-state laser source at 313 nm for cooling and manipulating trapped 9Be+ ions

We present a solid-state laser system that generates 750 mW of continuous-wave single-frequency output at 313 nm. Sum-frequency generation with fiber lasers at 1550 nm and 1051 nm produces up to 2 W at 626 nm. This visible light is then converted to UV by cavity-enhanced second-harmonic generation. The laser output can be tuned over a 495 GHz range, which includes the 9Be+ laser cooling and repumping transitions. This is the first report of a narrow-linewidth laser system with sufficient power to perform fault-tolerant quantum-gate operations with trapped 9Be+ ions by use of stimulated Raman transitions.Comment: 9 pages, 4 figure

Investigating the effects of vitreous humour (crude extract) on growth and differentiation of rat mesenchymal stem cells (rMSCs) and human NTERA2 cells

It is very well documented that retinoic acid (RA) reduces growth rate by induction of cell differentiation in certain conditions and cell lines. On the other hand, hyaluronic acid (HA) is known for its growth induction on cultured cells. A natural source of HA, rabbit vitreous humour (VH), was previously shown to promote wound repair in model animals. In search for its possible mechanisms, VH extract was tested on the cultured mesenchymal stem cells and NTERA2 as human embryonal carcinoma cells in the presence of RA. Changes in some cellular and molecular markers (A2B5, Oct4, Sox2) showed that VH and possibly HA interfere with differentiating effects of RA. Therefore, this reagent may affect cell proliferation and tissue regeneration by inhibition of cell differentiation.Хорошо известно, что ретиноевая кислота (RA) снижает темпы роста, индуцируя дифференциацию клеточных линий в определенных условиях. Вместе с тем известно, что гиалуроновая кислота (HA) индуцирует рост культивируемых клеток. Ранее было показано, что естественный источник НА, стекловидное тело (VH) кролика, вызывает заживление ран у модельных животных. В поисках возможного механизма этого процесса экстракт стекловидного тела был исследован на культивируемых мезенхимальных стволовых клетках и клетках NTERA2 эмбриональной карциномы человека в присутствии RA. Изменения некоторых клеточных и молекулярных маркеров (A2B5, Oct4, Sox2) показали, что VH и, возможно, HA влияют на дифференцирующие эффекты RA. Таким образом, это вещество может влиять на пролиферацию клеток и регенерацию тканей, ингибируя дифференциацию клеток.Добре відомо, що ретиноєва кислота (RA) знижує темпи росту, індукуючи диференціацію кліткових ліній в певних умовах. Разом з тим відомо, що гіалуронова кислота (НА) індукує ріст культиво- ваних клітин. Раніше було показано, що природне джерело НА, склоподібне тіло (VH) кроля, викликає загоєння ран у модельних тварин. В пошуках можливого механізму цього процесу екстракт склоподібного тіла був досліджений на культивованих мезенхімальних стовбурових клітинах та клітинах NTERA2 ембріональної карциноми людини в присутності RA. Зміни деяких клітинних та молекулярних маркерів (A2B5, Oct4, Sox2) показали, що VH і, можливо, НА впливають на диференціюючі ефекти RA. Таким чином, ця речовина може впливати на проліферацію і регенерацію тканин, інгібуючи диференціацію клітин

Population pharmacokinetics of factor IX in hemophilia B patients undergoing surgery

Essentials Factor IX (FIX) dosing using body weight frequently results in under and overdosing during surgery. We aimed to establish a population pharmacokinetic (PK) model describing the perioperative FIX levels. Population PK parameter values for clearance and V1 were 284 mL h−170 kg−1 and 5450 mL70 kg−1. Perioperative PK parameters differ from those during non-surgical prophylactic treatment. Summary: Background Hemophilia B is a bleeding disorder characterized by a deficiency of coagulation factor IX (FIX). In the perioperative setting, patients receive FIX concentrates to ensure hemostasis. Although FIX is usually dosed according to bodyweight, under- and overdosing occurs frequently during surgery. Aim The objective was to quantify and explain the interpatient variability of perioperatively administered plasma-derived (pd) and recombinant (r) FIX concentrates. Methods Data were collected from 118 patients (median age, 40 years [range, 0.2–90]; weight, 79 kg [range, 5.3–132]) with moderate (28%) or severe hemophilia B (72%), undergoing 255 surgical procedures. Population pharmacokinetic (PK) parameters were estimated using nonlinear mixed-effect modeling in NONMEM. Results Measured perioperative FIX level vs. time profiles were adequately described using a three-compartment PK model. For a typical 34-year-old patient receiving rFIX, clearance (CL), intercompartmental clearance (Q2, Q3), distribution volume of the central compartment (V1) and peripheral compartments (V2, V3) plus interpatient variability (%CV) were: CL, 284 mL h−170 kg−1 (18%); V1, 5450 mL70 kg−1 (19%); Q2, 110 mL h−170 kg−1; V2, 4800 mL70 kg−1; Q3, 1610 mL h−170 kg−1; V3, 2040 mL70 kg−1. From 0.2 years, CL and V1 decreased 0.89% and 1.15% per year, respectively, until the age of 34 years. Patients receiving pdFIX exhibited a lower CL (11%) and V1 (17%) than patients receiving rFIX. Interpatient variability was successfully quantified and explained. Conclusions The estimated perioperative PK parameters of both pdFIX and rFIX are different from those reported for prophylactic treatment. The developed model may be used to apply PK-guided dosing of FIX concentrates during surgery

America's Rural Hospitals: A Selective Review of 1980s Research

We review 1980s research on American rural hospitals within the context of a decade of increasing restrictiveness in the reimbursement and operating environments. Areas addressed include rural hospital definitions, organizational and financial performance, and strategic management activities. The latter category consists of hospital closure, diversification and vertical integration, swing-bed conversion, sole community provider designation, horizontal integration and multihospital system affiliation, marketing, and patient retention. The review suggests several research needs, including: developing more meaningful definitions of rural hospitals, engaging in methodologically sound work on the effects of innovative programs and strategic management activities—including conversion of the facility itself—on rural hospital performance, and completing studies of the effects of rural hospital closure or conversion on the health of the communities served.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74857/1/j.1748-0361.1990.tb00682.x.pd