Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Arbetslöshet och psykisk ohälsa 1980-1996 en meta-analys

A meta-analysis on the relationship between unemployment and mental health was carried out on studies published during 1980-1996. One aim of the meta-analysis was to summarise the "unemployment effect-field" consisting of 22 effect-classes derived from cross-sectional and longitudinal data. Another aim was to test three models of the mental health processes in relation to unemployment: A social causation model, a health selection model and a complementary model based on both models. Nine international databases were searched yielding 95 independent samples, and 189 effect sizes were computed from 88622 subjects. The effect sizes were clearly heterogenous, but in more than 90 percent of all the samples, employees had on average better mental health than unemployed persons. The average social causation effect, expressed as a point-biserial correlation, was r pb =0,16, while the health selection effect was r pb =0,08. These effects were significant and the complementary model was supported. Design differences, social status, geographical area and mental health scales moderated the effect sizes.Rapporten är slut i lager och kommer ej att nytryckas. Arbete och Hälsa 1998:7 ersätter. En meta-analys genomfördes på studier publicerade 1980-1996 av sambanden mellan arbetslöshet och psykisk ohälsa. Från internationella databaser erhölls 95 oberoende sampel och 189 effektstorlekar, hämtade från 88 622 personer. Det förelåg en betydande heterogenitet i effektstorlekarna, men i drygt 90 procent av samplen var hälsan bättre för arbetande än för arbetslösa. Den psykiska hälsan var beroende både av arbetslöshet och av hälsorelaterad selektion. Den genomsnittliga arbetslöshetseffekten, uttryckt i punktbiseriala korrelationer, var 0,16 medan selektionseffekten var 0,08. Effektstorlekarna hade samband med undersökningarnas design, undersökningsgrupper, geografiska hemvist och hälsoskalor. I rapporten utvecklas begreppen jämförelse- och effektfält, vilka skapas genom olika designer inom forskningen om sambanden mellan arbetslöshet och ohälsa

No increase of melanoma after kidney transplantation in the northern part of The Netherlands.

One medical problem of renal transplant patients who receive immunosuppression therapy is the development of a malignancy during the long-term follow-up. Existing studies, however, are not in agreement over whether patients who undergo renal transplantation have an increased risk of melanoma. The aim of this study was to determine the risk of melanoma in renal transplantation patients in the northern part of The Netherlands. We linked a cohort of 1,125 patients who received a renal transplantation in the University Medical Centre Groningen between 1989 and 2003 with the Cancer Registry of the Comprehensive Cancer Centre North-Netherlands, to identify all the melanoma patients in this cohort. The risk for melanoma after renal transplantation was calculated using the Standardized Incidence Ratio and the absolute excess risk. With a mean follow-up of 7.26 +/- 4.48 years, one patient developed a melanoma after the renal transplantation; the number of melanoma patients was among the lowest compared with other studies. The absolute excess risk for melanoma after renal transplantation was 0.5/10,000 person-years. Although several epidemiologic studies have shown that the risk of melanoma is increased in renal transplantation patients who receive immunosuppression therapy to prevent allograft rejection, this significant increase was not found in this study. The low net immunosuppressive agents given might be responsible for this low number of melanomas

Predictive capacity of pre-donation GFR and renal reserve capacity for donor renal function after living kidney donation.

Kidney transplantation from living donors is important to reduce organ shortage. Reliable pre-operative estimation of post-donation renal function is essential. We evaluated the predictive potential of pre-donation glomerular filtration rate (GFR) (iothalamate) and renal reserve capacity for post-donation GFR in kidney donors. GFR was measured in 125 consecutive donors (age 49 +/- 11 years; 36% male) 119 +/- 99 days before baseline GFR (GFRb) and 57 +/- 16 days after donation (GFRpost). Reserve capacity was assessed as GFR during stimulation by low-dose dopamine (GFRdopa), amino acids (GFRAA) and both (GFRmax). GFRb was 112 +/- 18, GFRdopa 124 +/- 22, GFRAA 127 +/- 19 and GFRmax 138 +/- 22 mL/min. After donation, GFR remained 64 +/- 7%. GFRpost was predicted by GFRb(R2 = 0.54), GFRdopa(R2 = 0.35), GFRAA(R2 = 0.56), GFRmax(R2 = 0.55)and age (R2 = -0.22; p < 0.001 for all). Linear regression provided the equation GFRpost = 20.01 + (0.46*GFRb). Multivariate analysis predicted GFRpost by GFRb, age and GFRmax(R2 = 0.61, p < 0.001). Post-donation renal function impairment (GFR < or = 60 mL/min/1.73 m2) occurred in 31 donors. On logistic regression, GFRb, body mass index (BMI) and age were independent predictors for renal function impairment, without added value of reserve capacity. GFR allows a relatively reliable prediction of post-donation GFR, improving by taking age and stimulated GFR into account. Long-term studies are needed to further assess the prognostic value of pre-donation characteristics and to prospectively identify subjects with higher risk for renal function loss

Changes of perceived control after kidney transplantation: a prospective study

The aim of this study was to determine if kidney transplantation is associated with increases of perceived control and how changes of perceived control affect the course of psychological distress until 1 year after transplantation.Low levels of perceived control are associated with reduced well-being among dialysis patients.Prospective longitudinal cohort study.Perceived control (Mastery Scale) and psychological distress (GHQ-12) were prospectively assessed before (T0; n = 470) and three (T1; n = 197), six (T2; n = 210) and twelve (T3; n = 183) months after transplantation. Differences between T1 and T0 perceived control were used to stratify the sample into three groups (control gain, stable control and control loss). Socio-demographic and clinical variables, including complications, were examined as potential correlates and the course of psychological was distress compared across groups. Data were collected between July 2008 - July 2013.Perceived control showed a small increase overall, with 35·1%, 50·0% and 14·9% reporting gain, stable level and loss respectively. Patients with secondary schooling were overrepresented in the control loss group. The course of psychological distress varied across perceived control change groups, with patients in the control gain group experiencing a significant reduction in psychological distress.A considerable number of patients report increased levels of perceived control after transplantation that are associated with a subsequent decrease in psychological distress. Results emphasize the importance of perceived control and could inform interventions to facilitate well-being after kidney transplantation. </p

Changes of perceived control after kidney transplantation: a prospective study

The aim of this study was to determine if kidney transplantation is associated with increases of perceived control and how changes of perceived control affect the course of psychological distress until 1and#160;year after transplantation.Low levels of perceived control are associated with reduced well-being among dialysis patients.Prospective longitudinal cohort study.Perceived control (Mastery Scale) and psychological distress (GHQ-12) were prospectively assessed before (T0; nand#160;=and#160;470) and three (T1; nand#160;=and#160;197), six (T2; nand#160;=and#160;210) and twelve (T3; nand#160;=and#160;183) months after transplantation. Differences between T1 and T0 perceived control were used to stratify the sample into three groups (control gain, stable control and control loss). Socio-demographic and clinical variables, including complications, were examined as potential correlates and the course of psychological was distress compared across groups. Data were collected between July 2008 - July 2013.Perceived control showed a small increase overall, with 35and#183;1%, 50and#183;0% and 14and#183;9% reporting gain, stable level and loss respectively. Patients with secondary schooling were overrepresented in the control loss group. The course of psychological distress varied across perceived control change groups, with patients in the control gain group experiencing a significant reduction in psychological distress.A considerable number of patients report increased levels of perceived control after transplantation that are associated with a subsequent decrease in psychological distress. Results emphasize the importance of perceived control and could inform interventions to facilitate well-being after kidney transplantation. </p

Validation of the prognostic Kidney Donor Risk Index (KDRI) scoring system of deceased donors for renal transplantation in the Netherlands

BACKGROUND: The prognostic Kidney Donor Risk Index (KDRI)—developed and internally validated in the US—is a widely-used tool to predict transplant outcome of a deceased donor kidney. The KDRI is currently used for longevity matching between donors and recipients in the US. METHODS: We aimed to externally validate the KDRI as proposed by Rao et al, (2009) containing 10 donor factors (KDRIdonor-only) and 1 with 4 additional transplant factors (KDRIfull), with stratification on recipient age and diabetes. We used the Dutch Organ Transplantation Registry to include 3201 adult recipients transplanted from 2002 to 2012. RESULTS: The median Dutch KDRI was 1.21, and comparable with the year 2012 in the US (median of 1.24). The calibration-slope was 0.98 and 0.96 for the KDRIfull and KDRIdonor-only, respectively, indicating that predictions of graft failure were on average similar. The discriminative ability (Harrell’s C) of the KDRIfull and the KDRIdonor-only at 5 years was 0.63 (95%CI 0.62-0.64), and 0.62 (95%CI 0.61-0.63), respectively. We found misspecification of 3 KDRI factors: age (p=.002), weight (p=.017), and cold ischemia time (p andlt; 0.001). Adding the use of inotropic drugs prior to donation (p=.040), and the interaction between circulatory-death donor kidneys and prolonged cold ischemic time ( andgt; 24h vs 12h, p=.059) could improve predictive ability. CONCLUSIONS: The KDRI performs equal in the Dutch population. Discriminative ability of the KDRI indicates limited clinical use for adequate individualized decisions. An updated KDRI may contribute to a standardized policy meeting the growing demand of donor kidneys in the Eurotransplant region.</p