Beschreibung: Background BCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs). If an unplanned intervention with a vaccine (a natural experiment) modifies the estimated effect in a randomised controlled trial (RCT), this suggests NSEs. We used this approach to test NSEs of triple oral polio vaccine (OPV). Methods During an RCT of 2 doses of MV at 4.5 and 9 months versus 1 dose of MV at 9 months of age, we experienced 2 natural experiments with OPV. We assessed whether these OPV experiments modified the effect of 2-dose MV in the MV trial. Setting MV RCT conducted in urban Guinea-Bissau 2003–2009. Interventions Natural experiments with OPV due to missing vaccine and the implementation of OPV campaigns. Main outcome measure Changes in the mortality rate ratio (MRR) for 2-dose MV versus 1-dose MV. Results First, the MRR (2-dose/1-dose MV) overall was 0.70 (0.52 to 0.94), but the MRR was 1.04 (0.53 to 2.04) when OPV at birth (OPV0) was not given, suggesting that early priming with OPV was important for the effect of 2-dose MV. The effect of OPV0 depended on age of administration; the MRR (2-dose/1-dose MV) was 0.45 (0.29 to 0.71) for children receiving OPV0 in the first week of life, but 3.63 (0.87 to 15.2) for those receiving OPV0 after the first month of life (p=0.007, test of no interaction). Second, campaign-OPV may have reduced the difference between the randomisation groups since the MRR (2-dose/1-dose MV) was 0.60 (0.42 to 0.85) for children who had not received campaign-OPV before RCT-enrolment versus 0.72 (0.23 to 2.31) and 1.42 (0.70 to 2.90) for children who had received 1 or 2 doses of campaign-OPV-before-enrolment, respectively. Conclusions Bissau had no polio infection during this trial, so OPV0 and campaign-OPV may have NSEs since they modified the effect of 2-dose MV in an RCT. Different interventions may interact to a much larger effect than usually assumed.

Beschreibung: Objective To examine the effect of the first introduction of measles vaccine (MV) in Guinea-Bissau in 1979. Setting Urban community study of the anthropometric status of all children under 6 years of age. Participants The study cohort included 1451 children in December 1978; 82% took part in the anthropometric survey. The cohort was followed for 2 years. Intervention In December 1979, the children were re-examined anthropometrically. The participating children, aged 6 months to 6 years, were offered MV if they did not have a history of measles infection. There were no routine vaccinations in 1979–1980. Primary and secondary outcome measures Age-adjusted mortality rate ratios (MRRs) for measles vaccinated and not vaccinated children; changes in nutritional status. Results The nutritional status deteriorated significantly from 1978 to 1979. Nonetheless, children who received MV at the December 1979 examination had significantly lower mortality in the following year (1980) compared with the children who had been present in the December 1978 examination but were not measles vaccinated. Among children still living in the community in December 1979, measles-vaccinated children aged 6–71 months had a mortality rate of 18/1000 person-years during the following year compared with 51/1000 person-years for absent children who were not measles vaccinated (MRR=0.30 (0.12–0.73)). The effect of MV was not explained by prevention of measles infection as the unvaccinated children did not die of measles infection. Conclusions MV may have beneficial non-specific effects on child survival not related to the prevention of measles infection.

Beschreibung: Objectives Evaluation of the demonstrator phase and first wave roll-out of the National Health Service (NHS) Diabetes Prevention Programme (DPP) in England. To examine: (1) intervention design, provision and fidelity assessment procedures; (2) risk assessment and recruitment pathways and (3) data collection for monitoring and evaluation. To provide recommendations informing decision makers on programme quality, improvements and future evaluation. Design We reviewed programme documents, mapping against the NHS DPP specification and National Institute for Health and Care Excellence (NICE) public health guideline: Type 2 diabetes (T2D) prevention in people at high risk (PH38), conducted qualitative research using individual interviews and focus group discussions with stakeholders and examined recruitment, fidelity and data collection procedures. Setting Seven NHS DPP demonstrator sites and, subsequently, 27 first wave areas across England. Interventions Intensive behavioural intervention with weight loss, diet and physical activity goals. The national programme specifies at least 13 sessions over 9 months, delivered face to face to groups of 15–20 adults with non-diabetic hyperglycaemia, mainly recruited from primary care and NHS Health Checks. Participants Participants for qualitative research were purposively sampled to provide a spread of stakeholder experience. Documents for review were provided via the NHS DPP Management Group. Findings The NHS DPP specification reflected current evidence with a clear framework for service provision. Providers, with national capacity to deliver, supplied intervention plans compliant with this framework. Stakeholders highlighted limitations in fidelity assessment and recruitment and retention challenges, especially in reach and equity, that could adversely impact on implementation. Risk assessment for first wave eligibility differed from NICE guidance. Conclusions The NHS DPP provides an evidence-based behavioural intervention for prevention of T2D in adults at high risk, with capacity to deliver nationally. Framework specification allows for balance between consistency and contextual variation in intervention delivery, with session details devolved to providers. Limitations in fidelity assurance, data collection procedures and recruitment issues could adversely impact on intervention effectiveness and restrict evaluation.

Beschreibung: Author(s): D. C. M. Rodrigues, A. Szilva, A. B. Klautau, A. Bergman, O. Eriksson, and C. Etz We evaluate how thermal effects soften the magnon dispersion in 6 layers of Fe(001) on top of Ir(001). We perform a systematic study considering noncollinear spin arrangement and calculate configuration-dependent exchange parameters J i j n c following the methodology described by Szilva et al. [ Phys. … [Phys. Rev. B 94, 014413] Published Mon Jul 11, 2016

Beschreibung: Background— Cardiovascular magnetic resonance (CMR) myocardial perfusion imaging (MPI) is a state-of-the-art noninvasive modality for detection of myocardial ischemia and coronary artery disease. Magnetic resonance coronary angiography (MRCA) allows visualization of the coronary tree, but its incremental value as part of a CMR protocol including MPI and late gadolinium enhancement (LGE) is not well established. We aimed to evaluate the additive diagnostic value of a 3-dimensional whole-heart MRCA integration into a 1.5T CMR-MPI/LGE protocol for the detection of functionally significant coronary artery disease. Methods and Results— Forty-three symptomatic patients (61±8.3 years; 65% men) with suspected coronary artery disease and intermediate/high-pretest probability underwent CMR (including CMR-MPI, MRCA, and LGE) and x-ray invasive coronary angiography (XA) with fractional flow reserve evaluation. Diagnostic performances of MRCA, CMR-MPI/LGE, and MRCA+CMR-MPI/LGE integration were determined having XA+fractional flow reserve as standard for coronary artery disease (≥90% stenosis/occlusion or fractional flow reserve≤0.80 in vessels〉2 mm). MRCA inclusion into the CMR protocol was associated with a mean increase of 7.9±4.69 (0–17.7) minutes in total examination duration (14%). On patient-based analysis, MRCA had 96% sensitivity, 68% specificity, positive predictive value of 79%, and negative predictive value of 93%. CMR-MPI/LGE had 79% sensitivity, 95% specificity, positive predictive value of 95%, and negative predictive value of 78%. Integration of MRCA with CMR-MPI/LGE further improved CMR performance to 96% sensitivity, 89% specificity, positive predictive value of 92%, and negative predictive value of 94%, with a global accuracy of 93%. Conclusions— In this intermediate/high-pretest population, integration of noncontrast-enhanced whole-heart MRCA nonsignificantly improved per-patient diagnostic accuracy of a comprehensive 1.5-T stress-rest CMR-MPI/LGE protocol at a cost of longer scanning times.

Beschreibung: Author(s): Leonarde N. Rodrigues, A. Arantes, C. Schüller, M. J. V. Bell, and V. Anjos In this paper we investigate the resonant intersubband Raman scattering of two-dimensional electron systems in GaAs-AlGaAs single quantum wells. Self-consistent calculations of the polarized and depolarized Raman cross sections show that the appearance of excitations at the unrenormalized single-par… [Phys. Rev. B 93, 205409] Published Fri May 06, 2016

Beschreibung: Rationale: An efficient and reproducible source of genotype-specific human macrophages is essential for study of human macrophage biology and related diseases. Objective: To perform integrated functional and transcriptome analyses of human induced pluripotent stem cell–derived macrophages (IPSDMs) and their isogenic human peripheral blood mononuclear cell–derived macrophage (HMDM) counterparts and assess the application of IPSDM in modeling macrophage polarization and Mendelian disease. Methods and Results: We developed an efficient protocol for differentiation of IPSDM, which expressed macrophage-specific markers and took up modified lipoproteins in a similar manner to HMDM. Like HMDM, IPSDM revealed reduction in phagocytosis, increase in cholesterol efflux capacity and characteristic secretion of inflammatory cytokines in response to M1 (lipopolysaccharide+interferon-) activation. RNA-Seq revealed that nonpolarized (M0) as well as M1 or M2 (interleukin-4) polarized IPSDM shared transcriptomic profiles with their isogenic HMDM counterparts while also revealing novel markers of macrophage polarization. Relative to IPSDM and HMDM of control individuals, patterns of defective cholesterol efflux to apolipoprotein A-I and high-density lipoprotein-3 were qualitatively and quantitatively similar in IPSDM and HMDM of patients with Tangier disease, an autosomal recessive disorder because of mutations in ATP-binding cassette transporter AI. Tangier disease-IPSDM also revealed novel defects of enhanced proinflammatory response to lipopolysaccharide stimulus. Conclusions: Our protocol-derived IPSDM are comparable with HMDM at phenotypic, functional, and transcriptomic levels. Tangier disease-IPSDM recapitulated hallmark features observed in HMDM and revealed novel inflammatory phenotypes. IPSDMs provide a powerful tool for study of macrophage-specific function in human genetic disorders as well as molecular studies of human macrophage activation and polarization.

Beschreibung: Author(s): E. H. Baffou, M. J. S. Houndjo, M. E. Rodrigues, A. V. Kpadonou, and J. Tossa We study the evolution of the cosmological parameters, namely, the deceleration parameter q ( z ) and the parameter of effective equation of state in a Universe containing, besides ordinary matter and dark energy, a self-interacting (collisional) matter, in the generalized f ( R , T ) theory of gravity, whe… [Phys. Rev. D 92, 084043] Published Tue Oct 20, 2015

Beschreibung: Objective— Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with coronary artery disease (CAD), and high HDL-C is generally associated with reduced risk of CAD. Extremely high HDL-C with CAD is an unusual phenotype, and we hypothesized that the HDL in such individuals may have an altered composition and reduced function when compared with controls with similarly high HDL-C and no CAD. Approach and Results— Fifty-five subjects with very high HDL-C (mean, 86 mg/dL) and onset of CAD at the age of 60 years with no known risk factors for CAD (cases) were identified through systematic recruitment. A total of 120 control subjects without CAD, matched for race, sex, and HDL-C level (controls), were identified. In all subjects, HDL composition was analyzed and HDL cholesterol efflux capacity was assessed. HDL phospholipid composition was significantly lower in cases (92±37 mg/dL) than in controls (109±43 mg/dL; P =0.0095). HDL cholesterol efflux capacity was significantly lower in cases (1.96±0.39) than in controls (2.11±0.43; P =0.04). Conclusions— In people with very high HDL-C, reduced HDL phospholipid content and cholesterol efflux capacity are associated with the paradoxical development of CAD.