Towards new recommendations to reduce the burden of alcohol-induced hypertension in the European Union.

BACKGROUND: Hazardous and harmful alcohol use and high blood pressure are central risk factors related to premature non-communicable disease (NCD) mortality worldwide. A reduction in the prevalence of both risk factors has been suggested as a route to reach the global NCD targets. This study aims to highlight that screening and interventions for hypertension and hazardous and harmful alcohol use in primary healthcare can contribute substantially to achieving the NCD targets. METHODS: A consensus conference based on systematic reviews, meta-analyses, clinical guidelines, experimental studies, and statistical modelling which had been presented and discussed in five preparatory meetings, was undertaken. Specifically, we modelled changes in blood pressure distributions and potential lives saved for the five largest European countries if screening and appropriate intervention rates in primary healthcare settings were increased. Recommendations to handle alcohol-induced hypertension in primary healthcare settings were derived at the conference, and their degree of evidence was graded. RESULTS: Screening and appropriate interventions for hazardous alcohol use and use disorders could lower blood pressure levels, but there is a lack in implementing these measures in European primary healthcare. Recommendations included (1) an increase in screening for hypertension (evidence grade: high), (2) an increase in screening and brief advice on hazardous and harmful drinking for people with newly detected hypertension by physicians, nurses, and other healthcare professionals (evidence grade: high), (3) the conduct of clinical management of less severe alcohol use disorders for incident people with hypertension in primary healthcare (evidence grade: moderate), and (4) screening for alcohol use in hypertension that is not well controlled (evidence grade: moderate). The first three measures were estimated to result in a decreased hypertension prevalence and hundreds of saved lives annually in the examined countries. CONCLUSIONS: The implementation of the outlined recommendations could contribute to reducing the burden associated with hypertension and hazardous and harmful alcohol use and thus to achievement of the NCD targets. Implementation should be conducted in controlled settings with evaluation, including, but not limited to, economic evaluation.

Significance of bending restraints for the stability of helical polymer conformations.

We performed parallel-tempering Monte Carlo simulations to investigate the formation and stability of helical tertiary structures for flexible and semiflexible polymers, employing a generic coarse-grained model. Structural conformations exhibit helical order with tertiary ordering into single helices, multiple helical segments organized into bundles, and disorganized helical arrangements. For both bending-restrained semiflexible and bending-unrestrained flexible helical polymers, the stability of the structural phases is discussed systematically by means of hyperphase diagrams parametrized by suitable order parameters, temperature, and torsion strength. This exploration lends insight into the restricted flexibility of biological polymers such as double-stranded DNA and proteins.

Identifying transitions in finite systems by means of partition function zeros and microcanonical inflection-point analysis: a comparison for elastic flexible polymers.

For the estimation of transition points of finite elastic, flexible polymers with chain lengths from 13 to 309 monomers, we compare systematically transition temperatures obtained by the Fisher partition function zeros approach with recent results from microcanonical inflection-point analysis. These methods rely on accurate numerical estimates of the density of states, which have been obtained by advanced multicanonical Monte Carlo sampling techniques. Both the Fisher zeros method and microcanonical inflection-point analysis yield very similar results and enable the unique identification of transition points in finite systems, which is typically impossible in the conventional canonical analysis of thermodynamic quantities.

Microcanonical entropy inflection points: key to systematic understanding of transitions in finite systems.

We introduce a systematic classification method for the analogs of phase transitions in finite systems. This completely general analysis, which is applicable to any physical system and extends toward the thermodynamic limit, is based on the microcanonical entropy and its energetic derivative, the inverse caloric temperature. Inflection points of this quantity signal cooperative activity and thus serve as distinct indicators of transitions. We demonstrate the power of this method through application to the long-standing problem of liquid-solid transitions in elastic, flexible homopolymers.

Comparative molecular dynamics and Monte Carlo study of statistical properties for coarse-grained heteropolymers.

Employing a simple hydrophobic-polar heteropolymer model, we compare thermodynamic quantities obtained from Andersen and Nosé-Hoover molecular dynamics as well as replica-exchange Monte Carlo methods. We find qualitative correspondence in the results, but serious quantitative differences using the Nosé-Hoover chain thermostat. For analyzing the deviations, we study different parameterizations of the Nosé-Hoover chain thermostat. Autocorrelations from molecular dynamics and Metropolis Monte Carlo runs are also investigated.

Thermodynamics of peptide aggregation processes: an analysis from perspectives of three statistical ensembles.

We employ a mesoscopic model for studying aggregation processes of proteinlike hydrophobic-polar heteropolymers. By means of multicanonical Monte Carlo computer simulations, we find strong indications that peptide aggregation is a phase separation process, in which the microcanonical entropy exhibits a convex intruder due to non-negligible surface effects of the small systems. We analyze thermodynamic properties of the conformational transitions accompanying the aggregation process from the multicanonical, canonical, and microcanonical perspective. It turns out that the microcanonical description is particularly advantageous as it allows for unraveling details of the phase-separation transition in the thermodynamic region, where the temperature is not a suitable external control parameter anymore.

Microcanonical analyses of peptide aggregation processes.

We propose the use of microcanonical analyses for numerical studies of peptide aggregation transitions. Performing multicanonical Monte Carlo simulations of a simple hydrophobic-polar continuum model for interacting heteropolymers of finite length, we find that the microcanonical entropy behaves convex in the transition region, leading to a negative microcanonical specific heat. As this effect is also seen in first-order-like transitions of other finite systems, our results provide clear evidence for recent hints that the characterization of phase separation in first-order-like transitions of finite systems profits from this microcanonical view.

Multicanonical chain-growth algorithm.

We present a temperature-independent Monte Carlo method for the determination of the density of states of lattice proteins that combines the fast ground-state search strategy of the new pruned-enriched Rosenbluth chain-growth method and multicanonical reweighting for sampling the complete energy space. Since the density of states contains all energetic information of a statistical system, we can directly calculate the mean energy, specific heat, Helmholtz free energy, and entropy for all temperatures. We apply this method to lattice proteins consisting of hydrophobic and polar monomers, and for the examples of sequences considered, we identify the transitions between native, globule, and random coil states. Since no special properties of heteropolymers are involved in this algorithm, the method applies to polymer models as well.