Reconstruction of haplotype-blocks selected during experimental evolution.

The genetic analysis of experimentally evolving populations typically relies on short reads from pooled individuals (Pool-Seq). While this method provides reliable allele frequency estimates, the underlying haplotype structure remains poorly characterized. With small population sizes and adaptive variants that start from low frequencies, the interpretation of selection signatures in most Evolve and Resequencing studies remains challenging. To facilitate the characterization of selection targets, we propose a new approach that reconstructs selected haplotypes from replicated time series, using Pool-Seq data. We identify selected haplotypes through the correlated frequencies of alleles carried by them. Computer simulations indicate that selected haplotype-blocks of several Mb can be reconstructed with high confidence and low error rates, even when allele frequencies change only by 20% across three replicates. Applying this method to real data from D. melanogaster populations adapting to a hot environment, we identify a selected haplotype-block of 6.93 Mb. We confirm the presence of this haplotype-block in evolved populations by experimental haplotyping, demonstrating the power and accuracy of our haplotype reconstruction from Pool-Seq data. We propose that the combination of allele frequency estimates with haplotype information will provide the key to understanding the dynamics of adaptive alleles

Telemonitoring and/or self-monitoring of blood pressure in hypertension (TASMINH4): protocol for a randomised controlled trial.

BACKGROUND: Self-monitoring of hypertension is associated with lower systolic blood pressure (SBP). However, evidence for the use of self-monitoring to titrate antihypertensive medication by physicians is equivocal. Furthermore, there is some evidence for the efficacy of telemonitoring in the management of hypertension but it is not clear what this adds over and above self-monitoring. This trial aims to evaluate whether GP led antihypertensive titration using self-monitoring results in lower SBP compared to usual care and whether telemonitoring adds anything to self-monitoring alone. METHODS/DESIGN: This will be a pragmatic primary care based, unblinded, randomised controlled trial of self-monitoring of BP with or without telemonitoring compared to usual care. Eligible patients will have poorly controlled hypertension (>140/90 mmHg) and will be recruited from primary care. Participants will be individually randomised to either usual care, self-monitoring alone, or self-monitoring with telemonitoring. The primary outcome of the trial will be difference in clinic SBP between intervention and control groups at 12 months adjusted for baseline SBP, gender, BP target and practice. At least 1110 patients will be sufficient to detect a difference in SBP between self-monitoring with or without telemonitoring and usual care of 5 mmHg with 90% power with an adjusted alpha of 0.017 (2-sided) to adjust for all three pairwise comparisons. Other outcomes will include adherence of anti-hypertensive medication, lifestyle behaviours, health-related quality of life, and adverse events. An economic analysis will consider both within trial costs and a model extrapolating the results thereafter. A qualitative sub study will gain insights into the views, experiences and decision making processes of patients and health care professionals focusing on the acceptability of self-monitoring and telemonitoring in the routine management of hypertension. DISCUSSION: The results of the trial will be directly applicable to primary care in the UK. If successful, self-monitoring of BP in people with hypertension would be applicable to hundreds of thousands of individuals in the UK. TRIAL REGISTRATION: ISRCTN 83571366 . Registered 17 July 2014.The trial is funded by an NIHR Programme grant, and by an NIHR Professorship awarded to Prof RJ McManus, the Chief Investigator. Omron have provided the blood pressure self-monitoring equipment via an unrestricted grant. Service support costs are administered through the NIHR Clinical Research Network: West Midlands. Professors Hobbs and Professor Farmer are NIHR Senior Investigators. This article presents independent research commissioned by the National Institute for Health Research (NIHR) under a Programme Grant for Applied Research (RP-PG-1209-10051)

Reference values for body composition and associations with blood pressure in Kenyan adults aged ≥50 years old

Objectives: To develop age and sex-specific centile reference curves for fat free mass (FFM) and fat mass (FM) adjusted for height in an adult Kenyan population and to investigate the association between FM, FFM and blood pressure (BP). Methods: Measures of body composition from bioimpedance analyses and BP were collected in 1,995 participants aged ≥50y in Nakuru County, Kenya. Reference curves were produced using the LMS method. Multivariable linear regression models were used to test the cross-sectional association between body composition indexes and BP. Results: The age and sex-specific reference curves for body composition (FMI and FFMI) confirm that FFMI is lower in both men and women with increasing age. FMI declines with age in women while among men the decline starts after 70 years. FFM was higher in men (47.4 ± 7.2 kg) than in women (38.8 ± 5.5 kg), while FM was lower in men (17.3 ± 8.1 kg) than in women (24.4 ± 10.2 kg). FMI, FFMI and BMI were all positively associated with systolic and diastolic BP, and after adjusting for body weight, FFMI remained positively associated with systolic BP and the FMI remained positively associated with diastolic BP. There was no evidence to suggest that FMI and FFMI were superior to measurement of BMI alone. Conclusion: These body composition reference curves provide normative data on body composition for older adults in Kenya. Further research should consider the prospective associations with health, including frailty-related outcomes

Perspective on satellite-based land data assimilation to estimate water cycle components in an era of advanced data availability and model sophistication

The beginning of the 21st century is marked by a rapid growth of land surface satellite data and model sophistication. This offers new opportunities to estimate multiple components of the water cycle via satellite-based land data assimilation (DA) across multiple scales. By resolving more processes in land surface models and by coupling the land, the atmosphere, and other Earth system compartments, the observed information can be propagated to constrain additional unobserved variables. Furthermore, access to more satellite observations enables the direct constraint of more and more components of the water cycle that are of interest to end users. However, the finer level of detail in models and data is also often accompanied by an increase in dimensions, with more state variables, parameters, or boundary conditions to estimate, and more observations to assimilate. This requires advanced DA methods and efficient solutions. One solution is to target specific observations for assimilation based on a sensitivity study or coupling strength analysis, because not all observations are equally effective in improving subsequent forecasts of hydrological variables, weather, agricultural production, or hazards through DA. This paper offers a perspective on current and future land DA development, and suggestions to optimally exploit advances in observing and modeling systems

The culture of olfactory ensheathing cells (OECs)—a distinct glial cell type

Olfactory ensheathing cells (OECs) have become a popular candidate for the transplant-mediated repair of the damaged CNS. In this review a description is made of the origins of these cells and a historical development of their purification and maintenance in culture. In addition, we illustrate the cellular and molecular characteristics of OECs and emphasise that although they share many properties with Schwann cells, they possess several inherent differences which may allow them to be more beneficial for CNS repair. In summary, OECs are distinct glial cells and the detailed understanding of their biological and molecular properties is essential in ensuring their clinical efficacy after cell transplantation. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair

Biology of tissue factor pathway inhibitor

Recent studies of the anticoagulant activities of the tissue factor (TF) pathway inhibitor (TFPI) isoforms, TFPIa and TFPIß, have provided new insight into the biochemical and physiological meagulant activities. An alternative splicing event in the 59 untranslated region allows for translational regulation of TFPIß expression. TFPIa has 3 Kunitz-type inhibitor domains (K1, K2, K3) and a basic C terminus, whereas TFPIß has the K1 and K2 domains attached to a glycosylphosphatidyl inositol-anchored C terminus. TFPIa is the only isoform present in platelets, whereas endothelial cells produce both isoforms, secreting TFPIa and expressing TFPIb on the cell surface. TFPIa and TFPIß inhibit both TF-factor VIIa-dependent factor Xa (FXa) generation and free FXa. ProteinSenhances FXa inhibition by TFPIa. TFPIa produces isoform-specific inhibition of prothrombinase during the initiation of coagulation, an anticoagulant activity that requires an exosite interaction between its basic C terminus and an acidic region in the factor Va B domain. Platelet TFPIa may be optimally localized to dampen initial thrombin generation. Similarly, endothelial TFPIß may be optimally localized to inhibit processes that occur when endothelial TF is present, such as during the inflammatory response. © 2014 by The American Society of Hematology