Amlodipine in the current management of hypertension.

Hypertension is the leading cause of death worldwide, affecting 1.4 billion people. Treatment options include the widely used calcium channel blockers, among which amlodipine, a dihydropyridine, has unique characteristics that distinguish it from other drugs within this class. This review aims to provide an updated overview of the evidence supporting the use of amlodipine over the past 30 years and highlights its cardiovascular benefits in current hypertension management. Amlodipine has low renal clearance (7 mL/min/mg) and long half-life (35-50 h) and duration of action, which allows it to sustain its anti-hypertensive effect for more than 24 h following a single dose. Additionally, blood pressure (BP) control is maintained even when a dose has been missed, providing continuous protection in case of incidental noncompliance. It has proven to reduce BP variability and successfully lower BP. Amlodipine also controls BP in patients with a systolic/diastolic BP of 130/80 mm Hg or higher, diabetes, or chronic kidney disease without worsening glycemic or kidney function. Additionally, amlodipine is a wise choice for older adults due to its ability to control BP and protect against stroke and myocardial infarction. Side effects of amlodipine include edema, palpitations, dizziness, and flushing, which are more common with the higher dose of 10 mg. Amlodipine is cost effective and predicted to be cost saving when compared with usual care

Direct determination of the air-sea CO₂ gas transfer velocity in Arctic sea-ice regions

The Arctic Ocean is an important sink for atmospheric CO₂. The impact of decreasing sea-ice extent and expanding marginal ice zones on Arctic air-sea CO₂ exchange depends on the rate of gas transfer in the presence of sea ice. Sea ice acts to limit air-sea gas exchange by reducing contact between air and water, but is also hypothesised to enhance gas transfer rates across surrounding open water surfaces through physical processes such as increased surface-ocean turbulence from ice-water shear and ice-edge form drag. Here we present the first direct determination of the CO₂ air-sea gas transfer velocity in a wide range of Arctic sea-ice conditions. We show that the gas transfer velocity increases near-linearly with decreasing sea-ice concentration. We also show that previous modeling approaches overestimate gas transfer rates in sea-ice regions

Designing Engaging Learning Experiences in Programming

In this paper we describe work to investigate the creation of engaging programming learning experiences. Background research informed the design of four fieldwork studies to explore how programming tasks could be framed to motivate learners. Our empirical findings from these four field studies are summarized here, with a particular focus upon one – Whack a Mole – which compared the use of a physical interface with the use of a screen-based equivalent interface to obtain insights into what made for an engaging learning experience. Emotions reported by two sets of participant undergraduate students were analyzed, identifying the links between the emotions experienced during programming and their origin. Evidence was collected of the very positive emotions experienced by learners programming with a physical interface (Arduino) in comparison with a similar program developed using a screen-based equivalent interface. A follow-up study provided further evidence of the motivation of personalized design of programming tangible physical artefacts. Collating all the evidence led to the design of a set of ‘Learning Dimensions’ which may provide educators with insights to support key design decisions for the creation of engaging programming learning experiences

Lessons learned in developing family medicine residency training programs in Japan

BACKGROUND: While family medicine is not well established as a discipline in Japan, a growing number of Japanese medical schools and training hospitals have recently started sougoushinryoubu (general medicine departments). Some of these departments are incorporating a family medicine approach to residency training. We sought to learn from family medicine pioneers of these programs lessons for developing residency training. METHODS: This qualitative project utilized a long interview research design. Questions focused on four topics: 1) circumstances when becoming chair/faculty member; 2) approach to starting the program; 3) how Western ideas of family medicine were incorporated; and 4) future directions. We analyzed the data using immersion/crystallization to identify recurring themes. From the transcribed data, we selected representative quotations to illustrate them. We verified the findings by emailing the participants and obtaining feedback. RESULTS: Participants included: five chairpersons, two program directors, and three faculty members. We identified five lessons: 1) few people understand the basic concepts of family medicine; 2) developing a core curriculum is difficult; 3) start with undergraduates; 4) emphasize clinical skills; and 5) train in the community. CONCLUSION: While organizational change is difficult, the identified lessons suggest issues that merit consideration when developing a family medicine training program. Lessons from complexity science could inform application of these insights in other countries and settings newly developing residency training

Economic and other barriers to adopting recommendations to prevent childhood obesity: results of a focus group study with parents

Abstract Background Parents are integral to the implementation of obesity prevention and management recommendations for children. Exploration of barriers to and facilitators of parental decisions to adopt obesity prevention recommendations will inform future efforts to reduce childhood obesity. Methods We conducted 4 focus groups (2 English, 2 Spanish) among a total of 19 parents of overweight (BMI ≥ 85th percentile) children aged 5-17 years. The main discussion focused on 7 common obesity prevention recommendations: reducing television (TV) watching, removing TV from child's bedroom, increasing physically active games, participating in community or school-based athletics, walking to school, walking more in general, and eating less fast food. Parents were asked to discuss what factors would make each recommendation more difficult (barriers) or easier (facilitators) to follow. Participants were also asked about the relative importance of economic (time and dollar costs/savings) barriers and facilitators if these were not brought into the discussion unprompted. Results Parents identified many barriers but few facilitators to adopting obesity prevention recommendations for their children. Members of all groups identified economic barriers (time and dollar costs) among a variety of pertinent barriers, although the discussion of dollar costs often required prompting. Parents cited other barriers including child preference, difficulty with changing habits, lack of information, lack of transportation, difficulty with monitoring child behavior, need for assistance from family members, parity with other family members, and neighborhood walking safety. Facilitators identified included access to physical activity programs, availability of alternatives to fast food and TV which are acceptable to the child, enlisting outside support, dietary information, involving the child, setting limits, making behavior changes gradually, and parental change in shopping behaviors and own eating behaviors. Conclusions Parents identify numerous barriers to adopting obesity prevention recommendations, most notably child and family preferences and resistance to change, but also economic barriers. Intervention programs should consider the context of family priorities and how to overcome barriers and make use of relevant facilitators during program development.http://deepblue.lib.umich.edu/bitstream/2027.42/78270/1/1471-2431-9-81.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78270/2/1471-2431-9-81.pdfPeer Reviewe

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity

Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread.Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR.This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations

The First New Zealanders? An Alternative Interpretation of Stable Isotope Data from Wairau Bar, New Zealand.

PLOS ONE Volume 8 includes an article “The First New Zealanders: Patterns of Diet and Mobility Revealed through Isotope Analysis”. The paper proposes that burial groups within the settlement phase site of Wairau Bar differ in terms of dietary stable isotopes and 87Sr/86Sr. The authors argue this difference is probably due to one group being a founding population while the other burials are later. Here we review the work of Kinaston et al. and present an alternative analysis and interpretation of the isotopic data. Treating the isotope data independently from cultural and biological factors we find that sex best explains dietary variation. Our reassessment of 87Sr/86Sr confirms the authors original finding of high mobility of early New Zealanders but suggests a larger range of individuals should be considered ‘non-local’ on current evidence

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update

This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry

Developing Single-Molecule TPM Experiments for Direct Observation of Successful RecA-Mediated Strand Exchange Reaction

RecA recombinases play a central role in homologous recombination. Once assembled on single-stranded (ss) DNA, RecA nucleoprotein filaments mediate the pairing of homologous DNA sequences and strand exchange processes. We have designed two experiments based on tethered particle motion (TPM) to investigate the fates of the invading and the outgoing strands during E. coli RecA-mediated pairing and strand exchange at the single-molecule level in the absence of force. TPM experiments measure the tethered bead Brownian motion indicative of the DNA tether length change resulting from RecA binding and dissociation. Experiments with beads labeled on either the invading strand or the outgoing strand showed that DNA pairing and strand exchange occurs successfully in the presence of either ATP or its non-hydrolyzable analog, ATPγS. The strand exchange rates and efficiencies are similar under both ATP and ATPγS conditions. In addition, the Brownian motion time-courses suggest that the strand exchange process progresses uni-directionally in the 5′-to-3′ fashion, using a synapse segment with a wide and continuous size distribution

Formal modeling and analysis of cognitive agent behavior

From an external perspective, cognitive agent behavior can be described by specifying (temporal) correlations of a certain complexity between stimuli (input states) and (re)actions (output states) of the agent. From an internal perspective the agent’s dynamics can be characterized by direct (causal) temporal relations between internal and mental states of the agent. The latter type of specifications can be represented in a relatively simple, executable format, which enables different types of analysis of the agent’s behavior. In particular, simulations of the agent’s behavior under different (environmental) circumstances can be explored. Furthermore, by applying verification techniques, automated analysis of the consequences of the agent’s behavior can be carried out. To enable such types of analysis when only given an external behavioral specification, this has to be transformed first into some type of executable format. An automated procedure for such a transformation is proposed in this paper. The application of the transformation procedure is demonstrated for a number of cases, showing examples of the types of analysis as mentioned for different forms of behavior