Establishment and cryptic transmission of Zika virus in Brazil and the Americas.

Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

Road to serenity: Individual variations in the efficacy of unobtrusive respiratory guidance for driving stress regulation.

Stress impacts driving-related cognitive functions like attention and decision-making, and may arise in automated vehicles due to non-driving tasks. Unobtrusive relaxation techniques are needed to regulate stress without distracting from driving. Tactile wearables have shown efficacy in stress regulation through respiratory guidance, but individual variations may affect their efficacy. This study assessed slow-breathing tactile guidance under different stress levels on 85 participants. Physiological, behavioral and subjective data were collected. The influence of individual variations (e.g., driving habits and behavior, personality) using logistic regression analysis was explored. Participants could follow the guidance and adjust breathing while driving, but subjective efficacy depended on individual variations linked to different efficiency in using the technique, in relation with its attentional cost. An influence of factors linked to the evaluation of context criticality was also found. The results suggest that considering individual and contextual variations is crucial in designing and using such techniques in demanding driving contexts. In this line some design recommendations and insights for further studies are provided.

Pseudomonas aeruginosa infection in augmented care: the molecular ecology and transmission dynamics in four large UK hospitals.

BACKGROUND: Pseudomonas aeruginosa is a common opportunistic pathogen and molecular typing in outbreaks has linked patient acquisition to contaminated hospital water systems. AIM: To elucidate the role of P. aeruginosa transmission rates in non-outbreak augmented care settings in the UK. METHODS: Over a 16-week period, all water outlets in augmented care units of four hospitals were sampled for P. aeruginosa and clinical isolates were collected. Outlet and clinical P. aeruginosa isolates underwent whole-genome sequencing (WGS), which with epidemiological data identified acquisition from water as definite (level 1), probable (level 2), possible (level 3), and no evidence (level 4). FINDINGS: Outlets were positive in each hospital on all three occasions: W (16%), X (2.5%), Y (0.9%) and Z (2%); and there were 51 persistently positive outlets in total. WGS identified likely transmission (at levels 1, 2 and 3) from outlets to patients in three hospitals for P. aeruginosa positive patients: W (63%), X (54.5%) and Z (26%). According to the criteria (intimate epidemiological link and no phylogenetic distance), approximately 5% of patients in the study 'definitely' acquired their P. aeruginosa from their water outlets in the intensive care unit. This study found extensive evidence of transmission from the outlet to the patients particularly in the newest hospital (W), which had the highest rate of positive outlets. CONCLUSIONS: The overall findings suggest that water outlets are the most likely source of P. aeruginosa nosocomial infections in some settings, and that widespread introduction of control measures would have a substantial impact on infections.

The tumour microenvironment: a novel target for cancer therapy.

Cancer therapy is in the midst of a major paradigm shift. Traditionally, cancer treatments have focused on tumour cells. However, studies over the past few decades have demonstrated that cancer is a vastly complex entity with multiple components affecting a tumour's growth, invasion and metastasis. These components, collectively termed the 'tumour microenvironment', include endothelial cells, pericytes, fibroblasts, inflammatory cells, leucocytes and elements of the extracellular matrix (ECM). Biological agents that target components of the tumour microenvironment may provide an interesting alternative to traditional tumour cell-directed therapy. Because of the complexity of the tumour milieu, the most beneficial therapy will likely involve the combination of one or more agents directed at this new target. This review highlights recent preclinical and clinical studies involving agents that target tumour vasculature, leucocytes, pericytes, cancer-associated fibroblasts and ECM components. We pay particular attention to combination therapies targeting multiple components of the tumour microenvironment, and aim to demonstrate that this strategy holds promise for the future of cancer treatment.

Genomic and epidemiological monitoring of yellow fever virus transmission potential.

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.

The AUSTRAL VLBI observing program.

The AUSTRAL observing program was started in 2011, performing geodetic and astrometric very long baseline interferometry (VLBI) sessions using the new Australian AuScope VLBI antennas at Hobart, Katherine, and Yarragadee, with contribution from the Warkworth (New Zealand) 12 m and Hartebeesthoek (South Africa) 15 m antennas to make a southern hemisphere array of telescopes with similar design and capability. Designed in the style of the next-generation VLBI system, these small and fast antennas allow for a new way of observing, comprising higher data rates and more observations than the standard observing sessions coordinated by the International VLBI Service for Geodesy and Astrometry (IVS). In this contribution, the continuous development of the AUSTRAL sessions is described, leading to an improvement of the results in terms of baseline length repeatabilities by a factor of two since the start of this program. The focus is on the scheduling strategy and increased number of observations, aspects of automated operation, and data logistics, as well as results of the 151 AUSTRAL sessions performed so far. The high number of the AUSTRAL sessions makes them an important contributor to VLBI end-products, such as the terrestrial and celestial reference frames and Earth orientation parameters. We compare AUSTRAL results with other IVS sessions and discuss their suitability for the determination of baselines, station coordinates, source coordinates, and Earth orientation parameters.

First Complete Genome Sequences of Zika Virus Isolated from Febrile Patient Sera in Ecuador.

Here, we present the complete genome sequences of two Zika virus (ZIKV) strains, EcEs062_16 and EcEs089_16, isolated from the sera of febrile patients in Esmeraldas City, in the northern coastal province of Esmeraldas, Ecuador, in April 2016. These are the first complete ZIKV genomes to be reported from Ecuador.

Identification, preparation, and characterization of several polymorphs and solvates of terazosin hydrochloride.

The phenomenon of polymorphism is prevalent in pharmaceuticals, yet it is unusual to identify more than three or four forms for any particular drug. Terazosin hydrochloride has been found to exist at room temperature in four solvent-free forms that can be isolated directly, one solvent-free form that can be prepared by desolvation of a methanolate, a methanol solvate, and a dihydrate. This study presents characterization and methods for preparation of each of these forms. Data are also presented demonstrating the relative stability of these forms.

Case-control study of the muscular compartments and osseous strength in neurofibromatosis type 1 using peripheral quantitative computed tomography.

Skeletal anomalies are observed in neurofibromatosis type 1 (NF1), but the pathogenesis is unknown. Given that muscle mass is important in the development of the strength of bone, peripheral quantitative computed tomography (pQCT) was utilized to compare measurements of muscle compartments between NF1 individuals and controls. Forty individuals with NF1 (age 5-18 years) were evaluated. Cross-sectional measurements, at the 66% tibial site, were obtained using pQCT (XCT-2000, Stratec) and variables were compared to controls without NF1 ((age 5-18 years, N=380) using analysis-of-covariance controlling for age, height, Tanner stage, and gender. The NF1 cohort showed decreased total cross-sectional area [p<0.001], decreased muscle plus bone cross-sectional area [p<0.001], decreased muscle cross-sectional area [p<0.001], and decreased Stress Strain Index [p=0.010]. These data indicate that NF1 individuals have decreased muscle cross-sectional area and decreased bone strength than individuals without NF1.

Emergence of ciprofloxacin resistance in nosocomial methicillin-resistant Staphylococcus aureus isolates. Resistance during ciprofloxacin plus rifampin therapy for methicillin-resistant S aureus colonization.

We initiated a randomized, single-blinded trial of ciprofloxacin plus rifampin vs sulfamethoxazole and trimethoprim plus rifampin in the therapy for patients who underwent colonization with methicillin-resistant Staphylococcus aureus (MRSA). Patients who were colonized with MRSA received 2 weeks of either regimen. The study was terminated after the enrollment of 21 subjects due to the recognition of ciprofloxacin resistance in 10 of 21 new MRSA isolates during the last 2 months of the study. Five of the 10 patients with ciprofloxacin-resistant MRSA isolates had never received ciprofloxacin. Long-term (6-month) eradication had been achieved in only three of 11 ciprofloxacin plus rifampin and four of 10 sulfamethoxazole and trimethoprim plus rifampin recipients. The use of this new fluoroquinolone for the eradication of MRSA colonization is usually not effective and may risk the development of ciprofloxacin resistance in MRSA within the hospital environment.

Part four: The research dissertation: planning, producing and writing a thesis.

Dissertations have become common inclusions to postgraduate degrees in healthcare. To the novice researcher, undertaking an extensive project of this kind can appear daunting. In this final article in the series 'Spotlight on Research', Julie Quick and Susan Hall advise perioperative practitioners on how to plan, produce and write a research dissertation. Guidance is also given on disseminating the results from research studies.

Part two: Qualitative research.

This second article in the series Spotlight on Research focuses on qualitative research, its applications, principles and methodologies. It provides an insight into how this approach can be used within the perioperative setting and gives advice for practitioners looking to undertake a qualitative research study.

Are you prepared to take the risk: Extending governance for perioperative roles.

In the 25 years since the Oxford Heart Centre in England appointed the first British nurse to be formally trained as a non-medically qualified surgical assistant, the number of nurses and allied health professionals (AHPs) undertaking advancing surgical roles has increased in order to backfill the deficit of a surgical workforce (Quick and Hall 2014). Despite initial concerns over nurses and AHPs undertaking roles and responsibilities which were previously performed solely by doctors, the role of non-medical surgical assistants has been shown to maintain surgical services, provide an additional career route for nurses, and enhance patient care (Abraham 2011, Quick 2013, Jones et al 2012). In the early days however, a lack of role specific regulation, practice guidelines and a variety of educational standards led to variances in job titles and role responsibilities for nurses and AHPs performing surgical assistance (Box 1).

Novel opiates and antagonists. 6. 7-Alkyl-6,7-didehydromorphinans.

A method for preparing a variety of 7-alkyl-6,7- didehydromorphinans from the corresponding 6- morphinanones is described. The key intermediates in this sequence are the 7-formyl derivatives. The two epimeric B/C-trans-7-(1- hydroxypentyl ) morphinans ( 16a ,b) are stereochemically similar to the endo- ethanotetrahydrooripavines and are extremely potent in the mouse writhing test. The corresponding B/C-cis -7-(1- hydroxypentyl ) morphinans are inactive in this test.

Novel opiates and antagonists. 4. 7-Alkanoylhydromorphones.

A series of 7-alkanoyl-substituted hydromorphone derivatives were prepared by acylation of the morpholine enamines. The most potent compound (6i) of the series was found to have agonist activity of the same order of magnitude as that of buprenorphine. The N-cyclopropylmethyl-substituted series was found to exhibit structure-activity relationships for analgesia and narcotic antagonism similar to those of the endo-ethanotetrahydrooripavines.

Intervention research to promote clinically effective and economically efficient use of pharmaceuticals: the International Network for Rational Use of Drugs.

Despite acceptance of the essential drug concept by over 100 countries, current drug use patterns frequently result in unsafe use, waste of scarce resources, non-compliance, excess adverse drug reactions and disease resistance. Even in countries where resources for research are available, most efforts to improve drug prescribing have never been properly evaluated. Proposed interventions should reflect the behavioral basis for current drug use, target priority public health areas, and be feasible in developing country contexts. Most importantly, they must be critically assessed for cost and effectiveness in well-controlled field trials. The International Network for Rational Use of Drugs (INRUD) is a cooperative organization of health professionals and researchers in developing countries whose aim is to promote improved quality of care through more clinically effective and economically efficient use of pharmaceuticals. To accomplish this, INRUD will strengthen regional and national capacities to develop and scientifically evaluate programs to improve drug use and disseminate information on practical strategies shown to be cost-effective.

Effectiveness of open-circuit and oxyhood delivery of helium-oxygen.

The combination of helium with oxygen is less dense than air and as such has been beneficial to patients with airflow obstruction within the large airways. The purpose of this study was to evaluate the effectiveness of delivering He-O2 by open-circuit systems by measuring DD50 in five adult volunteers. The mean (+/- SD) DD50 with a nonrebreathing mask was 1.32 +/- 0.89, with a simple mask was 1.21 +/- 0.87, and with a nasal cannula was 1.00 +/- 0.13; the DD50 with the nonrebreathing mask and the simple mask was statistically greater than with the cannula (p less than 0.05). Two infant oxygen hoods were assessed by measuring the nitrogen concentration at different locations in the hoods. The N2 concentration increased progressively from top to bottom, indicating that the helium was concentrated at the top. We conclude that the nonrebreathing mask and simple masks are probably satisfactory He-O2 delivery systems, that the infant oxyhood may be suboptimal, and that the nasal cannula is ineffective.

Occupational health psychology: historical roots and future directions.

Occupational health psychology (OHP) is a term first coined by Jonathan Raymond in 1990, yet OHP has historical, international roots dating at least to the early decades of the twentieth century. It involves research and practice to create healthy workplaces. This article has 4 sections. The 1st section discusses psychology's long history of concern for occupational health in industrial organizations, beginning with Hugo Münsterberg's study of industrial accidents and human safety in the late 1800s. The 2nd section focuses on OHP's movement from the convergence of public health and preventive medicine with health and clinical psychology in an industrial/organizational context. The 3rd section addresses the central issues of organizational and individual health through the framework of preventive management. The article concludes with OHP case examples drawn from the Chaparral Steel Company, the U.S. Air Force, and Johnson & Johnson.

Revolving drug funds: conducting business in the public sector.

Pharmaceuticals are essential for preventive and therapeutic health services. Unfortunately, significant demand, limited funds and high prices contribute to frequent shortages of drugs in many public health programs. One method for financing pharmaceutical supplies has been the establishment of revolving drug funds (RDFs) in which, after an initial capital investment, drug supplies are replenished with monies collected from the sale of drugs. All too often however, the funds actually recovered are insufficient to replenish supplies and the fund is soon depleted. In this paper we consider the potential benefits and common pitfalls of revolving drug funds and then focus on the central role of financial planning in establishing drug sales programs. Experiences from a variety of countries suggest several causes for the failure of some RDFs, including: under-estimation of capitalization costs, prices set below true replacement cost, frequent failure to collect payment, delays in cash flow which make funds unavailable for replenishment of drug stocks, rapid program expansion for which additional capital funds are not available, losses due to theft and deterioration of drugs, unanticipated price increases due to inflation or changes in parity rates and foreign exchange purchase restrictions. Common to many of these problems is the lack of a businesslike orientation to RDFs and, in particular, lack of careful financial planning and management. Financial planning for an RDF includes four analytical tasks: assessment of the potential market, estimation of the costs of an RDF, establishment of the cost-recovery objectives, definition of the role of subsidies and surcharges.(ABSTRACT TRUNCATED AT 250 WORDS)

Undercover careseekers: simulated clients in the study of health provider behavior in developing countries.

The simulated client method (SCM) has been used for over 20 years to study health care provider behavior in a first-hand way while minimizing observation bias. In developing countries, it has proven useful in the study of physicians, drug retailers, and family planning services. In SCM, research assistants with fictitious case scenarios (or with stable conditions or a genuine interest in the services) visit providers and request their assistance. Providers are not aware that these clients are involved in research. Simulated clients later report on the events of their visit and these data are analyzed. This paper reviews 23 developing country studies of physician, drug retail, and family planning services in order to draw conclusions about (1) the advantages and limitations of the methods; (2) considerations for design and implementation of a simulated client study; (3) validity and reliability; and (4) ethical concerns. Examples are also drawn from industrialized countries, related methodologies, and non-health fields to illustrate the issues surrounding SCM. Based on this review, we conclude that the information gathered through the use of simulated clients is unique and valuable for managers, intervention planners and evaluators, social scientist, regulators, and others. Areas that need to be explored in future work with this method include: ways to ensure data validity and reliability; research on additional types of providers and health care needs; and adaptation of the technique for routine use.