Natriuretic peptide-based screening and collaborative care for heart failure:the STOP-HF randomized trial

IMPORTANCE: Prevention strategies for heart failure are needed.

OBJECTIVE: To determine the efficacy of a screening program using brain-type natriuretic peptide (BNP) and collaborative care in an at-risk population in reducing newly diagnosed heart failure and prevalence of significant left ventricular (LV) systolic and/or diastolic dysfunction.

DESIGN, SETTING, AND PARTICIPANTS: The St Vincent's Screening to Prevent Heart Failure Study, a parallel-group randomized trial involving 1374 participants with cardiovascular risk factors (mean age, 64.8 [SD, 10.2] years) recruited from 39 primary care practices in Ireland between January 2005 and December 2009 and followed up until December 2011 (mean follow-up, 4.2 [SD, 1.2] years).

INTERVENTION: Patients were randomly assigned to receive usual primary care (control condition; n=677) or screening with BNP testing (n=697). Intervention-group participants with BNP levels of 50 pg/mL or higher underwent echocardiography and collaborative care between their primary care physician and specialist cardiovascular service.

MAIN OUTCOMES AND MEASURES: The primary end point was prevalence of asymptomatic LV dysfunction with or without newly diagnosed heart failure. Secondary end points included emergency hospitalization for arrhythmia, transient ischemic attack, stroke, myocardial infarction, peripheral or pulmonary thrombosis/embolus, or heart failure.

RESULTS: A total of 263 patients (41.6%) in the intervention group had at least 1 BNP reading of 50 pg/mL or higher. The intervention group underwent more cardiovascular investigations (control, 496 per 1000 patient-years vs intervention, 850 per 1000 patient-years; incidence rate ratio, 1.71; 95% CI, 1.61-1.83; P<.001) and received more renin-angiotensin-aldosterone system-based therapy at follow-up (control, 49.6%; intervention, 56.5%; P=.01). The primary end point of LV dysfunction with or without heart failure was met in 59 (8.7%) of 677 in the control group and 37 (5.3%) of 697 in the intervention group (odds ratio [OR], 0.55; 95% CI, 0.37-0.82; P = .003). Asymptomatic LV dysfunction was found in 45 (6.6%) of 677 control-group patients and 30 (4.3%) of 697 intervention-group patients (OR, 0.57; 95% CI, 0.37-0.88; P = .01). Heart failure occurred in 14 (2.1%) of 677 control-group patients and 7 (1.0%) of 697 intervention-group patients (OR, 0.48; 95% CI, 0.20-1.20; P = .12). The incidence rates of emergency hospitalization for major cardiovascular events were 40.4 per 1000 patient-years in the control group vs 22.3 per 1000 patient-years in the intervention group (incidence rate ratio, 0.60; 95% CI, 0.45-0.81; P = .002).

CONCLUSION AND RELEVANCE: Among patients at risk of heart failure, BNP-based screening and collaborative care reduced the combined rates of LV systolic dysfunction, diastolic dysfunction, and heart failure.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00921960.

Progression of left atrial volume index in a population at risk for heart failure:a substudy of the STOP-HF (St Vincent's Screening TO Prevent Heart Failure) trial

AIMS: Limited data are available concerning the evolution of the left atrial volume index (LAVI) in pre-heart failure (HF) patients. The aim of this study was to investigate clinical characteristics and serological biomarkers in a cohort with risk factors for HF and evidence of serial atrial dilatation.

METHODS AND RESULTS: This was a prospective substudy within the framework of the STOP-HF cohort (NCT00921960) involving 518 patients with risk factors for HF electively undergoing serial clinical, echocardiographic, and natriuretic peptide assessment. Mean follow-up time between assessments was 15 ± 6 months. 'Progressors' (n = 39) were defined as those with serial LAVI change ≥3.5 mL/m(2) (and baseline LAVI between 20 and 34 mL/m(2)). This cut-off was derived from a calculated reference change value above the biological, analytical, and observer variability of serial LAVI measurement. Multivariate analysis identified significant baseline clinical associates of LAVI progression as increased age, beta-blocker usage, and left ventricular mass index (all P < 0.05). Serological biomarkers were measured in a randomly selected subcohort of 30 'Progressors' matched to 30 'Non-progressors'. For 'Progressors', relative changes in matrix metalloproteinase 9 (MMP9), tissue inhibitor of metalloproteinase 1 (TIMP1), and the TIMP1/MMP9 ratio, markers of interstitial remodelling, tracked with changes in LAVI over time (all P < 0.05).

CONCLUSION: Accelerated LAVI increase was found to occur in up to 14% of all pre-HF patients undergoing serial echocardiograms over a relatively short follow-up period. In a randomly selected subcohort of 'Progressors', changes in LAVI were closely linked with alterations in MMP9, TIMP1, and the ratio of these enzymes, a potential aid in highlighting this at-risk group.

Intercity Bus Route Evaluation for Statewide Planning, 1981

The goal of this research was to evaluate the needs of the intercity common carrier bus service in Iowa. Within the framework of the overall goal, the objectives were to: (1) Examine the detailed operating cost and revenue data of the intercity carriers in Iowa; (2) Develop a model or models to estimate demand in cities and corridors served by the bus industry; (3) Develop a cost function model for estimating a carrier's operating costs; (4) Establish the criteria to be used in assessing the need for changes in bus service; (5) Outline the procedures for estimating route operating costs and revenues and develop a matrix of community and social factors to be considered in evaluation; and (6) Present a case study to demonstrate the methodology. The results of the research are presented in the following chapters: (1) Introduction; (2) Intercity Bus Research and Development; (3) Operating Characteristics of Intercity Carriers in Iowa; (4) Commuter Carriers; (5) Passenger and Revenue Forecasting Models; (6) Operating Cost Relationships; (7) Social and General Welfare Aspects of Intercity Bus Service; (8) Case Study Analysis; and (9) Additional Service Considerations and Recommendations.

Comments on: Static and dynamic source locations in undirected networks

SCOPUS: ed.j

Inductive Theorem Proving and Computer Algebra in the Mathweb Software Bus

Reasoning systems have reached a high degree of maturity in the last decade. However, even the most successful systems are usually not general purpose problem solvers but are typically specialised on problems in a certain domain. The MathWeb SOftware Bus (Mathweb-SB) is a system for combining reasoning specialists via a common osftware bus. We described the integration of the lambda-clam systems, a reasoning specialist for proofs by induction, into the MathWeb-SB. Due to this integration, lambda-clam now offers its theorem proving expertise to other systems in the MathWeb-SB. On the other hand, lambda-clam can use the services of any reasoning specialist already integrated. We focus on the latter and describe first experimnents on proving theorems by induction using the computational power of the MAPLE system within lambda-clam.

'Don't stop': re-thinking the function of endings in narrative television

This thesis argues that the study of narrative television has been limited by an adherence to accepted and commonplace conceptions of endings as derived from literary theory, particularly a preoccupation with the terminus of the text as the ultimate site of cohesion, structure, and meaning. Such common conceptions of endings, this thesis argues, are largely incompatible with the realities of television’s production and reception, and as a result the study of endings in television needs to be re-thought to pay attention to the specificities of the medium. In this regard, this thesis proposes a model of intra-narrative endings, islands of cohesion, structure, and meaning located within television texts, as a possible solution to the problem of endings in television. These intra-narrative endings maintain the functionality of traditional endings, whilst also allowing for the specificities of television as a narrative medium. The first two chapters set out the theoretical groundwork, first by exploring the essential characteristics of narrative television (serialisation, fragmentation, duration, repetition, and accumulation), then by exploring the unique relationship between narrative television and the forces of contingency. These chapters also introduce the concept of intra-narrative endings as a possible solution to the problems of television’s narrative structure, and the medium’s relationship to contingency. Following on from this my three case studies examine forms of television which have either been traditionally defined as particularly resistant to closure (soap opera and the US sitcom) or which have received little analysis in terms of their narrative structure (sports coverage). Each of these case studies provides contextual material on these televisual forms, situating them in terms of their narrative structure, before moving on to analyse them in terms of my concept of intra-narrative endings. In the case of soap opera, the chapter focusses on the death of the long running character Pat Butcher in the British soap EastEnders (BBC, 1985-), while my chapter on the US sitcom focusses on the varying levels of closure that can be located within the US sitcom, using Friends (NBC, 1993-2004) as a particular example. Finally, my chapter on sports coverage analyses the BBC’s coverage of the 2012 London Olympics, and focusses on the narratives surrounding cyclists Chris Hoy and Victoria Pendleton. Each of these case studies identifies their chosen events as intra-narrative endings within larger, ongoing texts, and analyses the various ways in which they operate within those wider texts. This thesis is intended to make a contribution to the emerging field of endings studies within television by shifting the understanding of endings away from a dominant literary model which overwhelmingly focusses on the terminus of the text, to a more televisually specific model which pays attention to the particular contexts of the medium’s production and reception.

An Exploration of Auditory Brainstem Encoding of Stop Consonants in Infants and Implications for Language Outcomes

Current trends in speech-language pathology focus on early intervention as the preferred tool for promoting the best possible outcomes in children with language disorders. Neuroimaging techniques are being studied as promising tools for flagging at-risk infants. In this study, the auditory brainstem response (ABR) to the syllables /ba/ and /ga/ was examined in 41 infants between 3 and 12 months of age as a possible tool to predict language development in toddlerhood. The MacArthur-Bates Communicative Development Inventory (MCDI) was used to assess language development at 18 months of age. The current study compared the periodicity of the responses to the stop consonants and phase differences between /ba/ and /ga/ in both at-risk and low-risk groups. The study also examined whether there are correlations among ABR measures (periodicity and phase differentiation) and language development. The study found that these measures predict language development at 18 months.

The RGBarrier assay: the parallel study of gene regulatory element performance at defined chromosomal locations

Vertebrate genomes are organised into a variety of nuclear environments and chromatin states that have profound effects on the regulation of gene transcription. This variation presents a major challenge to the expression of transgenes for experimental research, genetic therapies and the production of biopharmaceuticals. The majority of transgenes succumb to transcriptional silencing by their chromosomal environment when they are randomly integrated into the genome, a phenomenon known as chromosomal position effect (CPE). It is not always feasible to target transgene integration to transcriptionally permissive “safe harbour” loci that favour transgene expression, so there remains an unmet need to identify gene regulatory elements that can be added to transgenes which protect them against CPE. Dominant regulatory elements (DREs) with chromatin barrier (or boundary) activity have been shown to protect transgenes from CPE. The HS4 element from the chicken beta-globin locus and the A2UCOE element from a human housekeeping gene locus have been shown to function as DRE barriers in a wide variety of cell types and species. Despite rapid advances in the profiling of transcription factor binding, chromatin states and chromosomal looping interactions, progress towards functionally validating the many candidate barrier elements in vertebrates has been very slow. This is largely due to the lack of a tractable and efficient assay for chromatin barrier activity. In this study, I have developed the RGBarrier assay system to test the chromatin barrier activity of candidate DREs at pre-defined isogenic loci in human cells. The RGBarrier assay consists in a Flp-based RMCE reaction for the integration of an expression construct, carrying candidate DREs, in a pre-characterised chromosomal location. The RGBarrier system involves the tracking of red, green and blue fluorescent proteins by flow cytometry to monitor on-target versus off-target integration and transgene expression. The analysis of the reporter (GFP) expression for several weeks gives a measure of the protective ability of each candidate elements from chromosomal silencing. This assay can be scaled up to test tens of new putative barrier elements in the same chromosomal context in parallel. The defined chromosomal contexts of the RGBarrier assays will allow for detailed mechanistic studies of chromosomal silencing and DRE barrier element action. Understanding these mechanisms will be of paramount importance for the design of specific solutions for overcoming chromosomal silencing in specific transgenic applications.

Desenvolvimento de mediation e-health bus

Este relatório apresenta todo o trabalho desenvolvido na Portugal Telecom Inovação ao longo de 6 meses. Este projeto esteve inserido no produto Medigraf, o qual é uma plataforma de telemedicina, desenvolvida e comercializada pela Portugal Telecom Inovação, destinada a ser integrada em organizações de saúde. Um sistema de informação é um componente muito importante nas organizações de saúde. É através deste que toda a informação referente à organização é processada e comunicada. Para que um novo sistema, a ser incorporado na organização, seja capaz de atingir todas as suas potencialidades é necessário que haja uma integração e uma interoperabilidade total entre o novo sistema e o sistema de informação existente. Torna-se assim indispensável conseguir uma integração entre o Medigraf e o sistema de informação existente nas organizações de saúde. Para isso, é necessário apurar quais os requisitos necessários para haver uma integração e uma partilha de informação entre sistemas heterógenos, explicando o conceito de standards, interoperabilidade e terminologias. O estado da arte revelou que a integração entre sistemas heterogéneos em organizações de saúde é difícil de atingir. Das várias organizações existentes, destaquei a HL7 (Health Level Seven) pelos seus avanços nesta área e pelo desenvolvimento de duas versões de um standard de mediation de mensagens (HL7 v2.x e HL7 v3) com o objetivo de atingir uma interoperabilidade entre sistemas heterógenos. Com o estudo mais aprofundado do standard de mensagens HL7 v3, foi necessário adotar uma arquitetura/topologia de integração de forma a implementar o standard. Neste estudo, destaquei a família de soluções EAI (Enterprise Application Integration) como melhor solução. De modo a implementar o standard HL7 v3 com base na arquitetura escolhida, realizei um estudo sobre os softwares existentes. Desse estudo, resultou a escolha do Mirth Connect como melhor abordagem para implementação de uma interoperabilidade entre o Medigraf e um sistema de informação. Este software atua como um middleware de mediation na comunicação entre sistemas heterogéneos. Selecionei para implementação, dois casos de uso do standard, de modo a demonstrar a sua utilização. Nativamente, o Mirth Connect não suporta a validação das mensagens do standard HL7 v3, suportando apenas HL7 v2.x. O Mirth Connect, sendo um software Open Source, permitiu que eu pudesse desenvolver um método capaz de executar essa validação. O método foi publicado no fórum da Mirth Corporation, possibilitando a sua partilha. No final são tecidas algumas conclusões, referindo o trabalho futuro que pode ser desenvolvido.

Lot production size problem and simulation of urban transport

OBJECTIVES AND STUDY METHOD: There are two subjects in this thesis: “Lot production size for a parallel machine scheduling problem with auxiliary equipment” and “Bus holding for a simulated traffic network”. Although these two themes seem unrelated, the main idea is the optimization of complex systems. The “Lot production size for a parallel machine scheduling problem with auxiliary equipment” deals with a manufacturing setting where sets of pieces form finished products. The aim is to maximize the profit of the finished products. Each piece may be processed in more than one mold. Molds must be mounted on machines with their corresponding installation setup times. The key point of our methodology is to solve the single period lot-sizing decisions for the finished products together with the piece-mold and the mold-machine assignments, relaxing the constraint that a single mold may not be used in two machines at the same time. For the “Bus holding for a simulated traffic network” we deal with One of the most annoying problems in urban bus operations is bus bunching, which happens when two or more buses arrive at a stop nose to tail. Bus bunching reflects an unreliable service that affects transit operations by increasing passenger-waiting times. This work proposes a linear mathematical programming model that establishes bus holding times at certain stops along a transit corridor to avoid bus bunching. Our approach needs real-time input, so we simulate a transit corridor and apply our mathematical model to the data generated. Thus, the inherent variability of a transit system is considered by the simulation, while the optimization model takes into account the key variables and constraints of the bus operation. CONTRIBUTIONS AND CONCLUSIONS: For the “Lot production size for a parallel machine scheduling problem with auxiliary equipment” the relaxation we propose able to find solutions more efficiently, moreover our experimental results show that most of the solutions verify that molds are non-overlapping even if they are installed on several machines. We propose an exact integer linear programming, a Relax&Fix heuristic, and a multistart greedy algorithm to solve this problem. Experimental results on instances based on real-world data show the efficiency of our approaches. The mathematical model and the algorithm for the lot production size problem, showed in this research, can be used for production planners to help in the scheduling of the manufacturing. For the “Bus holding for a simulated traffic network” most of the literature considers quadratic models that minimize passenger-waiting times, but they are harder to solve and therefore difficult to operate by real-time systems. On the other hand, our methodology reduces passenger-waiting times efficiently given our linear programming model, with the characteristic of applying control intervals just every 5 minutes.

Fast food restaurant locations according to socioeconomic disadvantage, urban-regional locality, and schools within Victoria, Australia

Features of the built environment provide opportunities to engage in both healthy and unhealthy behaviours. Access to a high number of fast food restaurants may encourage greater consumption of fast food products. The distribution of fast food restaurants at a state-level has not previously been reported in Australia. Using the location of 537 fast food restaurants from four major chains (McDonald[U+05F3]s, KFC, Hungry Jacks, and Red Rooster), this study examined fast food restaurant locations across the state of Victoria relative to area-level disadvantage, urban-regional locality (classified as Major Cities, Inner Regional, or Outer Regional), and around schools. Findings revealed greater locational access to fast food restaurants in more socioeconomically disadvantaged areas (compared to areas with lower levels of disadvantage), nearby to secondary schools (compared to primary schools), and nearby to primary and secondary schools within the most disadvantaged areas of the major city region (compared to primary and secondary schools in areas with lower levels of disadvantage). Adjusted models showed no significant difference in location according to urban-regional locality. Knowledge of the distribution of fast food restaurants in Australia will assist local authorities to target potential policy mechanisms, such as planning regulations, where they are most needed.

Policing in cool and hot climates: legitimacy, power and the rise and fall of mass stop and search in Scotland

Prior to the amalgamation of Scotland’s eight police forces into Police Scotland in 2013 by the Scottish National Party government, Scottish policing generally enjoyed a ‘cool’ political climate, with low scrutiny and minimal political engagement. This paper argues these conditions hindered the critical interrogation of Scottish policing, allowing a policy of unregulated and unfettered stop and search to flourish unchallenged for two decades. We then show how this policy was swiftly dismantled in the ‘heated’ environment that followed centralization, a move that gave rise to the unprecedented scrutiny of Scottish policing by media and political commentators. The analysis suggests that the legitimacy and reputation of the police may owe a debt to political environments that encourage either ‘soft’ or ‘hard’ analysis. Also, that more heated political environments, often disparaged by academics and criminal justice practitioners, can drive accountability and contribute to more progressive outcomes.

Stop jumping the gun : a call for evidence-based invasive predator management

Invasive mammalian predators are major drivers of species extinctions globally. To protect native prey, lethal control is often used with the aim of reducing or exterminating invasive predator populations. The efficacy of this practice, however, is often not considered despite multiple practical and ecological factors that can limit success. Here, we summarize contemporary knowledge regarding the use and challenges of both lethal control and alternative approaches for reducing invasive predator impacts. As the prevailing management approach, we outline four key issues that can compromise the effectiveness of lethal control: release of herbivore and mesopredator populations, disruption of predator social systems, compensatory predator immigration, and ethical concerns. We then discuss the relative merits and limitations of four alternative approaches that may enhance conservation practitioner's ability to effectively manage invasive predators: top-predator conservation or reintroduction, maintaining habitat complexity, exclusion fencing, and behavioral and evolutionary ecology. Considerable uncertainty remains regarding the effectiveness of management approaches in different environmental contexts. We propose that the deficiencies and uncertainties outlined here can be addressed through a combination of adaptive management, expert elicitation, and cost-benefit analyses. Improved management of invasive predators requires greater consideration and assessment of the full range of management approaches available.

Variations in area-level disadvantage of Australian registered fitness trainers usual training locations

BACKGROUND: Leisure-time physical activity and strength training participation levels are low and socioeconomically distributed. Fitness trainers (e.g. gym/group instructors) may have a role in increasing these participation levels. However, it is not known whether the training location and characteristics of Australian fitness trainers vary between areas that differ in socioeconomic status.

METHODS: In 2014, a sample of 1,189 Australian trainers completed an online survey with questions about personal and fitness industry-related characteristics (e.g. qualifications, setting, and experience) and postcode of their usual training location. The Australian Bureau of Statistics 'Index of Relative Socioeconomic Disadvantage' (IRSD) was matched to training location and used to assess where fitness professionals trained and whether their experience, qualification level and delivery methods differed by area-level disadvantage. Linear regression analysis was used to examine the relationship between IRSD score and selected characteristics adjusting for covariates (e.g. sex, age).

RESULTS: Overall, 47 % of respondents worked in areas within the three least-disadvantaged deciles. In contrast, only 14.8 % worked in the three most-disadvantaged deciles. In adjusted regression models, fitness industry qualification was positively associated with a higher IRSD score (i.e. working in the least-disadvantaged areas) (Cert III: ref; Cert IV β:13.44 [95 % CI 3.86-23.02]; Diploma β:15.77 [95 % CI: 2.17-29.37]; Undergraduate β:23.14 [95 % CI: 9.41-36.86]).

CONCLUSIONS: Fewer Australian fitness trainers work in areas with high levels of socioeconomic disadvantaged areas than in areas with low levels of disadvantage. A higher level of fitness industry qualifications was associated with working in areas with lower levels of disadvantage. Future research should explore the effectiveness of providing incentives that encourage more fitness trainers and those with higher qualifications to work in more socioeconomically disadvantaged areas.

EVALUATION OF POTENTIAL TRANSLOAD FACILITY LOCATIONS IN THE UPPER PENINSULA (UP) OF MICHIGAN

Shippers want to improve their transportation efficiency and rail transportation has the potential to provide an economical alternative to trucking, but it also has potential drawbacks. The pressure to optimize transportation supply chain logistics has resulted in growing interest in multimodal alternatives, such as a combination of truck and rail transportation, but the comparison of multimodal and modal alternatives can be complicated. Shippers in Michigan’s Upper Peninsula (UP) face similar challenges. Adding to the challenge is the distance from major markets and the absence of available facilities for transloading activities. This study reviewed three potential locations for a transload facility (Nestoria, Ishpeming, and Amasa) where truck shipments could be transferred to rail and vice versa. These locations were evaluated on the basis of transportation costs for shippers when compared to the use of single mode transportation by truck to Wisconsin, Chicago, Minneapolis, and Sault Ste. Marie. In addition to shipping costs, the study also evaluated the potential impact of future carbon emission penalties on the shipping cost and the effects of changing fuel prices on shipping cost. The study used data obtained from TRANSEARCH database (2009) and found that although there were slight differences between percent savings for the three locations, any of them could provide potential benefits for movements to Chicago and Minneapolis, as long as final destination could be accessed by rail for delivery. Short haul movements of less than 200 miles (Wisconsin and Sault Ste. Marie) were not cost effective for multimodal transport. The study also found that for every dollar increase in fuel price, cost savings from multimodal option increased by three to five percent, but the inclusion of emission costs would only add one to two percent additional savings. Under a specific case study that addressed shipments by Northern Hardwoods, the most distant locations in Wisconsin would also provide cost savings, partially due to the possibility of using Michigan trucks with higher carrying capacity for the initial movement from the facility to transload location. In addition, Minneapolis movements were found to provide savings for Northern Hardwoods, even without final rail access.