Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up.

BACKGROUND: In Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. We evaluated durability of antiretroviral therapy (ART) and predictors of virologic failure among a pediatric cohort at four-year follow-up. METHODS: This was a prospective cross-sectional study with retrospective chart review evaluating a perinatally HIV-infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13. Demographic, clinical, and laboratory data were extracted from charts, resistance mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained. RESULTS: 161 (78%) participants of the original cohort consented to repeat HIV RNA. The average age was 12.2 years (55% adolescents ≥12 years). Average time on ART was 6.4 years with 41% receiving second-line (protease inhibitor based) therapy. Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed. Of those originally failing first-line, 88% were switched to second-line and 72% have suppressed virus. Increased level of viremia and duration of ART trended with an increased number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds of virologic failure (p = 0.18), as did adolescent age (p < 0.01). CONCLUSIONS: After viral load testing in 2008-09 many participants switched to second-line therapy. The majority achieved virologic suppression despite multiple resistance mutations. Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.

Are component positioning and prosthesis size associated with hip resurfacing failure?

BACKGROUND: Recent studies suggest that there is a learning curve for metal-on-metal hip resurfacing. The purpose of this study was to assess whether implant positioning changed with surgeon experience and whether positioning and component sizing were associated with implant longevity. METHODS: We evaluated the first 361 consecutive hip resurfacings performed by a single surgeon, which had a mean follow-up of 59 months (range, 28 to 87 months). Pre and post-operative radiographs were assessed to determine the inclination of the acetabular component, as well as the sagittal and coronal femoral stem-neck angles. Changes in the precision of component placement were determined by assessing changes in the standard deviation of each measurement using variance ratio and linear regression analysis. Additionally, the cup and stem-shaft angles as well as component sizes were compared between the 31 hips that failed over the follow-up period and the surviving components to assess for any differences that might have been associated with an increased risk for failure. RESULTS: Surgeon experience was correlated with improved precision of the antero-posterior and lateral positioning of the femoral component. However, femoral and acetabular radiographic implant positioning angles were not different between the surviving hips and failures. The failures had smaller mean femoral component diameters as compared to the non-failure group (44 versus 47 millimeters). CONCLUSIONS: These results suggest that there may be differences in implant positioning in early versus late learning curve procedures, but that in the absence of recognized risk factors such as intra-operative notching of the femoral neck and cup inclination in excess of 50 degrees, component positioning does not appear to be associated with failure. Nevertheless, surgeons should exercise caution in operating patients with small femoral necks, especially when they are early in the learning curve.

The Impact of Worsening Heart Failure in the United States.

In-hospital worsening heart failure represents a clinical scenario wherein a patient hospitalized for acute heart failure experiences a worsening of their condition, requiring escalation of therapy. Worsening heart failure is associated with worse in-hospital and postdischarge outcomes. Worsening heart failure is increasingly being used as an endpoint or combined endpoint in clinical trials, as it is unique to episodes of acute heart failure and captures an important event during the inpatient course. While prediction models have been developed to identify worsening heart failure, there are no known FDA-approved medications associated with decreased worsening heart failure. Continued study is warranted.

Thinking Outside the Box: Treating Acute Heart Failure Outside the Hospital to Improve Care and Reduce Admissions.

The management of acute heart failure is shifting toward treatment approaches outside of a traditional hospital setting. Many heart failure providers are now treating patients in less familiar health care settings, such as acute care clinics, emergency departments, and skilled nursing facilities. In this review we describe the current pressures driving change in the delivery of acute heart failure and summarize the evidence regarding treatments for acute heart failure outside of the inpatient setting. We also provide considerations for the design of future treatment strategies to be implemented in alternative care settings.

Ventricular conduction and long-term heart failure outcomes and mortality in African Americans: insights from the Jackson Heart Study.

BACKGROUND: QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. METHODS AND RESULTS: We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0-14.4) versus 7.1% (95% CI, 6.3-8.0) and 8.2% (95% CI, 6.9-9.7) versus 4.4% (95% CI, 3.7-5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03-1.56; P=0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01-1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation. CONCLUSIONS: QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities.

Identifying Barriers and Practical Solutions to Conducting Site-Based Research in North America: Exploring Acute Heart Failure Trials As a Case Study.

Although the prognosis of ambulatory heart failure (HF) has improved dramatically there have been few advances in the management of acute HF (AHF). Despite regional differences in patient characteristics, background therapy, and event rates, AHF clinical trial enrollment has transitioned from North America and Western Europe to Eastern Europe, South America, and Asia-Pacific where regulatory burden and cost of conducting research may be less prohibitive. It is unclear if the results of clinical trials conducted outside of North America are generalizable to US patient populations. This article uses AHF as a paradigm and identifies barriers and practical solutions to successfully conducting site-based research in North America.

Global value Chains, rising power firms and economic and social upgrading

© Emerald Group Publishing Limited.Purpose – The purpose of this paper is to introduce the global value chain (GVC) approach to understand the relationship between multinational enterprises (MNEs) and the changing patterns of global trade, investment and production, and its impact on economic and social upgrading. It aims to illuminate how GVCs can advance our understanding about MNEs and rising power (RP) firms and their impact on economic and social upgrading in fragmented and dispersed global production systems. Design/methodology/approach – The paper reviews theGVCliterature focusing on two conceptual elements of the GVC approach, governance and upgrading, and highlights three key recent developments in GVCs: concentration, regionalization and synergistic governance. Findings – The paper underscores the complicated role of GVCs in shaping economic and social upgrading for emerging economies, RP firms and developing country firms in general. Rising geographic and organizational concentration in GVCs leads to the uneven distribution of upgrading opportunities in favor of RP firms, and yet economic upgrading may be elusive even for the most established suppliers because of power asymmetry with global buyers. Shifting end markets and the regionalization of value chains can benefit RP firms by presenting alternative markets for upgrading. Yet, without further upgrading, such benefits may be achieved at the expense of social downgrading. Finally, the ineffectiveness of private standards to achieve social upgrading has led to calls for synergistic governance through the cooperation of private, public and social actors, both global and local. Originality/value – The paper illuminates how the GVC approach and its key concepts can contribute to the critical international business and RP firms literature by examining the latest dynamics in GVCs and their impacts on economic and social development in developing countries.

Operational scales, sources of finance, and firms’ performance: evidence from Vietnamese longitudinal data

This study investigates a longitudinal dataset consisting of financial and operational data from 37 listed companies listed on Vietnamese stock market, covering the period 2004-13. By performing three main types of regression analysis - pooled OLS, fixed-effect and random-effect regressions - the investigation finds mixed results on the relationships between operational scales, sources of finance and firms' performance, depending on the choice of analytical model and use of independent/dependent variables. In most situation, fixed-effect models appear to be preferable, providing for reasonably consistent results. Toward the end, the paper offers some further explanation about the obtained insights, which reflect the nature of a business environment of a transition economy and an emerging market.

Identification and doing without it, V: A formal mathematical analysis for a case of mix-up of individuals, and of recovery from failure to attain identification

Identification, when sought, is not necessarily obtained. Operational guidance that is normatively acceptable may be necessary for such cases. We proceed to formalize and illustrate modes of exchanges of individual identity, and provide procedures of recovery strategies in specific prescriptions from an ancient body of law for such situations when, for given types of purposes, individuals of some relevant kind had become intermixed and were undistinguishable. Rules were devised, in a variety of domains, for coping with situations that occur if and when the goal of identification was frustrated. We propose or discuss mathematical representations of such recovery procedures.

Use of a coupled mechanical-acoustic computational model to identify failure mechanisms in paper production

In this paper, a couple mechanical-acoustic system of equations is solved to determine the relationship between emitted sound and damage mechanisims in paper under controlled stress conditions. The simple classical expression describing the frequency of a plucked string to its material properties is used to generate a numberical representation of the microscopic structue of the paper, and the resulting numerical model is then used to simulate the vibration of a range of simple fibre structures when undergoing two distinct types of damange mechanisms: (a)fibre/fibre bond failure, (b) fibre failure. The numercial results are analysed to determine whether there is any detectable systematic difference between the resulting acoustic emissions of the two damage processes. Fourier techniques are then used to compare th computeed results against experimental measurements. Distinct frequency components identifying each type of damage are shown to exist, and in this respect theory and experiments show good correspondece. Hence, it is shown, that althrough the mathematical model represents a grossly-simplified view of the complex structure of the paper, it nevertheless provides a good understanding of the underlying micro-mechanisms characterising its proeperties as a stress-resisting structure. Use of the model and acoompanying software will enable operators to identify approaching failure conditions in the continuous production of paper from emitted sound signals and take preventative action.

Failure mechanisms of ACF joints under isothermal ageing

The possible failure mechanisms of anisotropic conductive film (ACF) joints under isothermal ageing conditions have been identified through experiments. It has been found that ACF joints formed at higher bonding temperatures can prevent increases in the contact resistance for any ageing temperature. The higher the ageing temperature the higher the electrical failure rate is. The formation of conduction gaps between the conductive particles and the pads and damages to the metal coatings of the particle have been identified as the reasons behind the electrical failures during ageing. In order to understand the mechanism for the formation of the conduction gap and damages in metal coatings during the isothermal ageing, computer modelling has been carried out and the results are discussed extensively. The computer analysis shows that stresses concentrate at the edges of the particle–pad interface, where the adhesive matrix meets the particle. This could lead to subsequent damages and reductions in the adhesion strength in that region and it is possible for the conductive particle to be detached from the pad and the adhesive matrix. It is believed that because of this a conduction gap appears. Furthermore, under thermal loading the thermal expansion of the adhesive matrix squeezes the conductive particle and damages the metal coatings. Experimental evidences support this computational finding. It is, therefore, postulated that if an ACF-based electronic component operates in a high temperature aging condition, its electrical and mechanical functionalities will be at risk.

Socialising young literacy learners into a discourse of failure: Dominant discourses in literacy teaching and assessment and their impact on the progression of young literacy learners into employment

This paper argues that contemporary literacy programmes are a mismatch for the expectations of both the government and employers as well as the goals of learners. It submits that the dominant discourses in literacy provision have led to the emergence of a learning culture which not only fails the learners but is also incapable of meeting the aspirations of both the government and employers. To support this argument, the paper reports a small scale research project that analyses the perceptions of learners, teachers and employers who were involved in a work placement scheme for young literacy learners in a college of further education. Data for the study were collected through focus group and face to face interviews and analysed using the framework of discourse analysis provided by Gill (2000) with findings codified and analysed thematically. The study found that teachers were aware that their learners were not adequately prepared for the world of work because of the demands of the dominant discourses of quality and performance measurement which were most obviously manifested in their assessment, teaching methods and the attitudes of learners. It found that employers perceive young learners as inadequate in terms of the workplace expectations. Learners in the study revealed that their workplace culture and expectations were totally different from the culture to which they had been socialised in their studies. The study concludes that unless the dominance of these discourses is ameliorated, young literacy learners will continue to be socialised into a discourse of failure.