Incorporating translational research with clinical research to increase effectiveness in healthcare for better health

BACKGROUND: The transfer of new scientific discoveries into healthcare interventions requires that basic and clinical researchers work together with health care providers to generate team science. These innovative models require translational teams, and need to extend beyond the academic environment. The future of translational science requires partnerships with the healthcare community as well as the broader, general community. This new integrated model of effective translational teams holds promise for addressing thorny and persistent health disparities, is consistent with the nation’s strategic priority of eliminating health disparities, and bodes well for increasing healthcare effectiveness aimed at better health for all. DISCUSSION: As part of the 13th Research Centers in Minority Institutions (RCMI) International Symposium on Health Disparities, several senior academic leaders joined efforts to hold a workshop to discuss a model that considers the incorporation of two translational research strategies in research career development programs: Comparative effectiveness research (CER) and community-based participatory research (CBPR) for increasing healthcare effectiveness and eliminating healthcare disparities. Discussion included what issues may be most germane to the concept of a unified model for research workforce development through formal training and career development leading to increased effectiveness in healthcare for better health. SUMMARY: We believe that there is a gap in knowledge and skills in formal research career development programs that will enable physicians, other clinicians, and basic scientists to actively participate in these two translational research strategies. The purpose of this paper is to share the outcomes of these discussions, and encourage further discussion and possible innovation in the formulation of a new model for translational research workforce development

Fit for purpose? Pattern cutting and seams in wearables development

This paper describes how a group of practitioners and researchers are working across disciplines at Nottingham Trent University in the area of Technical Textiles. It introduces strands of ongoing enquiry centred around the development and application of stretch sensors on the body, focusing on how textile and fashion knowledge are being reflexively revealed in the collaborative development of seamful wearable concepts, and on the tensions between design philosophies as revealed by definitions of purpose. We discuss the current research direction of the Aeolia project, which seeks to exploit the literal gaps found in pattern cutting for fitted stretch garments towards experiential forms and potential interactions. Normative goals of fitness for purpose and seamlessness are interrogated and the potential for more integrated design processes, which may at first appear ‘upside down’, is discussed

HLA-Associated viral mutations are common in human immunodeficiency virus type 1 elite controllers

Elite controllers (EC) of human immunodeficiency virus type 1 (HTV-1) maintain viremia below the limit of detection without antiretroviral treatment. Virus-specific cytotoxic CD8+ T lymphocytes are believed to play a crucial role in viral containment, but the degree of immune imprinting and compensatory mutations in EC is unclear. We obtained plasma gag, pol, and nef sequences from HLA-diverse subjects and found that 30 to 40% of the predefined HLA-associated polymorphic sites show evidence of immune selection pressure in EC., compared to approximately 50% of the sites in chronic progressors. These data indicate ongoing viral replication and escape from cytotoxic T lymphocytes are present even in strictly controlled HTV-1 infection

An evaluation of persistent meteorological drought using a homogeneous Island of Ireland precipitation network

This paper investigates the spatial and temporal properties of persistent meteorological droughts using the homogeneous Island of Ireland Precipitation (IIP) network. Relative to a 1961-1990 baseline period it is shown that the longest observed run of below average precipitation since the 1850s lasted up to 5 years (10 half-year seasons) at sites in southeast and east Ireland, or 3 years across the network as a whole. Dry- and wet-spell length distributions were represented by a first-order Markov model which yields realistic runs of below average rainfall for individual sites and IIP series. This model shows that there is relatively high likelihood (p=0.125) of a 5 year dry-spell at Dublin, and that near unbroken dry runs of 10 years or more are conceivable. We suggest that the IIP network and attendant rainfall deficit modelling provide credible data for stress testing water supply and drought plans under extreme conditions

Thirty Years After Michael E. Porter: What Do We Know About Business Exit?

Although a business exit is an important corporate change initiative, the buyer’s side seems to be more appealing to management researchers than the seller’s because acquisitions imply growth, i.e., success. Yet from an optimistic viewpoint, business exit can effectively create value for the selling company. In this paper we attempt to bring the relevance of the seller’s side back into our consciousness by asking: What do we know about business exit? We start our exploration with Porter (1976), focusing on literature that investigates the antecedents of, barriers to, and outcomes of business exit. We also include studies from related fields such as finance and economics.1 Through this research we determine three clusters of findings: factors promoting business exit, exit barriers, and exit outcomes. Overall, it is the intention of this paper to highlight the importance of business exit for research and practice. Knowing what we know about business exits and their high financial value we should bear in mind that exit need not mean failure but a new beginning for a corporation

Revisiting consistency conditions for quantum states of systems on closed timelike curves: an epistemic perspective

There has been considerable recent interest in the consequences of closed timelike curves (CTCs) for the dynamics of quantum mechanical systems. A vast majority of research into this area makes use of the dynamical equations developed by Deutsch, which were developed from a consistency condition that assumes that mixed quantum states uniquely describe the physical state of a system. We criticise this choice of consistency condition from an epistemic perspective, i.e., a perspective in which the quantum state represents a state of knowledge about a system. We demonstrate that directly applying Deutsch's condition when mixed states are treated as representing an observer's knowledge of a system can conceal time travel paradoxes from the observer, rather than resolving them. To shed further light on the appropriate dynamics for quantum systems traversing CTCs, we make use of a toy epistemic theory with a strictly classical ontology due to Spekkens and show that, in contrast to the results of Deutsch, many of the traditional paradoxical effects of time travel are present.Comment: 10 pages, 6 figures, comments welcome; v2 added references and clarified some points; v3 published versio

Processing of ultrafine-size particulate metal matrix composites by advanced shear technology

Copyright @ 2009 ASM International. This paper was published in Metallurgical & Materials Transactions A 40A(3) and is made available as an electronic reprint with the permission of ASM International. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or modification of the content of this paper are prohibited.Lack of efficient mixing technology to achieve a uniform distribution of fine-size reinforcement within the matrix and the high cost of producing components have hindered the widespread adaptation of particulate metal matrix composites (PMMCs) for engineering applications. A new rheo-processing method, the melt-conditioning high-pressure die-cast (MC-HPDC) process, has been developed for manufacturing near-net-shape components of high integrity. The MC-HPDC process adapts the well-established high shear dispersive mixing action of a twin-screw mechanism to the task of overcoming the cohesive force of the agglomerates under a high shear rate and high intensity of turbulence. This is followed by direct shaping of the slurry into near-net-shape components using an existing cold-chamber die-casting process. The results indicate that the MC-HPDC samples have a uniform distribution of ultrafine-sized SiC particles throughout the entire sample in the as-cast condition. Compared to those produced by conventional high-pressure die casting (HPDC), MC-HPDC samples have a much improved tensile strength and ductility.EP-SR

Checkpoints are blind to replication restart and recombination intermediates that result in gross chromosomal rearrangements

Replication fork inactivation can be overcome by homologous recombination, but this can cause gross chromosomal rearrangements that subsequently missegregate at mitosis, driving further chromosome instability. It is unclear when the chromosome rearrangements are generated and whether individual replication problems or the resulting recombination intermediates delay the cell cycle. Here we have investigated checkpoint activation during HR-dependent replication restart using a site-specific replication fork-arrest system. Analysis during a single cell cycle shows that HR-dependent replication intermediates arise in S phase, shortly after replication arrest, and are resolved into acentric and dicentric chromosomes in G2. Despite this, cells progress into mitosis without delay. Neither the DNA damage nor the intra-S phase checkpoints are activated in the first cell cycle, demonstrating that these checkpoints are blind to replication and recombination intermediates as well as to rearranged chromosomes. The dicentrics form anaphase bridges that subsequently break, inducing checkpoint activation in the second cell cycle

The “dirty dozen” of freshwater science: Detecting then reconciling hydrological data biases and errors

Sound water policy and management rests on sound hydrometeorological and ecological data. Conversely, unrepresentative, poorly collected or erroneously archived data introduces uncertainty regarding the magnitude, rate and direction of environmental change, in addition to undermining confidence in decision-making processes. Unfortunately, data biases and errors can enter the information flow at various stages, starting with site selection, instrumentation, sampling/ measurement procedures, post-processing and ending with archiving systems. Techniques such as visual inspection of raw data, graphical representation and comparison between sites, outlier and trend detection, and referral to metadata can all help uncover spurious data. Tell-tale signs of ambiguous and/or anomalous data are highlighted using 12 carefully chosen cases drawn mainly from hydrology (‘the dirty dozen’). These include evidence of changes in site or local conditions (due to land management, river regulation or urbanisation); modifications to instrumentation or inconsistent observer behaviour; mismatched or misrepresentative sampling in space and time; treatment of missing values, post-processing and data storage errors. As well as raising awareness of pitfalls, recommendations are provided for uncovering lapses in data quality after the information has been gathered. It is noted that error detection and attribution are more problematic for very large data sets, where observation networks are automated, or when various information sources have been combined. In these cases, more holistic indicators of data integrity are needed that reflect the overall information life-cycle and application(s) of the hydrological data