Hierarchical information clustering by means of topologically embedded graphs

We introduce a graph-theoretic approach to extract clusters and hierarchies in complex data-sets in an unsupervised and deterministic manner, without the use of any prior information. This is achieved by building topologically embedded networks containing the subset of most significant links and analyzing the network structure. For a planar embedding, this method provides both the intra-cluster hierarchy, which describes the way clusters are composed, and the inter-cluster hierarchy which describes how clusters gather together. We discuss performance, robustness and reliability of this method by first investigating several artificial data-sets, finding that it can outperform significantly other established approaches. Then we show that our method can successfully differentiate meaningful clusters and hierarchies in a variety of real data-sets. In particular, we find that the application to gene expression patterns of lymphoma samples uncovers biologically significant groups of genes which play key-roles in diagnosis, prognosis and treatment of some of the most relevant human lymphoid malignancies.Comment: 33 Pages, 18 Figures, 5 Table

The Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH) can measure the impairment, activity limitations and participation restriction constructs from the International Classification of Functioning, Disability and Health (ICF)

Background The International Classification of Functioning, Disability and Health (ICF) model of the consequences of disease identifies three health outcomes, impairment, activity limitations and participation restrictions. However, few orthopaedic health outcome measures were developed with reference to the ICF. This study examined the ability of a valid and frequently used measure of upper limb function, namely the Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH), to operationalise the ICF. Methods Twenty-four judges used the method of Discriminant Content Validation to allocate the 38 items of the DASH to the theoretical definition of one or more ICF outcome. One-sample t-tests classified each item as measuring, impairment, activity limitations, participation restrictions, or a combination thereof. Results The DASH contains items able to measure each of the three ICF outcomes with discriminant validity. The DASH contains five pure impairment items, 19 pure activity limitations items and three participation restriction items. In addition, seven items measured both activity limitations and participation restrictions. Conclusions The DASH can measure the three health outcomes identified by the ICF. Consequently the DASH could be used to examine the impact of trauma and subsequent interventions on each health outcome in the absence of measurement confound

Inheritance of Telomere Length in a Bird

Telomere dynamics are intensively studied in human ageing research and epidemiology, with many correlations reported between telomere length and age-related diseases, cancer and death. While telomere length is influenced by environmental factors there is also good evidence for a strong heritable component. In human, the mode of telomere length inheritance appears to be paternal and telomere length differs between sexes, with females having longer telomeres than males. Genetic factors, e.g. sex chromosomal inactivation, and non-genetic factors, e.g. antioxidant properties of oestrogen, have been suggested as possible explanations for these sex-specific telomere inheritance and telomere length differences. To test the influence of sex chromosomes on telomere length, we investigated inheritance and sex-specificity of telomere length in a bird species, the kakapo (Strigops habroptilus), in which females are the heterogametic sex (ZW) and males are the homogametic (ZZ) sex. We found that, contrary to findings in humans, telomere length was maternally inherited and also longer in males. These results argue against an effect of sex hormones on telomere length and suggest that factors associated with heterogamy may play a role in telomere inheritance and sex-specific differences in telomere length

Observation of superconductivity at 30 K~46 K in AxFe2Se2 (A = Li, Na, Ba, Sr, Ca, Yb, and Eu)

New iron selenide superconductors by intercalating smaller-sized alkali metals (Li, Na) and alkaline earths using high-temperature routes have been pursued ever since the discovery of superconductivity at about 30 K in KFe2Se2, but all have failed so far. Here we demonstrate that a series of superconductors with enhanced Tc=30~46 K can be obtained by intercalating metals, Li, Na, Ba, Sr, Ca, Yb, and Eu in between FeSe layers by the ammonothermal method at room temperature. Analysis on their powder X-ray diffraction patterns reveals that all the main phases can be indexed based on body-centered tetragonal lattices with a~3.755-3.831 {\AA} while c~15.99-20.54 {\AA}. Resistivities show the corresponding sharp transitions at 45 K and 39 K for NaFe2Se2 and Ba0.8Fe2Se2, respectively, confirming their bulk superconductivity. These findings provide a new starting point for studying the properties of these superconductors and an effective synthetic route for the exploration of new superconductors as well.Comment: 22 pages, 5 figure

Key Concepts for Estimating the Burden of Surgical Conditions and the Unmet Need for Surgical Care

Background: Surgical care is emerging as a crucial issue in global public health. Methodology is needed to assess the impact of surgical care from a public health perspective. Methods: A consensus opinion of a group of surgeons, anesthesiologists, and public health experts was established regarding the methodology for estimating the burden of surgical conditions and the unmet need for surgical care. Results: For purposes of analysis, we define surgical conditions as any disease state requiring the expertise of a surgically trained provider. Abnormalities resulting from a surgical condition or its treatment are termed surgical sequelae. Surgical care is defined as any measure that reduces the rates of physical disability or premature death associated with a surgical condition. To measure the burden of surgical conditions and unmet need for surgical care we propose using cumulative disability-adjusted life-year (DALY) curves generated from age-specific population-based data. This conceptual framework is based on the premise that surgically associated disability and death is determined by the incidence of surgical conditions and the quantity and quality of surgical care. The burden of surgical conditions is defined as the total disability and premature deaths that would occur in a population should there be no surgical care; the unmet need for surgical care is defined as the potentially treatable disability and premature deaths due to surgical conditions. Burden of surgical conditions should be expressed as DALYs and unmet need as potential DALYs avertable. Conclusions: Methodology is described for estimating the burden of surgical conditions and unmet need for surgical care. Using this approach it will be feasible to estimate the global burden of surgical conditions and help clarify where surgery fits among other global health priorities. These methods need to be validated using population-based data

An organizational framework and strategic implementation for system-level change to enhance research-based practice: QUERI Series

<p>Abstract</p> <p>Background</p> <p>The continuing gap between available evidence and current practice in health care reinforces the need for more effective solutions, in particular related to organizational context. Considerable advances have been made within the U.S. Veterans Health Administration (VA) in systematically implementing evidence into practice. These advances have been achieved through a system-level program focused on collaboration and partnerships among policy makers, clinicians, and researchers.</p> <p>The Quality Enhancement Research Initiative (QUERI) was created to generate research-driven initiatives that directly enhance health care quality within the VA and, simultaneously, contribute to the field of implementation science. This paradigm-shifting effort provided a natural laboratory for exploring organizational change processes. This article describes the underlying change framework and implementation strategy used to operationalize QUERI.</p> <p>Strategic approach to organizational change</p> <p>QUERI used an evidence-based organizational framework focused on three contextual elements: 1) cultural norms and values, in this case related to the role of health services researchers in evidence-based quality improvement; 2) capacity, in this case among researchers and key partners to engage in implementation research; 3) and supportive infrastructures to reinforce expectations for change and to sustain new behaviors as part of the norm. As part of a QUERI Series in <it>Implementation Science</it>, this article describes the framework's application in an innovative integration of health services research, policy, and clinical care delivery.</p> <p>Conclusion</p> <p>QUERI's experience and success provide a case study in organizational change. It demonstrates that progress requires a strategic, systems-based effort. QUERI's evidence-based initiative involved a deliberate cultural shift, requiring ongoing commitment in multiple forms and at multiple levels. VA's commitment to QUERI came in the form of visionary leadership, targeted allocation of resources, infrastructure refinements, innovative peer review and study methods, and direct involvement of key stakeholders. Stakeholders included both those providing and managing clinical care, as well as those producing relevant evidence within the health care system. The organizational framework and related implementation interventions used to achieve contextual change resulted in engaged investigators and enhanced uptake of research knowledge. QUERI's approach and progress provide working hypotheses for others pursuing similar system-wide efforts to routinely achieve evidence-based care.</p

Monocyte Scintigraphy in Rheumatoid Arthritis: The Dynamics of Monocyte Migration in Immune-Mediated Inflammatory Disease

Background: Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man. Methods/Principal Findings: We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT). We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99m-Tc-HMPAO). Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4x10(-3) (0.95-5.1x10(-3)) % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion. Conclusions/Significance: The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention

Implementing and evaluating a regional strategy to improve testing rates in VA patients at risk for HIV, utilizing the QUERI process as a guiding framework: QUERI Series

<p>Abstract</p> <p>Background</p> <p>We describe how we used the framework of the U.S. Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) to develop a program to improve rates of diagnostic testing for the Human Immunodeficiency Virus (HIV). This venture was prompted by the observation by the CDC that 25% of HIV-infected patients do not know their diagnosis – a point of substantial importance to the VA, which is the largest provider of HIV care in the United States.</p> <p>Methods</p> <p>Following the QUERI steps (or process), we evaluated: 1) whether undiagnosed HIV infection is a high-risk, high-volume clinical issue within the VA, 2) whether there are evidence-based recommendations for HIV testing, 3) whether there are gaps in the performance of VA HIV testing, and 4) the barriers and facilitators to improving current practice in the VA.</p> <p>Based on our findings, we developed and initiated a QUERI step 4/phase 1 pilot project using the precepts of the Chronic Care Model. Our improvement strategy relies upon electronic clinical reminders to provide <it>decision support</it>; audit/feedback as a <it>clinical information system</it>, and appropriate changes in <it>delivery system design</it>. These activities are complemented by academic detailing and social marketing interventions to achieve <it>provider activation</it>.</p> <p>Results</p> <p>Our preliminary formative evaluation indicates the need to ensure leadership and team buy-in, address facility-specific barriers, refine the reminder, and address factors that contribute to inter-clinic variances in HIV testing rates. Preliminary unadjusted data from the first seven months of our program show 3–5 fold increases in the proportion of at-risk patients who are offered HIV testing at the VA sites (stations) where the pilot project has been undertaken; no change was seen at control stations.</p> <p>Discussion</p> <p>This project demonstrates the early success of the application of the QUERI process to the development of a program to improve HIV testing rates. Preliminary unadjusted results show that the coordinated use of audit/feedback, provider activation, and organizational change can increase HIV testing rates for at-risk patients. We are refining our program prior to extending our work to a small-scale, multi-site evaluation (QUERI step 4/phase 2). We also plan to evaluate the durability/sustainability of the intervention effect, the costs of HIV testing, and the number of newly identified HIV-infected patients. Ultimately, we will evaluate this program in other geographically dispersed stations (QUERI step 4/phases 3 and 4).</p

Are Good Intentions Good Enough?: Informed Consent Without Trained Interpreters

OBJECTIVE: To examine the informed consent process when trained language interpreters are unavailable. BACKGROUND: Ensuring sufficient patient understanding for informed consent is especially challenging for patients with Limited English Proficiency (LEP). While US law requires provision of competent translation for LEP patients, such services are commonly unavailable. DESIGN AND PARTICIPANTS: Qualitative data was collected in 8 prenatal genetics clinics in Texas, including interviews and observations with 16 clinicians, and 30 Latina patients. Using content analysis techniques, we examined whether the basic criteria for informed consent (voluntariness, discussion of alternatives, adequate information, and competence) were evident for each of these patients, contrasting LEP patients with patients not needing an interpreter. We present case examples of difficulties related to each of these criteria, and compare informed consent scores for consultations requiring interpretation and those which did not. RESULTS: We describe multiple communication problems related to the use of untrained interpreters, or reliance on clinicians’ own limited Spanish. These LEP patients appear to be consistently disadvantaged in each of the criteria we examined, and informed consent scores were notably lower for consultations which occurred across a language barrier. CONCLUSIONS: In the absence of adequate Spanish interpretation, it was uncertain whether these LEP patients were provided the quality and content of information needed to assure that they are genuinely informed. We offer some low-cost practice suggestions that might mitigate these problems, and improve the quality of language interpretation, which is essential to assuring informed choice in health care for LEP patients