Expansion of Electronic Health Record-Based Screening, Prevention, and Management of Diabetes in New York City

To address the increasing burden of diabetes in New York City, we designed 2 electronic health records (EHRs)-facilitated diabetes management systems to be implemented in 6 primary care practices on the West Side of Manhattan, a standard system and an enhanced system. The standard system includes screening for diabetes. The enhanced system includes screening and ensures close patient follow-up; it applies principles of the chronic care model, including community–clinic linkages, to the management of patients newly diagnosed with diabetes and prediabetes through screening. We will stagger implementation of the enhanced system across the 6 clinics allowing comparison, through a quasi-experimental design (pre–post difference with a control group), of patients treated in the enhanced system with similar patients treated in the standard system. The findings could inform health system practices at multiple levels and influence the integration of community resources into routine diabetes care

Olfactory cues are sufficient to elicit social approach behaviors but not social transmission of food preference in C57BL/6J mice

Mouse models for the study of autistic-like behaviors are increasingly needed to test hypotheses about the causes of autism, and to evaluate potential treatments. Both the automated 3-chambered social approach test and social transmission of food preference have been proposed as mouse behavioral assays with face validity to diagnostic symptoms of autism, including aberrant reciprocal social interactions and impaired communication. Both assays measure aspects of normal social behavior in the mouse. However, little is known regarding the salient cues present in each assay that elicit normal social approach and communication. To deconstruct the critical components, we focused on delivering discrete social and non-social olfactory and visual cues within the context of each assay. Results indicate that social olfactory cues were sufficient to elicit normal sociability in the 3-chambered social approach test On social transmission of food preference, isolated social olfactory cues were sufficient to induce social investigation, but not sufficient to induce food preference. These findings indicate that olfactory cues are important in mouse social interaction, but that additional sensory cues are necessary in certain situations. The present evidence that both the 3-chambered social approach assay and the social transmission of food preference assay require socially relevant cues to elicit normal behavior supports the use of these two assays to investigate autism-related behavioral phenotypes in mice

Persist in place or shift in space? Evaluating the adaptive capacity of species to climate change

Assessing the vulnerability of species to climate change serves as the basis for climate-adaptation planning and climate-smart conservation, and typically involves an evaluation of exposure, sensitivity, and adaptive capacity (AC). AC is a species’ ability to cope with or adjust to changing climatic conditions, and is the least understood and most inconsistently applied of these three factors. We propose an attribute-based framework for evaluating the AC of species, identifying two general classes of adaptive responses: “persist in place” and “shift in space”. Persist-in-place attributes enable species to survive in situ, whereas the shift-in-space response emphasizes attributes that facilitate tracking of suitable bioclimatic conditions. We provide guidance for assessing AC attributes and demonstrate the framework's application for species with disparate life histories. Results illustrate the broad utility of this generalized framework for informing adaptation planning and guiding species conservation in a rapidly changing climate.publishedVersio

The Kinetics of Specific Immune Responses in Rhesus Monkeys Inoculated with Live Recombinant BCG Expressing SIV Gag, Pol, Env, and Nef Proteins

AbstractDevelopment of an effective preventive or therapeutic vaccine against HIV-1 is an important goal in the fight against AIDS. Effective virus clearance and inhibition of spread to target organs depends principally on the cellular immune response. Therefore, a vaccine against HIV-1 should elicit virus-specific cytotoxic lymphocyte (CTL) responses to eliminate the virus during the cell-associated stages of its life cycle. The vaccine should also be capable of inducing immunity at the mucosal surfaces, the primary route of transmission. Recombinant Bacille Calmette–Guérin (BCG) expressing viral proteins offers an excellent candidate vaccine in view of its safety and ability to persist intracellularly, resulting in the induction of long-lasting immunity and stimulation of the cellular immune response. BCG can be administered orally to induce HIV-specific immunity at the mucosal surfaces. The immunogenicity of four recombinant BCG constructs expressing simian immunodeficiency virus (SIV) Gag, Pol, Env, and Nef proteins was tested in rhesus macaques. A single simultaneous inoculation of all four recombinants elicited SIV-specific IgA and IgG antibody, and cellular immune responses, including CTL and helper T cell proliferation. Our results demonstrate that BCG recombinant vectors can induce concomitant humoral and cellular immune responses to the major proteins of SIV

Impaired sociability and cognitive function in Nrcam-null mice

NRCAM (Neuronal Cell Adhesion Molecule) has an important role in axonal guidance and the organization of neural circuitry during brain development. Association analyses in human populations have identified NRCAM as a candidate gene for autism susceptibility. In the present study, we evaluated Nrcam-null mice for sociability, social novelty preference, and reversal learning as a model for the social deficits, repetitive behavior, and cognitive rigidity characteristic of autism. Prepulse inhibition of acoustic startle responses was also measured, to reflect sensorimotor-gating deficits in autism spectrum disorders. Assays for anxiety-like behavior in an elevated plus maze and open field, motor coordination, and olfactory ability in a buried food test were conducted to provide control measures for the interpretation of results. Overall, the loss of Nrcam led to behavioral alterations in sociability, acquisition of a spatial task, and reversal learning, dependent on sex. In comparison to male wild type mice, male Nrcam-null mutants had significantly decreased sociability in a three-chambered choice task. Low sociability in the male null mutants was not associated with changes in anxiety-like behavior, activity, or motor coordination. Male, but not female, Nrcam-null mice had small decreases in prepulse inhibition. Nrcam deficiency in female mice led to impaired acquisition of spatial learning in the Morris water maze task. Reversal learning deficits were observed in both male and female Nrcam-null mice. These results provide evidence that NRCAM mediates domains of function relevant to symptoms observed in autism

The necessity and possibility of powerful ‘regional’ knowledge: curriculum change and renewal

© 2016 Taylor & Francis. The paper argues that powerful regional knowledge is necessary and possible and that there are historical precedents supporting these claims. Regional knowledge is being used in a double sense: the first Bernsteinian, the second in relation to knowledge generated outside the academy. Both are important if the debate is not to be confined solely to the global north and if the curriculum is to be responsive to geo-political realities. In order to think critically about access to higher education, we need to consider the sorts of knowledge, engagement, and opportunities that are open to newer actors. This includes recognising the contextual nature of professional practice and also that social movements beyond the academy can and do challenge academic knowledge. The paper concludes that many of issues addressed are not capable of theoretical resolution alone and that we need more empirical work to inform curriculum change and renewal

Transplantation in Remission Improves the Disease-Free Survival of Patients with Advanced Myelodysplastic Syndromes Treated with Myeloablative T Cell-Depleted Stem Cell Transplants from HLA-Identical Siblings

AbstractFrom 1985 to 2004, 49 patients with advanced myelodysplastic syndromes (MDS) (≥5% blasts) or acute myeloid leukemia (AML) transformed from MDS underwent T cell depleted bone marrow or peripheral blood hematopoietic stem cell transplantation (HSCT) from HLA-identical siblings following conditioning with a myeloablative regimen that included total body irradiation (44 patients) or busulfan (5 patients). Thirty-six patients received chemotherapy (3 low dose and 33 induction doses) before conditioning, and 13 patients did not receive any chemotherapy. Prior to transplantation, 22 of the 36 treated patients were in hematologic remission; 4 were in a second refractory cytopenia phase (26 responders); 8 had failed to achieve remission; and 2 of the responders had progression or relapse of their MDS (10 failures). No post-transplantation pharmacologic prophylaxis for graft-versus-host disease (GVHD) was given. The median age was 48 yrs (range 13-61). Forty-five of the 49 patients engrafted; 2 had primary graft failure; and 2 died before engraftment. Only 3 patients developed acute GVHD (aGVHD) (grades I and III) and 1 chronic GVHD (cGVHD). At 3 yrs post-transplantation, the overall survival (OS) was 54% in the responders; 31% in the untreated group; and 0% in the failure group (P=.0004). The disease free survival (DFS) was 50%, 15% and 0% in each group respectively (P=.0008). In multivariate analysis, disease status before cytoreduction remained highly correlated with DFS (P<.001). The cumulative incidence (CI) of relapse at 2-yrs post-transplantation for the responders was 23%; for the untreated group was 38%; and for the failures was 50%. The CI of non-relapse mortality at 2-yrs post-transplantation, for the responders was 23%; for the untreated group was 38%; and for the failures was 40%. All survivors achieved a Karnofsky Performance Status (KPS) of ≥90. These results indicate that patients with advanced MDS who achieve and remain in remission or a second refractory cytopenia phase with chemotherapy before conditioning can achieve successful long-term remissions following a myeloablative T cell depleted allogeneic HSCT

Influence of Beta-Blocker Continuation or Withdrawal on Outcomes in Patients Hospitalized With Heart Failure Findings From the OPTIMIZE-HF Program

ObjectivesThis study ascertains the relationship between continuation or withdrawal of beta-blocker therapy and clinical outcomes in patients hospitalized with systolic heart failure (HF).BackgroundWhether beta-blocker therapy should be continued or withdrawn during hospitalization for decompensated HF has not been well studied in a broad cohort of patients.MethodsThe OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) program enrolled 5,791 patients admitted with HF in a registry with pre-specified 60- to 90-day follow-up at 91 academic and community hospitals throughout the U.S. Outcomes data were prospectively collected and analyzed according to whether beta-blocker therapy was continued, withdrawn, or not started.ResultsAmong 2,373 patients eligible for beta-blockers at discharge, there were 1,350 (56.9%) who were receiving beta-blockers before admission and continued on therapy, 632 (26.6%) newly started, 79 (3.3%) in which therapy was withdrawn, and 303 (12.8%) eligible but not treated. Continuation of beta-blockers was associated with a significantly lower risk and propensity adjusted post-discharge death (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.37 to 0.99, p = 0.044) and death/rehospitalization (odds ratio: 0.69; 95% CI: 0.52 to 0.92, p = 0.012) compared with no beta-blocker. In contrast, withdrawal of beta-blocker was associated with a substantially higher adjusted risk for mortality compared with those continued on beta-blockers (HR: 2.3; 95% CI: 1.2 to 4.6, p = 0.013), but with similar risk as HF patients eligible but not treated with beta-blockers.ConclusionsThe continuation of beta-blocker therapy in patients hospitalized with decompensated HF is associated with lower post-discharge mortality risk and improved treatment rates. In contrast, withdrawal of beta-blocker therapy is associated with worse risk and propensity-adjusted mortality. (Organized Program To Initiate Lifesaving Treatment In Hospitalized Patients With Heart Failure [OPTIMIZE-HF]; NCT00344513