Dementia assessment and management in primary care settings: a survey of current provider practices in the United States.

BACKGROUND:Primary care providers (PCPs) are typically the first to screen and evaluate patients for neurocognitive disorders (NCDs), including mild cognitive impairment and dementia. However, data on PCP attitudes and evaluation and management practices are sparse. Our objective was to quantify perspectives and behaviors of PCPs and neurologists with respect to NCD evaluation and management. METHODS:A cross-sectional survey with 150 PCPs and 50 neurologists in the United States who evaluated more than 10 patients over age 55 per month. The 51-item survey assessed clinical practice characteristics, and confidence, perceived barriers, and typical practices when diagnosing and managing patients with NCDs. RESULTS:PCPs and neurologists reported similar confidence and approaches to general medical care and laboratory testing. Though over half of PCPs performed cognitive screening or referred patients for cognitive testing in over 50% of their patients, only 20% reported high confidence in interpreting results of cognitive tests. PCPs were more likely to order CT scans than MRIs, and only 14% of PCPs reported high confidence interpreting brain imaging findings, compared to 70% of specialists. Only 21% of PCPs were highly confident that they correctly recognized when a patient had an NCD, and only 13% were highly confident in making a specific NCD diagnosis (compared to 72 and 44% for neurologists, both p < 0.001). A quarter of all providers identified lack of familiarity with diagnostic criteria for NCD syndromes as a barrier to clinical practice. CONCLUSIONS:This study demonstrates how PCPs approach diagnosis and management of patients with NCDs, and identified areas for improvement in regards to cognitive testing and neuroimaging. This study also identified all providers' lack of familiarity with published diagnostic criteria for NCD syndromes. These findings may inform the development of new policies and interventions to help providers improve the efficacy of their decision processes and deliver better quality care to patients with NCDs

A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma

<p>Abstract</p> <p>Background</p> <p>Due to the lack of specific tumor antigens, the majority of tested cancer vaccines for renal cell carcinoma (RCC) are based on tumor cell lysate. The identification of the <it>von Hippel-Lindau </it>(<it>VHL</it>) gene mutations in RCC patients provided the potential for developing a novel targeted vaccine for RCC. In this pilot study, we tested the feasibility of vaccinating advanced RCC patients with the corresponding mutant VHL peptides.</p> <p>Methods</p> <p>Six patients with advanced RCC and mutated <it>VHL </it>genes were vaccinated with the relevant VHL peptides. Patients were injected with the peptide mixed with Montanide subcutaneously (SQ) every 4 weeks until disease progression or until the utilization of all available peptide stock.</p> <p>Results</p> <p>Four out of five evaluable patients (80%) generated specific immune responses against the corresponding mutant VHL peptides. The vaccine was well tolerated. No grade III or IV toxicities occurred. The median overall survival (OS) and median progression-free survival (PFS) were 30.5 and 6.5 months, respectively.</p> <p>Conclusions</p> <p>The vaccine demonstrated safety and proved efficacy in generating specific immune response to the mutant VHL peptide. Despite the fact that the preparation of these custom-made vaccines is time consuming, the utilization of VHL as a vaccine target presents a promising approach because of the lack of other specific targets for RCC. Accordingly, developing mutant VHL peptides as vaccines for RCC warrants further investigation in larger trials. Trial registration: 98C0139</p

Extragalactic Globular Clusters and Galaxy Formation

Globular cluster (GC) systems have now been studied in galaxies ranging from dwarfs to giants and spanning the full Hubble sequence of morphological types. Imaging and spectroscopy with the Hubble Space Telescope and large ground-based telescopes have together established that most galaxies have bimodal color distributions that reflect two subpopulations of old GCs: metal-poor and metal-rich. The characteristics of both subpopulations are correlated with those of their parent galaxies. We argue that metal-poor GCs formed in low-mass dark matter halos in the early universe and that their properties reflect biased galaxy assembly. The metal-rich GCs were born in the subsequent dissipational buildup of their parent galaxies and their ages and abundances indicate that most massive early-type galaxies formed the bulk of their stars at early times. Detailed studies of both subpopulations offer some of the strongest constraints on hierarchical galaxy formation that can be obtained in the near-field.Comment: 74 pages, including 14 figures. In press for Annual Reviews of Astronomy and Astrophysic

Dialectics and difference: against Harvey's dialectical post-Marxism

David Harvey`s recent book, Justice, nature and the geography of difference (JNGD), engages with a central philosophical debate that continues to dominate human geography: the tension between the radical Marxist project of recent decades and the apparently disempowering relativism and `play of difference' of postmodern thought. In this book, Harvey continues to argue for a revised `post-Marxist' approach in human geography which remains based on Hegelian-Marxian principles of dialectical thought. This article develops a critique of that stance, drawing on the work of Jacques Derrida, Gilles Deleuze and Felix Guattari. I argue that dialectical thinking, as well as Harvey's version of `post-Marxism', has been undermined by the wide-ranging `post-' critique. I suggest that Harvey has failed to appreciate the full force of this critique and the implications it has for `post-Marxist' ontology and epistemology. I argue that `post-Marxism', along with much contemporary human geography, is constrained by an inflexible ontology which excessively prioritizes space in the theory produced, and which implements inflexible concepts. Instead, using the insights of several `post-' writers, I contend there is a need to develop an ontology of `context' leading to the production of `contextual theories'. Such theories utilize flexible concepts in a multilayered understanding of ontology and epistemology. I compare how an approach which produces a `contextual theory' might lead to more politically empowering theory than `post-Marxism' with reference to one of Harvey's case studies in JNGD

Dietary carbohydrate restriction as the first approach in diabetes management:Critical review and evidence base

AbstractThe inability of current recommendations to control the epidemic of diabetes, the specific failure of the prevailing low-fat diets to improve obesity, cardiovascular risk, or general health and the persistent reports of some serious side effects of commonly prescribed diabetic medications, in combination with the continued success of low-carbohydrate diets in the treatment of diabetes and metabolic syndrome without significant side effects, point to the need for a reappraisal of dietary guidelines. The benefits of carbohydrate restriction in diabetes are immediate and well documented. Concerns about the efficacy and safety are long term and conjectural rather than data driven. Dietary carbohydrate restriction reliably reduces high blood glucose, does not require weight loss (although is still best for weight loss), and leads to the reduction or elimination of medication. It has never shown side effects comparable with those seen in many drugs. Here we present 12 points of evidence supporting the use of low-carbohydrate diets as the first approach to treating type 2 diabetes and as the most effective adjunct to pharmacology in type 1. They represent the best-documented, least controversial results. The insistence on long-term randomized controlled trials as the only kind of data that will be accepted is without precedent in science. The seriousness of diabetes requires that we evaluate all of the evidence that is available. The 12 points are sufficiently compelling that we feel that the burden of proof rests with those who are opposed

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Safety and Usage of C1-Inhibitor in Hereditary Angioedema: Berinert Registry Data

BackgroundThe plasma-derived, highly purified, nanofiltered C1-inhibitor concentrate (Berinert; “pnfC1-INH”) is approved in the United States for treating hereditary angioedema (HAE) attacks and in many European countries for attack treatment and short-term prophylaxis.ObjectiveThe objective of this study was to describe safety and usage patterns of pnfC1-INH.MethodsA multicenter, observational, registry was conducted between 2010 and 2014 at 30 United States and 7 European sites to obtain both prospective (occurring after enrollment) and retrospective (occurring before enrollment) safety and usage data on subjects receiving pnfC1-INH for any reason.ResultsOf 343 enrolled patients, 318 received 1 or more doses of pnfC1-INH for HAE attacks (11,848 infusions) or for prophylaxis (3142 infusions), comprising the safety population. Median dosages per infusion were 10.8 IU/kg (attack treatment) and 16.6 IU/kg (prophylaxis). Approximately 95% of infusions were administered outside of a health care setting. No adverse events (AEs) were reported in retrospective data. Among prospective data (n = 296 subjects; 9148 infusions), 252 AEs were reported in 85 (28.7%) subjects (rate of 0.03 events/infusion); 9 events were considered related to pnfC1-INH. Two thromboembolic events were reported in subjects with thrombotic risk factors. No patient was noted to have undergone viral testing for suspected blood-borne infection during registry participation.ConclusionsThe findings from this large, international patient registry documented widespread implementation of pnfC1-INH self-administration outside of a health care setting consistent with current HAE guidelines. These real-world data revealed pnfC1-INH usage for a variety of reasons in patients with HAE and showed a high level of safety regardless of administration setting or reason for use

Enacting Resilience: A Performative Account of Governing for Urban Resilience

Resilience is an increasingly important urban policy discourse that has been taken up at a rapid pace. Yet there is an apparent gap between the advocacy of social-ecological resilience in scientific literature and its take-up in policy discourse on the one hand, and the demonstrated capacity to govern for resilience in practice on the other. This paper explores this gap by developing a performative account of how social-ecological resilience is dealt with in practice through case study analysis of how protection of biodiversity was negotiated in response to Melbourne’s recent metropolitan planning initiative. It is suggested that a performative account expands the possible opportunities for governing for social-ecological resilience beyond the concept’s use as a metaphor, measurement, cognitive frame or programmatic statement of adaptive management/co-management and has the potential to emerge through what has been called the everyday ‘mangle of practice’ in response to social-ecological feedback inherent to policy processes