Tributes to Professor Alan Hornstein

Tributes to Professor Alan Hornstein upon his retirement from the University of Maryland School of Law

Understanding the barriers to accessing symptom-specific cognitive behavior therapy (CBT) for distressing voices: reflecting on and extending the lessons learnt from the CBT for psychosis literature

The experience of hearing voices ('auditory hallucinations') can cause significant distress and disruption to quality of life for people with a psychosis diagnosis. Psychological therapy in the form of Cognitive Behavior Therapy for psychosis is recommended for the treatment of positive symptoms, including distressing voices, but is rarely available to patients in the UK. Cognitive Behavior Therapy for psychosis has recently evolved with the development of symptom-specific therapies that focus upon only one symptom of psychosis at a time. Preliminary findings from randomized controlled trials suggest that these symptom-specific therapies can be more effective for distressing voices than the use of broad CBT protocols, and have the potential to target voices trans-diagnostically. Whilst this literature is evolving, consideration must be given to the potential for a symptom-specific approach to overcome some of the barriers to delivery of evidence-based psychological therapies within clinical services. These barriers are discussed in relation to the UK mental health services, and we offer suggestions for future research to enhance our understanding of these barriers

Hydroxyurea therapy for children with sickle cell disease: Describing how caregivers make this decision

Background: Hydroxyurea (HU) is underutilized in children with sickle cell disease (SCD) because caregivers frequently decline HU when it is offered. This study explores what impacts this decision. Results: Caregivers of children with clinically severe SCD whose children were offered HU previously were interviewed. We used a qualitative analytical approach to analyze their telephone interview transcripts. Caregivers who chose HU (n = 9) reported their children had severe SCD, sought detailed information about HU, and accepted HU as a preventative therapy. In contrast, caregivers who did not choose HU (n = 10) did not perceive their children as having severe SCD and did not question their child's provider about HU. Conclusions: This study identifies specific areas that providers should address to when they discuss HU with families so that they can make informed decisions. Our study also uncovered factors that are important to consider when designing future interventions to improve hydroxyurea acceptance and when developing decision-aid tools to assist caregivers of children with SCD who are considering disease modifying therapies

Synapsins I and II Are Not Required for Insulin Secretion from Mouse Pancreatic beta-cells

Synapsins are a family of phosphoproteins that modulate the release of neurotransmitters from synaptic vesicles. The release of insulin from pancreatic beta-cells has also been suggested to be regulated by synapsins. In this study, we have utilized a knock out mouse model with general disruptions of the synapsin I and II genes [synapsin double knockout (DKO)]. Stimulation with 20 mM glucose increased insulin secretion 9-fold in both wild-type (WT) and synapsin DKO islets, whereas secretion in the presence of 70 mM K+ and 1mM glucose was significantly enhanced in the synapsin DKO mice compared to WT. Exocytosis in single beta-cells was investigated using patch clamp. The exocytotic response, measured by capacitance measurements and elicited by a depolarization protocol designed to visualize exocytosis of vesicles from the readily releasable pool and from the reserve pool, was of the same size in synapsin DKO and WT beta-cells. The increase in membrane capacitance corresponding to readily releasable pool was approximately 50fF in both genotypes. We next investigated the voltage-dependent Ca2+ influx. In both WT and synapsin DKO beta-cells the Ca2+ current peaked at 0 mV and measured peak current (I-p) and net charge (Q) were of similar magnitude. Finally, ultrastructural data showed no variation in total number of granules (N-v) or number of docked granules (N-s) between the beta-cells from synapsin DKO mice and WT control. We conclude that neither synapsin I nor synapsin II are directly involved in the regulation of glucose-stimulated insulin secretion and Ca-2-dependent exocytosis in mouse pancreatic beta-cells. (Endocrinology 153: 2112-2119, 2012

Housing insecurity, housing conditions, and breastfeeding behaviors for medicaid-eligible families in urban settings

BACKGROUND: Research exploring associations between exposure to social determinants of health and breastfeeding is needed to identify breastfeeding barriers. Housing insecurity and household conditions (chaos and crowding) may affect breastfeeding by increasing maternal stress and discomfort and decreasing time available to breastfeed. RESEARCH AIM: We aimed to examine the relationships between housing insecurity, breastfeeding exclusivity intention during the early postnatal period, and breastfeeding exclusivity at 6 months postpartum among a sample "at risk" for suboptimal breastfeeding rates. METHODS: This study is a secondary data analysis of a longitudinal study at two time periods. Data were collected from English- and Spanish-speaking, Medicaid-eligible mother-infant dyads (N = 361) at near-birth and child aged 6 months, in New York City and Pittsburgh. Structural equation modeling was used to examine direct and indirect effects of housing insecurity on breastfeeding exclusivity at child aged 6 months. RESULTS: The path model showed that experiencing more markers of housing insecurity (i.e., foreclosure/eviction threat, history of homelessness, late rent) was predictive of significantly lower breastfeeding exclusivity at 6 months. This was partially mediated through less exclusive breastfeeding intention during the early postnatal period. Greater household crowding was associated with 6-month breastfeeding exclusivity when mediated by intention. Household crowding had differential effects by study site and participant race/ethnicity. CONCLUSION: Refinement of housing insecurity as a multi-dimensional construct can lead to the development of standardized data collection instruments, inform future methodological decisions in research addressing social determinants of health, and can inform the development of responsive individual- and structural-level interventions.The data used in this study were collected as part of the SMART Beginnings Randomized Controlled Trial (NCT02459327 registered at ClinicalTrials.gov)

Prototype Near-Field/GIS Model for Sequestered-CO2 Risk Characterization and Management

Detecting unmapped abandoned wells thus remains a major carbon sequestration (CS) technology gap. Many (>10{sup 5}) abandoned wells are thought to lie in potential sequestration sites. For such wells, risk analysis to date has focused on aggregate long-term future impacts of seepage at rates < or << {approx}1 g m{sup 2} d{sup -1} on storage goals as sequestered plumes encroach upon wells with assumed distributions of seal ineffectiveness (Oldenburg and Unger, 2003; Saripali et al. 2003; Celia, 2005). However, unmapped abandoned wells include an unknown number without any effective seal at all, venting through which may dominate CO{sub 2}-loss scenarios. A model of such a well is Crystal Geyser (CG), a prospective oil well abandoned in the 1930s with no barrier installed after it encountered a natural CO{sub 2} reservoir rather than oil (Baer and Rigby, 1978; Rinehart, 1980). CG demonstrates how an unimpeded conduit to the surface now regularly vents from 10{sup 3} to >10{sup 4} kg of CO{sub 2} gas to the terrestrial surface (Figure 1). Unique field data recently gathered from Crystal Geyser (CG) in Utah (Gouveia et al. 2005) confirm that, although resulting surface CO{sub 2} concentrations resulting from CG-like eruptions would likely be safe in general, they could accumulate to pose lethal hazards under relatively rare meteorological and topographic (MT) conditions. This source of foreseeable risk needs to be managed if carbon sequestration is to be publicly accepted. To address this concern, we used CG field data to estimate the source term for a prototype model that identifies zones at relatively highly elevated risk for sequestered-CO{sub 2} casualties. Such a model could be applied both to design and comply with future regulatory requirements to survey high-risk zones in each proposed sequestration site for improperly sealed wells

137Cs Inter-Plant Concentration Ratios Provide a Predictive Tool for Coral Atolls with Distinct Benefits Over Transfer Factors

Inter-plant concentration ratios (IPCR), [Bq g{sup -1} {sup 137}Cs in coral atoll tree food-crops/Bq g{sup -1} {sup 137}Cs in leaves of native plant species whose roots share a common soil volume], can replace transfer factors (TF) to predict {sup 137}Cs concentration in tree food-crops in a contaminated area with an aged source term. The IPCR strategy has significant benefits relative to TF strategy for such purposes in the atoll ecosystem. IPCR strategy applied to specific assessments takes advantage of the fact tree roots naturally integrate 137Cs over large volumes of soil. Root absorption of {sup 137}Cs replaces large-scale, expensive soil sampling schemes to reduce variability in {sup 137}Cs concentration due to inhomogeneous radionuclide distribution. IPCR [drinking-coconut meat (DCM)/Scaevola (SCA) and Tournefortia (TOU) leaves (native trees growing on all atoll islands)] are log normally distributed (LND) with geometric standard deviation (GSD) = 1.85. TF for DCM from Enewetak, Eneu, Rongelap and Bikini Atolls are LND with GSD's of 3.5, 3.0, 2.7, and 2.1, respectively. TF GSD for Rongelap copra coconut meat is 2.5. IPCR of Pandanus fruit to SCA and TOU leaves are LND with GSD = 1.7 while TF GSD is 2.1. Because IPCR variability is much lower than TF variability, relative sampling error of an IPCR field sample mean is up 6- to 10-fold lower than that of a TF sample mean if sample sizes are small (10 to 20). Other IPCR advantages are that plant leaf samples are collected and processed in far less time with much less effort and cost than soil samples

Accounting Problems Under the Excess Profits Tax

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p

From Dirty Data to Tidy Facts: Clustering Practices in Plant Phenomics and Business Cycle Analysis

This is the final version. Available on open access from Springer via the DOI in this recordThis chapter considers and compares the ways in which two types of data, economic observations and phenotypic data in plant science, are prepared for use as evidence for claims about phenomena such as business cycles and gene-environment interactions. We focus on what we call “cleaning by clustering” procedures, and investigate the principles underpinning this kind of cleaning. These cases illustrate the epistemic significance of preparing data for use as evidence in both the social and natural sciences. At the same time, the comparison points to differences and similarities between data cleaning practices, which are grounded in the characteristics of the objects of interests as well as the conceptual commitments, community standards and research tools used by economics and plant science towards producing and validating claims.European CommissionAlan Turing InstituteAustralian Research Counci

A stable aberrant immunophenotype characterizes nearly all cases of cutaneous T-cell lymphoma in blood and can be used to monitor response to therapy

BACKGROUND: Abnormal variations in the expression level of some commonly expressed T-cell antigens are a feature of many T-cell malignancies. METHODS: We sought to assess the frequency of such abnormal antigen expression by flow cytometry in peripheral blood (PB) samples from patients with mycosis fungoides (MF) and Sézary syndrome (SS). We correlated presence of morphologically identifiable tumor cells on PB smear with the frequency of abnormalities in the level of expression of CD3, CD4, CD7, CD8 and CD26. We also examined the degree of stability of these abnormal findings in tumor cells over the course of disease. The flow cytometric findings in 100 PB samples from 44 patients, including 38 who had multiple sequential PB samples (2–8 samples each), were assessed. RESULTS: Abnormalities were seen in the expression level of one or more T-cell markers in 41 cases (93%) including CD3 in 34% of patients, CD4 in 54%, CD26 in 86% and CD 45 in 40% (10 cases tested). In all but 2 cases, the abnormal T-cell immunophenotype remained similar over the course of treatment and correlated with the relative numbers of tumor cells counted on PB smear. CONCLUSIONS: Using a standard T-cell panel, stable phenotypically aberrant T-cell populations representing the tumor are detected in the vast majority of involved PB samples in MF/SS and can be used to monitor response to therapy