Health Starts at Home: Final Evaluation Report

Health Starts at Home was a multi-partner collaboration to improve child and family health for low-income families experiencing housing instability. The Boston Foundation funded four entities, each a partnership of at least one health-care and one housing organization, to design and implement programs to improve service delivery and reduce housing instability for participating families. The evaluators—Health Resources in Action and Urban Institute—tracked changes in these families' housing status, economic well-being, health status and health-care use for the caregivers and enrolled children at baseline, six-month, and 12-month follow-up surveys. The goal of the evaluation was to determine whether improvements in housing stability (achieved through delivery of the four Health Starts at Home program interventions) were associated with improvements in health-related outcomes. Survey data was supplemented by administrative data from the Massachusetts Department of Housing and Community Development (DHCD) on the use of shelters and state rental assistance programs.

Human monoclonal antibodies to Plasmodium falciparum circumsporozoite protein for transient passive protection of malaria travelers to endemic areas

Plasmodium falciparum, is a protozoa that causes over 214 million cases of Malaria worldwide and the World Health Organization reported an estimated 438,000 deaths attributed to malaria in 2015. Current prevention strategies have reduced malaria cases but they are either costly, have poor efficacy or resistance has begun to develop. There is a global need for an effective pre-exposure prophylaxis treatment. The leading Malaria vaccine candidate is RTS,S which contains a monovalent Plasmodium falciparum circumsporozoite protein (CSP). The goal of this vaccine is to induce anti-CSP antibodies that would block sporozoite invasion of hepatocytes and thereby hinder parasite development into a blood-stage infection that causes malaria morbidity and mortality. Antibodies isolated from individuals who have received the RTS,S vaccine have been shown to prevent infection of hepatocytes, suggesting that CSP antibodies could be used prophylactically. However, phase III trial results of the vaccine have shown underwhelming efficacy in children. Growing resistance to transient protection strategies for travelers and low efficacy in vaccine trials suggest there is a need for a new treatment strategy. The generation of CSP specific human monoclonal antibodies (mAbs) would be useful as prevention especially for individuals that are temporarily exposed to Malaria in endemic regions such as travelers or military personnel. Isolation and production of therapeutic mAbs traditionally utilizes a handful of techniques including antibody engineering, phage display or hybridoma generation from transgenic mice. We have sorted antigen-specific memory B-cells from the peripheral blood of children naturally infected with malaria to isolate CSP-specific memory B-cells. These cells were individually sorted and PCR was performed to amplify antibody variable regions of the B-cell’s antibody mRNA. Samples that produced heavy and light chain antibody sequence were cloned and transiently expressed. We plan to characterize these mAbs for binding and neutralization of CSP to identify functional therapeutic mAbs

Forest Change in the Driftless Area of the Midwest: From a Preferred to Undesirable Future

In the midwestern and eastern U.S., oaks (Quercus spp.) have been a dominant component of forests for at least the last 10,000 years, providing vital habitat for numerous wildlife and plant species that have adapted to oak forest conditions. However, the current state of these oak systems, in which there has been a general lack of successful oak regeneration and recruitment and an increase in the relative dominance of mesophytic species, may be nearing critical thresholds. If reached, restoring oak systems through natural regeneration and other methods, such as prescribed fire, may become especially challenging if not impossible. An understanding of spatial variation in oak dominance over time can inform and potentially improve the efficacy of intervention strategies. Using Public Land Survey and Forest Inventory and Analysis (FIA) inventories, we evaluated changes in the composition of timberland across ecoregional subsections in the Driftless Area of the Midwest at three time periods (pre-settlement 1800s, 1990s, and 2000s). We identified an overall decrease in oak dominance, and particularly dominance of the white oak (Quercus alba L., Q. macrocarpa Michx., and Q. bicolor Willd.) species group since the presettlement era, and an increase in other eastern soft hardwoods. Within the last 20 years, both the red oak (Q. rubra L., Q. ellipsoidalis E.J. Hill and Q. velutina Lam.) and white oak species groups decreased in dominance, with an increase in hard maple-basswood (A. saccharum Marsh., A. nigra L., and Tilia americana L.) species group dominance, indicating further mesophication of forests in the region. However, we found a notable decrease in hard maple-basswood relative dominance within the small diameter class across most of the regions within the last 10–20 years, with an increase in dominance of other, non-oak, species. Our findings complement qualitative evidence from interviews with natural resource professionals from the region and offer further information on the potential for forest conversion to ‘‘undesirable’’ forest conditions, as identified as a source of concern by some professionals. There was spatial variation in these trends, however, with some pronounced differences across adjacent state boundaries. The variation in forest change across state boundaries suggests the role of state-level socioeconomic and policy factors in affecting forest conditions, and thus the potential for a targeted and timely approach to promoting preferred pathways of change

Collateral projections innervate the mammillary bodies and retrosplenial cortex: A new category of hippocampal cells

To understand the hippocampus it is necessary to understand the subiculum. Unlike other hippocampal subfields, the subiculum projects to almost all distal hippocampal targets, highlighting its critical importance for external networks. The present studies, in male rats and mice, reveal a new category of dorsal subiculum neurons that innervate both the mammillary bodies and the retrosplenial cortex. These bifurcating neurons comprise almost half of the hippocampal cells that project to retrosplenial cortex. The termination of these numerous collateral projections was visualized within the medial mammillary nucleus and the granular retrosplenial cortex (area 29). These collateral projections included subiculum efferents that cross to the contralateral mammillary bodies. Within the granular retrosplenial cortex, the collateral projections form a particularly dense plexus in deep layer II and layer III. This retrosplenial termination site co-localized with markers for VGluT2 and neurotensin. While efferents from the hippocampal CA fields standardly collateralize, subiculum projections often have only one target site. Consequently, the many collateral projections involving the retrosplenial cortex and the mammillary bodies present a relatively unusual pattern for the subiculum, which presumably relates to how both targets have complementary roles in spatial processing. Furthermore, along with the anterior thalamic nuclei, the mammillary bodies and retrosplenial cortex are key members of a memory circuit, which is usually described as both starting and finishing in the hippocampus. The present findings reveal how the hippocampus simultaneously engages different parts of this circuit, so forcing an important revision of this networ

in silico verification and parallel reaction monitoring prevalidation of potential prostate cancer biomarkers

Purpose: Targeted proteomics of potential biomarkers is often challenging. Hence, we developed an intermediate workflow to streamline potential urinary biomarkers of prostate cancer (PCa). Materials & methods: Using previously discovered potential PCa biomarkers; we selected proteotypic peptides for targeted validation. Preliminary in silico immunohistochemical and single reaction monitoring (SRM) verification was performed. Successful PTPs were then prevalidated using parallel reaction monitoring (PRM) and reconfirmed in 15 publicly available databases. Results: Stringency-based targetable potential biomarkers were shortlisted following in silico screening. PRM reveals top 12 potential biomarkers including the top ranking seven in silico verification-based biomarkers. Database reconfirmation showed differential expression between PCa and benign/normal prostatic urine samples. Conclusion: The pragmatic penultimate screening step, described herein, would immensely improve targeted proteomics validation of ..

The syncytial Drosophila embryo as a mechanically excitable medium

Mitosis in the early syncytial Drosophila embryo is highly correlated in space and time, as manifested in mitotic wavefronts that propagate across the embryo. In this paper we investigate the idea that the embryo can be considered a mechanically-excitable medium, and that mitotic wavefronts can be understood as nonlinear wavefronts that propagate through this medium. We study the wavefronts via both image analysis of confocal microscopy videos and theoretical models. We find that the mitotic waves travel across the embryo at a well-defined speed that decreases with replication cycle. We find two markers of the wavefront in each cycle, corresponding to the onsets of metaphase and anaphase. Each of these onsets is followed by displacements of the nuclei that obey the same wavefront pattern. To understand the mitotic wavefronts theoretically we analyze wavefront propagation in excitable media. We study two classes of models, one with biochemical signaling and one with mechanical signaling. We find that the dependence of wavefront speed on cycle number is most naturally explained by mechanical signaling, and that the entire process suggests a scenario in which biochemical and mechanical signaling are coupled

Performance of PCA3 and TMPRSS2:ERG urinary biomarkers in prediction of biopsy outcome in the Canary Prostate Active Surveillance Study (PASS).

BackgroundFor men on active surveillance for prostate cancer, biomarkers may improve prediction of reclassification to higher grade or volume cancer. This study examined the association of urinary PCA3 and TMPRSS2:ERG (T2:ERG) with biopsy-based reclassification.MethodsUrine was collected at baseline, 6, 12, and 24 months in the multi-institutional Canary Prostate Active Surveillance Study (PASS), and PCA3 and T2:ERG levels were quantitated. Reclassification was an increase in Gleason score or ratio of biopsy cores with cancer to ≥34%. The association of biomarker scores, adjusted for common clinical variables, with short- and long-term reclassification was evaluated. Discriminatory capacity of models with clinical variables alone or with biomarkers was assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA).ResultsSeven hundred and eighty-two men contributed 2069 urine specimens. After adjusting for PSA, prostate size, and ratio of biopsy cores with cancer, PCA3 but not T2:ERG was associated with short-term reclassification at the first surveillance biopsy (OR = 1.3; 95% CI 1.0-1.7, p = 0.02). The addition of PCA3 to a model with clinical variables improved area under the curve from 0.743 to 0.753 and increased net benefit minimally. After adjusting for clinical variables, neither marker nor marker kinetics was associated with time to reclassification in subsequent biopsies.ConclusionsPCA3 but not T2:ERG was associated with cancer reclassification in the first surveillance biopsy but has negligible improvement over clinical variables alone in ROC or DCA analyses. Neither marker was associated with reclassification in subsequent biopsies

Prospective Relation of Circulating Adipokines to Incident Metabolic Syndrome: The Framingham Heart Study

BACKGROUND: Adipokines are elaborated by adipose tissue and are associated with glycemic, lipid, and vascular traits. We hypothesized that in a cross-sectional analysis circulating adipokines are altered among subsets of obesity stratified by presence versus absence of metabolic syndrome (MetS) and prospectively predict the incidence of MetS. METHODS AND RESULTS: Participants in the community-based Framingham Third Generation Cohort who attended examination cycle 1 were included in the study (2002-2005; N=3777, mean age, 40 years; 59% women). Circulating adiponectin, leptin, leptin receptor, fetuin-A, fatty acid-binding protein 4, and retinol binding protein 4 were assayed and related to incident MetS in follow-up (mean 6 years). The adipokines were compared among individuals with excess body weight (body mass index \u3e /=25 kg/m2) and prevalent MetS, excess body weight without MetS (metabolically healthy obese), and normal-weight with MetS (metabolically obese, normal-weight) with normal-weight participants without MetS as a referent. Metabolically healthy obese individuals (n=1467) had higher circulating levels of fetuin-A and fatty acid-binding protein 4 but lower levels of leptin, leptin receptor, and adiponectin (P \u3c 0.001 for all). The adipokine panel was associated with incident MetS (263 new-onset cases; P=0.002). Higher circulating concentrations of retinol-binding protein 4 and fetuin-A were associated with incidence of MetS (odds ratio per 1-SD increment log marker, 1.21; 95% CI, 1.03-1.41 [P=0.02] and 1.17; 95% CI, 1.01-1.34 [P=0.03], respectively). CONCLUSIONS: In our community-based sample of young to middle-aged adults, metabolically healthy obese individuals demonstrated an adverse adipokine profile. Higher circulating levels of retinol-binding protein 4 and fetuin-A marked future cardiometabolic risk

RSAT™ process development for post-combustion CO2 capture: Scale-up from laboratory and pilot test data to commercial process design

AbstractIt is believed that a RSAT™ (Regenerable Solvent Absorption Technology) process is the most viable nearterm technology for post-combustion CO2 capture from power plant flue gas. The Babcock & Wilcox Power Generation Group, Inc. (B&W) has deployed a suite of research tools to evaluate and develop the CO2 scrubbing technology, including laboratory, pilot-scale, and simulation modeling capabilities. Since the construction and operation of test facilities require significant resources, it is essential to effectively utilize these research tools by choosing a scale-up approach which provides robust design data for a commercial process while minimizing the amount of experimentation required.The scale-up protocol used for RSAT CO2 scrubbing processes was rigorously developed using rate-based modeling concurrent with acquiring fundamental laboratory and pilot plant data for process validation. These development activities were not conducted in series but rather overlapped to yield an optimized commercial CO2 scrubbing process in a reasonable time frame with a high degree of design confidence [1,2].This paper presents the scale-up protocol used in evaluating the RSAT process which encompasses both laboratory and pilot-scale testing as well as rate-based modeling to achieve a commercial-scale RSAT process design. This document demonstrates the qualification of test data from a packed tower scale-up point of view. Solvent screening research activities recently conducted within B&W successfully demonstrate the scale-up protocol used for RSAT process development. The time and cost of process development can be significantly reduced through rigorous rate-based modeling in conjunction with laboratory experiments and pilot plant validation