Aboriginal Children and Their Caregivers Living with Low Income: Outcomes from a Two-Generation Preschool Program

The development of preschool children of Aboriginal heritage is jeopardized by the inter-generational transmission of risk that has created, and continues to create, social disadvantage. Early intervention programs are intended to mitigate the impact of social disadvantage. Yet, evidence of the effectiveness of these programs for children of Aboriginal heritage is limited. The purpose of this study was to examine the effects of a two-generation, multi-cultural preschool program on 45 children of Aboriginal heritage and their caregivers. We used a single-group, pretest (program intake)/posttest (program exit) design with follow-up when the children were 7 years old. We used an observational measure of child receptive language (Peabody Picture Vocabulary Test–III) and caregiver-reported measures of child development (Nipissing District Developmental Screen), risk for child maltreatment (Adult-Adolescent Parenting Inventory; AAPI), parenting stress (Parenting Stress Index; PSI), self-esteem (Rosenberg Self-Esteem scale; RSE), and life skills (Community Life Skills scale; CLS). Using paired t-tests we found statistically significant increases in child receptive language scores between intake and exit, and repeated-measures ANOVA showed that these improvements were maintained up to age 7 years. For caregivers, Pearson’s correlations demonstrated that risk for child maltreatment, parenting stress, self-esteem, and life skills were stable over time. Results of this study suggest that children of Aboriginal heritage can benefit from participation in a two-generation, multi-cultural preschool program. Their caregivers may have received greater benefit if issues of intergenerational transmission of the negative influences of residential schools were addressed as part of programming

Temporal and spatial variations in the parasitoid complex of the horse chestnut leafminer during its invasion of Europe

The enemy release hypothesis posits that the initial success of invasive species depends on the scarcity and poor adaptation of native natural enemies such as predators and parasitoids. As for parasitoids, invading hosts are first attacked at low rates by a species-poor complex of mainly generalist species. Over the years, however, parasitoid richness may increase either because the invading host continuously encounters new parasitoid species during its spread (geographic spread-hypothesis) or because local parasitoids need different periods of time to adapt to the novel host (adjustment-hypothesis). Both scenarios should result in a continuous increase of parasitoid richness over time. In this study, we reconstructed the development of the hymenopteran parasitoid complex of the invasive leafminer Cameraria ohridella (Lepidoptera, Gracillariidae). Our results show that the overall parasitism rate increases as a function of host residence time as well as geographic and climatic factors, altogether reflecting the historic spread of C. ohridella. The same variables also explain the individual parasitism rates of several species in the parasitoid complex, but fail to explain the abundance of others. Evidence supporting the “geographic spread-hypothesis” was found in the parasitism pattern of Cirrospilus talitzkii (Hymenoptera, Eulophidae), while that of Pediobius saulius, another eulophid, indicated an increase of parasitism rates by behavioral, phenological or biological adjustments. Compared to fully integrated host-parasitoid associations, however, parasitism rates of C. ohridella are still very low. In addition, the parasitoid complex lacks specialists, provided that the species determined are valid and not complexes of cryptic (and presumably more specialized) species. Probably, the adjustment of specialist parasitoids requires more than a few decades, particularly to invaders which establish in ecological niches free of native hosts, thus eliminating any possibility of recruitment of pre-adapted parasitoids

Logical Development of the Cell Ontology

<p>Abstract</p> <p>Background</p> <p>The Cell Ontology (CL) is an ontology for the representation of <it>in vivo </it>cell types. As biological ontologies such as the CL grow in complexity, they become increasingly difficult to use and maintain. By making the information in the ontology computable, we can use automated reasoners to detect errors and assist with classification. Here we report on the generation of computable definitions for the hematopoietic cell types in the CL.</p> <p>Results</p> <p>Computable definitions for over 340 CL classes have been created using a genus-differentia approach. These define cell types according to multiple axes of classification such as the protein complexes found on the surface of a cell type, the biological processes participated in by a cell type, or the phenotypic characteristics associated with a cell type. We employed automated reasoners to verify the ontology and to reveal mistakes in manual curation. The implementation of this process exposed areas in the ontology where new cell type classes were needed to accommodate species-specific expression of cellular markers. Our use of reasoners also inferred new relationships within the CL, and between the CL and the contributing ontologies. This restructured ontology can be used to identify immune cells by flow cytometry, supports sophisticated biological queries involving cells, and helps generate new hypotheses about cell function based on similarities to other cell types.</p> <p>Conclusion</p> <p>Use of computable definitions enhances the development of the CL and supports the interoperability of OBO ontologies.</p

Enhancing Mental and Physical Health of Women through Engagement and Retention (EMPOWER): a protocol for a program of research

Abstract Background The Enhancing Mental and Physical health of Women through Engagement and Retention or EMPOWER program represents a partnership with the US Department of Veterans Health Administration (VA) Health Service Research and Development investigators and the VA Office of Women’s Health, National Center for Disease Prevention and Health Promotion, Primary Care-Mental Health Integration Program Office, Women’s Mental Health Services, and the Office of Patient Centered Care and Cultural Transformation. EMPOWER includes three projects designed to improve women Veterans’ engagement and retention in evidence-based care for high-priority health conditions, i.e., prediabetes, cardiovascular, and mental health. Methods/Design The three proposed projects will be conducted in VA primary care clinics that serve women Veterans including general primary care and women’s health clinics. The first project is a 1-year quality improvement project targeting diabetes prevention. Two multi-site research implementation studies will focus on cardiovascular risk prevention and collaborative care to address women Veterans’ mental health treatment needs respectively. All projects will use the evidence-based Replicating Effective Programs (REP) implementation strategy, enhanced with multi-stakeholder engagement and complexity theory. Mixed methods implementation evaluations will focus on investigating primary implementation outcomes of adoption, acceptability, feasibility, and reach. Program-wide organizational-, provider-, and patient-level measures and tools will be utilized to enhance synergy, productivity, and impact. Both implementation research studies will use a non-randomized stepped wedge design. Discussion EMPOWER represents a coherent program of women’s health implementation research and quality improvement that utilizes cross-project implementation strategies and evaluation methodology. The EMPOWER Quality Enhancement Research Initiative (QUERI) will constitute a major milestone for realizing women Veterans’ engagement and empowerment in the VA system. EMPOWER QUERI will be conducted in close partnership with key VA operations partners, such as the VA Office of Women’s Health, to disseminate and spread the programs nationally. Trial registration The two implementation research studies described in this protocol have been registered as required: Facilitating Cardiovascular Risk Screening and Risk Reduction in Women Veterans: Trial registration NCT02991534 , registered 9 December 2016. Implementation of Tailored Collaborative Care for Women Veterans: Trial registration NCT02950961 , registered 21 October 2016

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Cucurbitacin I Inhibits Cell Motility by Indirectly Interfering with Actin Dynamics

Cucurbitacins are plant natural products that inhibit activation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway by an unknown mechanism. They are also known to cause changes in the organization of the actin cytoskeleton. actin depolymerization experiments, cucurbitacin I had no effect on the rate of actin filament disassembly at the nanomolar concentrations that inhibit cell migration. At elevated concentrations, the depolymerization rate was also unaffected, although there was a delay in the initiation of depolymerization. Therefore, cucurbitacin I targets some factor involved in cellular actin dynamics other than actin itself. Two candidate proteins that play roles in actin depolymerization are the actin-severing proteins cofilin and gelsolin. Cucurbitacin I possesses electrophilic reactivity that may lead to chemical modification of its target protein, as suggested by structure-activity relationship data. However, mass spectrometry revealed no evidence for modification of purified cofilin or gelsolin by cucurbitacin I.Cucurbitacin I results in accumulation of actin filaments in cells by a unique indirect mechanism. Furthermore, the proximal target of cucurbitacin I relevant to cell migration is unlikely to be the same one involved in activation of the JAK2/STAT3 pathway

Endoscopic diagnosis of acute intestinal GVHD following allogeneic hematopoietic SCT: a retrospective analysis in 175 patients

Diagnosis of acute intestinal GVHD (aGVHD) following allogeneic hematopoietic cell transplantation is based on clinical symptoms and histological lesions. This retrospective analysis aimed to validate the ‘Freiburg Criteria' for the endoscopic grading of intestinal aGVHD. Grade 1: no clear-cut criteria; grade 2: spotted erythema; grade 3: aphthous lesions; and grade 4: confluent defects, ulcers, denudation of the mucosa. Having excluded patients with infectious diarrhea, we evaluated 175 consecutive patients between January 2001 and June 2009. Setting a cutoff between grade 1 (no change in therapy) and grade 2 (intensification of immunosuppression), macroscopy had a sensitivity of 89.2% (95% confidence interval (CI): 80.4–94.9%), a specificity of 79.4% (95% CI: 69.6–87.1%), a positive-predictive value of 79.6% (95% CI: 70.0–87.2%) and a negative-predictive value of 89.0% (95% CI: 80.2–94.9%). In all, 20% of patients with aGVHD in the lower gastrointestinal tract (GIT) had lesions only in the terminal ileum. In all patients with aGVHD ⩾2 of the upper GIT, typical lesions were also found in the lower GIT. Ileo-colonoscopy showed the highest diagnostic yield for aGVHD. In conclusion, the ‘Freiburg Criteria' for macroscopic diagnosis of intestinal aGVHD provide high accuracy for identifying aGVHD ⩾2

Actin binding domains direct actin-binding proteins to different cytoskeletal locations

<p>Abstract</p> <p>Background</p> <p>Filamin (FLN) and non-muscle α-actinin are members of a family of F-actin cross-linking proteins that utilize Calponin Homology domains (CH-domain) for actin binding. Although these two proteins have been extensively characterized, little is known about what regulates their binding to F-actin filaments in the cell.</p> <p>Results</p> <p>We have constructed fusion proteins consisting of green fluorescent protein (GFP) with either the entire cross-linking protein or its actin-binding domain (ABD) and examined the localization of these fluorescent proteins in living cells under a variety of conditions. The full-length fusion proteins, but not the ABD's complemented the defects of cells lacking both endogenous proteins indicating that they are functional. The localization patterns of filamin (GFP-FLN) and α-actinin (GFP-αA) were overlapping but distinct. GFP-FLN localized to the peripheral cell cortex as well as to new pseudopods of unpolarized cells, but was observed to localize to the rear of polarized cells during cAMP and folate chemotaxis. GFP-αA was enriched in new pseudopods and at the front of polarized cells, but in all cases was absent from the peripheral cortex. Although both proteins appear to be involved in macropinocytosis, the association time of the GFP-probes with the internalized macropinosome differed. Surprisingly, the localization of the GFP-actin-binding domain fusion proteins precisely reflected that of their respective full length constructs, indicating that the localization of the protein was determined by the actin-binding domain alone. When expressed in a cell line lacking both filamin and α-actinin, the probes maintain their distinct localization patterns suggesting that they are not functionally redundant.</p> <p>Conclusion</p> <p>These observations strongly suggest that the regulation of the binding of these proteins to actin filaments is built into the actin-binding domains. We suggest that different actin binding domains have different affinities for F-actin filaments in functionally distinct regions of the cytoskeleton.</p

Differential Genetic Susceptibility to Child Risk at Birth in Predicting Observed Maternal Behavior

This study examined parenting as a function of child medical risks at birth and parental genotype (dopamine D4 receptor; DRD4). Our hypothesis was that the relation between child risks and later maternal sensitivity would depend on the presence/absence of a genetic variant in the mothers, thus revealing a gene by environment interaction (GXE). Risk at birth was defined by combining risk indices of children's gestational age at birth, birth weight, and admission to the neonatal intensive care unit. The DRD4-III 7-repeat allele was chosen as a relevant genotype as it was recently shown to moderate the effect of environmental stress on parental sensitivity. Mothers of 104 twin pairs provided DNA samples and were observed with their children in a laboratory play session when the children were 3.5 years old. Results indicate that higher levels of risk at birth were associated with less sensitive parenting only among mothers carrying the 7-repeat allele, but not among mothers carrying shorter alleles. Moreover, mothers who are carriers of the 7-repeat allele and whose children scored low on the risk index were observed to have the highest levels of sensitivity. These findings provide evidence for the interactive effects of genes and environment (in this study, children born at higher risk) on parenting, and are consistent with a genetic differential susceptibility model of parenting by demonstrating that some parents are inherently more susceptible to environmental influences, both good and bad, than are others