Optical Tweezers as an Effective Tool for Spermatozoa Isolation from Mixed Forensic Samples

A single focus optical tweezer is formed when a laser beam is launched through a high numerical aperture immersion objective. This objective focuses the beam down to a diffraction-limited spot, which creates an optical trap where cells suspended in aqueous solutions can be held fixed. Spermatozoa, an often probative cell type in forensic investigations, can be captured inside this optical trap and dragged one by one across millimeter-length distances in order to create a cluster of cells which can be subsequently drawn up into a capillary for collection. Sperm cells are then ejected onto a sterile cover slip, counted, and transferred to a tube for DNA analysis workflow. The objective of this research was to optimize sperm cell collection for maximum DNA yield, and to determine the number of trapped sperm cells necessary to produce a full STR profile. A varying number of sperm cells from both a single-source semen sample and a mock sexual assault sample were isolated utilizing optical tweezers and processed using conventional STR analysis methods. Results demonstrated that approximately 50 trapped spermatozoa were required to obtain a consistently full DNA profile. A complete, single-source DNA profile was also achieved by isolating sperm cells via optical trapping from a mixture of sperm and vaginal epithelial cells. Based on these results, optical tweezers are a viable option for forensic applications such as separation of mixed populations of cells in forensic evidence

Phase 2 trial of montelukast for prevention of pain in sickle cell disease.

Cysteinyl leukotrienes (CysLTs) are lipid mediators of inflammation. In patients with sickle cell disease (SCD), levels of CysLTs are increased compared with controls and associated with a higher rate of hospitalization for pain. We tested the hypothesis that administration of the CysLT receptor antagonist montelukast would improve SCD-related comorbidities, including pain, in adolescents and adults with SCD. In a phase 2 randomized trial, we administered montelukast or placebo for 8 weeks. The primary outcome measure was a >30% reduction in soluble vascular cell adhesion molecule 1 (sVCAM), a marker of vascular injury. Secondary outcome measures were reduction in daily pain, improvement in pulmonary function, and improvement in microvascular blood flow, as measured by laser Doppler velocimetry. Forty-two participants with SCD were randomized to receive montelukast or placebo for 8 weeks. We found no difference between the montelukast and placebo groups with regard to the levels of sVCAM, reported pain, pulmonary function, or microvascular blood flow. Although montelukast is an effective treatment for asthma, we did not find benefit for SCD-related outcomes. This clinical trial was registered at www.clinicaltrials.gov as #NCT01960413

Geographically-weighted regression of knowledge and behaviour determinants to anti-malarial recommending and dispensing practice among medicine retailers in western Kenya: capacitating targeted interventions

Background Most patients with malaria seek treatment first in retail drug shops. Myriad studies have examined retailer behaviours and characteristics to understand the determinants to these behaviours. Geospatial methods are helpful in discovering if geographic location plays a role in the relationship between determinants and outcomes. This study aimed to discover if spatial autocorrelation exists in the relationship between determinants and retailer behaviours, and to provide specific geographic locations and target behaviours for tailoring future interventions. Methods Retailer behaviours and characteristics captured from a survey deployed to medicine retailers in the Webuye Demographic and Health Surveillance Site were analysed using geographic weighted regression to create prediction models for three separate outcomes: recommending the first-line anti-malarial therapy to adults, recommending the first-line anti-malarial therapy to children, and selling that therapy more than other anti-malarials. The estimated regression coefficients for each determinant, as well as the pseudo R2 values for each final model, were then mapped to assess spatial variability and local areas of best model fit. Results The relationships explored were found to be non-stationary, indicating that spatial heterogeneity exist in the data. The association between having a pharmacy-related health training and recommending the first-line anti-malarial treatment to adults was strongest around the peri-urban centre: comparing those with training in pharmacy to those without training (ORæ=æ5.75, pæ=æ0.021). The association between knowing the first-line anti-malarial and recommending it to children was strongest in the north of the study area compared to those who did not know the MOH-recommended anti-malarial (ORæ=æ2.34, pæ=æ0.070). This is also the area with the strongest association between attending a malaria workshop and selling the MOH-recommended anti-malarial more than other anti-malarials, compared to retailers who did not attend a workshop (ORæ=æ2.38, pæ=æ0.055). Conclusion Evidence suggests that spatial heterogeneity exists in these data, indicating that the relationship between determinants and behaviours varies across space. This is valuable information for intervention design, allowing efforts to focus on those factors that have the strongest relationship with their targeted behaviour within that geographic space, increasing programme efficiency and cost-effectiveness

Assessing the Need and Receptivity for an Integrated Healthy Sexual and Dating Relationships Intervention for Community College Students

Background: In emerging adulthood, youth often become involved in more serious romantic relationships. However, many lack the skills to avoid an unplanned pregnancy or sexually transmitted infection (STI), and to ensure a healthy dating relationship. Community college students serve nearly half of all undergraduate students in the United States; yet, community colleges typically lack resources for sexual health promotion. Purpose: To assess the need and receptivity for a web-based integrated healthy sexual and dating relationships intervention among community college students. Methods: In summer 2016, we partnered with three community colleges in South Central Texas to conduct an online survey of students’ sexual behaviors and dating relationships, and usability testing of activities from an integrated, web-based healthy sexual and dating relationship intervention. Results: Online survey participants (n=271) were 70% female, 38% Hispanic, 24% White, 17% Black, and 16% Asian; 20% self-identified as sexual minority; mean age was 20.8 years (SD = 2.05). Participants reported high rates of sexual risk behavior including sex without a condom or an effective birth control method, low use of long-acting reversible contraception, frequent use of emergency contraception, and low use of dual protection to prevent pregnancy and sexually transmitted infections. Two-thirds reported experiencing any type of dating violence perpetration or victimization in the past year. Usability testing participants (n=14) were 86% female, 42% Hispanic, 50% Asian/Pacific Islander, 14% Black, and 7% White; 71% were sexually experienced; mean age was 20.7 years (SD = 1.64). The web-based activities were highly rated in terms of usability parameters, and positively impacted short-term psychosocial outcomes related to condom use, accessing contraceptive health services, and constructive interpersonal conflict resolution. Conclusion: Findings underscore the high need and receptivity for an integrated healthy sexual and dating relationship web-based intervention among community college students, an understudied subgroup of youth in emerging adulthood

The Relationship between Marbling, Superoxide Dismutase, and Beef Tenderness

This study was conducted to evaluate the relationships between animal oxidative status (as indicated by superoxide dismutase [SOD] activity) to marbling and beef tenderness. Prime and Select-grade strip loins were selected and aged for 2, 7, 14, 21, and 28 days for Warner Bratzler shear force, Troponin-T, and SOD activity. Results showed that meat exhibiting higher levels of marbling had lower shear force values and thus were more tender. Low-marbled samples tended to have a greater tenderness response to aging. The effect of oxidative stress, however, was not evident in this study as SOD values were similar. Although the effects of oxidative stress on beef tenderness are still unclear, results from this study provide a conceptual foundation for a new research perspective on meat tenderness

Lessons Learned From all For them: Best Practices For a Cross-Collaboration approach to Hpv Vaccination in Public Schools

The Community Preventive Services Task Force endorses vaccination programs in schools to increase access to vaccinations. However, implementing a school-based approach requires substantial coordination, planning, and resources. All for Them (AFT) is a multilevel, multicomponent approach to increase HPV vaccination among adolescents attending public schools in medically underserved areas in Texas. AFT comprised a social marketing campaign, school-based vaccination clinics, and school nurse continuing education. Process evaluation metrics and key informant interviews to understand experiences with AFT program implementation informed lessons learned. Lessons emerged in six domains: strong champion, school-level support, tailored and cost-effective marketing approaches, mobile provider collaboration, community presence, and crisis management. Strong support at district and school levels is vital for gaining principal and school nurse buy-in. Social marketing strategies are integral to program implementation and should be adjusted to maximize their effectiveness in motivating parents to vaccinate children against HPV, which also can be achieved through increased community presence of the project team. Preparing contingency plans and flexibility within the program can facilitate appropriate responses to provider restrictions in mobile clinics or in the event of unforeseen crises. These important lessons can offer useful guidelines for the development of prospective school-based vaccination programs

A Novel Cross-Disciplinary Multi-Institute Approach to Translational Cancer Research: Lessons Learned from Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC)

Background: The Pennsylvania Cancer Alliance Bioinformatics Consortium (PCABC, http://www.pcabc.upmc.edu) is one of the first major project-based initiatives stemming from the Pennsylvania Cancer Alliance that was funded for four years by the Department of Health of the Commonwealth of Pennsylvania. The objective of this was to initiate a prototype biorepository and bioinformatics infrastructure with a robust data warehouse by developing a statewide data model (1) for bioinformatics and a repository of serum and tissue samples; (2) a data model for biomarker data storage; and (3) a public access website for disseminating research results and bioinformatics tools. The members of the Consortium cooperate closely, exploring the opportunity for sharing clinical, genomic and other bioinformatics data on patient samples in oncology, for the purpose of developing collaborative research programs across cancer research institutions in Pennsylvania. The Consortium’s intention was to establish a virtual repository of many clinical specimens residing in various centers across the state, in order to make them available for research. One of our primary goals was to facilitate the identification of cancer specific biomarkers and encourage collaborative research efforts among the participating centers.Methods: The PCABC has developed unique partnerships so that every region of the state can effectively contribute and participate. It includes over 80 individuals from 14 organizations, and plans to expand to partners outside the State. This has created a network of researchers, clinicians, bioinformaticians, cancer registrars, program directors, and executives from academic and community health systems, as well as external corporate partners - all working together to accomplish a common mission. The various sub-committees have developed a common IRB protocol template, common data elements for standardizing data collections for three organ sites, intellectual property/tech transfer agreements, and material transfer agreements that have been approved by each of the member institutions. This was the foundational work that has led to the development of a centralized data warehouse that has met each of the institutions’ IRB/HIPAA standards.Results: Currently, this “virtual biorepository” has over 58,000 annotated samples from 11,467 cancer patients available for research purposes. The clinical annotation of tissue samples is either done manually over the internet or semiautomated batch modes through mapping of local data elements with PCABC common data elements. The database currently holds information on 7188 cases (associated with 9278 specimens and 46,666 annotated blocks and blood samples) of prostate cancer, 2736 cases (associated with 3796 specimens and 9336 annotated blocks and blood samples) of breast cancer and 1543 cases (including 1334 specimens and 2671 annotated blocks and blood samples) of melanoma. These numbers continue to grow, and plans to integrate new tumor sites are in progress. Furthermore, the group has also developed a central web-based tool that allows investigators to share their translational (genomics/proteomics) experiment data on research evaluating potential biomarkers via a central location on the Consortium’s web site.Conclusions: The technological achievements and the statewide informatics infrastructure that have been established by the Consortium will enable robust and efficient studies of biomarkers and their relevance to the clinical course of cancer. Studies resulting from the creation of the Consortium may allow for better classification of cancer types, more accurate assessment of disease prognosis, a better ability to identify the most appropriate individuals for clinical trial participation, and better surrogate markers of disease progression and/or response to therapy

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

Analysis of Social Work Theory Progression Published in 2004

The authors reviewed 67 articles that discussed and/or tested human behavior theories from social work journals published in 2004 in order to assess the level and quality of theory progression. The articles were further sorted into Council on Social Work Education (CSWE) Educational Policy and Accreditation Standards (EPAS) Foundation Curriculum content areas of HBSE, practice, policy, field education, values & ethics, diversity, populations-at-risk/social and economic justice, and research for purposes of categorization. Results indicated that HBSE and practice were by far the largest group of articles reviewed.Also found was that social work has a limited amount of theory discussion in the content areas of field, values and ethics, diversity, and populations-at-risk/social and economic justice. Thirty-three articles were found to demonstrate theory progression, eight articles presented new/emerging theories, and 26 articles discussed or critiqued theories without presenting evidence of theory progression