Reproductive Coercion and Relationship Abuse Among Adolescents and Young Women Seeking Care at School Health Centers.

ObjectiveTo investigate demographic differences and evaluate how reproductive coercion and relationship abuse influences young females' care-seeking and sexual health behaviors.MethodsWe conducted a secondary analysis of cross-sectional baseline survey data from sexually active female students (aged 14-19 years) who sought care from school health centers. Outcomes included recent (previous 3 months) reproductive coercion, physical or sexual adolescent relationship abuse, and nonpartner sexual violence victimization. Cluster-adjusted χ tests compared demographics and generalized linear mixed models estimated associations among reproductive coercion, adolescent relationship abuse (physical and sexual abuse in romantic relationships), and care-seeking and sexual health behaviors.ResultsOf 550 sexually active high school females, 12% reported recent reproductive coercion and 17% reported physical or sexual adolescent relationship abuse, with no significant demographic differences. Prevalence of recent nonpartner sexual violence was 17%. There were no observed significant differences in care-seeking behaviors among those with recent reproductive coercion compared with those without. Physical or sexual adolescent relationship abuse was associated with increased odds of seeking testing or treatment for sexually transmitted infections (adjusted odds ratio [aOR] 2.08, 95% CI 1.05-4.13). Females exposed to both adolescent relationship abuse and reproductive coercion had higher odds of having a partner who was 5 or more years older (aOR 4.66, 95% CI 1.51-14.4), having two or more recent sexual partners (aOR 3.86, 95% CI 1.57-9.48), and using hormonal contraception only (aOR 3.77, 95% CI 1.09-13.1 vs hormonal methods with condoms).ConclusionAlmost one in eight females experienced recent reproductive coercion. We did not observe significant demographic differences in reproductive coercion. Partner age and number of sexual partners may elevate risk for abusive relationships. Relationship abuse is prevalent among high school students seeking care, with no clear pattern for case identification. By failing to identify factors associated with harmful partner behaviors, our results support universal assessment for reproductive coercion and relationship abuse among high school-aged adolescents, involving education, resources, and harm-reduction counseling to all patients.Clinical trial registrationClinicalTrials.gov, NCT01678378

Implementing a Coordinated Care Model for Sex Trafficked Minors in Smaller Cities

Background Addressing the social and clinical service needs of minors who have been sexually exploited remains a challenge across the United States. While larger metropolitan centers have established shelters and service provision specific for trafficked persons, in smaller cities and more rural settings, survivors of trafficking (especially minors) are usually served by multiple, disparate social service and health providers working across different systems. Sexually exploited minors present an even greater challenge due to intersections with child welfare and juvenile justice systems, histories of abuse by family that limit placement options, and limited services that address the complex medical, mental health, and psychosocial needs of these youth. Major health organizations have recommended a coordinated care model that integrates the therapeutic and social service needs of trafficked persons including housing and education; implementation of such service provision requires intensive, multi-sectoral collaboration. Methods We present two case studies from an anti-trafficking coalition established in a smaller urban area. Findings/Conclusions Multi-sector collaboration requires the development of policies and protocols for addressing the diverse needs (acute and ongoing) of trafficked minors who are often “dual jurisdiction,” involved in both the juvenile justice and child welfare systems. Principles of care including autonomy, empowerment, protection, and safety may be at odds as systems may approach these youth differently. A clearly identified care coordinator can help navigate across these systems and facilitate communication among service providers while protecting client privacy, confidentiality, and autonomy. Assessing the quality of services provided and accountability among service providers remain significant challenges, especially in resource limited settings

Cluster randomized controlled trial protocol: addressing reproductive coercion in health settings (ARCHES)

Background\ud Women ages 16–29 utilizing family planning clinics for medical services experience higher rates of intimate partner violence (IPV) and reproductive coercion (RC) than their same-age peers, increasing risk for unintended pregnancy and related poor reproductive health outcomes. Brief interventions integrated into routine family planning care have shown promise in reducing risk for RC, but longer-term intervention effects on partner violence victimization, RC, and unintended pregnancy have not been examined.\ud \ud Methods/Design\ud The ‘Addressing Reproductive Coercion in Health Settings (ARCHES)’ Intervention Study is a cluster randomized controlled trial evaluating the effectiveness of a brief, clinician-delivered universal education and counseling intervention to reduce IPV, RC and unintended pregnancy compared to standard-of-care in family planning clinic settings. The ARCHES intervention was refined based on formative research. Twenty five family planning clinics were randomized (in 17 clusters) to either a three hour training for all family planning clinic staff on how to deliver the ARCHES intervention or to a standard-of-care control condition. All women ages 16–29 seeking care in these family planning clinics were eligible to participate. Consenting clients use laptop computers to answer survey questions immediately prior to their clinic visit, a brief exit survey immediately after the clinic visit, a first follow up survey 12–20 weeks after the baseline visit (T2), and a final survey 12 months after the baseline (T3). Medical record chart review provides additional data about IPV and RC assessment and disclosure, sexual and reproductive health diagnoses, and health care utilization. Of 4009 women approached and determined to be eligible based on age (16–29 years old), 3687 (92 % participation) completed the baseline survey and were included in the sample.\ud \ud Discussion\ud The ARCHES Intervention Study is a community-partnered study designed to provide arigorous assessment of the short (3-4 months) and long-term (12 months) effects of a brief, clinician-delivered universal education and counseling intervention to reduce IPC, RC and unintended pregnancy in family planning clinic settings. The trial features a cluster randomized controlled trial design, a comprehensive data collection schedule and a large sample size with excellent retention.\ud \ud Trial Registration\ud ClinicialTrials.gov NCT01459458. Registered 10 October 2011

Preclinical Evaluation of the Novel, Orally Bioavailable Selective Inhibitor of Nuclear Export (SINE) KPT-335 in Spontaneous Canine Cancer: Results of a Phase I Study

The purpose of this study was to evaluate the activity of Selective Inhibitors of Nuclear Export (SINE) compounds that inhibit the function of the nuclear export protein Exportin 1 (XPO1/CRM1) against canine tumor cell lines and perform a Phase I clinical trial of KPT-335 in dogs with spontaneous cancer to provide a preliminary assessment of biologic activity and tolerability.Canine tumor cell lines derived from non-Hodgkin lymphoma (NHL), mast cell tumor, melanoma and osteosarcoma exhibited growth inhibition and apoptosis in response to nanomolar concentrations of SINE compounds; NHL cells were particularly sensitive with IC50 concentrations ranging from 2-42 nM. A Phase I clinical trial of KPT-335 was performed in 17 dogs with NHL (naive or relapsed), mast cell tumor or osteosarcoma. The maximum tolerated dose was 1.75 mg/kg given orally twice/week (Monday/Thursday) although biologic activity was observed at 1 mg/kg. Clinical benefit (CB) including partial response to therapy (PR, n = 2) and stable disease (SD, n = 7) was observed in 9/14 dogs with NHL with a median time to progression (TTP) for responders of 66 days (range 35-256 days). A dose expansion study was performed in 6 dogs with NHL given 1.5 mg/kg KPT-335 Monday/Wednesday/Friday; CB was observed in 4/6 dogs with a median TTP for responders of 83 days (range 35-354 days). Toxicities were primarily gastrointestinal consisting of anorexia, weight loss, vomiting and diarrhea and were manageable with supportive care, dose modulation and administration of low dose prednisone; hepatotoxicity, anorexia and weight loss were the dose limiting toxicities.This study provides evidence that the novel orally bioavailable XPO1 inhibitor KPT-335 is safe and exhibits activity in a relevant, spontaneous large animal model of cancer. Data from this study provides critical new information that lays the groundwork for evaluation of SINE compounds in human cancer

Early Evolution of Conserved Regulatory Sequences Associated with Development in Vertebrates

Comparisons between diverse vertebrate genomes have uncovered thousands of highly conserved non-coding sequences, an increasing number of which have been shown to function as enhancers during early development. Despite their extreme conservation over 500 million years from humans to cartilaginous fish, these elements appear to be largely absent in invertebrates, and, to date, there has been little understanding of their mode of action or the evolutionary processes that have modelled them. We have now exploited emerging genomic sequence data for the sea lamprey, Petromyzon marinus, to explore the depth of conservation of this type of element in the earliest diverging extant vertebrate lineage, the jawless fish (agnathans). We searched for conserved non-coding elements (CNEs) at 13 human gene loci and identified lamprey elements associated with all but two of these gene regions. Although markedly shorter and less well conserved than within jawed vertebrates, identified lamprey CNEs are able to drive specific patterns of expression in zebrafish embryos, which are almost identical to those driven by the equivalent human elements. These CNEs are therefore a unique and defining characteristic of all vertebrates. Furthermore, alignment of lamprey and other vertebrate CNEs should permit the identification of persistent sequence signatures that are responsible for common patterns of expression and contribute to the elucidation of the regulatory language in CNEs. Identifying the core regulatory code for development, common to all vertebrates, provides a foundation upon which regulatory networks can be constructed and might also illuminate how large conserved regulatory sequence blocks evolve and become fixed in genomic DNA

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.peer-reviewe

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes