Childhood Sexual Abuse Disclosure and Mental Health Outcomes: The Relationship Between Gender, Parental Style, and Masculinity Norms

Objective: The current study aims to investigate social reactions to childhood sexual abuse disclosure (CSA) in adult men and women. Additionally, the study explores the relationship between conformity to masculinity norms and perception of parental style on timing of disclosure and resulting internalizing and externalizing symptoms and substance abuse. Method: Using Amazon’s Mechanical Turk, 299 adult men and women residing in the U.S. (Mage = 35.9, SDage= 10.5; 53% female; 78% European American) completed an anonymous online series of survey items pertaining to childhood sexual abuse, internalizing and externalizing mental health symptoms, substance abuse, social reactions to their CSA disclosure, perception of parental style, conformity to masculinity norms, and CSA disclosure characteristics. Results: An independent samples t test revealed there was not a significant difference between time to disclosure for men and women. Hierarchical linear regression revealed that relationship to perpetrator, gender, and parental dysfunction did not account for a significant amount of variance in time until disclosure. A MANOVA revealed a trend in overall social reactions to CSA disclosure between men and women. Separate univariate tests revealed that women reported receiving significantly more positive and emotionally supportive responses than men. There were no differences between men and women on the other Social Reactions Questionnaire scales (e.g., Turning Against, Unsupportive Acknowledgement). Negative reactions to disclosure, and the heterosexual self-preservation and self-reliance masculinity norms were significant predictors of internalizing issues. Negative reactions to disclosure and the masculinity norm heterosexual self-preservation were also significant predictors of externalizing issues. Lastly, negative reactions to disclosure and perceived parental dysfunction were significant predictors of substance abuse. The main effect of negative reactions to disclosure on internalizing mental health outcomes was significant, but this relationship was not moderated by gender. The main effect of negative reactions to disclosure on externalizing mental health outcomes was significant, but this relationship was not moderated by gender. The main effects of a) negative reactions to disclosure on substance abuse and b) gender on substance abuse were significant. However, the relationship between negative reactions to disclosure and substance abuse was not moderated by gender. Conclusion: The findings have implications for better supporting CSA survivors; men and women may be similar in when they disclose but may receive different reactions to such disclosure. Negative reactions to disclosure, regardless of survivor gender, may increase risk for internalizing, externalizing, and substance abuse in CSA survivors. There remains much to be understood about the disclosure process and how changes in the way society views sexual abuse and assault impacts disclosure and its associated outcomes

Equity “On the Sideline”: A Mixed Methods Study of New England Evaluation Practice in 2020

Background: Centering equity in evaluations is increasingly recognized as an important professional responsibility of evaluators. While some theoretical and practical guidance exists, the evaluation field has limited empirical research on equity within evaluation practice. Purpose: This paper explores whether and how evaluators address inequities and advance equity throughout evaluation phases drawing on select findings from a larger study. Setting: The study focuses on American Evaluation Association-affiliated evaluators in the New England region of the United States who work in a variety of areas (e.g., health, education).   Intervention: Not applicable Research Design: The study uses a complementarity, sequential mixed methods design comprised of a researcher-developed online questionnaire administered to a census and snowball sample of practicing evaluators (n=82) and individual, semi-structured interviews with a subset of this sample selected to maximize variation (n=21). Quantitative data were analyzed using descriptive statistics (i.e., means and standard deviations, frequencies). Qualitative data were analyzed using a collaborative process of deductive and inductive coding followed by thematic analysis. Findings: Eight overarching findings suggest that despite evaluators’ attempts to center equity, it remains largely “on the sideline.” This is due to evaluators’ need to work against some conventional professional and methodological norms, within contractual and contextual constraints, and with limited professional preparation. &nbsp

Better Living Through Chemistry: Addressing Emerging Antibiotic Resistance

The increasing emergence of multidrug-resistant bacteria is recognized as a major threat to human health worldwide. While the use of small molecule antibiotics has enabled many modern medical advances, it has also facilitated the development of resistant organisms. This minireview provides an overview of current small molecule drugs approved by the US Food and Drug Administration (FDA) for use in humans, the unintended consequences of antibiotic use, and the mechanisms that underlie the development of drug resistance. Promising new approaches and strategies to counter antibiotic-resistant bacteria with small molecules are highlighted. However, continued public investment in this area is critical to maintain an edge in our evolutionary arms race against antibiotic-resistant microorganisms. Impact statement The alarming increase in antibiotic-resistant microorganisms is a rapidly emerging threat to human health throughout the world. Historically, small molecule drugs have played a major role in controlling bacterial infections and they continue to offer tremendous potential in countering resistant organisms. This minireview provides a broad overview of the relevant issues, including the diversity of FDA-approved small molecule drugs and mechanisms of drug resistance, unintended consequences of antibiotic use, the current state of development for small molecule antibacterials and financial challenges that impact progress towards novel therapies. The content will be informative to diverse stakeholders, including clinicians, basic scientists, translational scientists and policy makers, and may be used as a bridge between these key players to advance the development of much-needed therapeutics

Equity “On the Sideline”

Background: Centering equity in evaluations is increasingly recognized as an important professional responsibility of evaluators. While some theoretical and practical guidance exists, the evaluation field has limited empirical research on equity within evaluation practice. Purpose: This paper explores whether and how evaluators address inequities and advance equity throughout evaluation phases drawing on select findings from a larger study. Setting: The study focuses on American Evaluation Association-affiliated evaluators in the New England region of the United States who work in a variety of areas (e.g., health, education).   Intervention: Not applicable Research Design: The study uses a complementarity, sequential mixed methods design comprised of a researcher-developed online questionnaire administered to a census and snowball sample of practicing evaluators (n=82) and individual, semi-structured interviews with a subset of this sample selected to maximize variation (n=21). Quantitative data were analyzed using descriptive statistics (i.e., means and standard deviations, frequencies). Qualitative data were analyzed using a collaborative process of deductive and inductive coding followed by thematic analysis. Findings: Eight overarching findings suggest that despite evaluators’ attempts to center equity, it remains largely “on the sideline.” This is due to evaluators’ need to work against some conventional professional and methodological norms, within contractual and contextual constraints, and with limited professional preparation.

Absolute oxygen-guided radiation therapy improves tumor control in three preclinical tumor models

BackgroundClinical attempts to find benefit from specifically targeting and boosting resistant hypoxic tumor subvolumes have been promising but inconclusive. While a first preclinical murine tumor type showed significant improved control with hypoxic tumor boosts, a more thorough investigation of efficacy from boosting hypoxic subvolumes defined by electron paramagnetic resonance oxygen imaging (EPROI) is necessary. The present study confirms improved hypoxic tumor control results in three different tumor types using a clonogenic assay and explores potential confounding experimental conditions.Materials and methodsThree murine tumor models were used for multi-modal imaging and radiotherapy: MCa-4 mammary adenocarcinomas, SCC7 squamous cell carcinomas, and FSa fibrosarcomas. Registered T2-weighted MRI tumor boundaries, hypoxia defined by EPROI as pO2 ≤ 10 mmHg, and X-RAD 225Cx CT boost boundaries were obtained for all animals. 13 Gy boosts were directed to hypoxic or equal-integral-volume oxygenated tumor regions and monitored for regrowth. Kaplan–Meier survival analysis was used to assess local tumor control probability (LTCP). The Cox proportional hazards model was used to assess the hazard ratio of tumor progression of Hypoxic Boost vs. Oxygenated Boost for each tumor type controlling for experimental confounding variables such as EPROI radiofrequency, tumor volume, hypoxic fraction, and delay between imaging and radiation treatment.ResultsAn overall significant increase in LTCP from Hypoxia Boost vs. Oxygenated Boost treatments was observed in the full group of three tumor types (p < 0.0001). The effects of tumor volume and hypoxic fraction on LTCP were dependent on tumor type. The delay between imaging and boost treatments did not have a significant effect on LTCP for all tumor types.ConclusionThis study confirms that EPROI locates resistant tumor hypoxic regions for radiation boost, increasing clonogenic LTCP, with potential enhanced therapeutic index in three tumor types. Preclinical absolute EPROI may provide correction for clinical hypoxia images using additional clinical physiologic MRI

Regulation of learning and memory by meningeal immunity: a key role for IL-4

Proinflammatory cytokines have been shown to impair cognition; consequently, immune activity in the central nervous system was considered detrimental to cognitive function. Unexpectedly, however, T cells were recently shown to support learning and memory, though the underlying mechanism was unclear. We show that one of the steps in the cascade of T cell–based support of learning and memory takes place in the meningeal spaces. Performance of cognitive tasks led to accumulation of IL-4–producing T cells in the meninges. Depletion of T cells from meningeal spaces skewed meningeal myeloid cells toward a proinflammatory phenotype. T cell–derived IL-4 was critical, as IL-4−/− mice exhibited a skewed proinflammatory meningeal myeloid cell phenotype and cognitive deficits. Transplantation of IL-4−/− bone marrow into irradiated wild-type recipients also resulted in cognitive impairment and proinflammatory skew. Moreover, adoptive transfer of T cells from wild-type into IL-4−/− mice reversed cognitive impairment and attenuated the proinflammatory character of meningeal myeloid cells. Our results point to a critical role for T cell–derived IL-4 in the regulation of cognitive function through meningeal myeloid cell phenotype and brain-derived neurotrophic factor expression. These findings might lead to the development of new immune-based therapies for cognitive impairment associated with immune decline

Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study

Background Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country’s largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. Methods In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). Findings Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9·6 [95% CI 3·6 – 24]) and absence of an evening meal (2·2 [1·2–4·3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7·8 [95% CI 3·3–18·8], without evening meal; OR 3·6 [1·1–11·1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12·4 μg/g to 152·0 μg/g and MCPG ranged from 44·9 μg/g to 220·0 μg/g. Interpretation Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks

Genomic Footprints of Selective Sweeps from Metabolic Resistance to Pyrethroids in African Malaria Vectors Are Driven by Scale up of Insecticide-Based Vector Control

Insecticide resistance in mosquito populations threatens recent successes in malaria prevention. Elucidating patterns of genetic structure in malaria vectors to predict the speed and direction of the spread of resistance is essential to get ahead of the `resistance curve' and to avert a public health catastrophe. Here, applying a combination of microsatellite analysis, whole genome sequencing and targeted sequencing of a resistance locus, we elucidated the continent-wide population structure of a major African malaria vector, Anopheles funestus. We identified a major selective sweep in a genomic region controlling cytochrome P450-based metabolic resistance conferring high resistance to pyrethroids. This selective sweep occurred since 2002, likely as a direct consequence of scaled up vector control as revealed by whole genome and fine-scale sequencing of pre- and post-intervention populations. Fine-scaled analysis of the pyrethroid resistance locus revealed that a resistanceassociated allele of the cytochrome P450 monooxygenase CYP6P9a has swept through southern Africa to near fixation, in contrast to high polymorphism levels before interventions, conferring high levels of pyrethroid resistance linked to control failure. Population structure analysis revealed a barrier to gene flow between southern Africa and other areas, which may prevent or slow the spread of the southern mechanism of pyrethroid resistance to other regions. By identifying a genetic signature of pyrethroid-based interventions, we have demonstrated the intense selective pressure that control interventions exert on mosquito populations. If this level of selection and spread of resistance continues unabated, our ability to control malaria with current interventions will be compromised