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BACKGROUND: Little research has examined how anchor numbers affect choice, despite several decades of research showing that judgments typically and robustly assimilate toward irrelevant anchors. METHODS: In one experiment, HIV-positive patients (N = 99) judged the chances that sexual partners would become infected with HIV after sex using a defective condom and then indicated their choices of remedial action. In a second experiment, Iowa physicians (N =191) rated the chances that hypothetical patients had a pulmonary embolism and then formulated a treatment plan. RESULTS: Irrelevant anchor numbers dramatically affected judgments by HIV-infected patients of the chances of HIV infection after a condom broke during sex (43% v. 64% in the low- and high-anchor conditions, respectively) and judgments by doctors of the chances of pulmonary embolism (23% v. 53%, respectively). Despite large anchoring effects in judgement, treatment choices did not differ between low-and high-anchor conditions. Accountability did not reduce the anchoring bias in the doctors' judgments. DISCUSSION: The practical implications of anchoring for risk judgments are potentially large, but the bias may be less relevant to treatment choices. The findings suggest that the theoretical underpinnings of the anchoring bias may be more complex than previously thought. Key words: anchoring bias; assimilation effect; contrast effect; risk perception. (Med Decis Making 2007; 27: 203-211). [ABSTRACT FROM AUTHOR]

Purpose: Focal therapy aims to provide a durable oncologic treatment option for men with prostate cancer (PCa), while preserving their quality of life. Most focal therapy modalities rely on the direct tissue effect, resulting in a possible nontargeted approach to ablation. Here, we report the results of the first human feasibility trial utilizing nanoparticle-directed focal photothermal ablation for PCa., Materials and Methods: A prospective, open-label, single-arm, multicenter study of men with localized PCa in Gleason Grade Group 1 to 3 was conducted. Men received a single infusion of gold nanoparticles (AuroShells), followed by magnetic resonance (MR)/ultrasound (US) fusion-guided laser excitation of the target tissue to induce photothermal ablation. MRI was used to assess the effectiveness of prostate tissue ablation at 48 to 96 hours, 3 months, and 12 months post treatment. At 3 months, a targeted fusion biopsy of the lesion(s) was conducted. At 12 months, a targeted fusion biopsy and standard templated biopsy were performed. Treatment success was determined based on a negative MR/US fusion biopsy outcome within the treated area., Results: Forty-six men were enrolled in the study, and 44 men with 45 lesions completed nanoparticle infusion and laser treatment. Baseline mean PSA levels were 9.5 ng/mL, with a statistically significant decrease of   5.9 ng/mL at 3 months and 4.7 ng/mL at 12 months ( P  < .0001). The oncologic success rates at 3 and 12 months resulted in 29 (66%) and 32 (73%) of 44 patients, respectively, being successfully treated, confirmed with negative MR/US fusion biopsies within the ablation zone. Among Gleason Grade Group, maximum lesion diameter on MRI, prostate volume, and Prostate Imaging Reporting and Data System scoring, the maximum lesion diameter was significantly associated with the odds of treatment failure at 12 months ( P = .046)., Conclusions: Nanoparticle-directed focal laser ablation of neoplastic prostate tissue resulted in 73% of patients with successful treatment at 12 months post treatment, confirmed by negative MR/US fusion biopsy of the treated lesion and a systematic biopsy., Clinical Trial Registration No.: 02680535.

Yersinia pestis, one of the deadliest bacterial pathogens ever known, is responsible for three plague pandemics and several epidemics, with over 200 million deaths during recorded history. Due to high genomic plasticity, Y. pestis is amenable to genetic mutations as well as genetic engineering that can lead to the emergence or intentional development of pan-drug-resistant strains. Indeed, antibiotic-resistant strains (e.g., strains carrying multidrug-resistant or MDR plasmids) have been isolated in various countries and endemic areas. Thus, there is an urgent need to develop novel, safe, and effective treatment approaches for managing Y. pestis infections. This includes infections by antigenically distinct strains for which vaccines (none FDA approved yet) may not be effective and those that cannot be managed by currently available antibiotics. Lytic bacteriophages provide one such alternative approach. In this study, we examined post-exposure efficacy of a bacteriophage cocktail, YPP-401, to combat pneumonic plague caused by Y. pestis CO92. YPP-401 is a four-phage preparation effective against a panel of at least 68 genetically diverse Y. pestis strains. Using a pneumonic plague aerosol challenge model in gender-balanced Brown Norway rats, YPP-401 demonstrated ~88% protection when delivered 18 h post-exposure for each of two administration routes (i.e., intraperitoneal and intranasal) in a dose-dependent manner. Our studies provide proof-of-concept that YPP-401 could be an innovative, safe, and effective approach for managing Y. pestis infections, including those caused by naturally occurring or intentionally developed multidrug-resistant strains.IMPORTANCECurrently, there are no FDA-approved plague vaccines. Since antibiotic-resistant strains of Y. pestis have emerged or are being intentionally developed to be used as a biothreat agent, new treatment modalities are direly needed. Phage therapy provides a viable option against potentially antibiotic-resistant strains. Additionally, phages are nontoxic and have been approved by the FDA for use in the food industry. Our study provides the first evidence of the protective effect of a cocktail of four phages against pneumonic plague, the most severe form of disease. When treatment was initiated 18 h post infection by either the intranasal or intraperitoneal route in Brown Norway rats, up to 87.5% protection was observed. The phage cocktail had a minimal impact on a representative human microbiome panel, unlike antibiotics. This study provides strong proof-of-concept data for the further development of phage-based therapy to treat plague., Competing Interests: The YPP-401 cocktail was developed by Intralytix, Inc. The following authors report conflicts of interest with respect to Intralytix, Inc.: A.S. (co-founder, employee, shareholder); J.A.S. (employee, shareholder); J.W. (employee, shareholder); and L.H. (employee).

Background: Taken together, prior publications on the association between symptoms of depression and anxiety and contact with the criminal justice system (CJS) suggest a bi-directional relationship, but all the studies only focus on one direction in this relationship., Aims: To examine, in longitudinally collected data, period-specific within-individual change in anxiety and depression measures preceding arrest measurement and, separately, following arrest measurement., Methods: Data were obtained from the National Longitudinal Study of Youth 1997, a nationally representative sample of people born between 1980 and 1984 and first interviewed between ages 12-17 and a publicly accessible database. Our focus was on data for the 11 years 2000-2010. Using whole sample data, we tested for a reciprocal association between depression and anxiety during each 2-year period and arrests during the following year, and vice versa, allowing for relatively fixed characteristics such as sex, age and socio-economic indicators. We used period-specific change modelling to test relationships., Results: We found that within-individual increases in depression and anxiety scores over short periods (2-year periods) of time was associated with an increase in the number of arrests subsequent over the following year, consistently throughout the whole of the 10 years studies. The reciprocal association was also observed, albeit the magnitude of the effects was much smaller., Conclusion: This study adds to the literature on the association between mental health and CJS contact by showing that they may be reciprocally associated. This suggests that facilitating co-working or even formal partnerships between community mental health services and justice-related services could be beneficial., (© 2024 John Wiley & Sons Ltd.)

Bacterial diseases of the gastrointestinal (GI) tract continue to be a major worldwide cause of human morbidity and mortality. Among various enteric pathogens, Shigella spp. are some of the most common and deadly bacterial pathogens. They are responsible for ~125 million worldwide cases of shigellosis, and ~14,000 deaths annually, the majority in children under the age of 5 and occurring in developing countries. Preventing and treating shigellosis with conventional drugs (e.g., vaccines and antibiotics) has proven to be very difficult. Here, we assessed the safety and tolerability of ShigActive™, a lytic bacteriophage preparation targeting Shigella spp., in a randomized, placebo-controlled, double-blind Phase 1 clinical trial. Ten participants randomized 4:1 received ShigActive™ or placebo co-administered with sodium bicarbonate orally three times daily for 7 days. Solicited and unsolicited adverse events (AEs) were observed for 29 days. Fifty percent of the subjects receiving ShigActive™ reported mild GI-related symptoms, while one participant experienced moderate fatigue. No serious or medically attended AEs occurred through day 90. Additionally, no significant differences in GI-associated inflammatory mediators or fecal microbiome changes were observed between placebo- and ShigActive™-treated subjects, or from a participants' baseline value. The results of this first-in-human (FIH) randomized, controlled Phase 1 trial of ShigActive™ demonstrate that it is safe and well tolerated when orally administered with no significant differences compared to placebo controls.

Objective: The objective of this study was to determine if surface electromyography (sEMG) demonstrates differences in muscle activation between normal and dogs recovering from spinal cord injury due to intervertebral disk extrusion., Animals: Two groups of client-owned small-breed chondrodysplastic-type dogs were tested. Group 1 consisted of seven ambulatory paraparetic dogs that had undergone a hemilaminectomy procedure in the T3-L3 region for intervertebral disk extrusion 1 month prior. Group 2 was made up of seven normal dogs that had no history of intervertebral disk disease or spinal surgery., Procedures: Each subject walked 10 feet on a nonslip surface for at least five gait cycles for the sEMG to capture muscle activation of the vastus lateralis and gluteus medius, bilaterally. Muscle activation was quantified as the total myoelectric output area under the curve, averaged across all gait cycles., Results: Muscle activation was significantly greater in the post-operative hemilaminectomy group ( p  = 0.012). There was a significant difference in muscle activation between each hindlimb in the post-operative hemilaminectomy group, but not in the normal group. The muscle activation was significantly lower on the side that underwent surgery compared to the opposite limb ( p  = 0.0034)., Conclusion and Clinical Importance: Post-operative hemilaminectomy dogs have greater hindlimb muscle activation compared to normal dogs, which likely represents a lack of descending inhibition secondary to upper motor neuron syndrome. The side of surgery is correlated with decreased muscle activation. Surface EMG can be used to evaluate muscle activity in dogs recovering from spinal decompression surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Schwartz, Carrera-Justiz and Repac.)

AuroLase ® Therapy-a nanoparticle-enabled focal therapy-has the potential to safely and effectively treat localized prostate cancer (PCa), preserving baseline functionality. This article presents a detailed case of localized PCa treated with AuroLase, providing insight on expectations from the diagnosis of PCa to one year post-treatment. AuroLase Therapy is a two-day treatment consisting of a systemic infusion of gold nanoshells (~150-nm hydrodynamic diameter) on Day 1, and sub-ablative laser treatment on Day 2. Multiparametric MRI (mpMRI) was used for tumor visualization, treatment planning, and therapy response assessment. The PCa was targeted with a MR/Ultrasound-fusion (MR/US) transperineal approach. Successful treatment was confirmed at 6 and 12 months post-treatment by the absence of disease in MR/US targeted biopsies. On the mpMRI, confined void space was evident, an indication of necrotic tissues encompassing the treated lesion, which was completely resolved at 12 months, forming a band-like scar with no evidence of recurrent tumor. The patient's urinary and sexual functions were unchanged. During the one-year follow-up, changes on the DCE sequence and in the Ktrans and ADC values assist in qualitatively and quantitatively evaluating tissue changes. The results highlight the potential of gold-nanoparticle-enabled sub-ablative laser treatment to target and control localized PCa, maintain quality of life, and preserve baseline functionality.

Background: Chamomile administration may have desirable effects in the perioperative setting. Current practice, however, discourages perioperative chamomile use due to a theoretical increase in bleeding. Therefore, we evaluated if chamomile acutely (within 4 h of ingestion) prolongs coagulation assays., Methods: Eight healthy volunteers were randomized to receive 2 interventions in a crossover design: (a) single dose of chamomile extract capsule (500 mg) and (b) single dose of chamomile tea (3 g in 150 mL water). Interventions were separated at least 3 days apart from each other. Blood was sampled pre-ingestion, 2 h post-ingestion, and 4 h post-ingestion for each intervention. The primary outcome was the maximal change in prothrombin time (PT) before vs after each intervention. Secondary outcomes included changes in international normalized ratio, activated partial thromboplastin time, thrombin time, reptilase time, and fibrinogen levels., Results: All 8 subjects completed the study. The average pre-ingestion PT values for tea and capsules were 11.9 (1.1) s and 12.0 (0.9) s, respectively. Tea significantly increased the average maximum PT by 0.7 (0.2) s (P = 0.0078). Extract capsules increased the maximum PT by 0.3 (0.2) s (P = 0.06). Neither PT prolongation met the predefined 10% threshold for clinical significance. No significant changes in secondary outcomes were observed., Conclusions: Chamomile tea ingestion prolongs PT. However, the clinical significance of this is unclear at this time and warrants further investigation. ClinicalTrials.gov Registration Number: NCT05272475., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This paper provides a detailed summary and discussion of the concept of stress and how it relates to the health, wellbeing, and performance of corrections officers. In line with these objectives, we focus on three areas: (1) providing a more detailed definition of the concept of stress; (2) a discussion of the ways that increased exposure to stress may impact corrections officers' physical and mental health; and (3) a summary of prevention and intervention strategies that are relevant for corrections officers and have shown promise in dampening the consequences of increased stress exposure. More in-depth knowledge of the concept of stress and the underlying processes that link stress to negative outcomes will provide policy makers and corrections departments with an understanding of the characteristics of prevention and intervention strategies that are expected to be most effective in limiting the consequences of stress., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: In the interest of full disclosure, DAG is Scientific and Strategy Advisor at Salimetrics LLC and Salivabio LLC. These relationships are managed by the policies of the committees on conflict of interest at Johns Hopkins University School of Medicine and the University of California at Irvine.

Introduction: Overweight and obesity trends are on the rise among both civilian and military beneficiaries. The purpose of this narrative review was to evaluate nutrition, behavioral, lifestyle, pharmacotherapy, and alternative approaches to weight management (WM) among adults with a focus toward identifying gaps and evidence-based strategies that could support or enhance current and future WM programming among military adult beneficiaries., Materials and Methods: A trained research team identified publications (January 2013-January 2020) for abstract review using key search terms and inclusion criteria. Two independent researchers conducted both the abstract review and full-paper bias scoring using selected Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. All eligible studies were assessed for bias and categorized based on key themes. The study was registered in PROSPERO, the international prospective register of systematic reviews., Results: The research team identified 741 articles, with 278 meeting final inclusion criteria. The mean bias score was 7.5 ± 3.9 (score of 0-13; higher indicating fewer bias factors), with 64% scoring ≥9. Factors contributing to low bias included intervention compliance, dropout rate, and inability to blind participants. The most common published weight-loss interventions included a combination of therapies (59%), diet/supplement (17%), other approaches (12%), behavior change (7%), and exercise (6%). Themes identified to improve WM outcomes included leveraging technology, increasing intervention interactions, community support, emphasis on early weight loss, pharmacotherapy risk-benefit, enhanced behavioral component, resistance exercise, mindfulness, and benefits of quality-of-life measures., Conclusions: Reviewers identified several validated tools and techniques to augment and update existing WM programming to improve health and weight outcomes. The review affirmed use of individualized dietary patterns and not a "one-size-fits-all approach" as well as incorporating more comprehensive and team-approached treatments to make the best use of tools and strategies to enhance outcomes., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Studies examining the impact of early adversity on physiological responsivity to environmental challenges in later life yield a complex pattern of findings and ambiguity regarding the direction of effect, with some studies reporting heightened responses and others reporting dampened responses. One potential reason for these mixed findings is an oversimplified theoretical model surrounding the connection between early life stressor exposure and subsequent stress responsivity. The adaptive calibration model offersa contemporary set of assumptions aimed at providing a better understanding of the ways that early life experiences shape the stress response system to better align with current and future environments. The current study utilized a large subsample from the National Study of Daily Experiences ( N =  1,605) to examine the extent to which the association between daily stressor exposure and cortisol levels varies across levels of early life adversity. Results revealed that those individuals who experienced extremely low levels of early life adversity displayed the greatest increase in cortisol levels across the day as daily stressor exposure increased. Alternatively, those individuals who experienced extremely high levels of early life adversity displayed almost no change in diurnal production of cortisol as daily stressor exposure increased. The results are discussed within the evolutionary-developmental context of the adaptive calibration model along with suggestions for future research., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: In the interest of full disclosure, DAG is Scientific and Strategy Advisor at Salimetrics LLC and Salivabio LLC. These relationships are managed by the policies of the committees on conflict of interest at Johns Hopkins University School of Medicine and the University of California at Irvine.

Background: Chamomile is consumed worldwide for enjoyment and its potentially desirable properties. Widespread patient resource websites, however, discourage preoperative chamomile intake, lest bleeding could worsen. This precaution, though, stems largely from indirect evidence in one case report. To evaluate if chamomile ingestion impacts coagulation assays via coumarin-like substances, we designed a randomized, placebo-controlled, crossover study., Materials and Methods: Healthy volunteers were randomized to three interventions in a cross-over-design spanning 5 weeks per subject. Interventions included 7-day consumption of chamomile tea (3 tea bags × 3 times daily = 9 tea bags daily), a chamomile extract capsule (3 times daily), or a placebo capsule (3 times daily). A 7-day washout period elapsed between intervention periods. The primary outcome was the change in prothrombin time (PT) before vs. after each intervention. Secondary outcomes included changes in the international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time (TT), reptilase time (RT), and fibrinogen (FG) surrounding each intervention., Results: All 12 enrolled subjects were randomized and completed the study. The primary outcome of PT change (mean ± SD) was similar across interventions (chamomile tea =  - 0.2 ± 0.4 s, extract capsule =  - 0.2 ± 0.4 s, and placebo capsule = 0.1 ± 0.5 s; p = 0.34). INR change was 0 s (p = 0.07) for each intervention. The aPTT, TT, RT, and FG, did not change significantly across interventions (p = 0.8, p = 0.08, p = 0.8, and p = 0.2 respectively)., Conclusions: Chamomile intake by tea or capsule does not prolong PT. These findings challenge the notion to avoid perioperative chamomile intake in patients not taking warfarin., Trial Registration: ClinicalTrials.gov, NCT05006378; Principal Investigator: Jonathon Schwartz, M.D.; Registered August 16, 2021., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Incarcerated individuals experience increased health problems, presenting additional challenges as they leave prison and re-enter the community. These challenges are disproportionally experienced by racial and ethnic minorities. Despite these trends, little is known regarding the availability of medical services within the communities to which incarcerated individuals return., Methods: We examined all prison returns in the state of Florida between 2008 and 2017. We examined the odds of returning from prison to a community that is formally designated as medically underserved by the Health Resources and Services Administration. We also examined whether Florida communities with a greater proportion of racial and ethnic minority returns were more likely to be designated as medically underserved., Results: Overall, each SD increase in community return rate resulted in a 20% increase in the odds of medical underservice designation. For each SD increase in the proportion of black and Latino returns, the odds of medical underservice designation increased by 50% and 14%, respectively, compared with the proportion of white returns., Discussion: Within Florida, previously incarcerated individuals are more likely to return to communities with limited availability of medical services. These findings are even more pronounced for communities with more black returnees. Previously incarcerated individuals are more likely to return to communities that lack the medical infrastructure required to address their unique healthcare needs, potentially leading to worsened health, and increased racial and ethnic health disparities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Limited research has examined the extent to which adolescent delinquency predicts healthcare usage in young adulthood, including emergency department (ED) visits. This study used data from 3,310 adolescents (52.05% female; mean age at Wave I = 16.04 years) from the sibling subsample of the National Longitudinal Study of Adolescent to Adult Health (Add Health). We examined whether adolescent delinquency at Wave I predicted ED visits at Wave III using sibling fixed effects models to adjust estimates for within-family unobserved heterogeneity. Increased violent, but not nonviolent, delinquency predicted a higher number of ED visits in early adulthood in the sibling fixed effects models. To our knowledge, this is the first study to examine the relationship between delinquency and ED usage using a sibling fixed effects design. Findings demonstrate that violent adolescent delinquency may increase healthcare usage and suggest the potential role of healthcare providers in improving outcomes for delinquent youth.

Background: Widespread respiratory infections with high morbidity rates caused by respiratory viruses represent a significant global public health problem. Our objective was to describe cases and deaths from severe acute respiratory infection (SARI) in Brazil over the past 8 y as well as changes in the distribution and risk of illness and death from SARI before and in the first year of the coronavirus disease 2019 (COVID-19) pandemic (FYP)., Methods: We performed a descriptive epidemiological study of hospitalized SARI cases and deaths between 2013 and 2020 in Brazil, separated into pre-pandemic (2013 to 2019) and FYP (2020). We estimate the increase in SARI cases and deaths in the FYP as well as the mortality and infection risks attributable to the FYP (MRAP and IRAP, respectively)., Results: In 2020, an excess of 425 054 cases and 109 682 deaths was observed, with a significant increase in the risk of falling ill and dying from SARI, with an IRAP of 200.06 and an MRAP of 51.68 cases per 100 000 inhabitants. The increase in SARI cases and deaths was particularly prominent among patients with COVID-19, the elderly, males, those self-identifying as mixed race and patients with heart disease and diabetes. We conclude that an important increase in morbidity and mortality due to SARI was observed in the FYP. More vulnerable groups and those living in the Southeast, North and Center-West regions of the country suffered the most., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Aims: The current study examined the buffering effect of social support on the relationship between family history and alcohol use disorder symptoms (AUDsx)., Methods: The current study analyzes data from Waves 1 and 2 of the National Epidemiologic Survey of Alcohol and Related Conditions (N = 34,653). Count of AUDsx were measured using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version, the independent variable was a weighted density measure of family history of AUDsx and the moderating variable was social support measured using the 12-item Interpersonal Support Evaluation List (ISEL-12). Negative binomial regression models were used to estimate the association between (1) family history and AUDsx and (2) social support and AUDsx. Average marginal effects were estimated to explore the buffering effect of social support on the association between family history and AUDsx., Results: Family history was positively associated with AUDsx (incidence rate ratio (IRR) = 1.46, 95% CI = 1.39-1.54) and social support was negatively associated with AUDsx (IRR = 0.80, 95% CI = 0.74-0.86). The marginal effects of family history decreased at higher levels of social support, indicating a buffering influence of social support on the association between family history and AUDsx., Conclusions: Results reveal a buffering effect of social support, where greater levels of social support reduce the association between family history and AUDsx. These results indicate that the social context, and social support specifically, may be important for diminishing the risk of AUDsx., (© The Author(s) 2022. Medical Council on Alcohol and Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study uses Bayesian simulations to estimate the probability that published criminological research findings are wrong. Toward this end, we employ two equations originally popularized in John P.A. Ioannidis' (in)famous article, "Why Most Published Research Findings are False." Values for relevant parameters were determined using recent estimates for the field's average level of statistical power, level of research bias, level of factionalization, and quality of theory. According to our simulations, there is a very high probability that most published criminological research findings are false-positives, and therefore wrong. Further, we demonstrate that the primary factor contributing to this problem is the poor quality of theory. Stated differently, even when the overall level of research bias is extremely low and overall statistical power is extremely high, we find that poor theory still results in a high rate of false positives. We conclude with suggestions for improving the validity of criminological research claims., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Developmental perspectives recognize the importance of the development of impulsivity and sensation seeking for later life educational attainment. The current study examines the effect of developmental trajectories of impulsivity and sensation seeking across adolescence and into young adulthood on educational attainment in adulthood. The study sample consists of N = 5529 youth from a population-based sample from the United States (48.96% female; 46.95% Black or Hispanic). Latent growth curve models are used to examine associations between within-individual changes in impulsivity and sensation seeking and educational attainment. The findings point to the existence of multiple forms of risk taking during different developmental stages, with some offering a positive long-term effect on overall educational attainment., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Safe and effective vaccines are needed to end the COVID-19 pandemic. Here, we report the preclinical development of a lipid nanoparticle–formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern, including the Alpha, Beta, Gamma, and Delta lineages. No adverse effects were induced by PTX-COVID19-B in either mice or hamsters. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 2 clinical trial ongoing.

Experiencing severe and enduring adversity in childhood without the support of adult figures has been linked to an extensive list of physical health outcomes. This finding is closely tied to the concept of toxic stress, which is regularly studied using a combination of sources, including childhood adversity, unmet basic needs, and unmet social needs. Despite these findings, previous work has typically compiled various sources associated with toxic stress into a single construct, limiting existing knowledge on the contribution of each individual source to physical health. To address these concerns, the current study utilizes data from the National Longitudinal Study of Adolescent to Adult Health to examine the association between independent and collective sources of toxic stress in childhood and individual differences in biomarkers tapping cardiometabolic functioning in emerging adulthood. Results indicate a significant association between a composite measure of sources of toxic stress and cardiometabolic risk, with subsequent models examining the independent influence of each source revealing that this association was largely driven by childhood adversity and unmet basic needs, but not unmet social needs. These findings suggest that the individual sources of toxic stress may differentially contribute to physical health outcomes., Competing Interests: Conflict of InterestOn behalf of all authors, the corresponding author states that there is no conflict of interest. The authors did not receive support from any organization for the submitted work. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022.)

Nontyphoidal Salmonella bacteria are the causative agent of salmonellosis, which accounts for the majority of foodborne illness of bacterial etiology in humans. Here, we demonstrate the safety and efficacy of the prophylactic administration of a bacteriophage preparation termed FOP (foodborne outbreak pill), which contains lytic phages targeting Salmonella (SalmoFresh phage cocktail), Shiga toxin-producing Escherichia coli (STEC), and Listeria monocytogenes, for lowering Salmonella burdens in OMM 12 gnotobiotic mice. Prophylactic administration of FOP significantly reduced the levels of Salmonella in feces and in intestinal sections compared to the levels in controls. Moreover, the overall symptoms of the disease were also considerably lessened. Dose-dependent administration of FOP showed that phage amplification reached similarly high levels in less than 48 h independent of dose. In addition, 16S rRNA gene analysis showed that FOP did not alter the intestinal microbiota of healthy OMM 12 mice and reduced microbiota perturbations induced by Salmonella . FOP maintained its full potency against Salmonella in comparison to that of SalmoFresh, its Salmonella -targeting component phages alone. Altogether, the data support that preventive administration of FOP may offer a safe and effective approach for reducing the risk of foodborne infections caused by Salmonella and, potentially, other foodborne bacteria (namely, STEC and L. monocytogenes) targeted by the FOP preparation. IMPORTANCE Foodborne bacterial infections cause worldwide economic loss. During an epidemic, the use of antibiotics to slow down the spread of the disease is not recommended because of their side effects on the resident microbiota and the selection of antibiotic-resistant bacteria. Here, we investigated the potential for the prophylactic administration of bacteriophages (viruses infecting bacteria) to reduce the burden of Salmonella in vivo using mice colonized by a synthetic microbiota. We found that the repeated administration of bacteriophages was safe and efficient in lowering the Salmonella burden. Perturbations of the microbiota by the Salmonella infection were also reduced when mice received bacteriophages. Altogether, these data support the use of bacteriophages as a prophylactic intervention to lower the spread of foodborne epidemics.

The social structure and social learning (SSSL) model for crime and deviance has received an impressive amount of empirical support in the United States and other Western industrialized countries. Comparatively, less research, however, has examined whether the SSSL model offers a viable framework for explaining variation in delinquent behavior in other geographic contexts, particularly, countries that place a stronger emphasis on social control stemming from both formal and religious sources. The current study addresses this void in the literature by examining a sample of youth from Saudi Arabia, a Middle Eastern country that enforces Sharia (a set of laws based in Islamic tradition) and strict gender roles. The association between neighborhood exposure to violence and risk for violent and nonviolent delinquent behavior was examined using structural equation models. Subsequent models were aimed at more closely examining the mediating role of delinquent peer association between neighborhood exposure to violence and violent and nonviolent delinquent behavior. Results indicate that males exposed to neighborhood violence are more likely to engage in violent and nonviolent delinquent behavior, whereas females are more likely to engage in violent, but not nonviolent, delinquent behavior. In line with the SSSL model, delinquent peer association fully mediates the direct effect of neighborhood exposure to violence on delinquent behavior in both males and females. Findings from the current study suggest that the SSSL model may provide a useful framework for explaining individual differences in delinquent behavior in Saudi Arabia.

A major challenge for HIV vaccine development is to raise anti-envelope antibodies capable of recognizing and neutralizing diverse strains of HIV-1. Accordingly, a full length single chain (FLSC) of gp120-CD4 chimeric vaccine construct was designed to present a highly conserved CD4-induced (CD4i) HIV-1 envelope structure that elicits cross-reactive anti-envelope humoral responses and protective immunity in animal models of HIV infection. IHV01 is the FLSC formulated in aluminum phosphate adjuvant. We enrolled 65 healthy adult volunteers in this first-in-human phase 1a randomized, double-blind, placebo-controlled study with three dose-escalating cohorts (75 µg, 150 µg, and 300 µg doses). Intramuscular injections were given on weeks 0, 4, 8, and 24. Participants were followed for an additional 24 weeks after the last immunization. The overall incidence of adverse events (AEs) was not significantly different between vaccinees and controls. The majority (89%) of vaccine-related AE were mild. The most common vaccine-related adverse event was injection site pain. There were no vaccine-related serious AE, discontinuation due to AE, intercurrent HIV infection, or significant decreases in CD4 count. By the final vaccination, all vaccine recipients developed antibodies against IHV01 and demonstrated anti-CD4i epitope antibodies. The elicited antibodies reacted with CD4 non-liganded Env antigens from diverse HIV-1 strains. Antibody-dependent cell-mediated cytotoxicity against heterologous infected cells or gp120 bound to CD4+ cells was evident in all cohorts as were anti-gp120 T-cell responses. IHV01 vaccine was safe, well tolerated, and immunogenic at all doses tested. The vaccine raised broadly reactive humoral responses against conserved CD4i epitopes on gp120 that mediates antiviral functions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Although adverse childhood experiences (ACEs) have negative effects on subsequent wellbeing, questions remain regarding how and why they do so. Sex, environmental effects, and genetic influences may play a role in both one's exposure to ACEs as well as one's reactions to ACEs., Objective: To understand the combined genetic and environmental influences on males' and females' exposure and reactions to ACEs, and to determine whether sex differences in offending and depressive symptoms were partially impacted by genetic influences., Methods: We employed a sample of monozygotic twins (n = 217 pairs), same-sex dizygotic twins (n = 185 pairs), and same-sex full siblings (n = 446 pairs) from the National Longitudinal Study of Adolescent to Adult Health (N = 848 pairs) and estimated a series of multivariable biometric models. Participants were aged between 12 and 21 during Wave I, between 13 and 22 at Wave II, between 18 and 26 at Wave III, and 24 and 32 at Wave IV., Results: First, there appears to be a stronger genetic influence on ACEs exposure among males than females. Second, genetic influences were stronger on offending among males and depression among females. Third, ACEs moderate the genetic influences on offending and depressive symptomology among males and females: among males, genetic influences on offending decreased as exposure to ACEs increased, while among females, genetic influences on depressive symptoms decreased as exposure to ACEs increased., Conclusions: Systematic sex differences in the exposure and reactions to ACEs are at least partially due to genetic differences. Exposure to ACEs is partially influenced by genetics among males, but not females, and the more male and females' experience ACEs, the less influence genes have on their offending and depressive symptomology, respectively., (Published by Elsevier Ltd.)

The coronavirus disease 2019 (COVID-19) pandemic has infected millions of individuals and posed unprecedented challenges to health care systems. Acute care hospitals have been forced to expand hospital and intensive care capacity and deal with shortages in personal protective equipment. This guide will review 2 areas where the anesthesiologists will be caring for COVID-19 patients: the operating room and on airway teams. General principles for COVID-19 preparation and hospital procedures will be reviewed to serve as a resource for anesthesia departments to manage COVID-19 or future pandemics., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 International Anesthesia Research Society.)

Background: Existing research using nationally representative samples has provided valuable information regarding the prevalence and context of childhood adversity, but Native American persons have largely been absent from these studies., Objective: We examined adverse childhood experiences (ACEs) among persons identifying as White, Black, Asian, Hispanic, and Native American in the NESARC, a longitudinal study (Wave 1: 2001-2002; Wave 2: 2004-2005) using a nationally representative sample from the United States., Methods: Means tests and negative binomial regression were used to examine the prevalence and variety of ACEs across racial/ethnic groups and race/ethnicity-sex dyads., Results: Native American persons reported the greatest average number and variety of ACEs than persons from any other racial/ethnic group, and reported the highest rates of physical abuse, sexual abuse, parental substance abuse, and witnessing violence than members of any other racial/ethnic category. Native American females reported the greatest rates of emotional abuse, while Native American males reported the greatest rates of physical neglect; the highest rates of parental substance use among the race/ethnicity-sex dyads were reported by both Native American females and males. Significantly higher rates of sexual violence were reported by Native American females compared to other groups; almost 1 in 4 Native American females reported sexual violence., Conclusions: Future research should make a concerted effort to broaden examinations of ACEs to include Native American respondents and to include measures of historical trauma and racial discrimination. Broader support for system change as well as increased development and use of culturally responsive prevention and intervention programming is likely necessary to reduce ACEs among Native American persons., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Testing milk for antibiotics before acceptance into dairies is required by the U.S. Pasteurized Milk Ordinance. Technological advances in tests have reduced screening times and improved detection accuracy. This work describes the validation of the Charm Rapid One Step Assay Beta-Lactam 30 Second Test according to the U.S. Food and Drug Administration Center for Veterinary Medicine protocol for raw commingled milk. Milk is added to the lateral flow test strip in an incubator/reader to deliver a 30 second result. Independent laboratory validation followed sensitivity, interference, and incurred residue protocols. Sensitivity, in parts per billion (ppb = µg/kg), using a probit curve determined 90% percent detection with 95% confidence, which met National Conference of Interstate Milk Shipments (NCIMS) specifications. Six U.S. approved beta-lactam drugs were detected below, but within 50% of, target/tolerance levels for penicillin G 2.9 ppb, ampicillin 5.9 ppb, amoxicillin 5.8 ppb, cephapirin 13 ppb, cloxacillin 8.1 ppb, and ceftiofur metabolites 73 ppb. No interferences were observed from 33 animal drugs at 100 ppb, somatic cells at 1.2 million/mL, or bacterial levels of >300 000 CFU/mL. Incurred residue detection levels were similar to levels determined with the spiked parent compound. The data support NCIMS that the BL30SEC method met U.S. criteria for testing milk for beta-lactams., (© AOAC INTERNATIONAL 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A qualitative 3 min one-step assay for detecting beta-lactam, sulfonamide, and tetracycline antibiotics was validated following milk screening test guidelines developed by FDA-CVM, AOAC-RI, and IDF. The validated 90% detection levels with 95% confidence were: penicillin G 2 part per billion (ppb); amoxicillin 4 ppb; ampicillin 9 ppb; ceftiofur plus metabolites 50 ppb; cloxacillin 9 ppb; cephapirin 15 ppb; sulfadimethoxine 8 ppb; sulfamethazine 9 ppb; chlortetracycline 34 ppb; oxytetracycline 53 ppb; and tetracycline 42 ppb. Detection levels were lower than U.S. and Canadian allowable limits for milk and were consistent with most European Maximum Residue Limits. Tests of raw commingled cows' milk indicated a low positive error rate of <0.3% with no interferences demonstrated by 1.08 MM/mL somatic cells, Gram-positive or Gram-negative bacteria < 300 K/mL, freeze/thawing, or non-targeted drugs. Detection of incurred residues were similar to, or more sensitive to, fortified samples. Some cross reactivity across drug families occurred in interference studies and therefore initial positive samples should be confirmed with drug family specific screening methods. The National Conference of Interstate Milk Shipments approval as a bulk tank/tanker screening test was completed in three stages for each drug family, including a tetracycline confirmation procedure to target U.S. tolerance levels. Detection and robustness were found to be appropriate for multiple countries' regulatory requirements for screening tests. The method development, validation, and approval was intended to diversify and increase the verification tools for the control of the major antibiotic drug families used in managing cows' health and welfare., (© AOAC INTERNATIONAL 2020.)

Objective: Rats are an early preclinical model for cartilage tissue engineering, and a practical species for investigating the effects of aging. However, rats may be a poor aging model for mesenchymal stem cells (MSCs) based on laboratory reports of a severe decline in chondrogenesis beyond young adulthood. Such testing has not been conducted with MSCs seeded in a scaffold, which can improve the propensity of MSCs to undergo chondrogenesis. Therefore, the objective of this study was to evaluate chondrogenesis of middle-aged rat MSCs encapsulated in agarose., Design: MSCs from 14- to 15-month-old rats were expanded, seeded into agarose, and cultured in chondrogenic medium with or without 5% serum for 15 days. Samples were evaluated for cell viability and cartilaginous extracellular matrix (ECM) accumulation. Experiments were repeated using MSCs from 6-week-old rats., Results: During expansion, middle-aged rat MSCs demonstrated a diminishing proliferation rate that was improved ~2-fold in part by transient exposure to chondrogenic medium. In agarose culture in defined medium, middle-aged rat MSCs accumulated ECM to a much greater extent than negative controls. Serum supplementation improved cell survival ~2-fold, and increased ECM accumulation ~3-fold. Histological analysis indicated that defined medium supported chondrogenesis in a subset of cells, while serum-supplementation increased the frequency of chondrogenic cells. In contrast, young rat MSCs experienced robust chondrogenesis in defined medium that was not improved with serum-supplementation., Conclusions: These data demonstrate a previously-unreported propensity of middle-aged rat MSCs to undergo chondrogenesis, and the potential of serum to enhance chondrogenesis of aging MSCs.

An extensive body of research has examined the role that genetic influences play in the development of antisocial behavior. Even so, there remains much that is unknown regarding the intersections among antisocial behavior, environments, and genetic influences. The current study is designed to shed some light on this issue by examining whether gene-environment correlations are present in the lives of adopted adolescents. More specifically, this article seeks to contribute to scholarship efforts aimed at understanding whether biological parents' antisocial behavioral phenotypes-behaviors often attributed to an increased likelihood of receiving a genetic propensity for antisocial behaviors-predict variation in environments that are experienced by their adopted-away offspring. To do so, the biological parents of adoptees were assessed and used to identify ways in which children elicit certain responses from their adoptive parents based, in part, on their genotype. Correlational analyses were calculated on a sample of adoptees (the final analytic sample ranged between n = 229 and n = 293) drawn from the National Longitudinal Study of Adolescent to Adult Health (Add Health). The results of the study revealed very little evidence of gene-environment correlations. The implications of these findings are considered.

Recidivism remains a serious issue in the modern criminal justice system, with over 80% of those previously incarcerated being rearrested within 9 years of release (Alper, Durose, & Markman, 2018). Although previous studies have identified risk factors that increase the probability of rearrest, much remains unknown regarding the full constellation of risk factors. One potential risk factor that has received limited attention is intelligence, as individuals with lower IQ scores have been found to be more likely to come into initial contact with the criminal justice system. Collectively, previous studies have provided preliminary evidence of intelligence as a risk factor for rearrest but have not fully explored this association. More specifically, it remains unclear whether the association between IQ and recidivism persists after controlling for time-invariant, individual-specific sources of variance in criminal behavior. The current study aimed to address this limitation and more closely examine the longitudinal association between IQ and rearrest with data from the Pathways to Desistance Study (N = 1,331 individuals). To distinguish variance in intelligence from time-stable, individual-specific variance in criminality, we estimated a latent trait-state-occasion model. A subsequent series of survival models, which included the previously estimated measure of criminality as a covariate, revealed a small and negative association between IQ and rearrest (hazard ratio = .95; 95% confidence interval [.92; .98]), suggesting that IQ may play only a minor role in recidivism. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background: Vulvovaginal candidiasis is commonly diagnosed and has been associated in prospective studies with the acquisition of HIV. Little data is available on how the composition of the vaginal microbiota, and other risk factors, are associated with the molecular detection of Candida albicans-a common cause of vulvovaginal candidiasis., Methods: In a cross-sectional study, self-collected vaginal swabs were obtained from 394 nonpregnant, reproductive-age women. C. albicans was detected using polymerase chain reaction targeting C. albicans ITS1/2 region. Vaginal microbiota was characterized by 16S rRNA gene amplicon sequencing of the V3 to V4 hypervariable regions and clustered into community state types (CSTs). Multiple logistic regression identified factors associated with C. albicans detection., Results: Twenty-one percent had C. albicans detected and 46% reported vaginal symptoms in the prior 60 days. There was a 2-fold increase in the odds of C. albicans if a woman was in a L. crispatus-dominated CST compared to CSTs with low-Lactobacillus levels (adjusted odds ratio, 2.05; 95% confidence interval, 0.97-4.37). History of self-treatment with antifungals, L. crispatus relative abundance, and receptive oral sex were also significantly associated with C. albicans detection., Conclusions: A L. crispatus-dominated vaginal microbiota is thought to protect women from both development of bacterial vaginosis and incidence of sexually transmitted infections; however, our data suggest that L. crispatus is associated with increased C. albicans detection. Receptive oral sex may also be a risk factor for vaginal C. albicans colonization.

Previous research has indicated that genetic and environmental factors shape physiological activity. Cortisol levels, in particular, have received significant attention, with studies indicating substantive heritability estimates across various sampling techniques. A related line of research has indicated that genetic and environmental factors that explain variability in cortisol levels may vary across context and experiences by way of gene-environment interactions (G × Es). Despite these findings, a limited number of studies have examined the extent to which interpersonal relationships may operate as a moderator. The current study focused on co-twin relationship quality as a source of moderation, as twins are more likely to have contact with one another and to form close, interpersonal relationships with their co-twin relative to singleton siblings. Using a sample of 298 adult twins from the National Survey of Midlife Development in the United States (MIDUS), we examined the extent to which genetic and environmental factors that explain variability in urinary cortisol levels varied across levels of co-twin relationship quality. The heritability of cortisol levels was greater and nonshared environmental influences were lower at greater levels of relationship quality. These findings suggest that the heritability of cortisol may vary across context, and positive relationships with others may moderate such factors., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Biocompatible gold nanoparticles designed to absorb light at wavelengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance-ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function., Competing Interests: Conflict of interest statement: A.R.R. is the national principal investigator for the multiinstitutional trial of GSN-directed ablation, funded by Nanospectra Biosciences. He is also a consultant for Nanospectra Biosciences. J.L.W. and N.J.H. cofounded Nanospectra Biosciences in 2001 to transfer the photothermal therapeutics process from their labs into the clinic. They both have a small equity stake in this company but are not involved in any way with the company’s business or strategic decisions., (Copyright © 2019 the Author(s). Published by PNAS.)

Recently, research focusing on the implications of brain injuries for deleterious outcomes spanning a wide range of developmental domains has flourished. Findings from this literature suggest that brain injury is a potent source of risk for negative outcomes including neurodegenerative diseases, cognitive impairment, behavioral problems, and psychiatric diagnoses. Despite this evidence, few studies have examined the extent to which these findings represent a causal relationship. This review outlines the expansive literature in this developing area and provides a discussion of potential threats to internal validity. Finally, suggestions for future research are provided with a particular emphasis on leveraging existing findings to better understand the role of brain injury in the development of deleterious outcomes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Characterizing the antigen-binding and innate immune-recruiting properties of the humoral response offers the chance to obtain deeper insights into mechanisms of protection than revealed by measuring only overall antibody titer. Here, a high-throughput, multiplexed Fab-Fc Array was employed to profile rhesus macaques vaccinated with a gp120-CD4 fusion protein in combination with different genetically encoded adjuvants, and subsequently subjected to multiple heterologous simian immunodeficiency virus (SIV) challenges. Systems analyses modeling protection and adjuvant differences using Fab-Fc Array measurements revealed a set of correlates yielding strong and robust predictive performance, while models based on measurements of response magnitude alone exhibited significantly inferior performance. At the same time, rendering Fab-Fc measurements mathematically independent of titer had relatively little impact on predictive performance. Similar analyses for a distinct SIV vaccine study also showed that Fab-Fc measurements performed significantly better than titer. These results suggest that predictive modeling with measurements of antibody properties can provide detailed correlates with robust predictive power, suggest directions for vaccine improvement, and potentially enable discovery of mechanistic associations., (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)

Elysia chlorotica, a sacoglossan sea slug found off the East Coast of the United States, is well-known for its ability to sequester chloroplasts from its algal prey and survive by photosynthesis for up to 12 months in the absence of food supply. Here we present a draft genome assembly of E. chlorotica that was generated using a hybrid assembly strategy with Illumina short reads and PacBio long reads. The genome assembly comprised 9,989 scaffolds, with a total length of 557 Mb and a scaffold N50 of 442 kb. BUSCO assessment indicated that 93.3% of the expected metazoan genes were completely present in the genome assembly. Annotation of the E. chlorotica genome assembly identified 176 Mb (32.6%) of repetitive sequences and a total of 24,980 protein-coding genes. We anticipate that the annotated draft genome assembly of the E. chlorotica sea slug will promote the investigation of sacoglossan genetics, evolution, and particularly, the genetic signatures accounting for the long-term functioning of algal chloroplasts in an animal.

Background: Adverse childhood experiences (ACEs) are a potent risk factor. Despite these findings, studies have also recognized the importance of considering additional sources of genetic and environmental influence that cluster within families., Objective: To properly control for latent sources of genetic and within-family environmental influences and isolate the association between ACEs and the following outcomes in adulthood: physical health, depressive symptoms, educational attainment, income attainment, alcohol problems, and antisocial behavior., Participants and Setting: Two independent samples of twins and siblings from the United States: the Midlife Development in the United States (MIDUS) study (N = 862) and the National Longitudinal Study of Adolescent to Adult Health (Add Health; N = 3112)., Methods: Sibling comparison models, which control for latent sources of genetic and within-family environmental influences, were estimated to examine whether differential exposure to ACEs was associated with the examined outcomes., Results: Families that experienced more adversity also experienced more deleterious outcomes. However, siblings that experienced more adversity were no more likely to experience deleterious outcomes than their co-siblings. However, greater exposure to ACEs was associated with increases in depressive symptoms (Add Health). Additional models revealed that the similarity between siblings from the same family stemmed from latent sources of within-family environmental influences not captured by traditional ACEs measures., Conclusions: Considering genetic influences and additional latent sources of within-family influences is crucial in isolating the effects of ACEs. Currently employed ACEs measures may not adequately capture the full range of impactful sources of family-level environmental influence., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective To establish whether a novel biomaterial scaffold with tunable degradation profile will aid in cartilage repair of chondral defects versus microfracture alone in vitro and in a rat model in vivo. Design In vitro-Short- and long-term degradation scaffolds were seeded with culture expanded articular chondrocytes or bone marrow mesenchymal stem cells. Cell growth and differentiation were evaluated with cell morphological studies and gene expression studies. In vivo-A microfracture rat model was used in this study to evaluate the repair of cartilage and subchondral bone with the contralateral knee serving as the empty control. The treatment groups include (1) empty osteochondral defect, (2) polycaprolactone copolymer-based polyester polyurethane-urea (PSPU-U) caffold short-term degradative profile, and (3) PSPU-U scaffold long-term degradative profile. After placement of the scaffold, the rats were then allowed unrestricted activity as tolerated, and histological analyses were performed at 4, 8, and 16 weeks. The cartilage defect was measured and compared with the contralateral control side. Results In vitro-Long-term scaffolds showed statistically significant higher levels of aggrecan and type II collagen expression compared with short-term scaffolds. In vivo-Within 16 weeks postimplantation, there was new subchondral bone formation in both scaffolds. Short-term scaffolds had a statistically significant increase in defect filling and better qualitative histologic fill compared to control. Conclusions The PSPU short-term degradation scaffold may aid in cartilage repair by ultimately incorporating the scaffold into the microfracture procedure.

The lithium vapor box divertor is a concept for handling the extreme divertor heat fluxes in magnetic fusion devices. In a baffled slot divertor, plasma interacts with a dense cloud of Li vapor which radiates and cools the plasma, leading to recombination and detachment. Before testing on a tokamak, the concept should be validated: we plan to study detachment and heat redistribution by a Li vapor cloud in laboratory experiments. Mass changes and temperatures are measured to validate a direct simulation Monte Carlo model of neutral Li. The initial experiment involves a 5 cm diameter steel box containing 10 g of Li held at 650 °C as vapor flows out a wide nozzle into a similarly sized box at a lower temperature. Diagnosis is made challenging by the required material compatibility with lithium vapor. Vapor pressure is a steep function of temperature, so to validate mass flow models to within 10%, absolute temperature to within 4.5 K is required. The apparatus is designed to be used with an analytical balance to determine mass transport. Details of the apparatus and methods of temperature and mass flow measurements are presented.

Human immunodeficiency virus type 1 (HIV-1) infection often arises from a single transmitted/founder (TF) viral variant among a large pool of viruses in the quasispecies in the transmitting partner. TF variants are typically nondominant in blood and genital secretions, indicating that they have unique traits. The plasmacytoid dendritic cell (pDC) is the primary alpha interferon (IFN-α)-producing cell in response to viral infections and is rapidly recruited to the female genital tract upon exposure to HIV-1. The impact of pDCs on transmission is unknown. We investigated whether evasion of pDC responses is a trait of TF viruses. pDCs from healthy donors were stimulated in vitro with a panel of 20 HIV-1 variants, consisting of one TF variant and three nontransmitted (NT) variants each from five transmission-linked donor pairs, and secretion of IFN-α and tumor necrosis factor alpha (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA). No significant differences in cytokine secretion in response to TF and NT viruses were observed, despite a trend toward enhanced IFN-α and TNF-α production in response to TF viruses. NT viruses demonstrated polarization toward production of either IFN-α or TNF-α, indicating possible dysregulation. Also, for NT viruses, IFN-α secretion was associated with increased resistance of the virus to inactivation by IFN-α in vitro , suggesting in vivo evolution. Thus, TF viruses do not appear to preferentially subvert pDC activation compared to that with nontransmitted HIV-1 variants. pDCs may, however, contribute to the in vivo evolution of HIV-1. IMPORTANCE The plasmacytoid dendritic cell (pDC) is the first cell type recruited to the site of HIV-1 exposure; however, its contribution to the viral bottleneck in HIV-1 transmission has not been explored previously. We hypothesized that transmitted/founder viruses are able to avoid the pDC response. In this study, we used previously established donor pair-linked transmitted/founder and nontransmitted (or chronic) variants of HIV-1 to stimulate pDCs. Transmitted/founder HIV-1, instead of suppressing pDC responses, induced IFN-α and TNF-α secretion to levels comparable to those induced by viruses from the transmitting partner. We noted several unique traits of chronic viruses, including polarization between IFN-α and TNF-α production as well as a strong relationship between IFN-α secretion and the resistance of the virus to neutralization. These data rule out the possibility that TF viruses preferentially suppress pDCs in comparison to the pDC response to nontransmitted HIV variants. pDCs may, however, be important drivers of viral evolution in vivo ., (Copyright © 2018 American Society for Microbiology.)

Early exposure to multiple risk factors has been shown to predict criminal offending, but the mechanisms responsible for this association are poorly understood. Integrating social-environmental and dispositional theories of crime this research investigated the capacity of family socioeconomic disadvantage and individual psychological deficits to mediate the association between childhood cumulative risk and late adolescent criminal convictions. Male participants in the 1986 Northern Finland Birth Cohort Study (n = 3414) were followed from the prenatal period through age 19-20. The data were analyzed by estimating a structural equation model of the hypothesized pathways. The results found support for both processes of influence, and the model sustained a statistically significant direct effect of cumulative risk on crime. Socioeconomic disadvantage and psychological deficits contribute to criminal offending independently and with roughly equal magnitude. The results point to the utility of both environmental and psychological interventions to prevent criminality among children at risk., (Copyright © 2018. Published by Elsevier Ltd.)