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Hypertension is prevalent in the population at large and among hospitalized patients. Little has been reported regarding the attitudes and patterns of care of physicians managing nonemergent elevated blood pressure (BP) among inpatients. Resident physicians in internal medicine (IM), family medicine (FM), and surgery were surveyed regarding inpatient BP management. One hundred eighty-one questionnaires were completed across 3 sites. Respondents generally considered inpatient BP control a high priority. A majority of IM and FM residents indicated following the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) consensus guidelines for inpatients compared to 20% of surgery residents (P<.001). While trainees did not appear to strictly follow JNC 7 guidelines for goal BP of 140/90 mm Hg, they did report making frequent BP medication changes (∼51% reported changing regimens for >50% of hypertensive patients). Overall ∼90% indicated that discharging a hypertensive patient on a drug regimen established during hospitalization is preferable to reverting to the regimen in place at the time of admission. Resident physicians regard elevated BP inpatient management as important, but attitudes and practice vary between specialties. JNC 7 guidelines may not be appropriate for inpatient use. Future research should focus on developing functional diagnostic criteria for hypertension in the inpatient setting and determining best practices inpatient BP management. [ABSTRACT FROM AUTHOR]

The introduction of evidence-based practice (EBP) and the hierarchical approach to evidence it engenders within research and evaluation has aroused controversy in the mental health professions. The aim of this paper is to present a critique of EBP with a specific relationship to mental health nursing. It will be argued that in its current form, EBP presents a potential impediment to the facilitation of consumer participation in mental health services and to the recovery model. The need for the consumer voice and the importance of the lived experience of mental illness are not readily reconciled with a strong scientific paradigm that promotes detachment and objectivity. The importance of evidence in contemporary mental health care will also be acknowledged and discussed in light of the current climate of increased consumer knowledge, fiscal constraint, and extensive social criticism of mental health-care services. The current approach to EBP requires reconstruction to support the consumer-focused nature of mental health nursing, and to facilitate the implementation of a recovery model for mental health care. [ABSTRACT FROM AUTHOR]

Purpose: Gemcitabine, a pyrimidine nucleoside, is approved for the treatment of non-small cell lung cancer, pancreatic carcinoma, and breast cancer. Chemotherapy regimens are determined experimentally with static tissue culture systems, animal models, and in Phase I clinical trials. The aim of this study was to assess for gemcitabine-induced cell death following infusion of drug under clinically-relevant conditions of infusion rate and drug exposure in an in vitro bioreactor system.Methods: To estimate an appropriate harvest time for cells from the bioreactor after drug treatment, we estimated the temporal relationship between gemcitabine treatment for 1 h and cell death at a later time point with monolayer growth assays (i.e., static culture). Afterward, 5.3 mg gemcitabine was infused over 0.5 h in the bioreactor, followed by mono-exponential decay, simulating patient concentration-time profiles (n = 4). Controls were run with drug-free media (n = 4). Cells were harvested from the bioreactor at a later time point and assessed for cell death by flow cytometry.Results: According to monolayer growth assay results, cytotoxicity became more apparent with increasing time. The E Max for cells 48 h after treatment was 50% and after 144 h, 93% (P = 0.022; t test), while flow cytometry showed complete DNA degradation by 120 h. Gemcitabine was infused in the bioreactor. The gemcitabine area under the concentration-time curve (AUC) was 56.4 microM h and the maximum concentration was 87.5 +/- 2.65 microM. Flow cytometry results were as follows: the G1 fraction decreased from 65.1 +/- 4.91 to 28.6 +/- 12% (P = 0.005) and subG1 increased from 14.1 +/- 5.28 to 42.6 +/- 9.78% (P = 0.004) relative to control. An increase in apoptotic cells was observed by TUNEL assay.Conclusions: The in vitro bioreactor system will be expanded to test additional cell lines, and will serve as a useful model system for assessing the role of drug pharmacokinetics in delivery of optimized anticancer treatment. [ABSTRACT FROM AUTHOR]

Deterioration of verbal abilities is among the most debilitating consequences of Alzheimer's disease (AD). Recent research suggests that the common responses of conversational partners may contribute to excess verbal deficits in persons with AD in that they function to punish verbal behavior. The purpose of this study was to systematically evaluate two types of listener repair responses, indirect and direct repairs, on the conversational speech of older adults with AD. In an indirect repair, the listener paraphrases the speech of the person with AD. In a direct repair response, the listener interjects with corrective feedback. Three men diagnosed with AD participated in this study. A female confederate was trained in indirect and direct repair responses. An ABAC single subject design was used to evaluate the effects of listener repair responses on the amount, duration, and fluency of the speech of the participants during videotaped conversations with the confederate. The results indicate that the confederate's responses significantly impacted the conversational speech of older adults with AD. Indirect repair responses by the confederate were associated with higher levels of coherent speech for all participants compared to the direct repair and baseline conditions. The results indicate that indirect repair responses may decrease the risk of excess verbal deficits in persons with AD by functioning to reinforce (i.e., increase) speech. The findings have implications for the training of caregivers of persons with AD. Training caregivers in responses that reinforce rather than punish verbal behaviormay prevent or reduce excess disability thereby improving the quality of life for persons with AD and their caregivers. [ABSTRACT FROM AUTHOR]

Background: Fosamax (alendronate sodium, Merck & Co., Inc., Whitehouse Station, NJ, USA) is an effective oral bisphosphonate widely used to treat and prevent osteoporosis, with a safety and tolerability profile similar to placebo in clinical trials. It has been evaluated in clinical trials with over 20,000 participants and up to 10 years duration. Oral bisphosphonates have been associated with esophagitis, which involves events that occur prior to absorption and depends on factors such as the frequency of administration, dose, and formulation. Data on non- Fosamax alendronate (NFA) preparations, which contain a form of alendronate with differing excipients, are typically derived from small, single-dose, bioavailability studies. While these studies provide information on systemic effects, they do not address the risk of local esophageal irritation and may, therefore, inadequately characterize safety profiles.Objective: To compare the esophageal irritation potential of NFA preparations to that of the innovator medication, Fosamax.Methods: Two preclinical models of irritation were used. In the first, 24 rabbits were randomized to a single, subcutaneous injection of saline, 10.6 mg of Fosamax in saline, or 10.6 mg NFA in saline. Blinded measurements of skin thickness (a measure of inflammation), wet weight, and histopathology of injection site tissues were performed. In the second study, 16 dogs were anesthetized and a placebo tablet, a 10-mg Fosamax tablet, or a 10-mg NFA tablet was placed by endoscopy in the caudal third of the esophagus for 1 hour, followed by a saline rinse, daily for 5 days. After the final dose, the dogs were sacrificed and esophageal morphology was examined.Results: In the rabbit injection study, the NFA suspension elicited a significantly greater irritant response than an equivalent suspension of Fosamax. The mean wet weight increase at injection site tissues was 70% greater (P < 0.01) for NFA than Fosamax. Fosamax treatment induced smaller, predominantly foreign-body granuloma type lesions, while NFA induced larger, encapsulated cystic lesions containing the injected material, consistent with a post-inflammatory process. In the esophagus study, all 4 dogs (100%) treated with NFA for 5 days exhibited marked ulcerative esophagitis, whereas only 1 of the 5 dogs treated with Fosamax (20%) had marked ulceration; the remaining 4 dogs had more moderate esophageal changes than those observed in dogs treated with NFA.Conclusions: Generic drugs are expected to have similar efficacy and safety to innovator drugs; however, the greater irritant responses of NFA in rabbits and dogs suggest that important differences may exist between the effects of Fosamax and NFA preparations in the clinical setting. These findings, along with other data demonstrating differences in the disintegration/dissolution profiles of NFA preparations relative to Fosamax, suggest that bioavailability studies may not be adequate for meaningful assessment of the safety and efficacy of NFA or other bisphosphonate preparations. [ABSTRACT FROM AUTHOR]

Health-care students are frequently concerned and anxious about entering the mental health setting for their clinical placement. There are many situations in mental health clinical settings in which the student will witness or become involved in incidents that may challenge existing values, attitudes, ethics and provoke strong emotions in the student. This paper examines clinical critical incidents that have been identified and reflected on by a cohort of second-year student nurses while undertaking their mental health clinical practicum. Data were gathered from 260 critical incident reports and was sorted into three broad categories: (i) student description of incident; (ii) immediate emotional response of the student to the incident; and (iii) student thoughts and feelings' about the incident after the opportunity for structured reflection. The findings demonstrate a wide range of positive, but predominantly, negative experiences. Witnessing psychotic behaviour and incidents involving both actual and threatened violence and verbal abuse dominated the critical incidents with 52% describing one or both of these issues. To illustrate the range of student-identified critical incidents, verbatim examples of student work are included. [ABSTRACT FROM AUTHOR]

Abstract Background The prevalence of obesity among preschool-aged children has increased, especially among those in low-income households. Two promising behavioral targets for preventing obesity include limiting children’s portion sizes and their intake of foods high in solid fats and/or added sugars, but these approaches have not been studied in low-income preschoolers in the home setting. The purpose of this study was to understand the contextual factors that might influence how low-income mothers felt about addressing these behavioral targets and mothers’ aspirations in feeding their children. Methods We recruited 32 English-speaking women in Philadelphia, Pennsylvania who were eligible for the Supplemental Nutrition Assistance Program and who were the biologic mothers of children 36 to 66 months of age. Each mother participated in 1 of 7 focus groups and completed a brief socio-demographic questionnaire. Focus group questions centered on eating occasions, foods and drinks consumed in the home, and portion sizes. Each focus group lasted 90 minutes and was digitally recorded and transcribed verbatim. Three authors independently identified key themes and supporting quotations. Themes were condensed and modified through discussion among all authors. Results Thirty-one mothers identified themselves as black, 15 had a high school education or less, and 22 lived with another adult. Six themes emerged, with three about aspirations mothers held in feeding their children and three about challenges to achieving these aspirations. Mothers’ aspirations were to: 1) prevent hyperactivity and tooth decay by limiting children’s sugar intake, 2) use feeding to teach their children life lessons about limit setting and structure, and 3) be responsive to children during mealtimes to guide decisions about portions. Especially around setting limits with sweets and snacks, mothers faced the challenges of: 1) being nagged by children’s food requests, 2) being undermined by other adults in the family, and 3) having bad memories from childhood that made it hard to deny children’s food requests. Conclusions Although the primary aspirations of low-income mothers in feeding their preschool-aged children were not focused on children’s weight, these aspirations were compatible with obesity prevention strategies to limit children’s portion sizes and their intake of solid fats and/or added sugars.

Abstract Background Behavioral mechanisms that contribute to the association between breastfeeding and reduced obesity risk are poorly understood. The purpose of this study was to evaluate the hypothesis that feeding human milk from the breast (direct breastfeeding) has a more optimal association with subsequent child appetite regulation behaviors and growth, when compared to bottle-feeding. Methods Children (n = 109) aged 3- to 6- years were retrospectively classified as directly breastfed (fed exclusively at the breast), bottle-fed human milk, or bottle-fed formula in the first three months of life. Young children's appetite regulation was examined by measuring three constructs (satiety response, food responsiveness, enjoyment of food) associated with obesity risk, using the Child Eating Behavior Questionnaire. Multinomial logistic regression analyses were used to test whether children bottle-fed either human milk or formula had reduced odds of high satiety and increased odds of high food responsiveness and high enjoyment of food compared to children fed directly from the breast. Current child weight status and growth trends from 6-36 months were also examined for their relation to direct breastfeeding and appetite regulation behaviors in early childhood. Results Children fed human milk in a bottle were 67% less likely to have high satiety responsiveness compared to directly breastfed children, after controlling for child age, child weight status, maternal race/ethnicity, and maternal education. There was no association of bottle-feeding (either human milk or formula) with young children's food responsiveness and enjoyment of food. There was neither an association of direct breastfeeding with current child weight status, nor was there a clear difference between directly breastfed and bottle-fed children in growth trajectories from 6- to 36-months. More rapid infant changes in weight-for-age score were associated with lower satiety responsiveness, higher food responsiveness and higher enjoyment of food in later childhood Conclusion While direct breastfeeding was not found to differentially affect growth trajectories from infancy to childhood compared to bottle-feeding, results suggest direct breastfeeding during early infancy is associated with greater appetite regulation later in childhood. A better understanding of such behavioral distinctions between direct breastfeeding and bottle-feeding may identify new pathways to reduce the pediatric obesity epidemic.

Abstract Background Although general parenting styles and restrictive parental feeding practices have been associated with children's weight status, few studies have examined the association between feeding styles and proximal outcomes such as children's food intake, especially in multi-ethnic families with limited incomes. The purpose of this study was to evaluate the association of parental feeding styles and young children's evening food intake in a multiethnic sample of families in Head Start. Methods Participants were 715 Head Start children and their parents from Texas and Alabama representing three ethnic groups: African-American (43%), Hispanic (29%), and White (28%). The Caregivers Feeding Styles Questionnaire (Hughes) was used to characterize authoritative, authoritarian (referent), indulgent or uninvolved feeding styles. Food intake in several food groups was calculated from 3 days of dietary recalls for the child for evening food intakes from 3 PM until bedtime. Results Compared to children of authoritarian parents, intakes of fruits, juice and vegetables were lowest among children of indulgent or uninvolved parents (1.77 ± 0.09 vs 1.45 ± 0.09 and 1.42 ± 0.11 cups) as were intakes of dairy foods (0.84 ± 0.05 vs 0.67 ± 0.05 and 0.63+0.06 cups), respectively. Conclusion Findings suggest that permissive parent feeding styles like indulgent or uninvolved relate negatively to children's intake of nutrient-rich foods fruit, 100% fruit juice, vegetables and dairy foods from 3 PM until bedtime.

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Background: Associations between comorbid depression and grief with suicidal ideation (SI) have been inconsistent. To identify at-risk individuals, it is important to determine the role of symptom severity by examining both continuous and clinical-threshold grief and depression, in addition to other factors (i.e., hopelessness, reasons for living-RFL) associated with SI., Methods: Participants (n = 216) bereaved by combat, accident, or suicide completed an online survey. Associations between depression, grief, SI, RFL, and hopelessness were examined by multivariable logistic regressions and structural equation modeling (SEM)., Results: Across the sample, hopelessness and RFL were associated with SI while continuous measures of grief and depression were not. In contrast, clinical-threshold grief, clinical-threshold depression, hopelessness, and RFL each were associated with SI. In addition, of the grief characteristics, yearning was the most robust correlate of SI, and Survival/Coping Beliefs (SCB) was the RFL most associated with SI. SEM indicated that direct paths between grief and SI, hopelessness and SI, and RFL and SI were significant, but not between depression and SI. Instead, depression had a strong direct effect on hopelessness, and hopelessness had a direct effect on SI., Discussion: Results are consistent with previously-identified associations between SI and clinical levels of depression and grief. More nuanced findings suggest hopelessness, yearning, and SCB as additional targets for reducing risk for SI in bereaved individuals regardless of whether they meet clinical thresholds for grief or depression., Competing Interests: Declaration of competing interest Declarations of interest: none., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This report presents an overview of the objectives, design, and analytic strategy of the Child Maltreatment in Military Families Life Course Study , an investigation of factors associated with child maltreatment in active duty military families., Method: The study uses a case-control retrospective research design and discrete-time survival methodology to examine service member demographic characteristics, family characteristics, military-related characteristics, and military family life events associated with child maltreatment incidents that meet the Department of Defense definition of child abuse or neglect. The sample includes all active duty families with a first occurrence of child maltreatment anytime between Fiscal Year (FY) 2009 and FY 2018 ( n  = 28,684), and a representative sample of control families with children under age of 18 during the same period ( n  = 589,417). Analyses include child maltreatment and domestic abuse data from the Family Advocacy Program Central Registry; sponsor socio-demographic, military-related, and family data from the Active Duty Military Personnel Master and Defense Enrollment Eligibility Reporting System data files; deployment data from the Contingency Tracking System; and mental health data from the Medical Data Repository., Results and Conclusions: Study results identify risk and protective factors associated with child maltreatment in military families, subgroups at elevated risk of child maltreatment, and periods of heightened risk during the military family life course. These results are expected to improve the ability to identify families most at-risk for particular types of child maltreatment and inform prevention strategies that promote the health and safety of military families.

Resistant and refractory cytomegalovirus (CMV) viremia can limit the provision of chemotherapy due to myelosuppression and end-organ dysfunction. Few therapies are available for children with clinically significant CMV viremia. We successfully used maribavir for a 4-year-old patient with lymphoma to complete his chemotherapy course. Resistance to maribavir did result after many months of therapy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Psychologists address social-justice problems in their research and applied work, and their scholarly efforts have been influenced by assumptions, constructs, and hypotheses from the political left. Recently, some psychologists have called for increased intellectual and political diversity in psychology, particularly as such diversity may lead to improved problem-solving. As an attempt to increase intellectual diversity in psychology, we review here the scholarship of Thomas Sowell. His work represents a rich source of hypotheses for psychologists' future research. We focus on his views on the importance of freedom; the extent to which reforms can reduce freedom; the importance of free markets to human flourishing; the role of free markets in producing costs for discrimination; the way spontaneously ordered systems can contain knowledge that can be overlooked in reforms; and the importance of culture and cultural capital. We will also discuss Sowell's more thoroughgoing economic analyses of problems and solutions and his analyses of contingencies operating on politicians and reformers, as well as his views on conflicts in fundamental visions about human nature and the pivotal role of improvements in minority education.

Background: In response to the growing global need for pesticide residue testing, laboratories must develop versatile analytical methods and workflows to produce scientifically sound results. One of the many challenges faced by food chemists is acquiring suitable pesticide certified reference materials (CRMs) to calibrate analytical equipment, monitor method performance, and confirm the identity and concentration of hundreds of pesticide residues in food samples. CRM producers invest considerable resources to ensure the stability of their products., Objective: To present proper CRM handling and storage practices as guidance to ensure stability based on the results of several multiresidue pesticide stability studies., Methods: The open ampoule and combined multiresidue mix studies were conducted under controlled conditions. New ampoules containing multiresidue pesticide CRM mixtures were opened and compared to previously opened ampoules at multiple intervals while stored under freezing and refrigerated temperatures. Both LC- and GC-amenable pesticides (>200 residues) were combined and stored under typical laboratory conditions. Studies were performed with and without celery matrix., Results: The open ampoule study showed high levels of stability for all mixtures. All GC residues remained stable over the duration of the experiment. A week after opening LC multiresidue pesticide mixtures showed minor degradation. After combination of the multiresidue pesticide mixtures, degradation occurred rapidly for both the GC and LC mixtures., Conclusion: Multiresidue pesticide mixtures are stable as ampullated until they are opened. Once the contents of a kit were opened and combined, decreasing stability was observed over time. This was true for both the LC and GC kits. Working mixtures of CRMs for instrument calibration should be made daily., Highlights: This article shows a novel approach for measuring stability of CRM mixes. In-depth analysis of multiresidue pesticide mixtures and the stability that can be expected before and after mixing under typical storage conditions is described., (© The Author(s) 2023. Published by Oxford University Press on behalf of AOAC INTERNATIONAL.)

The COVID-19 coronavirus has caused 5.4 million deaths worldwide, including over 800,000 deaths in the United States (as of December 2021). In addition to these staggering statistics, an even greater number of individuals have died from other causes during the COVID-19 pandemic. As a result, a large portion of the global population has faced bereavement during the COVID-19 pandemic and resulting quarantine. The often rapid and unexpected nature of COVID-19 deaths and the presence of pandemic-related stressors and living restrictions make it more difficult for individuals bereaved during the pandemic to implement effective strategies for coping with the loss compared to non-pandemic periods. Quarantine-related constraints (e.g., social distancing, availability of and access to resources) impede coping strategies that have been found to be adaptive after a loss, such as supportive (e.g., seeking emotional and instrumental support) and active (e.g., problem-focused and cognitive reframing) coping, and they augment avoidant strategies (e.g., substance use, denial, and isolation) that have been found to be maladaptive. Poorer mental health outcomes (including prolonged grief disorder; PGD) have been associated with less healthy coping. This article reviews research findings regarding bereavement during the COVID-19 pandemic, discusses the effects of pandemic-related stressors on bereavement coping strategies, and proposes how different types of coping during the pandemic may account for the poorer mental health outcomes described in recent reports. Interventions for promoting adaptive coping strategies and minimizing maladaptive coping strategies are also outlined.

Background: Children who experience neglect typically endure multiple types of neglect and abuse during a single maltreatment incident. However, research on the phenomenology and predictors of neglect types has primarily examined neglect types in isolation., Objective: To advance understanding of neglect incidents that more accurately reflect the experiences of children who have been neglected, we examined latent classes of neglect defined by co-occurring neglect types and multiple forms of abuse. To inform efforts to identify families at-risk for particular classes of neglect, associations between child, parent, and family characteristics and latent classes were examined., Participants and Setting: 390 child neglect incidents substantiated at U.S. Army installations., Methods: Neglect types and incident severity were coded using the Modified Maltreatment Classification System. Child, parent, and family characteristics were coded using information drawn from case records., Results: Latent class analysis yielded 5 classes: exposure to violence, failure to provide, supervisory lapses, substance-related endangerment, and non-specific. The exposure to violence and substance-related endangerment classes were characterized as highly severe. High and low severity classes were associated with distinct child, parent, and family characteristics. The latent classes were also differentiated by distal outcomes, including probability of law enforcement investigation, child removal from home, and offender removal from home., Conclusions: By identifying the types of neglect and abuse that are likely to occur concomitantly as well as the child, parent, and family characteristics associated with increased risk of latent classes of neglect, results advance knowledge regarding the phenomenology of neglect types and inform prevention efforts., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The American Psychological Association's (APA's) Ethical Principles of Psychologists and Code of Conduct (American Psychological Association, 2017b; hereinafter referred to as the Ethics Code) does not contain an enforceable standard regarding psychologists' role in either honoring or protecting the free speech of others, or ensuring that their own free speech is protected, including an important corollary of free speech, the protection of academic freedom. Illiberal acts illegitimately restrict civil liberties. We argue that the ethics of illiberal acts have not been adequately scrutinized in the Ethics Code. Psychologists require free speech to properly enact their roles as scientists as well as professionals who wish to advocate for their clients and students to enhance social justice. This article delineates criteria for what ought to be included in the Ethics Code, argues that ethical issues regarding the protection of free speech rights meet these criteria, and proposes language to be added to the Ethics Code. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The ethically proper response to problematic speech is more speech and not censorship. To the extent that Jackson (2022) and Smith (2022) advocate for all to be able to criticize all, for example, for unempowered undergraduates to criticize privileged White male professors or for anyone to criticize racist or hate speech, we are in agreement. The speech involved in criticism can be risky and hence ought to be protected by the Ethical Principles of Psychologists and Code of Conduct (American Psychological Association, 2017). However, except in very circumscribed circumstances, to the extent that Jackson or Smith advocate for acts such as the suppression, censorship, or punishment of speech, we are in disagreement. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Although much has been learned about the physical and psychological impacts of deployment and combat injury on military service members, less is known about the effects of these experiences on military spouses., Methods: The present study examined self-reported mental health symptoms (using the Brief Symptom Inventory [BSI]-18 and the posttraumatic stress disorder [PTSD] Checklist [PCL-C]) in wives of service members who were combat-injured (CI; n = 60); noninjured with cumulative deployment longer than 11 months (NI-High; n = 51); and noninjured with cumulativel deployment less than 11 months (NI-Low; n = 53)., Results: 36.7% and 11.7% of CI wives endorsed above threshold symptoms on the PCL-C and overall BSI-18, respectively. Multivariate linear regressions revealed that being a CI wife was associated with higher PCL-C, overall BSI-18, and BSI-18 anxiety subscale scores compared to NI-Low wives in models adjusted for individual and family characteristics, as well as prior trauma and childhood adversities. Compared with the NI-High group, the CI group was associated with higher overall BSI-18 scores., Conclusions: While CI wives evidenced fewer mental symptoms than expected, these findings suggest a negative impact of service member's combat injury on wives' mental health above that attributable to deployment, highlighting the need for trauma-informed interventions designed to support the needs of military wives affected by combat injury., (© 2022 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Bereavement has been associated with increases in immune/inflammatory and neuroendocrine reactions, cardiovascular events, nonspecific physical symptoms, mental conditions, and health care utilization. However, little is known about bereavement effects in younger samples, multiple health effects within samples, or prebereavement to postbereavement health changes., Objective: To determine the effect of bereavement on the prevalence of medical conditions and utilization of health care., Methods: This study examined the prevalence of 15 medical conditions and health care utilization before and in the first and second years after bereavement in a population of 1375 U.S. military widows and compared them to those of 1375 nonbereaved U.S. military control wives., Results: Compared with controls, widows showed greater increases in prebereavement levels of prevalence of ill-defined conditions and mental health conditions in years 1 and 2 following bereavement. Health care utilization also increased for widows compared with controls. Utilization was highest for widows with comorbid ill-defined conditions and mental health conditions., Conclusions: The increased prevalence of both ill-defined conditions and mental health diagnoses following bereavement and the resultant need for increased health care utilization in this help-seeking sample suggest a need for proactive health monitoring of all military widows to identify and treat mental health conditions, as well as recognize manifestations of physical symptoms, in those who may not seek treatment., (Copyright © 2022 Academy of Consultation-Liaison Psychiatry. All rights reserved.)

We describe the development of an empirically-derived codebook for qualitative data concerning the impact of grief on the interpersonal relationships of bereaved individuals. Relatives ( N  = 39) of deceased military service members participated in focus groups concerning how grief influenced their relationships across multiple interpersonal domains, including family, friends, community, and with the deceased. Focus group transcripts were coded using a stepwise process consistent with grounded theory to identify and categorize recurrent themes. The process yielded a comprehensive codebook containing 44 nodes with definitions and examples. The codebook provides researchers with an empirically-grounded analytic tool for future studies on bereavement.

Better understanding of the causes and circumstances of maltreatment deaths of children is needed to prevent tragedy. The purpose of this article is to facilitate understanding of child maltreatment fatality review processes and their outcomes. A literature review was conducted through searches of the databases PubMed, PsycINFO, and EMBASE and through citations in publications. Over 165 publications were reviewed and 55 were selected for inclusion. Papers were from the United States, England, Ireland, Northern Ireland, Netherlands, France, Canada, Australia, South Africa, Switzerland, Saudi Arabia, Japan, and China. These were included if they described fatality review goals, authority, procedures, and outcomes. Although we searched databases on a continual basis during the preparation of this review, we could have missed publications, particularly those in newspapers and journals that are not included in large-scale databases or cited in other articles. Improvement of fatality review requires diligence by individuals and organizations that provide information to the reviewers. Among challenges to the review process are varying criteria for review, misclassifications of the manner of death, inadequate or incomplete forensic and medical investigations, lack of information about the perpetrator, diversity of the community, concealment of the cause of death by parents or other caregivers, and disagreement among reviewers about the results of their inquiries. Institutional challenges are also present, which include the need for funding, privacy issues on obtaining information, updating reviewer training, lack of follow-up by institutional authorities on the recommendations of the reviews, and research facilitating the review of maltreatment fatalities.

Objectives: To determine the accuracy of ultrasound estimation of fetal weight among fetuses with gastroschisis and how the diagnosis of fetal growth restriction (FGR) affects the timing of delivery., Methods: This was a retrospective cohort study including all fetuses with a diagnosis of gastroschisis at our institution from November 2012 through October 2017. We excluded multiple gestations, pregnancies with major structural or chromosomal abnormalities, and those for which prenatal and postnatal follow-up were unavailable. Performance characteristics of ultrasound to predict being small for gestational age (SGA) were calculated for the first and last ultrasound estimations of fetal weight., Results: Our cohort included 75 cases of gastroschisis. At the initial ultrasound estimation, 15 of 58 (25.9%) fetuses met criteria for FGR; 48 of 70 (68.6%) met criteria at the time of the last ultrasound estimation (median, 34.7 weeks). Cesarean delivery was performed for 37 of 75 (49.3%), with FGR and concern for fetal distress as the indication for delivery in 17 of 37 (45.9%). Only 6 of 17 (35.3%) of the neonates born by cesarean delivery for an indication of FGR and fetal distress were SGA. The initial ultrasound designation of FGR corresponded to SGA at birth in 8 of 15 (53.3%), whereas the last ultrasound estimation corresponded to SGA in 17 of 48 (35.4%). The initial ultrasound estimation agreed with the last ultrasound estimation before delivery with the diagnosis of FGR in 13 of 15 (86.7%)., Conclusions: Ultrasound in the third trimester was sensitive but had a low positive predictive value and low accuracy for the diagnosis of SGA at birth for fetuses with gastroschisis. A large proportion of fetuses were born by cesarean delivery with indications related to FGR or fetal concerns., (© 2020 American Institute of Ultrasound in Medicine.)

The targeted delivery of drugs by means of linking them to antibodies (Abs) to form antibody-drug conjugates (ADCs) has become an important approach in oncology and could potentially be used in other therapeutic areas. Targeted therapy is aimed at improving clinical efficacy while minimizing adverse reactions. The nonclinical safety assessment of ADCs presents several unique challenges involving the need to examine a complex molecule, each component of which can contribute to the effects observed, in appropriate animal models. Some considerations for the nonclinical safety evaluation of ADCs based on a literature review of ADCs in clinical development (currently or previously) are discussed.

Purpose of Review: Congenital lower urinary tract obstruction (LUTO) is a rare group of conditions characterized by high perinatal morbidity and mortality if associated with oligohydramnios or anhydramnios in early pregnancy. Although foetal intervention has the potential to improve perinatal survival in a select group of foetuses with LUTO, the actual selection of those candidates most likely to benefit from intervention remains challenging., Recent Findings: Foetuses with LUTO who are potential candidates for prenatal intervention should undergo detailed multidisciplinary evaluation to ensure proper assessment and counselling. Using a combination of multiple ultrasound-based renal parameters, including measurement of foetal bladder volumes before and after vesicocentesis and kidney size and morphology, combined with repeated foetal urine biochemistry may allow for better selection than any single test., Summary: Foetal intervention should be offered to women carrying a foetus with LUTO only after appropriate evaluation and counselling. A combined approach utilizing ultrasound and biochemical measurements of foetal renal function appears best. Research focusing on the development of more accurate markers is needed., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Returning human remains to family members after a loved one's death is thought to support grief adaptation. However, no known research has examined the effects that notifications of fragmented remains have on bereaved family members. We examined the number of notifications received, continuing questions about the death, grief severity, and posttraumatic stress (PTS) in family members bereaved by the September 11, 2001 attacks (N = 454). One notification was associated with fewer continuing questions compared to zero notifications, p = .037, or two or more notifications, p = .009. A model using notifications and continuing questions to predict grief severity showed there was no difference between receiving one and zero notifications, p = .244; however, receipt of two or more notifications was associated with higher grief severity compared to zero notifications, p = .032. A similar model demonstrated that receipt of any notifications was associated with PTS, ɳ p 2 = .026, p = .006. Having continuing questions was associated with grief severity, ɳ p 2 = .170, p < .001; and PTS, ɳ p 2 = .086, p < .001. Additionally, participants who received one notification and chose not to receive more had fewer continuing questions compared to all other participants, and participants who received two or more notifications and chose no future notifications had higher PTS levels compared to all other participants. The results indicate that human remains notification is not associated with reduced grief severity but is associated with PTS. These findings should inform notification policy and guide families' notification choice after traumatic deaths., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Bereavement by sudden and violent deaths can lead to increased grief severity, depression, and reduced posttraumatic growth compared to those bereaved by natural causes. These outcomes can be affected by coping strategies and whether a survivor had been "prepared" for the death. The present study examined the effect of coping and considering the possibility of death on grief severity, depression, and posttraumatic growth in those bereaved by sudden deaths., Methods: Participants bereaved by suicide, accident, or combat deaths completed an online survey about demographics (including the cause of death), coping, grief severity, depression, and posttraumatic growth. A factor analysis of the coping measure yielded factors representing three coping strategies: avoidant coping, supportive coping, and active coping. These three strategies, the causes of death and considering the possibility of death were used as predictors of either grief severity, depression, or posttraumatic growth in multivariate linear regression models., Results: Each coping strategy and cause of death was differentially associated with grief severity, depression, and posttraumatic growth. Specifically, supportive coping and active coping were each only associated with higher posttraumatic growth. In contrast, avoidant coping was associated with all outcomes (higher grief severity and depression and lower posttraumatic growth). In addition, accidents and suicides (compared to combat deaths) had independent effects on grief severity and posttraumatic growth. Considering the possibility of death interacted with avoidant coping and also with supportive coping to predict grief severity in combat-loss survivors., Discussion: Findings highlight the differential contributions of coping strategies and their complex relationships with cause of death in contributing to grief severity, depression, and posttraumatic growth. Avoidant coping contributed to negative outcomes and inhibited posttraumatic growth, suggesting its importance as a target for therapeutic intervention. Although supportive and active coping facilitated posttraumatic growth, they had less of a role in mitigating grief severity or depression in this study. Although considering the possibility of death appeared to mitigate negative outcomes among survivors of combat death, avoidance of that possibility is likely protective for the majority of family members whose loved ones return home safely., (Copyright © 2020 Fisher, Zhou, Zuleta, Fullerton, Ursano and Cozza.)

Background: Distinguishing a disorder of persistent and impairing grief from normative grief allows clinicians to identify this often undetected and disabling condition. As four diagnostic criteria sets for a grief disorder have been proposed, their similarities and differences need to be elucidated., Methods: Participants were family members bereaved by US military service death (N = 1732). We conducted analyses to assess the accuracy of each criteria set in identifying threshold cases (participants who endorsed baseline Inventory of Complicated Grief ⩾30 and Work and Social Adjustment Scale ⩾20) and excluding those below this threshold. We also calculated agreement among criteria sets by varying numbers of required associated symptoms., Results: All four criteria sets accurately excluded participants below our identified clinical threshold (i.e. correctly excluding 86-96% of those subthreshold), but they varied in identification of threshold cases (i.e. correctly identifying 47-82%). When the number of associated symptoms was held constant, criteria sets performed similarly. Accurate case identification was optimized when one or two associated symptoms were required. When employing optimized symptom numbers, pairwise agreements among criteria became correspondingly 'very good' (κ = 0.86-0.96)., Conclusions: The four proposed criteria sets describe a similar condition of persistent and impairing grief, but differ primarily in criteria restrictiveness. Diagnostic guidance for prolonged grief disorder in International Classification of Diseases, 11th Edition (ICD-11) functions well, whereas the criteria put forth in Section III of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) are unnecessarily restrictive.

Background: Bereavement is associated with cognitive difficulties, but it is unclear whether these difficulties are associated with normative and/or complicated grief (CG) and how comorbid depression and anxiety contribute to them. Self-reported "minor errors in thinking" (i.e., cognitive failures) may manifest following bereavement and be differentially affected by CG, anxiety, and depression., Methods: Associations between perceived cognitive failures and CG, anxiety, and depression were investigated in 581 bereaved participants. To examine both single and comorbid conditions across the spectrum of bereaved participants, these relationships were examined using both linear regressions and group comparisons., Results: Continuous measures of depression, anxiety, and grief each independently predicted perceived cognitive failures. Group comparisons indicated that the group with three comorbid conditions had the highest frequency of perceived cognitive failures and the group with no conditions had the lowest. In addition, groups with threshold depression levels (both alone and comorbid with another condition) had higher frequencies of perceived cognitive failures than other groups, suggesting that depression was more strongly associated with perceived cognitive failures than CG or anxiety., Conclusions: Future research about cognition following bereavement should address how multiple mental health symptoms or conditions combine to affect perceived and actual cognitive capacity., (© 2019 Wiley Periodicals, Inc.)

Extreme-groups designs (EGDs) are common in psychopathology research, often using diagnostic category as an independent variable. Continuous-variable analysis strategies drawing from a general linear model framework can be applied to such designs. The growing emphasis on dimensional examinations of psychological constructs, encouraged by the National Institute of Mental Health Research Domain Criteria framework, encourages continuous-variable analytic strategies. However, the interpretative implications of applying these strategies to various types of populations and sample score distributions, including those used in EGDs, are not always recognized. Appropriateness and utility of EGDs depend in part on whether the goal is to determine whether a relationship exists between 2 variables or to determine its strength. Whereas the literature investigating EGDs has emphasized symmetrical thresholds for defining extreme groups (e.g., bottom 10% vs. top 10%), psychopathologists often employ asymmetric thresholds (e.g., above a diagnostic threshold vs. a broader range of scores in a healthy comparison group). The present article selectively reviews literature on EGDs and extends it with simulations of symmetric and asymmetric selection criteria. Results indicate that including a wide range of scores in EGDs substantially mitigates problems (e.g., inflation of effect size) that arise when using statistical methods classically employed for continuous variables. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background/objectives: Bereavement is associated with increases in prevalence of mental health conditions and in healthcare utilization. Due to younger age and bereavement by sudden and violent deaths, military widows may be vulnerable to poor outcomes. No systematic research has examined these effects., Method: Using outpatient medical records from wives of active-duty military service members (SMs), we compared the prevalence of mental health conditions and mental healthcare visits among case widows (n = 1,375) to matched (on age, baseline healthcare utilization, SM deployment, and rank) nonbereaved control military wives (n = 1,375), from 1 year prior (Yr-1) to 2 years following (Yr+1 and Yr+2) SM death. Prevalence risk ratios and confidence intervals were compared to determine prevalence rates of mental health conditions and outpatient mental healthcare visits over time., Results: The prevalence of any mental health condition, as well as a distinct loss- and stress-related mental health conditions, significantly increased from Yr-1 to Yr+1 and Yr+2 for cases as did mental healthcare utilization. Widows with persistent disorders (from Yr+1 to Yr+2) exhibited more mental conditions and mental healthcare utilization than widows whose conditions remitted., Conclusion: Bereavement among military widows was associated with a two- to fivefold increase in the prevalence of depression, posttraumatic stress disorder, and adjustment disorder postdeath, as well as an increase in mental healthcare utilization. An increase in the prevalence of loss- and stress-related conditions beyond 1 year after death indicates persistent loss-related morbidity. Findings indicate the need for access to healthcare services that can properly identify and treat these loss-related conditions., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Studies of terrorism-related deaths are few and mostly focus on short-term effects. To characterize long-term bereavement outcomes, including resilience/recovery and patterns of comorbidity, following the September 11, 2001 (9/11), terrorist attacks, we report mental health conditions and grief-related impairment in 454 9/11 bereaved family members. In addition, the contribution of non-9/11 lifetime traumas, pre-9/11 mental health conditions, post-9/11 interim life events, grief services, income adequacy, and social support were examined. Latent class analyses yielded three groups: healthy, comorbid without PTSD (comorbid/noPTSD), and comorbid with PTSD and impaired (comorbid/PTSD+I). Participants in the healthy group (66.1%) were least likely to meet thresholds for mental conditions, whereas those in the comorbid/noPTSD (21.3%) and comorbid/PTSD+I (12.6%) groups had higher probabilities of meeting depression, grief, and anxiety thresholds. These groups also endorsed more negatively valenced post-9/11 interim life events than the healthy group: comorbid/noPTSD vs. healthy, odds ratio (OR) = 0.84, 95% CI [0.76, 0.94]; comorbid/PTSD+I vs. healthy, OR = 0.85, 95% CI [0.76, 0.96]. Comorbid/PTSD+I was the only group with elevated probabilities of meeting clinical thresholds for PTSD (.64) and grief-related impairment (.94). This group was also more likely to include bereaved parents: comorbid/PTSD+I vs. healthy, OR = 12.96, 95% CI [1.97, 85.41]; comorbid/PTSD+I vs. comorbid/noPTSD, OR = 15.55, 95% CI [1.63, 148.41]); and to experience more non-9/11 lifetime traumas: comorbid/PTSD+I vs. healthy, OR = 4.34, 95% CI [1.28, 14.70]; comorbid/PTSD+I vs. comorbid/noPTSD, OR = 6.54, 95% CI [1.53, 27.95]. Clinical and community programs should target this high-risk group to identify individuals in need of services., (© 2019 International Society for Traumatic Stress Studies.)

A survey was undertaken to evaluate juvenile animal studies conducted for drug applications reviewed by the Center for Drug Evaluation and Research between 2009 and 2014. Some conclusions about the nonclinical pediatric safety assessment based on studies performed in support of central nervous system-active compounds are presented here. A total of 44 completed studies from 32 New Drug Applications submitted to the Divisions of Psychiatry and Neurology Products were evaluated. Data on animal species and age range used, endpoints evaluated, and outcomes included in labeling were analyzed. Of the drugs evaluated, all but one had studies conducted in rats. In some cases, a second study in a nonrodent species (dog) was also conducted. Indices of growth and development and standard general toxicity parameters were included in all of the studies. Expanded neurohistopathology evaluations, bone mineral density measurements, and reproductive and neurobehavioral functional assessments were also generally carried out. A variety of neurological and neurobehavioral tests were employed. In the majority of rat studies, the potential for long-term cognitive impairment was evaluated using a complex water maze. Juvenile animal studies provided safety information considered relevant to drug use in children and that was included in labeling for 78% of the applications surveyed. The most commonly reported findings in labeling were for neurobehavioral effects, including changes in locomotor activity, auditory startle habituation, and learning and memory. Of the studies described in labeling with neurobehavioral effects, 54% found these effects to be persistent and to provide evidence of developmental neurotoxicity.

Recent theory and empirical research suggest that child neglect is a heterogeneous phenomenon characterized by various types. This study examined family risk factors associated with five neglect types including failure to provide physical needs, lack of supervision, emotional neglect, moral-legal neglect, and educational neglect in 390 substantiated cases of neglect in four U.S. Army communities. Family factors associated with elevated risk of each neglect type relative to other types were identified using multivariate regression. Relatively distinct sets of family risk factors were differentially associated with the neglect types. Family mental health problems and larger family size were associated with risk of failure to provide physical needs, childcare problems and larger family size were associated with risk of supervisory neglect, and family disagreements were associated with risk of emotional neglect. None of the family factors were associated with elevated risk of moral-legal or educational neglect. Results can inform the development of indicated and relapse prevention strategies for families affected by different neglect types.

Increases in combat deployments have been associated with rises in rates of child neglect in U.S. military families. Although various types of child neglect have been described in military families, it is unknown whether deployment status is associated with specific types of child neglect and whether other factors, such as substance misuse, play a role. To determine the contribution of service member deployment status to the risk of specific child neglect types, data were collected from 390 substantiated U.S. Army child neglect case files. The contributions of deployment status at the time of the neglect incident and parental alcohol or drug-related misuse to risk of neglect types were examined controlling for military family rank and child age. Compared to never deployed families, families with a service member concurrently deployed at the time of the neglect incident were at higher risk for failure to provide physical needs, lack of supervision, and educational neglect, but at lower risk for emotional neglect. Being previously deployed incurred risk for moral-legal neglect. Substance misuse added risk for moral-legal and educational neglect. Findings indicate the need for tailored prevention strategies to target different periods within the deployment cycle.

The ability of tumors to escape from immune destruction is attributed to the protein-protein interaction between programmed cell death protein 1 (PD1) and programmed cell death ligand 1 (PDL1) proteins expressed by immune T cells and cancer cells, respectively. Therefore, pharmacological inhibition of the PD1-PDL1 interaction presents an important therapeutic target against a variety of tumors expressing PDL1 on their cell surface. Recently, five antibodies have been approved and several are in clinical trials against the PD1-PDL1 protein-protein interaction target. In contrast, there are very few reports of small-molecule inhibitors of PD1-PDL1 interaction, and most of them have relatively modest or weak inhibition activities, emphasizing the difficulty in designing small-molecule inhibitors against this challenging target. Therefore, we focused our attention on macrocycles that are known to exhibit target activity comparable to large macromolecules despite having molecular weights closer to small, drug-like molecules. In this context, our present study led to the identification of several macrocyclic compounds from the ansamycin antibiotics class to be inhibitors of PD1-PDL1 interaction. Importantly, one of these macrocyclic antibiotics, Rifabutin, showed an IC 50 value of ca. 25 µM. This is remarkable considering it has a relatively low molecular weight and still is capable of inhibiting PD1-PDL1 protein-protein interaction whose binding interface spans over ca. 1970 Å 2 . Thus, these macrocycles may serve as guiding points for discovery and optimization of more potent, selective small-molecule inhibitors of PD1-PDL1 interaction, one of the most promising therapeutic targets against cancer.

Knowledge about the effect of a US service member's death on surviving family members is limited. In order to identify their grief-related health care needs, a first step is to identify the characteristics of persistent and elevated grief in a military family sample. The present study identified military family members (n = 232) bereaved more than six months who endorsed an elevated level of grief. A confirmatory factor analysis and test of measurement invariance of factor structure were used to compare the factor structure of their Inventory of Complicated Grief (ICG) responses to that of a bereaved non-military-related clinical research sample with similar grief levels. Results confirmed an equivalent five-factor structure of the ICG in both the military family sample and the clinical research sample. The similarity in factor structure was present despite differences in demographic characteristics and bereavement experiences between samples. Thus, the ICG reliably measures persistent and elevated grief in military family samples and provides grief symptom profiles that facilitates better understanding of their grief-related needs., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA.)

The mouse embryonic stem cell test (mEST) is a promising in vitro assay for predicting developmental toxicity. In the current study, early differentiation of D3 mouse embryonic stem cells (mESCs) under osteoblast culture conditions and embryotoxicity of cadmium sulfate were examined. D3 mESCs were exposed to cadmium sulfate for 24, 48 or 72h, and whole genome transcriptional profiles were determined. The results indicate a track of differentiation was identified as mESCs differentiate. Biological processes that were associated with differentiation related genes included embryonic development and, specifically, skeletal system development. Cadmium sulfate inhibited mESC differentiation at all three time points. Functional pathway analysis indicated biological pathways affected included those related to skeletal development, renal and reproductive function. In summary, our results suggest that transcriptional profiles are a sensitive indicator of early mESC differentiation. Transcriptomics may improve the predictivity of the mEST by suggesting possible modes of action for tested chemicals., (Published by Elsevier Inc.)

Background: U.S. military service members die from a variety of causes (i.e., accidents, combat, illnesses, homicide, suicide, and terrorism) while on duty and in greater numbers during times of war, leaving behind bereaved dependent family members. Identifying characteristics of these dependent families improves our understanding of their unique needs, helps educate service providers who offer assistance to these surviving family members, and better informs policy addressing their health and well-being. This study describes deceased U.S. military service members (DSMs) who died on active duty between September 11, 2001 and September 11, 2011 and their surviving dependent spouses and children., Methods: Characteristics of DSMs (service branch, rank, and cause of death) and characteristics of spouse-with-children and spouse-only families (ages of dependents, time since loss, and distance from a military installation) were examined., Results: 15,938 DSMs died from a variety of causes (e.g., accidents, combat, and illnesses). 55% of DSMs had dependent spouses and 56% of those spouses had children. Most surviving dependent spouses and children were young (mean ages = 32.8, 10.3 years; SD = 9.3, 7.3 years, respectively) at the time of DSM death. Many of these young dependents were related to a DSM who experienced a sudden and violent death. 60% of spouse-with-children families and 58% of spouse-only families lived farther than 60 miles from a military installation. Time since loss (range = 1.3-11.3 years) did not predict distance to installation., Conclusions: Findings characterize surviving spouses and their children, suggest potential risk for problematic grief outcomes, and underscore the importance of educating service providers about how to support military survivor family health and resilience., (Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.)