Elementary school-aged children's perceptions of academic dishonesty: Definitions and moral evaluations of cheating behaviors in school.

A total of 76 children (Mage = 9 years 5 months, SD = 2.22 years) participated in a structured interview about their experiences with and knowledge of academic dishonesty. Overall, 27% of the sample reported having cheated in school. Most of these children were 10 to 13 years old, and the most prevalent form of cheating behavior reported was using forbidden materials during a test. Children's age group was a significant positive predictor of their reported cheating history; however, no significant difference was found between children's gender and engagement with cheating. Children's moral evaluations of cheating did not predict their reported cheating history, nor did children's parents' cheating history. Vignette type (cheating vs. non-cheating), age group, and the interaction between vignette type and age group were significant predictors of children's ability to accurately identify behaviors that constitute cheating. Children rated cheating behaviors as significantly less moral than non-cheating behaviors. Overall, the current results provide insight into what forms of cheating behavior children engage in at the elementary school-age level.

Consensus Guidelines for Assessment and Comprehensive Outcomes Evaluation in Rural Pain Clinics.

Recent advancements in nurse anesthesiology fellowship training programs have helped to establish advanced pain management services for rural communities. Consensus guidelines to direct the rural provider toward the most valid and reliable measures for pain assessment and functional outcomes evaluation are not presently available. The primary aim of this initiative was to establish consensus guidelines for a comprehensive outcome evaluation program with specific time intervals for assessments that can be utilized by all rural pain clinics. The American Association of Nurse Anesthesiology Nonsurgical Pain Management Advisory Panel members provided formative and expert feedback for this initiative. The Delphi model was utilized to achieve consensus through multiple rounds of surveys. Items achieving >70% agree/strongly agree were kept; items with >70% disagree/strongly disagree were rejected; items meeting neither advanced to the following round for evaluation until consensus was met. During round I, consensus was reached for: (1) the use of the Numerical Rating Scale for pain severity; and (2) timing of pain severity & functional pain outcomes on each office visit and before/after each intervention. Round II, consensus was achieved for: (1) the use of Wong-Baker FACES Pain Rating Scale as a suitable instrument when literacy or communication pose a barrier but not as a primary assessment; and (2) the use of the Brief Pain Index-Short Form for functional outcome measures. During round III, consensus was reached for: (1) the use of the Oswestry Disability Index as a functional outcome measure; and (2) pain reassessment being performed within 14 days of intervention. This initiative provides rural pain clinics with a comprehensive outcome evaluation program with specific time intervals for assessments.

The effectiveness of bone anchored maxillary protraction (BAMP) in the management of class III skeletal malocclusion in children aged 11-14 years compared with an untreated control group: A multicentre two-arm parallel randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of bone anchored maxillary protraction (BAMP) in the management of class III skeletal malocclusion in children aged 11-14 years compared with an untreated control group in terms of perceived need for orthognathic surgery, skeletal and dental change, and psychological impact. DESIGN: A multicentre two-armed parallel randomised controlled trial. SETTING: Six UK hospital orthodontic units. METHODS: A total of 57 patients were randomly allocated into either the BAMP group (BAMPG) (n = 28) or a no treatment control group (CG) (n = 29). OUTCOMES: Data collection occurred at registration (DC1),18 months (DC2) and 3 years (DC3), where skeletal and dental changes were measured from lateral cephalograms and study models. Oral Aesthetic Subjective Impact Score (OASIS) and Oral Quality of Life (OHQOL) questionnaires were used to assess the psychological impact of treatment. RESULTS: The mean age was 12.9 ± 0.7 years and 12.6 ± 0.9 years in the BAMPG and CG, respectively. At DC2, the BAMPG achieved a class III ANB improvement of +0.6° compared with -0.7° in the CG (P = 0.004). The overjet improvement was +1.4 mm for the BAMPG and -0.2 mm for the CG (P = 0.002). There was no evidence of any other group differences for the other skeletal or dental cephalometric outcomes (P > 0.05) or the questionnaire data (OASIS P = 0.10, OHQOL P = 0.75). At DC2, the 18-month follow-up, 22% of the BAMPG achieved a positive overjet. At the 3-year follow-up (DC3), fewer patients in the BAMPG were perceived to need orthognathic surgery (48%) compared with 75% of patients in the CG (P = 0.04), with an odds ratio of 0.31 (95% confidence interval = 0.10-0.95). CONCLUSION: The BAMP technique did not show any social or psychological benefits; however, the skeletal class III improvement in ANB and the overjet change were sufficient to reduce the perceived need for orthognathic surgery by 27% compared with the CG.

'I can see what's going on without being nosey ': What matters to people living with dementia about home as revealed through visual home tours.

OBJECTIVES: This paper considers home from the perspective of people living with dementia supporting ongoing discourse around ageing in place and the significance of creating more inclusive communities. METHODS: Forty-six home tour interviews led by people living with dementia were conducted in England and Scotland to better understand the connectivity between home and neighbourhood for people living with dementia. These interviews used a range of participatory and creative approaches including video, photographic images and in situ interviews. Data were analysed via reflexive thematic analysis. RESULTS: Three themes were identified in data analysis. 1. Connected home and neighbourhood, where participants revealed the dynamic relationship between home and neighbourhood; 2. Practices of home, where participants discussed the everyday nature of their homes and routines; and 3. Displaying home and family, which reflected participant's biographical homes in the context of living with dementia. DISCUSSION: The findings show that home holds multiple meanings for people living with dementia. For example, home is understood as a part of the neighbourhood and an extension of the home space into gardens and backyards, thus extending existing discourses that solely focus on the inside of people's homes. For people living with dementia, homes are also sites of negotiation and renegotiation where new meanings are created to reflect the changing nature and context of the home. There is not one fixed solution to these issues. Support and understanding for people living with dementia will need to evolve to adapt to the shifting dynamics and multiple meanings of home.

Cough desensitization treatment for patients with refractory chronic cough: results of a second pilot randomized control trial.

OBJECTIVE: The purpose of this study was to collect pilot efficacy data on a novel treatment for refractory chronic cough (RCC), which we call cough desensitization treatment (CDT). DESIGN AND METHODS: In this parallel cohort, sham-controlled, randomized controlled trial, 21 adults with RCC were randomly assigned to 12 sessions of either CDT (progressive doses of aerosolized capsaicin while behaviorally suppressing cough; n = 11) or a sham treatment (repeated exposure to aerosolized saline; n = 9). The Leicester Cough Questionnaire (LCQ) was the primary outcome measure. Perceived cough severity with a visual analogue scale and cough challenge testing (for measuring cough-reflex sensitivity) were secondary outcome measures. Data were analyzed with mixed effects linear regression and follow-up contrasts. RESULTS: Results on all measures favored CDT. Excluding one sham participant, whose baseline LCQ scores were deemed unreliable, mean change in LCQ at 3-weeks post treatment was 6.35 and 2.17 in the CDT and sham groups, respectively. There was moderate to strong evidence of a greater improvement in the CDT group in total LCQ score (p = .058) and LCQ Psychological domain (p = .026) and Physical domain (p = .045) scores. Strong evidence was found for a greater reduction in urge-to-cough during CCT in the CDT group (p = .037) and marginal for a reduction in the capsaicin cough-reflex sensitivity (p = .094). There was weak evidence of a greater reduction in cough severity in the CDT group (p = .103). DISCUSSION: Although the study is limited due to the small sample size, the data provide additional evidence supporting further research on CDT. CDT resulted in a greater change in the primary efficacy measure (LCQ) than both pharmaceutical and behavioral treatments currently found in the literature. TRIAL REGISTRATION: This trial (NCT05226299) was registered on Clinicaltrials.gov on 07/02/2022.

Development of a brief support and education intervention for loved ones of veterans with posttraumatic stress disorder.

Clinical practice guidelines for managing posttraumatic stress disorder (PTSD) encourage incorporating loved ones into treatment, and supportive relationships can increase engagement in mental health care for veterans with PTSD. This study describes the iterative refinement, feasibility/acceptability testing, and national dissemination of a brief support and psychoeducation intervention for loved ones of veterans with PTSD. Loved ones (n = 181; range:1-11 per group) attended and qualitatively rated "PTSD 101 for Family and Friends: A Support and Education Workshop." Open-ended questions were used to gather data on suggestions for improvement and descriptions of helpful content, and the workshop was refined following participant and operational partner feedback using a quality improvement framework. Rating quantitative items on a 1-5 scale, participants found the overall quality (M = 4.76) and relevance (M = 4.82) to be excellent, noting they learned substantial new information (M = 4.45). Sense of support (M = 4.95), intentions to use the material (M = 4.87), PTSD self-efficacy (M = 4.41), and understanding of PTSD (M = 4.76) were rated favorably. Common themes among helpful elements were a sense of shared experience and optimism and increased knowledge of treatments/resources. Suggestions for improvement referenced logistics. Following continual stakeholder feedback and refinement, the workshop represents a novel method for providing loved ones with empirically supported psychoeducation, coping skills, and community. It is being disseminated by the Family Services Section of the Veterans Health Administration Office of Mental Health and Suicide Prevention.

A daily diary study of the romantic partner relationship dynamics associated with anger and other posttraumatic stress disorder symptoms.

Posttraumatic stress disorder (PTSD) is linked to negative relationship outcomes, but the relational processes that link specific PTSD symptoms to these outcomes over granular periods are not well understood. The current study used a daily diary methodology to investigate the associations between specific PTSD symptoms (i.e., anger, avoidance, reexperiencing, hyperarousal, and numbing) and proximal indices of relationship functioning (i.e., accommodation behaviors, disclosure, intimacy). Participants were members of 64 couples, each comprising a male service member (SM) and female romantic partner (RP), who completed daily assessments of PTSD symptoms and indices of relationship functioning for 2 weeks. The results suggest a somewhat unique role of anger on relationship dynamics: Although mean levels of PTSD symptom clusters were associated with negative relationship outcomes at the bivariate level, daily fluctuations in anger were uniquely related to accommodation behaviors and SM- and RP-reported intimacy in multilevel models, Bs = -0.08-0.50). These findings highlight the importance of considering the differential role of specific PTSD symptoms, like anger, in dyadic interventions for PTSD; several strategies for doing so in the context of contemporary evidence-based treatments are discussed.

Minimal important difference metrics and test-retest reliability of the PTSD Checklist for DSM-5 with a primary care sample.

The PTSD Checklist for DSM-5 (PCL-5) is a measure of posttraumatic stress disorder (PTSD) symptom severity that is widely used for clinical and research purposes. Although previous work has examined metrics of minimal important difference (MID) of the PCL-5 in veteran samples, no work has identified PCL-5 MID metrics among adults in primary care in the United States. In this secondary analysis, data were evaluated from primary care patients (N = 971) who screened positive for PTSD and participated in a large clinical trial in federally qualified health centers in three U.S. states. Participants primarily self-identified as women (70.2%) and White (70.3%). We calculated test-retest reliability using clinic registry data and multiple distribution- and anchor-based metrics of MID using baseline and follow-up survey data. Test-retest reliability (Pearson's r, Spearman's ρ, intraclass correlation coefficient) ranged from adequate to excellent (.79-.94), with the shortest time lag demonstrating the highest reliability estimate. The MID for the PCL-5 was estimated using multiple approaches. Distribution-based approaches indicated an MID range of 8.5-12.5, and anchor-based approaches indicated an MID range of 9.8-11.7. Taken together, the MID metrics indicate that PCL-5 change scores of 9-12 likely reflect real change in PTSD symptoms and indicate at least an MID for patients, whereas PCL-5 change scores of 5 or less likely are not reliable. These findings can help inform clinicians using the PCL-5 in similar populations to track patient responses to treatment and help researchers interpret PCL-5 score changes in clinical trials.

A mixed-methods evaluation of why an implementation trial failed to engage veterans with posttraumatic stress disorder in trauma-focused psychotherapy.

An effectiveness trial found that telemedicine collaborative care for posttraumatic stress disorder (PTSD) significantly increased engagement in trauma-focused psychotherapy (TFP) and improved PTSD symptoms. However, in a subsequent implementation trial, very few veterans enrolled in collaborative care initiated TFP. We conducted a mixed-methods evaluation to determine why veterans did not initiate TFP in the implementation trial. After conducting chart reviews of 1,071 veterans with PTSD enrolled in collaborative care, patients were categorized into four mutually exclusive TFP groups: TFP not discussed; TFP discussed, declined; TFP discussed, did not decline; and TFP initiated. We conducted semistructured interviews with 43 unique patients and 58 unique providers (i.e., care managers and mental health specialists). Almost half (48.6%) of the veterans had no documentation of discussing TFP with their care manager; another 28.9% discussed it but declined. Most veterans (77.1%) had an encounter with a mental health specialist, 36.8% of whom never discussed TFP, and 35.7% of whom discussed it but declined. Providers reported that many veterans were not able, willing, or ready to engage in TFP and that non-trauma-focused therapies were better aligned with their treatment goals. Veterans gave numerous reasons for not initiating TFP, including having bad prior experiences with TFP and wanting to avoid thinking about past traumatic experiences. Commonly cited reasons for noninitiation were providers never discussing TFP with veterans and veterans declining TFP after discussing it with their provider. Interventions, such as shared decision-making tools, may be needed to engage providers and patients in informed discussions about TFP.

CYP450 Genetic Polymorphisms: Generalized Tonic-Clonic Seizure after Intentional Fluoxetine and Melatonin Overdose.

Cytochrome P450 polymorphisms have gathered much attention regarding personalized psychopharmacological care. It is well documented that these drug metabolizing enzymes lead to interpatient variability in pharmacokinetic profiles. It appears that less functional genotype may increase of risk of higher side-effect burden. Here we highlight the importance of genetic polymorphisms to potentially predict a toxicity related phenotype after an intentional overdose. Genotyping may have a role in predicting serious side effects to help clinicians educate patients and their families, and implement more intensive monitoring and institute prophylactic treatment as needed.

Acoustic and postural displays in a miniature and transparent teleost fish, Danionella dracula.

Acoustic behavior is widespread across vertebrates, including fishes. We report robust acoustic displays during aggressive interactions for a laboratory colony of Danionella dracula, a miniature and transparent species of teleost fish closely related to zebrafish (Danio rerio), which are hypothesized to be sonic based on the presence of a hypertrophied muscle associated with the male swim bladder. Males produce bursts of pulsatile sounds and a distinct postural display - extension of a hypertrophied lower jaw, a morphological trait not present in other Danionella species - during aggressive but not courtship interactions. Females show no evidence of sound production or jaw extension in such contexts. Novel pairs of size-matched or -mismatched males were combined in resident-intruder assays where sound production and jaw extension could be linked to individuals. In both dyad contexts, resident males produced significantly more sound pulses than intruders. During heightened sonic activity, the majority of the highest sound producers also showed increased jaw extension. Residents extended their jaw more than intruders in size-matched but not -mismatched contexts. Larger males in size-mismatched dyads produced more sounds and jaw extensions compared with their smaller counterparts, and sounds and jaw extensions increased with increasing absolute body size. These studies establish D. dracula as a sonic species that modulates putatively acoustic and postural displays during aggressive interactions based on residency and body size, providing a foundation for further investigating the role of multimodal displays in a new model clade for neurogenomic and neuroimaging studies of aggression, courtship and other social interactions.

Taking time: The temporal politics of dementia, care and support in the neighbourhood.

Dementia is a global health challenge and currently the focus of a coordinated international response articulated through the notion of 'dementia-friendly communities and initiatives' (DFCIs). Yet, while increasing research attention has been paid to the social and spatial dimensions to life with dementia in a neighbourhood setting, the temporalities of dementia have been largely overlooked. This article sets out different aspects of the lived experience of time for people with dementia and unpaid carers, before exploring the temporal politics of formal dementia care and support. The authors show that time is a site for material struggle and a marker of unequal relations of power. People with dementia and unpaid carers are disempowered through access to formal care, and this is illustrated in their loss of (temporal) autonomy and limited options for changing the conditions of the care received. The authors advocate for a time-space configured understanding of the relationship with neighbourhood and foreground a tempo-material understanding of dementia. Set against the backdrop of austerity policy in the UK, the findings reveal that ongoing budgetary restrictions have diminished the capacity for social care to mediate in questions of social justice and inequality, at times even compounding inequity.

Associations Between Lifetime Panic Attacks, Posttraumatic Stress Disorder, and Substance Use Disorders in a Nationally Representative Sample.

Objective: Rates of lifetime substance use disorder (SUD) are high among people with lifetime posttraumatic stress disorder (PTSD). Panic attacks are also prevalent among trauma survivors and people with SUD, yet studies on PTSD/SUD have rarely examined comorbid panic. This potentially creates additional barriers to effective treatment for people with PTSD/SUD, in that panic may be under-diagnosed among people with PTSD/SUD and consequently attenuate treatment outcome. Additionally, research on PTSD/SUD often combines people with alcohol use disorder (AUD) and people with drug use disorders (DUDs) into a single group despite evidence that these two PTSD/SUD subgroups differ along important sociodemographic and clinical variables. This study tested the hypothesis that among adults with lifetime PTSD, panic attacks would be associated with greater lifetime risk for both AUD and DUD. We also explored whether panic attacks were associated with specific DUDs that frequently co-occur with PTSD (cannabis, sedatives/tranquilizers, heroin/opioids, and cocaine). Methods: Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III), a cross-sectional national study. Adults with lifetime PTSD (N = 2,230) were classified into one of three groups based on diagnostic interview data: adults with PTSD/AUD (i.e., met criteria for PTSD and AUD but not DUD; n = 656), adults with PTSD/DUD (i.e., met criteria for PTSD and DUD, regardless of AUD diagnostic status; n = 643), or adults with PTSD-only (i.e., met criteria for PTSD but not AUD or DUD; n = 1,031). Results: Weighted logistic regression analyses showed that lifetime risk of PTSD/AUD and PTSD/DUD, each relative to PTSD-only, was greater for adults who were younger at the time of data collection, were male, and had a history of panic attacks. Panic attacks did not predict specific DUD diagnoses comorbid with PTSD in exploratory analyses adjusting for sociodemographic and clinical covariates. Conclusions: Findings highlight the importance of assessing and targeting panic in PTSD/SUD clinics, but suggest panic may not discriminate between specific DUDs that commonly co-occur with PTSD. Study limitations and future directions are discussed.

An in-depth look at latent classes of DSM-5 psychiatric comorbidity among individuals with PTSD: Clinical indicators and treatment utilization.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with high comorbidity rates across the full range of psychiatric disorders. However, little is known about how psychiatric comorbidity manifests among people with PTSD, particularly with regard to concurrent diagnoses. METHOD: Latent class analysis (LCA) was used to characterize discrete classes of PTSD comorbidity using past year DSM-5 diagnostic standards among a large nationally representative epidemiologic sample of U.S. adults. Follow-up analyses compared participant characteristics across latent classes. RESULTS: The LCA was best characterized by five classes: low comorbidity, distress-fear, distress-externalizing, mania-fear-externalizing, and mania-externalizing. Excluding the low comorbidity class, proportions of borderline and schizotypal personality disorder were high across classes. CONCLUSION: Participant characteristics across classes of past year PTSD comorbidity are explored through the lens of case conceptualization and treatment planning utility.

Longitudinal Associations of Global and Daily Support with Marital Status.

The provision and receipt of emotional support demonstrates benefits for relationships; however, little research has investigated how either global or day-to-day spousal support influences marital stability. This project assessed how global perception of support from a partner and daily provision and receipt of emotional support over 1 week contributed to divorce 10 years later, accounting for demographic covariates. There were no significant associations of support variables with future divorce. Greater education attainment was the only factor significantly associated with decreased risk for divorce. Results suggest that despite potential short-term benefits, global and daily support may not predict long-term marital stability.

Relationship Between Posttraumatic Stress Disorder and Sexual Difficulties: A Systematic Review of Veterans and Military Personnel.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with sexual difficulties but the nuances of this relationship remain elusive. Research has increased in recent years, most notably following publication of several reviews in 2015. AIM: This systematic review examines the relationship between PTSD and sexual difficulties in veterans/military personnel. METHODS: A systematic review was conducted using PRISMA guidelines in PsycINFO and PubMed databases for studies examining a diagnosis of PTSD or PTSD severity in relation to a range of sexual difficulties. Forty-three studies were identified that met inclusion and exclusion criteria for this review. RESULTS: PTSD was associated with increased risk of experiencing at least one sexual difficulty. PTSD was most clearly associated with overall sexual function, sexual desire, sexual satisfaction, and sexual distress. Results were mixed for sexual arousal, orgasm function, erectile dysfunction, premature ejaculation, sexual pain, and frequency of sexual activity. PTSD symptom clusters of avoidance and negative alterations in cognition/mood were most commonly associated sexual difficulties. Few studies compared results by gender and trauma type. CLINICAL IMPLICATIONS: Clinicians should inquire about sexual health in relation to PTSD symptoms and target avoidance and negative mood symptoms by incorporating sexual exposure assignments and sexual activation exercises when appropriate. STRENGTHS & LIMITATIONS: This systematic review synthesizes an extensive literature that has grown substantially in the past 5 years and includes studies with low to moderate risk of bias. Limitations of the existing literature include challenges differentiating between PTSD and depression, inconsistent measurement of PTSD and trauma histories, inconsistent operationalization and measurement of sexual outcomes, and largely cross-sectional study designs. CONCLUSION: PTSD is linked to a range of sexual outcomes. The current literature suggests that PTSD is associated with sexual difficulties related to both the sexual response cycle (ie, sexual desire) and one's emotional relationship to sexual activity (eg, sexual distress). More research is needed to increase confidence in findings. Bird ER, Piccirillo M, Garcia N, et al. Relationship Between Posttraumatic Stress Disorder and Sexual Difficulties: A Systematic Review of Veterans and Military Personnel. J Sex Med 2021;18:1398-1426.

Differences in functional and structural social support among female and male veterans and civilians.

PURPOSE: Social support is an important correlate of health behaviors and outcomes. Studies suggest that veterans have lower social support than civilians, but interpretation is hindered by methodological limitations. Furthermore, little is known about how sex influences veteran-civilian differences. Therefore, we examined veteran-civilian differences in several dimensions of social support and whether differences varied by sex. METHODS: We performed a cross-sectional analysis of the 2012-2013 National Epidemiologic Survey of Alcohol and Related Conditions-III, a nationally representative sample of 34,331 respondents (male veterans = 2569; female veterans = 356). We examined veteran-civilian differences in functional and structural social support using linear regression and variation by sex with interactions. We adjusted for socio-demographics, childhood experiences, and physical and mental health. RESULTS: Compared to civilians, veterans had lower social network diversity scores (difference [diff] = - 0.13, 95% confidence interval [CI] - 0.23, - 0.03). Among women but not men, veterans had smaller social network size (diff = - 2.27, 95% CI - 3.81, - 0.73) than civilians, attributable to differences in religious groups, volunteers, and coworkers. Among men, veterans had lower social network diversity scores than civilians (diff = - 0.13, 95% CI - 0.23, - 0.03); while among women, the difference was similar but did not reach statistical significance (diff = - 0.13, 95% CI - 0.23, 0.09). There was limited evidence of functional social support differences. CONCLUSION: After accounting for factors that influence military entry and social support, veterans reported significantly lower structural social support, which may be attributable to reintegration challenges and geographic mobility. Findings suggest that veterans could benefit from programs to enhance structural social support and improve health outcomes, with female veterans potentially in greatest need.

Medical Device Industry Approaches for Addressing Sources of Failing Cytotoxicity Scores.

To ensure patient safety, medical device manufacturers are required by the Food and Drug Administration and other regulatory bodies to perform biocompatibility evaluations on their devices per standards, such as the AAMI-approved ISO 10993-1:2018 (ANSI/AAMI/ISO 10993-1:2018).However, some of these biological tests (e.g., systemic toxicity studies) have long lead times and are costly, which may hinder the release of new medical devices. In recent years, an alternative method using a risk-based approach for evaluating the toxicity (or biocompatibility) profile of chemicals and materials used in medical devices has become more mainstream. This approach is used as a complement to or substitute for traditional testing methods (e.g., systemic toxicity endpoints). Regardless of the approach, the one test still used routinely in initial screening is the cytotoxicity test, which is based on an in vitro cell culture system to evaluate potential biocompatibility effects of the final finished form of a medical device. However, it is known that this sensitive test is not always compatible with specific materials and can lead to failing cytotoxicity scores and an incorrect assumption of potential biological or toxicological adverse effects. This article discusses the common culprits of in vitro cytotoxicity failures, as well as describes the regulatory-approved methodology for cytotoxicity testing and the approach of using toxicological risk assessment to address clinical relevance of cytotoxicity failures for medical devices. Further, discrepancies among test results from in vitro tests, use of published half-maximal inhibitory concentration data, and the derivation of their relationship to tolerable exposure limits, reference doses, or no observed adverse effect levels are highlighted to demonstrate that although cytotoxicity tests in general are regarded as a useful sensitive screening assays, specific medical device materials are not compatible with these cellular/in vitro systems. For these cases, the results should be analyzed using more clinically relevant approaches (e.g., through chemical analysis or written risk assessment).

Boolean model of growth signaling, cell cycle and apoptosis predicts the molecular mechanism of aberrant cell cycle progression driven by hyperactive PI3K.

The PI3K/AKT signaling pathway plays a role in most cellular functions linked to cancer progression, including cell growth, proliferation, cell survival, tissue invasion and angiogenesis. It is generally recognized that hyperactive PI3K/AKT1 are oncogenic due to their boost to cell survival, cell cycle entry and growth-promoting metabolism. That said, the dynamics of PI3K and AKT1 during cell cycle progression are highly nonlinear. In addition to negative feedback that curtails their activity, protein expression of PI3K subunits has been shown to oscillate in dividing cells. The low-PI3K/low-AKT1 phase of these oscillations is required for cytokinesis, indicating that oncogenic PI3K may directly contribute to genome duplication. To explore this, we construct a Boolean model of growth factor signaling that can reproduce PI3K oscillations and link them to cell cycle progression and apoptosis. The resulting modular model reproduces hyperactive PI3K-driven cytokinesis failure and genome duplication and predicts the molecular drivers responsible for these failures by linking hyperactive PI3K to mis-regulation of Polo-like kinase 1 (Plk1) expression late in G2. To do this, our model captures the role of Plk1 in cell cycle progression and accurately reproduces multiple effects of its loss: G2 arrest, mitotic catastrophe, chromosome mis-segregation / aneuploidy due to premature anaphase, and cytokinesis failure leading to genome duplication, depending on the timing of Plk1 inhibition along the cell cycle. Finally, we offer testable predictions on the molecular drivers of PI3K oscillations, the timing of these oscillations with respect to division, and the role of altered Plk1 and FoxO activity in genome-level defects caused by hyperactive PI3K. Our model is an important starting point for the predictive modeling of cell fate decisions that include AKT1-driven senescence, as well as the non-intuitive effects of drugs that interfere with mitosis.

Social Support Moderates the Association Between Posttraumatic Stress Disorder Treatment Duration and Treatment Outcomes in Telemedicine-Based Treatment Among Rural Veterans.

For patients participating in trauma-focused psychotherapies for posttraumatic stress disorder (PTSD), such as cognitive processing therapy (CPT), pretreatment characteristics may moderate treatment effectiveness. For instance, preexisting supportive relationships may encourage skill utilization or provide contrasts to maladaptive cognitive biases highlighted in trauma-focused treatments for PTSD. Such pretreatment characteristics are important to study in rural individuals, who may experience barriers to initiating and completing treatment. The aim of this study was to examine whether pretreatment social support, measured using the Medical Outcomes Study Social Support Survey, would moderate the association between CPT duration (i.e., number of sessions attended) and change in PTSD symptoms, using data from a pragmatic randomized controlled trial of a telemedicine-based collaborative care intervention for rural veterans (N = 225). Social support moderated the association between CPT duration and PTSD symptom change, B = -0.016, SE = -.006; 95% CI [-0.028, -0.005], such that increased duration was associated with more PTSD symptom change only at average or higher levels of support. This effect was found for overall and emotional support but not tangible support. Additionally, on average, among participants who attended eight or more CPT sessions, only those at or above 1 standard deviation above the mean social support score demonstrated a reliable change in PTSD symptoms. The results indicate that the link between CPT treatment duration and treatment outcomes may be stronger for veterans with higher levels of pretreatment social support.