Validation of the BOADICEA model in a prospective cohort of BRCA1/2 pathogenic variant carriers.

BACKGROUND: No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically in BRCA1/2 pathogenic variant (PV) carriers to date. Here, we evaluated the performance of BOADICEA in predicting 5-year breast cancer risks in a prospective cohort of BRCA1/2 PV carriers ascertained through clinical genetic centres. METHODS: We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1614 BRCA1 and 1365 BRCA2 PV carriers (209 incident cases). Study participants had lifestyle, reproductive, hormonal, anthropometric risk factor information, a polygenic risk score based on 313 SNPs and family history information. RESULTS: The full multifactorial model considering family history together with all other risk factors was well calibrated overall (E/O=1.07, 95% CI: 0.92 to 1.24) and in quintiles of predicted risk. Discrimination was maximised when all risk factors were considered (Harrell's C-index=0.70, 95% CI: 0.67 to 0.74; area under the curve=0.79, 95% CI: 0.76 to 0.82). The model performance was similar when evaluated separately in BRCA1 or BRCA2 PV carriers. The full model identified 5.8%, 12.9% and 24.0% of BRCA1/2 PV carriers with 5-year breast cancer risks of <1.65%, <3% and <5%, respectively, risk thresholds commonly used for different management and risk-reduction options. CONCLUSION: BOADICEA may be used to aid personalised cancer risk management and decision-making for BRCA1 and BRCA2 PV carriers. It is implemented in the free-access CanRisk tool (https://www.canrisk.org/).

Reduced cardiac antioxidant defenses mediate increased susceptibility to workload-induced myocardial injury in males with genetic cardiomyopathy.

Ongoing cardiomyocyte injury is a major mechanism in the progression of heart failure, particularly in dystrophic hearts. Due to the poor regenerative capacity of the adult heart, cardiomyocyte death results in the permanent loss of functional myocardium. Understanding the factors contributing to myocyte injury is essential for the development of effective heart failure therapies. As a model of persistent cardiac injury, we examined mice lacking ß-sarcoglycan (ß-SG), a key component of the dystrophin glycoprotein complex (DGC). The loss of the sarcoglycan complex markedly compromises sarcolemmal integrity in this ß-SG-/- model. Our studies aim to characterize the mechanisms underlying dramatic sex differences in susceptibility to cardiac injury in ß-SG-/- mice. Male ß-SG-/- hearts display significantly greater myocardial injury and death following isoproterenol-induced cardiac stress than female ß-SG-/- hearts. This protection of females was independent of ovarian hormones. Male ß-SG-/- hearts displayed increased susceptibility to exogenous oxidative stress and were significantly protected by angiotensin II type 1 receptor (AT1R) antagonism. Increasing general antioxidative defenses or increasing the levels of S-nitrosylation both provided protection to the hearts of ß-SG-/- male mice. Here we demonstrate that increased susceptibility to oxidative damage leads to an AT1R-mediated amplification of workload-induced myocardial injury in male ß-SG-/- mice. Improving oxidative defenses, specifically by increasing S-nitrosylation, provided protection to the male ß-SG-/- heart from workload-induced injury. These studies describe a unique susceptibility of the male heart to injury and may contribute to the sex differences in other forms of cardiac injury.

Mechanisms of reduced myocardial energetics of the dystrophic heart.

Heart disease is a leading cause of death in patients with Duchenne muscular dystrophy (DMD), characterized by the progressive replacement of contractile tissue with scar tissue. Effective therapies for dystrophic cardiomyopathy will require addressing the disease before the onset of fibrosis, however, the mechanisms of the early disease are poorly understood. To understand the pathophysiology of DMD, we perform a detailed functional assessment of cardiac function of the mdx mouse, a model of DMD. These studies use a combination of functional, metabolomic, and spectroscopic approaches to fully characterize the contractile, energetic, and mitochondrial function of beating hearts. Through these innovative approaches, we demonstrate that the dystrophic heart has reduced cardiac reserve and is energetically limited. We show that this limitation does not result from poor delivery of oxygen. Using spectroscopic approaches, we provide evidence that mitochondria in the dystrophic heart have attenuated mitochondrial membrane potential and deficits in the flow of electrons in complex IV of the electron transport chain. These studies provide evidence that poor myocardial energetics precede the onset of significant cardiac fibrosis and likely results from mitochondrial dysfunction centered around complex IV and reduced membrane potential. The multimodal approach used here implicates specific molecular components in the etiology of reduced energetics. Future studies focused on these targets may provide therapies that improve the energetics of the dystrophic heart leading to improved resiliency against damage and preservation of myocardial contractile tissue.NEW & NOTEWORTHY Dystrophic hearts have poor contractile reserve that is associated with a reduction in myocardial energetics. We demonstrate that oxygen delivery does not contribute to the limited energy production of the dystrophic heart even with increased workloads. Cytochrome optical spectroscopy of the contracting heart reveals alterations in complex IV and evidence of depolarized mitochondrial membranes. We show specific alterations in the electron transport chain of the dystrophic heart that may contribute to poor myocardial energetics.

UK recommendations for SDHA germline genetic testing and surveillance in clinical practice.

SDHA pathogenic germline variants (PGVs) are identified in up to 10% of patients with paraganglioma and phaeochromocytoma and up to 30% with wild-type gastrointestinal stromal tumours. Most SDHA PGV carriers present with an apparently sporadic tumour, but often the pathogenic variant has been inherited from parent who has the variant, but has not developed any clinical features. Studies of SDHA PGV carriers suggest that lifetime penetrance for SDHA-associated tumours is low, particularly when identified outside the context of a family history. Current recommended surveillance for SDHA PGV carriers follows an intensive protocol. With increasing implementation of tumour and germline large panel and whole-genome sequencing, it is likely more SDHA PGV carriers will be identified in patients with tumours not strongly associated with SDHA, or outside the context of a strong family history. This creates a complex situation about what to recommend in clinical practice considering low penetrance for tumour development, surveillance burden and patient anxiety. An expert SDHA working group was formed to discuss and consider this situation. This paper outlines the recommendations from this working group for testing and management of SDHA PGV carriers in clinical practice.

Affective dynamics in mother-adolescent dyads: links to mental health and relationship quality.

Current research in developmental psychopathology has emphasised how emotion dynamics, such as affective variability, relate to psychosocial functioning. In this brief article, we examined mean differences in mothers' and adolescents' affective intensity and lability in positive and negative emotions and explored how these emotion dynamics related to depressive symptoms and mother-adolescent relationship quality. We administered individual surveys each day for one week to mother-adolescent dyads (N = 109) that inquired about positive and negative affective states. Affective intensity was measured by the mean across the week and lability by the standard deviation. Participants also reported on their depressive symptoms and adolescents reported on relationship quality. Results showed that positive affect was more intense and more variable than negative affect, and adolescents experienced more intense negative affective and less intense positive affect than mothers. Greater mother and adolescent negative affect intensity and less maternal positive affect intensity related to more depressive symptoms. Affective intensity in mothers and adolescents and affective lability in mothers related to mother-adolescent relationship quality. These findings extend the growing body of knowledge on individuals' affective intensity and variability by considering family dynamics.

Distinct effects of cardiac mitochondrial calcium uniporter inactivation via EMRE deletion in the short and long term.

Transport of Ca2+ into mitochondria is thought to stimulate the production of ATP, a critical process in the heart's fight or flight response, but excess Ca2+ can trigger cell death. The mitochondrial Ca2+ uniporter complex is the primary route of Ca2+ transport into mitochondria, in which the channel-forming protein MCU and the regulatory protein EMRE are essential for activity. In previous studies, chronic Mcu or Emre deletion differed from acute cardiac Mcu deletion in response to adrenergic stimulation and ischemia/reperfusion (I/R) injury, despite equivalent inactivation of rapid mitochondrial Ca2+ uptake. To explore this discrepancy between chronic and acute loss of uniporter activity, we compared short-term and long-term Emre deletion using a novel conditional cardiac-specific, tamoxifen-inducible mouse model. After short-term Emre deletion (3 weeks post-tamoxifen) in adult mice, cardiac mitochondria were unable to take up Ca2+, had lower basal mitochondrial Ca2+ levels, and displayed attenuated Ca2+-induced ATP production and mPTP opening. Moreover, short-term EMRE loss blunted cardiac response to adrenergic stimulation and improved maintenance of cardiac function in an ex vivo I/R model. We then tested whether the long-term absence of EMRE (3 months post-tamoxifen) in adulthood would lead to distinct outcomes. After long-term Emre deletion, mitochondrial Ca2+ handling and function, as well as cardiac response to adrenergic stimulation, were similarly impaired as in short-term deletion. Interestingly, however, protection from I/R injury was lost in the long-term. These data suggest that several months without uniporter function are insufficient to restore bioenergetic response but are sufficient to restore susceptibility to I/R.

FFAR4 regulates cardiac oxylipin balance to promote inflammation resolution in HFpEF secondary to metabolic syndrome.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome, but a predominant subset of HFpEF patients has metabolic syndrome (MetS). Mechanistically, systemic, nonresolving inflammation associated with MetS might drive HFpEF remodeling. Free fatty acid receptor 4 (Ffar4) is a GPCR for long-chain fatty acids that attenuates metabolic dysfunction and resolves inflammation. Therefore, we hypothesized that Ffar4 would attenuate remodeling in HFpEF secondary to MetS (HFpEF-MetS). To test this hypothesis, mice with systemic deletion of Ffar4 (Ffar4KO) were fed a high-fat/high-sucrose diet with L-NAME in their water to induce HFpEF-MetS. In male Ffar4KO mice, this HFpEF-MetS diet induced similar metabolic deficits but worsened diastolic function and microvascular rarefaction relative to WT mice. Conversely, in female Ffar4KO mice, the diet produced greater obesity but no worsened ventricular remodeling relative to WT mice. In Ffar4KO males, MetS altered the balance of inflammatory oxylipins systemically in HDL and in the heart, decreasing the eicosapentaenoic acid-derived, proresolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE), while increasing the arachidonic acid-derived, proinflammatory oxylipin 12-hydroxyeicosatetraenoic acid (12-HETE). This increased 12-HETE/18-HEPE ratio reflected a more proinflammatory state both systemically and in the heart in male Ffar4KO mice and was associated with increased macrophage numbers in the heart, which in turn correlated with worsened ventricular remodeling. In summary, our data suggest that Ffar4 controls the proinflammatory/proresolving oxylipin balance systemically and in the heart to resolve inflammation and attenuate HFpEF remodeling.

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses.

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Survival of cervical cancer patients at Moi teaching and Referral Hospital, Eldoret in western Kenya.

BACKGROUND: Cervical cancer is a major health burden and the second most common cancer after breast cancer among women in Kenya. Worldwide cervical cancer constitutes 3.1% of all cancer cases. Mortality rates are greatest among the low-income countries because of lack of awareness, screening and early-detection programs and adequate treatment facilities. The main aim was to estimate survival and determine survival predictors of women with cervical cancer and limited resources in western Kenya. METHODS: Retrospective charts review of women diagnosed with cervical cancer and follow-up for two years from the date of the histologic diagnosis. The outcome of interest was death or survival at two years. Kaplan Meier estimates of survival, log-rank test and Cox proportional hazards regression were used in the survival analysis. RESULTS: One hundred and sixty-two (162) participants were included in the review. The median duration was 0.8 (interquartile range (IQR) 0.3, 1.6) years. The mean age at diagnosis was 50.6 years (SD12.5). The mean parity was 5.9 (SD 2.6). Fifty percent (50%) did not have health insurance. Twenty six percent (26%) used hormonal contraceptives, 25.9% were HIV positive and 70% of them were on anti-retroviral treatment. The participants were followed up for 152.6 person years. Of the 162 women in the study, 70 (43.2%) died giving an overall incidence rate (IR) of 45.9 deaths per 100 person years of follow up. The hazard ratios were better for the patients who survived (0.44 vs 0.88, p-value < 0.001), those who had medical insurance (0.70 vs 0.48, p-value = 0.007) and those with early stage at diagnosis (0.88 vs 0.39, p-value < 0.001). Participants who were diagnosed at late stage of the disease according to the International Federation of Gynecology and Obstetrics staging for cervical cancer (FIGO stage 2B-4B) had more than eight times increased hazard of death compared to those who were diagnosed at early stage (1-2A): Hazard Ratio: 8.01 (95% CI 3.65, 17.57). Similarly, those who underwent surgical management had 84% reduced hazard of mortality compared to those who were referred for other modes of care: HR: 0.16 (95% CI: 0.07, 0.38). CONCLUSION: Majority of the participants were diagnosed late after presenting with symptoms. The 1 and 2-year survival probability after diagnosis of cervical cancer was 57% AND 45% respectively. It is imperative that women present early since surgery gives better prognosis or better still screening of all women prioritized.

Methotrexate vs expectant management for treatment of tubal ectopic pregnancy: An individual participant data meta-analysis.

INTRODUCTION: Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment. MATERIAL AND METHODS: We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times. TRIAL REGISTRATION NUMBER: PROSPERO: CRD42021214093. RESULTS: 1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95-1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23-1.14). Mean time to success was 19.7 days (95% CI 17.4-22.3) after MTX and 21.2 days (95% CI 17.8-25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group. CONCLUSIONS: Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.

"Work through it on your own": parent-centered emotion socialization beliefs and parenting stress.

Parent-centered emotion socialization beliefs that children should manage their emotions on their own without parent support may seem convenient for parents but may actually relate to greater parenting stress if this approach is incompatible with children's developmental needs. We explored relations between mothers' and fathers' parent-centered autonomy beliefs about children's emotions and their parenting stress, controlling for child behavior problems and parent education. We also examined whether these associations varied depending on child age. Participants included 142 mothers and 60 paired fathers with a 5- to 8-year-old child who completed survey measures on parenting and child behavior. The sample was primarily White (59%) or Hispanic (20%) and low (44%) to middle income (47%). Path analyses revealed significant actor effects, such that mothers and fathers who endorsed more parent-centered emotion socialization beliefs reported greater parenting stress. Partner effects showed that mothers also reported greater parenting stress when their partners endorsed more parent-centered emotion socialization beliefs. Child age did not moderate these associations. Findings are discussed in terms of developmentally appropriate parenting expectations, gender roles for family emotion work, and practical implications.

Engaging the creative heArts of nurse educators: a novel conceptual model.

OBJECTIVES: Nurse educators are increasingly challenged in preparing future nurses to be creative thinkers. The purpose of this innovative quality improvement initiative is to share nursing students' interpretations of the value arts-based pedagogy (ABP) brings to their nursing practice. METHODS: Braun and Clarke's approach to thematic analysis was utilized to identify and report patterns of ideas within learners' interpretations of engaging in an ABP assignment. RESULTS: The analysis of students' interpretations led to the creation of a novel conceptual model to encourage and support nurse educators in the use of innovative ABP approaches. CONCLUSIONS: ABP can be seamlessly integrated within teaching and learning methodologies to cultivate meaningful student learning. IMPLICATIONS FOR INTERNATIONAL AUDIENCE: The intent of the conceptual model is to encourage and support nurse educators in the use of innovative ABP approaches designed for engaging nursing students in active, creative, and challenging learning environments.

DMD carrier model with mosaic dystrophin expression in the heart reveals complex vulnerability to myocardial injury.

Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease that causes progressive muscle wasting and cardiomyopathy. This X-linked disease results from mutations of the DMD allele on the X-chromosome resulting in the loss of expression of the protein dystrophin. Dystrophin loss causes cellular dysfunction that drives the loss of healthy skeletal muscle and cardiomyocytes. As gene therapy strategies strive toward dystrophin restoration through micro-dystrophin delivery or exon skipping, preclinical models have shown that incomplete restoration in the heart results in heterogeneous dystrophin expression throughout the myocardium. This outcome prompts the question of how much dystrophin restoration is sufficient to rescue the heart from DMD-related pathology. Female DMD carrier hearts can shed light on this question, due to their mosaic cardiac dystrophin expression resulting from random X-inactivation. In this work, a dystrophinopathy carrier mouse model was derived by breeding male or female dystrophin-null mdx mice with a wild type mate. We report that these carrier hearts are significantly susceptible to injury induced by one or multiple high doses of isoproterenol, despite expressing ~57% dystrophin. Importantly, only carrier mice with dystrophic mothers showed mortality after isoproterenol. These findings indicate that dystrophin restoration in approximately half of the heart still allows for marked vulnerability to injury. Additionally, the discovery of divergent stress-induced mortality based on parental origin in mice with equivalent dystrophin expression underscores the need for better understanding of the epigenetic, developmental, and even environmental factors that may modulate vulnerability in the dystrophic heart.

Versatile, Cheap, Readily Modifiable Sample Delivery Method for Analysis of Air-/Moisture-Sensitive Samples Using Atmospheric Pressure Solids Analysis Probe Mass Spectrometry.

A cheap, versatile, readily modified, and reusable glass probe system enabling delivery of solid air-/moisture-sensitive samples for mass spectrometric (MS) analysis using an Atmospheric pressure Solids Analysis Probe (ASAP) is described. The simplicity of the design allows quick and easy ASAP MS analyses of sensitive solid and liquid samples without the need for any modifications to commercially available vertically loaded ASAP mass spectrometers. A comparison of ASAP mass spectra obtained for metal complexes under air and an inert atmosphere is given.

Going beyond 'regular and casual': development of a classification of sexual partner types to enhance partner notification for STIs.

OBJECTIVES: To develop a classification of sexual partner types for use in partner notification (PN) for STIs. METHODS: A four-step process: (1) an iterative synthesis of five sources of evidence: scoping review of social and health sciences literature on partner types; analysis of relationship types in dating apps; systematic review of PN intervention content; and review of PN guidelines; qualitative interviews with public, patients and health professionals to generate an initial comprehensive classification; (2) multidisciplinary clinical expert consultation to revise the classification; (3) piloting of the revised classification in sexual health clinics during a randomised controlled trial of PN; (4) application of the Theoretical Domains Framework (TDF) to identify index patients' willingness to engage in PN for each partner type. RESULTS: Five main partner types emerged from the evidence synthesis and consultation: 'established partner', 'new partner', 'occasional partner', 'one-off partner' and 'sex worker'. The types differed across several dimensions, including likely perceptions of sexual exclusivity, likelihood of sex reoccurring between index patient and sex partner. Sexual health professionals found the classification easy to operationalise. During the trial, they assigned all 3288 partners described by 2223 index patients to a category. The TDF analysis suggested that the partner types might be associated with different risks of STI reinfection, onward transmission and index patients' engagement with PN. CONCLUSIONS: We developed an evidence-informed, useable classification of five sexual partner types to underpin PN practice and other STI prevention interventions. Analysis of biomedical, psychological and social factors that distinguish different partner types shows how each could warrant a tailored PN approach. This classification could facilitate the use of partner-centred outcomes. Additional studies are needed to determine the utility of the classification to improve measurement of the impact of PN strategies and help focus resources.

Mechanical ventilation variables associated with high pulmonary artery pressures in ARDS patients: a post hoc analysis.

BACKGROUND: The relationship between indices of mechanical ventilation and pulmonary artery pressures remains ill-defined in ARDS. As our understanding of mechanical ventilation has progressed, there is now a greater appreciation of the impact of high driving pressures and mechanical power in perpetuating lung injury. However, the relationship between the newer derived indices of mechanical ventilation and pulmonary artery pressure is unclear. We performed a post hoc analysis of the Fluid and Catheters Treatment Trial (FACTT) trial to investigate the associations between mechanical ventilation indices in ARDS patients and the prevalence of pulmonary hypertension. This may help elucidate future clinical targets for more, right ventricular protective, mechanical ventilation strategies. METHODS: We performed a post hoc analysis of the FACTT database to identify ARDS patients who had a pulmonary artery catheter (PAC) inserted and pulmonary artery pressure readings recorded. We excluded any patient with a PAC inserted who was spontaneously breathing, as driving pressure and mechanical power are not validated in this cohort. Three independent analyses were performed: a univariate analysis, to assess for associations between mPAP and mechanical ventilation parameters using Pearson correlation coefficients, a multivariate analysis, to assess for independent associations with mPAP using a multiple regression model according to Akaike's information criteria and finally an analysis for nonlinearity, using the best-fitting model according to the Bayesian information criterion (BIC) from linear, quadratic, fractional polynomial and restricted cubic spline models. RESULTS: All the ventilation parameters demonstrated a significant correlation with mPAP, except tidal volume (once adjusted for respiratory rate) in the univariate analysis. The multivariate analysis demonstrated that the blood pH level, P/F ratio, PaCO2 level, mean airway pressure and the mechanical power indexed to compliance were independently associated with mPAP. In the final nonlinear analysis, associations did not differ from linearity except for 4 variables for which the fractional polynomial was the best-fitting model. These were mechanical power (p = 0.01 compared to the linear model), respiratory rate (p = 0.04), peak pressure (p = 0.03) and mean airway pressure (p = 0.01). Two nonlinear variables associated with mPAP were assessed in more detail, respiratory rate and mechanical power. Inflexion points at a respiratory rate of 16.8 cycles per minute and a mechanical power of 8.8 J/min were demonstrated. CONCLUSIONS: The associations identified between mPAP and mechanical ventilation variables in this analysis would suggest that classical ARDS lung protective strategies, including low tidal volume ventilation and permissive hypercapnia, may negatively impact the management of the subset of ARDS patients with associated right ventricular dysfunction or ACP. Additionally, respiratory rates above 17 cycles per minute show an incremental increase in mPAP. Therefore, increases in tidal volume (within the limitation of driving pressure < 18 cmH20) may represent a more right ventricular protective way to control CO2 and pH.

Daily variability in mothers' and fathers' feeding practices and associations with children's eating behaviors.

The current study explores daily variability in maternal and paternal pressuring, restrictive, and structure-related feeding practices and their associations with child energy regulation and food refusal. Multilevel models were run separately for mothers and fathers to understand these associations, as well as within a dyadic framework to account for the interdependence of partners. One hundred families with at least one child between 3- to 5-years old participated by completing seven days of daily diaries. Results suggest there is daily variability in feeding practices for mothers and fathers and children's energy regulation and food refusal. Mothers' daily reports (within family variability) suggested that on days when mothers used more pressure and less structure than usual, children showed more food refusal. Fathers' daily reports suggested that on days when fathers used more pressure or less structure, children showed less energy regulation. On average across the week (between family variability), maternal pressure and restriction was related to child energy regulation. Dyadic multilevel models suggested that fathers' daily feeding behavior was associated with child eating behavior, while mothers' pressure and restrictive feeding on average across the week was a better predictor of between family variability in child eating behavior. For provision of support or structure during feeding, maternal structure was related to less father-reported energy regulation and paternal structure was related to more father-reported energy regulation. The results highlight the necessity of considering both mothers' and fathers' behaviors from day-to-day to get a more authentic picture of the family feeding relationship.

Mothers' and fathers' perceptions of daily mealtime coparenting.

The current study is the first to examine mothers' and fathers' perceptions of mealtime-specific daily coparenting support from their partner. We investigated relations between parents' reports of mealtime-specific coparenting support, global coparenting support, and discrepancies in parents' controlling feeding practices. One-hundred families (67 participating partners) of 3- to 5-year-old children participated. Parents reported daily on coparenting support and feeding practices for seven consecutive days. Preliminary analyses pooling across the week were conducted using correlations, t-tests, and analyses of variance. Although parents' perceptions of global coparenting and mealtime-specific coparenting support were correlated, both mothers and fathers perceived less coparenting support at mealtime than overall in their parenting role. When partners were present at the dinnertime meal, parents perceived greater mealtime coparenting support and mothers also perceived greater global coparenting support from fathers compared to when partners were not present. Using a subsample of families where both mothers and fathers were present at the dinner meal, we used dyadic multilevel models to analyze daily behaviors. These models showed significant daily variability in mothers' mealtime-specific coparenting support from fathers. Fathers' mealtime coparenting support from mothers did not vary day-to-day. On days when mothers perceived greater global coparenting support from their partners, mothers also perceived greater mealtime support. After accounting for the main effects of mothers' and fathers' pressure and restriction, on days when parents reported greater discrepancies between their pressuring feeding practices, mothers perceived less mealtime coparenting support than usual. Results suggest that mealtimes are a challenging context for interparental teamwork, particularly for mothers who receive inconsistent support day-to-day.

Optimising partner notification outcomes for bacterial sexually transmitted infections: a deliberative process and consensus, United Kingdom, 2019.

Partner notification (PN) is an essential element of sexually transmitted infection (STI) control. It enables identification, treatment and advice for sexual contacts who may benefit from additional preventive interventions such as HIV pre- and post-exposure prophylaxis. PN is most effective in reducing STI transmission when it reaches individuals who are most likely to have an STI and to engage in sexual behaviour that facilitates STI transmission, including having multiple and/or new sex partners. Outcomes of PN practice need to be measurable in order to inform standards. They need to address all five stages in the cascade of care: elicitation of partners, establishing contactable partners, notification, testing and treatment. In the United Kingdom, established outcome measures cover only the first three stages and do not take into account the type of sexual partnership. We report an evidence-based process to develop new PN outcomes and inform standards of care. We undertook a systematic literature review, evaluation of published information on types of sexual partnership and a modified Delphi process to reach consensus. We propose six new PN outcome measures at five stages of the cascade, including stratification by sex partnership type. Our framework for PN outcome measurement has potential to contribute in other domains, including Covid-19 contact tracing.

Communicating and Connecting: Associations Between Daily Adolescent Disclosure and Mother-Adolescent Responsiveness.

Adolescents who share information with their parents tend to have more positive parent-adolescent relationships. This brief report examined daily variability in adolescents' disclosure to mothers and mother-adolescent responsiveness. Using a 7-day intensive longitudinal design with 109 mother-adolescent (14-18 years) pairs, multilevel models revealed the amount of information adolescents disclosed to mothers varied day-to-day, according to both adolescent and mother reports. On days when adolescents perceived mothers to be more responsive than usual, adolescents were more likely to disclose. On days when mothers perceived adolescents to be more responsive than usual, mothers perceived more adolescent disclosure. Lastly, more responsive adolescents disclosed more on average across the week according to both adolescent and mother reports of disclosure compared to less responsive adolescents.