Predicting Colonic Neoplasia Surgical Complications: A Machine Learning Approach.

BACKGROUND: A range of statistical approaches have been used to help predict outcomes associated with colectomy. The multifactorial nature of complications suggests that machine learning algorithms may be more accurate in determining postoperative outcomes by detecting nonlinear associations, which are not readily measured by traditional statistics. OBJECTIVE: The aim of this study was to investigate the utility of machine learning algorithms to predict complications in patients undergoing colectomy for colonic neoplasia. DESIGN: Retrospective analysis using decision tree, random forest, and artificial neural network classifiers to predict postoperative outcomes. SETTINGS: National Inpatient Sample database (2003-2017). PATIENTS: Adult patients who underwent elective colectomy with anastomosis for neoplasia. MAIN OUTCOME MEASURES: Performance was quantified using sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve to predict the incidence of anastomotic leak, prolonged length of stay, and inpatient mortality. RESULTS: A total of 14,935 patients (4731 laparoscopic, 10,204 open) were included. They had an average age of 67 ± 12.2 years, and 53% of patients were women. The 3 machine learning models successfully identified patients who developed the measured complications. Although differences between model performances were largely insignificant, the neural network scored highest for most outcomes: predicting anastomotic leak, area under the receiver operating characteristic curve 0.88/0.93 (open/laparoscopic, 95% CI, 0.73-0.92/0.80-0.96); prolonged length of stay, area under the receiver operating characteristic curve 0.84/0.88 (open/laparoscopic, 95% CI, 0.82-0.85/0.85-0.91); and inpatient mortality, area under the receiver operating characteristic curve 0.90/0.92 (open/laparoscopic, 95% CI, 0.85-0.96/0.86-0.98). LIMITATIONS: The patients from the National Inpatient Sample database may not be an accurate sample of the population of all patients undergoing colectomy for colonic neoplasia and does not account for specific institutional and patient factors. CONCLUSIONS: Machine learning predicted postoperative complications in patients with colonic neoplasia undergoing colectomy with good performance. Although validation using external data and optimization of data quality will be required, these machine learning tools show great promise in assisting surgeons with risk-stratification of perioperative care to improve postoperative outcomes. See Video Abstract . PREDICCIN DE LAS COMPLICACIONES QUIRRGICAS DE LA NEOPLASIA DE COLON UN ENFOQUE DE MODELO DE APRENDIZAJE AUTOMTICO: ANTECEDENTES:Se han utilizado una variedad de enfoques estadísticos para ayudar a predecir los resultados asociados con la colectomía. La naturaleza multifactorial de las complicaciones sugiere que los algoritmos de aprendizaje automático pueden ser más precisos en determinar los resultados posoperatorios al detectar asociaciones no lineales, que generalmente no se miden en las estadísticas tradicionales.OBJETIVO:El objetivo de este estudio fue investigar la utilidad de los algoritmos de aprendizaje automático para predecir complicaciones en pacientes sometidos a colectomía por neoplasia de colon.DISEÑO:Análisis retrospectivo utilizando clasificadores de árboles de decisión, bosques aleatorios y redes neuronales artificiales para predecir los resultados posoperatorios.AJUSTE:Base de datos de la Muestra Nacional de Pacientes Hospitalizados (2003-2017).PACIENTES:Pacientes adultos sometidos a colectomía electiva con anastomosis por neoplasia.INTERVENCIONES:N/A.PRINCIPALES MEDIDAS DE RESULTADO:El rendimiento se cuantificó utilizando la sensibilidad, especificidad, precisión y la característica operativa del receptor del área bajo la curva para predecir la incidencia de fuga anastomótica, duración prolongada de la estancia hospitalaria y mortalidad de los pacientes hospitalizados.RESULTADOS:Se incluyeron un total de 14.935 pacientes (4.731 laparoscópicos, 10.204 abiertos). Presentaron una edad promedio de 67 ± 12,2 años y el 53% eran mujeres. Los tres modelos de aprendizaje automático identificaron con éxito a los pacientes que desarrollaron las complicaciones medidas. Aunque las diferencias entre el rendimiento del modelo fueron en gran medida insignificantes, la red neuronal obtuvo la puntuación más alta para la mayoría de los resultados: predicción de fuga anastomótica, característica operativa del receptor del área bajo la curva 0,88/0,93 (abierta/laparoscópica, IC del 95%: 0,73-0,92/0,80-0,96); duración prolongada de la estancia hospitalaria, característica operativa del receptor del área bajo la curva 0,84/0,88 (abierta/laparoscópica, IC del 95%: 0,82-0,85/0,85-0,91); y mortalidad de pacientes hospitalizados, característica operativa del receptor del área bajo la curva 0,90/0,92 (abierto/laparoscópico, IC del 95%: 0,85-0,96/0,86-0,98).LIMITACIONES:Los pacientes de la base de datos de la Muestra Nacional de Pacientes Hospitalizados pueden no ser una muestra precisa de la población de todos los pacientes sometidos a colectomía por neoplasia de colon y no tienen en cuenta factores institucionales y específicos del paciente.CONCLUSIONES:El aprendizaje automático predijo con buen rendimiento las complicaciones postoperatorias en pacientes con neoplasia de colon sometidos a colectomía. Aunque será necesaria la validación mediante datos externos y la optimización de la calidad de los datos, estas herramientas de aprendizaje automático son muy prometedoras para ayudar a los cirujanos con la estratificación de riesgos de la atención perioperatoria para mejorar los resultados posoperatorios. (Traducción-Dr. Fidel Ruiz Healy ).

Daily perceptions of romantic partner autonomy support and undermining of health behavior.

OBJECTIVE: This study examined accuracy and bias in daily perceptions of a romantic partner's autonomy support and undermining of health behaviors and the associations between misperceptions and both partners' daily experiences. DESIGN: A sample of 106 cohabiting couples from the community completed daily reports (N = 2377) of their own and their partner's autonomy support and undermining, and their daily experiences. RESULTS: We found tracking accuracy and projection in perceptions of provider's autonomy support and undermining, and evidence of misperceptions: people over-perceived the provider's undermining and under-perceived the provider's autonomy support. Misperceptions were linked with more negative experiences, indicating support and undermining may have the most benefit and least harm when more accurately perceived. CONCLUSION: Although there is some accuracy in daily perceptions of provider support and undermining of health behaviors, there are also biases at play in perceptions and misperceptions are linked with more negative experiences, indicating that support and undermining have the most benefit and least harm to both perceiving and providing partners when such behaviors are accurately perceived.

Targeted Polymersome Delivery of a Stapled Peptide for Drugging the Tumor Protein p53:BCL-2-Family Axis in Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) remains a formidable diagnosis in need of new treatment paradigms. In this work, we elucidated an opportunity for therapeutic synergy in DLBCL by reactivating tumor protein p53 with a stapled peptide, ATSP-7041, thereby priming cells for apoptosis and enhancing their sensitivity to BCL-2 family modulation with a BH3-mimetic, ABT-263 (navitoclax). While this combination was highly effective at activating apoptosis in DLBCL in vitro, it was highly toxic in vivo, resulting in a prohibitively narrow therapeutic window. We, therefore, developed a targeted nanomedicine delivery platform to maintain the therapeutic potency of this combination while minimizing its toxicity via packaging and targeted delivery of a stapled peptide. We developed a CD19-targeted polymersome using block copolymers of poly(ethylene glycol) disulfide linked to poly(propylene sulfide) (PEG-SS-PPS) for ATSP-7041 delivery into DLBCL cells. Intracellular delivery was optimized in vitro and validated in vivo by using an aggressive human DLBCL xenograft model. Targeted delivery of ATSP-7041 unlocked the ability to systemically cotreat with ABT-263, resulting in delayed tumor growth, prolonged survival, and no overt toxicity. This work demonstrates a proof-of-concept for antigen-specific targeting of polymersome nanomedicines, targeted delivery of a stapled peptide in vivo, and synergistic dual intrinsic apoptotic therapy against DLBCL via direct p53 reactivation and BCL-2 family modulation.

Multi-staged vs Single-staged Pelvic Osteotomy in the Modern Treatment of Cloacal Exstrophy: Bridging the Gap.

PURPOSE: Staged pelvic osteotomy has been shown in the past to be an effective tool in the closure of the extreme pubic diastasis of cloacal exstrophy. The authors sought to compare orthopedic complications between non-staged pelvic osteotomies and staged pelvic osteotomies in cloacal exstrophy. METHODS: A prospectively maintained exstrophy-epispadias complex database of 1510 patients was reviewed for cloacal exstrophy bladder closure events performed with osteotomy at the authors' institution. Bladder closure failure was defined as any fascial dehiscence, bladder prolapse, or vesicocutaneous fistula within one year of closure. There was a total of 172 cloacal exstrophy and cloacal exstrophy variant patients within the database and only closures at the authors' institution were included. RESULTS: 64 closure events fitting the inclusion criteria were identified in 61 unique patients. Staged osteotomy was performed in 42 closure events and non-staged in 22 closures. Complications occurred in 46/64 closure events, with 16 grade III/IV complications. There were no associations between staged osteotomy and overall complication or grade III/IV complications (p = 0.6344 and p = 0.1286, respectively). Of the 46 total complications, 12 were orthopedic complications with 6 complications being grade III/IV. Staged osteotomy closure events experienced 10/42 orthopedic complications while non-staged osteotomy closures experienced 2/22 orthopedic complications, however this did not reach significance (p = 0.1519). Of the 64 closure events, 57 resulted in successful closure with 6 failures and one closure with planned cystectomy. CONCLUSION: This study confirms, in a larger series, superior outcomes when using staged pelvic osteotomy in cloacal exstrophy bladder closure. Staged osteotomy was shown to be a safe alternative to non-staged osteotomy that can decrease the risk of closure failure in this group. Staged pelvic osteotomy should be considered in all patients undergoing cloacal exstrophy bladder closure. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.

Protocol for detection of ferroptosis in cultured cells.

Mammalian cells can die by apoptosis or by one of several non-apoptotic mechanisms, such as ferroptosis. Here, we present a protocol to distinguish ferroptosis from other cell death mechanisms in cultured cells. We describe steps for seeding cells, administering mechanism-specific cell death inducers and inhibitors, and measuring cell death and viability. We then detail the use of molecular markers to verify mechanisms of cell death. This protocol can be used to identify and distinguish ferroptosis in 2D and 3D cultures. For complete details on the use and execution of this protocol, please refer to Ko, et al. (2019),1 Magtanong, et al. (2022),2 and Armenta, et al. (2022).3.

Infantile versus childhood posterior urethral valve diagnosis: management patterns and clinical outcomes at opposite ends of the spectrum.

BACKGROUND: Management patterns and outcomes are poorly defined in cases of late PUV diagnosis. OBJECTIVE: To compare post-ablation management and clinical outcomes of patients with infantile (<1 year) versus childhood (>5 year) PUV diagnosis to gain insight into the pathologies at opposite ends of the PUV spectrum. STUDY DESIGN: A multicenter retrospective cohort study was conducted using the TriNetX research network between 2006 and 2022. TriNetX synthesizes insurance claims and electronic medical record data for over 110 million patients from 92 healthcare organizations. We defined two cohorts: 1) The <1 year arm had an index diagnosis of PUV and cystoscopy with valve ablation within 1 year of life, 2) the >5 year arm had an index diagnosis of PUV and valve ablation after age 5. We report rates and time-to-first use of antispasmodics, alpha-blockers, CIC, bladder botox, enterocystoplasty or Mitrofanoff or secondary cutaneous vesicostomy, and CKD. RESULTS: We identified 569 patients (323 <1 year; 246 >5 year). Median age at diagnosis was 1 month (median follow-up 8 years) and 9 years (median follow-up 10 years) for the <1 year and >5 year cohorts, respectively. Following ablation, both arms were primarily managed with antispasmodics, with no difference between groups. The >5 year arm was significantly more likely to receive alpha-blockers or bladder botox. The <1 year arm was significantly more likely to be started on CIC, undergo enterocystoplasty, Mitrofanoff or secondary cutaneous vesicostomy, or renal transplantation. The <1 year arm had significantly higher rates and shorter time-to-progression to all stages of CKD. DISCUSSION: Despite higher utilization of conservative strategies among patients with a late PUV diagnosis, these patients had superior renal outcomes and low rates of progression to invasive treatments. Limitations include potential inaccuracies in medical coding as well as variations in thresholds to initiate CIC, perform surgical reconstruction, or proceed with renal transplantation at participating centers. CONCLUSIONS: These findings provide evidence that a late PUV diagnosis reflects an overall milder disease process.

Study protocol for The GOAL Trial: comprehensive geriatric assessment for frail older people with chronic kidney disease to increase attainment of patient-identified goals-a cluster randomised controlled trial.

BACKGROUND: An increasing number of older people are living with chronic kidney disease (CKD). Many have complex healthcare needs and are at risk of deteriorating health and functional status, which can adversely affect their quality of life. Comprehensive geriatric assessment (CGA) is an effective intervention to improve survival and independence of older people, but its clinical utility and cost-effectiveness in frail older people living with CKD is unknown. METHODS: The GOAL Trial is a pragmatic, multi-centre, open-label, superiority, cluster randomised controlled trial developed by consumers, clinicians, and researchers. It has a two-arm design, CGA compared with standard care, with 1:1 allocation of a total of 16 clusters. Within each cluster, study participants ≥ 65 years of age (or ≥ 55 years if Aboriginal or Torres Strait Islander (First Nations Australians)) with CKD stage 3-5/5D who are frail, measured by a Frailty Index (FI) of > 0.25, are recruited. Participants in intervention clusters receive a CGA by a geriatrician to identify medical, social, and functional needs, optimise medication prescribing, and arrange multidisciplinary referral if required. Those in standard care clusters receive usual care. The primary outcome is attainment of self-identified goals assessed by standardised Goal Attainment Scaling (GAS) at 3 months. Secondary outcomes include GAS at 6 and 12 months, quality of life (EQ-5D-5L), frailty (Frailty Index - Short Form), transfer to residential aged care facilities, cost-effectiveness, and safety (cause-specific hospitalisations, mortality). A process evaluation will be conducted in parallel with the trial including whether the intervention was delivered as intended, any issue or local barriers to intervention delivery, and perceptions of the intervention by participants. The trial has 90% power to detect a clinically meaningful mean difference in GAS of 10 units. DISCUSSION: This trial addresses patient-prioritised outcomes. It will be conducted, disseminated and implemented by clinicians and researchers in partnership with consumers. If CGA is found to have clinical and cost-effectiveness for frail older people with CKD, the intervention framework could be embedded into routine clinical practice. The implementation of the trial's findings will be supported by presentations at conferences and forums with clinicians and consumers at specifically convened workshops, to enable rapid adoption into practice and policy for both nephrology and geriatric disciplines. It has potential to materially advance patient-centred care and improve clinical and patient-reported outcomes (including quality of life) for frail older people living with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04538157. Registered on 3 September 2020.

Northern spotted owl nesting habitat under high potential wildfire threats along the California Coastal Redwood Forest.

Large and severe wildfires, exacerbated by climate change and human behavior, are occurring more frequently in many forests across the western United States. While wildfire is a natural part of most terrestrial ecosystems, rapidly changing fire regimes have the potential to alter habitat beyond the adaptive capabilities of species. Spatial assessments of wildfire risks to species habitat may allow managers to pinpoint locations for management activities. To illustrate this, we spatially assessed wildfire risk within habitat that supports the nesting activity of the federally threatened northern spotted owl (Strix occidentalis caurina) in the California redwood coast ecoregion. To accomplish this, we built a scale-optimized ensemble nesting habitat suitability model and identified habitat with the highest wildfire hazard potential. Percent canopy cover at 100-m scale, slope at 400-m scale, and January precipitation at 800-m scale were the most influential environmental covariates for predicting northern spotted owl nesting habitat. Nearly 60% of nesting habitat was predicted to be at high or very high (>1986 index value) wildfire risks. We identified three areas in the Maple Creek Area of Humboldt County, Jackson State Demonstration Forest in Mendocino County, and Point Reyes National Seashore in Marin County, California with a high concentration of nesting habitat that are at a very high risk of experiencing high severity wildfires. We recommend these areas be targeted for future research to understand the impact of wildfire on northern spotted owl as well as management attention.

Assessing Children's Relationships with Pet Dogs: A Multi-Method Approach.

Relationships with pet dogs are thought to provide substantial benefits for children, but the study of these relationships has been hindered by a lack of validated measures. Approaches to assessing the quality of children's pet dog relationships have tended to focus on positive relationship qualities and to rely on self-report questionnaires. The aim of this study was to develop and test multiple measures that could be used to assess both positive and negative features of children's relationships with pet dogs. In a sample of 115 children ages 9-14 years who were pet dog owners, we assessed six qualities of pet dog relationships: Affection, Nurturance of Pet, Emotional Support from Pet, Companionship, Friction with Pet, and Pets as Substitutes for People. All qualities were assessed with child questionnaires, parent questionnaires, and child daily reports of interactions with pets. We found substantial convergence in reports from different observers and across different measurement approaches. Principal components analyses and correlations suggested overlap for many of the positive qualities, which tended to be distinct from negative relationship qualities. The study provides new tools which could be used to test further how relationships with pets contribute to children's development.

Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-Related Autoimmune Diseases.

OBJECTIVE: Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including systemic lupus erythematosus and lupus nephritis. We undertook this study to develop and evaluate a high-affinity APRIL/BAFF antagonist to overcome the clinical limitations of existing B cell inhibitors. METHODS: A variant of TACI-Fc generated by directed evolution showed enhanced binding for both APRIL and BAFF and was designated povetacicept (ALPN-303). Povetacicept was compared to wild-type (WT) TACI-Fc and related molecules in vitro and in vivo. RESULTS: Povetacicept inhibited APRIL and BAFF more effectively than all evaluated forms of WT TACI-Fc and selective APRIL and BAFF inhibitors in cell-based reporter assays and primary human B cell assays, mediating potent suppression of B cell proliferation, differentiation, and immunoglobulin (Ig) secretion. In mouse immunization models, povetacicept significantly reduced serum immunoglobulin titers and antibody-secreting cells more effectively than anti-CD20 monoclonal antibodies, WT TACI-Fc, or APRIL and BAFF inhibitors. In the NZB × NZW mouse lupus nephritis model, povetacicept significantly enhanced survival and suppressed proteinuria, anti-double-stranded DNA antibody titers, blood urea nitrogen, glomerulonephritis, and renal immunoglobulin deposition. In the bm12 mouse lupus model, povetacicept significantly reduced splenic plasmablasts, follicular helper T cells, and germinal center B cells. In non-human primates, povetacicept was well tolerated, exhibited high serum exposure, and significantly decreased serum IgM, IgA, and IgG levels after a single dose. CONCLUSION: Enhanced APRIL and BAFF inhibition by povetacicept led to greater inhibition of B cell populations critical for autoantibody production compared to WT TACI-Fc and CD20-, APRIL-, or BAFF-selective inhibitors. Potent, dual inhibition by povetacicept has the potential to significantly improve clinical outcomes in autoantibody-related autoimmune diseases.

Perceptions of partner social control: accuracy, bias, and daily experience.

OBJECTIVE: We examined accuracy and bias in people's perceptions of their romantic partner's daily social control attempts of daily health behaviours and how misperceptions of partner daily social control are related to both partners' daily experiences. DESIGN: 106 cohabiting couples from the community reported on their own and their partner's daily social control attempts (i.e., persuasion, pressure) and their daily experiences (i.e., positive and negative affect, autonomy, relationship satisfaction) across 14 consecutive days (N = 2377 reports). Multilevel path models examined tracking accuracy, projection, and mean-level bias in perceptions of partner health social control attempts, and associations between mean-level bias and daily experiences. RESULTS: Perceptions of provider influence contained significant tracking accuracy, projection, and mean-level accuracy in provider use of social control. Underperceptions of persuasion were associated with negative outcomes for the perceiver and no outcomes for the provider. Overperceptions of persuasion were associated with negative outcomes for providers and marginally higher positive affect for perceivers. Misperceptions of pressure were associated with negative outcomes for both perceivers and providers. CONCLUSION: Results suggest that social control may have the most benefit and least harm to both partners when people accurately perceive the mean-levels of such influence attempts on their health behaviours.

Parental emotion socialization: Relations with adjustment, security, and maternal depression in early adolescence.

How parents approach and teach their children about emotions are key determinants of children's healthy adjustment (Denham, 2019). Parental emotion socialization has been mostly studied in parents of young children. Our study identified emotion socialization (ES) strategies used by parents of early adolescents (Study 1) and then examined the relations of ES strategies with early adolescent adjustment, parent-child attachment, and maternal depression (Study 2). Study 1 included 171 parents of 9- to 14-year-old children who completed an open-ended questionnaire about their reactions to their children's negative emotions, which was content coded for ES strategies. We found that parents do use the 6 traditional ES strategies (problem solving, emotion focused/comforting, encouragement, minimizing, punitive, and distress) with early adolescents, while also using 3 approaches not identified in studies of parents of younger children (self-regulation, parent seeking information, parent explaining). We also found that some ES strategies are context and gender specific. Study 2 included 218 mother and child dyads (children aged 9- to 14- years). Mothers completed the Revised Coping with Children's Negative Emotions Scale, adapted to include items assessing the 3 new strategies, and measures of child adjustment, attachment, and maternal depression. The ES strategies loaded on 3 factors: Collaborative Coping, Negative Reactions to Child's Distress, and Low Expectation for Child's Self-Regulation. Negative Reactions to Child's Distress showed associations with children's internalizing, externalizing, and prosocial behavior, and child attachment, while Collaborative Coping was related to prosocial behavior. Our results point to the importance of investigating additional ES strategies in early adolescence. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Anxiety, academic achievement, and academic self-concept: Meta-analytic syntheses of their relations across developmental periods.

This systematic review examined how anxiety symptoms and anxiety disorders relate to academic achievement, school dropout, and academic self-concept. Studies with children or adult samples were included in seven meta-analyses (ks for number of samples ranged from 5 to 156; N's for participants ranged from 780 to 37, 203). Results revealed significant but very small effect sizes for the relations between anxiety and overall academic achievement (r = -.06), language achievement (r = -.07), and math achievement (r = -.09), and a nonsignificant effect size for science achievement (r = -.01). Participants with greater anxiety were also significantly more likely to not complete high school (r = .11). They also had a poorer overall academic self-concept (r = -.25) and mathematics self-concept (r = -.30). Few methodological moderators (e.g., study design, age) were significant. Results show that anxiety does not strongly hinder academic achievement, but it is an important correlate of dropout and academic self-concept, which in turn could contribute to poorer life outcomes. Interventions and preventive programs need to consider ways to ameliorate the relations of anxiety with academic outcomes, especially school continuation and academic self-concept. Future studies should identify risk factors that may amplify these relations.

Forging a path toward a more sustainable laboratory.

Scientific discovery has advanced human society in countless ways, but research requires the expenditure of energy and resources. This Scientific Life article details one laboratory's efforts to reduce the environmental impact of wet-lab research and provides a series of resources to improve lab sustainability.

Increased Ion Temperature and Neutron Yield Observed in Magnetized Indirectly Driven D_{2}-Filled Capsule Implosions on the National Ignition Facility.

The application of an external 26 Tesla axial magnetic field to a D_{2} gas-filled capsule indirectly driven on the National Ignition Facility is observed to increase the ion temperature by 40% and the neutron yield by a factor of 3.2 in a hot spot with areal density and temperature approaching what is required for fusion ignition [1]. The improvements are determined from energy spectral measurements of the 2.45 MeV neutrons from the D(d,n)^{3}He reaction, and the compressed central core B field is estimated to be ∼4.9 kT using the 14.1 MeV secondary neutrons from the D(T,n)^{4}He reactions. The experiments use a 30 kV pulsed-power system to deliver a ∼3 µs current pulse to a solenoidal coil wrapped around a novel high-electrical-resistivity AuTa_{4} hohlraum. Radiation magnetohydrodynamic simulations are consistent with the experiment.

Testosterone and Male Sexual Function.

This article reviews the role of testosterone in normal male sexual anatomic development and function, the consequences of low testosterone on sexual function, and clinical standards for health care providers treating hypogonadal men with sexual dysfunction.

The Role of Ambulatory Blood Pressure Monitoring in Current Clinical Practice.

Hypertension continues to be the leading modifiable risk factor for stroke, kidney disease and cardiovascular disease, and it also plays a key role in a significant proportion of preventable deaths globally. Ambulatory blood pressure monitoring (ABPM) is an underutilised tool that augments the accurate diagnosis of hypertension. Out-of-office blood pressure measurements such as ABPM, permits the diagnosis of white coat hypertension and masked hypertension as well as determining a patient's nocturnal dipping status. These common clinical phenotypes have relevance with regard to clinical outcomes and may impact management. Overall, the diagnosis and management of hypertension presents numerous challenges, requiring the complementary use of multimodal blood pressure monitoring. Familiarity with the use of ABPM is important in the optimal management of patients, particularly as it becomes more accessible with the recent introduction of a Medicare Benefits Schedule item number.

Parent-Child Attachment Security and Depressive Symptoms in Early Adolescence: The Mediating Roles of Gratitude and Forgiveness.

Although greater parent-child attachment security is linked with children's lower levels of depressive symptoms, little research has evaluated potential explanatory mechanisms. We investigated whether dispositional gratitude and interpersonal forgiveness explain the relation between attachment security with parents and early adolescents' depressive symptoms. Early adolescents (N = 105; M age = 12.3 years; 51% girls) completed questionnaires assessing their attachment security to mother and father figures, depressive symptoms, and dispositional gratitude, and an interview assessing interpersonal forgiveness. Results revealed that greater attachment security to mothers and fathers was associated with fewer depressive symptoms and greater levels of dispositional gratitude and interpersonal forgiveness. Further, dispositional gratitude and interpersonal forgiveness were negatively associated with depressive symptoms. Dispositional gratitude emerged as a mediator between attachment security with each parent and depressive symptoms. Our findings suggest that greater parent-child security may promote early adolescents' appreciation of positive events, which in turn may relate to fewer depressive symptoms.

Clonal architecture predicts clinical outcomes and drug sensitivity in acute myeloid leukemia.

The impact of clonal heterogeneity on disease behavior or drug response in acute myeloid leukemia remains poorly understood. Using a cohort of 2,829 patients, we identify features of clonality associated with clinical features and drug sensitivities. High variant allele frequency for 7 mutations (including NRAS and TET2) associate with dismal prognosis; elevated GATA2 variant allele frequency correlates with better outcomes. Clinical features such as white blood cell count and blast percentage correlate with the subclonal abundance of mutations such as TP53 and IDH1. Furthermore, patients with cohesin mutations occurring before NPM1, or transcription factor mutations occurring before splicing factor mutations, show shorter survival. Surprisingly, a branched pattern of clonal evolution is associated with superior clinical outcomes. Finally, several mutations (including NRAS and IDH1) predict drug sensitivity based on their subclonal abundance. Together, these results demonstrate the importance of assessing clonal heterogeneity with implications for prognosis and actionable biomarkers for therapy.

Electrocardiographic QRS duration is influenced by body mass index and sex.

BACKGROUND: Electrocardiogram (ECG) measured QRS duration has been shown to influence cardiovascular outcomes. However, there is paucity of data on whether ECG QRS duration is influenced by obesity and sex in large populations. METHODS: All ECGs performed by a pathology provider over a 2-year period were included. ECGs with confounding factors and those not in sinus rhythm were excluded from the primary analysis. RESULTS: Of the 76,220 who met the inclusion criteria, 41,685 (55%) were females. The median age of the study cohort was 61 years (interquartile [IQR] range 48-71 years). The median QRS duration was 86 ms (IQR 80-94 ms). The median BMI was 27.6 kg/m2 (IQR 24.2-31.8 kg/m2). When stratified according to the World Health Organization classification of BMI < 18.50 kg/m2, 18.50-24.99 kg/m2, 25.00-29.99 kg/m2, and ≥ 30.00 kg/m2, the median QRS durations were 82 ms (IQR 76-88 ms), 86 ms (IQR 80-92 ms), 88 ms (IQR 80-94 ms) and 88 ms (IQR 82-94 ms), respectively (p < 0.001 for linear trend). Median QRS duration for females was 84 ms (IQR 78-88 ms); for males, it was 92 ms (IQR 86-98 ms), p < 0.001. Compared to males, females had narrower QRS complexes at similar age and similar BMI. In multiple linear regression analysis, BMI correlated positively with QRS duration (standardized beta 0.095, p < 0.001) independent of age, sex, and heart rate. CONCLUSIONS: In this large cohort there was a positive association between increasing BMI and QRS duration. Females had narrower QRS duration than males at similar age and similar BMI.