Crosstalk of MAP3K1 and EGFR signaling mediates gene-environment interactions that block developmental tissue closure.

Aberrant regulation of signal transduction pathways can adversely derail biological processes for tissue development. One such process is the embryonic eyelid closure that is dependent on the Mitogen-Activated Protein Kinase Kinase Kinase 1 (MAP3K1). Map3k1 knockout in mice results in defective eyelid closure and an autosomal recessive eye-open at birth phenotype. We have shown that in utero exposure to dioxin, a persistent environmental toxicant, induces the same eye defect in Map3k1+/- heterozygous but not wild type pups. Here we explore the mechanisms of the Map3k1 (gene) and dioxin (environment) interactions (GxE) underlying defective eyelid closure. We show that, acting through the Aryl Hydrocarbon Receptor (AHR), dioxin activates Epidermal Growth Factor Receptor (EGFR) signaling, which in turn depresses MAP3K1-dependent Jun N-terminal Kinase (JNK) activity. The dioxin mediated JNK repression is moderate but is exacerbated by Map3k1 heterozygosity. Therefore, dioxin exposed Map3k1+/- embryonic eyelids have a marked reduction of JNK activity, accelerated differentiation and impeded polarization in the epithelial cells. Knocking out Ahr or Egfr in eyelid epithelium attenuates the open-eye defects in dioxin-treated Map3k1+/- pups, whereas knockout of Jnk1 and S1pr that encodes the Sphigosin-1-phosphate (S1P) receptors upstream of the MAP3K1-JNK pathway potentiates the dioxin toxicity. Our novel findings show that the crosstalk of AHR, EGFR and S1P-MAP3K1-JNK pathways determines the outcome of dioxin exposure. Thus, gene mutations targeting these pathways are potential risk factors for the toxicity of environmental chemicals.

Nonparametric scanning tests of homogeneity for hierarchical models with continuous covariates.

In many applications of hierarchical models, there is often interest in evaluating the inherent heterogeneity in view of observed data. When the underlying hypothesis involves parameters resting on the boundary of their support space such as variances and mixture proportions, it is a usual practice to entertain testing procedures that rely on common heterogeneity assumptions. Such procedures, albeit omnibus for general alternatives, may entail a substantial loss of power for specific alternatives such as heterogeneity varying with covariates. We introduce a novel and flexible approach that uses covariate information to improve the power to detect heterogeneity, without imposing unnecessary restrictions. With continuous covariates, the approach does not impose a regression model relating heterogeneity parameters to covariates or rely on arbitrary discretizations. Instead, a scanning approach requiring continuous dichotomizations of the covariates is proposed. Empirical processes resulting from these dichotomizations are then used to construct the test statistics, with limiting null distributions shown to be functionals of tight random processes. We illustrate our proposals and results on a popular class of two-component mixture models, followed by simulation studies and applications to two real datasets in cancer and caries research.

A classification for complex imbalanced data in disease screening and early diagnosis.

Imbalanced classification has drawn considerable attention in the statistics and machine learning literature. Typically, traditional classification methods often perform poorly when a severely skewed class distribution is observed, not to mention under a high-dimensional longitudinal data structure. Given the ubiquity of big data in modern health research, it is expected that imbalanced classification in disease diagnosis may encounter an additional level of difficulty that is imposed by such a complex data structure. In this article, we propose a nonparametric classification approach for imbalanced data in longitudinal and high-dimensional settings. Technically, the functional principal component analysis is first applied for feature extraction under the longitudinal structure. The univariate exponential loss function coupled with group LASSO penalty is then adopted into the classification procedure in high-dimensional settings. Along with a good improvement in imbalanced classification, our approach provides a meaningful feature selection for interpretation while enjoying a remarkably lower computational complexity. The proposed method is illustrated on the real data application of Alzheimer's disease early detection and its empirical performance in finite sample size is extensively evaluated by simulations.

On testing for homogeneity with zero-inflated models through the lens of model misspecification.

In many applications of two-component mixture models such as the popular zero-inflated model for discrete-valued data, it is customary for the data analyst to evaluate the inherent heterogeneity in view of observed data. To this end, the score test, acclaimed for its simplicity, is routinely performed. It has long been recognized that this test may behave erratically under model misspecification, but the implications of this behavior remain poorly understood for popular two-component mixture models. For the special case of zero-inflated count models, we use data simulations and theoretical arguments to evaluate this behavior and discuss its implications in settings where the working model is restrictive with regard to the true data generating mechanism. We enrich this discussion with an analysis of count data in HIV research, where a one-component model is shown to fit the data reasonably well despite apparent extra zeros. These results suggest that a rejection of homogeneity does not imply that the underlying mixture model is appropriate. Rather, such a rejection simply implies that the mixture model should be carefully interpreted in the light of potential model misspecifications, and further evaluated against other competing models.

Fall Detection with the Spatial-Temporal Correlation Encoded by a Sequence-to-Sequence Denoised GAN.

Falling is a major cause of personal injury and accidental death worldwide, in particular for the elderly. For aged care, a falling alarm system is highly demanded so that medical aid can be obtained immediately when the fall accidents happen. Previous studies on fall detection lacked practical considerations to deal with real-world situations, including the camera's mounting angle, lighting differences between day and night, and the privacy protection for users. In our experiments, IR-depth images and thermal images were used as the input source for fall detection; as a result, detailed facial information is not captured by the system for privacy reasons, and it is invariant to the lighting conditions. Due to the different occurrence rates between fall accidents and other normal activities, supervised learning approaches may suffer from the problem of data imbalance in the training phase. Accordingly, in this study, anomaly detection is performed using unsupervised learning approaches so that the models were trained only with the normal cases while the fall accident was defined as an anomaly event. The proposed system takes sequential frames as the inputs to predict future frames based on a GAN structure, and it provides (1) multi-subject detection, (2) real-time fall detection triggered by motion, (3) a solution to the situation that subjects were occluded after falling, and (4) a denoising scheme for depth images. The experimental results show that the proposed system achieves the state-of-the-art performance and copes with the real-world cases successfully.

Prolonged mechanical ventilation increases diaphragm arteriole circumferential stretch without changes in stress/stretch: Implications for the pathogenesis of ventilator-induced diaphragm dysfunction.

INTRODUCTION: Prolonged mechanical ventilation (MV; ≥6 h) results in large, time-dependent reductions in diaphragmatic blood flow and shear stress. We tested the hypothesis that MV would impair the structural and material properties (ie, increased stress/stretch relation and/or circumferential stretch) of first-order arterioles (1A) from the medial costal diaphragm. METHODS: Shear stress was estimated from isolated arterioles and prior blood flow data from the diaphragm during spontaneous breathing (SB) and prolonged MV (6 h MV). Thereafter, female Sprague-Dawley rats (~5 months) were randomly divided into two groups, SB (n = 6) and 6 h MV (n = 6). Following SB and 6 h MV, 1A medial costal diaphragm arterioles were isolated, cannulated, and subjected to stepwise (0-140 cmH2 O) increases in intraluminal pressure in calcium-free Ringer's solution. Inner diameter and wall thickness were measured at each pressure step and used to calculate wall:lumen ratio, Cauchy-stress, and circumferential stretch. RESULTS: Compared to SB, there was a ~90% reduction in arteriolar shear stress with prolonged MV (9 ± 2 vs 78 ± 20 dynes/cm2 ; p ≤ .05). In the unloaded condition (0 cmH2 O), the arteriolar intraluminal diameter was reduced (37 ± 8 vs 79 ± 13 µm) and wall:lumen ratio was increased (120 ± 18 vs 46 ± 10%) compared to SB (p ≤ .05). There were no differences in the passive diameter responses or the circumferential stress/stretch relationship between groups (p > .05), but at each pressure step, circumferential stretch was increased with 6 h MV vs SB (p ≤ .05). CONCLUSION: During prolonged MV, medial costal diaphragm arteriolar shear stress is severely diminished. Despite no change in the material behavior (stress/stretch), prolonged MV resulted in altered structural and mechanical properties (ie, elevated circumferential stretch) of medial costal diaphragm arterioles. This provides important novel mechanistic insights into the impaired diaphragm blood flow capacity and vascular dysfunction following prolonged MV.

The effects of pulmonary hypertension on skeletal muscle oxygen pressures in contracting rat spinotrapezius muscle.

NEW FINDINGS: What is the central question of this study? Does impairment in the dynamics of O2 transport in skeletal muscle during a series of contractions constitute a potential mechanism underlying reduced exercise capacity in pulmonary hypertension? What is the main finding and its importance? Pulmonary hypertension compromises the dynamic matching of skeletal muscle O2 delivery-to-utilization following contraction onset in the rat spinotrapezius muscle. These results implicate a role for vascular dysfunction in the slow V̇O2 kinetics and exercise intolerance present in pulmonary hypertension. ABSTRACT: Pulmonary hypertension (PH) is characterized by pulmonary vascular dysfunction and exercise intolerance due, in part, to compromised pulmonary and cardiac function. We tested the hypothesis that there are peripheral (i.e., skeletal muscle) aberrations in O2 delivery ( Q̇O2 )-to-O2 utilization ( V̇O2 ) matching and vascular control that might help to explain poor exercise tolerance in PH. Furthermore, we investigated the peripheral effects of nitric oxide (NO) in attenuating these decrements. Male Sprague-Dawley rats (n = 21) were administered monocrotaline (MCT; 50 mg/kg, i.p.) to induce PH. Disease progression was monitored via echocardiography. Phosphorescence quenching determined the O2 partial pressure in the interstitial space ( PO2is ) in the spinotrapezius muscle at rest and during contractions under control (SNP-) and NO-donor (sodium nitroprusside, SNP+) conditions. MCT rats displayed right ventricular (RV) hypertrophy (right ventricle/(left ventricle + septum): 0.44 (0.13) vs. 0.28 (0.05)), pulmonary congestion, increased RV systolic pressure (48 (18) vs. 20 (8) mmHg) and arterial hypoxaemia ( PaO2 : 64 (9) vs. 82 (9) mmHg) compared to healthy controls (HC) (P < 0.05). PO2is was significantly lower in MCT rats during the first 30 s of SNP- contractions. SNP superfusion elevated PO2is in both groups; however, MCT rats demonstrated a lower PO2is throughout SNP+ contractions versus HC (P < 0.05). Thus, for small muscle mass exercise in MCT rats, muscle oxygenation is impaired across the rest-to-contractions transition and exogenous NO does not raise the Q̇O2 -to- V̇O2 ratio in contracting muscle to the same levels as HC. These data support muscle Q̇O2 -to- V̇O2 mismatch as a potential contributor to slow V̇O2 kinetics and therefore exercise intolerance in PH and suggest peripheral vascular dysfunction or remodelling as a possible mechanism.

HIV knowledge and stigma among dietetic students in Indonesia: implications for the nutrition education system.

BACKGROUND: Studies have demonstrated that health care students and practitioners are not immune to stigma towards people living with HIV (PLHIV). This attitude could lead to poor quality of care if it remains uncorrected. However, little is known about dietetic students' acceptance of PLHIV despite their substantial role in treatment. This study aimed to measure the extent of knowledge and stigma towards PLHIV among dietetic students and to determine the associated factors using the attribution theory. METHODS: Students from three dietetics schools in Indonesia (n = 516) were recruited to participate in this cross-sectional study. Survey questions covered demographic information, interaction with PLHIV, access to information sources, cultural values, and beliefs as predictor variables. The outcome variables were comprehensive knowledge of HIV, HIV and nutrition-specific knowledge, and attitudes. Analyses with linear regression and the stepwise selection were performed to determine factors related to the outcome. RESULTS: The levels of HIV comprehensive knowledge and HIV-nutrition specific knowledge among dietetic students were low, as indicated by the average score of 19.9 ± 0.19 (maximum score = 35) and 8.0 ± 0.11 (maximum score = 15), respectively. The level of negative attitudes towards PLHIV was high, with 99.6% of participants reported having a high stigma score. Types of university affiliation (public or private), beliefs and values, exposure to HIV discourse, access to printed media, and years of study were significantly related to HIV comprehensive knowledge (p < 0.05). Nutrition-specific knowledge was also correlated with university affiliation, beliefs and values, participation in HIV discussion, and years of study (p < 0.05). HIV comprehensive knowledge, university affiliation, discussion participation, and ethnicities were associated with attitudes (p < 0.05). CONCLUSIONS: Awareness and acceptance of PLHIV must be further improved throughout dietetic training to ensure patients' quality of care since students represent future dietary care providers. Considering the consistent findings that affiliation to education institution correlates with HIV knowledge and attitude, some examinations concerning the curriculum and teaching conduct might be necessary.

A sup-score test for the cure fraction in mixture models for long-term survivors.

The evaluation of cure fractions in oncology research under the well known cure rate model has attracted considerable attention in the literature, but most of the existing testing procedures have relied on restrictive assumptions. A common assumption has been to restrict the cure fraction to a constant under alternatives to homogeneity, thereby neglecting any information from covariates. This article extends the literature by developing a score-based statistic that incorporates covariate information to detect cure fractions, with the existing testing procedure serving as a special case. A complication of this extension, however, is that the implied hypotheses are not typical and standard regularity conditions to conduct the test may not even hold. Using empirical processes arguments, we construct a sup-score test statistic for cure fractions and establish its limiting null distribution as a functional of mixtures of chi-square processes. In practice, we suggest a simple resampling procedure to approximate this limiting distribution. Our simulation results show that the proposed test can greatly improve efficiency over tests that neglect the heterogeneity of the cure fraction under the alternative. The practical utility of the methodology is illustrated using ovarian cancer survival data with long-term follow-up from the surveillance, epidemiology, and end results registry.

Marginal mean models for zero-inflated count data.

Zero-inflated regression models have emerged as a popular tool within the parametric framework to characterize count data with excess zeros. Despite their increasing popularity, much of the literature on real applications of these models has centered around the latent class formulation where the mean response of the so-called at-risk or susceptible population and the susceptibility probability are both related to covariates. While this formulation in some instances provides an interesting representation of the data, it often fails to produce easily interpretable covariate effects on the overall mean response. In this article, we propose two approaches that circumvent this limitation. The first approach consists of estimating the effect of covariates on the overall mean from the assumed latent class models, while the second approach formulates a model that directly relates the overall mean to covariates. Our results are illustrated by extensive numerical simulations and an application to an oral health study on low income African-American children, where the overall mean model is used to evaluate the effect of sugar consumption on caries indices.

In utero exposure to polychlorinated biphenyls is associated with decreased fecundability in daughters of Michigan female fisheaters: a cohort study.

BACKGROUND: Multiple studies have suggested a relationship between adult exposures to environmental organochlorines and fecundability. There is a paucity of data, however, regarding fetal exposure to organochlorines via the mother's blood and fecundability of adult female offspring. METHODS: Data from a two-generation cohort of maternal fisheaters was investigated to assess female offspring fecundability. Serum concentrations of polychlorinated biphenyls (PCBs) and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (DDE) in Michigan female anglers were serially measured between 1973 and 1991 and used to estimate in utero exposure in their female offspring using two different methods. The angler cohort included 391 women of whom 259 provided offspring information. Of 213 daughters aged 20-50, 151 participated (71 %) and provided information for time intervals of unprotected intercourse (TUI). The daughters reported 308 TUIs (repeated observations), of which 288 ended in pregnancy. We estimated the fecundability ratio (FR) for serum-PCB and serum-DDE adjusting for confounders and accounting for repeated measurements. An FR below one indicates a longer time to pregnancy. RESULTS: Compared to serum-PCB of <2.5 µg/L, the FR was 0.60 for serum-PCB between 2.5-7.4 µg/L [95 % confidence intervals (CI) 0.36, 0.99], and 0.42 [95 % CI 0.20, 0.88] for serum-PCB >7.4 µg/L. Similar results were obtained using the alternative statistical method to estimate in utero serum-PCB. The association was stronger for TUIs when women planned a baby; FR = 0.50 for serum-PCB between 2.5-7.4 µg/L, [95 % CI 0.29, 0.89], and 0.30 [95 % CI 0.13, 0.68] for serum-PCB >7.4 µg/L. There was no relationship between in utero exposure to DDE and fecundability in daughters. CONCLUSIONS: Decreased fecundability in female offspring of fisheaters was found to be associated with PCB exposure in utero, possibly related to endocrine disruption in the oocyte and/or other developing organs influencing reproductive capacity in adulthood.

A score-type test for heterogeneity in zero-inflated models in a stratified population.

We propose a score-type statistic to evaluate heterogeneity in zero-inflated models for count data in a stratified population, where heterogeneity is defined as instances in which the zero counts are generated from two sources. Evaluating heterogeneity in this class of models has attracted considerable attention in the literature, but existing testing procedures have primarily relied on the constancy assumption under the alternative hypothesis. In this paper, we extend the literature by describing a score-type test to evaluate homogeneity against general alternatives that do not neglect the stratification information under the alternative hypothesis. The limiting null distribution of the proposed test statistic is a mixture of chi-squared distributions that can be well approximated by a simple parametric bootstrap procedure. Our numerical simulation studies show that the proposed test can greatly improve efficiency over tests of heterogeneity that ignore the stratification information. An empirical application to dental caries data in early childhood further shows the importance and practical utility of the methodology in using the stratification profile to detect heterogeneity in the population.

DDE and PCB serum concentration in maternal blood and their adult female offspring.

BACKGROUND: Dichlorodiphenyl dichloroethylene (DDE) and polychlorinated biphenyls (PCBs) can be passed from mother to offspring through placental transfer or breastfeeding. Unknown is whether maternal levels can predict concentrations in adult offspring. OBJECTIVES: To test the association between maternal blood levels of DDE and PCBs and adult female offspring levels of these compounds using data from the Michigan Fisheaters'Cohort. METHODS: DDE and PCB concentrations were determined in 132 adult daughters from 84 mothers. Prenatal exposures were estimated based on maternal DDE and PCB serum levels measured between 1973 and 1991. Levels in adult daughters were regressed on maternal and estimated prenatal exposure levels, adjusting for potential confounders using linear mixed models. Confounders included daughter's age, birth order, birth weight, number of pregnancies, the length of time the daughter was breast-fed, the length of time the daughter breast-fed her own children, last year fish-eating status, body mass index, and lipid weight. RESULTS: The median age of the participants was 40.4 years (range 18.4-65.4, 5-95 percentiles 22.5-54.6%, respectively). Controlling for confounders and intra-familial associations, DDE and PCB concentrations in adult daughters were significantly positively associated with estimated prenatal levels and with maternal concentrations. The proportion of variance in the adult daughters' organochlorine concentrations explained by the maternal exposure levels is approximately 23% for DDE and 43% for PCBs. The equivalent of a median of 3.67 µg/L prenatal DDE and a median of 2.56 µg/L PCBs were 15.64 and 10.49 years of fish consumption, respectively. When controlling for effects of the shared environment (e.g., fish diet) by using a subsample of paternal levels measured during the same time frames (n=53 and n=37), we determined that the direct maternal transfer remains important. CONCLUSIONS: Estimated intra-uterine DDE and PCB levels predicted concentrations in adult female offspring 40 years later. Interpretation of adverse health effects from intra-uterine exposures of persistent pollutants may need to consider the sustained impact of maternal DDE and PCB levels found in their offspring.

Examining multiracial youth in context: ethnic identity development and mental health outcomes.

Although multiracial individuals are the fastest growing population in the United States, research on the identity development of multiracial adolescents remains scant. This study explores the relationship between ethnic identity, its components (affirmation, exploration), and mental health outcomes (anxiety, depressive symptoms) within the contexts of schools for multiracial adolescents. The participants were multiracial and monoracial minority and majority high school students (n = 4,766; 54.6% female). Among the participants, 88.1% were Caucasian, 7.4% were African American, and 4.5% were multiracial. The research questions examined the relationship between ethnic identity exploration and affirmation on mental health outcomes and explored the role school context plays in this relationship. The findings suggested that multiracial youth experience more exploration and less affirmation than African Americans, but more than Caucasians. In addition, multiracial youth were found to have higher levels of mental health issues than their monoracial minority and majority peers. Specifically, multiracial youth had higher levels of depressive symptoms than their African American and Caucasian counterparts. Multiracial and Caucasian youth had similar levels of anxiety but these levels were significantly higher than African Americans. School diversity did not influence mental health outcomes for multiracial youth. These findings provide insight into the experiences of multiracial youth and underscore the importance of further investigating factors that contribute to their mental health outcomes.

Magnetic resonance imaging-ultrasound fusion guided focal cryoablation for men with intermediate-risk prostate cancer.

INTRODUCTION: Focal therapy (FT) is a form of ablative treatment offered to men with localized, organ-confined prostate cancer (CaP). Pelvic multiparametric magnetic resonance imaging (mpMRI) and mpMRI/transrectal ultrasound fusion (MRI-US) guidance enable the precise delivery of FT with limited ablation of adjacent benign tissue or vital genitourinary structures. This article presents our findings on using MRI-US to perform FT as a primary treatment for men with intermediate-risk CaP. METHODS: Thirty-six men underwent MRI-US fusion-guided FT cryoablation at a single center from 2018 to 2023 as a primary treatment for intermediate-risk CaP. Following FT, quarterly prostate-specific antigen (PSA) testing and a 6 to 9 month mpMRI and combined MRI-US targeted and systematic biopsy were performed. Oncological outcomes were determined using several endpoints containing biochemical recurrence, imaging failure, and pathological failure. Functional outcomes were measured using reported erectile dysfunction/potency rates, urinary incontinence rates, and the American Urologic Association Symptom Score (AUA-SS) and Sexual Health Inventory for Men (SHIM) indices. RESULTS: Median follow-up was 29.1 months, most (75%) of whom had grade group 2 CaP. Out of the 36 men, 32 (88.9%) completed the combined MRI-targeted and systematic biopsy follow-up after treatment. The study had no major complications, but 12 (33.3%) patients experienced Clavien-Dindo grade II or lower complications. For oncological outcomes, 6 (16.7%) men had biochemical recurrence, 9 (25%) showed imaging failure, and 8 (22.2%) met the criteria for positive biopsy- out-of-field vs. in-field. 88.2% of previously potent patients remained potent postoperatively at 12 months. All patients were continent at 12 months. There were no statistically significant changes in the AUA-SS and SHIM scores postoperatively. CONCLUSION: MRI-US-guided cryoablation to target lesions in intermediate-risk CaP appears to be a safe treatment option, with functional outcomes indicating minimal short and intermediate-term morbidity and acceptable oncological outcomes. However, despite close monitoring and follow-up, there is still a limitation in accurately predicting/detecting pathological failure after FT. The long-term durability of FT for intermediate-risk, organ-confined CaP remains uncertain.

Number Bias in Clinicians' Documentation of Actinic Keratosis Removal.

BACKGROUND: Actinic keratosis (AK) is a pre-cancerous skin condition caused by sun exposure. Number bias, a phenomenon that occurs when meaning other than numerical value is associated with numbers, may influence the reporting of AK removal. The present study aims to determine if number bias is affecting healthcare providers' documentation of patient-provider encounters. METHODS: A single-center retrospective chart review of 1415 patients' charts was conducted at the University of Cincinnati Medical Center. To determine if there was a significant difference between even and odd-numbered AK removals reported, an exact binomial test was used. The frequency of removals per encounter was fitted to a zero-truncated negative binomial distribution to predict the number of removals expected. All data were analyzed with RStudio. RESULTS: There were 741 odd and 549 even encounters. Odd removals were reported at a significantly greater frequency than even p < 0.001. Age may be contributing to the observed number bias (p < 0.001). One, two, and eight were reportedly removed more frequently, while nine, 13, and 14 were reportedly removed less frequently than expected, respectively. CONCLUSION: Number bias may be affecting clinicians' documentation of AK removal and should be investigated in other clinical settings.

Salvage Radical Prostatectomy after Primary Focal Ablative Therapy: A Systematic Review and Meta-Analysis.

CONTEXT: Focal therapy (FT) has been gaining popularity as a treatment option for localized intermediate-risk prostate cancer (PCa) due to the associated lower morbidity compared to whole-gland treatment. However, there is an increased risk of local cancer recurrence requiring subsequent treatment in a small proportion of patients. OBJECTIVE: To conduct a systematic review and meta-analysis to better describe and analyze patient postoperative, oncologic, and functional outcomes for those who underwent salvage radical prostatectomy (sRP) to manage their primary FT failure. EVIDENCE ACQUISITION: A systematic review was completed using three databases (PubMed, Embase, and CINAHL) from October to December 2021 to identify data on outcomes in patients who received sRP for cancer recurrence after prior focal treatment. EVIDENCE SYNTHESIS: 12 articles (482 patients) were included. Median time to sRP was 24 months. Median follow-up time was 27 months. A meta-analysis revealed a postoperative complication rate of 15% (95% CI: 0.09, 0.24), with 4.6% meeting criteria for a major complication Clavien (CG) grade ≥3. Severe GU toxicity was seen in 3.6% of the patients, and no patients had severe GI toxicity. Positive surgical margins (PSM) were found in 27% (95% CI: 0.19, 0.37). Biochemical recurrence (BCR) after sRP occurred in 23% (95% CI: 0.17, 0.30), indicating a BCR-free probability of 77% at 2 years. Continence (pad-free) and potency (ability to have penetrative sex) were maintained in 67% (95% CI: 0.53, 0.78) and 37% (95% CI: 0.18, 0.62) at 12 months, respectively. CONCLUSION: Our evidence shows acceptable complication rates and oncologic outcomes; however, with suboptimal functional outcomes for patients undergoing sRP for recurrent PCa after prior FT. Inferior outcomes were observed for salvage treatment compared to primary radical prostatectomy (pRP). More high-quality studies are needed to better characterize outcomes after this sequence of PCa treatments. PATIENT SUMMARY: We looked at treatment outcomes and toxicity for men treated with sRP for prior FT failure. We conclude that these patients will have significant detriment to genitourinary function, with outcomes being worse than those for pRP patients.

Exploring the potential effect of phospholipase A2 antibody to extend beef shelf-life in a beef liposome model system.

The objective of this study was to elucidate the effect of phospholipase A2 (PLA2) and a PLA2 antibody (aPLA2) on phospholipid (PL) hydrolysis in beef and to understand how the altered PL composition may affect lipid oxidation and antioxidant capacity of beef in an in vitro system. Various combinations of PLA2 and aPLA2 were introduced to a beef liposome model system and exposed to a retail display. The PL and free fatty acid (FFA) profiles, antioxidant capacity and lipid oxidation were measured for the liposome system. Key PL classes were reduced and the release of polyunsaturated FFAs was increased with the inclusion of PLA2 in the treatments (P < 0.05). There was no inhibition of PL hydrolysis with the addition of aPLA2. PLA2 showed strong antioxidant capacity in the liposome system (P < 0.01), but lipid oxidation still increased in samples treated with PLA2 throughout the retail display (P < 0.01). Finally, aPLA2 treatments demonstrated potential to decrease lipid oxidation (P < 0.01).

On the efficiency of score tests for homogeneity in two-component parametric models for discrete data.

In many applications of two-component mixture models for discrete data such as zero-inflated models, it is often of interest to conduct inferences for the mixing weights. Score tests derived from the marginal model that allows for negative mixing weights have been particularly useful for this purpose. But the existing testing procedures often rely on restrictive assumptions such as the constancy of the mixing weights and typically ignore the structural constraints of the marginal model. In this article, we develop a score test of homogeneity that overcomes the limitations of existing procedures. The technique is based on a decomposition of the mixing weights into terms that have an obvious statistical interpretation. We exploit this decomposition to lay the foundation of the test. Simulation results show that the proposed covariate-adjusted test statistic can greatly improve the efficiency over test statistics based on constant mixing weights. A real-life example in dental caries research is used to illustrate the methodology.

The effect of impulsivity and drinking motives on alcohol outcomes in college students: a 3-year longitudinal analysis.

Objective: Substance use is a public health concern and cross-sectional studies have found that impulsivity and drinking motives influence substance use in emerging adults. Despite these findings, longitudinal studies with nuanced measures of impulsivity and drinking motives are needed. Participants: The current study investigated the three-year relationship between impulsivity-related traits, drinking motives, sex, and drinking outcomes in a sample of 509 college students (47.47% male; 81% White). Methods: The effects of impulsivity traits and drinking motives on problematic drinking outcomes were evaluated using linear mixed effects models. Results: The results confirmed the hypothesized relationship between traits of impulsivity, drinking motives, and alcohol outcomes over time. Further, sex significantly interacted with drinking motives longitudinally in its relationship with alcohol use outcomes. Conclusions: These results indicate that intervention efforts may need to be tailored to specific individual attributes to target direct correlates of alcohol use behavior to increase effectiveness.