Prevalence of persistent SARS-CoV-2 in a large community surveillance study.

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks1-5, give rise to highly divergent lineages6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as 'persistent infections' as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.

Lineage replacement and evolution captured by 3 years of the United Kingdom Coronavirus (COVID-19) Infection Survey.

The Office for National Statistics Coronavirus (COVID-19) Infection Survey (ONS-CIS) is the largest surveillance study of SARS-CoV-2 positivity in the community, and collected data on the United Kingdom (UK) epidemic from April 2020 until March 2023 before being paused. Here, we report on the epidemiological and evolutionary dynamics of SARS-CoV-2 determined by analysing the sequenced samples collected by the ONS-CIS during this period. We observed a series of sweeps or partial sweeps, with each sweeping lineage having a distinct growth advantage compared to their predecessors, although this was also accompanied by a gradual fall in average viral burdens from June 2021 to March 2023. The sweeps also generated an alternating pattern in which most samples had either S-gene target failure (SGTF) or non-SGTF over time. Evolution was characterized by steadily increasing divergence and diversity within lineages, but with step increases in divergence associated with each sweeping major lineage. This led to a faster overall rate of evolution when measured at the between-lineage level compared to within lineages, and fluctuating levels of diversity. These observations highlight the value of viral sequencing integrated into community surveillance studies to monitor the viral epidemiology and evolution of SARS-CoV-2, and potentially other pathogens.

BRCA1 and BRCA2 carriers with breast, ovarian and prostate cancer demonstrate a different pattern of metastatic disease compared with non-carriers: results from a rapid autopsy programme.

AIM: To catalogue and compare the pattern of metastatic disease in germline BRCA1/2 pathogenic mutation carriers and non-carriers with breast, ovarian and prostate cancer from a rapid autopsy programme. METHODS AND RESULTS: The number of metastases in the major body systems and the proportion of participants with metastases were documented in 50 participants (19 germline mutation carriers). Analysis was conducted on the participants' pattern of disease for the different cancers and mutation subgroups. The four commonly affected organ systems were the digestive (liver only) (82%), respiratory (76%), gastrointestinal (65%) and reticuloendothelial (42%). There were significant differences in the pattern of metastatic breast cancer in BRCA1/2 germline carriers compared with non-carriers. Breast cancer carriers had significantly fewer organ systems involved (median n = 3, range = 1-3) compared with non-carriers (median n = 9, range = 1-7) (P = 0.03). BRCA1/2 carriers with ovarian carcinomas had significantly more organ systems with metastatic carcinoma (median n = 10, range = 3-8) than non-carriers (median n = 5, range = 3-5) (P < 0.001). There were no significant differences in the number of involved systems in BRCA2 carriers compared with non-carriers with prostate cancer (P = 1.0). There was an absence of locoregional disease (6.5%) compared with distant disease (93.5%) among the three cancer subtypes (P < 0.001). The majority of metastatic deposits (97%) collected during the autopsy were identified by recent diagnostic imaging. CONCLUSION: Even though a major limitation of this study is that our numbers are small, especially in the breast cancer carrier group, the metastatic patterns of breast and ovarian cancers may be impacted by BRCA1/2 carrier status, suggesting that tumours derived from patients with these mutations use different mechanisms of dissemination. The findings may focus clinical diagnostic imaging for monitoring metastases where whole-body imaging resources are scant.

REACT: Rapid Evaluation Assessment of Clinical Reasoning Tool.

INTRODUCTION: Clinical reasoning encompasses the process of data collection, synthesis, and interpretation to generate a working diagnosis and make management decisions. Situated cognition theory suggests that knowledge is relative to contextual factors, and clinical reasoning in urgent situations is framed by pressure of consequential, time-sensitive decision-making for diagnosis and management. These unique aspects of urgent clinical care may limit the effectiveness of traditional tools to assess, teach, and remediate clinical reasoning. METHODS: Using two validated frameworks, a multidisciplinary group of clinicians trained to remediate clinical reasoning and with experience in urgent clinical care encounters designed the novel Rapid Evaluation Assessment of Clinical Reasoning Tool (REACT). REACT is a behaviorally anchored assessment tool scoring five domains used to provide formative feedback to learners evaluating patients during urgent clinical situations. A pilot study was performed to assess fourth-year medical students during simulated urgent clinical scenarios. Learners were scored using REACT by a separate, multidisciplinary group of clinician educators with no additional training in the clinical reasoning process. REACT scores were analyzed for internal consistency across raters and observations. RESULTS: Overall internal consistency for the 41 patient simulations as measured by Cronbach's alpha was 0.86. A weighted kappa statistic was used to assess the overall score inter-rater reliability. Moderate reliability was observed at 0.56. DISCUSSION: To our knowledge, REACT is the first tool designed specifically for formative assessment of a learner's clinical reasoning performance during simulated urgent clinical situations. With evidence of reliability and content validity, this tool guides feedback to learners during high-risk urgent clinical scenarios, with the goal of reducing diagnostic and management errors to limit patient harm.

Integrating longitudinal clinical and microbiome data to predict growth faltering in preterm infants.

Preterm birth affects more than 10% of all births worldwide. Such infants are much more prone to Growth Faltering (GF), an issue that has been unsolved despite the implementation of numerous interventions aimed at optimizing preterm infant nutrition. To improve the ability for early prediction of GF risk for preterm infants we collected a comprehensive, large, and unique clinical and microbiome dataset from 3 different sites in the US and the UK. We use and extend machine learning methods for GF prediction from clinical data. We next extend graphical models to integrate time series clinical and microbiome data. A model that integrates clinical and microbiome data improves on the ability to predict GF when compared to models using clinical data only. Information on a small subset of the taxa is enough to help improve model accuracy and to predict interventions that can improve outcome. We show that a hierarchical classifier that only uses a subset of the taxa for a subset of the infants is both the most accurate and cost-effective method for GF prediction. Further analysis of the best classifiers enables the prediction of interventions that can improve outcome.

Graduate medical education-led continuous assessment of burnout and learning environments to improve residents' wellbeing.

BACKGROUND: Promoting residents' wellbeing and decreasing burnout is a focus of Graduate Medical Education (GME). A supportive clinical learning environment is required to optimize residents' wellness and learning. OBJECTIVE: To determine if longitudinal assessments of burnout and learning environment as perceived by residents combined with applying continuous quality Model for Improvement and serial Plan, Do, Study, Act (PDSA) cycles to test interventions would improve residents' burnout. METHODS: From November 2017 to January 2020, 271 GME residents in internal medicine, general surgery, psychiatry, emergency medicine, family medicine and obstetrics and gynecology, were assessed over five cycles by Maslach Burnout Inventory (MBI), and by clinical learning environment factors (which included personal/social relationships, self-defined burnout, program burnout support, program back-up support, clinical supervision by faculty, and sleep difficulties). The results of the MBI and clinical learning environment factors were observed and analyzed to determine and develop indicated Institutional and individual program interventions using a Plan, Do, Study, Act process with each of the five cycles. RESULTS: The response rate was 78.34%. MBI parameters for all GME residents improved over time but were not statistically significant. Residents' positive perception of the clinical supervision by faculty was significantly and independently associated with improved MBI scores, while residents' self-defined burnout; and impaired personal relations perceptions were independently significantly associated with adverse MBI scores on liner regression. For all GME, significant improvements improved over time in residents' perception of impaired personal relationships (p < 0.001), self-defined burnout (p = 0.013), program burn-out support (p = 0.002) and program back-up support (p = 0.028). For the Internal Medicine Residency program, there were statistically significant improvements in all three MBI factors (p < 0.001) and in clinical learning environment measures (p = 0.006 to < 0.001). Interventions introduced during the PDSA cycles included organization-directed interventions (such as: faculty and administrative leadership recruitment, workflow interventions and residents' schedule optimization), and individual interventions (such as: selfcare, mentoring and resilience training). CONCLUSION: In our study, for all GME residents, clinical learning environment factors in contrast to MBI factors showed significant improvements. Residents' positive perception of the clinical learning environment was associated with improved burnout measures. Residents in separate programs responded differently with one program reaching significance in all MBI and clinical learning environment factors measured. Continuous wellbeing assessment of all GME residents and introduction of Institutional and individual program interventions was accomplished.

Human milk oligosaccharide DSLNT and gut microbiome in preterm infants predicts necrotising enterocolitis.

OBJECTIVE: Necrotising enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm infants. The underlying mechanisms are poorly understood: mother's own breast milk (MOM) is protective, possibly relating to human milk oligosaccharide (HMO) and infant gut microbiome interplay. We investigated the interaction between HMO profiles and infant gut microbiome development and its association with NEC. DESIGN: We performed HMO profiling of MOM in a large cohort of infants with NEC (n=33) with matched controls (n=37). In a subset of 48 infants (14 with NEC), we also performed longitudinal metagenomic sequencing of infant stool (n=644). RESULTS: Concentration of a single HMO, disialyllacto-N-tetraose (DSLNT), was significantly lower in MOM received by infants with NEC compared with controls. A MOM threshold level of 241 nmol/mL had a sensitivity and specificity of 0.9 for NEC. Metagenomic sequencing before NEC onset showed significantly lower relative abundance of Bifidobacterium longum and higher relative abundance of Enterobacter cloacae in infants with NEC. Longitudinal development of the microbiome was also impacted by low MOM DSLNT associated with reduced transition into preterm gut community types dominated by Bifidobacterium spp and typically observed in older infants. Random forest analysis combining HMO and metagenome data before disease accurately classified 87.5% of infants as healthy or having NEC. CONCLUSION: These results demonstrate the importance of HMOs and gut microbiome in preterm infant health and disease. The findings offer potential targets for biomarker development, disease risk stratification and novel avenues for supplements that may prevent life-threatening disease.

Declining Gaze to Faces in Infants Developing Autism Spectrum Disorder: Evidence From Two Independent Cohorts.

Two independent cohorts (N = 155, N = 126) of infants at high and low risk for autism spectrum disorder (ASD) were followed prospectively between 6 and 36 months of age, when n = 46 were diagnosed with ASD. Gaze to adult faces was coded-during a developmental assessment (Cohort 1) or a play interaction (Cohort 2). Across both cohorts, most children developing ASD showed sharp declines in gaze to faces over time, relative to children without ASD. These findings suggest that declining developmental trajectories may be more common than previously recognized by retrospective methods. Trajectory-based screening methods could potentially identify children in the early stages of symptom onset and allow for early intervention before the full disorder has developed.

Can Familial Risk for ADHD Be Detected in the First Two Years of Life?

Objective: We evaluated trajectories of attention-deficit/hyperactivity (ADHD)-relevant behaviors in a sample of infants at high and low familial risk for ADHD who were prospectively evaluated at 12, 18, and 24 months of age.Method: Participants included 43 infants at risk for ADHD based on family history (i.e., diagnosed first-degree relative) and 40 low-risk infants (i.e., no family history of ADHD). Instances of inattention, out-of-seat, and grabbing behavior were coded from video; analogous constructs were rated by examiners unaware of familial risk status after completing structured standardized assessments with the infants/toddlers. At the end of each study visit, examiners solicited parents' concerns about their child's behavior. Differences in ADHD-related behaviors and parent concerns were examined between 12 and 24 months of age.Results: Infants with an older sibling or parent diagnosed with ADHD were distinguishable from infants with no family history of ADHD as early as 12 months of age based on directly observed and examiner reports of behavior, particularly with respect to hyperactive-impulsive behavior. Parents of infants at familial risk for ADHD also reported significantly more behavior/temperament concerns as early as 12 months of age compared to parents of infants at low risk for ADHD.Conclusions: These findings highlight the ability to detect genetic liability for ADHD by the end of the first year of life, suggesting that well-designed family risk studies of ADHD are feasible and may be clinically valuable. They also suggest the potential for earlier detection of risk for ADHD than has previously been possible.

Protein shape modulates crowding effects.

Protein-protein interactions are usually studied in dilute buffered solutions with macromolecule concentrations of <10 g/L. In cells, however, the macromolecule concentration can exceed 300 g/L, resulting in nonspecific interactions between macromolecules. These interactions can be divided into hard-core steric repulsions and "soft" chemical interactions. Here, we test a hypothesis from scaled particle theory; the influence of hard-core repulsions on a protein dimer depends on its shape. We tested the idea using a side-by-side dumbbell-shaped dimer and a domain-swapped ellipsoidal dimer. Both dimers are variants of the B1 domain of protein G and differ by only three residues. The results from the relatively inert synthetic polymer crowding molecules, Ficoll and PEG, support the hypothesis, indicating that the domain-swapped dimer is stabilized by hard-core repulsions while the side-by-side dimer shows little to no stabilization. We also show that protein cosolutes, which interact primarily through nonspecific chemical interactions, have the same small effect on both dimers. Our results suggest that the shape of the protein dimer determines the influence of hard-core repulsions, providing cells with a mechanism for regulating protein-protein interactions.

The Stool Volatile Metabolome of Pre-Term Babies.

The fecal metabolome in early life has seldom been studied. We investigated its evolution in pre-term babies during their first weeks of life. Multiple (n = 152) stool samples were studied from 51 babies, all <32 weeks gestation. Volatile organic compounds (VOCs) were analyzed by headspace solid phase microextraction gas chromatography mass spectrometry. Data were interpreted using Automated Mass Spectral Deconvolution System (AMDIS) with the National Institute of Standards and Technology (NIST) reference library. Statistical analysis was based on linear mixed modelling, the number of VOCs increased over time; a rise was mainly observed between day 5 and day 10. The shift at day 5 was associated with products of branched-chain fatty acids. Prior to this, the metabolome was dominated by aldehydes and acetic acid. Caesarean delivery showed a modest association with molecules of fungal origin. This study shows how the metabolome changes in early life in pre-term babies. The shift in the metabolome 5 days after delivery coincides with the establishment of enteral feeding and the transition from meconium to feces. Great diversity of metabolites was associated with being fed greater volumes of milk.

Predicting ASD Diagnosis in Children with Synthetic and Image-based Eye Gaze Data.

As early intervention is highly effective for young children with autism spectrum disorder (ASD), it is imperative to make accurate diagnosis as early as possible. ASD has often been associated with atypical visual attention and eye gaze data can be collected at a very early age. An automatic screening tool based on eye gaze data that could identify ASD risk offers the opportunity for intervention before the full set of symptoms is present. In this paper, we propose two machine learning methods, synthetic saccade approach and image based approach, to automatically classify ASD given children's eye gaze data collected from free-viewing tasks of natural images. The first approach uses a generative model of synthetic saccade patterns to represent the baseline scan-path from a typical non-ASD individual and combines it with the real scan-path as well as other auxiliary data as inputs to a deep learning classifier. The second approach adopts a more holistic image-based approach by feeding the input image and a sequence of fixation maps into a convolutional or recurrent neural network. Using a publicly-accessible collection of children's gaze data, our experiments indicate that the ASD prediction accuracy reaches 67.23% accuracy on the validation dataset and 62.13% accuracy on the test dataset.

Suppressive myeloid cells are expanded by biliary tract cancer-derived cytokines in vitro and associate with aggressive disease.

BACKGROUND: BTC is an aggressive disease exacerbated by inflammation and immune suppression. Expansion of immunosuppressive cells occurs in biliary tract cancer (BTC), yet the role of BTC-derived cytokines in this process is unclear. METHODS: Activated signalling pathways and cytokine production were evaluated in a panel of human BTC cell lines. Human peripheral blood mononuclear cells (PBMCs) were cultured with BTC supernatants, with and without cytokine neutralising antibodies, and analysed by flow cytometry or immunoblot. A human BTC tissue microarray (TMA, n = 69) was stained for IL-6, GM-CSF, and CD33+S100a9+ cells and correlated with clinical outcomes. RESULTS: Immunomodulatory factors (IL-6, GM-CSF, MCP-1) were present in BTC supernatants. BTC supernatants expanded CD33dimCD11b+HLA-DRlow/- myeloid-derived suppressor cells (MDSCs) from human PBMCs. Neutralisation of IL-6 and GM-CSF in BTC supernatants inhibited activation of STAT3/5, respectively, in PBMCs, with heterogeneous effects on MDSC expansion in vitro. Staining of a BTC TMA revealed a positive correlation between IL-6 and GM-CSF, with each cytokine and more CD33+S100a9+ cells. Increased CD33+S100a9+ staining positively correlated with higher tumour grade, differentiation and the presence of satellite lesions. CONCLUSION: BTC-derived factors promote suppressive myeloid cell expansion, and higher numbers of CD33+S100a9+ cells in resectable BTC tumours correlates with more aggressive disease.

A video-based measure to identify autism risk in infancy.

BACKGROUND: Signs of autism are present in the first 2 years of life, but the average age of diagnosis lags far behind. Instruments that improve detection of autism risk in infancy are needed. This study developed and tested the psychometric properties of a novel video-based approach to detecting ASD in infancy. METHODS: A prospective longitudinal study of children at elevated or lower risk for autism spectrum disorder was conducted. Participants were 76 infants with an older sibling with ASD and 37 infants with no known family history of autism. The Video-referenced Infant Rating System for Autism (VIRSA) is a web-based application that presents pairs of videos of parents and infants playing together and requires forced-choice judgments of which video is most similar to the child being rated. Parents rated participants on the VIRSA at 6, 9, 12, and 18 months of age. We examined split-half and test-retest reliability; convergent and discriminant validity; and sensitivity, specificity, and negative and positive predictive value for concurrent and 36-month ASD diagnoses. RESULTS: The VIRSA demonstrated satisfactory reliability and convergent and discriminant validity. VIRSA ratings were significantly lower for children ultimately diagnosed with ASD than children with typical development by 12 months of age. VIRSA scores at 18 months identified all children diagnosed with ASD at that age, as well as 78% of children diagnosed at 36 months. CONCLUSIONS: This study represents an initial step in the development of a novel video-based approach to detection of ASD in infancy. The VIRSA's psychometric properties were promising when used by parents with an older affected child, but still must be tested in community samples with no family history of ASD. If results are replicated, then the VIRSA's low-burden, web-based format has the potential to reduce disparities in communities with limited access to screening.

Acquisition and Development of the Extremely Preterm Infant Microbiota Across Multiple Anatomical Sites.

OBJECTIVES: Microbial communities influencing health and disease are being increasingly studied in preterm neonates. There exists little data, however, detailing longitudinal microbial acquisition, especially in the most extremely preterm (<26 weeks' gestation). This study aims to characterize the development of the microbiota in this previously under-represented cohort. METHODS: Seven extremely preterm infant-mother dyads (mean gestation 23.6 weeks) were recruited from a single neonatal intensive care unit. Oral and endotracheal secretions, stool, and breast milk (n = 157 total), were collected over the first 60 days of life. Targeted 16S rRNA gene sequencing identified bacterial communities present. RESULTS: Microbiota of all body sites were most similar immediately following birth and diverged longitudinally. Throughout the sampling period Escherichia, Enterococcus, Staphylococcus, and an Enterobacteriaceae were dominant and well dispersed across all sites. Temporal divergence of the stool from other microbiota was driven by decreasing diversity and significantly greater proportional abundance of Bifidobacteriaceae compared to other sites. CONCLUSIONS: Four taxa dominated all anatomical sampling sites. Rare taxa promoted dissimilarity. Cross-seeding between upstream communities and the stool was demonstrated, possibly relating to buccal colostrum/breast milk exposure and indwelling tubes. Given the importance of dysbiosis in health and disease of extremely preterm infants, better understanding of microbial acquisition within this context may be of clinical benefit.

The Developmental Sequence and Relations Between Gesture and Spoken Language in Toddlers With Autism Spectrum Disorder.

In typical development, gestures precede and predict language development. This study examines the developmental sequence of expressive communication and relations between specific gestural and language milestones in toddlers with autism spectrum disorder (ASD), who demonstrate marked difficulty with gesture production and language. Communication skills across five stages (gestures, word approximations, first words, gesture-word combinations, and two-word combinations) were assessed monthly by blind raters for toddlers with ASD participating in an randomized control trial of parent-mediated treatment (N = 42, 12-30 months). Findings revealed that toddlers acquired skills following a reliable (vs. idiosyncratic) sequence and the majority of toddlers combined gestures with words before combining words in speech, but in contrast to the pattern observed in typical development, a significant subset acquired pointing after first words.

Assessment of outcomes and novel immune biomarkers in metaplastic breast cancer: a single institution retrospective study.

BACKGROUND: Metaplastic breast cancer remains poorly characterized given its rarity and heterogeneity. The majority of metaplastic breast cancers demonstrate a phenotype of triple-negative breast cancer; however, differences in clinical outcomes between metaplastic breast cancer and triple-negative breast cancer in the era of third-generation chemotherapy remain unclear. METHODS: We compared the clinical outcomes between women with metaplastic breast cancer and women with triple-negative breast cancer diagnosed between 1994 and 2014. Metaplastic breast cancer patients were matched 1:3 to triple-negative breast cancer patients by stage and age at diagnosis. Distant disease-free survival (DDFS) and overall survival (OS) were estimated using Kaplan Meier methods and Cox proportional hazard regression models. Immune checkpoint markers were characterized by immunohistochemistry in a subset of samples. RESULTS: Forty-four metaplastic breast cancer patients (stage I 14%; stage II 73%; stage III 11%; stage IV 2%) with an average age of 55.4 (± 13.9) years at diagnosis. Median follow-up for the included metaplastic breast cancer and triple-negative breast cancer patients (n = 174) was 2.8 (0.1-19.0) years. The DDFS and OS between matched metaplastic breast cancer and triple-negative breast cancer patients were similar, even when adjusting for clinical covariates (DDFS: HR = 1.64, p = 0.22; OS: HR = 1.64, p = 0.26). Metaplastic breast cancer samples (n = 27) demonstrated greater amount of CD163 in the stroma (p = 0.05) and PD-L1 in the tumor (p = 0.01) than triple-negative breast cancer samples (n = 119), although more triple-negative breast cancer samples were positive for CD8 in the tumor than metaplastic breast cancer samples (p = 0.02). CONCLUSIONS: Patients with metaplastic breast cancer had similar outcomes to those with triple-negative breast cancer based on DDFS and OS. The immune checkpoint marker profile of metaplastic breast cancers in this study may prove useful in future studies attempting to demonstrate an association between immune profile and survival.

A Novel Tomato-Soy Juice Induces a Dose-Response Increase in Urinary and Plasma Phytochemical Biomarkers in Men with Prostate Cancer.

Background: Tomato and soy intake is associated with reduced prostate cancer risk or severity in epidemiologic and experimental studies. Objective: On the basis of the principle that multiple bioactives in tomato and soy may act on diverse anticancer pathways, we developed and characterized a tomato-soy juice for clinical trials. In this phase 2 dose-escalating study, we examined plasma, prostate, and urine biomarkers of carotenoid and isoflavone exposure. Methods: Men scheduled for prostatectomy were recruited to consume 0, 1, or 2 cans of tomato-soy juice/d before surgery (mean ± SD duration: 24 ± 4.6 d). The juice provided 20.6 mg lycopene and 66 mg isoflavone aglycone equivalents/177-mL can. Plasma carotenoids and urinary isoflavone metabolites were quantified by HPLC-photometric diode array and prostate carotenoids and isoflavones by HPLC-tandem mass spectrometry. Results: We documented significant dose-response increases (P < 0.05) in plasma concentrations of tomato carotenoids. Plasma concentrations were 1.86-, 1.69-, 1.73-, and 1.69-fold higher for lycopene, ß-carotene, phytoene, and phytofluene, respectively, for the 1-can/d group and 2.34-, 3.43-, 2.54-, and 2.29-fold higher, respectively, for the 2-cans/d group compared with 0 cans/d. Urinary isoflavones daidzein, genistein, and glycitein increased in a dose-dependent manner. Prostate carotenoid and isoflavone concentrations were not dose-dependent in this short intervention; yet, correlations between plasma carotenoid and urinary isoflavones with respective prostate concentrations were documented (R2 = 0.78 for lycopene, P < 0.001; R2 = 0.59 for dihydrodaidzein, P < 0.001). Secondary clustering analyses showed urinary isoflavone metabolite phenotypes. To our knowledge, this is the first demonstration of the phytoene and phytofluene in prostate tissue after a dietary intervention. Secondary analysis showed that the 2-cans/d group experienced a nonsignificant decrease in prostate-specific antigen slope compared with 0 cans/d (P = 0.078). Conclusion: These findings provide the foundation for evaluating a well-characterized tomato-soy juice in human clinical trials to define the impact on human prostate carcinogenesis. This trial is registered at clinicaltrials.gov as NCT01009736.

The dysregulation profile in preschoolers with and without a family history of autism spectrum disorder.

BACKGROUND: The 'dysregulation profile' (DP) is a measure of emotional and behavioral dysregulation that may cut across diagnostic boundaries. Siblings of children with autism spectrum disorder (ASD) who do not develop ASD themselves are at risk for atypical outcomes including behavioral challenges and therefore may be a useful population in which to investigate the structure of the DP in preschoolers. METHODS: We sought to examine the factor structure and predictors of the DP in a sample enriched for a wide range of phenotypic variation-36-month-olds with and without family histories of ASD-and to determine whether children with genetic liability for ASD are at risk for a phenotype characterized by elevated dysregulation. Data were collected from 415 children with (n = 253) and without (n = 162) an older sibling with ASD, all without ASD themselves, at 18, 24, and 36 months of age. RESULTS: Our findings replicate prior reports, conducted in predominantly clinically referred and older samples, supporting the superiority of a bifactor model of the DP in the preschool period compared to the second-order and one-factor models. Examiner ratings were longitudinally and concurrently associated with the DP at 36 months of age. Family history of ASD was associated with higher dysregulation in the Anxious/Depressed dimension. CONCLUSIONS: These findings support the relevance of examining the structure of psychopathology in preschoolers and suggest that examiner observations as early as 18 months of age, particularly of overactivity, may help identify risk for later DP-related concerns. Non-ASD preschoolers with family histories of ASD may be at risk for a phenotype characterized by elevated dysregulation particularly in the Anxious/Depressed dimension by age 3.

Increasing Adherence to Adjuvant Hormone Therapy Among Patients With Breast Cancer: A Smart Phone App-Based Pilot Study.

PURPOSE: This study tested the feasibility and efficacy of using a text-based intervention to increase initiation, decrease discontinuation, and improve adherence as prescribed to adjuvant hormone therapy (AHT) among hyphenate post-menopausal breast cancer survivors. METHODS: The 3-month intervention consisted of daily text message reminders to take medication, coupled with a dynamic (eg, feedback on progress) tailored intervention using weekly interactive surveys delivered by a smartphone app. Five clinic sites within the Alliance for Clinical Trials in Oncology participated. Hormone levels were measured prior to AHT initiation and at study exit. RESULTS: Of the 39 patients recruited to the pilot study, 27 (69.2%) completed all study requirements (completed both the baseline and the exit surveys, both blood draws, and did not miss more than 2 weekly surveys). Significant improvements were observed pre- to postintervention for self-reported medication adherence (P = .015), mental health functioning (P = .007), and perceived stress (P = .04). Significant decreases in estradiol, estrogen, and estrone hormone levels were observed from baseline to study exit (P < .001), indicating the accuracy of self-reported AHT adherence. Participants (91.9%) and physicians (100%) agreed that participant participation in the intervention was beneficial. CONCLUSIONS: The results of this pilot study established the general feasibility and efficacy of an app-based intervention to support patient AHT adherence. Larger controlled, randomized trials are needed to examine the effectiveness of the app-based intervention in improving AHT and quality of life among breast cancer survivors.