Multicenter Canadian case series of pediatric patients less than 12 years of age with moderate-to-severe atopic dermatitis treated with dupilumab.

BACKGROUND: Dupilumab is approved for moderate-severe atopic dermatitis (AD) in patients aged ≥6 months by the US Food and Drug Administration and Health Canada; however, there are little real-world data because providers have limited practical experience with this recently approved therapy. OBJECTIVES: To describe the real-world effectiveness and safety in patients aged <12 years with moderate-severe AD currently receiving or previously having received dupilumab. METHODS: A multicenter retrospective study was conducted at six Canadian sites. Cases were divided into Group 1 ≤2 years old, Group 2 >2 to <6 years old, and Group 3 ≥6 to <12 years old. Medical history and details of dupilumab treatment were collected. The primary outcome was to measure the improvement in eczema area and severity index. Secondary outcomes examined included the children's dermatology life quality index/infant's dermatitis quality of life, peak pruritus numerical rating scale, and delay to dupilumab access for patients who were considered off-label for dupilumab due to their age. RESULTS: Sixty three pediatric patients (37 males) with moderate-to-severe AD were included; the mean age was 6.4 years old (range: 2-11) when dupilumab treatment was started. Overall, 75% (36/48) achieved EASI-75% and 71% (34/48) achieved EASI-90. EASI-75 and EASI-90 were achieved in 90% (17/19) and 73% (12/19) in patients <6 years old, and 76% (22/29) and 59% (17/29) in patients >6 years old, respectively. No serious adverse events were reported. CONCLUSIONS: Dupilumab is safe and effective for patients under the age of 12. However, even for experienced providers, access to the medication was challenging.

Transferring Learned Behaviors between Similar and Different Radios.

Transfer learning (TL) techniques have proven useful in a wide variety of applications traditionally dominated by machine learning (ML), such as natural language processing, computer vision, and computer-aided design. Recent extrapolations of TL to the radio frequency (RF) domain are being used to increase the potential applicability of RFML algorithms, seeking to improve the portability of models for spectrum situational awareness and transmission source identification. Unlike most of the computer vision and natural language processing applications of TL, applications within the RF modality must contend with inherent hardware distortions and channel condition variations. This paper seeks to evaluate the feasibility and performance trade-offs when transferring learned behaviors from functional RFML classification algorithms, specifically those designed for automatic modulation classification (AMC) and specific emitter identification (SEI), between homogeneous radios of similar construction and quality and heterogeneous radios of different construction and quality. Results derived from both synthetic data and over-the-air experimental collection show promising performance benefits from the application of TL to the RFML algorithms of SEI and AMC.

Advances in Endocrine Therapy for Hormone Receptor-Positive Advanced Breast Cancer.

PURPOSE OF REVIEW: To provide an overview of the current management of hormone receptor-positive (HR +) advanced breast cancer as well as highlight ongoing clinical investigation and novel therapies in development. RECENT FINDINGS: CDK4/6 inhibition plus endocrine therapy is standard front-line therapy for HR + advanced breast cancer. Continuation of CDK4/6 inhibitors in combination with alternative endocrine therapy has been evaluated in the second-line setting. Alternatively, endocrine therapy in combination with PI3K/AKT pathway targeting agents has been studied, particularly in patients with PI3K pathway alterations. The oral SERD elacestrant has also been evaluated in patients with ESR1 mutation. Many novel endocrine agents and targeted agents are in development. An improved understanding of combination therapies and sequencing of therapies is needed to optimize the treatment paradigm. Biomarker development is needed to guide treatment decisions. Advances in the treatment of HR + breast cancer have resulted in improved patient outcomes in recent years. Continued development efforts with identification of biomarkers to better understand response and resistance to therapy are needed.

Transfer Learning for Radio Frequency Machine Learning: A Taxonomy and Survey.

Transfer learning is a pervasive technology in computer vision and natural language processing fields, yielding exponential performance improvements by leveraging prior knowledge gained from data with different distributions. However, while recent works seek to mature machine learning and deep learning techniques in applications related to wireless communications, a field loosely termed radio frequency machine learning, few have demonstrated the use of transfer learning techniques for yielding performance gains, improved generalization, or to address concerns of training data costs. With modifications to existing transfer learning taxonomies constructed to support transfer learning in other modalities, this paper presents a tailored taxonomy for radio frequency applications, yielding a consistent framework that can be used to compare and contrast existing and future works. This work offers such a taxonomy, discusses the small body of existing works in transfer learning for radio frequency machine learning, and outlines directions where future research is needed to mature the field.

Development and prospective evaluation of CAPLET, a cancer ambulatory patient physical function longitudinal evaluation tool for routine clinical practice.

PURPOSE: A patient's physical function is a critical outcome variable for measuring and improving chronic care management. However, patient-reported outcome measures of physical function are not routinely assessed in cancer outpatients, in part due to limitations of tools available. This study presents the development and evaluation of the Cancer Ambulatory Patient Physical Function Longitudinal Evaluation Tool (CAPLET) as an adaptive response tool for routinely screening for physical dysfunction in oncology clinical practice. METHODS: In phase 1, 407 adult outpatients at Princess Margaret Cancer Centre completed the World Health Organization Disability Assessment Schedule (WHODAS) 2.0, Health Assessment Questionnaire Disability Index (HAQ-DI), EuroQuol-5D-3L ( EQ-5D-3L), and patient-reported outcome (PRO)-Eastern Cooperative Oncology Group (ECOG). CAPLET was developed based on a branching logic algorithm navigating patients to appropriate domains of HAQ-DI/WHOAS using their responses to the PRO-ECOG/EQ-5D-3L as screeners. Sensitivity/specificity of CAPLET screeners for HAQ-DI/WHODAS items were reported. In phase 2, CAPLET vs the WHODAS/HAQ-DI were alternatively administrated to 318 adult outpatients in a two-arm trial comparing time to completion and acceptability between the tools. RESULTS: Using a patient's ECOG status and the sum of the mobility, self-care, and usual activity dimensions of the EQ-5D-3L to dichotomize patients as with or without difficulty, CAPLET achieved a sensitivity > 90% against recommended WHODAS and HAQ-DI cutoffs for significant dysfunction. Sensitivity of screeners for capturing dysfunction in individual WHODAS/HAQ-DI items ranged from 85 to 100%. Compared to the HAQ-DI/WHODAS, CAPLET was associated with a 50% reduction in administration times and improved patient acceptability, while reducing question burden by 84% for half the sample population. CONCLUSIONS: CAPLET improves the feasibility of capturing detailed assessments of patient-reported physical function in cancer outpatients.

Audience affects decision-making in a marmoset communication network.

An audience can have a profound effect on the dynamics of communicative interactions. As a result, non-human primates often adjust their social decision-making strategies depending on the audience composition at a given time. Here we sought to test how the unique vocal behaviour of multiple audience members affected decisions to communicate. To address this issue, we developed a novel experimental paradigm in which common marmosets directly interacted with multiple 'virtual monkeys' (VMs), each of whom represented an individual marmoset with distinct vocal behaviour. This active social signalling paradigm provided subjects an opportunity to interact with and learn about the behaviour of each VM in the network and apply this knowledge in subsequent communicative decisions. We found that subjects' propensity to interact with particular VMs was determined by the behaviour of each VM in the audience and suggests that marmoset social decision-making strategies are highly adaptive to nuances of the immediate communication network.

Multiple Types of Childhood and Adult Violence Among Homeless and Unstably Housed Women in San Francisco.

This study examined the relationship between different forms of childhood violence (emotional, physical, and sexual) and these same forms of violence in adulthood, using a crosssectional baseline survey of 298 homeless and unstably housed women in San Francisco, California. We also examined other related factors, including mental illnesses diagnosis, sex exchange, jail time, HIV status, and sociodemographic information. Regression analysis indicated that although several of these factors were associated with experiences of violence as an adult, specific types of child violence (e.g., sexual violence) predicted instances of that same type of violence as an adult but not necessarily other types. Thus, risk of adult violence among low-income women may be better predicted and addressed through histories of same-type childhood violence, despite years of intervening exposures and stressors.

Postoperative risk of venous thromboembolism in rheumatic disease patients.

Both traditional and disease-related risk factors for venous thromboembolism (VTE) must be considered when assessing rheumatic disease patients preoperatively. While many studies suggest that patients with rheumatic diseases are at higher risk of VTE overall, studies in rheumatoid arthritis patients do not demonstrate an increased risk of postoperative VTE. Here, we review the literature on VTE risk in patients with rheumatoid arthritis, systemic lupus erythematosus, Behcet's disease, and vasculitis. The data suggest that disease activity is a driver of VTE risk. While rheumatoid arthritis patients undergoing elective arthroplasty are not at elevated VTE risk, patients with systemic lupus erythematosus and antiphospholipid antibody syndrome undergoing surgery have an elevated risk of postoperative VTE.

Transitioning from epicutaneous to oral peanut immunotherapy.

Introduction: Epicutaneous immunotherapy (EPIT) has been tested in clinical trials for children with peanut allergy (PA) for its safety and efficacy in inducing desensitization. Aside from peanut avoidance and symptom management, oral immunotherapy (OIT) is another option for PA patients. However, OIT can be associated with adverse events and pose safety concerns to children and their caregivers. Methods: This study assessed 27 children who successfully completed a peanut EPIT trial. 18 of them transitioned to peanut OIT with starting doses ranging from 10-600 mg of peanut protein. Our aim was to learn more about the EPIT to OIT experience through descriptive survey responses and to gather information that may support the sequential use of the two immunotherapies for safe and positive outcomes that may not be achieved by either alone. Results: Overall, children and their caregivers had less anxiety about starting OIT after having had peanut exposure through EPIT. Most children who transitioned from EPIT to OIT had no or minor symptoms initially, with symptoms lessening later in OIT. Most were also able to maintain or increase their peanut dose over time, achieving maintenance doses of 60-2,000 mg. Discussion: In comparison with current literature on OIT for PA in children, the reported symptoms appeared less severe and less prevalent in the EPIT to OIT group. However, there were 3 participants who withdrew from OIT due to the development of intolerable symptoms. This study provides initial data in support of EPIT to OIT, and larger randomized controlled trials assessing effectiveness of the two therapies together are warranted.

Oral Immunotherapy in Children: Clinical Considerations and Practical Management.

Oral immunotherapy (OIT) in pediatric patients provides an alternative option to the current standard of care in food allergy, which is allergen avoidance and reactive treatment. Because patients are exposed to one or more food allergens during treatment, OIT is associated with adverse events and can be a cumbersome process for children, their caregivers, and clinicians. However, there have been an overwhelming number of studies that show high efficacy in both single- and multi-allergen OIT, and that quality of life is greatly improved for both patients and their families after undergoing immunotherapy. This review discusses clinical considerations for OIT in pediatrics, including efficacy and safety, practical management, and future directions of treatment.

The Impact of the Affordable Care Act on Dental Care: An Integrative Literature Review.

The goal of the Patient Protection and Affordable Care Act (ACA) is to increase access to health insurance and decrease health care cost while improving health care quality. With more articles examining the relationship between one of the ACA provisions and dental health outcomes, we systematically reviewed the effect of the ACA on dental care coverage and access to dental services. We searched literature using the National Library of Medicine's Medline (PubMed) and Thomson Reuters' Web of Science between January 2010 and November 2020. We identified 33 articles related to dental coverage, and access/utilization of dental care services. This systematic review of studies showed that the ACA resulted in gains in dental coverage for adults and children, whereas results were mixed with dental care access. Overall, we found that the policy led to a decrease in cost barriers, an increase in private dental coverage for young adults, and increased dental care use among low-income childless adults. The implementation of the ACA was not directly associated with dental insurance coverage among people in the U.S. However, results suggest positive spillover effects of the ACA on dental care coverage and utilization by people in the national level dataset.

Developing a Parental-Friendly Scoring System for Children with Congenital Hand Differences.

Background: Congenital hand differences (CHD) exhibit enormous diversity and heterogeneity. Surgeons and parents often have different concepts of severity, making things difficult during parental consultation. This study aims to align surgeon/parental views on the severity of the child's CHD using a novel severity classification. Methods: Parents of affected children were asked to score the severity of their child's abnormality pre- and post-consultation using a subjective scale (1-4) without any explanation. Furthermore, parents were asked to rate their concerns about the future function and appearance of their child's hand condition using a similar scale of 1-4. They were then asked to rate the severity of the CHD post-consultation and three months post-operatively following explanation of the 4-point scale, as follows: 1 = treatment possible to normal; 2 = treatment possible to near normal; 3 = treatment possible but always some hand differences; 4 = treatment not possible. The surgeon also independently scored all children using his perception of the scale. Results: Forty-three children with a range of CHD were recruited into the sample. Linear weighted kappa analyses comparing inter-rater agreement showed no agreement between surgeon and parents during the initial scoring without any explanations. However, with explanations added, agreement rose significantly (kappa = 0.437 post-consultation and kappa = 0.706 three months post-op). No correlation was found between severity with both appearance and function (r = 0.277 and r = -0.184, respectively). Conclusions: This study demonstrated that the use of a simple scoring system was able to improve parental understanding of the severity and prognosis of CHD. The system demonstrated a good correlation between surgeon and parents. Such a scoring system can be easily utilised in the outpatient department to manage expectations and reduce anxiety.

Offspring of obese mice display enhanced intake and sensitivity for palatable stimuli, with altered expression of taste signaling elements.

Maternal body mass index and gestational weight gain predict future obesity status of the offspring. In studies of both rodents and non-human primates, maternal obesity also predicts a preference for palatable foods in the offspring. In this study, we used C57BL/6J mice to investigate whether an underlying cause for an increase in palatable food consumption in the offspring of obese mice was a change in taste function. Adult female mice were fed a normal chow (NC) or a high fat diet (HFD) for 5 weeks before mating, then also during the gestation (3 weeks) and lactation (3 weeks) periods, with offspring always maintained on a normal chow diet; thus the only experience offspring had with high fat food was via maternal exposure. Offspring exhibited similar weight, blood glucose levels and baseline water and chow intake in adulthood. Taste response was assessed after reaching maturity, using brief-access taste testing, with female offspring of obese dams showing an enhanced response to sucrose, and both sexes consuming more sucrose, sucralose and high fat diet if from obese mothers. Offspring also exhibited increased taste bud expression of mRNA for sweet receptor subunits T1R (Taste receptor type) 2 and 3, as well as other markers associated with taste signaling. Taste morphology in both groups appeared similar. Results indicate that obesity in the mother may lead to unhealthy feeding behavior in the offspring, correlating with altered expression of taste signaling elements, which likely drive increased avidity for palatable foods.

Psychiatric Risk in Unstably Housed Sexual Minority Women: Relationship between Sexual and Racial Minority Status and Human Immunodeficiency Virus and Psychiatric Diagnoses.

BACKGROUND: Stress associated with minority statuses has been linked to mental health disorders. However, research conducted exclusively among impoverished women, a population known to be at risk for poor health owing to overlapping risks, is sparse. We sought to determine if homeless and unstably housed sexual minority (i.e., nonheterosexual) women were at greater psychiatric risk than their heterosexual counterparts. We also sought to determine if racial/ethnic minority and human immunodeficiency virus status contributed to psychiatric risks. METHODS: Homeless/unstably housed women living in San Francisco between 2008 and 2010 were followed biannually over 3 years. Generalized estimating equation analysis identified significant correlates of any substance use, mood, or anxiety disorder, as well as the total number of psychiatric disorders. RESULTS: Among 300 women, 24% reported nonheterosexual identity at the first study visit. Consistent with minority stress theory, lesbian and bisexual identity were associated with higher levels of mental health comorbidity, and bisexual identity was related to greater rates of substance use disorders and mood disorders. Unique to this study, we found that identity assessed 1 or 2 years prior does not predict current substance disorders, but current identity does. In addition, women who were infected with the human immunodeficiency virus also had higher rates of mental health comorbidity and substance use disorders. Contrary to psychosocial stress theory, racial/ethnic minority status was associated with reduced odds of substance use disorder in this population. Recent homelessness was related to greater risk of anxiety disorder. CONCLUSIONS: Best research and health care practices should include the assessment of sexual orientation and housing status when addressing risks for mental health and substance disorders among low-income women.

A longitudinal study of the aftermath of rape among rural South African women.

OBJECTIVE: Sexual assaults against women are a global health crisis, with alarmingly high rates in South Africa. However, we know very little about the circumstances and the aftermath of these experiences. Further, there is limited information about how factors specific to the rape (e.g., fighting back) versus those that are specific to the individual-and potentially modifiable-influence mental health outcomes. This study examined how situational characteristics of rape as well as individual and situational factors confer risk for symptoms of depression, posttraumatic stress disorder (PTSD), and dysfunctional sexual behavior at 12-month follow-up. METHOD: Two hundred nine (N = 209) South African women were recruited from rural rape clinics in the Limpopo Province (LP) and North West Province (NWP) of South Africa. Interviews were conducted at baseline (within 6 months of the rape incident) and at 6 and 12 months by trained staff at the clinics in English or the women's native languages. Women were interviewed after services were provided in a private room. RESULTS: One hundred thirty-two (n = 132) women were lost to follow-up at 12 months, resulting in 77 women with interview data for all time points. Undermining by the survivor's social support system and an increased belief in myths about rape were associated with increased dysfunctional sexual practices and symptoms of depression. CONCLUSIONS: These findings demonstrate the need for interventions that address the most pervasive effects of rape over time. These behaviors can increase risks for revictimization and reduce psychological well-being in the aftermath of rape. (PsycINFO Database Record

Physico-electrochemical Characterization of Pluripotent Stem Cells during Self-Renewal or Differentiation by a Multi-modal Monitoring System.

Monitoring pluripotent stem cell behaviors (self-renewal and differentiation to specific lineages/phenotypes) is critical for a fundamental understanding of stem cell biology and their translational applications. In this study, a multi-modal stem cell monitoring system was developed to quantitatively characterize physico-electrochemical changes of the cells in real time, in relation to cellular activities during self-renewal or lineage-specific differentiation, in a non-destructive, label-free manner. The system was validated by measuring physical (mass) and electrochemical (impedance) changes in human induced pluripotent stem cells undergoing self-renewal, or subjected to mesendodermal or ectodermal differentiation, and correlating them to morphological (size, shape) and biochemical changes (gene/protein expression). An equivalent circuit model was used to further dissect the electrochemical (resistive and capacitive) contributions of distinctive cellular features. Overall, the combination of the physico-electrochemical measurements and electrical circuit modeling collectively offers a means to longitudinally quantify the states of stem cell self-renewal and differentiation.

Autoshaping of chlordiazepoxide drinking in non-deprived rats.

Effects of autoshaping procedures (Paired versus Random) and sipper fluid [chlordiazepoxide (CDP) versus water] on sipper-directed drinking were evaluated in 32 male Long-Evans rats maintained with free access to food and water. For the Paired/CDP group (n = 16), autoshaping procedures consisted of the presentation of the CDP sipper conditioned stimulus (CS) followed by the response-independent presentation of the food unconditioned stimulus (US). The concentration of CDP in the sipper CS (0.05, 0.10, 0.15, 0.20, and 0.25 mg/ml CDP) was increased across sessions. The Paired/Water group (n = 8) received only water in the sipper CS. The Random/CDP group (n = 8) received the CDP sipper CS and food US randomly with respect to one another. The Paired/CDP group drank significantly more of the 0.20 mg/ml and 0.25 mg/ml CDP solutions than the Random/CDP control, and more fluid than the Paired/Water control group when the sipper CS for the Paired/CDP group contained the three highest concentrations of CDP. CS-Only extinction procedures reliably reduced sipper CS-directed drinking in the Paired/CDP and the Paired/Water groups, but not in the Random/CDP group. Data are consistent with the hypothesis that Pavlovian autoshaping procedures induce sipper CS-directed drinking of CDP in rats deprived of neither food nor fluid. Implications for the autoshaping model of drug abuse are discussed.

How reliable are self-reports of HIV status disclosure? Evidence from couples in Malawi.

INTRODUCTION: The majority of research on human immunodeficiency virus (HIV) disclosure utilizes the perspective from a single individual, which cannot be substantiated in the absence of supporting data such as from a primary partner. OBJECTIVES: The objectives of this study were to evaluate: (1) the extent to which self-reported HIV disclosure was confirmed by a primary partner; (2) individual and relationship-level predictors of self-reported versus confirmed disclosure; and (3) whether confirmed disclosure was a stronger predictor of correctly assessing a partner's HIV status compared to self-reported disclosure. METHODS: As part of an 8-wave longitudinal study from 2009 to 2011 in southern Malawi, 366 individuals (183 couples) were interviewed about their primary relationship (wave 3), individually tested for HIV (wave 4), and then asked whether they disclosed to their primary partner (wave 5). RESULTS: While 93% of respondents reported that they disclosed, only 64% of respondents had confirmed reports from their partner. Having communicated with partner about HIV was positively associated with self-reported disclosure; this association remained significant but became more precise in the models for confirmed disclosure. Confirmed disclosure, but not self-report, was a significant predictor of correctly assessing a partner's HIV status. Being male, having lower perceived partner infidelity, having higher relationship unity, and testing HIV-negative were positively and significantly associated with correct assessment. Dyadic data from two partners provide an improved measure of disclosure as compared to a single individual's self-report and could be used to identify behavioral and biomedical opportunities to prevent HIV transmission within couples.

The effects of electrospun substrate-mediated cell colony morphology on the self-renewal of human induced pluripotent stem cells.

The development of xeno-free, chemically defined stem cell culture systems has been a primary focus in the field of regenerative medicine to enhance the clinical application of pluripotent stem cells (PSCs). In this regard, various electrospun substrates with diverse physiochemical properties were synthesized utilizing various polymer precursors and surface treatments. Human induced pluripotent stem cells (IPSCs) cultured on these substrates were characterized by their gene and protein expression to determine the effects of the substrate physiochemical properties on the cells' self-renewal, i.e., proliferation and the maintenance of pluripotency. The results showed that surface chemistry significantly affected cell colony formation via governing the colony edge propagation. More importantly, when surface chemistry of the substrates was uniformly controlled by collagen conjugation, the stiffness of substrate was inversely related to the sphericity, a degree of three dimensionality in colony morphology. The differences in sphericity subsequently affected spontaneous differentiation of IPSCs during a long-term culture, implicating that the colony morphology is a deciding factor in the lineage commitment of PSCs. Overall, we show that the capability of controlling IPSC colony morphology by electrospun substrates provides a means to modulate IPSC self-renewal.