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AbstractBackground:Understanding characteristics of healthcare personnel (HCP) with SARS-CoV-2 infection supports the development and prioritization of interventions to protect this important workforce. We report detailed characteristics of HCP who tested positive for SARS-CoV-2 from April 20, 2020 through December 31, 2021.Methods:CDC collaborated with Emerging Infections Program sites in 10 states to interview HCP with SARS-CoV-2 infection (case-HCP) about their demographics, underlying medical conditions, healthcare roles, exposures, personal protective equipment (PPE) use, and COVID-19 vaccination status. We grouped case-HCP by healthcare role. To describe residential social vulnerability, we merged geocoded HCP residential addresses with CDC/ATSDR Social Vulnerability Index (SVI) values at the census tract level. We defined highest and lowest SVI quartiles as high and low social vulnerability, respectively.Results:Our analysis included 7,531 case-HCP. Most case-HCP with roles as certified nursing assistant (CNA) (444, 61.3%), medical assistant (252, 65.3%), or home healthcare worker (HHW) (225, 59.5%) reported their race and ethnicity as either non-Hispanic Black or Hispanic. More than one third of HHWs (166, 45.2%), CNAs (283, 41.7%), and medical assistants (138, 37.9%) reported a residential address in the high social vulnerability category. The proportion of case-HCP who reported using recommended PPE at all times when caring for patients with COVID-19 was lowest among HHWs compared with other roles.Conclusions:To mitigate SARS-CoV-2 infection risk in healthcare settings, infection prevention, and control interventions should be specific to HCP roles and educational backgrounds. Additional interventions are needed to address high social vulnerability among HHWs, CNAs, and medical assistants.

Nearly half of all sexually transmitted infections occur in adolescents and young adults. Among them, syphilis infections are on the rise in the United States. Sexually active adolescents, especially those who do not use condoms consistently or are men who have sex with men, are at particular risk for syphilis infection. With the rise in acquired syphilis infections, the incidence of congenital syphilis has also increased. Syphilis can have a variety of presentations based on infectious stage and central nervous system involvement. Careful physical examination and history can elicit the diagnosis. Screening with a nontreponemal test followed by treponemal testing can confirm the diagnosis, and staging is determined clinically. Testing for all sexually transmitted infections should be pursued because coinfections are common. Penicillin is the first-line treatment for syphilis, and duration of therapy depends on the presence of neurologic symptoms; all infants with possible congenital syphilis should receive treatment. Posttreatment monitoring is essential to confirm successful eradication of syphilis. All sexually active, at-risk patients, including pregnant persons, should be screened for syphilis, and those diagnosed as having syphilis should be counseled on disclosure to partners. Although not often found in a pediatric population, with the increasing incidence of syphilis infections in the United States, pediatric providers should have a low threshold for syphilis screening in adolescents and a high index of suspicion for congenital syphilis in infants.

Background: The relationship context is influential in shaping HIV risk and preventive behaviors. Yet, there is little understanding about how shared or separate residence of partners shapes perceptions that affect HIV prevention. Methods: We explored how shared or separate residence from one’s partner impacts HIV testing intentions among Latino immigrants in the USA. We analyzed data from 206 Latino immigrants residing in New York City, and examined three potential models to assess the relationships between partner residence, partner approval of HIV testing, and HIV testing behaviors. Results: Results indicated that shared residence was associated with greater partner approval to test for HIV (B= 0.48, 95% CI 0.01, 0.96, p= .04), and in turn, higher partner approval was associated with greater intention to test for HIV in the next 12 months (B= 0.38, 95% CI 0.15, 0.62., p< .01). Conclusions: Results suggest the need to consider partner residency as an important factor in shaping determinants of HIV testing behaviors. Conceptualization of couples as living separately, across national borders, is warranted for couple-based health interventions given the current socio-political climate in the USA. Future research focused on couple-based HIV prevention should examine strategies and policies to preserve or strengthen partner dynamics among couples living apart.

Despite current standard of care treatment, the period shortly after acute myocardial infarction (AMI) is associated with high residual cardiovascular (CV) risk, with high rates of recurrent AMI and CV death in the first 90 days following the index event. This represents an area of high unmet need that may be potentially addressed by novel therapeutic agents that optimize high-density lipoprotein cholesterol (HDL-C) function rather than increase HDL-C concentrations. Apolipoprotein A-I (apoA-I) is the major constituent of HDL and a key mediator of cholesterol efflux from macrophages within atherosclerotic plaque, a property especially relevant during the high-risk period immediately following an AMI when cholesterol efflux capacity is found to be reduced. CSL112 is a novel formulation of human plasma-derived apolipoprotein A-I (apoA-I), currently being evaluated in a Phase 3 clinical trial (AEGIS-II) for the reduction of major adverse CV events in the 90-day high-risk period post-AMI. In this review, we provide an overview of the biological properties of CSL112 that contribute to its proposed mechanism of action for potential therapeutic benefit. These properties include rapid and robust promotion of cholesterol efflux from cells abundant in atherosclerotic plaque, in addition to anti-inflammatory effects, which together, may have a stabilizing effect on atherosclerotic plaque. We provide a detailed overview of these mechanisms, in addition to information on the composition of CSL112 and how it is manufactured.

Objective: The objective of this paper is to examine how state-level characteristics relate to social support and mental health outcomes among Latino sexual minority men in the U.S. Methods: Multilevel linear regression analyses were used to estimate the effect of social support and contextual-level characteristics on mental health and alcohol use among Latino sexual minority men (n= 612). Individual-level data were collected via a national, online survey between November 2018 and May 2019. State-level data were drawn from the 2019 American Community Survey and the Human Rights Campaign’s 2018 State Equality Index score cards. Results: The interaction between friend support and supportive LGBTQ+ policies was associated with anxiety (B= 1.77; 95% CI 0.69, 2.85; p= 0.001) and depression (B= 2.25; 95% CI 0.99, 3.50; p<0.001). The interaction between friend support and Latino population size was associated with greater problematic alcohol use (B= 0.06; 95% CI 0.03, 0.10; p<0.001). The interaction between partner support and supportive LGBTQ+ policies were also associated problematic drinking (B= −1.72; 95% CI −3.05, −0.38; p<0.012). Conclusions: Contextual factors can affect the everyday experiences of Latino sexual minority men. The effect of social support on mental health outcomes may depend on state-level factors. Public health efforts that seek to address the mental health and problematic drinking behaviors of Latino sexual minority men must consider the impact of macro-level policies on program and intervention development.

AbstractDespite the growth of the Maker Movement, few studies have examined what learning opportunities in teacher education programs facilitate preservice teachers’ understanding of inclusive making for students from diverse backgrounds. This study explored how preservice teachers used their funds of knowledge for making projects in a STEM education course and how the use of these funds of knowledge influenced their perspectives on maker education. Guided by ethnographic research principles, we analyzed qualitative data collected from 15 preservice teachers. The findings show that preservice teachers used their diverse funds of knowledge in ways that: (a) transformed making practices into personally relevant learning activities, (b) positioned themselves as experts, (c) facilitated mutual learning, and (d) provided a significant resource for creative ideas in advancing making projects.

Molecular dynamics (MD) simulations have long had an important role in the study of equilibrium and nonequilibrium phase transitions. However, the effects of finite system sizes and periodic boundary conditions on such simulation are still not fully understood. In the present paper, we investigate this issue using simulations of the homogeneous melting of superheated crystals, specifically the effect of system size on the delay time before melting (which we call “melting time”). Because melting is a random and relatively rare event, we perform a systematic and extensive MD simulation study of a simple molecular system, solid-phase argon in a perfect fcc crystal superheated above the melting point. Using extensive replicate simulations, we first confirm that the distribution of melting times is accurately characterized by a gamma distribution. Next, we use the model of melting being triggered by random dislocations to derive an equation for the mean melting time as a function of system size and show that this model well-matches our MD data over a range of periodic boxes containing from 256 to 296,352 argon atoms. This equation shows that the system-size effect is inversely proportional to the number of atoms (or equivalently, proportional to L–3with Lbeing the side length of the periodic box) and could be used as a correction factor for melting times calculated in finite systems. We also study the effects of temperature on melting and find that the mean melting time exponentially decreases to a nonzero asymptotic value with increasing temperature. We observe that the melting time distributions shift toward more Gaussian-like forms of the gamma distribution (i.e., with larger values of the shape parameter) at elevated temperatures. Finally, we also present the results of the melting of water ice Ihto show that our findings apply to molecules and melting processes more complex than simple Lennard-Jones systems.

The study examines the future needs of young workers (18–35 years old) and how the labour union membership model in Singapore could evolve to continue to stay relevant to current and future workers. A combination of literature and qualitative research methods were used to examine the needs of youth and young workers. The insights and research findings indicated that the Singapore Labour Movement’s reputation amongst the youth is that of a place of “insurance”, in that it is a place only approached when one is in times of need. This has diminished the Labour Movement’s presence and reach amongst youth. To address this, we have adapted the Barbell Strategy’s principles and presented 4 actionable plans that aim to reposition the labour union as not just containing offerings of “insurance”, but also “investment”. The 4 actionable plans identify gaps in the market/society and leverage the union’s resources, as well as cater to the needs and interests of youth/young workers.

Phyllodes tumors (PT) are rare fibroepithelial lesions of the breast that commonly present as rapidly enlarging, palpable masses. Phyllodes tumors may be classified as benign, borderline, or malignant on the basis of histopathologic analysis. Although malignant PT cannot be distinguished from benign PT on the basis of imaging findings alone, studies suggest that malignant PT tend to be larger and irregular in shape, and they are less likely to have circumscribed margins. If biopsy results are indeterminate, excisional biopsy should be performed. Malignant PT can be difficult to distinguish histologically from sarcomas and spindle cell metaplastic breast carcinoma; the distinction is important for prognosis and treatment. Malignant PT are treated surgically with wide local excision, without a clear role for adjuvant radiation or chemotherapy in most cases. Nearly one-third of malignant PT recur locally, usually within a few years after initial diagnosis. Distant metastatic disease is rare, and the five-year overall survival rate of malignant PT is close to 80%. The purpose of this article is to review the clinical presentation, imaging appearance, histopathology, and management of malignant PT.

The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic.

With the development of percutaneously inserted devices, peripheral nerve stimulation (PNS) has been gaining attention within chronic pain literature as a less invasive neurostimulation alternative to spinal column and dorsal root ganglion stimulation. A majority of current PNS literature focuses on targeting individual distal nerves to treat individual peripheral mononeuropathies, limiting its applications. This article discusses our experience treating dermatomal pain with neurostimulation without needing to access the epidural space by targeting the proximal spinal nerve with peripheral nerve stimulation under ultrasound‐guidance. A temporary, percutaneous PNS was used to target the proximal spinal nerve in 11 patients to treat various dermatomal pain syndromes in patients seen in an outpatient chronic pain clinic. Four patients received stimulation targeting the lumbar spinal nerves and seven patient received stimulation targeting the cervical or thoracic spinal nerves. The case series presents 11 cases of PNS of the proximal spinal nerve. Seven patients, including a majority of the patients with lumbar radiculopathy, had analgesia during PNS. Four patients, all of whom targeted the cervical or thoracic spinal nerves, did not receive analgesia from PNS. PNS of the proximal spinal nerve may be an effective modality to treat dermatomal pain in patients who are not candidates for other therapies that require access to the epidural space. This technique was used to successfully treat lumbar radiculopathy, post‐herpetic neuralgia, and complex regional pain syndrome.

IMPORTANCE: Cardiorespiratory fitness is an important marker of childhood health and low fitness levels are a risk factor for disease later in life. Levels of children's fitness have declined in recent decades. Whether school-based physical activity interventions can increase fitness at the population level remains unclear. OBJECTIVE: To evaluate the effect of an internet-based intervention on children’s cardiorespiratory fitness across a large number of schools. DESIGN, SETTING, AND PARTICIPANTS: In this cluster randomized clinical trial, 22 government-funded elementary schools (from 137 providing consent) including 1188 students stratified from grades 3 and 4 in New South Wales, Australia, were randomized. The other schools received the intervention but were not included in the analysis. Eleven schools received the internet-based intervention and 11 received the control intervention. Recruitment and baseline testing began in 2016 and ended in 2017. Research assistants, blinded to treatment allocation, completed follow-up outcome assessments at 12 and 24 months. Data were analyzed from July to August 2020. INTERVENTIONS: The internet-based intervention included standardized online learning for teachers and minimal in-person support from a project mentor (9-10 months). MAIN OUTCOMES AND MEASURES: Multistage 20-m shuttle run test for cardiorespiratory fitness. RESULTS: Of 1219 participants (49% girls; mean [SD] age, 8.85 [0.71] years) from 22 schools, 1188 students provided baseline primary outcome data. At 12 months, the number of 20-m shuttle runs increased by 3.32 laps (95% CI, 2.44-4.20 laps) in the intervention schools and 2.11 laps (95% CI, 1.38-2.85 laps) in the control schools (adjusted difference = 1.20 laps; 95% CI, 0.17-2.24 laps). By 24 months, the adjusted difference was 2.22 laps (95% CI, 0.89-3.55 laps). The cost per student was AUD33 (USD26). CONCLUSIONS AND RELEVANCE: In this study, a school-based intervention improved children's cardiorespiratory fitness when delivered in a large number of schools. The low cost and sustained effect over 24 months of the intervention suggests that it may have potential to be scaled at the population level. TRIAL REGISTRATION: http://anzctr.org.au Identifier: ACTRN12616000731493

The Gulf of Maine (GOM) is one of the most productive and ecologically important marine environments on the planet. The Gulf of Maine Coastal Current (GMCC), which stretches along the western side of the GOM from the Bay of Fundy to Cape Cod, plays an important role in supporting this productivity by transporting nutrients, larvae and dinoflagellates southwestward along the Canadian and New England coastlines. Climate change has led to alterations in GOM ecosystems in recent years: GOM water temperatures have warmed and distributions of marine species have shifted. However, the impacts of the changing climate on the circulation within the GOM, including the path and velocity of the GMCC, have remained unclear. Here, we examine data collected by satellite tracked surface drifters and velocity data collected by the NERACOOS buoy array in order to investigate inter‐decadal changes to the flow of the GMCC. We find that over inter‐decadal timescales, the alongshore surface flow of the GMCC has slowed, particularly in the region southwest of Penobscot Bay. The slowdown observed in the GMCC surface flow is most likely attributed to a local strengthening of the southwesterly winds over the time period of interest. The Gulf of Maine (GOM) is the region of the ocean stretching between the Bay of Fundy and Cape Cod. The GOM is well known as a productive fishery and an important habitat for endangered species. The biological productivity of the GOM relies on the transport of things like nutrients and larvae throughout the region. In the western GOM, much of this transport is carried out by the Gulf of Maine Coastal Current (GMCC), which stretches from the Bay of Fundy to Cape Cod. Unfortunately, climate change is impacting the GOM: record breaking temperatures and changes in the distribution of species have been observed in recent years. In this study, we use data collected from surface drifters and anchored buoys to investigate whether the waters of the GMCC are changing as the temperatures warm. The results of this study indicate that the surface flow of the GMCC has slowed, particularly in the region southwest of Penobscot Bay. This slowdown is likely due to an increase in the strength of the local winds from the southwest, which may have disrupted the southwestward flow of the surface waters. Surface velocities in the Gulf of Maine Coastal Current have slowed on inter‐decadal timescales, particularly southwest of Penobscot BayAn intensification of the southwesterly component of the winds in the region likely contributed to the observed changes Surface velocities in the Gulf of Maine Coastal Current have slowed on inter‐decadal timescales, particularly southwest of Penobscot Bay An intensification of the southwesterly component of the winds in the region likely contributed to the observed changes

Both music-theoretic accounts and corpus analyses indicate that rock routinely employs chords that deviate from the norms of common-practice music. Yet we know little about how listeners experience the chords that make up rock’s liberal harmonic palette. In the present study, participants in two online experiments rated major chords that followed a short tonal sequence (a major scale + tonic major triad). Liking ratings obtained in Experiment 1 replicated earlier work showing that listeners prefer rock-typical targets—chords that are common in rock, but lie outside the basic diatonic set—to atypical, rarely used targets (Craton, Juergens, Michalak, & Poirier, 2016). Goodness of fit ratings with the same stimuli in Experiment 2 were similar to the liking ratings. High ratings for rock-typical target chords across the two experiments were not an artifact of their register and the pattern of responses was similar across four levels level of music training. In addition, the mean fitness ratings were approximated by simulations conducted with an auditory short-term memory (ASTM) model (Leman, 2000). Considered together, the findings provide evidence that listeners perceive rock-typical chords to be normal components of a key and that they may do so based on information in the auditory signal alone, without recourse to statistical learning mechanisms or representations of tonal knowledge. We speculate that bottom-up processes operating directly on the auditory signal create a perceptual ranking of chord fitness, which provides the harmonic palette from which composers/improvisers in different musical systems may conservatively (common-practice) or liberally (rock) choose. The mean data are available in tabular form for modelers in the online supplemental material.

The auditory experience of driving electric vehicles (EVs) has been studied as a means of conveying vehicle status information and improving user satisfaction. However, the driving experience and user preferences may vary depending on the driving context, including user characteristics. Thus, this study aims to 1) classify users based on their characteristics and 2) investigate their auditory experience preferences while driving EVs. For this purpose, 40 participants conducted questionnaires about their characteristics and performed a think-aloud task while driving 15.6 km in real EVs. As a result, three user characteristics and two user types were identified using factor analysis and K-means clustering, respectively. Text-formed think-aloud data were analyzed through network analysis to obtain insights for designing usercentered driving sound for EVs. These findings can contribute to the strategic management of EV sound design.

Background: The study examines the rate of alcohol, tobacco, and marijuana use among White, African American, and Latino adolescents and whether racial/ethnic bullying subtypes (victim-only, bullies-only, and bully/victim) are related to alcohol, tobacco, and marijuana use. Methods: We used data from the 2009–2010 Health Behaviour in School-aged Children study (n =9863) to examine differences in alcohol, tobacco, and marijuana use among White, African American, and Latino adolescents in the USA, and assessed whether racial/ethnic bullying involvement was associated with alcohol, tobacco, and marijuana use among these adolescents. Adolescents were categorized into four groups based on whether they had experienced racial bullying perpetration, victimization, both perpetration, and victimization, or neither perpetration nor victimization. Descriptive statistics were conducted to examine the distributions of the study variables and describe the samples. Spearman’s rank-order correlation analyses were used to examine the relationships among the variables. Multinomial logistic regression was conducted to examine alcohol, tobacco, and marijuana use among the racial bully victimization, perpetration, and victimization-perpetration groups compared to the non-involved group by race/ethnicity. Results: The White victim–only group was more likely to use alcohol but less likely to use tobacco. The African American victim–only group was more likely to use alcohol, and the bully/victim group was more likely to use marijuana. The Latino victim–only group was more likely to use alcohol, whereas the bully/victim group was more likely to use tobacco. Conclusion: Our findings have implications for the development and implementation of prevention and intervention programs across different racial/ethnic adolescent groups.

Increasingly, studies of entrepreneurship and migration have examined the role of immigrant entrepreneurs in revitalising and diversifying the economy of the host society. Further, recent transnational skilled entrepreneurs have been understood as being much more mobile in building international networks and collaborations between their home and host societies. These studies have tended to focus on the technically oriented entrepreneurs and to produce a single grand narrative about a particular migrant group that transfers knowledge and becomes a technical pioneer in their home society. This article scrutinises a group of first-generation Korean American female transnational entrepreneurs (FTEs) living in Silicon Valley and builds a nuanced understanding about the diversity and complexity of being transnational entrepreneurs. Through a multi-layered qualitative approach, the study illustrates that three major mechanisms are at play: 1) the ecosystem of Silicon Valley; 2) the dynamics of gender and ethnicity; and 3) the adoption to live in a transnational social field. These mechanisms shape the motivations, experiences, and performances of Korean American FTEs. This article reveals the contesting ways in which these three mechanisms work simultaneously with each other.

Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories.

Background: Hypomagnesemia is associated with poor clinical outcomes in cancer patients. Patients with bone metastasis from solid malignancies receiving denosumab (Dmab) to prevent skeletal-related events often receive concurrent antineoplastic agents for cancer treatment. The incidence and risk factors of hypomagnesemia in patients receiving Dmab and the optimal frequency of monitoring serum magnesium (Mg) levels have not been studied in these patient populations.Objective: The objective is to investigate the incidence and potential risk factors of hypomagnesemia and the optimal frequency of monitoring serum Mg levels.Methods: A retrospective chart review identified patients with solid malignancies with bone metastases treated with Dmab at the Loma Linda University Cancer Center between January 2013 and February 2024. The incidence of hypomagnesemia was determined using the number of patients with hypomagnesemia and the total number of patients in the study. Univariate and multivariate logistic regression analyses identified risk factors for hypomagnesemia.Results: Hypomagnesemia was observed in 19% (29/153) of patients, the majority of whom were on concurrent antineoplastic agents with ≥15% hypomagnesemia incidence (high-hypomagnesemic antineoplastics) or nonantineoplastic drugs with documented cases or incidence of hypomagnesemia (hypomagnesemic nonantineoplastics) in addition to high-hypomagnesemic antineoplastics. Multivariate analysis showed increased odds of developing hypomagnesemia with high-hypomagnesemic antineoplastics (odds ratio [OR]: 174.93, 95% confidence interval [CI]: 12.82 to 387.43, P< 0.001); hypomagnesemic nonantineoplastics plus high-hypomagnesemic antineoplastics (OR: 210.09, 95% CI: 11.80 to 3740.12, P< 0.001); and Mg level ≤ 0.85 prior to Dmab administration (OR: 16.79, 95% CI: 2.30 to 122.41, P= 0.005).Conclusion and relevance: This study describes the incidence and potential risk factors for hypomagnesemia in patients with solid malignancies and metastatic bone disease treated with Dmab. This study’s findings provide additional clinical insight into potential risk factors for hypomagnesemia and the need for more frequent serum Mg level monitoring of at-risk patients. Future prospective studies are needed to determine the exact frequencies most appropriate in monitoring serum Mg levels in this group of patients.

Images from NASA orbiter suggest that Europe’s Schiaparelli probe smashed on impact.

September’s sharpest science shots, selected by Nature’s photo team.

This article examines the peripheral experiences of skilled return migrants in their homeland and the wider social implications of global knowledge transfer. Through a case study of Korean New Zealander returnees, I argue that the process of skill transfer is not easy, as shown by the returnees’ difficulties and social alienation. Korean New Zealander returnees have a more alienated experience than Koreans of similar backgrounds returning from other Western countries.

Tissue macrophages have an embryonic origin and can be replenished in some tissues under steady-state conditions by blood monocytes. However, little is known about the residency and properties of infiltrating monocytes after an inflammatory challenge. The meninges of the central nervous system (CNS) are populated by a dense network of macrophages that act as resident immune sentinels. Here we show that, following lymphocytic choriomeningitis virus infection, resident meningeal macrophages (MMs) acquired viral antigen and interacted directly with infiltrating cytotoxic T lymphocytes, which led to macrophage depletion. Concurrently, the meninges were infiltrated by inflammatory monocytes that engrafted the meningeal niche and remained in situ for months after viral clearance. This engraftment led to interferon-γ-dependent functional changes in the pool of MMs, including loss of bacterial and immunoregulatory sensors. Collectively, these data indicate that peripheral monocytes can engraft the meninges after an inflammatory challenge, imprinting the compartment with long-term defects in immune function.

Supplemental digital content is available in the text.

Wildfires, cosmic rays and ancient-human hybrids are some of this year’s top stories.

This study examines how social support during childhood and adolescence is associated with self-rated good health and the incidence of depression among Latin American immigrants in the U.S. We focus on those who immigrated under age 18 (childhood arrivals) to understand the interplay between early social support and adult health outcomes. Data are from the 2012–2013 iteration of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III), which included a sample of 3441 immigrant respondents born in Latin America. Multivariable binomial logistic regression analyses indicated that childhood and interpersonal support in adulthood were negatively associated with lifetime major depressive disorder (LMDD) episodes. These associations differed between childhood arrival and adult arrival immigration samples. Findings from this study highlight the role that social support in critical developmental periods has on immigrant health and depression outcomes. Continued and more nuanced investigations are warranted to examine social resources across lifespans and their roles in mitigating adverse health outcomes among immigrants from Latin America.

IMPORTANCE: The relative outcomes of onabotulinum toxin A injections for treatment of adductor spasmodic dysphonia (ADSD), ADSD with lateral laryngeal tremor (ADSD+LT), and lateral LT without ADSD are unclear. OBJECTIVE: To compare the outcomes of onabotulinum toxin A treatment on ADSD, ADSD+LT, and lateral LT without ADSD. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted from January 1, 1990, to September 30, 2016, at a tertiary referral voice center. Participants included 817 patients treated with onabotulinum toxin A injections for diagnosis of ADSD, ADSD+LT, and lateral LT without ADSD. EXPOSURE: Injection of onabotulinum toxin A into the thyroarytenoid/lateral cricoarytenoid muscle complex. MAIN OUTCOMES AND MEASURES: Data from patient diaries were used to evaluate patient-perceived effectiveness of onabotulinum toxin A injection. Primary outcomes were (1) patient-reported good voice days (voice breaks or tremor minimized to patient satisfaction) and (2) percentage of injections in which maximal voice quality was reached (significant or complete reduction in vocal tremor or spasms during a treatment cycle). Multivariate analysis of variance tests compared differences in outcomes between groups. Subanalysis was performed to compare outcomes in patients with isolated LT with those who had mixed tremor (lateral with concomitant anterior-posterior and/or vertical components). RESULTS: Of 817 patients treated with onabotulinum toxin A injections for laryngeal movement disorders, 548 patients (12 771 injection sessions) met inclusion criteria (ADSD: n = 328, ADSD+LT: n = 77, lateral LT without ADSD: n = 143). Of these, 408 (80.8%) were women; mean (SD) age was 57.2 (13.7) years. Among patients with tremor, those with isolated LT had better outcomes than those with mixed tremor. In adjusted analysis, good voice days in patients with ADSD, ADSD+LT, and lateral LT without ADSD were 81.1, 75.4, and 71.3 days, respectively (partial η2, 0.05; 95% CI, 0.01-0.09). The percentage of maximally beneficial injections was 88.1% for ADSD, 83.4% for ADSD+LT, and 70.4% for LT without ADSD (partial η2, 0.12; 95% CI, 0.06-0.17). CONCLUSIONS AND RELEVANCE: Onabotulinum toxin A injections into the thyroarytenoid/lateral cricoarytenoid muscle complex are an effective treatment for ADSD, ADSD+LT, and LT without ADSD; however, the greatest effectiveness was observed among patients with ADSD. Defining tremor directionality may help to prognosticate the effectiveness of onabotulinum toxin A injection among patients presenting with tremor components.

How are closely related lineages, including liver, pancreas, and intestines, diversified from a common endodermal origin? Here, we apply principles learned from developmental biology to rapidly reconstitute liver progenitors from human pluripotent stem cells (hPSCs). Mapping the formation of multiple endodermal lineages revealed how alternate endodermal fates (e.g., pancreas and intestines) are restricted during liver commitment. Human liver fate was encoded by combinations of inductive and repressive extracellular signals at different doses. However, these signaling combinations were temporally re-interpreted: cellular competence to respond to retinoid, WNT, TGF-β, and other signals sharply changed within 24 hr. Consequently, temporally dynamic manipulation of extracellular signals was imperative to suppress the production of unwanted cell fates across six consecutive developmental junctures. This efficiently generated 94.1% ± 7.35% TBX3+HNF4A+human liver bud progenitors and 81.5% ± 3.2% FAH+hepatocyte-like cells by days 6 and 18 of hPSC differentiation, respectively; the latter improved short-term survival in the Fah−/−Rag2−/−Il2rg−/−mouse model of liver failure.

A giant iceberg, a quantum-entanglement experiment and the death of a spacecraft are among the year’s top stories.

IMPORTANCE: Gamification, the application of game design elements such as points and levels in nongame contexts, is often used in digital health interventions, but evidence on its effectiveness is limited. OBJECTIVE: To test the effectiveness of a gamification intervention designed using insights from behavioral economics to enhance social incentives within families to increase physical activity. DESIGN, SETTING, AND PARTICIPANTS: The Behavioral Economics Framingham Incentive Trial (BE FIT) was a randomized clinical trial with a 12-week intervention period and a 12-week follow-up period. The investigation was a community-based study between December 7, 2015, and August 14, 2016. Participants in the modified intent-to-treat analysis were adults enrolled in the Framingham Heart Study, a long-standing cohort of families. INTERVENTIONS: All participants tracked daily step counts using a wearable device or a smartphone, established a baseline, selected a step goal increase, and received daily individual feedback on goal performance by text message or email for 24 weeks. Families in the gamification arm could earn points and progress through levels based on physical activity goal achievement during the 12-week intervention. The game design was meant to enhance collaboration, accountability, and peer support. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of participant-days that step goals were achieved during the intervention period. Secondary outcomes included the proportion of participant-days that step goals were achieved during the follow-up period and the change in the mean daily steps during the intervention and follow-up periods. RESULTS: Among 200 adults comprising 94 families, the mean age was 55.4 years, and 56.0% (n = 112) were female. During the intervention period, participants in the gamification arm achieved step goals on a significantly greater proportion of participant-days (0.53 vs 0.32; adjusted difference, 0.27; 95% CI, 0.20-0.33; P &lt; .001) and had a significantly greater increase in the mean daily steps compared with baseline (1661 vs 636; adjusted difference, 953; 95% CI, 505-1401; P &lt; .001) than the control arm. During the follow-up period, physical activity in the gamification arm declined but remained significantly greater than that in the control arm for the proportion of participant-days achieving step goals (0.44 vs 0.33; adjusted difference, 0.12; 95% CI, 0.05-0.19; P &lt; .001) and the mean daily steps compared with baseline (1385 vs 798; adjusted difference, 494; 95% CI, 170-818; P &lt; .01). CONCLUSIONS AND RELEVANCE: Gamification designed to leverage insights from behavioral economics to enhance social incentives significantly increased physical activity among families in the community. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02531763

AbstractBackground:Medication adherence is critical for success of clinical trials.Objective:To assess oral riboflavin is an adherence marker.Methods:Riboflavin was incorporated into active treatment and placebo pills for a clinical trial lasting for 2 years.Results:The accuracy (area under the receiver operating curve) of urinary riboflavin was 0.91 as a binary classifier of adherence, and was similar or better than for two active study ingredients daidzein (0.92) and genistein (0.87) (all p < 0.0001). Decreased adherence over time was similar in the two study groups.Conclusion: Riboflavin is an accurate and useful biomarker for study pill ingestion.

ABSTRACTArsenic exposure may contribute to disease risk in humans through alterations in the epigenome. Previous studies reported that arsenic exposure is associated with changes in plasma histone concentrations. Posttranslational histone modifications have been found to differ between the brain tissue of human embryos with neural tube defects and that of controls. Our objectives were to investigate the relationships between plasma histone 3 levels, history of having an infant with myelomeningocele, biomarkers of arsenic exposure, and maternal folate deficiency. These studies took place in Bangladesh, a country with high environmental arsenic exposure through contaminated drinking water. We performed ELISA assays to investigate plasma concentration of total histone 3 (H3) and the histone modification H3K27me3. The plasma samples were collected from 85 adult women as part of a case-control study of arsenic and myelomeningocele risk in Bangladesh. We found significant associations between plasma %H3K27me3 levels and risk of myelomeningocele (P<0.05). Mothers with higher %H3K27me3 in their plasma had lower risk of having an infant with myelomeningocele (odds ratio: 0.91, 95% confidence interval: 0.84, 0.98). We also found that arsenic exposure, as estimated by arsenic concentration in toenails, was associated with lower total H3 concentrations in plasma, but only among women with folate deficiency (β = −9.99, standard error = 3.91, P=0.02). Our results suggest that %H3K27me3 in maternal plasma differs between mothers of infants with myelomeningocele and mothers of infants without myelomeningocele, and may be a marker for myelomeningocele risk. Women with folate deficiency may be more susceptible to the epigenetic effects of environmental arsenic exposure.