Harvard University

Objective: Supporting patient-clinician communication is key to implementing tailored, risk-based screening for older adults. Objectives of this multiphase mixed methods study were to identify factors that primary care clinicians consider influential when making screening mammography recommendations for women ≥ 75 years, develop a patient decision aid that incorporates these factors, and gather feasibility and acceptability from the patients' perspective. Methods: Clinicians from a Mid-Atlantic practice network completed online surveys. Women in the same network completed surveys before and after receiving a tailored booklet that included information about the benefits and harms of screening for women ≥ 75 years, a breast cancer risk-estimate, and a question prompt list to support patient-clinician communication. Results: Clinicians (N = 21) were primarily women [57.1%] and practiced family medicine [81.0%]. They cited patients' age ≥ 75 years [95.4%], comorbidity [86.4%], functional status [77.3%], cancer family history [63.6%], U.S. Preventive Services Task Force guidelines [81.8%] and new research [77.3%] as factors influencing their recommendations. Fourteen women completed baseline surveys and received personalized decision aids (Mean age = 79.1 years). Eleven completed the post-intervention survey. All were satisfied with the booklet length, 81.8% found the booklet easy to understand and 72.7% helpful in decision-making Perceived lifetime breast cancer risk decreased significantly from pre- to post-intervention (p = 0.02). Conclusions: Results suggest this decision aid, which incorporates key decisional factors from the clinician's perspective, is feasible and acceptable to patients. Innovation: A tailored decision aid booklet is innovative as it provides information on personalized risk and potential benefits and harms to older women considering screening.

Each year, several disasters occur, resulting in enormous human, infrastructural, and economic losses. To minimize losses and ensure an adequate emergency response, it is vital to prepare the community for greater shock absorption and recovery after an occurrence. This raises the concept of community resilience and also demands appropriate metrics and prediction models for improved preparedness and adaptability. While a community is impacted in three main ways during a disaster-namely social, physical, and cyber-there are currently no tools to model their interrelationship. Thus, this paper presents a multi-agent cyber-physical-social model of community resilience, taking into account the interconnection of power systems, emergency services, social communities, and cyberspace. To validate the model, we used data on two hurricanes (Irma and Harvey) collected from Twitter, GoogleTrends, FEMA, power utilities, CNN, and Snopes (a fact-checking organization). We also describe methods for quantifying social metrics such as the level of anxiety, risk perception, and cooperation using social sensing, natural language processing, and text mining tools. We examine the suggested paradigm through three different case studies: 1) hurricanes Irma and Harvey; 2) a group of nine agents; and 3) a society comprised of six distinct communities. According to the results, cooperation can positively change individual behavior. Relationships within a community are so crucial that a smaller population with greater empathy may be more resilient. Similar dynamic changes in social characteristics occur when two empathetic communities share resources after a disaster.

Background Safe drinking water is a fundamental human right, yet more than 785 million people do not have access to it. The burden of water management disproportionately falls on women and young girls, and they suffer the health, psychosocial, political, educational, and economic effects. While water conditions and disease outcomes have been widely studied, few studies have summarized the research on drinking water and implications for gender equity and empowerment (GEE). Methods A systematic review of primary literature published between 1980 and 2019 was conducted on drinking water exposures and management and the implications for GEE. Ten databases were utilized (EMBASE, PubMed, Web of Science, Cochrane, ProQuest, Campbell, the British Library for Development Studies, SSRN, 3ie International Initiative for Impact Evaluation, and clinicaltrials.gov). Drinking water studies with an all-female cohort or disaggregated findings according to gender were included. Results A total of 1280 studies were included. GEE outcomes were summarized in five areas: health, psychosocial stress, political power and decision-making, social-educational conditions, and economic and time-use conditions. Water quality exposures and implications for women's health dominated the literature reviewed. Women experienced higher rates of bladder cancer when exposed to arsenic, trihalomethanes, and chlorine in drinking water and higher rates of breast cancer due to arsenic, trichloroethylene, and disinfection byproducts in drinking water, compared to men. Women that were exposed to arsenic experienced higher incidence rates of anemia and adverse pregnancy outcomes compared to those that were not exposed. Water-related skin diseases were associated with increased levels of psychosocial stress and social ostracization among women. Women had fewer decision-making responsibilities, economic independence, and employment opportunities around water compared to men. Conclusion This systematic review confirms the interconnected nature of gender and WaSH outcomes. With growing attention directed towards gender equity and empowerment within WaSH, this analysis provides key insights to inform future research and policy.

Studies of the impacts of solar geoengineering have mostly ignored tropospheric chemistry. By decreasing the sunlight reaching Earth's surface, geoengineering may help mitigate anthropogenic climate change, but changing sunlight also alters the rates of chemical reactions throughout the troposphere. Using the GEOS‐Chem atmospheric chemistry model, we show that stratospheric aerosol injection (SAI) with sulfate, a frequently studied solar geoengineering method, can perturb tropospheric composition over a span of 10 years, increasing tropospheric oxidative capacity by 9% and reducing methane lifetime. SAI decreases the overall flux of shortwave radiation into the troposphere, but increases flux at certain UV wavelengths due to stratospheric ozone depletion. These radiative changes, in turn, perturb tropospheric photochemistry, driving chemical feedbacks that can substantially influence the seasonal and spatial patterns of radiative forcing beyond what is caused by enhanced stratospheric aerosol concentrations alone. For example, chemical feedbacks decrease the radiative effectiveness of geoengineering in northern high latitude summer by 20%. Atmospheric chemical feedbacks also imply the potential for net global public health benefits associated with stratospheric ozone depletion, as the decreases in mortality resulting from SAI‐induced improvements in air quality outweigh the increases in mortality due to increased UV radiation exposure. Such chemical feedbacks also lead to improved plant growth. Our results show the importance of including fuller representations of atmospheric chemistry in studies of solar geoengineering and underscore the risk of surprises from this technology that could carry unexpected consequences for Earth's climate, the biosphere, and human health.

Polycomb repressive complex 2 (PRC2) silences genes through trimethylation of histone H3K27. PRC2 associates with numerous precursor messenger RNAs (pre-mRNAs) and long noncoding RNAs (lncRNAs) with a binding preference for G-quadruplex RNA. In this work, we present a 3.3-Å-resolution cryo–electron microscopy structure of PRC2 bound to a G-quadruplex RNA. Notably, RNA mediates the dimerization of PRC2 by binding both protomers and inducing a protein interface composed of two copies of the catalytic subunit EZH2, thereby blocking nucleosome DNA interaction and histone H3 tail accessibility. Furthermore, an RNA-binding loop of EZH2 facilitates the handoff between RNA and DNA, another activity implicated in PRC2 regulation by RNA. We identified a gain-of-function mutation in this loop that activates PRC2 in zebrafish. Our results reveal mechanisms for RNA-mediated regulation of a chromatin-modifying enzyme.

This chapter provides a conceptual foundation for the book, discussing how the COVID-19 pandemic created an opportunity to re-examine the relationship of schools to society. The chapter introduces the study, examines the educational effects which could have been expected from the pandemic, reviews some of the available empirical evidence about such effects, introduces each chapter, and discusses the theoretical implications of the study.

Editorial for: A new science of suffering, the wisdom of the soul, and the new behavioral economics of happiness: towards a general theory of well-being This Research Topic is designed to extend the theme of existential positive psychology (EPP) to new research areas. Theoretically, it is oriented toward a general theory of global well-being, which incorporates three pillars of EPP (Wong et al., 2022).

Background Opsins are the primary proteins responsible for light detection in animals. Cnidarians (jellyfish, sea anemones, corals) have diverse visual systems that have evolved in parallel with bilaterians (squid, flies, fish) for hundreds of millions of years. Medusozoans (e.g., jellyfish, hydroids) have evolved eyes multiple times, each time independently incorporating distinct opsin orthologs. Anthozoans (e.g., corals, sea anemones,) have diverse light-mediated behaviors and, despite being eyeless, exhibit more extensive opsin duplications than medusozoans. To better understand the evolution of photosensitivity in animals without eyes, we increased anthozoan representation in the phylogeny of animal opsins and investigated the large but poorly characterized opsin family in the sea anemone Nematostella vectensis. Results We analyzed genomic and transcriptomic data from 16 species of cnidarians to generate a large opsin phylogeny (708 sequences) with the largest sampling of anthozoan sequences to date. We identified 29 opsins from N. vectensis (NvOpsins) with high confidence, using transcriptomic and genomic datasets. We found that lineage-specific opsin duplications are common across Cnidaria, with anthozoan lineages exhibiting among the highest numbers of opsins in animals. To establish putative photosensory function of NvOpsins, we identified canonically conserved protein domains and amino acid sequences essential for opsin function in other animal species. We show high sequence diversity among NvOpsins at sites important for photoreception and transduction, suggesting potentially diverse functions. We further examined the spatiotemporal expression of NvOpsins and found both dynamic expression of opsins during embryonic development and sexually dimorphic opsin expression in adults. Conclusions These data show that lineage-specific duplication and divergence has led to expansive diversity of opsins in eyeless cnidarians, suggesting opsins from these animals may exhibit novel biochemical functions. The variable expression patterns of opsins in N. vectensis suggest opsin gene duplications allowed for a radiation of unique sensory cell types with tissue- and stage-specific functions. This diffuse network of distinct sensory cell types could be an adaptive solution for varied sensory tasks experienced in distinct life history stages in Anthozoans.

Bulk acoustic resonators can be fabricated on the same substrate as other components and can operate at various frequencies with high quality factors. Mechanical dynamic metrology of these devices is challenging as the surface information available through laser Doppler vibrometry lacks information about the acoustic energy stored in the bulk of the resonator. Here we report the spin-acoustic control of naturally occurring negatively charged silicon monovacancies in a lateral overtone bulk acoustic resonator that is based on 4H silicon carbide. We show that acoustic driving can be used at room temperature to induce coherent population oscillations. Spin-acoustic resonance is shown to be useful as a frequency-tunable probe of bulk acoustic wave resonances, highlighting the dynamical strain distribution inside a bulk acoustic wave resonator at ambient operating conditions. Our approach could be applied to the characterization of other high-quality-factor microelectromechanical systems and has the potential to be used in mechanically addressable quantum memory.

The CDF Collaboration recently reported a new precise measurement of the W-boson mass MW with a central value significantly larger than the SM prediction. We explore the effects of including this new measurement on a fit of the Standard Model (SM) to electroweak precision data. We characterize the tension of this new measurement with the SM and explore potential beyond the SM phenomena within the electroweak sector in terms of the oblique parameters S, T and U. We show that the large MW value can be accommodated in the fit by a large, nonzero value of U, which is difficult to construct in explicit models. Assuming U=0, the electroweak fit strongly prefers large, positive values of T. Finally, we study how the preferred values of the oblique parameters may be generated in the context of models affecting the electroweak sector at tree and loop level. In particular, we demonstrate that the preferred values of T and S can be generated with a real SU(2)L triplet scalar, the humble swino, which can be heavy enough to evade current collider constraints, or by (multiple) species of singlet-doublet fermion pairs. We highlight challenges in constructing other simple models for explaining a large MW value and several directions for further study.

Objective To estimate the associations between gestational weight gain (GWG) during pregnancy and neonatal outcomes in low and middle income countries. Design Individual participant data meta-analysis. Setting Prospective pregnancy studies from 24 low and middle income countries. Main outcome measures Nine neonatal outcomes related to timing (preterm birth) and anthropometry (weight, length, and head circumference) at birth, stillbirths, and neonatal death. Analysis methods A systematic search was conducted in PubMed, Embase, and Web of Science which identified 53 prospective pregnancy studies published after the year 2000 with data on GWG, timing and anthropometry at birth, and neonatal mortality. GWG adequacy was defined as the ratio of the observed maternal weight gain over the recommended weight gain based on the Institute of Medicine body mass index specific guidelines, which are derived from data in high income settings, and the INTERGROWTH-21st GWG standards. Study specific estimates, adjusted for confounders, were generated and then pooled using random effects meta-analysis models. Maternal age and body mass index before pregnancy were examined as potential modifiers of the associations between GWG adequacy and neonatal outcomes. Results Overall, 55% of participants had severely inadequate (<70%) or moderately inadequate (70% to <90%) GWG, 22% had adequate GWG (90-125%), and 23% had excessive GWG (≥125%). Severely inadequate GWG was associated with a higher risk of low birthweight (adjusted relative risk 1.62, 95% confidence interval 1.51 to 1.72; 48 studies, 93 337 participants; τ ² =0.006), small for gestational age (1.44, 1.36 to 1.54; 51 studies, 93 191 participants; τ ² =0.016), short for gestational age (1.47, 1.29 to 1.69; 40 studies, 83 827 participants; τ ² =0.074), and microcephaly (1.57, 1.31 to 1.88; 31 studies, 80 046 participants; τ ² =0.145) compared with adequate GWG. Excessive GWG was associated with a higher risk of preterm birth (1.22, 1.13 to 1.31; 48 studies, 103 762 participants; τ ² =0.008), large for gestational age (1.44, 1.33 to 1.57; 47 studies, 90 044 participants; τ ² =0.009), and macrosomia (1.52, 1.33 to 1.73; 29 studies, 68 138 participants; τ ² =0) compared with adequate GWG. The direction and magnitude of the associations between GWG adequacy and several neonatal outcomes were modified by maternal age and body mass index before pregnancy. Conclusions Inadequate and excessive GWG are associated with a higher risk of adverse neonatal outcomes across settings. Interventions to promote optimal GWG during pregnancy are likely to reduce the burden of adverse neonatal outcomes, however further research is needed to assess optimal ranges of GWG based on data from low and middle income countries.

Out-toeing gait may cause alterations in lower limb biomechanics that could lead to an increased risk of overuse injuries. Surgery and physical therapy are conventional methods for mitigating such gait, but they are costly and time-consuming. Wearable devices like braces and orthoses are used as affordable alternatives, but they apply non-negligible stress on the skin. Haptic feedback-delivering shoes were also recently developed, but they require actuators and power sources. The purpose of our study is to develop compression tights with inward directing taping lines that apply compression to lower limb muscles and segments to facilitate inward rotation of the foot, overcoming the drawbacks of previous methods. These compression tights were manufactured to fit the average height, leg length, hip girth, and waist girth of South Korean females in their twenties. The efficacy of these compression tights was evaluated by comparing walking kinematics and user satisfaction of 12 female dancers with an out-toeing gait under three conditions: wearing tights with taping lines, tights without taping lines, and basic bicycle shorts. The foot rotation angles and joint kinematics were recorded using a pressure-pad treadmill and motion capture system, respectively. Multiple pairwise comparisons revealed that the compression tights with inward-directing lines significantly reduced foot rotation angles (up to an average of 20.1%) compared with the bicycle shorts (p = 0.002 and 0.001 for dominant and non-dominant foot, respectively) or the compression tights without taping lines (p = 0.005 and p = 0.001 for dominant and non-dominant foot, respectively). Statistical parametric mapping revealed significant main effects of the tight type on joint kinematics. Also, t-tests revealed that the participants reported significantly higher ratings of perceived functionality and usability on the compression tights with inward-directing taping lines. In conclusion, we developed a comfortable and practical apparel-type wearable and demonstrated its short-term efficacy in mitigating out-toeing gait.

Background Suicidal behaviors are prevalent among college students; however, students remain reluctant to seek support. We developed a predictive algorithm to identify students at risk of suicidal behavior and used telehealth to reduce subsequent risk. Methods Data come from s everal waves of a prospective cohort study (2016–2022) of college students ( n = 5454). All first-year students were invited to participate as volunteers. (Response rates range: 16.00–19.93%). A stepped-care approach was implemented: (i) all students received a comprehensive list of services; (ii) those reporting past 12-month suicidal ideation were directed to a safety planning application; (iii) those identified as high risk of suicidal behavior by the algorithm or reporting 12-month suicide attempt were contacted via telephone within 24-h of survey completion. Intervention focused on support/safety-planning, and referral to services for this high-risk group. Results 5454 students ranging in age from 17–36 ( s.d. = 5.346) participated; 65% female. The algorithm identified 77% of students reporting subsequent suicidal behavior in the top 15% of predicted probabilities (Sensitivity = 26.26 [95% CI 17.93–36.07]; Specificity = 97.46 [95% CI 96.21–98.38], PPV = 53.06 [95% CI 40.16–65.56]; AUC range: 0.895 [95% CIs 0.872–0.917] to 0.966 [95% CIs 0.939–0.994]). High-risk students in the Intervention Cohort showed a 41.7% reduction in probability of suicidal behavior at 12-month follow-up compared to high-risk students in the Control Cohort. Conclusions Predictive risk algorithms embedded into universal screening, coupled with telehealth intervention, offer significant potential as a suicide prevention approach for students.

Social learning (SL) through experience with conspecifics can facilitate the acquisition of many behaviors. Thus, when Mongolian gerbils are exposed to a demonstrator performing an auditory discrimination task, their subsequent task acquisition is facilitated, even in the absence of visual cues. Here, we show that transient inactivation of auditory cortex (AC) during exposure caused a significant delay in task acquisition during the subsequent practice phase, suggesting that AC activity is necessary for SL. Moreover, social exposure induced an improvement in AC neuron sensitivity to auditory task cues. The magnitude of neural change during exposure correlated with task acquisition during practice. In contrast, exposure to only auditory task cues led to poorer neurometric and behavioral outcomes. Finally, social information during exposure was encoded in the AC of observer animals. Together, our results suggest that auditory SL is supported by AC neuron plasticity occurring during social exposure and prior to behavioral performance.

We sought to quantify the relationship between morning, afternoon or evening physical activity and consistency (e.g. routine) and risk of type 2 diabetes. A cohort of 93,095 UK Biobank participants (mean age 62 years) without a history of type 2 diabetes wore a wrist-worn accelerometer for 1 week. We converted accelerometer information to estimate metabolic equivalent of task (MET), summing MET h of total physical activity completed within three intra-day time segments (morning, afternoon and evening). We quantified physical activity consistency as the SD of participants’ daily total physical activity. We ultimately associated each of the following with incident type 2 diabetes: (1) morning, afternoon or evening ‘time-segmented’ MET h per week; and (2) consistency. We also considered moderate-to-vigorous physical activity (MVPA) and vigorous physical activity (VPA) in association with type 2 diabetes incidence. When considering MET as the physical activity measure, we observed protective associations of morning (HR 0.90 [95% CI 0.86, 0.93], p=7×10−8) and afternoon (HR 0.91 [95% CI 0.87, 0.95], p=1×10−5) but did not have evidence for evening physical activity (HR 0.95 [95% CI 0.90, 1.00], p=0.07) with type 2 diabetes. There was no difference between MET-measured morning and afternoon physical activity. Our substitution model highlighted the importance of adjusting for lifestyle factors (e.g. sleep time and diet); the effect of a substitution between afternoon and evening physical activity was attenuated after adjustment for lifestyle variables. Consistency of MET-measured physical activity was not associated with type 2 diabetes (p=0.07). MVPA and VPA were associated with decreased risk for type 2 diabetes at all times of the day. Total metabolic equivalents of physical activity in the morning and afternoon had a protective effect on diabetes risk and evening activity was not associated with diabetes. Consistency of physical activity did not play a role in decreasing risk for diabetes. Vigorous activity is associated with lower risk no matter the time of day of activity.

Flat sheets patterned with folds, cuts or swelling regions can deform into complex three-dimensional shapes under external stimuli1–24. However, current strategies require prepatterning and lack intrinsic shape selection5–24. Moreover, they either rely on permanent deformations6,12–14,17,18, preventing corrections or erasure of a shape, or sustained stimulation5,7–11,25, thus yielding shapes that are unstable. Here we show that shape-morphing strategies based on mechanical multistability can overcome these limitations. We focus on undulating metasheets that store memories of mechanical stimuli in patterns of self-stabilizing scars. After removing external stimuli, scars persist and force the sheet to switch to sharply selected curved, curled and twisted shapes. These stable shapes can be erased by appropriate forcing, allowing rewritable patterns and repeated and robust actuation. Our strategy is material agnostic, extendable to other undulation patterns and instabilities, and scale-free, allowing applications from miniature to architectural scales.