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The environmental impacts of livestock agriculture include the production of greenhouse gasses (GHG) such as methane (CH4) through enteric fermentation. Recent advances in our understanding of methanogenesis have led to the development of animal feed additives (AFA) that can reduce enteric CH4 emissions. However, many interacting factors impact hydrogen (H2) and CH4 production and AFA efficacy, including animal factors, basal diet, particle and fluid outflow, microbial populations, rumen fluid pH, and fermentative cofactor dynamics. Characterizing the response of rumen fermentation to AFA is essential for optimizing AFA implementation. Mechanistic models of enteric fermentation are constructed to represent physiological and microbial processes in the rumen and can be updated to characterize the dependency of AFA efficacy on basal diet and the impacts of AFA on fermentation. The objective of this article is to review the current state of rumen mechanistic modeling, contrasting the representation of key pools in extant models with a particular emphasis on representation of CH4 production. Additionally, we discuss the first rumen mechanistic models to include AFA and emphasize future model needs for improved representation of rumen dynamics under CH4-inhibition due to AFA supplementation, including the representation of microbial populations, rumen pH, fractional outflow rates, and thermodynamic control of fermentative pathways.

BACKGROUND AND OBJECTIVES: TMEM106B has been proposed as a modifier of disease risk in FTLD-TDP, particularly in GRN pathogenic variant carriers. Furthermore, TMEM106B has been investigated as a disease modifier in the context of healthy aging and across multiple neurodegenerative diseases. The objective of this study was to evaluate and compare the effect of TMEM106B on gray matter volume and cognition in each of the common genetic FTD groups and in patients with sporadic FTD. METHODS: Participants were enrolled through the ARTFL/LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study, which includes symptomatic and presymptomatic individuals with a pathogenic variant in C9orf72, GRN, MAPT, VCP, TBK1, TARDBP, symptomatic nonpathogenic variant carriers, and noncarrier family controls. All participants were genotyped for the TMEM106B rs1990622 SNP. Cross-sectionally, linear mixed-effects models were fitted to assess an association between TMEM106B and genetic group interaction with each outcome measure (gray matter volume and UDS3-EF for cognition), adjusting for education, age, sex, and CDR+NACC-FTLD sum of boxes. Subsequently, associations between TMEM106B and each outcome measure were investigated within the genetic group. For longitudinal modeling, linear mixed-effects models with time by TMEM106B predictor interactions were fitted. RESULTS: The minor allele of TMEM106B rs1990622, linked to a decreased risk of FTD, associated with greater gray matter volume in GRN pathogenic variant carriers under the recessive dosage model (N = 82, beta = 3.25, 95% CI [0.37-6.19], p = 0.034). This was most pronounced in the thalamus in the left hemisphere (beta = 0.03, 95% CI [0.01-0.06], p = 0.006), with a retained association when considering presymptomatic GRN pathogenic variant carriers only (N = 42, beta = 0.03, 95% CI [0.01-0.05], p = 0.003). The minor allele of TMEM106B rs1990622 also associated with greater cognitive scores among all C9orf72 pathogenic variant carriers (N = 229, beta = 0.36, 95% CI [0.05-0.066], p = 0.021) and in presymptomatic C9orf72 pathogenic variant carriers (N = 106, beta = 0.33, 95% CI [0.03-0.63], p = 0.036), under the recessive dosage model. DISCUSSION: We identified associations of TMEM106B with gray matter volume and cognition in the presence of GRN and C9orf72 pathogenic variants. The association of TMEM106B with outcomes of interest in presymptomatic GRN and C9orf72 pathogenic variant carriers could additionally reflect TMEM106Bs effect on divergent pathophysiologic changes before the appearance of clinical symptoms.

IntroductionCardiovascular health is important for brain aging, yet its role in the clinical manifestation of autosomal dominant or atypical forms of dementia has not been fully elucidated. We examined relationships between Life's Simple 7 (LS7) and clinical trajectories in individuals with autosomal dominant frontotemporal lobar degeneration (FTLD).MethodsTwo hundred forty-seven adults carrying FTLD pathogenic genetic variants (53% asymptomatic) and 189 non-carrier controls completed baseline LS7, and longitudinal neuroimaging and neuropsychological testing.ResultsAmong variant carriers, higher baseline LS7 is associated with slower accumulation of frontal white matter hyperintensities (WMHs), as well as slower memory and language declines. Higher baseline LS7 associated with larger baseline frontotemporal volume, but not frontotemporal volume trajectories.DiscussionBetter baseline cardiovascular health related to slower cognitive decline and accumulation of frontal WMHs in autosomal dominant FTLD. Optimizing cardiovascular health may be an important modifiable approach to bolster cognitive health and brain integrity in FTLD.HighlightsBetter cardiovascular health associates with slower cognitive decline in frontotemporal lobar degeneration (FTLD). Lifestyle relates to the accumulation of frontal white matter hyperintensities in FTLD. More optimal cardiovascular health associates with greater baseline frontotemporal lobe volume. Optimized cardiovascular health relates to more favorable outcomes in genetic dementia.

IntroductionAlthough frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype.MethodsRetrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments.ResultsCommon symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations.DiscussionThis study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients.HighlightsThis project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

AimsAccurate cardiac chamber quantification is essential for clinical decisions and ideally should be consistent across different echocardiography systems. This study evaluates variations between the Philips EPIQ CVx (version 9.0.3) and Canon Aplio i900 (version 7.0) in measuring cardiac volumes, ventricular function, and valve structures.Methods and resultsIn this gender-balanced, single-centre study, 40 healthy volunteers (20 females and 20 males) aged 40 years and older (mean age 56.75 ± 11.57 years) were scanned alternately with both systems by the same sonographer using identical settings for both 2D and 4D acquisitions. We compared left ventricular (LV) and right ventricular (RV) volumes using paired t-tests, with significance set at P < 0.05. Correlation and Bland-Altman plots were used for quantities showing significant differences. Two board-certified cardiologists evaluated valve anatomy for each platform. The results showed no significant differences in LV end-systolic volume and LV ejection fraction between platforms. However, LV end-diastolic volume (LVEDV) differed significantly (biplane: P = 0.018; 4D: P = 0.028). Right ventricular (RV) measurements in 4D showed no significant differences, but there were notable disparities in 2D and 4D volumes within each platform (P < 0.01). Significant differences were also found in the LV systolic dyssynchrony index (P = 0.03), LV longitudinal strain (P = 0.04), LV twist (P = 0.004), and LV torsion (P = 0.005). Valve structure assessments varied, with more abnormalities noted on the Philips platform.ConclusionAlthough LV and RV volumetric measurements are generally comparable, significant differences in LVEDV, LV strain metrics, and 2D vs. 4D measurements exist. These variations should be considered when using different platforms for patient follow-ups.

BACKGROUND: Murine data suggest that the placenta downregulates ferroportin (FPN) when iron is limited to prioritize iron for its own needs. Human data on the impact of maternal and neonatal iron status on placental FPN expression are conflicting. OBJECTIVES: This study aimed to identify determinants of placental FPN protein abundance and to assess the utility of the placental iron deficiency index (PIDI) as a measure of maternal/fetal iron status in newborns at high risk for anemia. METHODS: Placental FPN protein abundance was measured by western blots in placentae collected from 133 neonates born to adolescents (17.4 ± 1.1 y) carrying singletons (delivery gestational age [GA]: 39.9 ± 1.3 wk) and from 130 neonates born to 65 females (30.4 ± 5.2 y) carrying multiples (delivery GA: 35.0 ± 2.8 wk). Placental FPN and the PIDI (FPN:transferrin receptor 1) were evaluated in relation to neonatal and maternal iron-related markers (hemoglobin [Hb], serum ferritin [SF], soluble transferrin receptor [sTfR], total body iron [TBI], hepcidin, erythropoietin [EPO], erythroferrone). RESULTS: FPN protein was detected in all placentae delivered between 25 and 42 wk GA. Placental FPN protein abundance was associated with neonatal iron and erythropoietic markers (EPO: β: 0.10; 95% confidence interval [CI]: 0.06, 0.35; sTfR: β: 0.20; 95% CI: 0.03, 0.18; hepcidin: β: -0.06; 95% CI: -0.13, -0.0003; all P < 0.05). Maternal sTfR was only indirectly associated with placental FPN, with neonatal sTfR as the mediator (β-indirect: 0.06; 95% CI; 0.03, 0.11; P = 0.003). The PIDI was associated with neonatal Hb (β: -0.02; 95% CI: -0.03, -0.003), EPO (β: 0.07; 95% CI: 0.01, 0.14), and sTfR (β: 0.13; 95% CI: 0.004, 0.3) and with maternal SF (β: 0.08, 95% CI: 0.02, 0.14), TBI (β: 0.02; 95% CI: 0.009, 0.04), EPO (β: -0.10; 95% CI: -0.19, -0.01), sTfR (β: -0.16: 95% CI: -0.27, -0.06), and hepcidin (β: 0.05; 95% CI: 0.002, 0.11) at delivery (all P < 0.05). CONCLUSIONS: Placental FPN abundance was positively associated with neonatal indicators of increased erythropoietic activity and poor iron status. The PIDI was associated with maternal and neonatal iron-related markers but in opposite directions. More data are needed from a lower-risk normative group of females to assess the generalizability of findings. These trials were registered at clinicaltrials.gov as NCT01019902 and NCT01582802.

BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged

Rosmarinic acid is a polyphenol found in numerous fruits and vegetables, consumed in supplement form, and tested in numerous clinical trials for therapeutic applications due to its putative chemopreventive properties. Rosmarinic acid has been extensively studied at the cellular, whole animal, and molecular mechanism levels, presenting a complex array of multi-system biological effects. Rosmarinic acid-induced hormetic dose responses are widespread, occurring in numerous biological models and cell types for a broad range of endpoints. Consequently, this article provides the first assessment of rosmarinic acid-induced hormetic concentration/dose responses, their quantitative features, mechanistic foundations, extrapolative strengths/limitations, and their biomedical, clinical, and public health implications.

Background and objectivesProgressive focal anterior temporal lobe (ATL) neurodegeneration has been historically called semantic dementia. More recently, semantic variant primary progressive aphasia (svPPA) and semantic behavioral variant frontotemporal dementia (sbvFTD) have been linked with predominant left and right ATL neurodegeneration, respectively. Nonetheless, clinical tools for an accurate diagnosis of sbvFTD are still lacking. Expressive prosody refers to the modulation of pitch, loudness, tempo, and quality of voice used to convey emotional and linguistic information and has been linked to bilateral but right-predominant frontotemporal functioning. Changes in expressive prosody can be detected with semiautomated methods and could represent a useful diagnostic marker of socioemotional functioning in sbvFTD.MethodsParticipants underwent a comprehensive neuropsychological and language evaluation and a 3T MRI at the University of California San Francisco. Each participant provided a verbal description of the picnic scene from the Western Aphasia Battery. The fundamental frequency (f0) range, an acoustic measure of pitch variability, was extracted for each participant. We compared the f0 range between groups and investigated associations with an informant-rated measure of empathy, a facial emotion labeling task, and gray matter (GM) volumes using voxel-based morphometry.ResultsTwenty-eight patients with svPPA, 18 with sbvFTD, and 18 healthy controls (HCs) were included. f0 range was significantly different across groups: patients with sbvFTD showed reduced f0 range in comparison with both patients with svPPA (mean difference of -1.4 ± 2.4 semitones; 95% CI -2.4 to -0.4]; p < 0.005) and HCs (mean difference of -1.9 ± 3.0 semitones; 95% CI -3.0 to -0.7]; p < 0.001). A higher f0 range was correlated with a greater informant-rated empathy (r = 0.355; p ≤ 0.05), but not facial emotion labeling. Finally, the lower f0 range was correlated with lower GM volume in the right superior temporal gyrus, encompassing anterior and posterior portions (p < 0.05 FWE cluster corrected).DiscussionExpressive prosody may be a useful clinical marker of sbvFTD. Reduced empathy is a core symptom in sbvFTD; the present results extend this to prosody, a core component of social interaction, at the intersection of speech and emotion. They also inform the long-standing debate on the lateralization of expressive prosody in the brain, highlighting the critical role of the right superior temporal lobe.

ObjectiveTo determine whether inequities in COVID-19 infection and hospitalization differ from those for common medical conditions: influenza, appendicitis, and all-cause hospitalization.DesignRetrospective study based on electronic health records of three healthcare systems in San Francisco (university, public, and community) examining (1) racial/ethnic distribution in cases and hospitalization among patients with diagnosed COVID-19 (March-August 2020) and patients with diagnosed influenza, diagnosed appendicitis, or all-cause hospitalization (August 2017-March 2020), and (2) sociodemographic predictors of hospitalization among those with diagnosed COVID-19 and influenza.ResultsPatients 18 years or older with diagnosed COVID-19 (N = 3934), diagnosed influenza (N = 5932), diagnosed appendicitis (N = 1235), or all-cause hospitalization (N = 62,707) were included in the study. The age-adjusted racial/ethnic distribution of patients with diagnosed COVID-19 differed from that of patients with diagnosed influenza or appendicitis for all healthcare systems, as did hospitalization from these conditions compared to any cause. For example, in the public healthcare system, 68% of patients with diagnosed COVID-19 were Latine, compared with 43% of patients with diagnosed influenza, and 48% of patients with diagnosed appendicitis (p

ObjectiveThere is a need for a brief affect scale that also encompasses different components of affect relevant for researchers interested in physiological and health outcomes. The Subcomponents of Affect Scale (SAS) meets this need. This 18-item scale has nine positive and nine negative affect items encompassing six subscales (calm, well-being, vigour, depression, anxiety, anger). Previous research using the SAS has demonstrated its predictive validity, but no work has tested its subscale structure or longitudinal validity.DesignData from the Common Cold Project in which individuals (N = 610) completed the SAS over the course of seven days were used.ResultsConfirmatory factor analysis demonstrated the reliability of the subscale structure of the SAS across seven days (positive affect subscale structure: CFIs ≥ 0.98; negative affect subscale structure: CFIs ≥ 0.94 with day 6 CFI = 0.91) and tests of factorial invariance showed the scale is valid to use over time.ConclusionsThese results confirm the psychometric validity of the subscale structure of the SAS and imply that the subscales can be used longitudinally, allowing for its use in health research as well as non-health research that can benefit from its subscale structure and longitudinal capabilities.

Introduction A diverse workforce improves health care, educational outcomes, and research agendas. Currently, faculty from historically excluded groups remain underrepresented in academic medicine. Resources are needed in academic medical centers for those charged with recruiting and retaining a diverse and talented workforce. Methods Informed by the successful use of holistic review in medical student admissions, the Association of American Medical Colleges (AAMC) developed and piloted a toolkit for use in faculty recruitment and retention at five academic medical centers. Institutions led toolkit-guided holistic review workshops ranging from 2.5 to 3 hours in duration for leaders and faculty to identify and prioritize selection criteria used to modify faculty recruitment and retention materials and processes. AAMC surveys at pilot initiation and at two time points during implementation assessed satisfaction with and perceptions of the toolkit. Results At the first survey time point, the average toolkit rating across five institutions ranged from 3.2 to 4.4 (out of a maximum of 5.0) for helpfulness and from 3.5 to 4.9 for ease of use. At the second survey time point, the helpfulness of the tools received average ratings of 3.0–4.8. In respondents’ qualitative comments, we identified varying strategies for implementation and few barriers to implementation other than reluctance of some faculty to use scripted tools and concerns about anonymity in the exit interviews. Discussion The toolkit was well received and easy to implement. It will be important to study the use of these materials across other institutions, with attention to their impact on faculty diversity.

Objective The onset of the COVID-19 pandemic engendered a host of different behavioral responses in key areas such as resource purchasing and compliance with COVID regulations. This study explores why participation in these behaviors may have varied by examining the role of perseverative cognition (i.e., worry, rumination).Method A representative sample of U.S. adults (N = 230, Mage = 45.4, 50% female) was recruited online early in the COVID-19 pandemic (June 2020), approximately three months into safety-related school and business shutdowns. Participants completed a series of questionnaires on COVID-19-related worry, non-specific rumination, and a range of behaviors observed during the early stages of the pandemic (e.g., excessive shopping, purchasing guns, following isolation guidelines). Exploratory principal axis factoring and reliability studies of the newly created COVID-19 worry and behavior scales were performed, followed by an examination of the associations between worrying, ruminating and COVID-19-related early behaviors.Results COVID-related worry and reflective rumination were positively associated with purchasing behavior (i.e., purchasing household items, items for security, and items for entertainment). COVID-related worry was also positively associated with compliance behavior (i.e., watching the news, following government directives strictly, and staying home but contacting family and friends remotely). Brooding rumination was not significantly associated with either type of behavior.Conclusions Perseverative cognition can help explain patterns in COVID-related behaviors, what motivated differences in these behaviors and, thereby, help explain how people coped during this trying time.

IntroductionEarly caregiving interactions and experiences profoundly shape a child's brain development. The American Academy of Pediatrics (AAP) recently advocated for a public-health approach to promoting safe, stable, nurturing relationships that is “founded on universal primary preventions”, including consistent messaging on fostering family resilience, nurturing connections, and positive childhood experiences. Hospitals have unique access to families with children ages 0–5 and therefore play a key role in supporting these early experiences. This project sought to shift the organizational culture of maternity and pediatric units at a hospital towards promoting early relationships and child development through a physical messaging campaign paired with staff training. This study examined whether the messaging campaign and staff training shifted staff's self-reported knowledge, attitudes, and behavior.MethodsNon-physician staff across six pediatric and maternity units in a large urban hospital participated in the intervention. Staff completed surveys before and after message installation and training.ResultsAnalysis of 356 pre-intervention surveys and 320 post-intervention surveys showed significant changes in staff's knowledge, attitudes, and behaviors that promote early learning and parent-child relationships. Most staff also reported feeling more empowered in their work (88%) and that the hospital environment had become a friendlier place for parents and families (89%).DiscussionA messaging and training intervention can create a culture whereby staff support early caregiving and child development in the hospital setting. Further research is needed to understand whether the intervention impacts caregivers and their children.

The environmental impacts of livestock agriculture include the production of greenhouse gasses (GHG) such as methane (CH4) through enteric fermentation. Recent advances in our understanding of methanogenesis have led to the development of animal feed additives (AFA) that can reduce enteric CH4 emissions. However, many interacting factors impact hydrogen (H2) and CH4 production and AFA efficacy, including animal factors, basal diet, particle and fluid outflow, microbial populations, rumen fluid pH, and fermentative cofactor dynamics. Characterizing the response of rumen fermentation to AFA is essential for optimizing AFA implementation. Mechanistic models of enteric fermentation are constructed to represent physiological and microbial processes in the rumen and can be updated to characterize the dependency of AFA efficacy on basal diet and the impacts of AFA on fermentation. The objective of this article is to review the current state of rumen mechanistic modeling, contrasting the representation of key pools in extant models with a particular emphasis on representation of CH4 production. Additionally, we discuss the first rumen mechanistic models to include AFA and emphasize future model needs for improved representation of rumen dynamics under CH4-inhibition due to AFA supplementation, including the representation of microbial populations, rumen pH, fractional outflow rates, and thermodynamic control of fermentative pathways.

BACKGROUND: Measuring systemic inflammatory markers may improve clinical prognosis and help identify targetable pathways for treatment in patients with autosomal dominant forms of frontotemporal lobar degeneration (FTLD). METHODS: We measured plasma concentrations of IL-6, TNFα and YKL-40 in pathogenic variant carriers (MAPT, C9orf72, GRN) and non-carrier family members enrolled in the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration consortium. We evaluated associations between baseline plasma inflammation and rate of clinical and neuroimaging changes (linear mixed effects models with standardised (z) outcomes). We compared inflammation between asymptomatic carriers who remained clinically normal (asymptomatic non-converters) and those who became symptomatic (asymptomatic converters) using area under the curve analyses. Discrimination accuracy was compared with that of plasma neurofilament light chain (NfL). RESULTS: We studied 394 participants (non-carriers=143, C9orf72=117, GRN=62, MAPT=72). In MAPT, higher TNFα was associated with faster functional decline (B=0.12 (0.02, 0.22), p=0.02) and temporal lobe atrophy. In C9orf72, higher TNFα was associated with faster functional decline (B=0.09 (0.03, 0.16), p=0.006) and cognitive decline (B=-0.16 (-0.22, -0.10), p

INTRODUCTION: Over the past decade, numerous efforts have encouraged the realization of the learning health system (LHS) in the United States. Despite these efforts, and promising aims of the LHS, the full potential and value of research conducted within LHSs have yet to be realized. New technology coupled with a catalyzing global pandemic have spurred momentum. In addition, the LHS has lacked a consistent framework within which best evidence can be identified. Positive deviance analysis, itself reinvigorated by recent advances in health information technology (IT) and ubiquitous adoption of electronic health records (EHRs), may finally provide a framework through which LHSs can be operationalized and optimized. METHODS: We describe the synergy between positive deviance and the LHS and how they may be integrated to achieve a continuous cycle of health system improvement. RESULTS: As we describe below, the positive deviance approach focuses on learning from high-performing teams and organizations. CONCLUSION: Such learning can be enabled by EHRs and health IT, providing a lens into how digital clinical interventions are successfully developed and deployed.

In postoperative care, patient education and follow-up are pivotal for enhancing the quality of care and satisfaction. Artificial intelligence virtual assistants (AIVA) and large language models (LLMs) like Google BARD and ChatGPT-4 offer avenues for addressing patient queries using natural language processing (NLP) techniques. However, the accuracy and appropriateness of the information vary across these platforms, necessitating a comparative study to evaluate their efficacy in this domain. We conducted a study comparing AIVA (using Google Dialogflow) with ChatGPT-4 and Google BARD, assessing the accuracy, knowledge gap, and response appropriateness. AIVA demonstrated superior performance, with significantly higher accuracy (mean: 0.9) and lower knowledge gap (mean: 0.1) compared to BARD and ChatGPT-4. Additionally, AIVA’s responses received higher Likert scores for appropriateness. Our findings suggest that specialized AI tools like AIVA are more effective in delivering precise and contextually relevant information for postoperative care compared to general-purpose LLMs. While ChatGPT-4 shows promise, its performance varies, particularly in verbal interactions. This underscores the importance of tailored AI solutions in healthcare, where accuracy and clarity are paramount. Our study highlights the necessity for further research and the development of customized AI solutions to address specific medical contexts and improve patient outcomes.

IntroductionRemote smartphone assessments of cognition, speech/language, and motor functioning in frontotemporal dementia (FTD) could enable decentralized clinical trials and improve access to research. We studied the feasibility and acceptability of remote smartphone data collection in FTD research using the ALLFTD Mobile App (ALLFTD-mApp).MethodsA diagnostically mixed sample of 214 participants with FTD or from familial FTD kindreds (asymptomatic: CDR®+NACC-FTLD = 0 [N = 101]; prodromal: 0.5 [N = 49]; symptomatic ≥1 [N = 51]; not measured [N = 13]) were asked to complete ALLFTD-mApp tests on their smartphone three times within 12 days. They completed smartphone familiarity and participation experience surveys.ResultsIt was feasible for participants to complete the ALLFTD-mApp on their own smartphones. Participants reported high smartphone familiarity, completed ∼ 70% of tasks, and considered the time commitment acceptable (98% of respondents). Greater disease severity was associated with poorer performance across several tests.DiscussionThese findings suggest that the ALLFTD-mApp study protocol is feasible and acceptable for remote FTD research.HighlightsThe ALLFTD Mobile App is a smartphone-based platform for remote, self-administered data collection.The ALLFTD Mobile App consists of a comprehensive battery of surveys and tests of executive functioning, memory, speech and language, and motor abilities.Remote digital data collection using the ALLFTD Mobile App was feasible in a multicenter research consortium that studies FTD. Data was collected in healthy controls and participants with a range of diagnoses, particularly FTD spectrum disorders.Remote digital data collection was well accepted by participants with a variety of diagnoses.

Semantic variant primary progressive aphasia is a clinical syndrome characterized by marked semantic deficits, anterior temporal lobe atrophy and reduced connectivity within a distributed set of regions belonging to the functional network associated with semantic processing. However, to fully depict the clinical signature of semantic variant primary progressive aphasia, it is necessary to also characterize preserved neural networks and linguistic abilities, such as those subserving speech production. In this case-control observational study, we employed whole-brain seed-based connectivity on task-free MRI data of 32 semantic variant primary progressive aphasia patients and 46 healthy controls to investigate the functional connectivity of the speech production network and its relationship with the underlying grey matter. We investigated brain-behaviour correlations with speech fluency measures collected through clinical tests (verbal agility) and connected speech (speech rate and articulation rate). As a control network, we also investigated functional connectivity within the affected semantic network. Patients presented with increased connectivity in the speech production network between left inferior frontal and supramarginal regions, independent of underlying grey matter volume. In semantic variant primary progressive aphasia patients, preserved (verbal agility) and increased (articulation rate) speech fluency measures correlated with increased connectivity between inferior frontal and supramarginal regions. As expected, patients demonstrated decreased functional connectivity in the semantic network (dependent on the underlying grey matter atrophy) associated with average nouns' age of acquisition during connected speech. Collectively, these results provide a compelling model for studying compensation mechanisms in response to disease that might inform the design of future rehabilitation strategies in semantic variant primary progressive aphasia.

Meta-analyses indicate that positive psychological interventions are effective at increasing positive affect, as well as reducing anxiety and depression; however, it is unclear how well these effects generalize during periods of high stress. Therefore, the current study tested whether a 2-week online positive psychological intervention delivered during the COVID-19 pandemic, a naturalistic stressor, (1) increased positive affect; (2) improved psychological well-being, optimism, life satisfaction, perceived social support, and loneliness; (3) and reduced negative affect in college students, a group known to have high pandemic distress. Participants (N = 250; 76.9% female) ages 18-45 were recruited from the University of Pittsburgh undergraduate subject pool between September and November of 2020. Participants were randomized to the online positive psychological intervention or active control condition and stratified by trait positive affect, sex, and year in college. Participants in both conditions completed one writing activity every other day for two consecutive weeks. Control participants documented their activities for that day (e.g., meals, going to gym). Intervention participants chose from six positive psychology activities. All outcome variables were assessed pre- and post-intervention by validated questionnaires. Across both conditions, positive and negative affect decreased from pre- to post-intervention. No other psychological factor differed by condition, time, or their interaction. The current null findings are in line with a more recent meta-analysis indicating that positive psychological interventions may have smaller effects on psychological well-being and depressive symptoms than was reported pre-pandemic. Study findings may suggest reduced efficacy of virtual positive psychological interventions under highly stressful circumstances.Supplementary informationThe online version contains supplementary material available at 10.1007/s42761-022-00148-z.

Psychosocial factors are related to immune, viral, and vaccination outcomes. Yet, this knowledge has been poorly represented in public health initiatives during the COVID-19 pandemic. This review provides an overview of biopsychosocial links relevant to COVID-19 outcomes by describing seminal evidence about these associations known prepandemic as well as contemporary research conducted during the pandemic. This focuses on the negative impact of the pandemic on psychosocial health and how this in turn has likely consequences for critically relevant viral and vaccination outcomes. We end by looking forward, highlighting the potential of psychosocial interventions that could be leveraged to support all people in navigating a postpandemic world and how a biopsychosocial approach to health could be incorporated into public health responses to future pandemics.

Ruminants, particularly dairy and beef cattle, contribute to climate change through mostly enteric methane emissions. Several mitigating options have been proposed, including the feed additive 3-nitrooxypropanol (3-NOP). The objectives of this study were to explain the variability in the mitigating effect of 3-NOP and to investigate the interaction between diet composition and 3-NOP dose, using meta-analytical approaches. Data from 13 articles (14 experiments) met the selection criteria for inclusion in the meta-analysis, and 48 treatment means were used for the analysis. Mean differences were calculated as 3-NOP treatment mean minus control treatment mean and then expressed as a percentage of the control mean. Three types of models were developed: (1) one including 3-NOP dose, overall mean, and individual covariate; (2) a combination of neutral detergent fiber (NDF), 3-NOP dose, and overall mean; and (3) one selected model from all combinations of up to 5 covariates, which were compared using a leave-one-out cross validation method. Models including only 3-NOP dose resulted in a significant reduction of 32.7%, 30.9%, and 32.6% for CH4 production (g/d), yield (g/kg dry matter intake), and intensity (g/kg energy-corrected milk), respectively, at an average 3-NOP dose of 70.5 mg/kg dry matter (DM). The greater the NDF content in the diet, the lower the reduction efficiency for a given 3-NOP dose. For 10 g/kg DM increase in NDF content from its mean (329 g of NDF/kg of DM) the 3-NOP effect on CH4 production was impaired by 0.633%, the 3-NOP effect on CH4 yield by 0.647%, and the 3-NOP effect on CH4 intensity by 0.723%. The analysis based on leave-one-out cross validation showed an increase in NDF and crude fat content reduces efficacy of 3-NOP and an increase in 3-NOP dose increases efficacy. A 1% (10 g/kg) DM decrease in dietary NDF content from its mean may increase the efficacy of 3-NOP in reducing CH4 production by 0.915%. A 1% (10 g/kg DM) decrease in dietary crude fat content from its mean enhances the efficacy of 3-NOP on CH4 production by 3.080% at a given dose and NDF level. For CH4 yield, next to 3-NOP dose, dietary NDF content and dietary crude fat content were included in the selected model, but also dietary starch content with an opposite direction to NDF and crude fat. The effect of 3-NOP dose on CH4 intensity was similar to its effect on CH4 production, whereas the effect of dietary NDF content was slightly lower. Expanding the previously published models with the newly available data published from trials since then improved model performance, hence demonstrating the value of regularly updating meta-analyses if a wider range of data becomes available.

Background Observational and retrospective studies suggest that people with narcolepsy may have an increased prevalence of cardiovascular and cardiometabolic comorbidities and may be at greater risk for future cardiovascular events. An expert consensus panel was formed to establish agreement on the risk of hypertension and cardiovascular/cardiometabolic disease in people with narcolepsy and to develop strategies to mitigate these risks. Methods and Results Experts in sleep medicine and cardiology were selected to participate in the panel. After reviewing the relevant literature, the experts identified key elements, drafted recommendation statements, and developed discussion points to provide supporting evidence for the recommendations. The draft and final recommendations were rated on a scale from 0 (not at all agree) to 4 (very much agree). All experts had an agreement rating of 4.0 for all 14 revised recommendation statements for patients with narcolepsy. These statements comprised 3 themes: (1) recognize the risk of hypertension and cardiovascular/cardiometabolic disease, (2) reduce the risk of hypertension and cardiovascular/cardiometabolic disease, and (3) reduce sodium intake to lower the risk of hypertension and cardiovascular disease. Conclusions These consensus recommendations are intended to increase awareness of potential cardiovascular/cardiometabolic risks in patients with narcolepsy for all clinicians. Early monitoring for, and prevention of, cardiovascular risks in this population are of great importance, especially as narcolepsy usually develops in adolescents and young adults, who will be exposed to adverse effects of the disease for decades. Prospective systematic studies are needed to determine association and causation of narcolepsy with cardiovascular/cardiometabolic disorders.

Introduction: Carbon dioxide (CO2) and methane (CH4) are two of the primary greenhouse gases (GHG) responsible for global warming. The “stock gas” CO2 accumulates in the atmosphere even if rates of CO2 emission decline. In contrast, the “flow gas” CH4 has an e-folding time of about 12 years and is removed from the atmosphere in a relatively short period of time. The climate impacts of cumulative pollutants such as CO2 and short-lived climate pollutants (SLCP) such as CH4 are often compared using Global Warming Potential (GWP), a metric that converts non-CO2 GHG into CO2-equivalent emissions. However, GWP has been criticized for overestimating the heating effects of declining SLCP emissions and conversely underestimating the heating impact of increasing SLCP emissions. Accurate quantification of the temperature effects of different CH4 emissions scenarios is particularly important to fully understanding the climate impacts of animal agriculture, whose GHG emissions are dominated by CH4. Methods: A modified GWP metric known as Global Warming Potential Star (GWP*) has been developed to directly quantify the relationship between SLCP emissions and temperature change, which GWP cannot do. In this California dairy sector case study, we contrasted GWP- versus GWP*-based estimates of historical warming dynamics of enteric and manure CH4 from lactating dairy cattle. We predicted future dairy CH4 emissions under business-as-usual and reduction scenarios and modeled the warming effects of these various emission scenarios. Results: We found that average CO2 warming equivalent emissions given by GWP* were greater than those given by GWP under increasing annual CH4 emissions rates, but were lower under decreasing CH4 emissions rates. We also found that cumulative CO2 warming equivalent emissions given by GWP* matched modeled warming driven by decreasing CH4 emissions more accurately than those given by GWP. Discussion: These results suggest that GWP* may provide a more accurate tool for quantifying SLCP emissions in temperature goal and emissions reduction-specific policy contexts.

OBJECTIVE: Emotional reactivity normally involves a synchronized coordination of subjective experience and facial expression. These aspects of emotional reactivity can be uncoupled by neurological illness and produce adverse consequences for patient and caregiver quality of life because of misunderstandings regarding the patients presumed internal state. Frontotemporal dementia (FTD) is often associated with altered social and emotional functioning. FTD is a heterogeneous disease, and socioemotional changes in patients could result from altered internal experience, altered facial expressive ability, altered language skills, or other factors. The authors investigated how individuals with FTD subtypes differ from a healthy control group regarding the extent to which their facial expressivity aligns with their self-reported emotional experience. METHODS: Using a compound measure of emotional reactivity to assess reactions to three emotionally provocative videos, the authors explored potential explanations for differences in alignment of facial expressivity with emotional experience, including parkinsonism, physiological reactivity, and nontarget verbal responses. RESULTS: Participants with the three main subtypes of FTD all tended to express less emotion on their faces than they did through self-report. CONCLUSIONS: Exploratory analyses suggest that reasons for this incongruence likely differ not only between but also within diagnostic subgroups.

The Emotional Well-Being and Economic Burden (EMOT-ECON) Research Network is one of six research networks funded by the National Institutes of Health (NIH) to advance research about emotional well-being (EWB), and the only one that focuses on addressing how economic burden due to disease or illness affects EWB. The network convened researchers, patients, patient advocates, health care providers and other stakeholders from across the US to discuss the significance of addressing the impact of the economic burden of disease on EWB, the complexity of this prevalent problem for patients and families, and the research gaps that still need to be studied to ultimately develop strategies to reduce the impact of economic burden of disease on EWB and health. Participants identified some important future areas of research as those investigating: (i) prevalent and relevant emotions for patients experiencing economic burden of disease and financial hardship, and how their broader outlook on life is impacted; (ii) constructs and contexts that influence whether the economic burden is stressful; (iii) strategies to deal and cope and their positive or negative effects on EWB and health; and (iv) multi-level and multi-stakeholder interventions to address economic factors (e.g., costs, ability to pay), administrative burdens, education and training, and especially patients' emotional as well as financial status.

The natural process of mimicking the facial expressions of others is well established, as are the deficits in this reflexive behavior for individuals with clinical disorders such as depression. This study examines the extent of this deficit in non-clinical individuals with high transient negative mood, and whether it extends to both automatic and effortful emotion expression behavior. One hundred and thirty-six participants were shown happy, sad, and neutral faces, while electromyography (EMG) recorded facial muscle responses. Automatic (reflexive) mimicry was assessed while participants simply viewed facially expressive photographs, while effortful mimicry was monitored when individuals were told to intentionally copy the expressions in the photographs. Results indicated that high levels of negative mood were primarily associated with deficits in effortful mimicry of happy expressions, although some similar evidence was found in automatic mimicry of happy faces. Surprisingly, there were also ties between negative moods and inaccuracies in effortful mimicry of sad expressions (but not automatic mimicry). Inaccurate automatic and effortful mimicry were also tied with lower self-reported social support and greater loneliness. These results indicate that even in healthy individuals, transient and minor changes in negative mood are tied to deficiencies in facial mimicry at both the automatic and effortful level.

Primary Care Physicians (PCPs) are the first point of contact in healthcare. Because PCPs face the challenge of managing diverse patient populations while maintaining up-to-date medical knowledge and updated health records, this study explores the current outcomes and effectiveness of implementing Artificial Intelligence-based Clinical Decision Support Systems (AI-CDSSs) in Primary Healthcare (PHC). Following the PRISMA-ScR guidelines, we systematically searched five databases, PubMed, Scopus, CINAHL, IEEE, and Google Scholar, and manually searched related articles. Only CDSSs powered by AI targeted to physicians and tested in real clinical PHC settings were included. From a total of 421 articles, 6 met our criteria. We found AI-CDSSs from the US, Netherlands, Spain, and China whose primary tasks included diagnosis support, management and treatment recommendations, and complication prediction. Secondary objectives included lessening physician work burden and reducing healthcare costs. While promising, the outcomes were hindered by physicians’ perceptions and cultural settings. This study underscores the potential of AI-CDSSs in improving clinical management, patient satisfaction, and safety while reducing physician workload. However, further work is needed to explore the broad spectrum of applications that the new AI-CDSSs have in several PHC real clinical settings and measure their clinical outcomes.

This work introduces the Queen's University Agent-Based Outbreak Outcome Model (QUABOOM). This tool is an agent-based Monte Carlo simulation for modelling epidemics and informing public health policy. We illustrate the use of the model by examining capacity restrictions during a lockdown. We find that public health measures should focus on the few locations where many people interact, such as grocery stores, rather than the many locations where few people interact, such as small businesses. We also discuss a case where the results of the simulation can be scaled to larger population sizes, thereby improving computational efficiency.

OBJECTIVE: Emerging research has connected abundances of specific bacteria to differences in psychosocial behaviors in animals and adult humans. However, research assessing mind-microbiome associations in children is sparse with extant work primarily focused on populations with autism, making it unclear whether links are also present in typically developing children. The current study fills this gap by examining associations between prosocial-self-regulating temperaments (effortful control; EC) and the gut microbiome in typically developing children. METHODS: Maternal ratings of temperament were assessed in 77 toddlers 18 to 27 months of age (46.7% female, mean age = 23.14 months). Next-generation pyrosequencing of the V1-V3 region of the 16S rRNA gene was used to classify childrens gut microbial composition from fecal samples. EC included the following subcategories: cuddliness, attentional focusing, attentional shifting, inhibitory control, and low-intensity pleasure. RESULTS: After adjusting for covariates, EC was positively associated with relative abundances of Akkermansia (Δ R2 = 0.117, b = 0.022, SE = 0.007, p = .002), with cuddliness (i.e., joy and ease of being held) driving the relation. Furthermore, attentional focusing was negatively associated with Alistipes (Δ R2 = 0.062, b = -0.011, SE = 0.005, p = .028). Permutational analysis of variance revealed no significant differences in community structure between high and low EC groups on the phylum level ( R2 = 0.00372, p = .745) or the genus level ( R2 = 0.01559, p = .276). CONCLUSIONS: Findings suggest that certain microbes may be linked to prosocial behaviors used to regulate emotion in typically developing children. Further research is needed to test whether these observations replicate in larger samples.

Background: Coronary in-stent restenosis (ISR) is a major clinical challenge of contemporary percutaneous revascularization and portends adverse cardiovascular outcomes. Objectives: We aimed to evaluate gender, race, and ethnicity related outcomes in acute coronary syndromes (ACS) with ISR. Methods: Primary hospitalizations for ACS and ISR in the National Inpatient Sample database from 2016 to 2019 were included. Patients were stratified by gender, race, and ethnicity. The primary end points were all cause in-hospital mortality and coronary revascularization defined as composite of percutaneous coronary intervention (PCI), balloon angioplasty and/or coronary artery bypass grafting (CABG). Results: During the study period, a nationally weighted total of 97,680 patients with ACS and ISR were included. There was substantial variation in comorbidities, with greatest burden among Black and Hispanic women. All-cause in-hospital mortality was 2.4 % in the study cohort, but significantly higher in women (2.1 % vs. 2.1 %; aOR: 1.282, 95 % CI: 1.174–1.4; p

BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged

Background Mendelian randomization (MR) studies suggest a causal effect of iron status on cardiovascular disease (CVD) risk, but it is unknown if these associations are confounded by pleiotropic effects of the instrumental variables on CVD risk factors. We aimed to investigate the effect of iron status on CVD risk controlling for CVD risk factors. Methods and Results Iron biomarker instrumental variables (total iron‐binding capacity [n=208 422], transferrin saturation [n=198 516], serum iron [n=236 612], ferritin [n=257 953]) were selected from a European genome‐wide association study meta‐analysis. We performed 2‐sample univariate MR of each iron trait on CVD outcomes (all‐cause ischemic stroke, cardioembolic ischemic stroke, large‐artery ischemic stroke, small‐vessel ischemic stroke, and coronary heart disease) from MEGASTROKE (n=440 328) and CARDIoGRAMplusC4D (Coronary Artery Disease Genome Wide Replication and Meta‐Analysis Plus the Coronary Artery Disease Genetics) (n=183 305). We then implemented multivariate MR conditioning on 7 CVD risk factors from independent European samples to evaluate their potential confounding or mediating effects on the observed iron–CVD associations. With univariate MR analyses, we found higher genetically predicted iron status to be associated with a greater risk of cardioembolic ischemic stroke (transferrin saturation: odds ratio, 1.17 [95% CI, 1.03–1.33]; serum iron: odds ratio, 1.21 [95% CI, 1.02–1.44]; total iron‐binding capacity: odds ratio, 0.81 [95% CI, 0.69–0.94]). The detrimental effects of iron status on cardioembolic ischemic stroke risk remained unaffected when adjusting for CVD risk factors (all P0.05). Conclusions Higher iron status was associated with a greater risk of cardioembolic ischemic stroke independent of CVD risk factors, and this effect was partly mediated by diastolic blood pressure. These findings support a role of iron status as a modifiable risk factor for cardioembolic ischemic stroke.

Background: The effectiveness of acupuncture for chronic low back pain (cLBP) has not been studied specifically in the 65-and-older population. To inform the validity and generalizability of future acupuncture studies among older adults, we characterized elderly participants’ prior experience with and views toward acupuncture and tested for clinical and sociodemographic differences between acupuncture-naïve and non-naïve participants. Methods: Data for this study were collected during the baseline telephone interview from the participants enrolled in the Kaiser Permanente Northern California site of an NIH-funded, multicenter clinical trial of acupuncture for cLBP in older adults. Results: Nearly two-thirds (65.6 %) of participants surveyed reported they had previously received acupuncture treatment with the vast majority seeking acupuncture treatment for pain-related issues (84.8 %). The majority of these participants reported relatively modest levels of exposure to acupuncture with most participants (63.1 %) reporting fewer than 10 treatment sessions over their lifetimes. There were no significant differences in age, sex, race, ethnicity, disability scores, income levels, or pain levels between the acupuncture-naïve and non-naïve groups. Conclusion: Contextual consideration for prior acupuncture utilization rates is warranted and may be higher than expected or previously reported. We found few differences in baseline characteristics between participants who were acupuncture-naïve and those with prior acupuncture experience; thus, future pragmatic clinical trials might relax previous acupuncture-use considerations in their recruitment criteria. For trials focused on acupuncture-naive patients, it may be more feasible to expand the definition of ''acupuncture-naive'' based on lifetime acupuncture visits or time since last treatment. Trial registration: The protocol was registered at clinicaltrials.gov (#NCT04982315).

BACKGROUND: Hypertensive disorders of pregnancy are increasing in prevalence and a leading cause of early postpartum readmissions. Stricter blood pressure target goals for treatment of hypertension during pregnancy have recently been proposed, however, the treatment goals for management of postpartum hypertension are less well established. OBJECTIVE: We sought to evaluate the clinical factors associated with early postpartum readmissions for hypertensive disease and to evaluate blood pressure thresholds associated with these readmissions. STUDY DESIGN: We conducted a retrospective cohort study of women delivering at a tertiary care center between January 2018 and May 2022 who experienced a hospital readmission for postpartum hypertension or new onset postpartum preeclampsia. Charts were reviewed for clinical and sociodemographic data. Patients with early readmission (1 vitals check during their hospitalization) to be started on antihypertensives before initial delivery discharge; of those 25 (93%) were discharged with a new prescription for an antihypertensive. After controlling for confounding variables, predischarge blood pressure between 130–140 mmHg/80–90 mmHg (adjusted odds ratio, 2.4 [1.5–4.0]) was associated with an increased likelihood of early readmission. CONCLUSION: Patients with delivery for hypertensive disorders of pregnancy and predischarge blood pressure ≥140/90 mmHg were less likely to have an early readmission within 3 days of initial discharge, however, patients with predischarge blood pressure 130–139 mmHg/80–89 mmHg were more likely to have an early readmission for hypertensive disorders of pregnancy and postpartum preeclampsia. Further research is indicated to evaluate interventions to prevent postpartum readmission in patients at high risk for persistent hypertension or new onset postpartum preeclampsia.

BackgroundIn the United States (US), urinary tract infections (UTI) lead to more than 10 million office visits each year. Temperature and season are potentially important risk factors for UTI, particularly in the context of climate change.MethodsWe examined the relationship between ambient temperature and outpatient UTI diagnoses among patients followed from 2015 to 2017 in two California healthcare systems: Kaiser Permanente Southern California (KPSC) and Sutter Health in Northern California. We identified UTI diagnoses in adult patients using diagnostic codes and laboratory records from electronic health records. We abstracted patient age, sex, season of diagnosis, and linked community-level Index of Concentration at the Extremes (ICE-I, a measure of wealth and poverty concentration) based on residential address. Daily county-level average ambient temperature was assembled from the Parameter-elevation Regressions on Independent Slopes Model (PRISM). We implemented distributed lag nonlinear models (DLNM) to assess the association between UTI and lagged daily temperatures. Main analyses were confined to women. In secondary analyses, we stratified by season, healthcare system, and community-level ICE-I.ResultsWe observed 787,186 UTI cases (89% among women). We observed a threshold association between ambient temperature and UTI among women: an increase in daily temperature from the 5th percentile (6.0 ˚C) to the mean (16.2 ˚C) was associated with a 3.2% (95% CI: 2.4, 3.9%) increase in same-day UTI diagnosis rate, whereas an increase from the mean to 95th percentile was associated with no change in UTI risk (0.0%, 95% CI: -0.7, 0.6%). In secondary analyses, we observed the clearest monotonic increase in the rate of UTI diagnosis with higher temperatures in the fall. Associations did not differ meaningfully by healthcare system or community-level ICE-I. Results were robust to alternate model specifications.DiscussionIncreasing temperature was related to higher rate of outpatient UTI, particularly in the shoulder seasons (spring, autumn).

Researchers typically assume that all forms of positive affect (PA) are equally beneficial for attenuating the physiological stress response. We tested whether this association is more nuanced by examining the role of arousal level of PA on physiological responses to acute pain. Participants (N = 283, 75.6% female, Mage = 20.6) were randomized to a low, mid, or high arousal (calm, happy, and excited, respectively) induction condition or to a neutral control and then completed an acute pain-inducing cold pressor task. Sympathetic and parasympathetic responses along with self-reported pain and distress were assessed. Results indicated that the calm condition had a flatter sympathetic reactivity and subsequent recovery compared with the control condition. Additionally, calm and excited were associated with steeper increases in parasympathetic reactivity versus controls. These results support past PA stress buffering findings and indicate that not all types of PA are equal when it comes to improving the pain stress response. Abbreviations: PA: positive affect; PEP: pre-ejection period; RMSSD: root mean square of successive differences.

Abstract Objective Evaluations of lifestyle modification interventions (LMIs), modeled after the Diabetes Prevention Program, have repeatedly shown a dose‐response relationship between session attendance and weight loss. Despite this, not all participants had “average” weight loss experiences. Nearly one‐third of LMI participants experienced unexpected, paradoxical outcomes (i.e., high attendance with little weight loss, and low attendance with clinically significant weight loss). Paradoxical weight‐loss outcomes were characterized based on session attendance among participants in a group‐based LMI in a real‐world healthcare setting. This group‐based LMI was delivered over 1 year to participants with the possibility of attending up to 25 sessions total. Methods LMI participants identified in 2010–2017 from electronic health records were characterized as having low (