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BackgroundThe United States Food and Drug Administration authorized COVID-19 vaccines for children ages 5–11 years in October 2021 during the Omicron predominant period. Parental vaccine hesitancy was prevalent during this time, resulting in low childhood COVID-19 vaccine uptake. Most studies exploring factors influencing parental vaccine hesitancy have focused on racial and ethnic minorities and lower socioeconomic populations; however, there is little knowledge of the drive drivers of vaccine hesitancy among White parents with higher education and socioeconomic statuses.MethodsWe conducted semi-structured interviews with a sample of 15 White mothers of children ages 5–11 years in Atlanta, GA, between October–December 2021. Thematic analysis was performed using NVivo 12.ResultsMothers were college-educated, homeowners, and fully vaccinated against COVID-19. Key findings included decreased pediatrician’s recommendations for COVID-19 vaccines, reliance on information from specialized doctors and scientists, distrust in public health authorities, high risk-perception of COVID-19 vaccines, and low risk-perception of COVID-19 disease. Factors related to vaccine acceptance were altruism and practicality.ConclusionThis study adds to the sparse literature on reasons for vaccine hesitancy among White mothers of children ages 5–11 years with higher educational and socioeconomic status. Improving vaccine uptake among this group is critical for protecting the health of their children and other vulnerable populations. Tailored vaccine messaging and intervention are warranted to address their unique attitudes, beliefs, and behaviors. An enhanced understanding of the factors influencing subpopulations of parents can help vaccine policymakers and healthcare providers improve efforts to reduce vaccine hesitancy, particularly for new vaccines.

BackgroundAdverse Childhood Experiences (ACEs) have been associated with long-term physical and mental health conditions, toxic stress levels, developing unstable interpersonal relationships, and substance use disorders due to unresolved childhood adversities.AimsThis study assessed the perspectives of mental health providers (MHPs) regarding their adult patients’ coping with ACEs during COVID-19 in Houston, Texas. Specifically, we explored how individuals with ACEs are coping with the increased stresses of the pandemic, how MHPs may provide therapeutic support for individuals with ACEs during this pandemic, pandemic-related challenges of accessing and utilizing mental health services for individuals with ACEs, and the awareness and treatment of ACEs among MHPs.MethodsTen in-depth semi-structured virtual interviews were conducted with licensed MHPs from November 2021 to April 2022 in Houston, Texas. Interviews were coded and analyzed for emerging themes through an inductive open coding approach to discover insights regarding coping with ACEs during COVID-19.ResultsFour key themes experienced by individuals with ACEs emerged from the MHP interviews: (1) Maladaptive emotional dissonance and coping outlets during the pandemic, (2) Difficulties with social connectedness and significance of social support, (3) Heightened daily life stressors and coping with the ongoing disruption of the pandemic, and (4) Changing interactions with the mental health system. Themes from this study highlighted that resilience, seeking treatment, and strong social support can help develop healthy coping strategies among individuals with ACEs.ConclusionThis study may help inform best clinical practices to develop interventions and policies regarding ACEs such as a resilience-promotion approach that targets all the socio-ecological levels. In addition, findings highlight the synergy of psychotherapeutic and pharmacological management via tele-health modalities, in helping individuals with ACEs continue receiving the care they deserve and need during a persistent pandemic and an uncertain future.

Public health impacts can be achieved when evidence-based interventions are implemented to those most in need. Too often implementation never or slowly occurs. The community-wide campaign intervention Tu Salud ¡Si Cuenta! has evidence of improving health outcomes related to chronic disease among low-income, Latinos. Using the RE-AIM Framework, this study examined if the scaled-up version of the intervention is associated with improvements in hypertension and obesity in 12 locations. Each element of the RE-AIM framework was examined. For “Effectiveness,” we examined outcomes overall and by implementing location. We used linear and logistic regression to assess if exposure in the intervention was associated with improvement in hypertension and weight loss. Participants were stratified into “low exposure” (2–3 outreach visits) vs. “high exposure” (4–5 outreach visits). Based on the RE-AIM Framework, the intervention “reached” its intended population of low-income Latinos, demonstrated “effectiveness” in improving hypertension and obesity, was “adopted” at a high level in all but one site, was “implemented” with fidelity to the intervention model with moderate success across locations, and showed high “maintenance” over time. For effectiveness specifically, we found that out of 5,019 participants, 2,508 (50%) had a baseline hypertensive blood pressure (BP) reading. Of the 2,508, 1,245 (49.9%) recovered to normal blood pressure or pre-hypertension stage by last follow-up. After adjusting for baseline BP and potential confounders in multivariable linear regression models, the high exposure group had significantly more reduction in systolic BP (adjusted mean difference in % change = −0.96; p = 0.002) and diastolic BP (adjusted mean difference in % change = −1.61; p < 0.0001) compared to the low exposure group. After controlling for baseline weight and other confounders, the high exposure group had significantly greater decrease in weight compared to the low exposure group (adjusted mean difference in % change = −1.28; p < 0.0001). Results from the multivariable logistic regression models indicated that compared to the low exposure group the high exposure group was more likely to achieve a clinically significant minimum 5% weight loss [adjusted odds ratio (OR) = 2.97; p < 0.0001). This study contributes evidence that a Community-Wide Campaign model holds promise for addressing hypertension and obesity among low-income Latinos.

Estimating parameters accurately in groundwater models for aquifers is challenging because the models are non-explicit solutions of complex partial differential equations. Modern research methods, such as Monte Carlo methods and metaheuristic algorithms, for searching an efficient design to estimate model parameters require hundreds, if not thousands of model calls, making the computational cost prohibitive. One method to circumvent the problem and gain valuable insight on the behavior of groundwater is to first apply a Galerkin method and convert the system of partial differential equations governing the flow to a discrete problem and then use a Proper Orthogonal Decomposition to project the high-dimensional model space of the original groundwater model to create a reduced groundwater model with much lower dimensions. The reduced model can be solved several orders of magnitude faster than the full model and able to provide an accurate estimate of the full model. The task is still challenging because the optimization problem is non-convex, non-differentiable and there are continuous variables and integer-valued variables to optimize. Following convention, heuristic algorithms and a combination is used search to find efficient designs for the reduced groundwater model using various optimality criteria. The main goals are to introduce new design criteria and the concept of design efficiency for experimental design research in hydrology. The two criteria have good utility but interestingly, do not seem to have been implemented in hydrology. In addition, design efficiency is introduced. Design efficiency is a method to assess how robust a design is under a change of criteria. The latter is an important issue because the design criterion may be subjectively selected and it is well known that an optimal design can perform poorly under another criterion. It is thus desirable that the implemented design has relatively high efficiencies under a few criteria. As applications, two heuristic algorithms are used to find optimal designs for a small synthetic aquifer design problem and a design problem for a large-scale groundwater model and assess their robustness properties to other optimality criteria. The results show the proof of concept is workable for finding a more informed and efficient model-based design for a water resource study.

Abstract  Highly nonlinear advection–dispersion-reaction equations govern numerous transport phenomena. Robust, accurate, and efficient algorithms to solve these equations hold the key to the success of applying numerical models to field problems. This paper presents the development and verification of a computational algorithm to approximate the highly nonlinear transport equations of reactive chemical transport and multiphase flow. The algorithm was developed based on the Lagrangian-Eulerian decoupling method with an adaptive ZOOMing and Peak/valley Capture (LEZOOMPC) scheme. It consists of both backward and forward node tracking, rough element determination, peak/valley capturing, and adaptive local grid refinement. A second-order tracking was implemented to accurately and efficiently track all fictitious particles. Shanks’ method was introduced to deal with slowly converging case. The accuracy and efficiency of the algorithm were verified with the Burger equation for a variety of cases. The robustness of the algorithm to achieve convergent solutions was demonstrated by highly nonlinear reactive contaminant transport and multiphase flow problems. [ABSTRACT FROM AUTHOR]

In recent years, considerable progress has been made in the development of fast network flow algorithms aiming at solving linear programming problems with network substructures. Recognizing the fact that the basic structure of a water-supply system is a network, network algorithms have been used for system operation and management. However, to date, most algorithms are designed to solve transshipment problems in a pure network setting with total demand being equal to total supply. The non–network-type constraints and variables are precluded from the network models. Consequently, network models are used to perform optimization only for the network portion of the water-supply system under certain overall operational guidelines. In this study, an algorithm, EMNET, is introduced for solving the regional-water-supply-system optimization that corresponds to a generalized network problem with additional non–network-type constraints and non–network-type variables. The multiperiod, multiobjective optimization model for the regional water-supply system of the Metropolitan Water District of Southern California is used for case study. The results show that, depending on the network substructure in the model, EMNET is 11–117 times faster than standard linear programming codes, such as MINOS. [ABSTRACT FROM AUTHOR]

Kreweras considered the problem of counting noncrossing partitions of the set $\{1,2,\cdots,n\}$, whose elements are arranged into a cycle in its natural order, into $p$ parts of given sizes $n_1,n_2,\cdots,n_p$ (but not specifying which part gets which size). He gave a beautiful and surprising result whose proof resorts to a recurrence relation. In this paper we give a direct, entirely bijective, proof starting from the same initial idea as Kreweras' proof. [ABSTRACT FROM AUTHOR]

The five NF-κB family members and three nuclear IκB proteins play important biological roles, but the mechanisms by which distinct members of these protein families contribute to selective gene transcription remain poorly understood, especially at a genome-wide scale. Using nascent transcript RNA-seq, we observed considerable overlap between p50-dependent and IκBζ-dependent genes in Toll-like receptor 4 (TLR4)-activated macrophages. Key immunoregulatory genes, including Il6 , Il1b , Nos2 , Lcn2, and Batf, are among the p50-IκBζ-codependent genes. IκBζ-bound genomic sites are occupied at earlier time points by NF-κB dimers. However, p50-IκBζ codependence does not coincide with preferential binding of either p50 or IκBζ, as RelA co-occupies hundreds of genomic sites with the two proteins. A common feature of p50-IκBζ-codependent genes is a nearby p50/RelA/IκBζ-cobound site exhibiting p50-dependent binding of both RelA and IκBζ. This and other results suggest that IκBζ acts in concert with RelA:p50 heterodimers. Notably, p50-IκBζ-codependent genes comprise a high percentage of genes exhibiting the greatest differential expression between TLR4-stimulated and tumor necrosis factor receptor (TNFR)-stimulated macrophages. Thus, our genome-centric analysis reveals a defined p50-IκBζ pathway that selectively activates a set of key immunoregulatory genes and serves as an important contributor to differential TNFR and TLR4 responses., (© 2024 Daly et al.; Published by Cold Spring Harbor Laboratory Press.)

Mindfulness-based interventions (MBIs) have demonstrated therapeutic efficacy for various psychological conditions, and smartphone apps that facilitate mindfulness practice can enhance the reach and impact of MBIs. The goal of this review was to summarize the published evidence on the impact of mindfulness apps on the psychological processes known to mediate transdiagnostic symptom reduction after mindfulness practice. A literature search from January 1, 1993, to August 7, 2023 was conducted on three databases, and 28 randomized controlled trials involving 5963 adults were included. Across these 28 studies, 67 outcome comparisons were made between a mindfulness app group and a control group. Between-group effects tended to favor the mindfulness app group over the control group in three psychological process domains: repetitive negative thinking, attention regulation, and decentering/defusion. Findings were mixed in other domains (i.e., awareness, nonreactivity, non-judgment, positive affect, and acceptance). The range of populations examined, methodological concerns across studies, and problems with sustained app engagement likely contributed to mixed findings. However, effect sizes tended to be moderate to large when effects were found, and gains tended to persist at follow-up assessments two to six months later. More research is needed to better understand the impact of these apps on psychological processes of change. Clinicians interested in integrating apps into care should consider app-related factors beyond evidence of a clinical foundation and use app databases to identify suitable apps for their patients, as highlighted at the end of this review., (© 2024. The Author(s).)

Intravenous (IV) infiltration is a common problem associated with IV infusion therapy in clinical practice. A multitude of factors can cause the leakage of IV fluids into the surrounding tissues, resulting in symptoms ranging from temporary swelling to permanent tissue damage. Severe infiltration outcomes can be avoided or minimized if the patient's care provider is alerted of the infiltration at its earliest onset. However, there is a lack of real-time, continuous infiltration monitoring solutions, especially those suited for clinical use for critically ill patients. Our design of the sensor-integrated ATTENTIV catheter allows direct detection of catheter dislodgement, a root cause of IV infiltration. We verify two detection methods: blood-tissue differentiation with a support vector machine and signal peak identification with a thresholding algorithm. We present promising preliminary testing results on biological and phantom models that utilize bioimpedance as the sensing modality. Clinical relevance- The sensor-embedded ATTENTIV catheter demonstrates potential to automate IV infiltration detection in lieu of using traditional infusion catheters and manual detection methods.

This study investigated the water quality parameters (dissolved oxygen, electrical conductivity, salinity, pH, and temperature) and the mass flux of eight heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in five years (2015-2019) of the Houjing River. The river flows through a heavily-industrialized zone in Kaohsiung City in southern Taiwan. The surface water was sampled 4 times per year from five sampling locations: upstream sites (H1 and H2), industrial wastewater discharge point sites (H3 and H4), and downstream (H5). Our findings show that the water quality parameters improved in the study period, especially dissolved oxygen. However, some parameters, such as electrical conductivity (mean = 1152.50 ± 414.21 μS cm -1 ), were still higher than the Taiwan water quality irrigation standards. The heavy metal pollution was investigated in the aspect of mass fluxes and sources contribution. The spatial variation of the total heavy metal mass flux increased gradually from upstream to downstream, with H5 having the highest total mass flux of 74.1 kg d -1 . H2, located near an industrial zone, had a total mass flux of 33.7 kg d -1 and contributed to the most Ni, Cr, Pb, Zn, and Hg fluxes. This study indicates that the water quality improvements observed are still not enough to meet the regulations. Stricter enforcement is required as well as further investigation to identify any illegal pollution sources., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

One of the most industrially affected rivers in Taiwan, the Houjing River, was studied in this research. The water and sediment samples were collected at five locations to measure the concentration of eight metals (As, Cd, Cr, Cu, Hg, Pb, Ni, and Zn). In order to assess the heavy metal contamination and its adverse biological effect, the heavy metal pollution index (HPI), the degree of contamination index (DC), the contamination factor (CF), the index of geo-accumulation (I geo ), and hazard quotients (HQs) were employed. The results showed that the Houjing River's water and sediment were contaminated with heavy metals. The annually averaged values of HPI (128.3) and DC (21.3) indicate that the water is unsafe for potable use and the sediment contamination level is at considerable degree of contamination. CF and I geo calculation show that Zn, Cu, and Cd are the three main metals contributing to heavy metal contamination in sediment. Evaluation of adverse biological effects suggests that Zn, Cu, and Ni are the major metals that cause adverse effects on organisms. This study provides an overview of the synergistic heavy metal contamination degree of the Houjing River and its adverse biological effects, which should be a reliable reference for future contamination control and management plans.

Prenatal polybrominated diphenyl ether (PBDE) exposures are a public health concern due to their persistence and potential for reproductive and developmental harm. However, we have little information about the extent of fetal exposures during critical developmental periods and the variation in exposures for groups that may be more highly exposed, such as communities of color and lower socioeconomic status (SES). To characterize maternal-fetal PBDE exposures among potentially vulnerable groups, PBDE levels were examined in the largest sample of matched maternal serum, placenta, and fetal liver tissues during mid-gestation among a geographically, racially/ethnically, and socially diverse population of pregnant women from Northern California and the Central Valley (n = 180; 2014-16). Maternal-fetal PBDE levels were compared to population characteristics using censored Kendall's tau correlation and linear regression. PBDEs were commonly detected in all biomatrices. Before lipid adjustment, wet-weight levels of all four PBDE congeners were highest in the fetal liver (p < 0.001), whereas median PBDE levels were significantly higher in maternal serum than in the fetal liver or placenta after lipid-adjustment (p < 0.001). We also found evidence of racial/ethnic disparities in PBDE exposures (Non-Hispanic Black > Latina/Hispanic > Non-Hispanic White > Asian/Pacific Islander/Other; p < 0.01), with higher levels of BDE-100 and BDE-153 among non-Hispanic Black women compared to the referent group (Latina/Hispanic women). In addition, participants living in Fresno/South Central Valley had 34% (95% CI: - 2.4 to 84%, p = 0.07) higher wet-weight levels of BDE-47 than residents living in the San Francisco Bay Area. PBDEs are widely detected and differentially distributed in maternal-fetal compartments. Non-Hispanic Black pregnant women and women from Southern Central Valley geographical populations may be more highly exposed to PBDEs. Further research is needed to identify sources that may be contributing to differential exposures and associated health risks among these vulnerable populations.

We tested the hypothesis that maternal perinatal serum levels of poly and perfluoroalkyl substances (PFASs) predict risk for breast cancer in daughters in a 54-year follow-up of 9300 daughters born 1959-1967 in the Child Health and Development Studies pregnancy cohort. Total cholesterol and PFASs were measured in archived maternal perinatal serum for 102 daughter breast cancer cases diagnosed by age 52, and 310 controls matched on birth year and blood draw trimester. High maternal N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), a precursor of perfluorooctane sulfonic acid (PFOS), in combination with high maternal total cholesterol predicted a 3.6-fold increased risk of breast cancer (p interaction <0.05). Conversely, maternal PFOS was associated with decreased daughters' breast cancer risk. Predictions were robust to alternative modeling and independent of other maternal factors. Future generations continue to be exposed to ubiquitous, persistent PFASs. These findings are relevant to breast cancer prevention if confirmed experimentally and where possible, in additional epidemiology studies of internal doses of PFASs and other chemical mixtures especially during vulnerable windows in early life., (Copyright © 2019. Published by Elsevier Inc.)

The Ehlers-Danlos syndromes (EDS) and associated hypermobility spectrum disorders (HSD) are a heterogenous group of connective tissue disorders associated with significant morbidity. The urogenital aspects of these disorders are understudied and there is little guidance on the prevalence, types, or outcomes of urogenital complications in EDS/HSD. Our objective was to perform a scoping review to characterize and synthesize the literature reporting urogenital and pelvic complications in EDS/HSD patients. We performed a systematic search of three databases (Medline, CINAHL, Embase) to January 2019. English language, full-text articles reporting on urogenital or pelvic complications in EDS/HSD were included. A total of 105 studies were included (62 case reports/series, 43 observational) involving patients with hypermobile (23%), vascular (20%), classical (12%) EDS, and HSD (24%). Some studies looked at multiple subtypes (11%) or did not report subtype (33%). Reported complications included urinary (41%), gynecological (36%), obstetrical (25%), renal (9%), and men's health problems (7%), with some studies reporting on multiple areas. Urinary and gynecological complications were most prevalent in patients with HSD, while a broad range of complications were reported in EDS. While further research is required, results suggest a higher index of suspicion for urogenital problems is probably warranted in this population., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The G AL4 T echnique for R eal-time a nd C lonal E xpression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide., (Copyright © 2019 Olson et al.)

In this study, tissues of five fish species prevalent in the Houjing River were analyzed for heavy metal concentrations. Results show concentrations of such metals to be much higher than internationally recommended standard limits (as determined by the WHO and FAO) and other similar studies. Heavy metal contamination of fish in the Houjing River is hence significant. High hazard and carcinogenic risk related to the Houjing River's fish was proven based on target hazard quotient (THQ) and target cancer risk (TR) estimations. In fact, four of the five species studied present THQ levels higher than 1, and seven TRs of zinc (Zn) and arsenic (As) are higher than 10 -4 . Despite lower estimated daily intake (EDI) of fish in the area (per recommended daily allowance guidelines), possible heavy metal bioaccumulations in fish stock pose a high health risk for human consumption. From our analyses, the highest bioaccumulation factor (BAF) estimated above 1000 was of Zn. Among the fish species studied, Oreochromis niloticus possesses the ability to accumulate copper (Cu) and Zn dramatically. Pearson's correlation matrix showed a positive correlation between Cu and As, attributed to multiple industrial activities along the river. Hierarchical cluster analysis of results based on sampling stations exhibits three clusters and may be linked to the type of industrial activities specific to that area. More intensive study is needed in order to further determine the toxic metals in fish. Reporting of contaminant levels must be compared with optimal health criteria guidelines. Our study, while showing the severity of heavy metal contamination in fish stock, calls for urgent, sustained, and targeted actions by both governmental authorities and the local scientific community-to help prevent and mitigate the situation and ensure the physical well-being of local inhabitants.

Context: Currently no direct evidence links in utero dichlorodiphenyltrichloroethane (DDT) exposure to human breast cancer. However, in utero exposure to another xenoestrogen, diethylstilbestrol, predicts an increased breast cancer risk. If this finding extends to DDT, it could have far-reaching consequences. Many women were heavily exposed in utero during widespread DDT use in the 1960s. They are now reaching the age of heightened breast cancer risk. DDT exposure persists and use continues in Africa and Asia without clear knowledge of the consequences for the next generation., Hypothesis: In utero exposure to DDT is associated with an increased risk of breast cancer., Design: This was a case-control study nested in a prospective 54-year follow-up of 9300 daughters in the Child Health and Development Studies pregnancy cohort (n = 118 breast cancer cases, diagnosed by age 52 y and 354 controls matched on birth year)., Setting and Participants: Kaiser Foundation Health Plan members who received obstetric care in Alameda County, California, from 1959 to 1967, and their adult daughters participated in the study., Main Outcome Measure: Daughters' breast cancer diagnosed by age 52 years as of 2012 was measured., Results: Maternal o,p'-DDT predicted daughters' breast cancer (odds ratio fourth quartile vs first = 3.7, 95% confidence interval 1.5-9.0). Mothers' lipids, weight, race, age, and breast cancer history did not explain the findings., Conclusions: This prospective human study links measured DDT exposure in utero to risk of breast cancer. Experimental studies are essential to confirm results and discover causal mechanisms. Findings support classification of DDT as an endocrine disruptor, a predictor of breast cancer, and a marker of high risk.

Introduction: Cardiac rehabilitation (CR) programs reduce overall and cardiovascular mortality in patients with a history of acute coronary events or revascularization procedures, but only 30% of patients enroll in CR and attrition rates reach up to 60%. Tai chi, a mind-body practice based on light/moderate aerobic exercise accompanied by meditative components could be a possible exercise option for patients who do not attend CR., Methods/design: Sixty patients will be randomized to a "LITE" condition (one tai chi session twice weekly for 12 weeks) or to a "PLUS" condition (one tai chi session 3 times weekly for 12 weeks, followed by maintenance classes 1-2 times weekly for an additional 12 weeks). Measurements will be conducted at baseline, 3-, 6-, and 9 months after enrollment. The primary outcome is to determine the feasibility, acceptability and safety of each dose. Secondary outcomes include estimates of effect size of each dose on accelerometry-assessed physical activity; the proportion of patients meeting current recommendations for physical activity; and measures of fitness, quality of life, body weight, and sleep. In addition, we will collect exploratory information on possible mediators (exercise self-efficacy, perceived social support, resilience, mindfulness, and depression)., Conclusions: Findings from this pilot study will provide preliminary indications about the usefulness of tai chi as an exercise option for patients not attending traditional CR programs. Results will also shed light on the possible mechanisms by which tai chi practice may improve overall physical activity among patients with atherosclerotic coronary heart disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Data on the use of oral anticoagulation (OAC) and antiplatelet therapy and the risk of bleeding and stroke amongst Asian patients with atrial fibrillation (AF) are limited. We investigated the risks of bleeding and stroke with use of oral anticoagulation (OAC) and antiplatelet therapy as mono- or combination therapy, in patients with AF from a Chinese nationwide cohort study., Methods: We studied a cohort of 10384 patients (57.2% men, age 67.8 ± 13.2 yrs) between 1999 and 2010 from the National Health Insurance Research Database in Taiwan. Records of prescriptions were obtained during follow-up. The main outcome was a recurrent stroke during the follow-up period. Time-dependent Cox proportional hazards models were used for this analysis., Results: We documented 1009 events for bleeding, as well as 224 hemorrhagic stroke and 1642 ischemic stroke events during a median 3.2 (interquartile range, 1.05-6.54) years' follow-up. Compared with warfarin users, patients with antiplatelet therapy had a lower risk of bleeding (adjusted relative risk [RR], 0.59, 95% confidence interval [CI], 0.49-0.71, p<0.001) whilst combination therapy had a non-statistically significant higher bleeding risk (RR, 1.33, 95%, 0.91-1.94, p = 0.20). Patients on antiplatelet monotherapy had a similar risk for ischemic stroke compared with OAC (RR 1.05, 95% CI, 0.89-1.25, p = 0.50), whilst those on combination therapy had a significantly higher risk (RR 1.90, 95% CI, 1.34-2.70, p<0.001)., Conclusion: In a national representative cohort, antiplatelet therapy had no significant difference in ischemic stroke risk to warfarin. For bleeding, aspirin had a lower risk compared to warfarin. This may reflect poor anticoagulation control, highlighting important missed opportunities for improved stroke prevention, especially in countries where anticoagulation management is suboptimal.

Objective: To examine correlates of complementary and alternative medicine (CAM) use in a pediatric population with chronic pain, and to determine whether CAM use is positively correlated with adaptive coping skills., Methods: We examined patient data from 1175 children aged 7 to 18 years with chronic pain who completed the intake assessment at the time of initial evaluation at Boston Children's multidisciplinary Pain Treatment Service between 2003 and 2011. The intake assessment included validated measures of anxiety, depression, pain coping skills, and functional disability. Parents were also asked whether their child had tried CAM modalities in the past. We used a multivariable logistic regression model to determine correlates of CAM use and a multivariable linear regression model to determine the relationship between biobehavioral CAM (relaxation training, hypnosis, and biofeedback) and accommodative coping., Results: In our multivariable model, we found that female gender (odds ratio [OR] 1.48, 95% confidence interval [95% CI] 1.07-2.02), level of parental education (OR 1.11 per year, 95% CI 1.06-1.16), greater pain intensity (OR 1.06 per point on an 11-point numerical analog scale, 95% CI 1.01-1.11), and more functional disability (OR 1.19 per 10-point increment on the Functional Disability Inventory, 95% CI 1.06-1.34) were independently associated with CAM use. Biobehavioral CAM was found to have a statistically significant correlation with accommodative coping skills (β = 0.2, P = .004)., Conclusions: In a pediatric chronic pain center, CAM users tended to have higher pain intensity and greater functional disability. Exposure to biobehavioral CAM techniques was associated with adaptive coping skills., (Copyright © 2014 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: The reduction in adrenergic activity and anxiety associated with meditation may be beneficial for patients with implantable cardioverter defibrillators., Purpose: This study aims to determine the feasibility of a phone-delivered mindfulness intervention in patients with defibrillators and to obtain preliminary indications of efficacy on mindfulness and anxiety., Methods: Clinically stable outpatients were randomized to a mindfulness intervention (eight weekly individual phone sessions) or to a scripted follow-up phone call. We used the Hospital Anxiety and Depression Scale and the Five Facets of Mindfulness to measure anxiety and mindfulness, and multivariate linear regression to estimate the intervention effect on pre-post-intervention changes in these variables., Results: We enrolled 45 patients (23 mindfulness and 22 control; age, 43-83; 30 % women). Retention was 93 %; attendance was 94 %. Mindfulness (beta = 3.31; p = 0.04) and anxiety (beta = -1.15; p = 0.059) improved in the mindfulness group., Conclusions: Mindfulness training can be effectively phone-delivered and may improve mindfulness and anxiety in cardiac defibrillator outpatients.

Objective: In 2002 the American Medical Student Association (AMSA) created a fourth-year medical student elective known as the Humanistic Elective in alternative medicine, Activism, and Reflective Transformation (HEART) that provided the opportunity for students to explore humanism in medicine, self-care, complementary and alternative medicine modalities, communication, activism, and community building in a four-week immersion experience. The educational effects of this elective, and whether it has met its stated goals, are unknown., Method: The authors conducted a web-based, cross-sectional survey of the first eight cohorts of HEART graduates in 2010. Survey questions assessed respondents' demographics and perspectives on the educational impact of the elective. Descriptive statistics were used to characterize the sample and qualitative analyses were guided by grounded theory., Results: Of 168 eligible alumni, 122 (73%) completed the survey. The majority were female (70%), age ≤35 (77%) years, and trained in primary care specialties (66%). Half were attendings in practice. The majority of respondents felt the elective taught professionalism (89%) and communication skills (92%) well or very well. The majority highly agreed that the elective helped them better cope with stress during residency training (80%), taught them self-care skills (75%), and improved their ability to empathize and connect with patients (71%). Qualitative analysis of the personal and professional impact of the elective identified twelve common themes with self-discovery, self-care, and collegial development/community most frequently cited., Conclusions: The majority of HEART graduates endorse learning important skills and benefiting from the experience both personally and professionally. Aspects of the HEART curriculum may help training programs teach professionalism and improve trainee well-being., (© 2013 Elsevier Inc. All rights reserved.)

Objective: This study examined the feasibility, safety, and efficacy of using tai chi for treating major depressive disorder., Design: Thirty-nine Chinese Americans with major depressive disorder were randomized into a 12-wk tai chi intervention or a waitlisted control group in a 2:1 ratio. The key outcome measurement was the 17-item Hamilton Rating Scale for Depression. Positive response was defined as a decrease of 50% or more on the 17-item Hamilton Rating Scale for Depression, and remission was defined as a score of 7 or lower on the 17-item Hamilton Rating Scale for Depression., Results: Of the participants (n = 39), 77% were women, and mean (SD) age was 55 (10) years. There were 26 (67%) participants in the tai chi intervention group and 13 (33%) in the control group. Of the participants in the tai chi group, 73% completed the intervention; no adverse events were reported. We observed trends toward improvement in the tai chi intervention group, compared with the control group, in positive treatment-response rate (24% vs. 0%) and remission rate (19% vs. 0%), although the differences in our small sample did not reach statistical significance., Conclusions: A randomized controlled trial of tai chi is feasible and safe in Chinese American patients with major depressive disorder. These promising pilot study results inform the design of a more definitive trial.

Background: Extreme temperatures have been associated with hospitalization and death among individuals with heart failure, but few studies have explored the underlying mechanisms., Objectives: We hypothesized that outdoor temperature in the Boston, Massachusetts, area (1- to 4-day moving averages) would be associated with higher levels of biomarkers of inflammation and myocyte injury in a repeated-measures study of individuals with stable heart failure., Methods: We analyzed data from a completed clinical trial that randomized 100 patients to 12 weeks of tai chi classes or to time-matched education control. B-type natriuretic peptide (BNP), C-reactive protein (CRP), and tumor necrosis factor (TNF) were measured at baseline, 6 weeks, and 12 weeks. Endothelin-1 was measured at baseline and 12 weeks. We used fixed effects models to evaluate associations with measures of temperature that were adjusted for time-varying covariates., Results: Higher apparent temperature was associated with higher levels of BNP beginning with 2-day moving averages and reached statistical significance for 3- and 4-day moving averages. CRP results followed a similar pattern but were delayed by 1 day. A 5°C change in 3- and 4-day moving averages of apparent temperature was associated with 11.3% [95% confidence interval (CI): 1.1, 22.5; p = 0.03) and 11.4% (95% CI: 1.2, 22.5; p = 0.03) higher BNP. A 5°C change in the 4-day moving average of apparent temperature was associated with 21.6% (95% CI: 2.5, 44.2; p = 0.03) higher CRP. No clear associations with TNF or endothelin-1 were observed., Conclusions: Among patients undergoing treatment for heart failure, we observed positive associations between temperature and both BNP and CRP-predictors of heart failure prognosis and severity.

Background. Meditation practices are associated with a reduction in adrenergic activity that may benefit patients with severe cardiac arrhythmias. This paper describes the design and methods of a pilot study testing the feasibility of a phone-delivered mindfulness-based intervention (MBI) for treatment of anxiety in patients with implantable cardioverter defibrillators (ICDs). Design and Methods. Consecutive, clinically stable outpatients (n = 52) will be screened for study eligibility within a month of an ICD-related procedure or ICD shock and will be randomly assigned to MBI or to usual care. MBI patients will receive eight weekly individual phone sessions based on two mindfulness practices (awareness of breath and body scan) plus home practice with a CD for 20 minutes daily. Patients assigned to usual care will be offered the standard care planned by the hospital. Assessments will occur at baseline and at the completion of the intervention (between 9 and 12 weeks after randomization). The primary study outcome is feasibility; secondary outcomes include anxiety, mindfulness, and number of administered shocks during the intervention period. Conclusions. If proven feasible and effective, phone-delivered mindfulness-based interventions could improve psychological distress in ICD outpatients with serious cardiovascular conditions.

The objective of this study was to define the role of complement activation in the acute and transient toxicities associated with administration of phosphorothioate oligonucleotides in monkeys. In the absence of complement inhibitor, complement activation blocker-2 (CAB-2), i.v. infusion of 20 mg/kg ISIS 2302 produced increases in the concentrations of the complement split products Bb and C5a (100- and 7-fold, respectively). Monkeys also experienced marked changes in bloodpressure (hypertension and hypotension), clinical signs of toxicity (lethargy and periorbital edema), fluctuations in circulating neutrophil counts, and elevations in serum cytokine levels (45-, 12-, and 4-fold increases in IL-6, MCP-1, and IL-12, respectively). Changes occurred at or near the end of infusion and returned to normal over time. One of the three animals died approximately 4 h following infusion of 20 mg/kg ISIS 2302 alone. In contrast, prior treatment with CAB-2 effectively blocked complement activation, as well as the ISIS 2302-induced hemodynamic and clinical responses. Importantly, plasma concentration of ISIS 2302 were unaffected by CAB-2 pretreatment. Thus, the protection afforded by CAB-2 was due to its inhibition of complement activation rather than to any impact on the disposition of ISIS 2302. These results clearly demonstrate the causal relationship between activation of the alternative complement pathway and the hemodynamic and clinical responses associated with rapid infusion of phosphorothioate oligonucleotides. Demonstration of this relationship underscores the importance of avoiding complement activation in patients to ensure the continued safe use of phosphorothioate oligodeoxynucleotides.

We present a case of a 37-year-old man who sustained a rupture of his left patellar tendon approximately 48 hours after rupturing his right patellar tendon. This temporal pattern illustrates two important aspects of patellar tendon injury-that rupture of the degenerated patellar tendon may occur without any prodromal warning and that it may elude detection even if the patient is examined by several physicians.

Multiple epiphyseal dysplasia (MED) is an inherited chondrodystrophy that results in deformity of articular surfaces and in subsequent degenerative joint disease. The disease is inherited as an autosomal dominant trait with high penetrance. An MED mutation has been mapped by genetic linkage analysis of DNA polymorphisms in a single large pedigree. Close linkage of MED to 130 tested chromosomal markers was ruled out by discordant inheritance patterns. However, strong evidence for linkage of MED to markers in the pericentromeric region of chromosome 19 was obtained. The most closely linked marker was D19S215, with a maximum LOD score of 6.37 at theta = .05. Multipoint linkage analysis indicated that MED is located between D19S212 and D19S215, a map interval of 1.7 cM. Discovery of the map location of MED in this family will facilitate identification of the mutant gene. The closely linked DNA polymorphisms will also provide the means to determine whether other inherited chondrodystrophies have underlying defects in the same gene.

We have studied a family with an autosomal dominant form of multiple epiphyseal dysplasia (MED) inherited through at least 5 generations. Bilateral deformity of the hips with subsequent degenerative arthritis was the most common and most severe change observed in the affected relatives. Abnormalities of the knees, ankles, and shoulders were also noted in some affected individuals. Radiological examination showed changes in affected joints consistent with epiphyseal dysplasia. In early stages, the articular surfaces appeared flattened or irregular in shape. In advanced stages, epiphyseal fragmentation, joint surface erosion, and extensive remodeling were observed. The abnormalities of the epiphyses suggested that the primary defect might be in a structural component of the epiphyseal cartilage matrix. The gene encoding type II collagen (COL2A1) was tested for genetic linkage to MED in this family by restriction fragment length polymorphism (RFLP) analysis. Recombination between COL2A1 and MED was observed, ruling out COL2A1 as the site of the mutation. The genes encoding the 3 chains of type VI collagen were also excluded on the basis of discordant inheritance. The disease in this family is therefore not the result of mutations in the genes encoding type II or type VI collagen.

Objective: Some of the genomic instability that is observed in solid tumors may be due to the loss of telomeric sequences. These experiments were designed to compare the number of telomeric repeat sequences in endometrial adenocarcinoma with that found in adjacent normal tissue., Study Design: Deoxyribonucleic acid was extracted from normal and malignant uterine tissue of 11 patients undergoing hysterectomy for treatment of endometrial adenocarcinoma and also from five endometrial carcinoma cell lines. The relative number of telomeric repeat sequences in each sample was measured by hybridization of these deoxyribonucleic acids to a probe specific for the human telomeric repeat. Hybridization signals were quantified by autoradiography and a beta-particle detection system., Results: A reduction of telomeric repeat sequences in tumor versus normal tissue was found in 10 of 11 cases. Telomere reduction was also seen in endometrial carcinoma cell lines., Conclusions: Telomere reduction is a genetic characteristic of many endometrial tumors. Telomere reduction may contribute to the genesis and progression of endometrial carcinoma, or it may be a secondary effect of the tumorigenesis process.

Immunoblastic sarcoma has been observed in association with, or subsequent to, chronic immune stimulation, connective tissue disorders, and immunoblastic lymphadenopathy. A case of Waldenström's macroglobulinemia progressinng after a few years into immunoblastic sarcoma is reported. Splenectomy led to disappearance of hemolytic anemia and of pulmonary infiltrates, as well as to marked reduction of macroglobulins. Although immunoblastic sarcoma usually terminates fatally within two or three months, complete remission was induced by combination chemotherapy. It is speculated that Waldenström's macroglobulinemia, immunoblastic lymphadenopathy, and immunoblastic sarcoma are related disorders reflecting a clonal nature of immunoblastic lymphoma cells and the plasmacytic cells.