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In their chapter, Bach and Presnall-Shvorin (this volume) introduce guidelines for incorporating empirically-driven trait models of personality pathology, codified in the DSM-5 and ICD-11, into therapeutic practice. Though the authors of this commentary are supportive of the effort to bridge research with clinical practice, they suggest that a mechanistic model which accounts for personality processes underlying descriptive traits could offer greater precision than traits alone. Furthermore, they argue that clinical dysfunction can only be meaningfully defined and treated with an understanding of dynamic, contextualized aspects of personality. To illustrate how a mechanistic model could complement and extend Bach and Presnall’s recommendations, the authors present a case conceptualization using cybernetic theory. Finally, they review how idiographic data gleaned from ambulatory assessment methods provide insight into pathological processes ideal for therapeutic intervention. To achieve a generalizable approach flexible enough to adapt to the individual, they encourage the development of treatment models that go beyond traits to mechanistically link stable and dynamic personality features into a unified framework.
We present the analysis of global sympagic primary production (PP) from 300 years of pre-industrial and historical simulations of the E3SMv1.1-BGC model. The model includes a novel, eight-element sea ice biogeochemical component, MPAS-Seaice zbgc, which is resolved in three spatial dimensions and uses a vertical transport scheme based on internal brine dynamics. Modeled ice algal chlorophyll-a concentrations and column-integrated values are broadly consistent with observations, though chl-a profile fractions indicate that upper ice communities of the Southern Ocean are underestimated. Simulations of polar integrated sea ice PP support the lower bound in published estimates for both polar regions with mean Arctic values of 7.5 and 15.5 TgC/a in the Southern Ocean. However, comparisons of the polar climate state with observations, using a maximal bound for ice algal growth rates, suggest that the Arctic lower bound is a significant underestimation driven by biases in ocean surface nitrate, and that correction of these biases supports as much as 60.7 TgC/a of net Arctic PP. Simulated Southern Ocean sympagic PP is predominantly light-limited, and regional patterns, particularly in the coastal high production band, are found to be negatively correlated with snow thickness.
Scientific quality and feasibility are part of ethics review by Institutional Review Boards (IRBs). Scientific Review Committees (SRCs) were proposed to facilitate this assessment by the Clinical and Translational Science Award (CTSA) SRC Consensus Group. This study assessed SRC feasibility and impact at CTSA-affiliated academic health centers (AHCs).
SRC implementation at 10 AHCs was assessed pre/post-intervention using quantitative and qualitative methods. Pre-intervention, four AHCs had no SRC, and six had at least one SRC needing modifications to better align with Consensus Group recommendations.
Facilitators of successful SRC implementation included broad-based communication, an external motivator, senior-level support, and committed SRC reviewers. Barriers included limited resources and staffing, variable local mandates, limited SRC authority, lack of anticipated benefit, and operational challenges. Research protocol quality did not differ significantly between study periods, but respondents suggested positive effects. During intervention, median total review duration did not lengthen for the 40% of protocols approved within 3 weeks. For the 60% under review after 3 weeks, review was lengthened primarily due to longer IRB review for SRC-reviewed protocols. Site interviews recommended designing locally effective SRC processes, building buy-in by communication or by mandate, allowing time for planning and sharing best practices, and connecting SRC and IRB procedures.
The CTSA SRC Consensus Group recommendations appear feasible. Although not conclusive in this relatively short initial implementation, sites perceived positive impact by SRCs on study quality. Optimal benefit will require local or federal mandate for implementation, adapting processes to local contexts, and employing SRC stipulations.
Non-invasive prenatal testing (NIPT) for the detection of foetal aneuploidy through analysis of cell-free DNA (cfDNA) in maternal blood is offered routinely by many healthcare providers across the developed world. This testing has recently been recommended for evaluative implementation in the UK National Health Service (NHS) foetal anomaly screening pathway as a contingent screen following an increased risk of trisomy 21, 18 or 13. In preparation for delivering a national service, we have implemented cfDNA-based NIPT in our Regional Genetics Laboratory. Here, we describe our validation and verification processes and initial experiences of the technology prior to rollout of a national screening service.
Data are presented from more than 1000 patients (215 retrospective and 840 prospective) from ‘high- and low-risk pregnancies’ with outcome data following birth or confirmatory invasive prenatal sampling. NIPT was by the Illumina Verifi® test.
Our data confirm a high-fidelity service with a failure rate of ~0.24% and a high sensitivity and specificity for the detection of foetal trisomy 13, 18 and 21. Secondly, the data show that a significant proportion of patients continue their pregnancies without prenatal invasive testing or intervention after receiving a high-risk cfDNA-based result. A total of 46.5% of patients referred to date were referred for reasons other than high screen risk. Ten percent (76/840 clinical service referrals) of patients were referred with ultrasonographic finding of a foetal structural anomaly, and data analysis indicates high- and low-risk scan indications for NIPT.
NIPT can be successfully implemented into NHS regional genetics laboratories to provide high-quality services. NHS provision of NIPT in patients with high-risk screen results will allow for a reduction of invasive testing and partially improve equality of access to cfDNA-based NIPT in the pregnant population. Patients at low risk for a classic trisomy or with other clinical indications are likely to continue to access cfDNA-based NIPT as a private test.
Stellarators are a promising route to steady-state fusion power. However, to achieve the required confinement, the magnetic geometry must be highly optimized. This optimization requires navigating high-dimensional spaces, often necessitating the use of gradient-based methods. The gradient of the neoclassical fluxes is expensive to compute with classical methods, requiring
flux computations, where
is the number of parameters. To reduce the cost of the gradient computation, we present an adjoint method for computing the derivatives of moments of the neoclassical distribution function for stellarator optimization. The linear adjoint method allows derivatives of quantities which depend on solutions of a linear system, such as moments of the distribution function, to be computed with respect to many parameters from the solution of only two linear systems. This reduces the cost of computing the gradient to the point that the finite-collisionality neoclassical fluxes can be used within an optimization loop. With the neoclassical adjoint method, we compute solutions of the drift kinetic equation and an adjoint drift kinetic equation to obtain derivatives of neoclassical quantities with respect to geometric parameters. When the number of parameters in the derivative is large (
), this adjoint method provides up to a factor of 200 reduction in cost. We demonstrate adjoint-based optimization of the field strength to obtain minimal bootstrap current on a surface. With adjoint-based derivatives, we also compute the local sensitivity to magnetic perturbations on a flux surface and identify regions where tight tolerances on error fields are required for control of the bootstrap current or radial transport. Furthermore, the solve for the ambipolar electric field is accelerated using a Newton method with derivatives obtained from the adjoint method.
The Antarctic Treaty of 1959, which dedicates the continent to peace and international scientific cooperation in the face of rising east–west tensions, is informed in part by a shared scientific imaginary created by the UK and other nations which maintained scientific bases in Antarctica at the time. In this article, the poet offers works extracted from her longer sequence “Met Obs,” based on meteorological reports and journals from the UK station at Port Lockroy written in advance of the 1957–1958 International Geophysical Year (IGY). The poems engage with the work and circumstances which helped foster such an imaginary, as well as with the nexus of Antarctic “values” endorsed by the Treaty, and the later Madrid Protocol. The commentary further contextualises these literary responses in terms of the attitudes of the men working there as well as the “wilderness and aesthetic values” recognised by the later Protocol on Environmental Protection. The world of the poems may belong to 1950s Antarctica, but their observations reach beyond that experience, making a case for the continued relevance of Treaty values, and for the importance of artistic, as well as scientific, responses to the environment in a world under threat from accelerating climate change and competition for resources.
To sustainably improve cleaning of high-touch surfaces (HTSs) in acute-care hospitals using a multimodal approach to education, reduction of barriers to cleaning, and culture change for environmental services workers.
The study was conducted in 2 academic acute-care hospitals, 2 community hospitals, and an academic pediatric and women’s hospital.
Frontline environmental services workers.
A 5-module educational program, using principles of adult learning theory, was developed and presented to environmental services workers. Audience response system (ARS), videos, demonstrations, role playing, and graphics were used to illustrate concepts of and the rationale for infection prevention strategies. Topics included hand hygiene, isolation precautions, personal protective equipment (PPE), cleaning protocols, and strategies to overcome barriers. Program evaluation included ARS questions, written evaluations, and objective assessments of occupied patient room cleaning. Changes in hospital-onset C. difficile infection (CDI) and methicillin-resistant S. aureus (MRSA) bacteremia were evaluated.
On average, 357 environmental service workers participated in each module. Most (93%) rated the presentations as ‘excellent’ or ‘very good’ and agreed that they were useful (95%), reported that they were more comfortable donning/doffing PPE (91%) and performing hand hygiene (96%) and better understood the importance of disinfecting HTSs (96%) after the program. The frequency of cleaning individual HTSs in occupied rooms increased from 26% to 62% (P < .001) following the intervention. Improvement was sustained 1-year post intervention (P < .001). A significant decrease in CDI was associated with the program.
A novel program that addressed environmental services workers’ knowledge gaps, challenges, and barriers was well received and appeared to result in learning, behavior change, and sustained improvements in cleaning.
To determine the preliminary feasibility, acceptability, and effects of Meaning-Centered Grief Therapy (MCGT) for parents who lost a child to cancer.
Parents who lost a child to cancer and who were between six months and six years after loss and reporting elevated levels of prolonged grief were enrolled in open trials of MCGT, a manualized, one-on-one cognitive-behavioral-existential intervention that used psychoeducation, experiential exercises, and structured discussion to explore themes related to meaning, identity, purpose, and legacy. Parents completed 16 weekly sessions, 60–90 minutes in length, either in person or through videoconferencing. Parents were administered measures of prolonged grief disorder symptoms, meaning in life, and other assessments of psychological adjustment preintervention, mid-intervention, postintervention, and at three months postintervention. Descriptive data from both the in-person and videoconferencing open trial were pooled.
Eight of 11 (72%) enrolled parents started the MCGT intervention, and six of eight (75%) participants completed all 16 sessions. Participants provided positive feedback about MCGT. Results showed postintervention longitudinal improvements in prolonged grief (d = 1.70), sense of meaning (d = 2.11), depression (d = 0.84), hopelessness (d = 1.01), continuing bonds with their child (d = 1.26), posttraumatic growth (ds = 0.29–1.33), positive affect (d = 0.99), and various health-related quality of life domains (d = 0.46–0.71). Most treatment gains were either maintained or increased at the three-month follow-up assessment.
Significance of results
Overall, preliminary data suggest that this 16-session, manualized cognitive-behavioral-existential intervention is feasible, acceptable, and associated with transdiagnostic improvements in psychological functioning among parents who have lost a child to cancer. Future research should examine MCGT with a larger sample in a randomized controlled trial.
Subcutaneous immunoglobulin (SCIg) treatment has been shown to control symptoms and improve overall satisfaction in patients with neurological disorders. However, a large injection volume can be overwhelming and a barrier to successful SCIg treatment. We established a nurse-led individualized approach program to facilitate a smooth and successful treatment transition from intravenous immunoglobulin (IVIg) to SCIg. The program involved a lead nurse to provide two or more individual educational sessions on SCIg administration, establish a written transition plan, and liaise care with physicians.
We aimed to evaluate the impact of our program to a successful transition defined as SCIg retention or adherence without a need to restart IVIg by six or twelve months.
We reviewed medical charts of all patients with immune-mediated neuromuscular disorders who were in our program during January 2010 to Dec 2016.
Nineteen patients were identified. Mean IVIg treatment duration was 31.5 months (range 4-98) before the transition. Mean steady state SCIg dosage was 26.2 g/week (SD 10.3). All patients were initially able to switch to SCIg, with a retention rate of 17/19 (89.5%) at six months and 15/19 (78.9%) at twelve months. Two patients reverted back to IVIg treatment due to worsening of their symptoms at two and three months, while two required supplemental IVIg infusions. There were no major adverse events reported during the twelve-month period, but one minor cutaneous adverse event (redness around the injection site).
Successful treatment transition may be achieved with the nurse led individualized approach program.
To identify potential participants for clinical trials, electronic health records (EHRs) are searched at potential sites. As an alternative, we investigated using medical devices used for real-time diagnostic decisions for trial enrollment.
To project cohorts for a trial in acute coronary syndromes (ACS), we used electrocardiograph-based algorithms that identify ACS or ST elevation myocardial infarction (STEMI) that prompt clinicians to offer patients trial enrollment. We searched six hospitals’ electrocardiograph systems for electrocardiograms (ECGs) meeting the planned trial’s enrollment criterion: ECGs with STEMI or > 75% probability of ACS by the acute cardiac ischemia time-insensitive predictive instrument (ACI-TIPI). We revised the ACI-TIPI regression to require only data directly from the electrocardiograph, the e-ACI-TIPI using the same data used for the original ACI-TIPI (development set n = 3,453; test set n = 2,315). We also tested both on data from emergency department electrocardiographs from across the US (n = 8,556). We then used ACI-TIPI and e-ACI-TIPI to identify potential cohorts for the ACS trial and compared performance to cohorts from EHR data at the hospitals.
Receiver-operating characteristic (ROC) curve areas on the test set were excellent, 0.89 for ACI-TIPI and 0.84 for the e-ACI-TIPI, as was calibration. On the national electrocardiographic database, ROC areas were 0.78 and 0.69, respectively, and with very good calibration. When tested for detection of patients with > 75% ACS probability, both electrocardiograph-based methods identified eligible patients well, and better than did EHRs.
Using data from medical devices such as electrocardiographs may provide accurate projections of available cohorts for clinical trials.
A 3-yr watermelon experiment was established in fall 2013 to evaluate cover crop, polyethylene mulch, tillage, and herbicide application components for weed control, yield, and profitability. Conservation tillage, either with a cereal rye cover crop alone or integrated with polyethylene mulch, was compared to the standard industry practice of conventional tillage with bedded polyethylene mulch. The study also used a non-bedded conventional tillage system without polyethylene to determine polyethylene and cover crop residue effects. Within each of the four systems, herbicide treatments comprised halosulfuron applied (1) at 26.3 g ai ha–1 PRE, (2) at 26.3 g ai ha–1 POST, or (3) sequentially at 26.3 g ai ha–1 PRE and POST. Each system also had a nontreated control. In addition, clethodim was applied in all plots twice POST at 140 g ai ha–1, except for nontreated in each system. In 2014, polyethylene or cereal rye cover crop effectively controlled tall morningglory, coffee senna, and carpetweed early season in nontreated plots, whereas the integration of the two was effective at controlling common purslane. Tall morningglory and purslane control was insufficient late season regardless of production system and herbicide application. In 2015, polyethylene effectively controlled cutleaf eveningprimrose, sicklepod, and arrowleaf sida early season in nontreated plots. Yellow nutsedge control was insufficient late season regardless of production system and herbicide application. Utilizing sequential halosulfuron applications did not increase weed control over PRE or POST alone in all years. Polyethylene use resulted in yields higher than systems without in all years. Across all 3 yr, net returns were highest for polyethylene mulch systems. The results of this experiment underscore the need for more progress in developing integrated conservation systems for watermelon production. Effective herbicides, low-disturbance cultivation, and/or hand weeding are most likely the key to success in conservation specialty crop systems.
The combination of sensitivity and large sky coverage of the ALFALFA HI survey has enabled the detection of difficult to observe low mass galaxies in large numbers, including dwarf galaxies overlooked in optical surveys. Three different, but connected, studies of dwarf galaxies from the ALFALFA survey are of particular interest: SHIELD (Survey of HI in Extremely Low-mass Dwarfs), candidate gas-rich ultra-faint dwarf galaxies, and the (Almost) Dark population. SHIELD is a systematic multiwavelength study of all dwarf galaxies from ALFALFA with MHI < 107.2M⊙ and clear optical counterparts. Candidate gas-rich ultra-faint dwarf galaxies extend the dwarf galaxy population to even lower masses. These galaxies are identified as isolated HI clouds with no discernible optical counterpart but subsequent observations reveal that some are extremely faint, gas-dominated galaxies. Leo P, discovered first as an HI detection, and then found to be an actively star-forming galaxy, bridges the gap between these candidate galaxies and the SHIELD sample. The (Almost) Dark sample consists of galaxies whose optical counterparts are overlooked in current optical surveys but which are clear detections in ALFALFA. This sample includes field gas-rich ultra-diffuse galaxies. Coma P, with a peak surface brightness of only ∼26.4 mag arcsec−2 in g’, demonstrates the sort of extreme low surface brightness galaxy that can be discovered in an HI survey.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).
Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.
Analyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.
This is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.
OBJECTIVES/SPECIFIC AIMS: To build a multisite de-identified database of female adolescents, aged 12–21 years (January 2011–December 2012), and their subsequent offspring through 24 months of age from electronic health records (EHRs) provided by participating Community Health. METHODS/STUDY POPULATION: We created a community-academic partnership that included New York City Community Health Centers (n=4) and Hospitals (n=4), The Rockefeller University, The Sackler Institute for Nutrition Science and Clinical Directors Network (CDN). We used the Community-Engaged Research Navigation model to establish a multisite de-identified database extracted from EHRs of female adolescents aged 12–21 years (January 2011–December 2012) and their offspring through 24 months of age. These patients received their primary care between 2011 and 2015. Clinical data were used to explore possible associations among specific measures. We focused on the preconception, prenatal, postnatal periods, including pediatric visits up to 24 months of age. RESULTS/ANTICIPATED RESULTS: The analysis included all female adolescents (n=122,556) and a subset of pregnant adolescents with offspring data available (n=2917). Patients were mostly from the Bronx; 43% of all adolescent females were overweight (22%) or obese (21%) and showed higher systolic and diastolic blood pressure, blood glucose levels, hemoglobin A1c, total cholesterol, and triglycerides levels compared with normal-weight adolescent females (p<0.05). This analysis was also performed looking at the nonpregnant females and the pregnant females separately. Overall, the pregnant females were older (mean age=18.3) compared with the nonpregnant females (mean age=16.5), there was a higher percentage of Hispanics among the pregnant females (58%) compared with the nonpregnant females (43.9%). There was a statistically significant association between the BMI status of mothers and infants’ birth weight, with underweight/normal-weight mothers having more low birth weight (LBW) babies and overweight/obese mothers having more large babies. The odds of having a LBW baby was 0.61 (95% CI: 0.41, 0.89) lower in obese compared with normal-weight adolescent mothers. The risk of having a preterm birth before 37 weeks was found to be neutral in obese compared with normal-weight adolescent mothers (OR=0.81, 95% CI: 0.53, 1.25). Preliminary associations are similar to those reported in the published literature. DISCUSSION/SIGNIFICANCE OF IMPACT: This EHR database uses available measures from routine clinical care as a “rapid assay” to explore potential associations, and may be more useful to detect the presence and direction of associations than the magnitude of effects. This partnership has engaged community clinicians, laboratory, and clinical investigators, and funders in study design and analysis, as demonstrated by the collaborative development and testing of hypotheses relevant to service delivery. Furthermore, this research and learning collaborative is examining strategies to enhance clinical workflow and data quality as well as underlying biological mechanisms. The feasibility of scaling-up these methods facilitates studying similar populations in different Health Systems, advancing point-of-care studies of natural history and comparative effectiveness research to identify service gaps, evaluate effective interventions, and enhance clinical and data quality improvement.
OBJECTIVES/SPECIFIC AIMS: Transforming growth factor-beta (TGFβ) is a genetic modifier of cystic fibrosis (CF) lung disease. TGFβ’s pulmonary levels in young CF patients and its mechanism of action in CF are unknown. We examined TGFβ levels in children with CF and investigated responses of human airway epithelial cells (AECs) and mice to TGFβ. METHODS/STUDY POPULATION: TGFβ levels in bronchoalveolar lavage fluid from CF patients (n=15) and non-CF control patients (n=21)<6 years old were determined by ELISA. CF mice and non-CF mice were intratracheally treated with an adenoviral TGFβ1 vector or PBS; lungs were collected for analysis at day 7. Human CF and non-CF AECs were treated with TGFβ or PBS for 24 hours then collected for analysis. RESULTS/ANTICIPATED RESULTS: Young CF patients had higher bronchoalveolar lavage fluid TGFβ than non-CF controls (p=0.03). Mouse lungs exposed to TGFβ demonstrated inflammation, goblet cell hyperplasia, and decreased CFTR expression. CF mice had greater TGFβ-induced lung mechanics abnormalities than controls; both CF human AECs and CF mice showed higher TGFβ induced MAPK and PI3K signaling compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT: For the first time, we show increased TGFβ levels very early in CF. TGFβ drives CF lung abnormalities in mouse and human models; CF models are more sensitive to TGFβ’s effects. Understanding the role of TGFβ in promoting CF lung disease is critical to developing patient specific treatments.
The Batocrinidae are characteristic faunal elements in Lower Mississippian shallow-marine settings in North America. Recent delineation of objectively defined genera allows a reexamination of batocrinid species and their distribution in the Fort Payne Formation (early Viséan, late Osagean), a well-studied array of carbonate and siliciclastic facies. The Fort Payne batocrinid fauna has 14 species assigned to six genera, plus hybrid specimens. Magnuscrinus spinosus (Miller and Gurley, 1895a) is reassigned to its original placement in Eretmocrinus. Hybrid specimens (Ausich and Meyer, 1994) are regarded as Eretmocrinus magnificus×Eretmocrinus spinosus. Macrocrinus casualis is the dominant species of Macrocrinus in the Fort Payne, and M. mundulus and M. strotobasilaris are recognized in the Fort Payne Formation for the first time. Magnuscrinus cumberlandensis n. sp. is named, 13 species are designated as junior synonyms, the name for the hybrid specimens is changed to Eretmocrinus magnificus×Eretmocrinus spinosus, and the previous occurrences of two species in the Fort Payne are rejected. The Eastern Interior Seaway was a mixed carbonate-siliciclastic setting with both shallow- and deep-water epicontinental sea facies ranging from relatively shallow autochthonous green shales to deep-water turbidite facies. Dizygocrinus was restricted to shallow-water carbonate and siliciclastic facies, Eutrochocrinus was restricted to shallow-water carbonate facies, and Magnuscrinus was restricted to deep-water facies. Species distributions varied from Abatocrinus steropes, Alloprosallocrinus conicus, Macrocrinus mundulus, and Uperocrinus nashvillae, which occurred throughout the Eastern Interior Seaway, to species that were restricted to a single facies. Eretmocrinus magnificus, Alloprosallocrinus conicus, and Uperocrinus robustus were the dominant batocrinids in the Fort Payne Formation.