To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
OBJECTIVES/GOALS: Supported by the State of Alabama, the Alabama Genomic Health Initiative (AGHI) is aimed at preventing and treating common conditions with a genetic basis. This joint UAB Medicine-HudsonAlpha Institute for Biotechnology effort provides genomic testing, interpretation, and counseling free of charge to residents in each of Alabama’s 67 counties. METHODS/STUDY POPULATION: Launched in 2017, as a state-wide population cohort, AGHI (1.0) enrolled 6,331 Alabamians and returned individual risk of disease(s) related to the ACMG SF v2.0 medically actionable genes. In 2021, the cohort was expanded to include a primary care cohort. AGHI (2.0) has enrolled 750 primary care patients, returning individual risk of disease(s) related to the ACMG SF v3.1 gene list and pre-emptive pharmacogenetics (PGx) to guide medication therapy. Genotyping is done on the Illumina Global Diversity Array with Sanger sequencing to confirm likely pathogenic / pathogenic variants in medically actionable genes and CYP2D6 copy number variants using Taqman assays, resulting in a CLIA-grade report. Disease risk results are returned by genetic counselors and Pharmacogenetics results are returned by Pharmacists. RESULTS/ANTICIPATED RESULTS: We have engaged a statewide community (>7000 participants), returning 94 disease risk genetic reports and 500 PGx reports. Disease risk reports include increased predisposition to cancers (n=38), cardiac diseases (n=33), metabolic (n=12), other (n=11). 100% of participants harbor an actionable PGx variant, 70% are on medication with PGx guidance, 48% harbor PGx variants and are taking medications affected. In 10% of participants, pharmacists sent an active alert to the provider to consider/ recommend alternative medication. Most commonly impacted medications included antidepressants, NSAIDS, proton-pump inhibitors and tramadol. To enable the EMR integration of genomic information, we have developed an automated transfer of reports into the EMR with Genetics Reports and PGx reports viewable in Cerner. DISCUSSION/SIGNIFICANCE: We share our experience on pre-emptive implementation of genetic risk and pharmacogenetic actionability at a population and clinic level. Both patients and providers are actively engaged, providing feedback to refine the return of results. Real time alerts with guidance at the time of prescription are needed to ensure future actionability and value.
Gaps in the implementation of effective interventions impact nearly all cancer prevention and control strategies in the US including Massachusetts. To close these implementation gaps, evidence-based interventions must be rapidly and equitably implemented in settings serving racially, ethnically, socioeconomically, and geographically diverse populations. This paper provides a brief overview of The Implementation Science Center for Cancer Control Equity (ISCCCE) and describes how we have operationalized our commitment to a robust community-engaged center that aims to close these gaps. We describe how ISCCCE is organized and how the principles of community-engaged research are embedded across the center. Principles of community engagement have been operationalized across all components of ISCCCE. We have intentionally integrated these principles throughout all structures and processes and have developed evaluation strategies to assess whether the quality of our partnerships reflects the principles. ISCCCE is a comprehensive community-engaged infrastructure for studying efficient, pragmatic, and equity-focused implementation and adaptation strategies for cancer prevention in historically and currently disadvantaged communities with built-in methods to evaluate the quality of community engagement. This engaged research center is designed to maximize the impact and relevance of implementation research on cancer control in community health centers.
We investigate the entropy for a class of upper semi-continuous set-valued functions, called Markov set-valued functions, that are a generalization of single-valued Markov interval functions. It is known that the entropy of a Markov interval function can be found by calculating the entropy of an associated shift of finite type. In this paper, we construct a similar shift of finite type for Markov set-valued functions and use this shift space to find upper and lower bounds on the entropy of the set-valued function.
To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).
Descriptive retrospective cohort with nested case-control study.
Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.
Children≤18 years ventilated for≥1 calendar day.
We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.
Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.
Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.
Individuals with schizophrenia have deficits in social cognition that are associated with poor functional outcome. Unfortunately, current treatments result in only modest improvement in social cognition. Oxytocin, a neuropeptide with pro-social effects, has significant benefits for social cognition in the general population. However, studies examining the efficacy of oxytocin in schizophrenia have yielded inconsistent results. One reason for inconsistency may be that oxytocin has typically not been combined with psychosocial interventions. It may be necessary for individuals with schizophrenia to receive concurrent psychosocial treatment while taking oxytocin to have the context needed to make gains in social cognitive skills.
The current study tested this hypothesis in a 24-week (48 session) double-blind, placebo-controlled trial that combined oxytocin and Cognitive-Behavioral Social Skills Training (CBSST), which included elements from Social Cognition and Interaction Training (SCIT). Participants included 62 outpatients diagnosed with schizophrenia (placebo n = 31; oxytocin n = 31) who received 36 IU BID, with supervised administration 45 min prior to sessions on CBSST group therapy days. Participants completed a battery of measures administered at 0, 12, and 24 weeks that assessed social cognition.
CBSST generally failed to enhance social cognition from baseline to end of study, and there was no additive benefit of oxytocin beyond the effects of CBSST alone.
Findings suggest that combined CBSST and oxytocin had minimal benefit for social cognition, adding to the growing literature indicating null effects of oxytocin in multi-dose trials. Methodological and biological factors may contribute to inconsistent results across studies.
The study investigated the seasonal changes in the compositional, physicochemical and processing characteristics of milk from a mixed-herd of spring- and autumn-calving cows during the year 2014–2015. The volume proportion of autumn-calving milk (% of total milk) varied with season, from ~10–20 in Spring (March–May), 5–13 in Summer (June–August), 20–40 in Autumn (September–November) and 50–100 in Winter (December–February). While all characteristics varied somewhat from month to month, variation was inconsistent, showing no significant trend with progression of time (year). Consequently, season did not significantly affect many parameters including concentrations of total protein, casein, whey protein, NPN, total calcium, pH, rennet gelation properties or heat stability characteristics. However, season had a significant effect on the concentrations of total P and serum P, levels of αs1- and β-caseins as proportions of total casein, casein micelle size, zeta potential and ethanol stability. The absence of a significant effect of season for most compositional parameters, rennet gelation and heat-stability characteristics suggest that milk from a mixed-herd of spring- and autumn-calving cows is suitable for the manufacture of cheese and milk powder on a year-round basis, when the volume proportion of autumn milk, as a % of total, is similar to that of the current study.
Adult ventilator-associated event (VAE) definitions include ventilator-associated conditions (VAC) and subcategories for infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (PVAP). We explored these definitions for children.
Pediatric, cardiac, or neonatal intensive care units (ICUs) in 6 US hospitals
Patients ≤18 years old ventilated for ≥1 day
We identified patients with pediatric VAC based on previously proposed criteria. We applied adult temperature, white blood cell count, antibiotic, and culture criteria for IVAC and PVAP to these patients. We matched pediatric VAC patients with controls and evaluated associations with adverse outcomes using Cox proportional hazards models.
In total, 233 pediatric VACs (12,167 ventilation episodes) were identified. In the cardiac ICU (CICU), 62.5% of VACs met adult IVAC criteria; in the pediatric ICU (PICU), 54.2% of VACs met adult IVAC criteria; and in the neonatal ICU (NICU), 20.2% of VACs met adult IVAC criteria. Most patients had abnormal white blood cell counts and temperatures; we therefore recommend simplifying surveillance by focusing on “pediatric VAC with antimicrobial use” (pediatric AVAC). Pediatric AVAC with a positive respiratory diagnostic test (“pediatric PVAP”) occurred in 8.9% of VACs in the CICU, 13.3% of VACs in the PICU, and 4.3% of VACs in the NICU. Hospital mortality was increased, and hospital and ICU length of stay and duration of ventilation were prolonged among all pediatric VAE subsets compared with controls.
We propose pediatric AVAC for surveillance related to antimicrobial use, with pediatric PVAP as a subset of AVAC. Studies on generalizability and responsiveness of these metrics to quality improvement initiatives are needed, as are studies to determine whether lower pediatric VAE rates are associated with improvements in other outcomes.
Despite evidence for the effectiveness of structured psychological
therapies for bipolar disorder no psychological interventions have been
specifically designed to enhance personal recovery for individuals with
recent-onset bipolar disorder.
A pilot study to assess the feasibility and effectiveness of a new
intervention, recovery-focused cognitive–behavioural therapy (CBT),
designed in collaboration with individuals with recent-onset bipolar
disorder intended to improve clinical and personal recovery outcomes.
A single, blind randomised controlled trial compared treatment as usual
(TAU) with recovery-focused CBT plus TAU (n = 67).
Recruitment and follow-up rates within 10% of pre-planned targets to
12-month follow-up were achieved. An average of 14.15 h (s.d. = 4.21) of
recovery-focused CBT were attended out of a potential maximum of 18 h.
Compared with TAU, recovery-focused CBT significantly improved personal
recovery up to 12-month follow-up (Bipolar Recovery Questionnaire mean
score 310.87, 95% CI 75.00–546.74 (s.e. = 120.34), P =
0.010, d=0.62) and increased time to any mood relapse
during up to 15 months follow-up (χ2 = 7.64,
P<0.006, estimated hazard ratio (HR) = 0.38, 95%
CI 0.18–0.78). Groups did not differ with respect to medication
Recovery-focused CBT seems promising with respect to feasibility and
potential clinical effectiveness. Clinical- and cost-effectiveness now
need to be reliably estimated in a definitive trial.
Children with neurofibromatosis-1 (NF1), a neurodevelopmental disorder resulting from a mutation of the NF1 gene (17q11.2), often have difficulties with learning and attention, but there is little research in the early childhood years. In this study, the cognitive and psychosocial functioning of 40 young children with NF1 (ages 3 through 6) was examined and compared both to normative data and to a contrast group comprised of unaffected siblings and community members matched for age and socio-economic status (n = 37). Children with NF1 showed significantly weaker cognitive abilities across all domains and for the vast majority of subtests. Consistent with research in older children, a variety of patterns of intra-individual strength and weakness were present for young children with NF1. Few significant group differences in psychosocial functioning were observed, but the children with NF1 showed significantly greater functional communication problems than did the unaffected group. Overall, the results indicate that in participant groups matched for age and socioeconomic status, cognitive vulnerabilities are evident for close to half of young children with NF1, with some relations to psychosocial functioning, particularly functional communication, attention problems and social skills. (JINS, 2014, 1, 1–11)
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
The arousal system involves multiple distributed neural networks working in harmony to permit normal sleep-wake cycles, satisfy internal drive states, and respond to environmental demands. Disorders of arousal involve pathology of the brainstem, thalamus, or widespread areas of both cerebral hemispheres. A parallel series of distinct neural networks using dopamine, histamine, serotonin, acetylcholine, and norepinephrine as neurotransmitters originates in the brainstem. Brain death represents the most severe disturbance of arousal, with total and irreversible cessation of any brain function. Coma is the state of neurological unconsciousness exhibited by unarousable unawareness of the external environment that is due to extensive damage to or depressed function of both cerebral hemispheres, bilateral diencephalic structures, or the ascending reticular activating system. A specific rehabilitative strategy is coma stimulation, in which structured sensory stimulation is administered for the purposes of improving sensory awareness and facilitating improvements in arousal and awareness.
Sport-related concussion (SRC) is typically followed by clinical recovery within days, but reports of prolonged symptoms are common. We investigated the incidence of prolonged recovery in a large cohort (n = 18,531) of athlete seasons over a 10-year period. A total of 570 athletes with concussion (3.1%) and 166 controls who underwent pre-injury baseline assessments of symptoms, neurocognitive functioning and balance were re-assessed immediately, 3 hr, and 1, 2, 3, 5, 7, and 45 or 90 days after concussion. Concussed athletes were stratified into typical (within 7 days) or prolonged (> 7 days) recovery groups based on symptom recovery time. Ten percent of athletes (n = 57) had a prolonged symptom recovery, which was also associated with lengthier recovery on neurocognitive testing (p < .001). At 45–90 days post-injury, the prolonged recovery group reported elevated symptoms, without deficits on cognitive or balance testing. Prolonged recovery was associated with unconsciousness [odds ratio (OR), 4.15; 95% confidence interval (CI) 2.12–8.15], posttraumatic amnesia (OR, 1.81; 95% CI, 1.00–3.28), and more severe acute symptoms (p < .0001). These results suggest that a small percentage of athletes may experience symptoms and functional impairments beyond the typical window of recovery after SRC, and that prolonged recovery is associated with acute indicators of more severe injury. (JINS, 2012, 18, 1–12)