A naturalistic study of medication reduction in a residential treatment setting

The primary aim of this pilot study was to ascertain if psychiatric medications could be reduced in a convenience sample of seriously emotionally disturbed children and adolescents over the course of residential treatment. We also sought to understand factors correlated with reduction in the number of medications during treatment. A review of the treatment of 141 patients (n = 112 admitted on medication and n = 29 admitted on no medication) admitted to, and discharged from, a residential treatment setting between 1992 and 2001 was undertaken. Significantly more children were discharged from treatment on no medications than were admitted to residential treatment on no medications. In children receiving more than 1 medication at admission, the number of combined medications was significantly reduced over the course of residential treatment. However, the majority of children admitted on medications continued on some psychiatric medications, indicating that psychopharmacology continued to play an important role in their treatment. In 112 patients admitted on psychoactive medications, our pilot data suggests that improvement in externalizing, internalizing, psychotic, and autistic psychopathology while in residential treatment, the presence of an intact family (adoptive or biological), the absence of a history of either sexual or physical abuse, and the type of medication used appear to be factors that correlate with a reduced use of medications in this population

Enkephalin Therapy Improves Relapsing-Remitting Multiple Sclerosis

Multiple sclerosis (MS) is accompanied by decreases in serum endogenous enkephalin/endorphins and alterations in inflammatory cytokines. This retrospective analysis of serum levels was conducted in 53 patients with established relapsing-remitting MS treated with the disease-modifying therapies (DMT) glatiramer acetate, dimethyl fumarate or with the biotherapeutic low dose naltrexone (LDN) to elevate enkephalins, an off-label alternative. Opioid growth factor (OGF), an inhibitory endogenous opioid involved in modulating cellular replication, was measured and correlated to serum β-endorphin, IL-17A and TNFα. Results revealed that MS leads to a significant reduction in OGF levels in subjects on DMTs, but patients on LDN had OGF levels comparable to non-MS controls. Individuals on DMTs had significantly elevated TNFα levels, while IL-17A levels were significantly elevated only in patients taking dimethyl fumarate. A direct correlation was established between OGF and IL17A indicating a potential interaction between the OGF-OGFr axis and pro-inflammatory T-helper cells providing insight into the disease etiology

Hatching the behavioral addiction egg: Reward Deficiency Solution System (RDSS)™ as a function of dopaminergic neurogenetics and brain functional connectivity linking all addictions under a common rubric

Abstract Background Following the first association between the dopamine D2 receptor gene polymorphism and severe alcoholism, there has been an explosion of research reports in the psychiatric and behavioral addiction literature and neurogenetics. With this increased knowledge, the field has been rife with controversy. Moreover, with the advent of Whole Genome-Wide Studies (GWAS) and Whole Exome Sequencing (WES), along with Functional Genome Convergence, the multiple-candidate gene approach still has merit and is considered by many as the most prudent approach. However, it is the combination of these two approaches that will ultimately define real, genetic allelic relationships, in terms of both risk and etiology. Since 1996, our laboratory has coined the umbrella term Reward Deficiency Syndrome (RDS) to explain the common neurochemical and genetic mechanisms involved with both substance and non-substance, addictive behaviors. Methods This is a selective review of peer-reviewed papers primary listed in Pubmed and Medline. Results A review of the available evidence indicates the importance of dopaminergic pathways and resting-state, functional connectivity of brain reward circuits. Discussion Importantly, the proposal is that the real phenotype is RDS and impairments in the brain's reward cascade, either genetically or environmentally (epigenetically) induced, influence both substance and non-substance, addictive behaviors. Understanding shared common mechanisms will ultimately lead to better diagnosis, treatment and prevention of relapse. While, at this juncture, we cannot as yet state that we have “hatched the behavioral addiction egg”, we are beginning to ask the correct questions and through an intense global effort will hopefully find a way of “redeeming joy” and permitting homo sapiens live a life, free of addiction and pain

CLAM-Accelerated K-Nearest Neighbors Entropy-Scaling Search of Large High-Dimensional Datasets via an Actualization of the Manifold Hypothesis

Many fields are experiencing a Big Data explosion, with data collection rates outpacing the rate of computing performance improvements predicted by Moore's Law. Researchers are often interested in similarity search on such data. We present CAKES (CLAM-Accelerated $K$-NN Entropy Scaling Search), a novel algorithm for $k$-nearest-neighbor ($k$-NN) search which leverages geometric and topological properties inherent in large datasets. CAKES assumes the manifold hypothesis and performs best when data occupy a low dimensional manifold, even if the data occupy a very high dimensional embedding space. We demonstrate performance improvements ranging from hundreds to tens of thousands of times faster when compared to state-of-the-art approaches such as FAISS and HNSW, when benchmarked on 5 standard datasets. Unlike locality-sensitive hashing approaches, CAKES can work with any user-defined distance function. When data occupy a metric space, CAKES exhibits perfect recall.Comment: As submitted to IEEE Big Data 202

Asymmetry of bifurcated features in radio pulsar profiles

High-quality integrated radio profiles of some pulsars contain bifurcated, highly symmetric emission components (BECs). They are observed when our line of sight traverses through a split-fan shaped emission beam. It is shown that for oblique cuts through such a beam, the features appear asymmetric at nearly all frequencies, except from a single `frequency of symmetry' nu_sym, at which both peaks in the BEC have the same height. Around nu_sym the ratio of flux in the two peaks of a BEC evolves in a way resembling the multifrequency behaviour of J1012+5307. Because of the inherent asymmetry resulting from the oblique traverse of sightline, each minimum in double notches can be modelled independently. Such a composed model reproduces the double notches of B1929+10 if the fitted function is the microscopic beam of curvature radiation in the orthogonal polarisation mode. These results confirm our view that some of the double components in radio pulsar profiles directly reveal the microscopic nature of the emitted radiation beam as the microbeam of curvature radiation polarised orthogonally to the trajectory of electrons.Comment: 10 pages, 7 figures, printed in MNRA

A Comparison of Recruitment Strategies for a Long-Term Study at Two Maternal Stages: Effectiveness of Recruitment During Pregnancy vs. After Childbirth

Introduction. National Children’s Study (NCS) Provider Based Sampling (PBS) aims to conduct a pilot study to test cost, acceptability and feasibility of recruiting a representative sample of women/children using two recruitment strategies: through prenatal providers and hospitals. Methods. A sampling frame consisting of all providers of prenatal and delivery care within and 10-miles outside Worcester County, 16 provider and 3 hospital locations were selected as point of entry for study recruitment. During 1st prenatal care visits or post-delivery at these locations, face-to-face contact was utilized to: a) identify study eligibility and b) assess study recruitment. Preliminary Results. Certified Data Collectors made contact with prescreened women. Consent rates of women at prenatal provider locations were lower than the consent rates in hospital locations. On average, results have shown twice as many consents could be obtained per day at hospital locations than at provider locations. Preliminary Conclusions. Although both strategies utilized direct rapport, the two recruitment methods were associated with different consent rates. Consideration of preliminary results may lead one to consider recruitment after childbirth for several reasons: 1) greater likelihood of having opportunity to discuss study with the woman and partner from outset; 2) opportunity to check back with undecided women easily 3) longer periods to answer questions and conduct screening and consent; 4) support of nursing staff to foster participation; 5) daily presence of NCS staff; and 6) reality of infant’s birth to spur mother to consent. Recruitment during pregnancy visits may yield lower rates; further examination may be necessary to overcome challenges such as: 1) burden of adding recruitment session to often long and anxiety-laden1st prenatal visit; 2) need to develop rapport quickly during brief time periods; 3) making contact with potential participants outside of provider office when recruitment is not completed

Framing Hospital Engagement for the Recruitment of a Birth Cohort for the NCS: Lessons Learned for Ensuring Collaboration in Worcester County

In 2011, three designated NCS Study Centers began preparatory work for field implementation of a planned recruitment strategy called Provider Based Sampling (PBS). In each PBS primary sampling unit, three hospitals were selected to test the feasibility of recruiting a cohort of 125 women and their babies around delivery time. The selected hospitals for Worcester account for nearly 80% of County births and can be categorized into three distinct facility types and patient catchment areas: an academic medical center; a university-affiliated but independent community hospital; and a private for-profit community hospital with market share competitor of the academic medical center. Methods: We used tailored negotiations and engagement strategies to gain the cooperation and engagement of targeted hospitals/birthing centers. Preliminary Conclusions: The lessons learned from this exercise are:• Time to gain hospital engagement and clearance to initiate study activities ranges anywhere from 2 weeks to 2 months and depends largely upon the type of the institution, the profile of the Negotiator, and the nature of the scope of work.• A greater likelihood of hospital engagement in the NCS seems to be associated with the depth of existing relationships between the Study Center and targeted hospitals.• Thoughtful interactions and timely discussions with the key institutional stakeholders (either individually or in groups) are important to achieve collaboration and engagement.• Balancing sensitivity to clinical cultures and settings while preserving research integrity is essential for study implementation in busy hospital/clinical environments.• Planning for site compensation and/or the ability to support local clerical staff to help with study activities must be considered as a means to facilitate negotiations and site engagement.• Adequate resources must be planned for successful implementation and execution of research activities in settings (e.g community hospitals) unfamiliar with research activities.• Involvement of nursing personnel is crucial for successful implementation of any protocol

PepSeeker: a database of proteome peptide identifications for investigating fragmentation patterns

Proteome science relies on bioinformatics tools to characterize proteins via their proteolytic peptides which are identified via characteristic mass spectra generated after their ions undergo fragmentation in the gas phase within the mass spectrometer. The resulting secondary ion mass spectra are compared with protein sequence databases in order to identify the amino acid sequence. Although these search tools (e.g. SEQUEST, Mascot, X!Tandem, Phenyx) are frequently successful, much is still not understood about the amino acid sequence patterns which promote/protect particular fragmentation pathways, and hence lead to the presence/absence of particular ions from different ion series. In order to advance this area, we have developed a database, PepSeeker (), which captures this peptide identification and ion information from proteome experiments. The database currently contains >185 000 peptides and associated database search information. Users may query this resource to retrieve peptide, protein and spectral information based on protein or peptide information, including the amino acid sequence itself represented by regular expressions coupled with ion series information. We believe this database will be useful to proteome researchers wishing to understand gas phase peptide ion chemistry in order to improve peptide identification strategies. Questions can be addressed to [email protected]

Validating criteria for identifying core concepts using many-facet rasch measurement

IntroductionCore concepts are foundational, discipline-based ideas considered necessary for students to learn, remember, understand, and apply. To evaluate the extent to which a concept is “core,” experts often rate concepts using various criteria, such as importance, complexity, and timeliness. However, there is a lack of validity evidence for core concepts criteria.MethodsUsing a three-facet Many-Facet Rasch Measurement (MFRM) model, we analyzed 7,558 ratings provided by 21 experts/raters for 74 pharmacology core concepts using five criteria measured on a five-point scale.ResultsAll of the criteria had Infit or Outfit MnSq values within the expected range (0.5 < MnSq < 1.7), suggesting the criteria contained an acceptable amount of variability; a reliability index of approximately 1.00 suggested that the criteria were reliably separated with a high degree of confidence. The rating scale Outfit MnSq statistics also fell within the 0.5–1.7 model fit limits; the “average measure” and “Rasch-Andrich thresholds” increased in magnitude as the rating scale categories increased, suggesting that core concepts with higher ratings were in fact meeting the criteria more convincingly than those with lower ratings. Adjusting expert ratings using the MFRM facets (e.g., rater severity) resulted in reorganization of core concepts rankings.ConclusionThis paper is a novel contribution to core concepts research and is intended to inform other disciplines seeking to develop, implement, and refine core concepts within the biomedical sciences and beyond