Psychosis-Spectrum Screening and Assessment Within a College Counseling Center: A Pilot Study Exploring Feasibility and Clinical Need.

Evidence supports the use of brief psychosis-spectrum screening tools for identifying individuals at an increased risk of developing a psychotic disorder. Screening has not been well studied in general mental health settings that serve young adults in the age range associated with highest risk for psychosis. This study explored the feasibility of psychosis-risk screening and assessment among help-seeking students at a university counseling center. The PRIME Screen-Revised was administered to students at clinic intake. Participants who screened positively were offered a follow-up assessment using the Structured Interview for Psychosis-risk Syndromes (SIPS). At intake, 510 students completed the PRIME Screen-Revised, with 132 (25.9%) screening positive. Comprehensive psychosis-spectrum evaluations were completed with 38 participants, and 22 met criteria for a psychosis-spectrum disorder, representing 57.9% of this subsample. Findings suggest that psychosis-risk screening in a college clinic is a promising approach to identifying those at high risk for or in the early stages of psychosis.

Gastrointestinal medication burden among persons with the Ehlers-Danlos syndromes.

BACKGROUND: The Ehlers-Danlos syndromes (EDSs) are a group of heritable disorders of connective tissue associated with an increased prevalence of both structural and functional GI conditions. METHODS: We used 10 years (2005-2014) of administrative claims data comprised of 4294 people with clinician-diagnosed EDS, aged 5-62 years, and compared their frequency of GI drug prescription claims to their age-, sex-, state of residence-, and earliest claim date-matched controls. We categorized the GI medications into the following groups: acid suppressants, anti-emetics, irritable bowel syndrome drugs, and visceral hypersensitivity (VHS) medications. KEY RESULTS: Compared to controls, a significantly higher proportion of persons with EDS had prescription claims for at least one GI drug group, as well as for drugs in each of the four GI drug groups included in our study. By age-group, 25.7% children and 45.1% adults with EDS had prescription claims for at least one GI drug group compared with only 7.4% and 21.0% of controls, respectively (p < 0.0001). By gender, 44.0% of women and 25.3% of men with EDS had prescription claims for at least one class of GI drugs compared with 19.2% and 9.6% of controls, respectively (p < 0.0001). CONCLUSIONS AND KEY INFERENCES: Predominant medication burden occurs among women with EDS, beginning peri-pubertally for anti-emetics and VHS drugs. High GI medication burden underscores previous evidence that GI dysmotility is common among persons with EDS.

Preliminary support for using the Atypicality Scale from the Behavior Assessment System for Children, Second Edition, to screen for psychosis-spectrum disorders within a college counselling centre.

AIM: Evidence supports the use of brief psychosis-spectrum screeners for identifying individuals at risk for psychosis. Screening has not been well-studied in help-seeking college samples. This study investigated the use of the Behavior Assessment System for Children, Second Edition (BASC-2) Atypicality Scale as a psychosis-spectrum screening tool within a university counselling centre. METHODS: Atypicality scores from the BASC-2 were compared to interview-based assessment, the Structured Interview for Psychosis-risk Syndromes (SIPS), to explore associations across the measures and evaluate the scale's ability to identify individuals who meet criteria for a psychosis-spectrum diagnosis. RESULTS: Forty-three participants completed the BASC-2 and SIPS, and 23 were SIPS-positive. Compared to the SIPS-negative group, the SIPS-positive group had significantly higher Atypicality scores. Exploratory results indicated that Atypicality scores identified SIPS-positive individuals with an overall accuracy of 72% (78% sensitivity, 65% specificity). CONCLUSION: The Atypicality Scale may be an appropriate first-line psychosis-spectrum screening tool in college counselling centres.

Improved Assessment of Response Status in Patients with Pancreatic Cancer Treated with Neoadjuvant Therapy using Somatic Mutations and Liquid Biopsy Analysis.

PURPOSE: To evaluate somatic mutations, circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in patients with Pancreatic ductal adenocarcinoma (PDAC) with pathologic complete response (pCR) to neoadjuvant therapy (NAT) and find their associations with outcome. EXPERIMENTAL DESIGN: Thirty-six patients with PDAC with pCR were identified from 2009 to 2017. Macrodissection was performed on resected specimens to isolate DNA from 332 regions of interest including fibrosis, normal duct, normal parenchyma, and undefined ductal cells (UDCs). Cell-free DNA and CTCs were also extracted. Next-generation sequencing was used to detect mutations of KRAS, CDKN2A, SMAD4, TP53, GNAS, and BRAF. RESULTS: KRAS mutation was detected in UDCs and fibrosis while SMAD4, TP53, and GNAS were only seen in UDCs. Patients with TP53 mutation showed relatively worse overall survival (HR, 3.596, 95% CI, 0.855-15.130; P = 0.081). Five patients available for CTCs data were all positive for CTCs and seven of 16 patients with pCR were detected with ctDNA at surgery. We proposed a new concept of regression assessment combining genomic analysis of resected specimens and liquid biopsy data for PDAC, namely, molecular complete response (mCR). Three of six patients with mCR recurred as compared with six in 15 non-mCR patients. Seven of 15 non-mCR patients died during follow-up, while there was only one in six patients with mCR. CONCLUSIONS: This study first reports that somatic mutations, CTCs, and ctDNA existed even in patients with PDAC with pCR to NAT, which could possibly predict early recurrence and reduced survival. The current regression evaluation system of PDAC needs to be reassessed at a molecular level.

Amsterdam International Consensus Meeting: tumor response scoring in the pathology assessment of resected pancreatic cancer after neoadjuvant therapy.

Histopathologically scoring the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant treatment can guide the selection of adjuvant therapy and improve prognostic stratification. However, several tumor response scoring (TRS) systems exist, and consensus is lacking as to which system represents best practice. An international consensus meeting on TRS took place in November 2019 in Amsterdam, The Netherlands. Here, we provide an overview of the outcomes and consensus statements that originated from this meeting. Consensus (≥80% agreement) was reached on a total of seven statements: (1) TRS is important because it provides information about the effect of neoadjuvant treatment that is not provided by other histopathology-based descriptors. (2) TRS for resected PDAC following neoadjuvant therapy should assess residual (viable) tumor burden instead of tumor regression. (3) The CAP scoring system is considered the most adequate scoring system to date because it is based on the presence and amount of residual cancer cells instead of tumor regression. (4) The defining criteria of the categories in the CAP scoring system should be improved by replacing subjective terms including "minimal" or "extensive" with objective criteria to evaluate the extent of viable tumor. (5) The improved, consensus-based system should be validated retrospectively and prospectively. (6) Prospective studies should determine the extent of tissue sampling that is required to ensure adequate assessment of the residual cancer burden, taking into account the heterogeneity of tumor response. (7) In future scientific publications, the extent of tissue sampling should be described in detail in the "Materials and methods" section.

Application of Kotter's Theory of Change to Achieve Baby-Friendly Designation.

Creating an environment that optimally supports exclusive breastfeeding can require a cultural transformation. Our initial attempt at obtaining Baby-Friendly Hospital Initiative (BFHI) designation was unsuccessful when surveyors determined insufficient enculturation of BFHI practices. Using Kotter's theory of change, we overcame the barriers, enhanced our practices, and effectively transformed the culture, and our facility ultimately became the first maternity hospital in Pennsylvania to obtain BFHI designation. Nursing leadership was essential to this process. Our experience serves as a template for others seeking to achieve Healthy People 2020 goals related to breastfeeding.

Assessment of Nutrition Competency of Graduating Agriculture Students in Ethiopia: A Cross-sectional Study.

OBJECTIVE: To assess the level of nutrition-sensitive agriculture competencies of graduating midlevel animal and plant sciences students in Ethiopia and identify factors associated with the attainment of competencies. DESIGN: A cross-sectional study design using structured skills observation checklists, objective written questions, and structured questionnaires was employed. SETTING: Two agriculture technical vocational education and training colleges in the 2 regions of Ethiopia. PARTICIPANTS: A total of 145 students were selected using stratified random sampling techniques from a population of 808 students with the response rate of 93%. MAIN OUTCOME MEASURES: Nutrition-sensitive agriculture competency (knowledge and skills attributes) of graduating students. ANALYSIS: Bivariate and multivariable statistical analyses were used to examine the association between the variables of students' gender, age, department, institutional ownership, and perception of learning environment and their performance in nutrition competency. RESULTS: Combined scores showed that 49% of students demonstrated mastery of nutrition competencies. Gender and institutional ownership were associated with the performance of students (P < .001); male students and students at a federal institution performed better. CONCLUSIONS AND IMPLICATIONS: The study showed low performance of students in nutrition competency and suggested the need for strengthening the curriculum, building tutors' capacity, and providing additional support to female students and regional colleges.

Context matters: The impact of neighborhood crime and paranoid symptoms on psychosis risk assessment.

Psychosis risk assessment measures probe for paranoid thinking, persecutory ideas of reference, and suspiciousness as part of a psychosis risk construct. However, in some cases, these symptoms may reflect a normative, realistic, and even adaptive response to environmental stressors rather than psychopathology. Neighborhood characteristics, dangerousness for instance, are linked to levels of fear and suspiciousness that can be theoretically unrelated to psychosis. Despite this potential confound, psychosis-risk assessments do not explicitly evaluate neighborhood factors that might (adaptively) increase suspiciousness. In such cases, interviewers run the risk of misinterpreting adaptive suspiciousness as a psychosis-risk symptom. Ultimately, the degree to which neighborhood factors contribute to psychosis-risk assessment remains unclear. The current study examined the relation between neighborhood crime and suspiciousness as measured by the SIPS among predominantly African American help-seeking adolescents (N=57) living in various neighborhoods in Baltimore City. Uniform Crime Reports, including violent and property crime for Baltimore City, were used to calculate a proxy of neighborhood crime. This crime index correlated with SIPS suspiciousness (r(55)=.32, p=.02). Multiple regression analyses demonstrated that increased neighborhood crime significantly predicted suspiciousness over and above the influence of the other SIPS positive symptoms in predicting suspiciousness. Findings suggest that neighborhood crime may in some cases account for suspiciousness ascertained as part of a psychosis risk assessment, and therefore sensitivity to contextual factors is important when evaluating risk for psychosis.

Bypass Rapid Assessment Triage: How Culture Change Improved One Emergency Department's Safety, Throughput and Patient Satisfaction.

PROBLEM: Emergency department waiting rooms are high risk, high liability areas for hospitals. Patients who are greeted by non-clinical personnel or who are not being placed in available beds increases wait times and prevent patients from receiving timely treatment and access to care. METHODS: A multidisciplinary team was convened to review best practice literature and develop and implement an immediate bedding process. The process included placing a greeter nurse in the waiting room who performs a quick patient assessment to determine acuity. Based on that acuity, the greeter nurse then places the patient in the appropriate available bed. RESULTS: We established our Bypass Rapid Assessment Triage process and improved door-to-triage, door-to-bed, and door-to-physician times while enhancing patient satisfaction. IMPLICATIONS FOR PRACTICE: A system should be in place that allows for immediate bedding wherever possible. Transitioning to immediate bedding requires a culture change. Staff engagement is essential to achieving such a culture shift.

Bayesian inference of local trees along chromosomes by the sequential Markov coalescent.

We propose a genealogy-sampling algorithm, Sequential Markov Ancestral Recombination Tree (SMARTree), that provides an approach to estimation from SNP haplotype data of the patterns of coancestry across a genome segment among a set of homologous chromosomes. To enable analysis across longer segments of genome, the sequence of coalescent trees is modeled via the modified sequential Markov coalescent (Marjoram and Wall, Genetics 7:16, 2006). To assess performance in estimating these local trees, our SMARTree implementation is tested on simulated data. Our base data set is of the SNPs in 10 DNA sequences over 50 kb. We examine the effects of longer sequences and of more sequences, and of a recombination and/or mutational hotspot. The model underlying SMARTree is an approximation to the full recombinant-coalescent distribution. However, in a small trial on simulated data, recovery of local trees was similar to that of LAMARC (Kuhner et al. Genetics 156:1393-1401, 2000a), a sampler which uses the full model.

Detection of Mendelian consistent genotyping errors in pedigrees.

Detection of genotyping errors is a necessary step to minimize false results in genetic analysis. This is especially important when the rate of genotyping errors is high, as has been reported for high-throughput sequence data. To detect genotyping errors in pedigrees, Mendelian inconsistent (MI) error checks exist, as do multi-point methods that flag Mendelian consistent (MC) errors for sparse multi-allelic markers. However, few methods exist for detecting MC genotyping errors, particularly for dense variants on large pedigrees. Here, we introduce an efficient method to detect MC errors even for very dense variants (e.g., SNPs and sequencing data) on pedigrees that may be large. Our method first samples inheritance vectors (IVs) using a moderately sparse but informative set of markers using a Markov chain Monte Carlo-based sampler. Using sampled IVs, we considered two test statistics to detect MC genotyping errors: the percentage of IVs inconsistent with observed genotypes (A1) or the posterior probability of error configurations (A2). Using simulations, we show that this method, even with the simpler A1 statistic, is effective for detecting MC genotyping errors in dense variants, with sensitivity almost as high as the theoretical best sensitivity possible. We also evaluate the effectiveness of this method as a function of parameters, when including the observed pattern for genotype, density of framework markers, error rate, allele frequencies, and number of sampled inheritance vectors. Our approach provides a line of defense against false findings based on the use of dense variants in pedigrees.

Joint inference of identity by descent along multiple chromosomes from population samples.

There has been much interest in detecting genomic identity by descent (IBD) segments from modern dense genetic marker data and in using them to identify human disease susceptibility loci. Here we present a novel Bayesian framework using Markov chain Monte Carlo (MCMC) realizations to jointly infer IBD states among multiple individuals not known to be related, together with the allelic typing error rate and the IBD process parameters. The data are phased single nucleotide polymorphism (SNP) haplotypes. We model changes in latent IBD state along homologous chromosomes by a continuous time Markov model having the Ewens sampling formula as its stationary distribution. We show by simulation that this model for the IBD process fits quite well with the coalescent predictions. Using simulation data sets of 40 haplotypes over regions of 1 and 10 million base pairs (Mbp), we show that the jointly estimated IBD states are very close to the true values, although the presence of linkage disequilibrium decreases the accuracy. We also present comparisons with the ibd_haplo program, which estimates IBD among sets of four haplotypes. Our new IBD detection method focuses on the scale between genome-wide methods using simple IBD models and complex coalescent-based methods that are limited to short genome segments. At the scale of a few Mbp, our approach offers potentially more power for fine-scale IBD association mapping.

Using parent and youth reports from the Behavior Assessment System for Children, Second Edition to identify individuals at clinical high-risk for psychosis.

Brief self-report screening can help facilitate early identification of individuals at risk for or in early stages of psychosis. Existing screening tools focus on self-reported attenuated positive symptoms to detect potential risk; however, parent reports may also be helpful for assessing symptoms, especially in younger patients. Recent evidence has shown that the "atypicality" scale within the self-report form of the Behavior Assessment System for Children, Second Edition (BASC-2) may be useful for identifying high-risk youth within a more clinically comprehensive and potentially minimally stigmatizing format. The BASC-2 parent report form also includes the atypicality scale, but no research has investigated the relation of this scale to psychosis risk. The aim of the current study is to evaluate the association of parent along with youth reports of BASC-2 atypicality with attenuated positive symptoms as assessed by the Structured Interview for Psychosis-Risk Syndromes (SIPS), in a sample of help-seeking adolescents (n=63). Results indicate that both parent and youth reports of atypicality predict clinician-rated symptoms. Moreover, the combination of parent and youth report significantly improved prediction of SIPS scores over either single-informant scale. These findings suggest that parent report scales, as ascertained through part of a larger, commonly used measure, may help identify youth at risk for psychosis, particularly if used in conjunction with youth self-report.

Identifying youth at risk for psychosis using the Behavior Assessment System for Children, Second Edition.

Identification of youth at risk for or with early psychosis has become the focus of many research and clinical initiatives, as early intervention may be linked to better long-term outcomes. Efforts to facilitate identification have led to the development of several self-report instruments that intend to quickly assess "attenuated" psychosis, potentially screening people for further evaluation. The widely used Behavior Assessment System for Children, Second Edition (BASC-2) includes the atypicality scale, a scale that may be useful for risk screening as it is designed to recognize emerging symptoms of psychosis. The current study aimed to evaluate the utility of the BASC-2 for identifying youth at high clinical risk or with early psychosis within a sample of 70 help-seeking participants aged 12-22. Atypicality scores were compared to risk status (low-risk, high-risk or early psychosis) as determined by the clinician-administered Structured Interview for Psychosis-Risk Syndromes (SIPS). The relative accuracy of the atypicality scale was evaluated against three self-report screeners specifically designed to identify this population. Results indicate that the BASC-2 atypicality scale may be a useful tool for identifying youth in early stages of psychosis. Moreover, the atypicality scale is comparable if not superior to other specialized risk screening instruments in terms of predictive ability. Given the widespread use of the BASC-2 across educational and mental health settings, evidence for convergent validity between the BASC-2 atypicality scale and SIPS diagnoses has the potential to make screening available to a greater population and facilitate earlier detection and intervention.

GIGI: an approach to effective imputation of dense genotypes on large pedigrees.

Recent emergence of the common-disease-rare-variant hypothesis has renewed interest in the use of large pedigrees for identifying rare causal variants. Genotyping with modern sequencing platforms is increasingly common in the search for such variants but remains expensive and often is limited to only a few subjects per pedigree. In population-based samples, genotype imputation is widely used so that additional genotyping is not needed. We now introduce an analogous approach that enables computationally efficient imputation in large pedigrees. Our approach samples inheritance vectors (IVs) from a Markov Chain Monte Carlo sampler by conditioning on genotypes from a sparse set of framework markers. Missing genotypes are probabilistically inferred from these IVs along with observed dense genotypes that are available on a subset of subjects. We implemented our approach in the Genotype Imputation Given Inheritance (GIGI) program and evaluated the approach on both simulated and real large pedigrees. With a real pedigree, we also compared imputed results obtained from this approach with those from the population-based imputation program BEAGLE. We demonstrated that our pedigree-based approach imputes many alleles with high accuracy. It is much more accurate for calling rare alleles than is population-based imputation and does not require an outside reference sample. We also evaluated the effect of varying other parameters, including the marker type and density of the framework panel, threshold for calling genotypes, and population allele frequencies. By leveraging information from existing genotypes already assayed on large pedigrees, our approach can facilitate cost-effective use of sequence data in the pursuit of rare causal variants.

A system for exact and approximate genetic linkage analysis of SNP data in large pedigrees.

MOTIVATION: The use of dense single nucleotide polymorphism (SNP) data in genetic linkage analysis of large pedigrees is impeded by significant technical, methodological and computational challenges. Here we describe Superlink-Online SNP, a new powerful online system that streamlines the linkage analysis of SNP data. It features a fully integrated flexible processing workflow comprising both well-known and novel data analysis tools, including SNP clustering, erroneous data filtering, exact and approximate LOD calculations and maximum-likelihood haplotyping. The system draws its power from thousands of CPUs, performing data analysis tasks orders of magnitude faster than a single computer. By providing an intuitive interface to sophisticated state-of-the-art analysis tools coupled with high computing capacity, Superlink-Online SNP helps geneticists unleash the potential of SNP data for detecting disease genes. RESULTS: Computations performed by Superlink-Online SNP are automatically parallelized using novel paradigms, and executed on unlimited number of private or public CPUs. One novel service is large-scale approximate Markov Chain-Monte Carlo (MCMC) analysis. The accuracy of the results is reliably estimated by running the same computation on multiple CPUs and evaluating the Gelman-Rubin Score to set aside unreliable results. Another service within the workflow is a novel parallelized exact algorithm for inferring maximum-likelihood haplotyping. The reported system enables genetic analyses that were previously infeasible. We demonstrate the system capabilities through a study of a large complex pedigree affected with metabolic syndrome. AVAILABILITY: Superlink-Online SNP is freely available for researchers at http://cbl-hap.cs.technion.ac.il/superlink-snp. The system source code can also be downloaded from the system website. CONTACT: omerw@cs.technion.ac.il SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Computationally efficient multipoint linkage analysis on extended pedigrees for trait models with two contributing major Loci.

We have developed a computationally efficient method for multipoint linkage analysis on extended pedigrees for trait models having a two-locus quantitative trait loci (QTL) effect. The method has been implemented in the program, hg_lod, which uses the Markov chain Monte Carlo (MCMC) method to sample realizations of descent patterns conditional on marker data, then calculates the trait likelihood for each realization by efficient exact computation. Given its computational efficiency, hg_lod can handle data on large pedigrees with a lot of unobserved individuals, and can compute accurate estimates of logarithm of odds (lod) scores at a much larger number of hypothesized locations than can any existing method. We have compared hg_lod to lm_twoqtl, the first publically available linkage program for trait models with two major loci, using simulated data. Results show that our method is orders of magnitude faster while the accuracy of QTL localization is retained. The efficiency of our method also facilitates analyses with multiple trait models, for example, sensitivity analysis. Additionally, since the MCMC sampling conditions only on the marker data, there is no need to resample the descent patterns to compute likelihoods under alternative trait models. This achieves additional computational efficiency.

Medical management of children with achondroplasia: evaluation of an Australasian cohort aged 0-5 years.

AIMS: Achondroplasia is the most common form of osteochondrodysplasia and is associated with a number of life-threatening complications. The complexity of the condition led to the development of Heath Supervision Guidelines published by the American Academy of Pediatrics in 1995 and revised in 2005. There remains limited population-based information on utilisation of medical and therapy services for children with achondroplasia. Increased information regarding use of these services will assist in future service development. METHODS: Data regarding frequency and timing of medical and allied health consultations, investigations and interventions were collected from 53 Australasian families via questionnaire, based on recommendations of the Health Supervision Guidelines, an expert reference group and literature review. RESULTS: Rates varied with age for medical consultations (geneticist, paediatric rehabilitation physician/paediatrician, respiratory physician, orthopaedic consultant, neurologist, neurosurgeon), medical investigations (sleep study, magnetic resonance imaging/computed tomography), operative procedures (brain-stem decompression, tonsillectomy/adenoidectomy, shunt insertion, shunt revision and insertion of grommets) and allied health consultations (physiotherapist, occupational therapist, speech pathologist, dietician and orthotist). CONCLUSIONS: Access to geneticists and paediatricians within the first year is high as recommended by the 2005 American Academy of Pediatrics guidelines. Utilisation of craniocervical magnetic resonance imaging/computed tomography, polysomnography studies and formal speech review appears low, reflecting more emphasis on clinical monitoring for cervical cord compression and disordered sleep breathing as well as possible difficulties in accessing services for polysomnography and speech pathology. Grommet insertion, tonsillectomy/adenoidectomy and cervicomedullary decompression rates are similar to results reported previously. Over half of the children accessed physiotherapy and/or occupational therapy services, warranting consideration of these professionals in future guideline recommendations.

Using a nursing productivity committee to achieve cost savings and improve staffing levels and staff satisfaction.

Challenged by rising costs, higher registered nurse vacancy rates and declining staff morale, a Nursing Productivity Committee was formed to analyze productive and nonproductive hours and seek improvements in our staffing models and scheduling processes. The changes implemented led to lower nurse to patient ratios, better control of labor costs, elimination of agency staff, greater staff satisfaction, and introduction of new technologies. Nurse managers, nursing supervisors, and frontline staff are now more knowledgeable and empowered to use creative solutions to manage their budgets and schedules in these times of fluctuating census and varying vacancy rates.