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PubMed2006

One percent ability and ninety-nine percent perspiration: a study of a Japanese memorist.

In 1987, Hideaki Tomoyori, a Japanese memorist, set a world record for reciting the first 40,000 digits of pi. The authors report results from a series of tests that give a view of Tomoyori's memory performance compared with that of a control group, matched for age and educational level. He showed very good scores on tasks with digits, such as digit memory span tasks and 5 x 5 number matrix learning, although some of the control participants were nearly as good. In contrast, his performance was not particularly good for learning word lists and story recall. Overall, his performance on the tasks does not suggest that he has superior cognitive abilities. We believe that his extraordinary memory performance in reciting the digits of pi results from his effective use of a combination of digit-syllable transformations and imagery mnemonics developed from extensive practice. These results are consistent with the skilled memory framework.

Aged↗
PubMed2007

The semantic and episodic subcomponents of famous person knowledge: dissociation in healthy subjects.

Fifty-two subjects between ages 40 and 79 years were administered a questionnaire assessing their ability to recall semantic information about famous people from 4 different decades and to recollect its episodic source of acquisition together with autonoetic consciousness via the remember-know paradigm. In addition, they underwent a battery of standardized neuropsychological tests to assess episodic and semantic memory and executive functions. The analyses of age reveal differences for the episodic source score but no differences between age groups for the semantic scores within each decade. Regardless of the age of people, the analyses also show that semantic memory subcomponents of the famous person test are highly associated with each other as well as with the source component. The recall of semantic information on the famous person test relies on participants' semantic abilities, whereas the recall of its episodic source depends on their executive functions. The present findings confirm the existence of an episodic-semantic distinction in knowledge about famous people. They provide further evidence that personal source and semantic information are at once distinct and highly interactive within the framework of remote memory.

Adult↗
PubMed2006

Model-based analysis of tiling-arrays for ChIP-chip.

We propose a fast and powerful analysis algorithm, titled Model-based Analysis of Tiling-arrays (MAT), to reliably detect regions enriched by transcription factor chromatin immunoprecipitation (ChIP) on Affymetrix tiling arrays (ChIP-chip). MAT models the baseline probe behavior by considering probe sequence and copy number on each array. It standardizes the probe value through the probe model, eliminating the need for sample normalization. MAT uses an innovative function to score regions for ChIP enrichment, which allows robust P value and false discovery rate calculations. MAT can detect ChIP regions from a single ChIP sample, multiple ChIP samples, or multiple ChIP samples with controls with increasing accuracy. The single-array ChIP region detection feature minimizes the time and monetary costs for laboratories newly adopting ChIP-chip to test their protocols and antibodies and allows established ChIP-chip laboratories to identify samples with questionable quality that might contaminate their data. MAT is developed in open-source Python and is available at http://chip.dfci.harvard.edu/ approximately wli/MAT. The general framework presented here can be extended to other oligonucleotide microarrays and tiling array platforms.

Algorithms↗
PubMedDate not supplied

Creating and validating practical measures for assessing public health practices in local communities.

Efforts to develop a surveillance system to measure local public health performance were initiated in 1991. The organizing framework for the proposed system consisted of three core functions formulated by the Institute of Medicine and linked with 10 practices previously defined. A surveillance protocol was developed using local public health jurisdictions rather than specific agencies within the jurisdictions, as the units of study. Selection of 84 indicators was assisted by follow-up study of a group of departments analyzed in 1979 and by review of recent public health literature. Each of the 84 performance indicators was linked to one of the 10 practices. Responses to the survey were obtained from local health department directors. Results yielded scores for the surveyed jurisdiction with regard to adequacy of performance for each practice, the proportional contribution to performance by the local health department, and the identification of other providers contributing to the coverage of each practice within the jurisdiction. A shortened version of the protocol (26 indicators) was tested in all local jurisdictions in six states and shown to correlate reliably with scores obtained from the longer protocol for overall public health performance, as well as for performance of each of the three core functions and for some of the 10 practices. A subset of four indicators was shown to predict reliably the overall score. The findings support the proposition that public health practice can be defined, measured, and monitored and that current widely accepted definitions of core functions and practices have utility. Measurement and surveillance tools for these functions and practices are available and tested.

Community Health Services↗
PubMed1998

Guideline generation from data by induction of decision tables using a Bayesian network framework.

Decision tables can be used to represent practice guidelines effectively. In this study we adopt the powerful probabilistic framework of Bayesian Networks (BN) for the induction of decision tables. We discuss the simplest BN model, the Naive Bayes and extend it to the Two-Stage Naive Bayes. We show that reversal of edges in Naive Bayes and Two-stage Naive Bayes results in simple decision table and hierarchical decision table respectively. We induce these graphical models for dementia severity staging using the Clinical Dementia Rating Scale (CDRS) database from the University of California, Irvine, Alzheimer's Disease Research Center. These induced models capture the two-stage methodology clinicians use in computing the global CDR score by first computing the six category scores of memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care, and then the global CDRS. The induced Two-Stage models also attain a clinically acceptable performance when compared to domain experts and could serve as useful guidelines for dementia severity staging.

Algorithms↗
PubMed2026

CRISPGen: A deep generative framework for multi-objective CRISPR/Cas9 guide RNA design via Conditional Latent Diffusion and Dual-Critic Reinforcement Learning.

MOTIVATION: The CRISPR-Cas9 system offers transformative potential for precision genome editing, yet its clinical translation remains constrained by the risk of unintended off-target double-strand breaks. While current discriminative models excel at evaluating pre-specified candidate guides, resolving the fundamental antagonism between on-target cleavage efficiency and off-target specificity within a fixed sequence search space remains a major challenge. RESULTS: We present CRISPGen, a unified deep generative framework that reframes sgRNA design as a multi-objective constrained sequence synthesis problem. It integrates (i) DNABERT-2 genomic-language embeddings, (ii) a conditional latent diffusion generator conditioned on a user-specified on-target efficiency target, and (iii) a dual-critic reinforcement-learning (RL) stage that couples a frozen on-target efficiency critic with a cross-attention off-target discriminator (validation Pearson R=0.8157) trained on a unified corpus of experimental off-target events from six detection platforms. Across 1000 generated sgRNAs, CRISPGen reduces the mean off-target discriminator score by 99.7% relative to the pre-RL baseline and, under an exhaustive whole-genome screen of all 302,631,056 NGG PAM sites in GRCh38, yields zero perfect-match and only 55 one-mismatch genomic hits. We further show, transparently, that the internal on-target critic saturates under RL optimization - an instance of Goodhart's Law - and therefore assess on-target viability using an independent external CRISPRon screen (mean 47.10/100). Repeating the RL fine-tuning stage under three random seeds (with the diffusion generator, DNABERT-2 embeddings, and off-target discriminator held fixed) yields a stable operating point across seeds. Full diversity, per-mismatch, and reproducibility statistics are reported in the Results. AVAILABILITY: Source code is available at https://github.com/malekpouri/CRISPGen; the pre-trained checkpoints and the 3,000,000-sequence library are hosted on Hugging Face (https://huggingface.co/malekpouri/CRISPGen-Checkpoints) and archived on Zenodo under DOI 10.5281/zenodo.21428641.

CRISPR-Cas9↗
PubMed2006

Diet quality among Yup'ik Eskimos living in rural communities is low: the Center for Alaska Native Health Research Pilot Study.

OBJECTIVE: The objectives of this pilot study were to describe the nutrient intake of Yup'ik Eskimos in comparison with national intake, identify dietary sources of key nutrients, and assess the utility of the Healthy Eating Index (HEI) to measure diet quality of Yup'ik Eskimos living in rural Alaskan Native communities. PARTICIPANTS AND DESIGN: A single 24-hour recall was collected from 48 male and 44 female Yup'ik Eskimos (aged 14 to 81 years), who resided in three villages in the Yukon Kuskokwim River Delta, AK, during September 2003. MAIN OUTCOME MEASURES: HEI scores, nutrient intake, and traditional food intake. STATISTICAL ANALYSES PERFORMED: Spearman correlations for associations between variables. RESULTS: Youth scored higher than elders despite similar nutrient intakes. Overall diet quality was generally low; 63% of all participants' diets were classified as poor. Although the HEI serves to identify areas of concern with respect to diet quality, it is limited in its ability to detect the positive value of traditional foods. CONCLUSIONS: Traditional foods and healthful market foods, including rich sources of fiber and calcium, should be encouraged. Although traditional foods were important sources of energy and nutrients, market foods composed the preponderance of the diet, emphasizing the importance of appropriately modifying a diet quality index based on a Western framework, such as the HEI.

Adolescent↗
PubMed2001

Collaborative exercise on the use of FISH chromosome painting for retrospective biodosimetry of Mayak nuclear-industrial personnel.

PURPOSE: To investigate within the framework of a multilaboratory study the suitability of FISH chromosome painting to measure so-called stable translocations in peripheral lymphocytes of Mayak nuclear-industrial workers (from the Southern Urals) and their use for retrospective biodosimetry. MATERIALS AND METHODS: Chromosime analyses were carried out from 69 workers who had received protracted occupational radiation exposures (0.012-6.065 Gy) up to approximately 40 years before blood sampling. Twenty-one unexposed people living in the same area were controls. A multicolour FISH-painting protocol with the target chromosomes 1, 4 and 8 simultaneously with a pancentromeric probe was used to score potentially transmissible chromosome-type aberrations (reciprocal translocations 2B and related 'one-way' patterns I-III according to the S&S classification). RESULTS: Individual biodosimetry estimates were obtained in terms of these potentially long-term surviving aberration types based on the linear component of a low dose-rate gamma-ray calibration curve produced using identical staining and scoring protocols. For comparison, the workers personal and total background doses were converted to red bone marrow doses. The estimated doses were mainly lower than would be predicted by the calibration curve, particularly at accumulated higher dose levels. CONCLUSIONS: Owing to the limited life-time of circulating T-lymphocytes, the long-term persistence of translocations in vivo requires the assumption of a clonal repopulation of these naturally senescing cells from the haemopoietic stem cell compartments. Obviously such a replacement cannot be fully achieved, leading to a temporal decline even of the yield of transmissible aberrations types. Assuming further a highly selective capacity of stem cells against any type of chromosomal damage and the fact that one must rely on partial genome findings, the potential of FISH chromosome painting for retrospective dose reconstruction is probably limited to a decade or so after high-level protracted radiation exposure.

Adult↗
PubMed2025

Baseline metabolomic profile as potential biomarker for weight change after Roux-en-Y gastric bypass (RYGB) surgery.

Metabolic and bariatric surgery (MBS) is the most effective intervention for sustained weight loss and cardiometabolic improvement in individuals with severe obesity. However, long-term outcomes vary, with many patients experiencing weight regain. The biological determinants of this variability remain incompletely understood. Given the integrative nature of the metabolome-capturing interactions among host genetics, diet, microbiota, and environmental exposures-we hypothesized that baseline circulating metabolites could stratify individuals into distinct long-term weight trajectory groups. We profiled untargeted fasting plasma metabolites in a nested case-control study within the Longitudinal Assessment of Bariatric Surgery (LABS-2) cohort. From these metabolites, a 13-metabolite risk score (MetRS) predictive of weight regain five years after Roux-en-Y gastric bypass was derived. The MetRS, which captures pathways including fatty acid oxidation, bile acid conjugation, and microbial-host co-metabolism, outperformed clinical variables in predicting long-term weight outcomes. Its performance was evaluated in two independent cohorts, including one assessed a median of seven years post-surgery. Genomic analyses identified common variants in loci including AGXT2 and SLC7A5 associated with key MetRS metabolites, suggesting a heritable component to the observed metabolic signature. Together, these findings lay the groundwork for a clinically actionable framework to identify individuals at risk for weight recidivism and support the integration of metabolic profiling into preoperative assessment for personalized obesity care.

Journal Article↗
PubMed2006

Psychometric evaluation and establishing norms of Croatian SF-36 health survey: framework for subjective health research.

AIM: To provide population norms and evaluate metric characteristics of the Croatian version of SF-36 Health Survey, an internationally used instrument for assessing subjective health. METHOD: The questionnaire was administered to a representative sample of Croatian adult population (n=9070). Three standard techniques were used in data analysis: reliability tests, descriptive statistics, and factor analysis. The population norms were presented in two standard forms--the SF-36 Health Profile and percentile values for different age groups of men and women. RESULTS: The Croatian version of the SF-36 had generally acceptable metric characteristics including its construct validity. The internal consistency of the SF-36 scales ranged from 0.78 to 0.94. Pearson bivariate correlations showed moderate associations between SF-36 scales, and factor analysis provided one latent dimension underlying all SF-36 scales which explained 63.3% of the score variance. Less favorable results were obtained concerning its discriminative validity. All SF-36 scales showed negative asymmetry of score distributions, and some had high floor and ceiling effects--skewness estimations ranged from -0.12 to -0.91, with the highest floor effect of 30% and ceiling effect of 63%. CONCLUSION: Presented population norms for the Croatian version of SF-36 Health Survey showed that SF-36 may be used as a valid and reliable instrument in research in subjective health of Croatian population.

Adolescent↗
PubMed2006

The impact of susceptibility gradients on cartesian and spiral EPI for BOLD fMRI.

High sensitivity to magnetic susceptibility changes and accurate localization of functional activations are key requisites for pulse sequences used for BOLD fMRI. This paper seeks to develop a framework for analysing the performance of various k-space sampling techniques in this respect, with special emphasis on spiral EPI (spiral) and cartesian EPI (EPI) and their performance under influence of induced field gradients (SFGs) and stochastic noise. A numerical method for calculating synthetic MR images is developed and used to simulate BOLD fMRI experiments using EPI and spirals. The data is then examined for activation using a pixel-wise t test. Nine subjects are scanned with both techniques while performing a motor task. SPM99 is used for analysing the experimental data. The simulated spirals provide generally higher t scores at low SFGs but lose more strength than EPI at higher SFGs, where EPI activation is offset from the true position. In the primary motor area spirals provide significantly higher t scores (P < 0.0002). In-plane variation of EPI is higher in phase-encoding direction than in frequency-encoding direction (P < 0.003). In the low SFG areas spirals provide stronger activation than EPI and less spatial variability. Thus, spirals are recommended for fMRI in motor area and language areas.

Algorithms↗
PubMed2005

Validity and reliability of the Italian version of the Chronic Liver Disease Questionnaire (CLDQ-I) for the assessment of health-related quality of life.

BACKGROUND: The Chronic Liver Disease Questionnaire is a specific health-related quality of life assessment designed for patients with liver diseases. AIM: The aim of this paper is to report on the validity, reliability and sensitivity to change of the Italian version (Chronic Liver Disease Questionnaire-I) in subjects with HCV infection. SUBJECTS: The Chronic Liver Disease Questionnaire-I was administered to 350 subjects with HCV infection together with the World Health Organization Quality of Life Assessment, abbreviated version, a generic quality of life assessment. METHODS: The instrument was translated from English, backtranslated and reviewed in focus groups in the framework of a large multicentre study. Exploratory factor analysis identified five factors accounting for 65% of the variance of Chronic Liver Disease Questionnaire-I items and only partially overlapping with those found in the original version. RESULTS: The Chronic Liver Disease Questionnaire-I proved to discriminate between subjects with and without comorbid diseases at baseline (t-test = 3.59, p < 0.001). Test-retest reliability was moderate (ICC = 0.60). The Chronic Liver Disease Questionnaire-I was sensitive to change in patients who deteriorated after one month of treatment. Change in the overall Chronic Liver Disease Questionnaire-I score in deteriorated patients was correlated with changes in World Health Organization Quality of Life Assessment, abbreviated version scores in the physical, psychological and environment, but not in the social area. CONCLUSIONS: The Italian version of Chronic Liver Disease Questionnaire is a valid and reliable instrument to be used in cross-sectional and longitudinal studies.

Chronic Disease↗
PubMed2004

A cross-media content analysis of motivational themes in direct-to-consumer prescription drug advertising.

BACKGROUND: Direct-to-consumer (DTC) advertising of prescription drugs is a widely discussed issue in health care. However, little is known about the characteristics of the motivational themes used in this type of advertising. OBJECTIVES: The aim of this study was to investigate the concurrent presentation of motivational themes in DTC print and television advertisements. METHODS: The content analyses focused on advertisements of 2 targeted drug classes (cyclooxygenase-2 enzyme inhibitors and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) in magazines and on television. Targeted print advertisements (for celecoxib, rofecoxib, atorvastatin, pravastatin, and simvastatin) from September to December 2001 and targeted television advertisements (for celecoxib, rofecoxib, and simvastatin) from November 2001 were investigated. The motivational themes were assessed using a theoretical framework based on self-regulatory focus theory and cultural orientation. Self-regulatory focus was examined in terms of goal orientation (promotion vs prevention) and emotional aspects, (e.g., cheerfulness, dejection, quiescence, agitation). The cultural orientation was examined in terms of individualism versus collectivism. The visual-verbal match was categorized as direct if the audio and visual information was semantically redundant, as partial if it was partially related, and as no match at all if it was different or conflicting. RESULTS: Twelve print advertisements in 10 magazines and 4 television advertisements on 4 television networks were examined; the interrater reliability scores from 3 independent, trained judges ranged from 0.93 to 0.99. The score was low (0.57) in the visual-verbal match measurement for television advertisements. Products in the same category appeared to be promoted using different self-regulatory foci. For example, celecoxib and atorvastatin advertisements tended to be promotion oriented, whereas pravastatin advertisements tended to be prevention oriented. Motivational themes were found throughout the print advertisements (e.g., pictures, headlines, main text). Only a few advertisements illustrated factual information about a product in a pictorial format. The cultural orientation of the advertisements was similar across brands, with individualistic appeals being common. On television, visual-verbal matches (either direct or partial matches) were generally found, except in the section where risk information was presented. CONCLUSION: In this content analysis, prescription drugs in the same class appeared to be promoted using different self-regulatory foci, but individualistic appeals were found more often than collectivistic appeals across brands.

Advertising↗
PubMed1999

Knowledge about the assessment and management of undernutrition: a pilot questionnaire in a UK teaching hospital.

BACKGROUND & AIMS: The detection, prevention and treatment of undernutrition in hospitals is often poor. This study assesses the knowledge about undernutrition of staff in a UK teaching hospital. METHODS: Twenty nine doctors, 65 final year medical students, 45 nurses, 11 dietitians, and 11 pharmacists anonymously completed a questionnaire of 20 multiple choice questions. One of five possible answers was considered correct. Twelve questions were about adult nutritional assessment and requirements, five about oral/enteral nutrition and three about parenteral nutrition. RESULTS: Dietitians scored significantly more (median 16) than the other groups (doctors: seven, medical students: eight, nurses: seven and pharmacists: nine) (P < 0.0001). Medical students scored more than doctors (P < 0.001). Examples of areas in which knowledge could be improved are: 67% respondents thought the prevalence of hospital undernutrition to be less than 30%. While 91% of respondents correctly chose a well 70 kg man to need about 2000 kcal/day, only 23% knew that approximately the same amount was needed for a febrile post-operative patient. Sixteen percent knew antibiotic treatment to be the most common reason for enteral feeding-related diarrhoea. CONCLUSIONS: Knowledge about the assessment and management of undernutrition among doctors, medical students, nurses and pharmacists was poor. This questionnaire provides a framework for teaching and auditing the effectiveness of an educational program.

Adult↗
PubMed2001

Relationship of core self-evaluations traits--self-esteem, generalized self-efficacy, locus of control, and emotional stability--with job satisfaction and job performance: a meta-analysis.

This article presents meta-analytic results of the relationship of 4 traits--self-esteem, generalized self-efficacy, locus of control, and emotional stability (low neuroticism) with job satisfaction and job performance. With respect to job satisfaction, the estimated true score correlations were .26 for self-esteem, .45 for generalized self-efficacy, .32 for internal locus of control, and .24 for emotional stability. With respect to job performance, the correlations were .26 for self-esteem, .23 for generalized self-efficacy, .22 for internal locus of control, and .19 for emotional stability. In total, the results based on 274 correlations suggest that these traits are among the best dispositional predictors of job satisfaction and job performance. T. A. Judge, E. A. Locke. and C. C. Durham's (1997) theory of core self-evaluations is used as a framework for discussing similarities between the 4 traits and their relationships to satisfaction and performance.

Affect↗
PubMed1994

Can we define indispensable amino acid requirements and assess protein quality in adults?

Adult indispensable amino acid (IAA) requirements, as exemplified by lysine, are examined in a metabolic framework in which dietary IAA are needed to replace both regulatory losses (extrinsic and adaptive IAA oxidation) and obligatory losses (intrinsic metabolic consumption). Thus requirements need to be defined as minimal, operational and optimal. For minimal needs, animal studies show different patterns for maintenance and growth, with lower lysine and leucine in the former compared with the latter pattern, which mirrors tissue protein. Reliable human studies also confirm a low minimum lysine requirement, 15 mg/kg or less, compared with growth needs, supporting the 1985 FAO adult value and lower than the value for preschool children proposed as the basis of a scoring pattern for adults by FAO/WHO in 1991. This pattern derives from studies in children depositing considerable nitrogen and is unsuitable for an adult scoring pattern. Stable isotope lysine balance studies do not provide unequivocal support for an increased minimum requirement value for lysine. As for operational requirements, these are higher because of increased regulatory losses due to the higher intakes of IAA in habitual diets and because of the diurnal feeding pattern. Definition of optimal needs requires value judgements of the beneficial metabolic influence of intakes in excess of minimal. This influence (the anabolic drive) is a tangible phenomenon in growing animals, but is yet to be identified in humans. Thus optimal requirements are not yet definable, and there is no suitable scoring pattern to replace the 1985 FAO values, which may accurately reflect minimal needs.

Adult↗
PubMed2002

A computer-based OSCE station to measure competence in evidence-based medicine skills in medical students.

OBJECTIVE: To create a feasible, valid, and reliable tool to measure third-year medical students' skills in evidence-based medicine (EBM). DESCRIPTION: EBM skills-asking clinical questions, finding appropriate medical information resources, and appraising and applying them to patients-involve higher-order critical thinking abilities and are essential to being a competent physician. Students at our institution must pass a required OSCE exam at the end of their third year. As part of this exam, we developed a new 20-minute computer-based station to assess students' EBM skills. Using a specific case scenario, we asked the students to (1) ask a question using the population/intervention/comparison/outcome (PICO) framework; (2) generate appropriate search terms, given a specific question; and (3) select an appropriate abstract to answer a given question and state why two other abstracts were not appropriate. Prior to the assessment, we determined grading and passing criteria for each of the three components and for the station overall. Of the 140 students who completed the station, the percentages that passed the components were 71%, 81%, and 49% respectively, with only 29% passing all three parts. Preliminary analysis of psychometric properties of the station shows very good to excellent interrater reliability, with 65%, 67%, and 94% agreement on the scoring for the components, and kappas of.64,.82, and.94, respectively. DISCUSSION: Although there are many curricula for teaching EBM concepts, there are few tools to measure whether students are competent in applying their EBM skills. Our pilot station appears to be an innovative and promising tool to measure several EBM skills independently. By being computer-based, it is relatively simple to administer, grade, and evaluate. While preliminary data show good inter-rater reliability with our use of a single case, future work will include further testing of reliability and assessment of different types of cases. We will also use the results of this assessment to drive continuous improvement in our EBM curriculum. The students who completed this pilot station had not received an extensive formal EBM curriculum, whereas future groups will. We also will explore whether scores on our station correlate with those on other OSCE stations that also assess critical thinking skills, or if scores correlate with a student's clinical grades or overall class standing. We hope to test these hypotheses: (1) skills used in EBM are useful and valid measures of critical thinking abilities in learners and (2) tools such as ours will help to measure these essential competencies.

Clinical Competence↗
PubMed2004

[Study of paranoid ideation in college students: an approach using the diathesis-stress model].

A recent study reported that normal people who have social anxiety and attention to social and interpersonal cues show paranoid ideation (Martin & Penn, 2001). The purpose of the present study was to examine whether people with these diatheses show paranoid ideation in the diathesis-stress framework. Questionnaires were administered to 177 college students three times. At Time I, social anxiety and attention to social and interpersonal cues were assessed. These variables were used in Martin and Penn (2001) as the diathesis factor of paranoid ideation. At Time 2, paranoid ideation during the period, and at Time 3, paranoid ideation and stress events between Time 2 and Time 3 were assessed. Setwise hierarchical multiple regression analysis was used to predict the change in the incidence of paranoid ideation from Time 2 to Time 3. Result revealed significant interaction effects between social anxiety and stress. Students with high score on the social anxiety scale showed an increase in paranoid ideation when they experienced more stress events.

Adolescent↗