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PubMed2002

The use of constrained optimization to facilitate admission decisions.

Weighting models do not adequately represent admission goals. A constrained optimization (CO) decision-analysis model is an alternative that allows a more useful and accurate translation of goals in the admission process. CO allows easy translation of class composition objectives into the model. The author used simulated data to demonstrate the CO technique within a medical-school-admission context. Variables related to class diversity and individual achievement were used to select a class from a simulated final applicant pool. Constraints in the model were evaluated for their effects on the class. The model performed well and yielded significant advantages over weighting equations.

Decision Support Techniques↗

PubMed2004

Scoring the computer-based case simulation component of USMLE Step 3: a comparison of preoperational and operational data.

PURPOSE: Operational USMLE(TM) computer-based case simulation results were examined to determine the extent to which rater reliability and regression model performance met expectations based on preoperational data. METHOD: Operational data resulted from Step 3 examinations given between 1999 and 2004. Plots were produced using reliability and multiple correlation coefficients. RESULTS: Operational testing reliabilities increased over the four years but were lower than the preoperational reliability. Multiple correlation coefficient results are somewhat superior to the results reported during the preoperational period and suggest that the operational scoring algorithms have been relatively consistent. CONCLUSIONS: Changes in the rater population, changes in the rating task, and enhancements to the training procedures are several factors that can explain the identified differences between preoperational and operational results. The present findings have important implications for test development and test validity.

Algorithms↗

PubMed2002

Diagnosis and follow-up of infections in intensive care patients: value of C-reactive protein compared with other clinical and biological variables.

OBJECTIVE: To evaluate diagnostic and prognostic values of C-reactive protein (CRP) dosage in critically ill patients. DESIGN: Prospective, observational study. SETTING: Medical intensive care unit (ICU) in a university hospital. PATIENTS: A consecutive series of 74 patients admitted to the ICU. INTERVENTION: CRP measurements at admission and every 4 days thereafter. MEASUREMENTS AND MAIN RESULTS: At admission, 28 patients (38%) had microbiologically proven infections. Compared with uninfected patients, their mean +/- SD CRP level was 191 +/- 123 vs. 83 +/- 91 mg/L (p < .0001), respectively, white blood cell count was 15.3 +/- 7.5 vs. 11.4 +/- 5.3 G/L (p = .01), and the systemic inflammatory response syndrome (SIRS) was present for 96% vs. 67% (p = .008). No threshold value could be identified to discriminate between these two populations. Multivariate analysis retained CRP and SIRS as the only variables independently associated with the presence of an infection. The combination of CRP > or = 50 mg/L with SIRS was identified as the best model to diagnose infection at admission. This multivariate model performed better than temperature, CRP alone, and white blood cell count. Among the 28 infected patients, 10 recovered; CRP values decreased significantly in this population as compared with patients with persistent infection (-130 +/- 110 vs. 12 +/- 97 mg/L, respectively; p = .004). A CRP decrease > or = 50 mg/L between admission and day 4 was the best cutoff value to diagnose recovery (sensitivity 89%, specificity 79%). CONCLUSION: CRP in combination with SIRS was useful to diagnose infection in ICU patients; a CRP decrease > or = 50 mg/L between admission and day 4 was the best predictor of recovery.

Biomarkers↗

PubMed2025

CNV-Finder: Streamlining Copy Number Variation Discovery.

Copy Number Variations (CNVs) play pivotal roles in the etiology of complex diseases and are variable across diverse populations. Understanding the association between CNVs and disease susceptibility is significant in disease genetics research and often requires analysis of large sample sizes. One of the most cost-effective and scalable methods for detecting CNVs is based on normalized signal intensity values, such as Log R Ratio (LRR) and B Allele Frequency (BAF), from Illumina genotyping arrays. In this study, we present CNV-Finder, a novel pipeline integrating deep learning techniques on array data, specifically a Long Short-Term Memory (LSTM) network, to expedite the large-scale identification of CNVs within predefined genomic regions. This facilitates efficient prioritization of samples for time-consuming or costly subsequent analyses such as Multiplex Ligation-dependent Probe Amplification (MLPA), short-read, and long-read whole genome sequencing. We incorporate four genes to establish our methods-Parkin (PRKN), Leucine Rich Repeat And Ig Domain Containing 2 (LINGO2), Microtubule Associated Protein Tau (MAPT), and alpha-Synuclein (SNCA)-which may be relevant to neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Progressive Supranuclear Palsy (PSP), or related disorders such as essential tremor (ET). By training our models on expert-annotated samples and validating them across diverse cohorts, including those from the Global Parkinson's Genetics Program (GP2) and additional dementia-specific databases, we demonstrate the efficacy of CNV-Finder in accurately detecting deletions and duplications. Our pipeline outputs app-compatible files for visualization within CNV-Finder's interactive web application. This interface enables researchers to review predictions and filter displayed samples by model prediction values, LRR range, and variant count in order to explore or confirm results. Our pipeline integrates this human feedback to enhance model performance and reduce false positive rates. Through a series of comprehensive analyses and validations using visual inspection, MLPA, short-read, and long-read sequencing data, we demonstrate the robustness and adaptability of CNV-Finder in identifying CNVs with regions of varied size, probe density, and noise. Our findings highlight the significance of contextual understanding and human expertise in enhancing the precision of CNV identification, particularly in complex genomic regions like 17q21.31. The CNV-Finder pipeline is a scalable, publicly available resource for the scientific community, available on GitHub (https://github.com/GP2code/CNV-Finder; DOI 10.5281/zenodo.14182563). CNV-Finder not only expedites accurate candidate identification but also significantly reduces the manual workload for researchers, enabling future targeted validation and downstream analyses in regions or phenotypes of interest.

Copy Number Variation (CNV)↗

PubMed2001

Liquid/vapor surface tension of metals: embedded atom method with charge gradient corrections.

Molecular dynamics simulations for three embedded atom method (EAM) function sets are used to determine the liquid/vapor surface tension gamma for Al, Ni, Cu, Ag, and Au. The three EAM models differ in both the functional forms employed and the fitting procedure used. All the EAM potentials underestimate gamma but one of the models performs consistently better than the others. We show that including a correction to the local charge density associated with gradients in the density together with exploiting the invariance of the EAM potentials to appropriate transformations in the charge density can lead to improved values for gamma, as well as for solid free surface energies, within existing EAM function sets.

Journal Article↗

PubMed2003

Transition radiation by matter-wave solitons in optical lattices.

We demonstrate that matter-wave solitary pulses formed from Bose condensed atoms moving inside optical lattices continuously radiate dispersive matter waves with prescribed momentum. Our analytical results for the radiation parameters and the soliton decay rate are found to be in excellent agreement with numerical modeling performed for experimentally relevant parameters.

Journal Article↗

PubMed2005

Classifiability-based omnivariate decision trees.

Top-down induction of decision trees is a simple and powerful method of pattern classification. In a decision tree, each node partitions the available patterns into two or more sets. New nodes are created to handle each of the resulting partitions and the process continues. A node is considered terminal if it satisfies some stopping criteria (for example, purity, i.e., all patterns at the node are from a single class). Decision trees may be univariate, linear multivariate, or nonlinear multivariate depending on whether a single attribute, a linear function of all the attributes, or a nonlinear function of all the attributes is used for the partitioning at each node of the decision tree. Though nonlinear multivariate decision trees are the most powerful, they are more susceptible to the risks of overfitting. In this paper, we propose to perform model selection at each decision node to build omnivariate decision trees. The model selection is done using a novel classifiability measure that captures the possible sources of misclassification with relative ease and is able to accurately reflect the complexity of the subproblem at each node. The proposed approach is fast and does not suffer from as high a computational burden as that incurred by typical model selection algorithms. Empirical results over 26 data sets indicate that our approach is faster and achieves better classification accuracy compared to statistical model select algorithms.

Algorithms↗

PubMed1995

Individual differences in infancy and later IQ.

In recent years it has been demonstrated that cognitive development from infancy to later childhood displays some degree of (correlational) continuity. Studies that have demonstrated this continuity are reviewed, focusing on measures of visual information processing, means-ends problem-solving and other cognitive indices of infant performance. Models of continuity are described and evaluated, and the relevance of the findings and models to the Nature-Nurture issue are considered, with particular attention to the related issues of the role of experience in early life, and the extent to which infant development is canalized. Theoretical and practical applications of the research are discussed.

Child↗

PubMed2000

Prospective evaluation of three different models for the pre-operative diagnosis of ovarian cancer.

OBJECTIVE: To test the accuracy of the risk of malignancy index, the revised risk of malignancy index and Tailor's regression model to diagnose malignancy in women with known adnexal masses. DESIGN: Prospective collaborative study. SETTING: Gynaecology Assessment Unit, Department of Obstetrics and Gynaecology, King's College Hospital, London. SAMPLE: Sixty-one women with known adnexal masses were examined pre-operatively. Women were recruited from three South London hospitals. METHODS: The demographic, biochemical and sonographic data recorded for each patient included: age; menopausal status; CA125 levels; tumour volume; ultrasound characteristics; and Doppler blood flow analysis (peak and mean blood velocities, the pulsatility and resistance indices). The diagnosis of malignancy was made for each woman using all three models and the results compared with the final histopathological diagnosis. RESULTS: Thirty-eight women had benign tumours and 23 had ovarian cancer. Women with malignant tumours were significantly older than those with benign masses. There were also significant differences in CA125 levels, locularity, presence of papillary proliferations and ascites between the two groups. Tailor's regression model achieved a 43% sensitivity and 92% specificity in the diagnosis of malignancy. This compared with a 74% sensitivity and 92% specificity with the risk of malignancy model, and a 74% sensitivity and 89% specificity with the revised risk of malignancy model. CONCLUSION: When applied prospectively all three diagnostic models performed less accurately than originally reported, despite clinical signs of malignancy being present in many cases. It is likely that their accuracy would be even less in a population of women in whom there was a substantial clinical uncertainty. Intra-tumoral blood velocity and CA125 levels were the best individual parameters for discrimination between benign and malignant tumours.

Adult↗

PubMed2006

Changes in reaction time and search time with background luminance in the mesopic range.

Vision relies on both rod and cone signals over a large range of ambient illumination that encompasses a number of common situations. It is important, therefore, to understand how performance changes with light level in functional visual tasks. We measured reaction times and search times using achromatic targets to examine the relationship between latency and luminance contrast as a function of background luminance. Visual search was more robust to changes in luminance than reaction time; search performance could be made invariant by scaling the effects of contrast, but the range of reaction time changed significantly over the mesopic range. We also investigated the extent to which two mesopic visual performance models described the dependence of reaction time and search time on stimulus spectra, using coloured stimuli. The 'effective contrast' model that we examined described the spectral dependence of both reaction time and search time well. A model for mesopic luminous efficiency based on reaction times described the spectral dependence of each response only in conditions where there was little influence of chromatic signals.

Adult↗

PubMed1989

Clinical precision of paralleling instruments.

A method for measuring pin- or pinhole-deviation was developed and tested on nine consecutive bridge cases with parallel pin retention, in order to assess paralleling precision of guiding instruments used clinically. Measurements were performed on rubber base impressions including pinholes, involving the use of a stereomicroscope. The maximum pinhole error angle for the bridges investigated ranged between 5.9 and 16.1 degrees. The corresponding interval for abutments was 1.3-10.8 degrees. The experimental observations concerning the rather large values for the greatest pinhole deviation of fitting bridges could be satisfactorily explained theoretically. The results indicated that the magnitude of the largest permissible angular deviation for a restoration with parallel pin retention was significantly larger than that previously presented in the literature. Compared with results from a previously performed model study carried out during ideal preparatory conditions, the current investigation suggested that the paralleling precision of guiding instruments used clinically in fact decreases considerably, remaining, however, at an acceptable level.

Dental Abutments↗

PubMed2002

A nonlinear model of thermoacoustic devices.

This paper presents a nonlinear, time-domain model of thermoacoustic devices based on cross-sectional averaged equations. Heat transfer perpendicular to the device axis--which lies at the core of thermoacoustic effects--is modeled in a novel and more realistic way. Heat conduction in the solid surfaces surrounding the fluid medium is included. Contrary to the previous versions of this model [Watanabe et al., J. Acoust. Soc. Am. 102, 3484-3496 (1997)], the present version does not require artificial damping and is numerically robust. The model performance is illustrated on several examples: a prime mover, an externally driven thermoacoustic refrigerator, and a combined prime mover/refrigerator system.

Acoustics↗

PubMed2000

General coordination principles elucidated by forward dynamics: minimum fatique does not explain muscle excitation in dynamic tasks.

The target article presents a framework for coordination of one- and two-joint muscles in a variety of tasks. Static optimization analyses were performed that minimize muscle fatigue, and it is claimed that the predicted muscle forces account for essential features of EMG activity qualitatively well. However, static optimization analyses use the observed joint moments, which implicitly assumes that they minimize the total muscle fatigue of the task. We use a forward dynamics (i.e., relationship between muscle forces and the kinematics and kinetics of task performance) modeling approach to show that this assumption does not appear to be true in cycling (which was used as an example task in the target article). Our results challenge the hypothesized coordination framework and the underlying concept that general coordination principles for dynamic tasks can be elucidated using inverse-dynamics-based analyses.

Biomechanical Phenomena↗

PubMed2026

Large-scale multiethnic electronic health record resource for diabetes complications research: the North West London Diabetes Cohort (NWLDC) - cohort profile.

PURPOSE: The North West London Diabetes Cohort is established to provide systematic characterisation of a large diabetes population as a foundation for complications research and prognostic modelling. Many predictive modelling studies neglect the essential descriptive characterisation of underlying cohorts, focusing narrowly on model accuracy. This cohort profile addresses this gap by comprehensively describing the demographic composition, clinical characteristics and complication incidence patterns. The notably diverse, multiethnic population enables examination of ethnic disparities and supports future development of reliable prognostic models and evidence-based prevention strategies for diabetes complications. PARTICIPANTS: At baseline, 337 271 patients with diabetes were identified. It includes 279 067 patients with type 2 diabetes, 17 638 with type 1 diabetes, 33 590 with gestational diabetes and 6916 with unspecified diabetes. The earliest diabetes diagnosis dates to January 1932, with data updated to 27 May 2025. FINDINGS TO DATE: This cohort profile describes baseline characteristics of patients with comprehensive data collected on demographics (age, sex, Deprivation Index, ethnicity), clinical measures (glycated haemoglobin, body mass index, blood pressure, lipids and estimated glomerular filtration rate) and 14 major diabetes complications tracked longitudinally. Key findings for patients with type 2 diabetes reveal diabetic retinopathy as the most common complication (74.6 per 1000 person-years), followed by hypertension (51.0) and kidney disease (31.4). Cumulative incidence analyses using the Aalen-Johansen estimator, which accounts for mortality as a competing risk, demonstrated significant ethnic disparities, with black, Asian, mixed and other ethnic groups showing elevated risk compared with white patients. Time-varying Cox models identified strong clustering between cardiovascular and renal complications, confirming a cardiometabolic-renal syndrome. Mental health conditions (depression and anxiety) were prevalent throughout the disease timeline, occurring both before and after diabetes diagnosis. FUTURE PLANS: This cohort will be used as a platform for developing and validating prognostic models for diabetes complications, enabling risk stratification and targeted interventions. Future work will incorporate medication data to refine diabetes type classification, examine the effectiveness of antidiabetic medications in preventing different complications and address demographic differences in prognostic model performance and prediction accuracy. To better characterise lifestyle, further interrogation of electronic health record data will examine recording of advice given, including dietary advice, referral to weight management schemes and presence of alcohol consumption codes.

Humans↗

PubMed2003

Updated gestational age specific birth weight, crown-heel length, and head circumference of Chinese newborns.

OBJECTIVE: To construct gestation specific standards of birth weight, crown-heel length, and head circumference of Chinese infants. DESIGN: A prospective cross sectional population study. METHODS: The birth weight, crown-heel length, and head circumference were prospectively measured using standard equipment in newborns delivered at 24-42 weeks gestation in the maternity units of 10 public hospitals and two private hospitals in Hong Kong. The findings were used to construct gestation specific standards of these variables. The LMS method using maximum penalised likelihood was used to perform model fitting. The results were compared with those obtained from a cohort of infants born in the same locality between 1982 and 1986. RESULTS: From October 1998 to September 2000, a total of 10 032 infants were measured, representing 9.6% of the total deliveries in Hong Kong during that period. An extra 307 infants with gestation < or = 35 weeks were recruited from October 2000 to June 2001. Each of the three variables showed a normal distribution at each gestational week. Gestation specific reference standards for each variable were constructed for male and female infants separately. Comparison with the 1982-1986 cohort showed a significant secular trend to increased birth weight. The trend was small, but significant, for crown-heel length and head circumference. CONCLUSION: These growth standards will provide useful references for the care of newborns of ethnic Chinese origin. These standards, especially that for birth weight, should be updated regularly.

Birth Weight↗

PubMed1995

Angiotensin converting enzyme gene deletion allele is independently and strongly associated with coronary atherosclerosis and myocardial infarction.

OBJECTIVE: To investigate the association of the three angiotensin converting enzyme (ACE) genotypes, DD, ID, and II, with the occurrence or absence of coronary atherosclerosis and with myocardial infarction and hypertension. DESIGN: Cohort analysis study. SETTING: North-Italy reference centre. SUBJECTS: 388 white Italian patients (281 males; mean age 60.7 (SD 12.5) years) with proven coronary atherosclerosis (n = 255) or with angiographically normal coronary arteries (n = 133). A further group of 290 healthy blood donors was tested for allele frequency comparison. INTERVENTIONS: ACE/ID polymorphism was analysed with polymerase chain reaction on DNA from white blood cells. MAIN OUTCOME MEASURES: Coronary atherosclerosis, myocardial infarction, hypertension. RESULTS: The D and I allele frequencies were respectively 0.63 and 0.37 in the overall healthy blood donor group and 0.66 and 0.34 in the overall study group. In the latter, univariate analysis showed (1) that coronary atherosclerosis (255 patients) was associated with the deletion allele, with an odds ratio (OR) of 5.78 for DD/II, P < 0.001, and 2.39 for ID/II, P = 0.006; and (2) that myocardial infarction (154 patients) was associated with the DD genotype (OR DD/II = 2.56, P = 0.007), but not with the ID genotype (OR DD/II = 1.96, P = 0.056). Finally, hypertension proved to be unrelated with the ACE genotype. The distribution between the three genotypes of known risk factors for coronary artery disease was similar. Logistic regression modelling, performed to test the association of the selected risk factors simultaneously with coronary atherosclerosis and myocardial infarction, showed that the deletion allele (whether DD or ID) was the strongest risk factor for atherosclerosis, and that the D allele was significantly associated with the risk of infarction (although to a lesser extent than with coronary atherosclerosis). CONCLUSION: ACE deletion polymorphism is strongly and independently associated with coronary atherosclerosis and, to a lesser extent, with myocardial infarction. As such, the results are analogous to what has already been reported in French white, Japanese, and Welsh coronary patients.

Adolescent↗

PubMed2000

Neural representation of salts in the rat solitary nucleus: brain stem correlates of taste discrimination.

One mechanism of salt taste transduction by gustatory receptor cells involves the influx of cations through epithelial sodium channels that can be blocked by oral application of amiloride. A second mechanism is less clearly defined but seems to depend on electroneutral diffusion of the salt through the tight junctions between receptor cells; this paracellular pathway is insensitive to amiloride. Because the first mechanism is more sensitive to sodium salts and the second to nonsodium salts, these peripheral events could underlie the ability of rats to discriminate sodium from nonsodium salts on the basis of taste. Behavioral experiments indicate that amiloride, at concentrations that are tasteless to rats, impairs a rat's ability to discriminate NaCl from KCl and may do so by making both salts taste like KCl. In the present study, we examined the neural representation of NaCl and KCl (0.05-0.2 M), and mixtures of these salts with amiloride (0, 3, and 30 microM), to explore the neural correlates of this behavioral result. NaCl and KCl were represented by distinct patterns of activity in the nucleus of the solitary tract. Amiloride, in a concentration-dependent manner, changed the pattern for NaCl to one more characteristic of KCl, primarily by reducing activity in neurons responding best to NaCl and sucrose. The effect of amiloride concentration on the response to 0.1 M NaCl in NaCl-best neurons was virtually identical to its effect on behavioral discrimination performance. Modeling the effects of blocking the amiloride-insensitive pathway also resulted in highly similar patterns of activity for NaCl and KCl. These results suggest that activity in both the amiloride-sensitive and -insensitive pathways is required for the behavioral discrimination between NaCl and KCl. In the context of published behavioral data, the present results suggest that amiloride-sensitive activity alone is not sufficient to impart a unique signal for the taste of sodium salts.

Action Potentials↗

PubMed2005

Limbs anthropometry of singleton Chinese newborns of 28-42 weeks' gestation.

Abnormalities of limbs are important features of some syndromes recognizable at birth. The purpose of this study was to establish normal standards of limbs including arm length, arm circumference, upper arm length, lower arm length, leg length, thigh circumference, upper leg length, and lower leg length. 10,226 infants (5,422 males, 4,804 females) with gestation 28-42 weeks from 12 hospitals were included. The LMS method using maximum penalized likelihood was used to perform model fitting of the anthropometric centiles for these parameters. This study provided the first set of references for the limbs of the infants by gestation and gender. Racial differences were found when comparing with other populations. The parameters are useful for evaluation of morphologic disorders involving the limbs.

Americas↗