LLukas22/scidocs huggingface dataset:
Basic Concepts in Population Modeling, Simulation, and Model-Based Drug Development—Part 2: Introduction to Pharmacokinetic Modeling Methods

Population pharmacokinetics is the study of pharmacokinetics at the population level, in which data from all individuals in a population are evaluated simultaneously using a nonlinear mixedeffects model. “Nonlinear” refers to the fact that the dependent variable (e.g., concentration) is nonlinearly related to the model parameters and independent variable(s). “Mixed-effects” refers to the parameterization: parameters that do not vary across individuals are referred to as “fixed effects,” parameters that vary across individuals are called “random effects.” There are five major aspects to developing a population pharmacokinetic model: (i) data, (ii) structural model, (iii) statistical model, (iv) covariate models, and (v) modeling software. Structural models describe the typical concentration time course within the population. Statistical models account for “unexplainable” (random) variability in concentration within the population (e.g., betweensubject, between-occasion, residual, etc.). Covariate models explain variability predicted by subject characteristics (covariates). Nonlinear mixed effects modeling software brings data and models together, implementing an estimation method for finding parameters for the structural, statistical, and covariate models that describe the data.1 A primary goal of most population pharmacokinetic modeling evaluations is finding population pharmacokinetic parameters and sources of variability in a population. Other goals include relating observed concentrations to administered doses through identification of predictive covariates in a target population. Population pharmacokinetics does not require “rich” data (many observations/subject), as required for analysis of single-subject data, nor is there a need for structured sampling time schedules. “Sparse” data (few observations/ subject), or a combination, can be used. We examine the fundamentals of five key aspects of population pharmacokinetic modeling together with methods for comparing and evaluating population pharmacokinetic models. DATA CONSIDERATIONS
Biosorption of Acid Black 172 and Congo Red from aqueous solution by nonviable Penicillium YW 01: kinetic study, equilibrium isotherm and artificial neural network modeling.

The main objective of this work was to investigate the biosorption performance of nonviable Penicillium YW 01 biomass for removal of Acid Black 172 metal-complex dye (AB) and Congo Red (CR) in solutions. Maximum biosorption capacities of 225.38 and 411.53 mg g(-1) under initial dye concentration of 800 mg L(-1), pH 3.0 and 40 °C conditions were observed for AB and CR, respectively. Biosorption data were successfully described with Langmuir isotherm and the pseudo-second-order kinetic model. The Weber-Morris model analysis indicated that intraparticle diffusion was the limiting step for biosorption of AB and CR onto biosorbent. Analysis based on the artificial neural network and genetic algorithms hybrid model indicated that initial dye concentration and temperature appeared to be the most influential parameters for biosorption process of AB and CR onto biosorbent, respectively. Characterization of the biosorbent and possible dye-biosorbent interaction were confirmed by Fourier transform infrared spectroscopy and scanning electron microscopy.
Daily exercises and education for preventing low back pain in children: cluster randomized controlled trial.

BACKGROUND
Children report low back pain (LBP) as young as 8 years. Preventing LBP in children may prevent or delay adult incidence.


OBJECTIVES
The purpose of this study was to determine whether education and daily exercise affect LBP episodes in children compared with education alone.


DESIGN
This was a prospective, multicenter cluster randomized controlled trial.


SETTING
The study was conducted at 7 New Zealand primary schools.


PARTICIPANTS
Children (n=708), aged 8 to 11 years, from 7 schools stratified by sample size (36, 114, 151, 168, 113, 45, 83) were randomized and allocated to 2 masked groups: intervention (4 schools, n=469) or control (3 schools, n=239).


INTERVENTIONS
Participants in the intervention group were taught 4 spinal movements for daily practice. Both groups participated in education that emphasized "back awareness."


MEASUREMENTS
Low back pain history at baseline was assessed. Children reported episodes of LBP during the previous week on trial days 7, 21, 49, 105, 161, and 270. Analysis was at the individual participant level, with adjustment for school clusters.


RESULTS
There were no significant differences between groups in the odds of reporting no LBP in the previous week during the study period (odds ratio [OR]=0.72; 95% confidence interval [95% CI]=0.46, 1.14; P=.16). The intervention group reported significantly fewer episodes of LBP (OR=0.54; 95% CI=0.39, 0.74; P<.001) and significantly fewer lifetime first episodes of LBP (n=86 [34%]) compared with the control group (n=58 [47%]) (OR=0.60; 95% CI=0.39, 0.91; P=.02). The odds of an episode of LBP were greater in participants with a history of LBP (OR=4.21; 95% CI=3.07, 5.78; P<.001). Low back pain episodes decreased across the trial period for both groups (OR=0.89; 95% CI=0.84, 0.95; P<.001). Adherence to exercise was poor.


LIMITATIONS
Replication in other settings is needed.


CONCLUSIONS
Regular exercise and education appear to reduce LBP episodes in children aged 8 to 11 years compared with education alone.
Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial.

CONTEXT
The Women's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks, including invasive breast cancer, exceeded benefits. Outstanding issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography.


OBJECTIVE
To determine the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations.


DESIGN, SETTING, AND PARTICIPANTS
Following a comprehensive breast cancer risk assessment, 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were randomly assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40 clinical centers. Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter.


MAIN OUTCOME MEASURES
Breast cancer number and characteristics, and frequency of abnormal mammograms by estrogen plus progestin exposure.


RESULTS
In intent-to-treat analyses, estrogen plus progestin increased total (245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001) and invasive (199 vs 150 cases; HR, 1.24; weighted P =.003) breast cancers compared with placebo. The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P =.04) and were at more advanced stage (regional/metastatic 25.4% vs 16.0%, respectively; P =.04) compared with those diagnosed in the placebo group. After 1 year, the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.


CONCLUSIONS
Relatively short-term combined estrogen plus progestin use increases incident breast cancers, which are diagnosed at a more advanced stage compared with placebo use, and also substantially increases the percentage of women with abnormal mammograms. These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis.
In greedy PURSUIT of new directions: (Nearly) Orthogonal Matching Pursuit by directional optimisation

Matching Pursuit and orthogonal Matching Pursuit are greedy algorithms used to obtain sparse signal approximations. Orthogonal Matching Pursuit is known to offer better performance, but Matching Pursuit allows more efficient implementations. In this paper we propose novel greedy Pursuit algorithms based on directional updates. Using a conjugate direction, the algorithm becomes a novel implementation of orthogonal Matching Pursuit, with computational requirements similar to current implementations based on QR factorisation. A significant reduction in memory requirements and computational complexity can be achieved by approximating the conjugate direction. Further computational savings can be made by using a steepest descent direction. The two resulting algorithms are then comparable to Matching Pursuit in their computational requirements, their performance is however shown to be closer to that of orthogonal Matching Pursuit with the (slightly slower) approximate conjugate direction based approach outperforming the gradient descent method.
Managing the integration problem in concurrent engineering

Concurrent engineering in large-scale product development generally involves multiple cross-functional teams working simultaneously on separate aspects of the overall development effort. The often complex technical coupling among such teams makes integrating their activities an essential yet difficult task for project management. We refer to this challenge of integrating teams as the integration problem in concurrent engineering. This paper presents a methodology for determining the needs for integration and coordination by studying the underlying technical structure of a project. We use a project modeling tool known as the Design Structure Matrix (DSM) to depict the patterns of required information flow in a project. This matrix representation allows us to identify where coordination is most essential and then to design integration mechanisms based on the specific technical information needs of the project. The utility of this methodology in an industrial setting is demonstrated by an application to the development of a new automobile engine at General Motors. Thesis Advisor: Steven D. Eppinger Associate Professor of Management Science Sloan School of Management Acknowledgments This research was funded by General Motors and the Leaders for Manufacturing Program, a partnership involving eleven major U.S. manufacturing firms and M.I.T.'s schools of engineering and management. I would like to thank Steven Eppinger for his patience, Chris Huber and Mark Morelli for their diversion, my mother, Louise M. McCord, for her support, and Debbie for her love. Table of
Referral to a Commercial Weight Management Program in Patients With Coronary Heart Disease: A PILOT STUDY IN THE NETHERLANDS.

PURPOSE
To quantify the impact of a commercial weight management program on weight change in obese patients with coronary heart disease.


METHODS
An observational, single-center pilot study in the Netherlands. Forty-five patients diagnosed with a recent acute coronary syndrome and a body mass index of >30 kg/m2 were recruited. The commercial weight management intervention (Weight Watchers) promotes a hypoenergetic and balanced diet, increased physical activity, and group support. The program included weekly 30-minute in-hospital meetings with an experienced coach. The program was offered in parallel with a cardiac rehabilitation program.


RESULTS
Thirty-five patients completed the program. Of these patients, 32 patients (91%) decreased body weight. Mean weight change was -5.8 kg (range: +0.6 kg to -15.4 kg), and 20 patients (57%) achieved the target of 5% weight loss of their initial weight. Twenty-seven patients continued the commercial weight loss program after 14 weeks, the mean followup of these patients was 34 weeks and their mean weight change was -9.1 kg (range: 0.0-23.0 kg).


CONCLUSIONS
Obese patients, discharged after an acute coronary syndrome, who were referred to a commercial weight management program, achieved significant weight loss. Although this is a nonrandomized pilot study with patients who were selected by motivation and by the ability to participate in the program, the proportion of weight loss is significant and promising.
Teachers in a World of Change: Teachers' Knowledge and Attitudes towards the Implementation of Innovative Technologies in Schools

The implementation of innovative technologies in school is a complex process that enquires creating a pedagogical, technological, and managerial systemic change in the school-culture – a process that usually fails to meet the high expectations and to create the systemic change. In light of the many recent studies, which indicate that teachers' perception and attitudes play a pivotal role of in the success or the failure of technology-implementation projects, the present study explores the teachers' perceptions and attitudes towards the implementation of an innovative technology (smart class) in school by analyzing the inter-relationships between the major pedagogical factors that act in a technology-implementation process: (1) the teachers' attitudes towards change, (2) the teachers' technological-pedagogical content knowledge, and (3) the teachers' perception of school as a learning organization. Data was gathered using questionnaires that captured the teachers' level of "Technological Pedagogical Content Knowledge" (TPACK), their perception of school as a learning organization, and their attitude towards change. Findings indicate a positive correlation between TPACK and the teachers' attitudes towards change, and a positive correlation between teachers' attitudes towards change and their perception of school as a learning organization. Participants who scored high in TPACK and in perceiving their school as a learning organization also scored high in their positive attitudes towards change.
The ability of three different models of frailty to predict all-cause mortality: results from the European Male Aging Study (EMAS).

Few studies have directly compared the ability of the most commonly used models of frailty to predict mortality among community-dwelling individuals. Here, we used a frailty index (FI), frailty phenotype (FP), and FRAIL scale (FS) to predict mortality in the EMAS. Participants were aged 40-79 years (n=2929) at baseline and 6.6% (n=193) died over a median 4.3 years of follow-up. The FI was generated from 39 deficits, including self-reported health, morbidities, functional performance and psychological assessments. The FP and FS consisted of five phenotypic criteria and both categorized individuals as robust when they had 0 criteria, prefrail as 1-2 criteria and frail as 3+ criteria. The mean FI increased linearly with age (r(2)=0.21) and in Cox regression models adjusted for age, center, smoking and partner status the hazard ratio (HR) for death for each unit increase of the FI was 1.49. Men who were prefrail or frail by either the FP or FS definitions, had a significantly increased risk of death compared to their robust counterparts. Compared to robust men, those who were FP frail at baseline had a HR for death of 3.84, while those who were FS frail had a HR of 3.87. All three frailty models significantly predicted future mortality among community-dwelling, middle-aged and older European men after adjusting for potential confounders. Our data suggest that the choice of frailty model may not be of paramount importance when predicting future risk of death, enabling flexibility in the approach used.
Fox-Fordyce disease following axillary laser hair removal.

BACKGROUND
Fox-Fordyce disease (FFD) is a relatively rare entity with a typical clinical presentation. Numerous studies have described unifying histopathological features of FFD, which together suggest a defect in the follicular infundibulum resulting in follicular dilation with keratin plugging, subsequent apocrine duct obstruction, and apocrine gland dilation, with eventual extravasation of the apocrine secretions as the primary histopathogenic events in the evolution of the disease.


OBSERVATIONS
We describe a case of FFD that developed in a 41-year-old woman 3 months after completing a series of axillary laser hair removal treatments, and we detail the clinical and histopathological changes typical for FFD.


CONCLUSION
Because defective infundibular maturation has been suggested to play a central role in the evolution of FFD, the close temporal relationship of laser hair therapy with the development of FFD suggests a causal role, which we continue to explore.
Inequalities involving circular, hyperbolic and exponential functions

This paper is aimed at obtaining some new lower and upper bounds for the functions cosx , sinx/x , x/coshx , thus establishing inequalities involving circulr, hyperbolic and exponential functions.
From Facial Parts Responses to Face Detection: A Deep Learning Approach

In this paper, we propose a novel deep convolutional network (DCN) that achieves outstanding performance on FDDB, PASCAL Face, and AFW. Specifically, our method achieves a high recall rate of 90.99% on the challenging FDDB benchmark, outperforming the state-of-the-art method [23] by a large margin of 2.91%. Importantly, we consider finding faces from a new perspective through scoring facial parts responses by their spatial structure and arrangement. The scoring mechanism is carefully formulated considering challenging cases where faces are only partially visible. This consideration allows our network to detect faces under severe occlusion and unconstrained pose variation, which are the main difficulty and bottleneck of most existing face detection approaches. We show that despite the use of DCN, our network can achieve practical runtime speed.
End-to-End Relation Extraction using Markov Logic Networks

The task of end-to-end relation extraction consists of two sub-tasks: i) identifying entity mentions along with their types and ii) recognizing semantic relations among the entity mention pairs. It has been shown that for better performance, it is necessary to address these two sub-tasks jointly [22,13]. We propose an approach for simultaneous extraction of entity mentions and relations in a sentence, by using inference in Markov Logic Networks (MLN) [21]. We learn three different classifiers : i) local entity classifier, ii) local relation classifier and iii) “pipeline” relation classifier which uses predictions of the local entity classifier. Predictions of these classifiers may be inconsistent with each other. We represent these predictions along with some domain knowledge using weighted first-order logic rules in an MLN and perform joint inference over the MLN to obtain a global output with minimum inconsistencies. Experiments on the ACE (Automatic Content Extraction) 2004 dataset demonstrate that our approach of joint extraction using MLNs outperforms the baselines of individual classifiers. Our end-to-end relation extraction performance is better than 2 out of 3 previous results reported on the ACE 2004 dataset.
Scalar σ meson effects in ρ and ω decays into π0π0γ

Abstract The complementarity between chiral perturbation theory and the linear sigma model in the scalar channel is exploited to study π 0 π 0 production in ρ and ω radiative decays, where the effects of a low mass scalar resonance σ (500) should manifest. The recently reported data on ρ → π 0 π 0 γ seem to require the contribution of a low mass and moderately narrow σ (500). The properties of this controversial state could be fixed by improving the accuracy of these measurements. Data on ω → π 0 π 0 γ can also be accommodated in our framework, but are much less sensitive to the σ (500) properties.
Low-dose baclofen therapy raised plasma insulin-like growth factor-1 concentrations, but not into the normal range in a predictable and sustained manner in men with chronic spinal cord injury.

OBJECTIVE
To evaluate, whether once-daily oral baclofen administration increases and/or sustains plasma insulin-like growth factor-1 (IGF-1) concentration in 11 men with chronic spinal cord injury (SCI) and IGF-1 deficiency (i.e. <250 ng/ml).


DESIGN
Prospective, open-label, dose titration study. Baclofen was administered at 20 mg/day for 8 weeks; then increased to 40 mg/day for another 8 weeks. Plasma IGF-1 and self-reported side effects were measured at baseline and every other week for the duration of the study.


RESULTS
The subjects were 43 ± 12 years old, had duration of injury of 20 ± 12 years; eight subjects had a complete motor injury, and eight had paraplegia. Nine of 11 subjects completed the 20 mg/day treatment and 5 subjects completed the 40 mg/day treatment. Plasma IGF-1 levels improved with each baclofen dose; however, only one subject increased from baseline and remained above the targeted physiological range of 250 ng/ml throughout treatment. A significant increase in IGF-1concentration was observed between baseline and week 2 (154 ± 63 vs. 217 ± 69 ng/ml; P < 0.05), weeks 8 and 10 (188 ± 95 vs. 228 ± 93 ng/ml; P < 0.05), and weeks 8 and 16 (188 ± 95 vs. 259 ± 92 ng/ml; P < 0.05). No serious side effects were observed at 20 mg/day; the 40 mg/day dose was less well tolerated.


CONCLUSION
Baclofen was not effective at sustaining plasma IGF-1 concentrations in the physiological range in men with chronic SCI.
Compound ion salt, a novel low-sodium salt substitute: from animal study to community-based population trial.

BACKGROUND
Salt restriction, an important approach for primary and secondary prevention of hypertension, is undermined by unsatisfactory adherence. A salt-restriction study tested the efficacy and safety of a compound ion salt (CISalt) with low sodium content in an animal model and in a community-based population.


METHODS
In part 1, 8-week-old male spontaneously hypertensive rats (SHRs) were fed 1% CISalt in the study group and 8% or 1% normal salt (NSalt) in controls (n = 10 each) for 12 weeks. Blood pressure (BP) and urinary electrolytes were measured every 3 weeks. After 12 weeks, collagen deposition in the heart and kidney and the levels of angiotensin II (Ang II) and nitric oxide (NO) in plasma and renal cortex were measured. In part 2, a single-blind, randomized, 6-month controlled trial with CISalt was conducted in 248 persons (age >or=65 years) in 10 rural communities. Plasma renin activity and Ang II were included in blood and urinary measures at baseline and 6 months.


RESULTS
Reduced BP urinary protein excretion and reduced collagen in the heart and kidneys were significantly different in animals fed CISalt compared to controls. In human studies, at 6 months, mean systolic BP (SBP) was decreased by 9.6 mm Hg (95% confidence interval (CI): 13.1 to 6.1, P < 0.001) and diastolic BP (DBP) by 5.3 mm Hg (95% CI: 7.9 to 2.6, P < 0.001), respectively, compared to controls; urinary sodium excretion also decreased by 67.4 mmol/24 h (95% CI: 84.8 to 50.0, P < 0.001), and plasma renin activity was slightly increased by 0.19 ng/ml/h (95% CI: 0.04-0.33, P = 0.013). No adverse cardiovascular events were reported.


CONCLUSIONS
In these studies, CISalt lowered BP and showed end-organ protection in hypertensive animals and BP reduction in humans. CISalt appears to be a safe and acceptable strategy to reduce BP.