Global Function Research Articles

Machine learning models for diagnosing Alzheimer's disease using brain cortical complexity.

This study aimed to develop and validate machine learning models (MLMs) to diagnose Alzheimer's disease (AD) using cortical complexity indicated by fractal dimension (FD). A total of 296 participants with normal cognitive (NC) function and 182 with AD from the AD Neuroimaging Initiative database were randomly divided into training and internal validation cohorts. Then, FDs, demographic characteristics, baseline global cognitive function scales [Montreal Cognitive Assessment (MoCA), Functional Activities Questionnaire (FAQ), Global Deterioration Scale (GDS), Neuropsychiatric Inventory (NPI)], phospho-tau (p-tau 181), amyloidβ-42/40, apolipoprotein E (APOE) and polygenic hazard score (PHS) were collected to establish multiple MLMs. Receiver operating characteristic curves were used to evaluate model performance. Participants from our institution (n = 66; 33 with NC and 33 with AD) served as external validation cohorts to validate the MLMs. Decision curve analysis was used to estimate the models' clinical values. The FDs from 30 out of 69 regions showed significant alteration. All MLMs were conducted based on the 30 significantly different FDs. The FD model had good accuracy in predicting AD in three cohorts [area under the receiver operating characteristic (ROC) curve (AUC) = 0.842, 0.808, and 0.803]. There were no statistically significant differences in AUC values between the FD model and the other combined models in the training and internal validation cohorts except MoCA + FD and FAQ + FD models. Among MLMs, the MoCA + FD model showed the best predictive efficiency in three cohorts (AUC = 0.951, 0.931, and 0.955) and had the highest clinical net benefit. The FD model showed favorable diagnostic performance for AD. Among MLMs, the MoCA + FD model can predict AD with the highest efficiency and could be used as a non-invasive diagnostic method.

Association Between Oral Hygiene Behaviours and Cognitive Decline in Adults: A Systematic Review and Meta-Analysis.

To evaluate the association between oral hygiene behaviour and cognitive decline in adults. The outcomes include changes in global cognitive function, visual attention, task switching and the risk of dementia. We conducted a systematic review following the preferred reporting items for systematic reviews and meta-analyses guidelines. A systematic search of 11 databases and grey literature sources was conducted from inception to January 2024. We included interventional trials or cohort studies that investigated the effect of oral hygiene behaviours (e.g., toothbrushing, mouth washing, flossing, using toothpicks and cleaning dentures) on cognitive decline in adults. Data extraction and risk of bias assessment were performed by two independent reviewers with expertise in conducting systematic reviews. Meta-analyses were conducted using random-effects models, and heterogeneity was assessed with the I2 statistic and χ2 test. A total of eight studies (six intervention studies and two cohort studies) met inclusion criteria, including 261,772 participants. Follow-up periods ranged from 30 days to 48 months for interventions and 9 to 18 years for cohorts. Toothbrushing was associated with a significantly slower decline in global cognitive overtime. Toothbrushing in older adults with moderate/severe dementia could achieve significant changes in cognitive decline. There was no significant difference between the effectiveness of toothbrushing performed by professionals and caregivers. Other oral hygiene behaviours, including dental flossing, using mouthwash, using toothpicks and cleaning dentures, were not associated with the risk of dementia. Toothbrushing is linked to a decreased risk of dementia and improved global cognitive function. Promoting toothbrushing at least twice daily may significantly reduce the risk of cognitive decline and dementia. These findings highlight the urgent need for programmes that encourage daily toothbrushing, particularly in nursing home settings and among older adults with moderate-to-severe dementia.

Distributed Fixed-Time Optimal Flocking for Second-Order Multi-Agent Systems

In this paper, we investigate the problem of distributed optimization for second-order multi-agent systems with fixed-time flocking. The objective is to concurrently steer the agents towards a common velocity while optimizing the global objective function. To solve the problem, we first design a fixed-time estimator to predict the global gradient of the objective functions, then based on which, each agent is endowed with fixed-time tracking controller to track the optimal solution. Motivated by the fact that the relative velocity information is difficult to obtain accurately, the proposed algorithm is designed without using neighbors’ velocity. The upper bounds of the settling time are provided without relying on the initial states of the agents, only requiring the adjustment of parameters. The effectiveness of the proposed control protocol is also demonstrated through numerical simulations.

Handgrip strength is associated with functioning in patients with mental disorders: A two-center cross-sectional study

Physical and mental health are intricated, however, there is a paucity of studies investigating the association between self-reported global functioning and handgrip strength and functional capacity in people with mental disorders. This study investigated the association between functioning, handgrip strength, and functional capacity in outpatients with a range of mental disorders. This was a two-center, cross-sectional study. Functioning was assessed with the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). Handgrip strength was assessed with a hand dynamometer, and functional exercise capacity through the 2-min walk test (2 MW T). Multiple linear regression analysis was used to identify the association between WHODAS 2.0, handgrip strength, and functional capacity, adjusted for study site, age, educational level, and severity of psychiatric symptoms. A total of 91 outpatients (mean age = 40.16 ± 13.49, 63.7% females) participated in the study. The mean functioning score was 26.77 (±8.74) out of 60 points, while the mean distance walked was 142.20 ± 34.40 m and the mean handgrip strength was 30.62 ± 11.17 kgf. The adjusted multiple linear regression analysis revealed that only handgrip strength (p = 0.008, 95%CI = −0.327 to −0.050) was associated with functioning. Thus, our results revealed that muscular strength is associated with functioning in patients with mental disorders. This study suggests the importance of incorporating physical health assessment into mental health care for a comprehensive assessment of functioning levels, which is usually restricted to mental symptoms.

Experimental design and multiple response optimization of batch leaching tests of volcanic ashes.

Volcanic eruptions can release large amounts of tephra, lava, and gases, drawing attention due to their magnitude, energy, and impact on life and the environment. Among the most documented and sometimes dramatic effects of volcanic ashes are those linked to the input of diverse elements in the environment, which are released as a consequence of ash weathering. Laboratory studies have been conducted to investigate and predict the environmental input of chemical elements from volcanic ashes. This research paper describes the optimization of batch leaching tests used to investigate the release of ions from ashes collected in the Andes Cordillera after the eruption of the Puyehue volcano in 2011. Chemometric multivariate strategies were employed to evaluate the influence of variables affecting the leaching of volcanic ash. The effects of the main variables, namely contact time, the acidity of the leaching agent, the solid/liquid ratio, the particle size, and the stirring speed, were studied in leaching tests. To determine the optimal conditions for selected metal determinations, we employ Darringer's desirability function, which allows for the simultaneous optimization of the selected responses (element concentrations during the leaching process). Multielemental analysis (Na, Mg, Al, Si, P, Cl, K, Ca, V, Cr, Mn, Fe, Ni, Cu, Zn, Sr, Cd, Hg, Tl, and Pb) was quantified by ICP-MS (inductively coupled plasma-mass spectrometry) following adequate dilution of test leaching. These results established the optimal experimental conditions for leaching volcanic ash. The most significant variables were the solid/liquid ratio and the stirring speed, resulting in two groups of elements with an adequate global desirability function (D) value.

Speckle tracking of left ventricle in pediatric patients with hemodynamically significant patent ductus arteriosus (PDA): case–control study

BackgroundLeft ventricle (LV) volume overload is observed with hemodynamically significant PDA as it causes left to right shunting, leading to increased pulmonary blood flow. This overload causes LV remodeling as LV increases stroke volume in trial for compensation, but in larger shunts, patients may develop symptoms of congestive heart failure. Two-dimensional (2D) speckle-tracking echocardiography has emerged as a technique for objective and quantitative evaluation of global and regional myocardial function, independent of the angle of myocardial insonation.Aim of the workThis study aimed to evaluate left ventricular function by 2-dimensional speckle tracking in children with hemodynamically significant PDA.MethodsThis prospective controlled study was performed on 54 children divided into two groups (34 as cases and 20 as controls) to compare echocardiographic measurements. Conventional Echocardiography, tissue Doppler, and Speckle tracking were done for all patients, and measurements were compared.ResultsThere was a statistically significant difference (p value < 0.001) in global longitudinal strain (GLS) in the PDA group indicating a decrease in LV function in PDA patients. This difference was observed in several conventional echocardiographic parameters but not in tissue Doppler in our study.ConclusionLeft ventricle global strain is an important predictor of the myocardial performance index of the Left ventricle in patients with hemodynamically significant PDA and outweighs other conventional echocardiographic parameters and tissue Doppler indices.

Improving Predictions of Spin-Crossover Complex Properties through DFT Calculations with a Local Hybrid Functional.

We conducted a study on the performance of the local hybrid exchange-correlation functional PBE0r for a set of 95 experimentally characterized iron spin-crossover (SCO) complexes [Vennelakanti, V.; J. Chem. Phys. 2023, 159, 024120]. The PBE0r functional is a variant of PBE0 where the exchange correction is restricted to on-site terms formulated on the basis of local orbitals. We determine the free parameters of the PBE0r functional against the experimental data and other hybrid functionals. With a Hartree-Fock (HF) exchange factor of 4%, the PBE0r functional accurately reproduces the electronic and free-energy trends predicted in prior DFT studies for these 95 complexes by using the B3LYP functional. Larger values of HF exchange stabilize high-spin states. The PBE0r-predicted bond lengths tend to exceed the experimental bond lengths, although bond lengths are less sensitive to HF exchange than in global hybrids. The predicted SCO transition temperatures T1/2 from PBE0r correlate moderately with the experimental transition temperatures, showing a slight improvement compared to the previous modB3LYP-predicted T1/2. This study suggests that the PBE0r functional is computationally cost-effective and offers the possibility of simulating larger complexes with accuracy comparable to global hybrid functionals, provided the HF-exchange parameter is carefully optimized.

DCPNet: Deformable Control Point Network for image enhancement

In this paper, we present a novel image enhancement network consisting of global and local color enhancement. The proposed network model is constructed using global transformation functions, which are formed by a set of piece-wise quadratic curves and a local color enhancement network based on the encoder–decoder network. To adaptively and dynamically control the ranges of each piece-wise curve, we introduce deformable control points (DCPs), which determine the overall structure of the global transformation functions. The parameters for piece-wise quadratic curve fitting and DCPs are estimated using the proposed DCP network (DCPNet). DCPNet processes a down-sampled image to derive the DCP parameters: The DCP offsets and the curve parameters. Then, we obtain a set of DCPs from the DCP offsets and connect each adjacent DCP pair by using the curve parameter to construct a global transformation function for each color channel. The original input images are then transformed based on the resulting transformation functions to obtain globally enhanced images. Finally, the intermediate image is fed into the local enhancement network, which has a U-Net architecture, to produce the spatially enhanced images. Extensive experimental results demonstrate the superiority of the proposed method over state-of-the-art methods in various image enhancement tasks, such as image retouching, tone-mapping, and underwater image enhancement.

Design, Synthesis, and Preclinical Evaluation of a High-Affinity 18F-Labeled Radioligand for Myocardial Growth Hormone Secretagogue Receptor Before and After Myocardial Infarction.

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post-myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics. We designed a high-affinity GHSR ligand labeled with 18F for imaging by PET and characterized its invivo properties in a canine model of MI. Methods: We rationally designed and radiolabeled with 18F a quinazolinone derivative ([18F]LCE470) with subnanomolar binding affinity to GHSR. We determined the sensitivity and invivo and ex vivo specificity of [18F]LCE470 in a canine model of surgically induced MI using PET/MRI, which allowed for anatomic localization of tracer uptake and simultaneous determination of global cardiac function. Uptake of [18F]LCE470 was determined by time-activity curve and SUV analysis in 3 regions of the left ventricle-area of infarct, territory served by the left circumflex coronary artery, and remote myocardium-over a period of 1.5 y. Changes in cardiac perfusion were tracked by [13N]NH3 PET. Results: The receptor binding affinity of LCE470 was measured at 0.33 nM, the highest known receptor binding affinity for a radiolabeled GHSR ligand. In vivo blocking studies in healthy hounds and ex vivo blocking studies in myocardial tissue showed the specificity of [18F]LCE470, and sensitivity was demonstrated by a positive correlation between tracer uptake and GHSR abundance. Post-MI changes in [18F]LCE470 uptake occurred independently of perfusion tracer distributions and changes in global cardiac function. We found that the regional distribution of [18F]LCE470 within the left ventricle diverged significantly within 1 d after MI and remained that way throughout the 1.5-y duration of the study. Conclusion: [18F]LCE470 is a high-affinity PET tracer that can detect changes in the regional distribution of myocardial GHSR after MI. In vivo PET molecular imaging of the global dynamics of GHSR may lead to improved GHSR-based therapeutics in the treatment of post-MI remodeling.

Exploring the Peaks and Potholes: Understanding positive and negative effects of concentrated exposure treatment for obsessive-compulsive disorder

The Bergen 4-Day Treatment offers brief concentrated exposure with response prevention (cERP) for obsessive-compulsive disorder (OCD). To date, this intervention has primarily been studied in Norway, and no study has been done on its side effects. We tested the safety, feasibility, and effectiveness of cERP in Germany and compared cERP to a historical inpatient control group.Thirty-three patients with OCD were treated with cERP. We assessed severity of OCD (primary outcome: Y-BOCS), depression, global functioning, self-esteem, self-efficacy, experiential avoidance, and quality of life at baseline (t0), two weeks after t0 (t1), and three months after t1 (t2). Side effects were assessed at t1 and t2. The changes in OCD were compared to a matched historical inpatient control group (n = 33) treated at the same site.The cERP group improved over time, with a large effect size in OCD symptoms and other outcome measures. Improvement of OCD symptoms over treatment was superior in the cERP group compared to the historical control group, with a medium effect size for OCD symptoms. 53–56% of the participants reported at least one side effect (e.g., exhaustion). cERP is safe and effective in the treatment of OCD and can be successfully implemented in Germany.

Telomere length and 4-year changes in cognitive function in an older Mediterranean population at high risk of cardiovascular disease.

Cognitive decline, a common process of brain ageing, has been associated with telomere length (TL). Delving into the identification of reliable biomarkers of brain ageing is essential to prevent accelerated cognitive impairment. We selected 317 non-smoking 'Prevención con Dieta Mediterránea-Plus' (PREDIMED-Plus) participants (mean age, 65.8 ± 5.0years) with metabolic syndrome from two trial centres who were following a lifestyle intervention. We measured TL and cognitive function at baseline and after 3 and 4years of follow-up, respectively. Associations between baseline or 3-year changes in TL and baseline or 4-year changes in cognitive function were analysed using multivariable regression models. Baseline TL was not associated with baseline cognitive performance. Nevertheless, longer baseline TL was associated with improved 4-year changes in the Executive Function domain (β: 0.29; 95%CI: 0.12 to 0.44; P < 0.001) and the Global Cognitive Function domain (β: 0.19; 95%CI: 0.05 to 0.34; P =0.010). Besides, a positive association was found between longer baseline TL and improved 4-year changes in the animal version of the Verbal Fluency Test (β: 0.33; 95%CI: 0.12 to 0.52; P =0.002). By contrast, 3-year changes in TL were not associated with changes in cognitive function after 4years. Longer baseline TL could protect from cognitive decline and be used as a useful biomarker of brain ageing function in an older Mediterranean population at risk of cardiovascular disease and cognitive impairment.

Mechanical dyssynchrony in patients with chronic heart failure and left bundle branch block

Background. The main problem in patient selection for cardiac resynchronization therapy (CRT) is the lack of unified approaches to the definition of mechanical dyssynchrony (MD) and selection criteria, particularly, in patients with left bundle branch block (LBBB).Aim: To study mechanical dyssynchrony indices and three-dimensional Echo (3DE) criteria of global and local contractility function in patients with chronic heart failure (CHF) and LBBB during different types of isolated left ventricle (LV) pacing.Methodology and Research Methods. The experimental intraoperative study involved 88 points obtained from 12 patients with CRT class IA indications and LBBB. During isolated LV pacing as part of CRT implantation procedure endocardial and epicardial pacing were obtained. Transesophageal Echo (TEE) cineloops recording and paced QRS complex morphology registrations by means of LabSystem Pro Electrophysiological Recording System (Bard Electrophysiology, USA) were performed during each stimulation episode. Philips Qlab 10 software was used for TEE data analysis.Results. The global (3D EF, 23.8 [22; 28.4], GLS, –5.33% [10.90%; –15.4%]) and local contractility (ExсAvg 3.5 [2.1; 5.6]) criteria and dyssyncrony indices (SDI-16, 14.9 [8.9; 23.1]) showed severe systolic dysfunction and intraventricular dyssynchrony – typical signs in this patient group, and differed significantly (3D EF, p = 0.003; GLS, p = 0.004; ExcAvg, p &lt; 0.001; Tmsv-6 SD, р = 0.03) depending on the stimulation method and site. A moderate direct correlation between SDI-16 and the QRS duration (common electical dyssynchrony criterium) and inverse correlation with ExcAvg and 3D LVEF also describes LV response.

Adaptive changes in multiple aspects of emotion regulation in the offspring of pregnant persons receiving a diet-and-exercise intervention relative to usual pregnancy care: A randomized controlled trial

BackgroundHuman studies examining the influence of prenatal diet and/or exercise interventions on offspring neurodevelopment are mixed. Interventions that include the provision of whole foods, nutritional counselling, address exercise behaviors, and that utilize multimethod assessments of offspring emotion regulation may better reveal the impact of these interventions on neurodevelopment. ObjectiveTo explore whether the Be Healthy in Pregnancy (BHIP) prenatal diet-and-exercise intervention improves emotion regulation (ER) in 22-month-old offspring. MethodsPregnant persons (>18 years, singleton pregnancy) were recruited between 12-17 weeks gestation and randomized to the intervention [high protein energy-controlled diet via the provision of cottage cheese, Greek yogurt, low-fat milk, individualized biweekly nutritional counselling, a controlled walking program, and usual pregnancy care (UPC)] or control (UPC alone) groups. ER in offspring (mage=22.2(SD=4.04); 50.9% female; intervention: n=29, control: n=28) was assessed using reports from pregnant persons and their partners on the Child Behavior Checklist, and the Behavior Rating Inventory of Executive Function-Preschool Version, laboratory observational tasks examining inhibitory control, attention, and empathy, and high frequency heart rate variability (HF-HRV). ResultsChildren exposed to the BHIP intervention exhibited medium to large effect size reductions in pregnant person and partner reported externalizing (effect size ƞ2pmother=0.08, 95% CI of the difference[0.05,7.14]; ƞ2ppartner=0.17[1.68,9.65]), internalizing ƞ2pmother=0.08[0.09,5.32]; ƞ2ppartner=0.13[0.84,8.88]) and total behavior problems ƞ2pmother=0.09[0.72,11.87];; ƞ2ppartner=0.17 [3.17,17.88]) relative to control participants’ children. Pregnant persons, but not partners, reported fewer problems with inhibitory control (ƞ2p=0.13[1.40,8.55]), cognitive flexibility (ƞ2p=0.08[0.18,4.85]), emergent metacognition (ƞ2p=0.14[2.00,11.59]), and global executive function (ƞ2p=0.14[3.37,20.12]). Intervention children displayed fewer impulsive behaviors (ƞ2p=0.11[0.16,1.77]) and a longer attention span (ƞ2p=0.08[0.30,13.34]). Finally, intervention children exhibited greater baseline HF-HRV (ƞ2p=0.10[0.16,2.01]), and adaptive HF-HRV reactivity during the impulsivity (ƞ2p=0.12[0.20,2.19]) and attention tasks (ƞ2p=0.21[0.74,2.77]). ConclusionsThis intervention was associated with medium/large effect size improvements in offspring ER. Larger trials are needed to confirm the potential of these interventions on offspring neurodevelopment. Clinical Trial RegistryNCT01689961, Sept 21, 2012

Distributed Adaptive Optimization Algorithm for High-Order Nonlinear Multi-Agent Stochastic Systems with Lévy Noise.

An adaptive neural network output-feedback control strategy is proposed in this paper for the distributed optimization problem (DOP) of high-order nonlinear stochastic multi-agent systems (MASs) driven by Lévy noise. On the basis of the penalty-function method, the consensus constraint is removed and the global objective function (GOF) is reconstructed. The stability of the system is analyzed by combining the generalized Itô's formula with the Lyapunov function method. Moreover, the command filtering mechanism is introduced to solve the "complexity explosion" problem in the process of designing virtual controller, and the filter errors are compensated by introducing compensating signals. The proposed algorithm has been proved that the outputs of all agents converge to the optimal solution of the DOP with bounded errors. The simulation results demonstrate the effectiveness of the proposed approach.

Interleukin-5: an indicator of mild cognitive impairment in patients with type 2 diabetes mellitus - a comprehensive investigation ranging from bioinformatics analysis to clinical research.

Neuroinflammation constitutes an underlying mechanism for cognitive impairment. Here, we endeavor to scrutinize the potential contribution of interleukin-5 (IL-5) towards mild cognitive impairment (MCI), and to assess its diagnostic value for MCI in patients with type 2 diabetes mellitus (T2DM). RNA-seq was used to explore the potential neuroinflammation factors in the hippocampus of diabetic mice with cognitive decline. Additionally, the promising risk factor was verified in animals. Finally, the association between IL-5 levels and cognitive function and its diagnostic value for MCI were assessed. In animals, up-regulated IL-5 mRNA and protein levels were detected by RNA-seq and (or) verified experiments in the hippocampus of diabetic db/db mice with cognitive decline, compared to those of db/m mice without diabetes. In human, compared to diabetic patients without MCI, those with MCI demonstrate elevated levels of IL-5. It is natively associated with Montreal Cognitive Assessment (MoCA) scores, reflecting global cognitive function, and positively correlated with Trail Making Test A (TMTA) scores, reflecting information processing speed. Furthermore, an elevated level of IL-5 is identified as a risk factor for MCI, and a factor that influences TMTA scores. Finally, it is recommended that the cut-off value for IL-5 in the diagnosis of MCI is 22.98 pg/mL, with a sensitivity of 68.6% and specificity of 72.9%. IL-5 is considered a risk factor for MCI in T2DM patients and is associated with their performance in information processing speed. Moreover, an elevated level of IL-5 is a plausible biomarker for MCI in T2DM patients.

Concurrent Validity of Performance-Based Measures of Daily Functioning with Cognitive Measures and Informant Reported Everyday Functioning.

Despite the substantial need for reliable and valid assessment of functional ability in older adults, there is currently limited research on the emergence of early functional declines during prodromal dementia stages, such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). This study uses novel performance-based assessments to characterize subtle, yet clinically meaningful, changes in functional ability. A sample of 93 older adults classified as cognitively unimpaired (CU; n = 30, Mage = 73.57 ± 6.66), SCD (n = 34, Mage = 72.56 ± 6.43), or MCI (n = 29, Mage = 78.28 ± 7.55) underwent neuropsychological testing along with an informant-rated daily functional skills measure (Assessment of Functional Capacity Interview). Participants also completed the Night Out Task (NOT), an open-ended performance-based measure of functional assessment, and the Financial Capacity Instrument-Short Form (FCI-SF) that assesses financial skills. The MCI group performed worse on the NOT and FCI-SF relative to SCD and CU. NOT and FCI scores were associated with measures of global cognitive function, executive function, processing speed, language and memory, and FCI-SF overall score was correlated with informant-rated functional ability. The NOT and FCI-SF were also predictive of informant-reported daily functioning over and above traditional cognitive data and demographics. Performance-based measures of IADL may allow for earlier detection of subtle functional changes that might not be adequately captured by traditional measures. The measurement of early functional changes is an important global outcome to evaluate the efficacy of interventions in dementia research.

ERS technical standard: Global Lung Function Initiative reference values for multiple breath washout indices.

Multiple breath washout is a lung function test based on tidal breathing that assesses lung volume and ventilation distribution. The aim of this analysis was to use the Global Lung Function Initiative methodology to develop all-age reference equations for the multiple breath washout indices lung clearance index (LCI) and functional residual capacity (FRC). Multiple breath washout data from healthy individuals were collated from sites. Data were re-analysed using the latest software versions. Reference equations were derived using the lambda-mu-sigma (LMS) method using the generalised additive models of location shape and scale programme in R. The impact of equipment type, inert tracer gas, and equipment dead space volume on the derived reference ranges were investigated. Data from 23 sites (n=3647 test occasions) were submitted. Reference equations were derived from 1581 unique observations from participants between the ages of 2 and 81 years. Equipment type, inert tracer gas, and equipment dead space volume did not significantly affect the prediction equations for either LCI or FRC. Reference equations for LCI include age as the only predictor, whereas sex-specific reference equations for FRC included height and age. Global Lung Function Initiative reference equations for multiple breath washout variables provide a standard for reporting and interpretation of LCI and FRC.

Verification of successful maintenance by serum drug level during a guided antipsychotic reduction to reach minimum effective dose (GARMED) trial.

Inconsistent results regarding the risk of relapse and better subjective outcomes of previous antipsychotic dose reduction trials in patients with remitted psychosis have not been verified using therapeutic drug monitoring (TDM). This study examined plasma drug concentrations of a dose-tapering trial which exhibited the potential of successful maintenance under lower antipsychotic dosages. A 2-year open-label randomized prospective trial recruited remitted patients to undergo guided antipsychotic tapering. Blood samples were collected at baseline, annually, and after each dose reduction. Plasma aripiprazole/dehydroaripiprazole concentrations were determined using LC-MS/MS. The relationship between the dose and serum drug levels was examined using Spearman's correlation. Divided at 120 ng/mL, relapse rate, global function, quality of life, and psychopathology were compared between high- and low- drug level groups. A total of 126 blood samples were collected, after excluding13 samples due of non-adherence. The correlation coefficients between dosage and drug level were 0.853 (aripiprazole) and 0.864 (dehydroaripiprazole), and the dose and concentration plots were parallel along the tapering trajectories, except patients with non-adherence. The concentration-to-dose ratio of aripiprazole in this cohort, 17.79 ± 7.23 ng/mL/mg, was higher than that in Caucasian populations. No significant differences were observed in the clinical outcomes between the high- and low-level groups. Remarkably, 12 of 15 patients maintained remission at plasma aripiprazole concentrations of <120 ng/mL. The lower-than-expected doses reached in our antipsychotic tapering trial were substantiated to provide adequate prophylactic effects by TDM results in a subset of patients treated with aripiprazole, even considering the differences in pharmacogenomics between ethnicities.

Scaling-Up for the Counter-Rotating Twin Screw Extrusion of Polymers.

A novel and original computer scaling-up system for the counter-rotating twin screw extrusion of polymers was developed. In the system, each scaling parameter (scaling criterion) may be considered as an objective function to be minimized for the single parameters or the functional relationships along the length of the screw. Scaling was based on the process simulation, which was performed using the comprehensive (or global) counter-rotating twin screw extrusion program called TSEM (Twin Screw Extrusion Model). The extrusion process was scaled by applying GASESTWIN (Genetic Algorithms Screw Extrusion Scaling) software developed for this purpose using genetic algorithms. Scaling up the extrusion process was carried out to enhance extrusion process throughput according to the scaling criteria specified by the single quantities of polymer melt temperature at the die exit and relative melting length, and by distributions along the screw length of the extrusion parameters of the polymer melt temperature and polymer plasticating. The global objective function had the lowest value for the selected extrusion parameters, which means the minimal differences between the values of the scaled-up processes and extrusion throughput was significantly increased. The solution to the problem of scaling the counter-rotating process presented in this paper complements the existing solutions for optimizing and scaling basic variants of the extrusion process, i.e., flood-fed and starve (metered)-fed single-screw extrusion, as well as co-rotating and counter-rotating twin-screw extrusion.

Health-related quality of life in patients with progressive glioblastoma treated with combined bevacizumab and lomustine versus lomustine only: Secondary outcome of the randomized phase III EORTC 26101 study

Abstract Background Progression-free survival, but not overall survival, was prolonged with bevacizumab and lomustine compared to lomustine only in the randomized phase 3 European Organization for Research and Treatment of Cancer (EORTC) 26101 study. Objective To evaluate the impact of treatment on health-related quality of life (HRQoL) in progressive glioblastoma patients participating in the EORTC 26101 study. Methods Patients with progressive glioblastoma, after standard radio-chemotherapy, were 2:1 randomized to either BEV/LOM or LOM. HRQoL was a secondary trial outcome and assessed using the EORTC QLQ-C30 and QLQ-BN20 questionnaires at baseline, and subsequently every 12 weeks. Predefined scales for analysis were global health status (GH), physical functioning, social functioning (SF), motor dysfunction, and communication deficit. The primary endpoint was HRQoL during the last assessment up to week 36. Moreover, time to HRQoL deterioration (TTD) and HRQoL deterioration-free survival (DFS) were calculated. Results Out of 437 patients, 402 (92%) patients had a baseline HRQoL assessment, which dropped to 66% at week 36. During the last assessment up to week 36, no differences were observed for predefined scales, apart from SF being clinically relevant lower in the combination arm (mean 66.0 versus 81.0, p = .001). Of note, the baseline SF score was 66.4 for patients in the combination arm, showing stable SF. Median DFS was significantly longer in the combination arm (12.4 weeks) compared to lomustine alone (6.7 weeks), reflecting the difference in time to progression between arms. TTD, not including progression as an event, was not different between treatment arms (median 13.0 versus 12.9 weeks). Conclusion The addition of bevacizumab to lomustine did not negatively affect HRQoL during the progression-free period.