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Covariate analysis in population pharmacokinetics is key for adjusting doses for patients. The main objective of this work was to compare the adequacy of various modeling approaches on covariate clinical relevance decision-making. The full model, stepwise covariate model (SCM) and SCM+ PsN algorithms were compared in a clinical trial simulation of a 383-patient population pharmacokinetic study mixing rich and sparse designs. A one-compartment model with first-order absorption was used. A base model including a body weight effect on CL/F and V/F and a covariate model including 4 additional covariates-parameters relationships were simulated. As for forest plots, ratios between covariates at a specific value and that of a typical individual were calculated with their 90% confidence interval (CI90) using standard errors. Covariates on CL, V and KA were considered relevant if their CI90 fell completely outside the reference area [0.8-1.2]. All approaches provided unbiased covariate ratio estimates. For covariates with a simulated effect, the 3 approaches correctly identify their clinical relevance. However, significant covariates were missed in up to 15% of cases with SCM/SCM+. For covariate with no simulated effects, the full model mainly identified them as non-relevant or with insufficient information while SCM/SCM+ mainly did not select them. SCM/SCM+ assume that non-selected covariates are non-relevant when it could be due to insufficient information, whereas the full model does not make this assumption and is faster. This study must be extended to other methods and completed by a more complex high-dimensional simulation framework., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Understanding bacterial adhesion at the nanoscale is crucial for elucidating biofilm formation, enhancing biosensor performance, and designing advanced biomaterials. However, the dynamics of the critical transition from reversible to irreversible adhesion has remained elusive due to analytical constraints. Here, we probed this adhesion transition, unveiling nanoscale, step-like bacterial approaches to substrates using a plasmonic imaging technique. This method reveals the discontinuous nature of adhesion, emphasizing the complex interplay between bacterial extracellular polymeric substances (EPS) and substrates. Our findings not only deepen our understanding of bacterial adhesion but also have significant implications for the development of theoretical models for biofilm management. By elucidating these nanoscale step-like adhesion processes, our work provides avenues for the application of nanotechnology in biosensing, biofilm control, and the creation of biomimetic materials.

Prediction of the antibacterial activity of new chemical compounds is an important task, due to the growing problem of bacterial drug resistance. Generalized linear models (GLMs) were created using 85 amidrazone derivatives based on the results of antimicrobial activity tests, determined as the minimum inhibitory concentration (MIC) against Gram-positive bacteria: Staphylococcus aureus , Enterococcus faecalis , Micrococcus luteus , Nocardia corallina , and Mycobacterium smegmatis . For the analysis of compounds characterized by experimentally measured MIC values, we included physicochemical properties (e.g., molecular weight, number of hydrogen donors and acceptors, topological polar surface area, compound percentages of carbon, nitrogen, and oxygen, melting points, and lipophilicity) as potential predictors. The presence of R1 and R2 substituents, as well as interactions between melting temperature and R1 or R2 substituents, were also considered. The set of potential predictors also included possible biological effects (e.g., antibacterial, antituberculotic) of tested compounds calculated with the PASS (Prediction of Activity Spectra for Substances) program. Using GLMs with least absolute shrinkage and selection (LASSO), least-angle regression, and stepwise selection, statistically significant models with the optimal value of the adjusted determination coefficient and of seven fit criteria were chosen, e.g., Akaike's information criterion. The most often selected variables were as follows: molecular weight, PASS_antieczematic, PASS_anti-inflam, squared melting temperature, PASS_antitumor, and experimental lipophilicity. Additionally, relevant to the bacterial strain, the interactions between melting temperature and R1 or R2 substituents were selected, indicating that the relationship between MIC and melting temperature depends on the type of R1 or R2 substituent.

Purpose: External snapping hip syndrome (ESHS) was historically attributed to isolated iliotibial band (ITB) contracture. However, the gluteus maximus complex (GMC) may also be involved. This study aimed to intraoperatively identify the ESHS origin and assess the outcomes of endoscopic treatment based on the identified aetiological type., Methods: From 2008-2014, 30 consecutive patients (34 hips) with symptomatic ESHS cases refractory to conservative treatment underwent endoscopic stepwise "fan-like" release, gradually addressing all known reasons of ESHS: from the isolated ITB, through the fascial part of the GMC until a partial release of gluteus maximus femoral attachment occurred. Snapping was assessed intra-operatively after each surgical step and prospectively recorded. Functional outcomes were assessed via the MAHORN Hip Outcome Tool (MHOT-14)., Results: Twenty seven patients (31 hips) were available to follow-up at 24-56 months. In all cases, complete snapping resolution was achieved intra-operatively: in seven cases (22.6%) after isolated ITB release, in 22 cases (70.9%), after release of ITB + fascial part of the GMC, and in two cases (6.5%) after ITB + fascial GMC release + partial release of GM femoral insertion. At follow-up, there were no snapping recurrences and MHOT-14 score significantly increased from a pre-operative average of 46 to 93(p<0.001)., Conclusion: Intraoperative identification and gradual addressing of all known causes of ESHS allows for maximum preservation of surrounding tissue during surgery while precisely targeting the directly involved structures. Endoscopic stepwise "fan-like" release of the ITB and GMC is an effective, tailor-made treatment option for ESHS regardless of the snapping origin in the patients with possibility to manually reproduce the snapping., (© 2023. The Author(s).)

Cattle weight development is highly correlated with some body measurements. Based on the relationship between morphometric measurements and body mass, our aim was to develop regression equations to estimate the body weight of Curraleiro Pé-Duro (CPD) cattle to be used in farms that lack access to weighting scales. Data from 1023 animals from four farms on withers height (WH), body length (BL), body score (BS), heart girth (HG), permanent teeth (PT), scrotal perimeter (SP), and live weight were used. The animals were classified into five categories depending on age and/or sex: newborns (NB), calves, weaned animals, cows, and bulls. The best models are GLM with Gamma, Gamma, inverse Gaussian, Gaussian, and Gamma distributions for NB, calves, weaned animals, cows, and bulls, respectively. Predictive modeling for bulls was the best performing overall, with a correlation of 0.97 between the estimated by the model and the obtained with a weighting scale. For NB, calves, weaned animals, and cows, the correlation (r) was 0.85, 0.90, 0.95, and 0.87, respectively. The evaluated models are adequate to be used as a technical solution to estimate weight in a cattle production system., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Compared to supervised machine learning (ML), the development of feature selection for unsupervised ML is far behind. To address this issue, the current research proposes a stepwise feature selection approach for clustering methods with a specification to the Gaussian mixture model (GMM) and the k -means. Rather than the existing GMM and k -means which are carried out based on all the features, the proposed method selects a subset of features to implement the two methods, respectively. The research finds that a better result can be obtained if the existing GMM and k -means methods are modified by nice initializations. Experiments based on Monte Carlo simulations show that the proposed method is more computationally efficient and the result is more accurate than the existing GMM and k -means methods based on all the features. The experiment based on a real-world dataset confirms this finding.

Introduction: The length of hospital stay (LOHS) caused by COVID-19 has imposed a financial burden, and cost on the healthcare service system and a high psychological burden on patients and health workers. The purpose of this study is to adopt the Bayesian model averaging (BMA) based on linear regression models and to determine the predictors of the LOHS of COVID-19., Methods: In this historical cohort study, from 5100 COVID-19 patients who had registered in the hospital database, 4996 patients were eligible to enter the study. The data included demographic, clinical, biomarkers, and LOHS. Factors affecting the LOHS were fitted in six models, including the stepwise method, AIC, BIC in classical linear regression models, two BMA using Occam's Window and Markov Chain Monte Carlo (MCMC) methods, and GBDT algorithm, a new method of machine learning., Results: The average length of hospitalization was 6.7 ± 5.7 days. In fitting classical linear models, both stepwise and AIC methods (R 2  = 0.168 and adjusted R 2  = 0.165) performed better than BIC (R 2  = 0.160 and adjusted = 0.158). In fitting the BMA, Occam's Window model has performed better than MCMC with R 2  = 0.174. The GBDT method with the value of R 2  = 0.64, has performed worse than the BMA in the testing dataset but not in the training dataset. Based on the six fitted models, hospitalized in ICU, respiratory distress, age, diabetes, CRP, PO2, WBC, AST, BUN, and NLR were associated significantly with predicting LOHS of COVID-19., Conclusion: The BMA with Occam's Window method has a better fit and better performance in predicting affecting factors on the LOHS in the testing dataset than other models., (© 2023. The Author(s).)

Alveolar recruitment manoeuvres (ARM) performed during general anaesthesia improve oxygenation; however cardiovascular depression may be observed. The aim of the study was to compare the effects of sustained inflation (SI) and stepwise ARMs on cardiac output (CO), mean arterial blood pressure and arterial oxygen tension (PaO 2 ) in ten mechanically ventilated goats anaesthetised with isoflurane. In the SI ARM, peak inspiratory presure (PIP) was increased to 30 cmH 2 O and sustained for 20 s. In the stepwise ARM, the PIP was increased by 5 cmH 2 O each minute for three minutes from 10 to 25 cmH 2 O. Both ARMs were followed by positive end-expiratory pressure of 5 cmH 2 O. Paired lithium dilution CO measurements and arterial blood samples were obtained before and after each ARM. The order of the ARM was randomised and each goat was subjected to both techniques. Data was reported as median and interquartile range (IQR). Significance was set at 0.05. The median change in CO (measured by subtracting values after and before ARM) was -0.15 L min -1 (IQR -0.51; 0.03) and - 0.90 L min -1 (IQR -1.69; -0.58) for SI and stepwise ARM respectively (p = 0.04). The median change in PaO 2 was 3 kPa (IQR -2.7; 7.6) and 0.4 kPa (IQR -3.4; 5.5) for SI and stepwise ARM respectively (p = 0.03). In conclusion, SI ARM causes less impact on CO and provides a better improvement in PaO 2 compared to stepwise ARM in goats., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

During anaerobic digestion (AD) of protein-rich wastewater, ammonium (NH 4 + ) is released by amino acid degradation. High NH 4 + concentrations disturb the AD microbiome balance, leading to process impairments. The sensitivity of the AD microbiome to NH 4 + and the inhibition threshold depend on multiple parameters, especially the previous microbial acclimation to ammonium stress. However, little is known about the effect of different NH 4 ) in batch assays fed with synthetic wastewater, according to two different strategies: (i) direct independent inputs at a unique target concentration and (ii) successive inputs in a stepwise manner. In both strategies, along the NH + acclimation strategies on the differential expression of key active microbial taxa. Here, we applied NH 4 + inputs of increasing intensity (from 1.7 to 15.2 g N-NH 4 + liters -1 ) in batch assays fed with synthetic wastewater, according to two different strategies: (i) direct independent inputs at a unique target concentration and (ii) successive inputs in a stepwise manner. In both strategies, along the NH 4 + gradient, the active methanogens shifted from acetoclastic Methanosaeta to Methanosarcina and eventually hydrogenotrophic Methanoculleus . Despite shorter latency times, the successive input modality led to lower methane production rate, lower soluble chemical oxygen demand (sCOD) removal efficiency, and lower half maximal inhibitory concentration, together with higher volatile fatty acid (VFA) accumulation, compared to the independent input modality. These differential performances were associated with a drastically distinct succession pattern of the active bacterial partners in both experiments. In particular, the direct exposure modality was characterized by a progressive enrichment of VFA producers (mainly Tepidimicrobium ) and syntrophic VFA oxidizers (mainly Syntrophaceticus ) with increasing NH 4 + concentration, while the successive exposure modality was characterized by a more dynamic succession of VFA producers (mainly Clostridium , Sporanaerobacter , Terrisporobacter ) and syntrophic VFA oxidizers (mainly Tepidanaerobacter , Syntrophomonas ). These results bring relevant insights for improved process management through inoculum adaptation, bioaugmentation, or community-driven optimization. IMPORTANCE Anaerobic digestion (AD) is an attractive biotechnological process for wastewater bioremediation and bioenergy production in the form of methane-rich biogas. However, AD can be inhibited by ammonium generated by protein-rich effluent, commonly found in agro-industrial activities. Insights in the microbial community composition and identification of AD key players are crucial for anticipating process impairments in response to ammonium stress. They can also help in defining an optimal microbiome adapted to high ammonium levels. Here, we compared two strategies for acclimation of AD microbiome to increasing ammonium concentration to better understand the effect of this stress on the methanogens and their bacterial partners. Our results suggest that long-term cumulative exposure to ammonia disrupted the AD microbiome more strongly than direct (independent) ammonium additions. We identified bioindicators with different NH 4 + tolerance capacity among VFA producers and syntrophic VFA oxidizers.

Kabwe is a mining town in Zambia that has been ranked among "the ten most polluted places in the world" with previous findings of serious lead (Pb) pollution. In this study, we aim to examine the impact of childhood Pb poisoning on the health-related quality of life (HRQoL) of mothers in Kabwe. The HRQoL was assessed using the Short-Form 36 survey for 404 mothers coming from residences in 40 randomly selected standard enumeration areas (SEAs). Blood lead levels (BLLs) of the household members including the mothers themselves were measured. We found a significant positive correlation between the BLLs of the mothers and their children (R = 0.6385, p < 0.0001), while the BLLs of preschool-aged and school-aged children were significantly higher than those of their mothers and fathers. Using the data sets containing the BLLs of the household members, the age of the mothers, the household income, and the household SEA, we performed stepwise multiple linear regression analyses. The results showed significant negative associations between the representative BLL of household children and the BLL of preschool-aged children with the vitality and mental health scores of their mothers. Additionally, the BLL of school-aged children was only significantly associated with the mental health score of their mothers. By contrast, there was a significant negative association between the BLLs of the mothers with the social role functioning score. This suggests that elevated BLLs in children have a negative impact on the mental health conditions of their mothers regardless of the mothers' BLL., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Dearomative heterocyclic [4+2] cycloaddition between the N-(2,4-dinitrophenyl)pyridinium ion of nicotinamide and an enol ether was analyzed by Density Functional Theory (DFT) calculations. The calculation revealed that the reaction undergoes stepwise bond formation rather than occurring in a concerted manner. The experimental products were found to be both kinetically and thermodynamically favored. The calculated transition states and intermediate suggested that the high diastereoselectivity is derived from the electrostatic interaction between the 2-nitro group of the pyridinium ion and the hydrogen of the enol ether., (© 2021 The Authors. Published by Wiley-VCH GmbH.)

Background: Tobacco is a leading cause of death and illness despite > 50 years of antitobacco efforts., Aims: To establish the determinants of current and former smoking and smokeless tobacco use in Sudan as measured by the STEPwise Survey 2016., Methods: A household-based cross-sectional World Health Organization STEPwise Survey was conducted among 7745 Sudanese citizens aged 18-69 years across 11 states in Sudan. A 4-stage stratified cluster sampling design was implemented. The generic STEPS Instrument (version 3.2) was used and questions were tailored to the Sudanese context., Results: Among current male smokers, 63.7% were aged ≤ 35 years, 50.7% were illiterate or did not complete primary school, 84.5% were employed and 52.4% were in the lowest 2 quintiles of income. Among male smokeless tobacco users, 54.8% were aged ≤ 35 years, 48.4% were illiterate or did not complete primary school, 89.7% were employed and 52.2% were in the lowest 2 quintiles of income. Using multivariate logistic regression models, current smoking in men was associated with older age, informal education, unemployment and lower income. Smokeless tobacco use was associated with age 18-25 years, informal education, unemployment and lower income., Conclusions: Both forms of tobacco use were associated with poor socioeconomic status and unemployment. Smokeless tobacco use was associated with age 18-25 years as opposed to smoking tobacco use. These results can inform the target audience of the future tobacco control plans., (Copyright © World Health Organization (WHO) 2021. Open Access. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

Background: One in four Kenyans aged 18-69 years have raised blood pressure. Despite this high prevalence of hypertension and known association between socioeconomic status and hypertension, there is limited understanding of factors explaining inequalities in raised blood pressure in Kenya. Hence, we quantified the socioeconomic inequality in hypertension in Kenya and decomposed the determinants contributing to such inequality., Methods: We used data from the 2015 Kenya STEPwise survey for non-communicable diseases risk factors. We included 4422 respondents aged 18-69 years. We estimated the socioeconomic inequality using the concentration index (C) and decomposed the C using Wagstaff decomposition analysis., Results: The overall concentration index of hypertension in Kenya was - 0.08 (95% CI: - 0.14, - 0.02; p = 0.005), showing socioeconomic inequalities in hypertension disfavouring the poor population. About half (47.1%) of the pro-rich inequalities in hypertension was explained by body mass index while 26.7% by socioeconomic factors (wealth index (10.4%), education (9.3%) and paid employment (7.0%)) and 17.6% by sociodemographic factors (female gender (10.5%), age (4.3%) and marital status (0.6%)). Regional differences explained 7.1% of the estimated inequality with the Central region alone explaining 6.0% of the observed inequality. Our model explained 99.7% of the estimated socioeconomic inequality in hypertension in Kenya with a small non-explained part of the inequality (- 0.0002)., Conclusion: The present study shows substantial socioeconomic inequalities in hypertension in Kenya, mainly explained by metabolic risk factors (body mass index), individual health behaviours, and socioeconomic factors. Kenya needs gender- and equity-focused interventions to curb the rising burden of hypertension and inequalities in hypertension.

Objective: To compare multiple-procedure catheter ablation outcomes of a stepwise approach versus left atrial posterior wall isolation (LA PWI) in patients undergoing nonparoxysmal atrial fibrillation (NPAF) ablation., Background: Unfavorable outcomes for stepwise ablation of NPAF in large clinical trials may be attributable to proarrhythmic effects of incomplete ablation lines. It is unknown if a more extensive initial ablation strategy results in improved outcomes following multiple ablation procedures., Methods: Two hundred twenty two consecutive patients with NPAF underwent first-time ablation using a contact-force sensing ablation catheter utilizing either a stepwise (Group 1, n = 111) or LA PWI (Group 2, n = 111) approach. The duration of follow-up was 36 months. The primary endpoint was freedom from atrial arrhythmia >30 s. Secondary endpoints were freedom from persistent arrhythmia, repeat ablation, and recurrent arrhythmia after repeat ablation., Results: There was similar freedom from atrial arrhythmias after index ablation for both stepwise and LA PWI groups at 36 months (60% vs. 69%, p = .1). The stepwise group was more likely to present with persistent recurrent arrhythmia (29% vs. 14%, p = .005) and more likely to undergo second catheter ablation (32% vs. 12%, p < .001) compared to LA PWI patients. Recurrent arrhythmia after repeat ablation was more likely in the stepwise group compared to the LA PWI group (15% vs. 4%, p = .003)., Conclusions: Compared to a stepwise approach, LA PWI for patients with NPAF resulted in a similar incidence of any atrial arrhythmia, lower incidence of persistent arrhythmia, and fewer repeat ablations. Results for repeat ablation were not improved with a more extensive initial approach., (© 2020 Wiley Periodicals LLC.)

Primary focal hyperhidrosis is a common reason for dermatology outpatient visit and has significant impact on patient's social and professional activities. The study describes the clinical profile of those patients and response with aluminum chloride hexahydrate lotion (ACH 20%) and oral glycopyrrolate (OGP). A retrospective study was carried out at a tertiary care center between the year 2016 and 2018. Details of history, baseline assessment, treatment response recorded in specially designed proformas were analyzed. Initially, the patients received topical ACH daily at night. Non-responders were advised OGP 1 mg BD and increased to 2 mg BD if they did not respond. Response was measured according to patient global assessment and objective evaluation of sweating. Among total 69 patients 57 had onset <10 years of age. There was male preponderance and most common trigger was situations causing anxiety (n = 15). Around 15.3% patients got adequate response with ACH lotion. The cumulative response increased to 45.8% by addition of OGP 1 mg BD and to 55.9% by increasing the dose to 2 mg BD. Addition of OGP to topical ACH increases the treatment efficacy in patients with primary focal hyperhidrosis. Increasing the glycopyrrolate dose augments the response further. However, the current medical treatment options are able to give moderate response., (© 2020 Wiley Periodicals LLC.)

Objective: The objective of this study was to compare the effects of cognitive load and surgical performance in medical students that performed the open inguinal hernia repair after preparation with step-by-step video-demonstration versus continuous video-demonstration. Hypothetically, the step-by-step group will perceive lower extraneous load during the preparation of the surgical procedure compared to the continuous group. Subsequently, fewer errors will be made in the surgical performance assessment by the step-by-step group, resulting in better surgical performance., Design: In this prospective study, participants were randomly assigned to the step-by-step or continuous video-demonstration. They completed questionnaires regarding perceived cognitive load during preparation (10-point Likert scale). Their surgical performance was assessed on a simulation hernia model using the Observational Clinical Human Reliability Assessment., Setting: Erasmus University Medical Center, Rotterdam, the Netherlands., Participants: Participants included medical students who were enrolled in extracurricular anatomy courses., Results: Forty-three students participated; 23 students in the step-by-step group and 20 in the continuous group. As expected, the step-by-step group perceived a lower extraneous cognitive load (2.92 ± 1.21) compared to the continuous group (3.91 ± 1.67, p = 0.030). The surgical performance was not statistically significantly different between both groups; however, in subanalyses on a selection of students that prepared for 1 to 2 hours, the step-by-step group made less procedural errors, 1.67 ± 1.11, compared to the continuous group, 3.06 ± 1.91, p = 0.018., Conclusions: Our results suggest that preparation using step-by-step video-based learning results in lower extraneous cognitive load and subsequently fewer procedural errors during the surgical performance. For learning purposes, demonstration videos of surgical procedures should be presented in a segmented format., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Due to a lack of standardized guidelines, it is necessary to verify the effectiveness of educational programmes for nursing students' systematic handover training., Aims: This study aimed to develop a stepwise nursing handover programme and to examine its effects on awareness of handover Situation, Background, Assessment, Recommendation, communication self-efficacy and satisfaction with handover education., Design: This was a single-group repeated measures ANOVA study., Methods: This study was conducted in a nursing department, using a convenience sample of 25 senior nursing students from April 2 to June 22, 2018. The programme was divided into lectures, scenario role-playing and nursing case role-playing. The research questions were analysed using repeated measures ANOVA., Results: Awareness of handover Situation, Background, Assessment, Recommendation, communication self-efficacy and satisfaction with handover education gradually increased after each step of the programme. The stepwise nursing handover programme, progressing from low to high levels of learning, can be used to improve the nursing handover system and handover communication ability., Competing Interests: No conflict of interest has been declared by the author(s)., (© 2020 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Introduction: Clinical trials have failed to reliably show improved outcomes with utilization of contact-force sensing (CFS) radiofrequency (RF) ablation catheters. It is unknown whether the unfavorable outcomes observed in these trials are attributable to inexperience with CFS technology., Objectives: To compare catheter ablation outcomes of stepwise linear ablation with versus without CFS technology and to assess the impact of operator experience with CFS technology on procedural outcomes., Methods: Clinical outcomes were evaluated in 228 consecutive NPAF patients undergoing first-time left atrial ablation using a stepwise linear approach. Arrhythmia recurrence was assessed using 2-week event monitors at 3-month intervals following index ablation., Results: A total of 228 patients were included in our study. There was no statistically significant difference in risk of recurrent atrial arrhythmias at 12 and 24 months between CFS and non-CFS patients (p = 0.5 and p = 0.169). The time to recurrence of atrial arrhythmias at 24 months in the second half of CFS patients was significantly lower when compared to both the first half of CFS patients (p = 0.002) and non-CFS patients (p = 0.005)., Conclusion: While there was no difference in overall outcomes between CFS and non-CFS ablation using a stepwise linear approach in patients with NPAF, procedural efficacy of the second half of CFS patients was significantly improved compared to both the first half of CFS patients and all non-CFS patients. Lack of benefit seen in clinical trials using CFS technology may be related to operator inexperience with CFS ablation catheters at the time of the trials.

Background: Noncommunicable diseases (NCDs) are a major public health problem worldwide. Despite improvement in the health situation, Afghanistan's health indicators are the worst in the Region. About 37% of Afghan adults die due to NCDs., Aims: We aimed to estimate the proportion of major risk factors for NCDs in Afghanistan., Methods: We analysed the dataset of studies conducted in 5 provinces, Kabul, Balkh, Hirat, Nangarhar and Kandahar, during 2013-2015, using the WHO STEPwise approach to NCD surveillance. This involved multistage cluster sampling from urban citizens aged 25-70 years. EpiInfo, version 7, and SPSS, version 20, were used for data management., Results: In total, 5897 records were included in the analysis; 54% were females. Mean age was 39.56 (standard deviation12.29) years; illiteracy rate was 61.5% and 83.2% were married. Smoking and snuff use was 8% and 11.1% respectively. On average the subjects were consuming fruits 2.76 and vegetable 3.85 days per week. Overweight, general and abdominal obesity was 19%, 33.7% and 57.1% respectively. Typically, 32.4% had high blood pressure and 12.5% had high blood sugar., Conclusions: The modifiable risk factors of NCDs were prevalent in the major cities of the country. Their identification is vital in attempting to focus on prevalence of NCDs in urban cities. Tailored interventions are needed to focus on NCDs in Afghanistan., (Copyright © World Health Organization (WHO) 2020. Open Access. Some rights reserved. This work is available under the CC BY-NC-SA 3.0 IGO license (https://creativecommons.org/licenses/by-nc-sa/3.0/igo).)

As a core component of most cognitive diagnosis models, the Q-matrix, or item and attribute association matrix, is typically developed by domain experts, and tends to be subjective. It is critical to validate the Q-matrix empirically because a misspecified Q-matrix could result in erroneous attribute estimation. Most existing Q-matrix validation procedures are developed for dichotomous responses. However, in this paper, we propose a method to empirically detect and correct the misspecifications in the Q-matrix for graded response data based on the sequential generalized deterministic inputs, noisy 'and' gate (G-DINA) model. The proposed Q-matrix validation procedure is implemented in a stepwise manner based on the Wald test and an effect size measure. The feasibility of the proposed method is examined using simulation studies. Also, a set of data from the Trends in International Mathematics and Science Study (TIMSS) 2011 mathematics assessment is analysed for illustration., (© 2019 The British Psychological Society.)

Purpose: To evaluate the fatigue failure load of distinct lithium disilicate restoration designs cemented on a chairside titanium base for maxillary anterior implant-supported restorations., Materials and Methods: A left-maxillary incisor restoration was virtually designed and sorted into 3 groups: (n = 10/group; CTD: lithium disilicate crowns cemented on custom-milled titanium abutments; VMLD: monolithic full-contour lithium disilicate crowns cemented on a chairside titanium-base; VCLD: lithium disilicate crowns bonded to lithium disilicate customized anatomic structures and then cemented onto a chairside titanium base). The chairside titanium base was air-abraded with aluminum oxide particles. Subsequently, the titanium base was steam-cleaned and air-dried. Then a thin coat of a silane agent was applied. The intaglio surface of the ceramic components was treated with 5% hydrofluoric acid (HF) etching gel, followed by silanization, and bonded with a resin cement. The specimens were fatigued at 20 Hz, starting with a 100 N load (5000× load pulses), followed by stepwise loading from 400 N up to 1400 N (200 N increments) at a maximum of 30,000 cycles each. The failure loads, number of cycles, and fracture analysis were recorded. The data were statistically analyzed using one-way ANOVA, followed by pairwise comparisons (p < 0.05). Kaplan-Meier survival plots and Weibull survival analyses were reported., Results: For catastrophic fatigue failure load and the total number of cycles for failure, VMLD (1260 N, 175,231 cycles) was significantly higher than VCLD (1080 N, 139,965 cycles) and CDT (1000 N, 133,185 cycles). VMLD had a higher Weibull modulus demonstrating greater structural reliability., Conclusion: VMLD had the best fatigue failure resistance when compared with the other two groups., (© 2018 by the American College of Prosthodontists.)

This study investigated the effect of three ageing methods (dry, wet and stepwise wet-then-dry) and ageing time on pH, colour, yield, lipid and protein oxidation and eating quality of beef loins using Meat Standards Australia (MSA) sensory protocols with 900 and 540 consumers in Australia and Japan, respectively. Australian beef loins (Longissimus thoracis et lumborum) at four days post mortem were subjected to wet ageing (boneless; for 7, 21, 35 or 56 days), dry ageing (bone-in; for 35 or 56 days) or a wet-then-dry ageing method (bone-in; 21 days wet ageing followed by 35 days dry ageing). The pH was higher in dry aged than wet aged beef loins (P < .001). Instrumental measurement of surface colour of trimmed dry and wet aged steaks showed significant differences in a*, b* and hue angle. Weight loss was higher in dry aged primals (P < .001), however, total water content was similar among the two ageing methods (P = .934). Retail yield did not differ between 35 and 56 days dry aged primals. Lipid (TBARS) and protein (total carbonyl content) oxidation between the dry and wet aged samples differed depending on the ageing time. When comparing the wet-then-dry and 56 days dry aged samples, only pH and retail yield differed. Australian and Japanese consumers rated dry aged steaks significantly higher (P < .001) than the wet aged counterparts for tenderness, juiciness, flavour, overall liking and weighted palatability scores. The wet-then-dry steaks were also rated higher than the 56 days wet aged steaks for flavour, overall liking and palatability within the Japanese sensory panels. The Japanese consumers also consistently rated all MSA sensory attributes lower (P < .001) than the Australian consumers. The results from this study show dry ageing provides a value adding opportunity for the meat industry in both domestic and export markets., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

A series of 2-benzoxazolinone, diazocoumarin and quinazoline derivatives have been shown to inhibit HIV replication in cell culture. To understand the pharmacophore properties of selected molecules and design new anti-HIV agents, quantitative structure-activity relationship (QSAR) study was developed using a descriptor selection approach based on the stepwise method. Multiple linear regression method was applied to relate the anti-HIV activities of dataset molecules to the selected descriptors. Obtained QSAR model was statistically significant with correlation coefficient R 2 of 0.84 and leave one out coefficient Q 2 of 0.73. The model was validated by test set molecules giving satisfactory prediction value (R 2 test ) of 0.79. Molecules also were docked on HIV integrase enzyme and showed important interactions with the key residues in enzyme active site. These data might be helpful for design and discovery of novel anti-HIV compounds.

Background: In Malaysia, more than 330 000 individuals are estimated to be chronically infected with hepatitis C virus (HCV), but less than 2% have been treated to date., Objectives: To estimate the required coverage and costs of a national screening strategy to inform the launch of an HCV elimination program., Methods: We designed an HCV screening strategy based on a "stepwise" approach. This approach relied on targeting of people who inject drugs in the early years, with delayed onset of widespread general population screening. Annual coverage requirements and associated costs were estimated to ensure that the World Health Organization elimination treatment targets were met., Results: In total, 6 million individuals would have to be screened between 2018 and 2030. Targeting of people who inject drugs in the early years would limit annual screening coverage to less than 1 million individuals from 2018 to 2026. General population screening would have to be launched by 2026. Total costs were estimated at MYR 222 million ($58 million). Proportional to coverage targets, 60% of program costs would fall from 2026 to 2030., Conclusions: This exercise was one of the first attempts to conduct a detailed analysis of the required screening coverage and costs of a national HCV elimination strategy. These findings suggest that the stepwise approach could delay the onset of general population screening by more than 5 years after the program's launch. This delay would allow additional time to mobilize investments required for a successful general population screening program and also minimize program costs. This strategy prototype could inform the design of effective screening strategies in other countries., (Copyright © 2019 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

In this Review, we have summarized and generalized the results of the investigation of the microstructural mechanisms of the tautomerization by the counter movement of the protons along the neighboring intermolecular H-bonds in 22 biologically important pairs of nucleotide bases in the framework of the original method, which allows to trace the evolution of the physicochemical parameters, that characterize these processes along the intrinsic reaction coordinate (IRC). It was demonstrated the performance of the introduction of the conception of the key points (KPs) (from nine to five, depending on the symmetry and nature of system), which exhaustively characterize the flow of the tautomerization processes. It was proved that for all tautomerizing base pairs the extrema of the first derivative of the electron energy of the complex by IRC coincide with the second and penultimate KPs, in which the Laplacian of the electron density equals zero at the corresponding (3,-1) bond critical points of the H-bonds. It was established the linear dependence of the width of the transition state zone of the DPT tautomerization on the degree of its asynchrony. Authors emphasize that the tautomerization reaction through the DPT of the H-bonded pairs of nucleotide bases can be considered successful in those and only in those case if the tautomerized complex is a dynamically stable system, during lifetime of which low-frequency intermolecular vibrations could develop. Perspectives of the application of the obtained approaches to the thorough study of the proton transfer processes in the biologically important objects have been briefly discussed.

Background: Despite the tremendous therapeutic advances that have stemmed from somatic oncogenetics, survival of some cancers has not improved in 50 years. Osteosarcoma still has a 5-year survival rate of 66%. We propose the natural canine osteosarcoma model can change that: it is extremely similar to the human condition, except for being highly heritable and having a dramatically higher incidence. Here we reanalyze published genome scans of osteosarcoma in three frequently-affected dog breeds and report entirely new understandings with immediate translational indications., Results: First, meta-analysis revealed association near FGF9, which has strong biological and therapeutic relevance. Secondly, risk-modeling by multiple logistic regression shows 22 of the 34 associated loci contribute to risk and eight have large effect sizes. We validated the Greyhound stepwise model in our own, independent, case-control cohort. Lastly, we updated the gene annotation from approximately 50 genes to 175, and prioritized those using cross-species genomics data. Mostly positional evidence suggests 13 genes are likely to be associated with mapped risk (including MTMR9, EWSR1 retrogene, TANGO2 and FGF9). Previous annotation included seven of those 13 and prioritized four by pathway enrichment. Ten of our 13 priority genes are in loci that contribute to risk modeling and thus can be studied epidemiologically and translationally in pet dogs. Other new candidates include MYCN, SVIL and MIR100HG., Conclusions: Polygenic osteosarcoma-risk commonly rises to Mendelian-levels in some dog breeds. This justifies caninized animal models and targeted clinical trials in pet dogs (e.g., using CDK4/6 and FGFR1/2 inhibitors).

Background: Despite its advantages, few trainees outside of North America have access to simulation training. We hypothesized that a stepwise training method using tele-mentoring system would be an efficient technique for training in basic laparoscopic skills., Methods: Residents were randomized into two groups and trained to proficiency in intracorporeal suturing. The stepwise group (SG) practiced the task step-by-step, while the other group practiced comprehensively (CG). Each participant received weekly coaching via two-way web conferencing software. The duration of the coaching sessions and self-practice time were compared between the two groups., Results: Twenty residents from 15 institutions participated, and all achieved proficiency. Coaching sessions using tele-mentoring system were completed without difficulties. The SG required significantly shorter coaching time per session than the CG (p = .002). There was no significant difference in self-practice time., Conclusions: The stepwise training method with the tele-mentoring system appears to make efficient use of surgical trainees' and trainers' time., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Two clinical ablation protocols, 2C3L and stepwise, have been routinely used in our group to treat atrial fibrillation (AF), but with a less than 60% long-term arrhythmia-free outcome achieved in patients. The goal of this study was to examine the underlying mechanism of low success in clinical outcome. MRI images from one patient were used to reconstruct a human atrial anatomical model, and fibrotic tissue was manually added to represent the arrhythmia substrate. AF was induced with standard protocols used in clinical practice. 2C3L and stepwise were then used to test the efficacy of arrhythmia termination in our model. The results showed that re-entries induced in our model could not be terminated by using either 2C3L or the stepwise protocol. Although some of the induced re-entries were terminated, others emerged in new areas. Ablation using only the 2C3L or stepwise method was not sufficient to terminate all re-entries in our model, which may partially explain the poor long-term arrhythmiafree outcomes in clinical practice. Our findings also suggest that computational heart modelling is an important tool to assist in the establishment of optimal ablation strategies.

Herein we disclose the radical cation Diels-Alder reaction of aryl vinyl ethers by electrocatalysis, which is triggered by an oxidative SET process. The reaction clearly proceeds in a stepwise fashion, which is a rare mechanism in this class. We also found that two distinctive pathways, including "direct" and "indirect", are possible to construct the Diels-Alder adduct.

The Strengthening Laboratory Management Toward Accreditation (SLMTA) program and subsequent Stepwise Laboratory Quality Improvement Process Toward Accreditation (SLIPTA) checklist were a response to the need for high-quality laboratories to combat the human immunodeficiency virus (HIV) epidemic and provide patients with the highest-quality care. The two tools work together to create a culture of quality in laboratories and allow the identification of gaps. The ultimate goal for any laboratory is to achieve a standard benchmark for quality and these programs have been highly successful in initially affecting the HIV epidemic but continuously improving laboratory quality across all diseases., (Copyright © 2017 Elsevier Inc. All rights reserved.)

On the surface of water ice, a quasi-liquid layer (QLL) has been extensively reported at temperatures below its bulk melting point at 273 K. Approaching the bulk melting temperature from below, the thickness of the QLL is known to increase. To elucidate the precise temperature variation of the QLL, and its nature, we investigate the surface melting of hexagonal ice by combining noncontact, surface-specific vibrational sum frequency generation (SFG) spectroscopy and spectra calculated from molecular dynamics simulations. Using SFG, we probe the outermost water layers of distinct single crystalline ice faces at different temperatures. For the basal face, a stepwise, sudden weakening of the hydrogen-bonded structure of the outermost water layers occurs at 257 K. The spectral calculations from the molecular dynamics simulations reproduce the experimental findings; this allows us to interpret our experimental findings in terms of a stepwise change from one to two molten bilayers at the transition temperature., Competing Interests: The authors declare no conflict of interest.

Background: Quantitative structure-activity relationship (QSAR) models could provide both statistical significance and useful chemical insights for drug design. The QSAR method has found applications for predicting diverse properties of organic compounds, including antiviral activities, toxicities and biological activities. In this work, a quantitative structure-activity relationship was utilized for the prediction of allosteric BRAF (V600E) inhibitory activities., Methods: A data set which contains 54 molecules was classified into training and test sets. Stepwise (SW) and genetic algorithm (GA) methods were employed for feature selection. The models were validated using the cross-validation and external test set., Results: Results showed that the GA approach is a more powerful technique than SW for the selection of suitable descriptors. The squared cross-validated correlation coefficient for leave-one-out of 0.702 and squared correlation coefficient of 0.793 was obtained for the training set compounds by GA-MLR model., Conclusion: The obtained GA-MLR model could be applied as a worthwhile model for designing similar groups of the mentioned inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Objectives: A systematic review was performed to compare the long-term survival of deep dentine caries-affected permanent teeth treated with partial-caries-removal (PCR) versus similar teeth treated with stepwise-caries-removal techniques (SWT)., Data: Clinical studies investigating long-term PCR and SWT outcomes in unrestored permanent teeth with deep dentine caries were evaluated. Failures were defined as loss of pulp vitality or restorative failures following treatment., Sources: PubMed, Web of Science, Dentistry and Oral Sciences Source, and Central databases were systematically searched., Study Selection: From 136 potentially relevant articles, 9 publications utilizing data from 5 studies (2 RCTs, and 3 observational case-series) reporting outcomes for 426 permanent teeth over two to ten years were analyzed. Regarding restorative failures, >88% success at two years for both techniques was reported. For loss of pulp vitality, observational studies reported >96% vitality at two years for each technique, while one RCT reported significantly higher vitality (p<0.05) at three years for PCR (96%) compared to SWT (83%). Risk of bias was high in all studies., Conclusion: Successful vitality and restorative outcomes for both PCR and SWT have been demonstrated at two years and beyond in permanent teeth with deep dentine caries. Partial-caries-removal may result in fewer pulpal complications over a three year period than SWT, although claims of a therapeutic advantage are based on very few, limited-quality studies., Clinical Significance: Partial-caries-removal and SWT are deep caries management techniques that reduce pulp exposure risk. Permanent teeth with deep dentine caries treated with either technique have a high likelihood for survival beyond two years., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Current guidelines differ slightly on the recommendations for treatment of Chronic Obstructive Pulmonary Disease (COPD) patients, and although there are some undisputed recommendations, there is still debate regarding the management of COPD. One of the hindrances to deciding which therapeutic approach to choose is late diagnosis or misdiagnosis of COPD. After a proper diagnosis is achieved and severity assessed, the choice between a stepwise or "hit hard" approach has to be made. For GOLD A patients the stepwise approach is recommended, whilst for B, C and D patients this remains debatable. Moreover, in patients for whom inhaled corticosteroids (ICS) are recommended, a step-up or "hit hard" approach with triple therapy will depend on the patient's characteristics and, for patients who are being over-treated with ICS, ICS withdrawal should be performed, in order to optimize therapy and reduce excessive medications. This paper discusses and proposes stepwise, "hit hard", step-up and ICS withdrawal therapeutic approaches for COPD patients based on their GOLD group. We conclude that all approaches have benefits, and only a careful patient selection will determine which approach is better, and which patients will benefit the most from each approach., (Copyright © 2016 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Spatial cluster detection is an important tool in many areas such as sociology, botany and public health. Previous work has mostly taken either a hypothesis testing framework or a Bayesian framework. In this paper, we propose a few approaches under a frequentist variable selection framework for spatial cluster detection. The forward stepwise methods search for multiple clusters by iteratively adding currently most likely cluster while adjusting for the effects of previously identified clusters. The stagewise methods also consist of a series of steps, but with a tiny step size in each iteration. We study the features and performances of our proposed methods using simulations on idealized grids or real geographic areas. From the simulations, we compare the performance of the proposed methods in terms of estimation accuracy and power. These methods are applied to the the well-known New York leukemia data as well as Indiana poverty data., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Bifrontal contusion is a common clinical brain injury. In the early stage, it is often mild, but it progresses rapidly and frequently worsens suddenly. This condition can become life threatening and therefore requires surgery. Conventional decompression craniectomy is the commonly used treatment method. In this study, the effect of intracranial pressure (ICP) monitored stepwise intracranial decompression surgery on the prognosis of patients with acute severe bifrontal contusion was investigated., Method: A total of 136 patients with severe bifrontal contusion combined with deteriorated intracranial hypertension admitted from March 2001 to March 2014 in our hospital were selected and randomly divided into two groups, i.e., a conventional decompression group and an ICP monitored stepwise intracranial decompression group (68 patients each), to conduct a retrospective study. The incidence rates of acute intraoperative encephalocele, delayed hematomas, and postoperative cerebral infarctions and the Glasgow outcome scores (GOSs) 6 months after the surgery were compared between the two groups., Results: (1) The incidence rates of acute encephalocele and contralateral delayed epidural hematoma in the stepwise decompression surgery group were significantly lower than those in the conventional decompression group; the differences were statistically significant (P < 0.05); (2) 6 months after the surgery, the incidence of vegetative state and mortality in the stepwise decompression group were significantly lower than those in the conventional decompression group (P < 0.05); the rate of favorable prognosis in the stepwise decompression group was also significantly higher than that in the conventional decompression group (P < 0.05)., Conclusion: The ICP monitored stepwise intracranial decompression technique reduced the perioperative complications of traumatic brain injury through the gradual release of ICP and was beneficial to the prognosis of severe traumatic brain injury treatment.

While purposeful selection is performed partly by software and partly by hand, the stepwise and best subset approaches are automatically performed by software. Two R functions stepAIC() and bestglm() are well designed for stepwise and best subset regression, respectively. The stepAIC() function begins with a full or null model, and methods for stepwise regression can be specified in the direction argument with character values "forward", "backward" and "both". The bestglm() function begins with a data frame containing explanatory variables and response variables. The response variable should be in the last column. Varieties of goodness-of-fit criteria can be specified in the IC argument. The Bayesian information criterion (BIC) usually results in more parsimonious model than the Akaike information criterion.

Background: Long-term success rates using ablation for persistent atrial fibrillation (AF) are disappointing and usually do not exceed 60%., Objectives: This study sought to compare arrhythmia-free survival between pulmonary vein isolation (PVI) and a stepwise approach (full defrag) consisting of PVI, ablation of complex fractionated electrograms, and additional linear ablation lines in the setting of atrial tachycardias (AT) in patients with persistent AF after PVI., Methods: From November 2010 to February 2013, 205 patients (151 men; 61.7 ± 10.2 years of age) underwent de novo ablation for persistent AF. Subsequently, patients were prospectively randomized to either PVI alone (n = 78) or full defrag (n = 75), with 52 patients not randomized due to AF termination with the original PVI. The primary endpoint was recurrence of any AT after a blanking period of 3 months., Results: During the entire study, 241 ablations were performed (mean: 1.59 in the PVI-alone group, 1.55 in the full-defrag group). With the stepwise approach, termination of AF occurred in 45 (60%) patients. However, arrhythmia-free survival did not differ whether patients underwent single or multiple procedures (p = 0.468). Procedure duration, fluoroscopy time, and radiofrequency duration were significantly longer in the full-defrag group (all p < 0.001)., Conclusions: A stepwise approach aimed at AF termination does not seem to provide additional benefit over PVI alone in patients with persistent AF, but it is associated with significantly longer procedural and fluoroscopic duration as well as radiofrequency application time. (The Randomized Catheter Ablation of Persist End Atrial Fibrillation Study [CHASE-AF]; NCT01580124)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

As glycaemic control deteriorates with the progression of type 2 diabetes, treatment guidelines advocate starting basal insulin therapy, and then progressing to a basal-bolus regimen as needed. Nevertheless, although timely intensification of therapy is important to minimise the risk of diabetic complications, considerable clinical inertia exists, not only in the initiation of insulin but also in the progression to multiple-dose insulin regimens. One barrier has been the lack of guidance about how to make the transition from basal-only to basal-bolus insulin therapy. In this review, we discuss how data from the recent FullSTEP study, along with other randomised studies, will help to bridge this gap. Prandial boluses can be added to basal insulin in a stepwise manner, using a straightforward, patient-led dose titration approach and simple estimation of which meal to add the initial prandial bolus to. Reducing the complexity of progression to multiple-dose insulin regimens and empowering patients will lessen the burden on clinicians, improve treatment satisfaction and facilitate timely implementation of treatment guidelines., Competing Interests: Disclosure: Helena W Rodbard has served as a principal investigator in clinical trials sponsored by Novo Nordisk, has served as a consultant on advisory panels and as a speaker for Novo Nordisk and has served in similar capacities for several pharmaceutical companies that have or are developing various forms of insulin therapy. Boris Karolicki is employed by Novo Nordisk Inc. as a Medical Director for modern insulins and insulin-delivery devices.

Traditionally, three ports are used in laparoscopic appendicectomy. However to reduce surgical incision and cost, it is feasible to remove the appendix using fewer ports. In this study, we compared the efficacy of stepwise and standard approach in laparoscopic appendicectomies in children. Between August 2008 and September 2010, 378 children with appendicitis were allotted to either the stepwise or standard laparoscopy group depending on the operating surgeon's preference. In the former group, an operating telescope was inserted first. The number of ports used was based on the pathology (stepwise approach). In the latter group, three ports were inserted in all patients (standard approach). The two groups were similar. In the stepwise group, we performed 95 single port (utilising a scope with an instrument channel), 37 two ports and 13 three ports appendicectomies. In the stepwise group, operating time was shorter (not yet statistically significant) and it reduced the port numbers by more than 50 %. The stepwise approach provides an evidence-based management of appendicitis with comparable outcomes. This procedure further reduces incision trauma, operating times and the cost of operation. However, the reduction of post-operative analgesic requirement needs further study.