Ondokuz Mayıs University

BACKGROUND: Older patients with acute myeloid leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine added to venetoclax had promising efficacy in a previous phase 1b study. METHODS: We randomly assigned previously untreated patients with confirmed AML who were ineligible for standard induction therapy because of coexisting conditions, because they were 75 years of age or older, or both to azacitidine plus either venetoclax or placebo. All patients received a standard dose of azacitidine (75 mg per square meter of body-surface area subcutaneously or intravenously on days 1 through 7 every 28-day cycle); venetoclax (target dose, 400 mg) or matching placebo was administered orally, once daily, in 28-day cycles. The primary end point was overall survival. RESULTS: The intention-to-treat population included 431 patients (286 in the azacitidine-venetoclax group and 145 in the azacitidine-placebo [control] group). The median age was 76 years in both groups (range, 49 to 91). At a median follow-up of 20.5 months, the median overall survival was 14.7 months in the azacitidine-venetoclax group and 9.6 months in the control group (hazard ratio for death, 0.66; 95% confidence interval, 0.52 to 0.85; P<0.001). The incidence of complete remission was higher with azacitidine-venetoclax than with the control regimen (36.7% vs. 17.9%; P<0.001), as was the composite complete remission (complete remission or complete remission with incomplete hematologic recovery) (66.4% vs. 28.3%; P<0.001). Key adverse events included nausea of any grade (in 44% of the patients in the azacitidine-venetoclax group and 35% of those in the control group) and grade 3 or higher thrombocytopenia (in 45% and 38%, respectively), neutropenia (in 42% and 28%), and febrile neutropenia (in 42% and 19%). Infections of any grade occurred in 85% of the patients in the azacitidine-venetoclax group and 67% of those in the control group, and serious adverse events occurred in 83% and 73%, respectively. CONCLUSIONS: In previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone. The incidence of febrile neutropenia was higher in the venetoclax-azacitidine group than in the control group. (Funded by AbbVie and Genentech; VIALE-A ClinicalTrials.gov number, NCT02993523.).

BACKGROUND: The COVID-19 pandemic is having negative effects on societies' mental health. Both the pandemic and the measures taken to combat it can affect individuals' mental health. AIMS: The purpose of this study was to evaluate the levels of depression, anxiety and health anxiety in Turkish society during the COVID-19 pandemic, and to examine the factors affecting these. METHOD: The study was performed using an online questionnaire. Participants were asked to complete a sociodemographic data form, the Hospital Anxiety and Depression Scale (HADS) and the Health Anxiety Inventory (HAI). The effects on depression, anxiety and health anxiety levels of factors such as age, sex, marital status, living with an individual aged above 60, the presence of a new Coronavirus+ patient among friends or relatives, previous and current psychiatric illness and presence of accompanying chronic disease were then investigated. RESULTS: = 155) scored above the cut-off point for anxiety. In regression analysis, female gender, living in urban areas and previous psychiatric illness history were found as risk factors for anxiety; living in urban areas was found as risk factor for depression; and female gender, accompanying chronic disease and previous psychiatric history were found as risk factors for health anxiety. CONCLUSION: The results of this cross-sectional study suggest that the groups most psychologically affected by the COVID-19 pandemic are women, individuals with previous psychiatric illness, individuals living in urban areas and those with an accompanying chronic disease. Priority might therefore be attached to these in future psychiatric planning.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of cases are associated with aquaporin-4 antibodies (AQP4-IgG) and complement-mediated damage to the central nervous system. In a previous small, open-label study involving patients with AQP4-IgG-positive disease, eculizumab, a terminal complement inhibitor, was shown to reduce the frequency of relapse. METHODS: In this randomized, double-blind, time-to-event trial, 143 adults were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first four doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or matched placebo. The continued use of stable-dose immunosuppressive therapy was permitted. The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death). RESULTS: The trial was stopped after 23 of the 24 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. The mean (±SD) annualized relapse rate in the 24 months before enrollment was 1.99±0.94; 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval [CI], 0.02 to 0.20; P<0.001). The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01 to 0.15; P<0.001). The mean change in the EDSS score was -0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, -0.29; 95% CI, -0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was one death from pulmonary empyema in the eculizumab group. CONCLUSIONS: Among patients with AQP4-IgG-positive NMOSD, those who received eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression. (Funded by Alexion Pharmaceuticals; PREVENT ClinicalTrials.gov number, NCT01892345; EudraCT number, 2013-001150-10.).

PURPOSE Ibrutinib has shown activity in non–germinal center B-cell diffuse large B-cell lymphoma (DLBCL). This double-blind phase III study evaluated ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non–germinal center B-cell DLBCL. PATIENTS AND METHODS Patients were randomly assigned at a one-to-one ratio to ibrutinib (560 mg per day orally) plus R-CHOP or placebo plus R-CHOP. The primary end point was event-free survival (EFS) in the intent-to-treat (ITT) population and the activated B-cell (ABC) DLBCL subgroup. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety. RESULTS A total of 838 patients were randomly assigned to ibrutinib plus R-CHOP (n = 419) or placebo plus R-CHOP (n = 419). Median age was 62.0 years; 75.9% of evaluable patients had ABC subtype disease, and baseline characteristics were balanced. Ibrutinib plus R-CHOP did not improve EFS in the ITT (hazard ratio [HR], 0.934) or ABC (HR, 0.949) population. A preplanned analysis showed a significant interaction between treatment and age. In patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS (HR, 0.579), PFS (HR, 0.556), and OS (HR, 0.330) and slightly increased serious adverse events (35.7% v 28.6%), but the proportion of patients receiving at least six cycles of R-CHOP was similar between treatment arms (92.9% v 93.0%). In patients age 60 years or older, ibrutinib plus R-CHOP worsened EFS, PFS, and OS, increased serious adverse events (63.4% v 38.2%), and decreased the proportion of patients receiving at least six cycles of R-CHOP (73.7% v 88.8%). CONCLUSION The study did not meet its primary end point in the ITT or ABC population. However, in patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS, PFS, and OS with manageable safety. In patients age 60 years or older, ibrutinib plus R-CHOP was associated with increased toxicity, leading to compromised R-CHOP administration and worse outcomes. Further investigation is warranted.

The purpose of this study was to evaluate the discoloration of two nanohybrids, two microhybrids, and a posterior composite resin restorative material upon exposure to different drinks--namely tea, cola, coffee, red wine, and water. The colors of all specimens before and after storage in the solutions were measured by a colorimeter based on CIE Lab system, and the color differences thereby calculated. Data were analyzed by two-way analysis of variance (ANOVA) and Tukey's HSD test. According to ANOVA, the restorative material, staining agent, and their interaction were found to play a statistically significant role (P = 0.0001) in color change. Among the staining agents, water consistently showed the lowest deltaE* value for all materials, whereas red wine showed the highest deltaE* value. In other words, for all the materials tested, their color change in staining agents ranked in this increasing order: water < cola < tea < coffee < red wine. In terms of comparison among the five restorative materials, Filtek P60 and Z250 were observed to manifest less color change than the nanohybrids and Quadrant LC.

BACKGROUND: Health care-associated infections from invasive medical devices in the intensive care unit (ICU) are a major threat to patient safety. Most published studies of ICU-acquired infections have come from industrialized western countries. In a Centers for Disease Control and Prevention (CDC) National Nosocomial Infections Surveillance (NNIS) System report, the U.S. pooled mean rates of central venous catheter (CVC)-related bloodstream infections, ventilator-associated pneumonia, and catheter-associated urinary tract infections were 4.0 per 1000 CVC days, 5.4 per 1000 mechanical ventilator days, and 3.9 per Foley catheter days, respectively. OBJECTIVE: To ascertain the incidence of device-associated infections in the ICUs of developing countries. DESIGN: Multicenter, prospective cohort surveillance of device-associated infection by using the CDC NNIS System definitions. SETTING: 55 ICUs of 46 hospitals in Argentina, Brazil, Colombia, India, Mexico, Morocco, Peru, and Turkey that are members of the International Nosocomial Infection Control Consortium (INICC). MEASUREMENTS: Rates of device-associated infection per 100 patients and per 1000 device days. RESULTS: During 2002-2005, 21,069 patients who were hospitalized in ICUs for an aggregate 137,740 days acquired 3095 device-associated infections for an overall rate of 14.7% or 22.5 infections per 1000 ICU days. Ventilator-associated pneumonia posed the greatest risk (41% of all device-associated infections or 24.1 cases [range, 10.0 to 52.7 cases] per 1000 ventilator days), followed by CVC-related bloodstream infections (30% of all device-associated infections or 12.5 cases [range, 7.8 to 18.5 cases] per 1000 catheter days) and catheter-associated urinary tract infections (29% of all device-associated infections or 8.9 cases [range, 1.7 to 12.8 cases] per 1000 catheter days). Notably, 84% of Staphylococcus aureus infections were caused by methicillin-resistant strains, 51% of Enterobacteriaceae isolates were resistant to ceftriaxone, and 59% of Pseudomonas aeruginosa isolates were resistant to fluoroquinolones. The crude mortality rate for patients with device-associated infections ranged from 35.2% (for CVC-associated bloodstream infection) to 44.9% (for ventilator-associated pneumonia). LIMITATIONS: These initial data are not adequate to represent any entire country, and likely variations in the efficiency of surveillance and institutional resources may have affected the rates that were detected. CONCLUSIONS: Device-associated infections in the ICUs of these developing countries pose greater threats to patient safety than in U.S. ICUs. Active infection control programs that perform surveillance of infection and implement guidelines for prevention can improve patient safety and must become a priority in every country.

Importance: Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressive MS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition. Objective: To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition. Design, Setting, and Participants: Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remitting MS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up. Exposures: The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017). Main Outcome and Measure: Conversion to objectively defined secondary progressive MS. Results: Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressive MS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P < .001; 5-year absolute risk, 12% [49 of 407] vs 27% [58 of 213]; median follow-up, 7.6 years [IQR, 5.8-9.6]), as did fingolimod (HR, 0.37; 95% CI, 0.22-0.62; P < .001; 5-year absolute risk, 7% [6 of 85] vs 32% [56 of 174]; median follow-up, 4.5 years [IQR, 4.3-5.1]); natalizumab (HR, 0.61; 95% CI, 0.43-0.86; P = .005; 5-year absolute risk, 19% [16 of 82] vs 38% [62 of 164]; median follow-up, 4.9 years [IQR, 4.4-5.8]); and alemtuzumab (HR, 0.52; 95% CI, 0.32-0.85; P = .009; 5-year absolute risk, 10% [4 of 44] vs 25% [23 of 92]; median follow-up, 7.4 years [IQR, 6.0-8.6]). Initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion than initial treatment with glatiramer acetate or interferon beta (HR, 0.66; 95% CI, 0.44-0.99; P = .046); 5-year absolute risk, 7% [16 of 235] vs 12% [46 of 380]; median follow-up, 5.8 years [IQR, 4.7-8.0]). The probability of conversion was lower when glatiramer acetate or interferon beta was started within 5 years of disease onset vs later (HR, 0.77; 95% CI, 0.61-0.98; P = .03; 5-year absolute risk, 3% [4 of 120] vs 6% [2 of 38]; median follow-up, 13.4 years [IQR, 11-18.1]). When glatiramer acetate or interferon beta were escalated to fingolimod, alemtuzumab, or natalizumab within 5 years vs later, the HR was 0.76 (95% CI, 0.66-0.88; P < .001; 5-year absolute risk, 8% [25 of 307] vs 14% [46 of 331], median follow-up, 5.3 years [IQR], 4.6-6.1). Conclusions and Relevance: Among patients with relapsing-remitting MS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressive MS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies' risks, may help inform decisions about DMT selection.

At least 600000 individuals worldwide annually die of hepatitis B virus (HBV)-related diseases, such as chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Many viral factors, such as viral load, genotype, and specific viral mutations, are known to affect disease progression. HBV reverse transcriptase does not have a proofreading function, therefore, many HBV genotypes, sub-genotypes, mutants, and recombinants emerge. Differences between genotypes in response to antiviral treatment have been determined. To date, 10 HBV genotypes, scattered across different geographical regions, have been identified. For example, genotype A has a tendency for chronicity, whereas viral mutations are frequently encountered in genotype C. Both chronicity and mutation frequency are common in genotype D. LC and progression to HCC are more commonly encountered with genotypes C and D than the other genotypes. Pathogenic differences between HBV genotypes explain disease intensity, progression to LC, and HCC. In conclusion, genotype determination in CHB infection is important in estimating disease progression and planning optimal antiviral treatment.

This study evaluated the dimensionality, invariance, and reliability of the Depression, Anxiety, and Stress Scale–21 (DASS-21) within and across Brazil, Canada, Hong Kong, Romania, Taiwan, Turkey, United Arab Emirates, and the United States ( N = 2,580) in college student samples. We used confirmatory factor analyses to compare the fit of four different factor structures of the DASS-21: a unidimensional model, a three-correlated-factors model, a higher order model, and a bifactor model. The bifactor model, with three specific factors (depression, anxiety, and stress) and one general factor (general distress), presented the best fit within each country. We also calculated ancillary bifactor indices of model-based dimensionality of the DASS-21 and model-based reliability to further examine the validity of the composite total and subscale scores and the use of unidimensional modeling. Results suggested the DASS-21 can be used as a unidimensional scale. Finally, measurement invariance of the best fitting model was tested across countries indicating configural invariance. The traditional three-correlated-factors model presented scalar invariance across Canada, Hong Kong, Romania, Taiwan, and the United States. Overall, these analyses indicate that the DASS-21 would best be used as a general score of distress rather than three separate factors of depression, anxiety, and stress, in the countries studied.

The removal of heavy metals from wastewater using adsorbants such as waste tea, Turkish coffee, exhausted coffee, nut and walnut shells has investigated. Batch studies were conducted at room temperature and adsorption experiments were carried out by shaking 0.3 g of adsorbent with 100 ml synthetic wastewater containing Cr (VI). Cd (II) and A1 (III) metal ions. The remaining concentration of heavy metals in each samples after adsorption at various time intervals was determined spectrophotometrically. Batch studies showed that these adsorbents exhibit a good adsorption potential for A1 (III) metalions. The adsorption ratios of A1(HI) were as 98, 99, 96, 99.5 and 96% for waste tea, Turkish coffee, exhausted coffee, nut and walnut shells, respectively. These results were compared with those obtained using activated carbon as adsorbent. The batch adsorption kinetics and adsorption equilibria were examined and described by a first order reversible reaction and Freundlich isotherm, respectively. The first order rate and isotherm constants have been calculated.

Forecasting electricity demand requires accurate and sustainable data acquisition systems which rely on smart grid systems. To predict the demand expected by the grid, many smart meters are required to collect sufficient data. However, the problem is multi-dimensional and simple power aggregation techniques may fail to capture the relational similarities between the various types of users. Therefore, accurate forecasting of energy demand plays a key role in planning, setting up, and implementing networks for the renewable energy systems, and continuously providing energy to consumers. This is also a key element for planning the requirement for storage devices and their storage capacity. Additionally, errors in hour-to-hour forecasting may cause considerable economic and consumer losses. This paper aims to address the knowledge gap in techniques based on machine learning (ML) for predicting load by using two forecasting methods: Auto Regressive Integrated Moving Average (ARIMA) and Artificial Neural Network (ANN); and compares the performance of both methods using Mean Absolute Percentage Error (MAPE). The study is based on daily real load electricity data for 709 individual households were randomly chosen over an 18-month period in Ireland. The results reveal that the (ANN) offers better results than ARIMA for the non-linear load data.

BACKGROUND: Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterised by hypotonia, ataxia, cognitive impairment, abnormal eye movements, respiratory control disturbances and a distinctive mid-hindbrain malformation. JS demonstrates substantial phenotypic variability and genetic heterogeneity. This study provides a comprehensive view of the current genetic basis, phenotypic range and gene-phenotype associations in JS. METHODS: We sequenced 27 JS-associated genes in 440 affected individuals (375 families) from a cohort of 532 individuals (440 families) with JS, using molecular inversion probe-based targeted capture and next-generation sequencing. Variant pathogenicity was defined using the Combined Annotation Dependent Depletion algorithm with an optimised score cut-off. RESULTS: We identified presumed causal variants in 62% of pedigrees, including the first B9D2 mutations associated with JS. 253 different mutations in 23 genes highlight the extreme genetic heterogeneity of JS. Phenotypic analysis revealed that only 34% of individuals have a 'pure JS' phenotype. Retinal disease is present in 30% of individuals, renal disease in 25%, coloboma in 17%, polydactyly in 15%, liver fibrosis in 14% and encephalocele in 8%. Loss of CEP290 function is associated with retinal dystrophy, while loss of TMEM67 function is associated with liver fibrosis and coloboma, but we observe no clear-cut distinction between JS subtypes. CONCLUSIONS: This work illustrates how combining advanced sequencing techniques with phenotypic data addresses extreme genetic heterogeneity to provide diagnostic and carrier testing, guide medical monitoring for progressive complications, facilitate interpretation of genome-wide sequencing results in individuals with a variety of phenotypes and enable gene-specific treatments in the future.

The Internet of Things (IoT) ecosystem has proliferated based on the use of the internet and cloud-based technologies in the industrial area. IoT technology used in the industry has become a large-scale network based on the increasing amount of data and number of devices. Industrial IoT (IIoT) networks are intrinsically unprotected against cyber threats and intrusions. It is, therefore, significant to develop Intrusion Detection Systems (IDS) in order to ensure the security of the IIoT networks. Three different models were proposed to detect intrusions in the IIoT network by using deep learning architectures of Convolutional Neural Network (CNN), Long Short Term Memory (LSTM), and CNN + LSTM generated from a hybrid combination of these. In the study conducted by using the UNSW-NB15 and X-IIoTID datasets, normal and abnormal data were determined and compared with other studies in the literature following a binary and multi-class classification. The hybrid CNN + LSTM model attained the highest accuracy value for intrusion detection in both datasets among the proposed models. The proposed CNN + LSTM architecture attained an accuracy of 93.21% for binary classification and 92.9% for multi-class classification in the UNSW-NB15 dataset while the same model attained a detection accuracy of 99.84% for binary classification and 99.80% for multi-class classification in the X-IIoTID dataset. In addition, the accurate detection success of the implemented models regarding the types of attacks within the datasets was evaluated.

BACKGROUND: The objective of this study was to determine the contamination rate of the healthcare workers' (HCWs') mobile phones and hands in operating room and ICU. Microorganisms from HCWs' hands could be transferred to the surfaces of the mobile phones during their use. METHODS: 200 HCWs were screened; samples from the hands of 200 participants and 200 mobile phones were cultured. RESULTS: In total, 94.5% of phones demonstrated evidence of bacterial contamination with different types of bacteria. The gram negative strains were isolated from mobile phones of 31.3% and the ceftazidime resistant strains from the hands were 39.5%. S. aureus strains isolated from mobile phones of 52% and those strains isolated from hands of 37.7% were methicillin resistant. Distributions of the isolated microorganisms from mobile phones were similar to hands isolates. Some mobile phones were contaminated with nosocomial important pathogens. CONCLUSION: These results showed that HCWs' hands and their mobile phones were contaminated with various types of microorganisms. Mobile phones used by HCWs in daily practice may be a source of nosocomial infections in hospitals.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for their anti-inflammatory, analgesic, and antipyretic effects. NSAIDs generally work by blocking the production of prostaglandins (PGs) through the inhibition of two cyclooxygenase enzymes. PGs are key factors in many cellular processes, such as gastrointestinal cytoprotection, hemostasis and thrombosis, inflammation, renal hemodynamics, turnover of cartilage, and angiogenesis. Interest has grown in the various effects of NSAIDs during the last decade. Epidemiological studies have revealed the reduced risk of several cancer types and neurodegenerative diseases by prolonged use of NSAIDs. Recent advances in the understanding of the cellular and molecular mechanisms of NSAIDs will accelerate the processes of discovery and clinical implementation. This review summarizes the molecular mechanisms of NSAIDs on the body systems.

Many studies have reported that the contents of cigarette smoke negatively affect sperm parameters, seminal plasma, and various other fertility factors. Nevertheless, the actual effect of smoking on male fertility is not clear. The effect of smoking on semen parameters is based on the well-established biological finding that smoking increases the presence of reactive oxygen species, thereby resulting in oxidative stress (OS). OS has devastating effects on sperm parameters, such as viability and morphology, and impairs sperm function, hence reducing male fertility. However, not all studies have come to the same conclusions. This review sheds light upon the arguable association between smoking and male fertility and also assesses the impact of non-smoking routes of tobacco consumption on male infertility. It also highlights the evidence that links smoking with male infertility, including newly emerging genetic and epigenetic data, and discusses the clinical implications thereof.

Technological devices have become essential components of daily life. However, their deleterious effects on the body, particularly on the nervous system, are well known. Electromagnetic fields (EMF) have various chemical effects, including causing deterioration in large molecules in cells and imbalance in ionic equilibrium. Despite being essential for life, oxygen molecules can lead to the generation of hazardous by-products, known as reactive oxygen species (ROS), during biological reactions. These reactive oxygen species can damage cellular components such as proteins, lipids and DNA. Antioxidant defense systems exist in order to keep free radical formation under control and to prevent their harmful effects on the biological system. Free radical formation can take place in various ways, including ultraviolet light, drugs, lipid oxidation, immunological reactions, radiation, stress, smoking, alcohol and biochemical redox reactions. Oxidative stress occurs if the antioxidant defense system is unable to prevent the harmful effects of free radicals. Several studies have reported that exposure to EMF results in oxidative stress in many tissues of the body. Exposure to EMF is known to increase free radical concentrations and traceability and can affect the radical couple recombination. The purpose of this review was to highlight the impact of oxidative stress on antioxidant systems.

Prevention of irreversible disability is currently the most important goal of disease modifying therapy for multiple sclerosis. The disability outcomes used in most clinical trials rely on progression of Expanded Disability Status Scale score confirmed over 3 or 6 months. However, sensitivity and stability of this metric has not been extensively evaluated. Using the global MSBase cohort study, we evaluated 48 criteria of disability progression, testing three definitions of baseline disability, two definitions of progression magnitude, two definitions of long-term irreversibility and four definitions of event confirmation period. The study outcomes comprised the rates of detected progression events per 10 years and the proportions of the recorded events persistent at later time points. To evaluate the ratio of progression frequency and stability for each criterion, we calculated the proportion of events persistent over the five subsequent years once progression was achieved. Finally, we evaluated the clinical and demographic determinants characterising progression events and, for those that regressed back to baseline, determinants of their subsequent regression. The study population consisted of 16 636 patients with the minimum of three recorded disability scores, totalling 112 584 patient-years. The progression rates varied between 0.41 and 1.14 events per 10 years, with the length of required confirmation interval as the most important determinant of the observed variance. The concordance among all tested progression criteria was only 17.3%. Regression of disability occurred in 11-34% of the progression events over the five subsequent years. The most important determinant of progression stability was the length of the confirmation period. For the most accurate set of the progression criteria, the proportions of 3-, 6-, 12- or 24-month confirmed events persistent over 5 years reached 70%, 74%, 80% and 89%, respectively. Regression post progression was more common in younger patients, relapsing-remitting disease course, and after a smaller change in disability, and was inflated by higher visit frequency. These results suggest that the disability outcomes based on 3-6-month confirmed disability progression overestimate the accumulation of permanent disability by up to 30%. This could lead to spurious results in short-term clinical trials, and the issue may be magnified further in cohorts consisting predominantly of younger patients and patients with relapsing-remitting disease. Extension of the required confirmation period increases the persistence of progression events.

We collected developmental, survival, and reproduction data for Aphis fabae Scopoli (Hemiptera: Aphididae) reared on faba bean, Vicia faba L. 'Sevilla' at four constant temperatures (15, 20, 25, and 30°C), 70% relative humidity, and a photoperiod of 16:8 (L:D) h. The highest intrinsic rate of increase (r = 0.4347 d(-1)) and finite rate (λ = 1.5445 d(-1)) were observed at 25°C. The population projection based on the age-stage, two-sex life table quantitatively revealed the growth potential and stage structure of the aphid. We have included the following suggestions to aid researchers in life table studies: 1) The bootstrap method should be used to estimate the variance and SEs of developmental time, survival rate, fecundity, and population parameters. 2) The required number of bootstraps is dependent on the life table data--the higher the variation among individuals, the higher the number of bootstraps should be. In most cases, we suggest that 100,000 bootstraps should be used to obtain a stable estimate of variance and SEs. 3) Computer projection based on the age-stage, two-sex life table should be used to reveal the stage structure during population growth. 4) We used a simple equation based on the total fecundity, survival rate to adult stage, and first reproductive age to detect possible errors in life table parameters. 5) To assist readers in comprehending results, life table studies should include the cohort size, preadult survival rate, number of emerged female adults, mean fecundity, survival and fecundity curves, and population parameters.

Abstract This study discusses preservice teachers' achievement barriers to technology integration, using principles of technological pedagogical content knowledge (TPACK) as an evaluative framework. Technology‐capable participants each freely chose a content area to comprise project. Data analysis based on interactions among core components of TPACK revealed that participants struggled with developing new knowledge. Lack of pedagogical experience limited development of appropriate technology integration approaches. Creating new knowledge bases based on different teaching components can be difficult for preservice teachers because it requires a deep understanding of core knowledge and interpretation of the teaching context and its dynamics. Developing pedagogical content knowledge (PCK) is an important factor in overall technology integration; teachers must make it a priority to acquire PCK before integrating technology. In preservice teacher education, PCK development must be supported with actual teaching experience. We believe that the results of the study may provide valuable insight with respect to proper focus on technology integration and recognizing limitations and challenges within TPACK principles to both those who teach technology integration and those who design TPACK‐based activities.