An Expert System for Weed Management in Winter Wheat

Making weed control decisions is often a challenging process. The broad spectrum of weeds found in many fields, combined with the many herbicides on the market, can make choosing an herbicide or tank-mixture for a particular field difficult. Because of the important strategic role of wheat, a practical expert system is necessary to manage of weed control in wheat fields. This expert system has a step-by- step problem-solving procedure based on important factors relating to weed management. Expert system for weed management provides advice on the base of interactions of weeds and wheat including chemical and mechanical weeds control treatments and selects the best herbicide with optimum dosage and method of application. Economical recommendation can be made by estimating yield loss due to the weeds, wheat price, expected yield and herbicide cost. Recommendations are base on wheat variety, date of planting; growth stages of wheat, weed species, weed and crop density, history of herbicide use and climatic factors

An Overview of Longitudinal Data Analysis Methods for Neurological Research

The purpose of this article is to provide a concise, broad and readily accessible overview of longitudinal data analysis methods, aimed to be a practical guide for clinical investigators in neurology. In general, we advise that older, traditional methods, including (1) simple regression of the dependent variable on a time measure, (2) analyzing a single summary subject level number that indexes changes for each subject and (3) a general linear model approach with a fixed-subject effect, should be reserved for quick, simple or preliminary analyses. We advocate the general use of mixed-random and fixed-effect regression models for analyses of most longitudinal clinical studies. Under restrictive situations or to provide validation, we recommend: (1) repeated-measure analysis of covariance (ANCOVA), (2) ANCOVA for two time points, (3) generalized estimating equations and (4) latent growth curve/structural equation models

Validity, Significance, Strengths, Limitations, and Evidentiary Value of Real-World Clinical Data for Combination Therapy in Alzheimer's Disease: Comparison of Efficacy and Effectiveness Studies

Background: Randomized controlled efficacy trials (RCTs), the scientific gold standard, are required for regulatory approval of Alzheimer's disease (AD) interventions, yet provide limited information regarding real-world therapeutic effectiveness. Objective: To compare the nature of evidence regarding the combination of approved AD treatments from RCTs versus long-term observational controlled studies (LTOCs). Methods: Comparisons of strengths, limitations, and evidence level for monotherapy [cholinesterase inhibitor (ChEI) or memantine] and combination therapy (ChEI + memantine) in RCTs versus LTOCs. Results: RCTs examined highly selected populations over months. LTOCs collected data across multiple AD stages in large populations over many years. RCTs and LTOCs show similar patterns favoring combination over monotherapy over placebo/no treatment. Long-term combination therapy compared to monotherapy reduced cognitive and functional decline and delayed time to nursing home admission. Persistent treatment was associated with slower decline. While LTOCs used control groups, adjusted for multiple covariates, had higher external validity, and favorable ethical, practical and cost considerations, their limitations included potential selection bias due to lack of placebo comparisons and randomization. Conclusions: Naturalistic LTOCs provide complementary long-term level II evidence to complement level I evidence from short-term RCTs regarding therapeutic effectiveness in AD that may otherwise be unobtainable. A coordinated strategy/consortium to pool LTOC data from multiple centers to estimate long-term comparative effectiveness, risks/benefits, and costs of AD treatments is needed

In the Information Age, Do Dementia Caregivers Get the Information They Need? Semi-Structured Interviews to Determine Informal Caregivers’ Education Needs, Barriers, and Preferences

Most patients with dementia or cognitive impairment receive care from family members, often untrained for this challenging role. Caregivers may not access publicly available caregiving information, and caregiver education programs are not widely implemented clinically. Prior large surveys yielded broad quantitative understanding of caregiver information needs, but do not illuminate the in-depth, rich, and nuanced caregiver perspectives that can be gleaned using qualitative methodology. We aimed to understand perspectives about information sources, barriers and preferences, through semi-structured interviews with 27 caregivers. Content analysis identified important theme

Memantine in patients with Alzheimer's disease receiving donepezil: new analyses of efficacy and safety for combination therapy

Introduction: Memantine and cholinesterase inhibitors potentially offer additional benefits in Alzheimer's disease (AD) when used together. This study assessed the efficacy and safety of combination treatment with memantine added to stable donepezil in patients with moderate to severe AD, and in a subset with moderate AD. Methods: Post hoc meta-analyses of data combined from two 24-week, randomised, double-blind, placebo-controlled trials of memantine 20 mg/day versus placebo, added to a stable cholinesterase inhibitor, were conducted. Data were included for all patients receiving donepezil 10 mg/day with Mini-Mental State Examination (MMSE) scores < 20 (n = 510). Efficacy was assessed using measures of cognition, function, and global status. Furthermore, marked clinical worsening, defined as concurrent deterioration from baseline in the three main efficacy domains, and safety, measured by treatment-emergent adverse events, were assessed. Analyses were performed for patients with moderate to severe AD (MMSE 5-19; MOD-SEV subgroup), and also for patients with moderate AD (MMSE 10-19; MOD subgroup; n = 367). Results: At week 24, in the MOD-SEV subgroup, patients receiving memantine added to donepezil significantly outperformed those receiving placebo added to donepezil in measures of cognition (P < 0.0001), function (P = 0.02), and global status (P = 0.010), with standardised mean differences (SMDs) of 0.36, 0.21, and 0.23, respectively (all last observation carried forward). Similarly, in the MOD subgroup, significant benefits were observed for cognition (P = 0.008), function (P = 0.04) and global status (P = 0.008), with SMDs of 0.28, 0.21, and 0.28, respectively. Significantly fewer patients receiving memantine added to donepezil showed marked clinical worsening than those receiving placebo added to donepezil, in both subgroups (MOD-SEV: 8.7% versus 20.4%, P = 0.0002; MOD: 5.9% versus 15.0%, P = 0.006). The incidence of adverse events was similar between treatment groups. Conclusions: These results support and extend previous evidence that combination treatment with memantine added to stable donepezil in patients with moderate AD, and in those with moderate to severe AD, is associated with significant benefits in reducing 24-week decline in cognition, function and global status. Combination treatment produces substantially reduced rates of marked clinical worsening, has good safety and tolerability, and generates effect sizes that are both statistically significant and clinically meaningful

A web-based normative calculator for the uniform data set (UDS) neuropsychological test battery

Introduction: With the recent publication of new criteria for the diagnosis of preclinical Alzheimer's disease (AD), there is a need for neuropsychological tools that take premorbid functioning into account in order to detect subtle cognitive decline. Using demographic adjustments is one method for increasing the sensitivity of commonly used measures. We sought to provide a useful online z-score calculator that yields estimates of percentile ranges and adjusts individual performance based on sex, age and/or education for each of the neuropsychological tests of the National Alzheimer's Coordinating Center Uniform Data Set (NACC, UDS). In addition, we aimed to provide an easily accessible method of creating norms for other clinical researchers for their own, unique data sets. Methods: Data from 3,268 clinically cognitively-normal older UDS subjects from a cohort reported by Weintraub and colleagues (2009) were included. For all neuropsychological tests, z-scores were estimated by subtracting the raw score from the predicted mean and then dividing this difference score by the root mean squared error term (RMSE) for a given linear regression model. Results: For each neuropsychological test, an estimated z-score was calculated for any raw score based on five different models that adjust for the demographic predictors of SEX, AGE and EDUCATION, either concurrently, individually or without covariates. The interactive online calculator allows the entry of a raw score and provides five corresponding estimated z-scores based on predictions from each corresponding linear regression model. The calculator produces percentile ranks and graphical output. Conclusions: An interactive, regression-based, normative score online calculator was created to serve as an additional resource for UDS clinical researchers, especially in guiding interpretation of individual performances that appear to fall in borderline realms and may be of particular utility for operationalizing subtle cognitive impairment present according to the newly proposed criteria for Stage 3 preclinical Alzheimer's disease

Insights into globalization: comparison of patient characteristics and disease progression among geographic regions in a multinational Alzheimer’s disease clinical program

Background: Globalization of clinical trials has important consequences for trial planning and interpretation. This study investigated heterogeneity in patient characteristics and outcomes among world regions in the global idalopirdine Phase 3 clinical program. Methods: Data were pooled from three 24-week randomized controlled trials in patients aged ≥ 50 years with mild-to-moderate Alzheimer’s disease (AD) (n = 2506). Patients received idalopirdine (10, 30, or 60 mg/day) or placebo, added to cholinesterase inhibitor treatment. Patients were categorized into the following regions: Eastern Europe/Turkey (n = 759), Western Europe/Israel (n = 709), USA/Canada (n = 444), South America/Mexico (n = 361), Asia (n = 134), and Australia/South Africa (n = 99). For each region, operational characteristics, baseline demographic and clinical characteristics, adverse events, and mean change from baseline to week 24 in clinical rating scale scores (placebo group only) were summarized using descriptive statistics. Results: Completion rates were 0.86–0.90 in all regions. Heterogeneity among global regions was evident. Protocol deviations were twice as common in South America/Mexico as in USA/Canada (2.64 vs 1.35 per patient screened). Educational level ranged from 9.2 years in South America/Mexico to 13.4 years in USA/Canada. APOE ε4 carriage was 80.6% in Australia/South Africa, 63.1% in Western Europe/Israel, and &lt; 60% in other regions. Screening Mini-Mental State Examination scores were higher in Eastern Europe/Turkey (18.0) and USA/Canada (17.5) than in other regions (16.9–17.1). Baseline AD Assessment Scale-Cognitive subscale (ADAS-Cog) scores ranged from 24.3 in USA/Canada to 27.2 in South America/Mexico. Baseline AD Cooperative Study - Activities of Daily Living, 23-item version (ADCS-ADL23) scores ranged from 58.5 in USA/Canada to 53.5 in Eastern Europe/Turkey. In the placebo group, adverse events were 1.6–1.7 times more common in Western Europe/Israel, USA/Canada, and Australia/South Africa than in Eastern Europe/Turkey. On the ADAS-Cog, Australia/South Africa and Western Europe/Israel showed the most worsening among patients receiving placebo (1.56 and 1.40 points, respectively), whereas South America/Mexico showed an improvement (−0.71 points). All regions worsened on the ADCS-ADL23, from −3.21 points in Western Europe/Israel to −0.59 points in Eastern Europe/Turkey. Conclusions: Regional heterogeneity - in terms of study conduct, patient characteristics, and outcomes-exists, and should be accounted for, when planning and conducting multinational AD clinical trials. Trial registration ClinicalTrials.gov, NCT01955161. Registered on 27 September 2013. ClinicalTrials.gov, NCT02006641. Registered on 5 December 2013. ClinicalTrials.gov, NCT02006654. Registered on 5 December 2013

Inter-Rater Reliability of Preprocessing EEG Data: Impact of Subjective Artifact Removal on Associative Memory Task ERP Results

The processing of EEG data routinely involves subjective removal of artifacts during a preprocessing stage. Preprocessing inter-rater reliability (IRR) and how differences in preprocessing may affect outcomes of primary event-related potential (ERP) analyses has not been previously assessed. Three raters independently preprocessed EEG data of 16 cognitively healthy adult participants (ages 18–39 years) who performed a memory task. Using intraclass correlations (ICCs), IRR was assessed for Early-frontal, Late-frontal, and Parietal Old/new memory effects contrasts across eight regions of interest (ROIs). IRR was good to excellent for all ROIs; 22 of 26 ICCs were above 0.80. Raters were highly consistent in preprocessing across ROIs, although the frontal pole ROI (ICC range 0.60–0.90) showed less consistency. Old/new parietal effects had highest ICCs with the lowest variability. Rater preprocessing differences did not alter primary ERP results. IRR for EEG preprocessing was good to excellent, and subjective rater-removal of EEG artifacts did not alter primary memory-task ERP results. Findings provide preliminary support for robustness of cognitive/memory task-related ERP results against significant inter-rater preprocessing variability and suggest reliability of EEG to assess cognitive-neurophysiological processes multiple preprocessors are involved