A NOVEL STUDY PARADIGM FOR LONG-TERM PREVENTION TRIALS IN ALZHEIMER DISEASE: THE PLACEBO GROUP SIMULATION APPROACH (PGSA). APPLICATION TO MCI DATA FROM THE NACC DATABASE

2014 ◽  
pp. 1-11
Author(s):  
M. Berres ◽  
W.A. Kukull ◽  
A.R. Miserez ◽  
A.U. Monsch ◽  
S.E. Monsell ◽  
...  
Keyword(s):  
Placebo Group ◽  
Mixed Model ◽  
Ethical Issues ◽  
Neuropsychological Test ◽  
Simulated Data ◽  
Test Battery ◽  
Simulation Approach ◽  
Prevention Trials ◽  
Neuropsychological Outcomes

INTRODUCTION: The PGSA (Placebo Group Simulation Approach) aims at avoiding problems of sample representativeness and ethical issues typical of placebo-controlled secondary prevention trials with MCI patients. The PGSA uses mathematical modeling to forecast the distribution of quantified outcomes of MCI patient groups based on their own baseline data established at the outset of clinical trials. These forecasted distributions are then compared with the distribution of actual outcomes observed on candidate treatments, thus substituting for a concomitant placebo group. Here we investigate whether a PGSA algorithm that was developed from the MCI population of ADNI 1*, can reliably simulate the distribution of composite neuropsychological outcomes from a larger, independently selected MCI subject sample. Methods: Data available from the National Alzheimer's Coordinating Center (NACC) were used. We included 1523 patients with single or multiple domain amnestic mild cognitive impairment (aMCI) and at least two follow-ups after baseline. In order to strengthen the analysis and to verify whether there was a drift over time in the neuropsychological outcomes, the NACC subject sample was split into 3 subsamples of similar size. The previously described PGSA algorithm for the trajectory of a composite neuropsychological test battery (NTB) score was adapted to the test battery used in NACC. Nine demographic, clinical, biological and neuropsychological candidate predictors were included in a mixed model; this model and its error terms were used to simulate trajectories of the adapted NTB. Results The distributions of empirically observed and simulated data after 1, 2 and 3 years were very similar, with some over-estimation of decline in all 3 subgroups. The by far most important predictor of the NTB trajectories is the baseline NTB score. Other significant predictors are the MMSE baseline score and the interactions of time with ApoE4 and FAQ (functional abilities). These are essentially the same predictors as determined for the original NTB score. Conclusion: An algorithm comprising a small number of baseline variables, notably cognitive performance at baseline, forecasts the group trajectory of cognitive decline in subsequent years with high accuracy. The current analysis of 3 independent subgroups of aMCI patients from the NACC database supports the validity of the PGSA longitudinal algorithm for a NTB. Use of the PGSA in long-term secondary AD prevention trials deserves consideration.

Long-term seizure outcomes after pediatric temporal lobectomy: does brain MRI lesion matter?

2019 ◽  
Vol 24 (2) ◽  
pp. 200-208
Author(s):  
Ravindra Arya ◽  
Francesco T. Mangano ◽  
Paul S. Horn ◽  
Sabrina K. Kaul ◽  
Serena K. Kaul ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Hippocampal Sclerosis ◽  
Brain Mri ◽  
Temporal Lobectomy ◽  
Seizure Freedom ◽  
Seizure Onset

OBJECTIVEThere is emerging data that adults with temporal lobe epilepsy (TLE) without a discrete lesion on brain MRI have surgical outcomes comparable to those with hippocampal sclerosis (HS). However, pediatric TLE is different from its adult counterpart. In this study, the authors investigated if the presence of a potentially epileptogenic lesion on presurgical brain MRI influences the long-term seizure outcomes after pediatric temporal lobectomy.METHODSChildren who underwent temporal lobectomy between 2007 and 2015 and had at least 1 year of seizure outcomes data were identified. These were classified into lesional and MRI-negative groups based on whether an epilepsy-protocol brain MRI showed a lesion sufficiently specific to guide surgical decisions. These patients were also categorized into pure TLE and temporal plus epilepsies based on the neurophysiological localization of the seizure-onset zone. Seizure outcomes at each follow-up visit were incorporated into a repeated-measures generalized linear mixed model (GLMM) with MRI status as a grouping variable. Clinical variables were incorporated into GLMM as covariates.RESULTSOne hundred nine patients (44 females) were included, aged 5 to 21 years, and were classified as lesional (73%), MRI negative (27%), pure TLE (56%), and temporal plus (44%). After a mean follow-up of 3.2 years (range 1.2–8.8 years), 66% of the patients were seizure free for ≥ 1 year at last follow-up. GLMM analysis revealed that lesional patients were more likely to be seizure free over the long term compared to MRI-negative patients for the overall cohort (OR 2.58, p < 0.0001) and for temporal plus epilepsies (OR 1.85, p = 0.0052). The effect of MRI lesion was not significant for pure TLE (OR 2.64, p = 0.0635). Concordance of ictal electroencephalography (OR 3.46, p < 0.0001), magnetoencephalography (OR 4.26, p < 0.0001), and later age of seizure onset (OR 1.05, p = 0.0091) were associated with a higher likelihood of seizure freedom. The most common histological findings included cortical dysplasia types 1B and 2A, HS (40% with dual pathology), and tuberous sclerosis.CONCLUSIONSA lesion on presurgical brain MRI is an important determinant of long-term seizure freedom after pediatric temporal lobectomy. Pediatric TLE is heterogeneous regarding etiologies and organization of seizure-onset zones with many patients qualifying for temporal plus nosology. The presence of an MRI lesion determined seizure outcomes in patients with temporal plus epilepsies. However, pure TLE had comparable surgical seizure outcomes for lesional and MRI-negative groups.

Concussion, neuroethics, and sport: Policies of the past do not suffice for the future

2017 ◽  
Author(s):  
Brad Partridge ◽  
Wayne Hall
Keyword(s):  
Mental Health ◽  
Head Trauma ◽  
Mental Health Problems ◽  
Ethical Issues ◽  
Cognitive Impairments ◽  
Concussion Management ◽  
Design And Implementation ◽  
The Past ◽  
Management Policies

Concussion management policies have become a major priority worldwide for sports that involve frequent collisions between participants because repeated head trauma has been associated with long-term cognitive impairments, mental health problems, and some forms of neurological degeneration. A number of concussion management policies have been developed by professional bodies and subsequently adopted by various sporting leagues. These have offered little guidance on how to navigate ethical issues in identifying and managing concussion. This chapter discusses ethical issues that arise in the diagnosis of concussion, debates about the longer-term consequences of repeated concussion injuries, and the design and implementation of policies that aim to prevent and manage concussion injuries in sporting matches.

scholarly journals Improved Cardiovascular Tolerance to Hemorrhage after Oral Resveratrol Pretreatment in Dogs

2021 ◽  
Vol 8 (7) ◽  
pp. 129
Author(s):  
Jennifer Davis ◽  
Anthea L. Raisis ◽  
Claire R. Sharp ◽  
Rachel E. Cianciolo ◽  
Steven C. Wallis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Placebo Group ◽  
Blood Loss ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Kidney Injury ◽  
Bleeding Risk ◽  
Canine Model ◽  
Coagulation Parameters ◽  
Renal Tubular

Resveratrol has been shown to preserve organ function and improve survival in hemorrhagic shock rat models. This study investigated whether seven days of oral resveratrol could improve hemodynamic response to hemorrhage and confer benefits on risk of acute kidney injury (AKI) without inducing coagulopathy in a canine model. Twelve greyhound dogs were randomly allocated to receive oral resveratrol (1000 mg/day) or placebo for seven days prior to inducing hemorrhage until a targeted mean blood pressure of ≤40 mmHg was achieved. AKI biomarkers and coagulation parameters were measured before, immediately following, and two hours after hemorrhage. Dogs were euthanized, and renal tissues were examined at the end of the experiment. All investigators were blinded to the treatment allocation. A linear mixed model was used to assess effect of resveratrol on AKI biomarkers and coagulation parameters while adjusting for volume of blood loss. A significant larger volume of blood loss was required to achieve the hypotension target in the resveratrol group compared to placebo group (median 64 vs. 55 mL/kg respectively, p = 0.041). Although histological evidence of AKI was evident in all dogs, the renal tubular injury scores were not significantly different between the two groups, neither were the AKI biomarkers. Baseline (pre-hemorrhage) maximum clot firmness on the Rotational Thromboelastometry (ROTEM®) was stronger in the resveratrol group than the placebo group (median 54 vs. 43 mm respectively, p = 0.009). In summary, seven days of oral resveratrol did not appear to induce increased bleeding risk and could improve greyhound dogs’ blood pressure tolerance to severe hemorrhage. Renal protective effect of resveratrol was, however, not observed.

scholarly journals Transdisciplinary AI Observatory—Retrospective Analyses and Future-Oriented Contradistinctions

Philosophies ◽  
2021 ◽  
Vol 6 (1) ◽  
pp. 6
Author(s):  
Nadisha-Marie Aliman ◽  
Leon Kester ◽  
Roman Yampolskiy
Keyword(s):  
Ethical Issues ◽  
Descriptive Analysis ◽  
Research Direction ◽  
Short Term ◽  
Safety Critical ◽  
Safety Research ◽  
Hands On ◽  
Near Term ◽  
Ai Safety

In the last years, artificial intelligence (AI) safety gained international recognition in the light of heterogeneous safety-critical and ethical issues that risk overshadowing the broad beneficial impacts of AI. In this context, the implementation of AI observatory endeavors represents one key research direction. This paper motivates the need for an inherently transdisciplinary AI observatory approach integrating diverse retrospective and counterfactual views. We delineate aims and limitations while providing hands-on-advice utilizing concrete practical examples. Distinguishing between unintentionally and intentionally triggered AI risks with diverse socio-psycho-technological impacts, we exemplify a retrospective descriptive analysis followed by a retrospective counterfactual risk analysis. Building on these AI observatory tools, we present near-term transdisciplinary guidelines for AI safety. As further contribution, we discuss differentiated and tailored long-term directions through the lens of two disparate modern AI safety paradigms. For simplicity, we refer to these two different paradigms with the terms artificial stupidity (AS) and eternal creativity (EC) respectively. While both AS and EC acknowledge the need for a hybrid cognitive-affective approach to AI safety and overlap with regard to many short-term considerations, they differ fundamentally in the nature of multiple envisaged long-term solution patterns. By compiling relevant underlying contradistinctions, we aim to provide future-oriented incentives for constructive dialectics in practical and theoretical AI safety research.

Halstead-Reitan Test Battery: A Problem of Differential Diagnosis

1980 ◽  
Vol 50 (2) ◽  
pp. 611-630
Author(s):  
Irmingard I. Lenzer
Keyword(s):  
Brain Damage ◽  
Test Performance ◽  
Construct Validation ◽  
Neuropsychological Test ◽  
Summary Score ◽  
Test Battery ◽  
Medical Patients ◽  
Test Taking ◽  
Limited Applicability ◽  
Schizophrenic Patients

The Halstead-Reitan Test Battery is one of the most widely recognized neuropsychological test batteries. Many claims have been made as to its validity. Despite these claims, doubts persist. A critical review of the literature shows that the battery can separate brain-damaged patients from normal patients, general medical patients, and patients with certain psychiatric disorders. However, the battery cannot separate brain-damaged patients as a group from schizophrenics as a group, though in individual cases there may exist pathognomonic signs indicating brain damage. The impairment index, as a summary score of the basic tests, as well as other “methods of inference,” fail at this point. Four alternatives are discussed. First, brain-damaged patients differ from schizophrenic patients not in test performance but in test-taking behavior. Second, the battery is a valid measure of brain damage but has limited applicability. Third, the battery is a measure not of brain damage but of degree of degradation of psychological processes. And fourth, schizophrenics perform poorly on the battery because they have undetected brain damage. Only the third and fourth alternatives appear viable. Both question the validity of the traditional criteria of brain damage. It is argued that future validation studies of the battery should be of construct validation type and not of the criterion-oriented type, as these are defined by Cronbach and Meehl (1955). Possible procedures for construct validation are briefly discussed.

scholarly journals Novel robust time series analysis for long-term and short-term prediction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroshi Okamura ◽  
Yutaka Osada ◽  
Shota Nishijima ◽  
Shinto Eguchi
Keyword(s):  
Robust Regression ◽  
Simulated Data ◽  
New Method ◽  
Short Term ◽  
Least Absolute Deviations ◽  
Term Prediction ◽  
Regression Approach ◽  
Short Term Prediction ◽  
Long Term Prediction

AbstractNonlinear phenomena are universal in ecology. However, their inference and prediction are generally difficult because of autocorrelation and outliers. A traditional least squares method for parameter estimation is capable of improving short-term prediction by estimating autocorrelation, whereas it has weakness to outliers and consequently worse long-term prediction. In contrast, a traditional robust regression approach, such as the least absolute deviations method, alleviates the influence of outliers and has potentially better long-term prediction, whereas it makes accurately estimating autocorrelation difficult and possibly leads to worse short-term prediction. We propose a new robust regression approach that estimates autocorrelation accurately and reduces the influence of outliers. We then compare the new method with the conventional least squares and least absolute deviations methods by using simulated data and real ecological data. Simulations and analysis of real data demonstrate that the new method generally has better long-term and short-term prediction ability for nonlinear estimation problems using spawner–recruitment data. The new method provides nearly unbiased autocorrelation even for highly contaminated simulated data with extreme outliers, whereas other methods fail to estimate autocorrelation accurately.

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