Trial And Error Research Articles

Déclaration des erreurs médicamenteuses dans les recherches portant sur le médicament : place du pharmacien des essais cliniques ?

The investigational drugs circuit has specific risks, and medication errors may occur in clinical trials, possibly associated with adverse reactions. These risks must therefore be managed. In fact, there are few reports of medication errors during clinical trials. In a context of regulatory interpretation difficulties on this subject, we conducted a national survey that highlighted the heterogeneity of the methods used by academic sponsors to collect, code and report medication errors and the need to develop a culture of reporting these errors in clinical trials. This is why the REVISE group (safety officers of French institutional sponsors) has issued recommendations to clarify the sponsor and investigator responsibilities and guide them in the management of medication errors. These new guidelines recommend that any serious or potentially serious medication error or other "special situation" (e.g. overdose, misuse, quality defect) should be notified immediately to the sponsor by the investigator. The clinical research pharmacist place is strategic to detect medication errors and other special situations. The integration of the pharmacist into the reporting system, in collaboration with the investigator, could be discussed with clinical research professionals and health authorities.

Examining the development of memory for temporal context and its underlying neural processes using event-related potentials

Time is a critical feature of episodic memory—memory for events from a specific time and place (Tulving, 1972). Previous research indicates that temporal memory (memory for ‘when’) is slower to develop than memory for other details (e.g., ‘what’ and ‘where’), with improvements observed across middle and late childhood. The factors that drive these changes are not yet clear. We used an event-related potential (ERP) recognition memory paradigm to investigate the underlying processes of memory for temporal context in middle to late childhood (7−9-year-olds; 10−12-year-olds) and young adulthood. Behaviorally, we observed age-related improvements in the ability to place events in temporal context. ERP analyses showed old/new effects for children and adults. We also found brain-behavior relations for 1) episodic memory (ERP mean amplitude difference between source hits and correctly identified new trials was correlated to behavioral accuracy), and 2) temporal memory (ERP mean amplitude difference between source hits and source error trials was correlated to accuracy of temporal memory judgments). This work furthers our understanding of the cognitive processes and neural signatures supporting temporal memory development in middle to late childhood, and has implications for episodic memory development more broadly.

A Brief Elementary Proof for Fermat’s Last Theorem Using Ramanujan-Nagell Equation

Fermat's Last Theorem states that it is impossible to find natural numbers A, B and C satisfying the equation (where is any integer ). Fermat himself proved the theorem for the index and Euler proved for [1]. In the equation we hypothesize that all r, s and are non-zero integers, and prove the theorem by the method of contradiction. Merly for supporting the proof in the above equation, we include another equation without loss of generality, we assert that both and as non-zero integers; a non-zero integer; and irrational. By trial and error method, we have created transformation equations to the above two equations, into which we have incorporated the Ramanujan-Nagell Equation and on solving the two transformation equations with the aid of Ramanujan--Nagell Equation, we prove the theorem by showing

Premotor Ramping of Thalamic Neuronal Activity Is Modulated by Nigral Inputs and Contributes to Control the Timing of Action Release.

The ventromedial (VM)/ventro-anterior-lateral (VAL) motor thalamus is a key junction within the brain circuits sustaining normal and pathologic motor control functions and decision-making. In this area of thalamus, on one hand, the inhibitory nigro-thalamic pathway provides a main output from the basal ganglia, and, on the other hand, motor thalamo-cortical loops are involved in the maintenance of ramping preparatory activity before goal-directed movements. To better understand the nigral impact on thalamic activity, we recorded electrophysiological responses from VM/VAL neurons while male and female mice were performing a delayed right/left decision licking task. Analysis of correct (corr) and error trials revealed that thalamic ramping activity was stronger for premature licks (impulsive action) and weaker for trials with no licks [omission (omi)] compared with correct trials. Suppressing ramping activity through optogenetic activation of nigral terminals in the motor thalamus during the delay epoch of the task led to a reduced probability of impulsive action and an increased amount of omissions trials. We propose a parsimonious model explaining our data and conclude that a thalamic ramping mechanism contributes to the control of proper timing of action release and that inhibitory nigral inputs are sufficient to interrupt this mechanism and modulate the amount of motor impulsivity in this task.SIGNIFICANCE STATEMENT Coordinated neural activity in motor circuits is essential for correct movement preparation and execution, and even slight imbalances in neural processing can lead to failure in behavioral tasks or motor disorders. Here we focused on how failure to regulate the control of activity balance in the motor thalamus can be implicated in impulsive action release or omissions to act, through an activity ramping mechanism that is required for proper action release. Using optogenetic activation of inhibitory basal ganglia terminals in motor thalamus we show that basal ganglia input is well positioned to control this ramping activity and determine the timing of action initiation.

Isothermal crystallization and time-temperature-transformation diagram of the organic semiconductor 5,11-bis(triethylsilylethynyl)anthradithiophene

The time-temperature-transformation diagram describing crystallization of the semiconducting molecule TES-ADT from its melt was constructed and found to correlate with the thin-film micro/nanostructure and electronic performance.

Dynamic expressions of confidence within an evidence accumulation framework

Human observers can reliably report their confidence in the choices they make. An influential framework conceptualizes decision confidence as the probability of a decision being correct, given the choice made and the evidence on which it was based. This framework accounts for three diagnostic signatures of human confidence reports, including an opposite dependence of confidence on evidence strength for correct and error trials. However, the framework does not account for the temporal evolution of these signatures, because it only describes the transformation of a static representation of evidence into choice and the associated confidence. Here, we combine this framework with another influential framework: dynamic accumulation of evidence over time, and build on the notion that confidence reflects the probability of being correct, given the choice and accumulated evidence up until that point. Critically, we show that such a dynamic model predicts that the diagnostic signatures of confidence depend on time; most critically, it predicts a stronger opposite dependence of confidence on evidence strength and choice correctness as a function of time. We tested, and confirmed, these predictions in human behaviour during random dot motion discrimination, in which confidence judgments were queried at different points in time. We conclude that human confidence reports reflect the dynamics of the probability of being correct given the accumulated evidence and choice.

Analisis Kualitas Air dan Daya Tampung Sungai dengan Metode Qual2Kw (Studi Kasus: Sungai Code, Yogyakarta)

Code River is one of the rivers in the D.I Province Yogyakarta that crosses the administrative areas of Sleman Regency, Bantul Regency and Yogyakarta City. Each administrative region provides input of waste with various contents and affects the capacity of the pollution load with the study area along ± 21 km. The study was conducted at the point of Ngentak, Gondolayu, Sayidan, Keparakan, Tungkak, Ngoto and Wonokromo. The study area is divided into 6 segments for water sampling. In the study conducted with 4 scenario simulations based on existing conditions, prediction of population in the next 5 years, conformity of class I quality standards without pollutant burden and trial error. The method used to analyze water quality is the QUAL2Kw method. By using this software, it can be easier to simulate changes in the upstream to downstream areas. This study aims to analyze the capacity of the pollution load on the concentration of Ammonia, Phosphate and TSS in order to determine the strategy of water quality management in the Code River

Eye movement performance and clinical outcomes among female athletes post-concussion

ABSTRACT Background Most post-concussion eye movement (EM) research involves predominantly male samples. We evaluated pro- (PRO; reflexive shift of visual attention to target) and anti- (ANTI; executive control of visual attention away from target) computer-based saccade task performance among female, collegiate athletes with recent concussion (CON) versus healthy-control athletes (HC). We evaluated the relationship between EM performance and post-concussion outcomes. We hypothesized ANTI performance would differ among CON and HC due to greater executive control demands, and that EM performance (both tasks) would be associated with clinical outcomes in CON. Methods 16 CON (assessed 4–10 days post-injury [M = 6.87, SD = 2.15 days]) and 16 age-matched HC athletes were recruited. General linear mixed modeling and Pearson’s correlations were used. Results On ANTI, CON demonstrated higher error rate [F(1,2863) = 12.650, p<.001] and shorter latency on error trials [F(1,469) = 5.976, p=.015] relative to HC. Multiple EM measures were associated with clinical outcomes: PRO duration predicted days to symptom remission (r=.44, p <.05); ANTI error rate was associated with symptom burden on the day of testing (r=.27, p <.05). Conclusion This study demonstrates promising utility of EM measures to detect cognitive control and sensorimotor effects of concussion among female athletes and their use as a prognostic indicators of recovery.

Cingulate oscillatory activity reflects the quality of memory representations in visuospatial working memory

ABSTRACT The human brain has the high likelihood for committing errors when confronted by a day-to-day situation that demands to process more than four integrated items in working memory, for example driving a car to a new destination in high traffic. However, neural mechanisms underlying the response outcome in working memory is still unclear. High temporal resolution and improved spatial resolution of dense array electroencephalogram (EEG) make it an ideal tool to investigate the dynamics of brain networks. In the present study, the brain activity of twenty healthy male volunteers was investigated during correct and error trials of visuospatial working memory task using dense array EEG. Independent brain components were identified using independent component analysis (ICA). Event-related spectral perturbations (ERSP) were computed for each independent component using Morlet wavelet transform for the frequency range of 3–70 Hz. ERSP of independent component clusters identified using K-means algorithm were statistically compared between correct and error trials. Delta and theta power increased in the component cluster located at cingulate gyrus before the error response of visuospatial working memory task. The current study findings suggest that cingulate oscillatory activity might reflect the quality of memory representation and intensity of target uncertainty during the visuospatial search.

Association of rs1801133 polymorphism with migraine susceptibility: A case-control study followed by updated meta-analysis and trial sequential analysis

Migraine is a multi-factorial neurovascular disorder causes nausea and headache. This study was aimed to determine the association between MTHFR gene rs1801133 polymorphism with migraine risk in South-Indian population using ARMS-PCR and DNA sequencing. Further, we have performed an updated meta-analysis of case-control studies relating rs1801133 polymorphism with migraine. Additionally, to identify the risk of type-I error trial sequential analysis was executed. The genotyping results of MTHFR gene polymorphism from our study revealed a positive association with migraine in a homozygous recessive (TT) genotype (OR = 2.52 (95% CI [0.96–6.64]), P = 0.046). For meta analysis, twenty case-control studies were assessed which revealed positive relationship between rs1801133 polymorphism with migraine in mixed ethnic populations (TT vs CT + CC, OR = 1.33 (95% CI [1.04–1.68]), P = 0.02; CT vs CC, OR = 0.85 (95% CI [0.74–0.97]), P = 0.02; TT vs CC, OR = 1.37 (95% CI [1.03–1.82]), P = 0.03; T vs C, OR = 1.20 (95% CI [1.02–1.41]), P = 0.03) of all analyzed genetic models. Further, ethnicity-based stratification analyses showed consistent results in Asian ethnic population. To conclude, our findings from meta-analysis confirm that rs1801133 MTHFR gene polymorphism might play a significant role in migraine susceptibility.

Minimally dependent activity subspaces for working memory and motor preparation in the lateral prefrontal cortex.

The lateral prefrontal cortex is involved in the integration of multiple types of information, including working memory and motor preparation. However, it is not known how downstream regions can extract one type of information without interference from the others present in the network. Here, we show that the lateral prefrontal cortex of non-human primates contains two minimally dependent low-dimensional subspaces: one that encodes working memory information, and another that encodes motor preparation information. These subspaces capture all the information about the target in the delay periods, and the information in both subspaces is reduced in error trials. A single population of neurons with mixed selectivity forms both subspaces, but the information is kept largely independent from each other. A bump attractor model with divisive normalization replicates the properties of the neural data. These results provide new insights into neural processing in prefrontal regions.

Simulation-Based Coyote Optimization Algorithm to Determine Gains of PI Controller for Enhancing the Performance of Solar PV Water-Pumping System

In this study, a simulation-based coyote optimization algorithm (COA) to identify the gains of PI to ameliorate the water-pumping system performance fed from the photovoltaic system is presented. The aim is to develop a stand-alone water-pumping system powered by solar energy, i.e., without the need of electric power from the utility grid. The voltage of the DC bus was adopted as a good candidate to guarantee the extraction of the maximum power under partial shading conditions. In such a system, two proportional-integral (PI) controllers, at least, are necessary. The adjustment of (Proportional-Integral) controllers are always carried out by classical and tiresome trials and errors techniques which becomes a hard task and time-consuming. In order to overcome this problem, an optimization problem was reformulated and modeled under functional time-domain constraints, aiming at tuning these decision variables. For achieving the desired operational characteristics of the PV water-pumping system for both rotor speed and DC-link voltage, simultaneously, the proposed COA algorithm is adopted. It is carried out through resolving a multiobjective optimization problem employing the weighted-sum technique. Inspired on the Canis latrans species, the COA algorithm is successfully investigated to resolve such a problem by taking into account some constraints in terms of time-domain performance as well as producing the maximum power from the photovoltaic generation system. To assess the efficiency of the suggested COA method, the classical Ziegler–Nichols and trial–error tuning methods for the DC-link voltage and rotor speed dynamics, were compared. The main outcomes ensured the effectiveness and superiority of the COA algorithm. Compared to the other reported techniques, it is superior in terms of convergence rapidity and solution qualities.

Cannabidiol aqueous solubility enhancement: Comparison of three amorphous formulations strategies using different type of polymers

Poor aqueous solubility of terpenophenolic compound Cannabidiol (CBD) is a major issue in the widespread use of this promising therapeutic polyphenol. Moreover, choosing the appropriate strategy to overcome this challenge is time-consuming and based on trial-error processes. The amorphous form of CBD provided higher aqueous solubility as well as faster dissolution rate in comparison with crystalline CBD. Nevertheless, amorphous forms of CBD tend to recrystallize. The aim of this study was to use three different strategies based on the stabilization of the amorphous form. Cyclodextrins (CH3αCD, HPβCD and HPγCD.), mesoporous silicas (Silsol® and Syloid® AL-1FP) and water soluble polymers (Kollidon® VA64, Kollidon® 12PF and Soluplus®) were processed by using the following techniques: freeze-drying, spray-drying, subcritical carbon dioxide impregnation or hot-melt extrusion. All the obtained formulations provided complete amorphous CBD, although the drug loading depend highly of the excipients. CBD-cyclodextrin formulations, processed by freeze-drying or spray-drying, and CBD-mesoporous silica formulations, processed by subcritical CO2 or by atmospheric impregnation, provided significant increase of aqueous solubility. While the use of Kollidon® 12PF did not provided significant increased solubility within 90min, Kollidon® VA64 has been highlighted as the excipient that exhibits the highest increase of aqueous solubility of this study. Finally, all formulations, excepted CBD-ALFP formulations, showed adequate stability within at least two months.

Domestication past and future of tribal agriculture in Bastar

Wild edible fruits play an important role in the nutrition, medicinal and traditional lifestyles of the local people. Bastar region is rich in its biodiversity and tribal communities who are dependent on wild resources for the sustenance. The main forest is sal, Harra, Bahera, Char, Tendu, Palash. Most of the people are either engaged in livelihood through agriculture or forestry-related options. The economic condition of the people is also below the national level as reflected in per capita income. Wild edible fruits of this region are not only consumed but are also sold in local markets. There is a need to domesticate the fruits at the same time there is a need to develop cultivable improved varieties and the study nutritional aspect to design better foods for the future. Although these wild edible plants play an important role in food security, they are ignored. The primitive man through trial and error has selected many wild edible plants, which are edible and subsequently domesticated them. Allopatric speciation, also referred to as geographic speciation, vicariant speciation, or its earlier name, the dumbbell model, is a mode of speciation that occurs when biological populations of the same species become isolated from each other to an extent that prevents or interferes with gene flow. Wild edible is less susceptible to diseases, can be grown easily without the application of pesticides. Ironically these plants are still unknown or less known to other parts of the world. The wild edible plant species will be popularized after phytochemical analysis and nutritional studies. The present study on the review of “Domesticable Hidden Wild Botanical Gems of Forest” will be helpful in pooling different types of edible plant species utilized by various tribes in different parts of the forest.

Accelerated Monte Carlo analysis of flow-based system reliability through artificial neural network-based surrogate models

Conventional Monte Carlo simulation-based methods for seismic risk assessment of water networks often require excessive computational time costs due to the hydraulic analysis. In this study, an Artificial Neural Network-based surrogate model was proposed to efficiently evaluate the flow-based system reliability of water distribution networks. The surrogate model was constructed with appropriate training parameters through trial-and-error procedures. Furthermore, a deep neural network with hidden layers and neurons was composed for the high-dimensional network. For network training, the input of the neural network was defined as the damage states of the k-dimensional network facilities, and the output was defined as the network system performance. To generate training data, random sampling was performed between earthquake magnitudes of 5.0 and 7.5, and hydraulic analyses were conducted to evaluate network performance. For a hydraulic simulation, EPANET-based MATLAB code was developed, and a pressure-driven analysis approach was adopted to represent an unsteady-state network. To demonstrate the constructed surrogate model, the actual water distribution network of A-city, South Korea, was adopted, and the network map was reconstructed from the geographic information system data. The surrogate model was able to predict network performance within a 3% relative error at trained epicenters in drastically reduced time. In addition, the accuracy of the surrogate model was estimated to within 3% relative error (5% for network performance lower than 0.2) at different epicenters to verify the robustness of the epicenter location. Therefore, it is concluded that ANN-based surrogate model can be utilized as an alternative model for efficient seismic risk assessment to within 5% of relative error.

Rancang Bangun Prototype Mesin Pengering Gabah Otomatis Menggunakan Metode PID sebagai Kendali Temperatur

The value of rice grain content after harvest is quite high, around 20-23% in the dry season, and around 24-27% in the wet season. It was drying grain after harvest was processed by the conventional or manual method that carried out the grain drying in the sun. This method has several disadvantages, such as the dependence on the weather, requires a large area, and 54 hours for drying so that the grain becomes dry with a moisture content of 14.12%. From this problem, the researchers made a grain drying machine that could work automatically. The drying machine is made to solve the issues of conventional grain drying so that the machine was completed with a K type thermocouple temperature sensor and grain moisture content. Whereas the heating media uses a fire that is fueled with LPG gas, and then the heat from the fire has flowed into the furnace or grain drying chamber. The heating arrangement was made by regulating of flowing LPG gas to the nozzle through the opened and closed variable valve where the valve shaft was connected to the DC motor shaft. The application of the PID method also used in this drying machine, which has a purpose while controlling the drying temperature to match the Set Value (SV) or the desired temperature at 38oC. The grain moisture content value is considered to have dried up when the grain moisture content value is 14%. The PID method that is implanted into the ATmega16 microcontroller will give a signal to the motor driver circuit to regulate the direction of rotation of the DC motor connected to the opened and closed valve variable. PID method testing was done by trial error and has produced a steady-state error of 5.2% at S0056=38oC with constant values Kp=2, Ki=2, and Kd=10. Whereas for drying grain testing on harvested is done by selecting Ciherang grain with a moisture content of 20% and a weight of 3 kg. The grain drying process takes 30 minutes so that the value of the water content becomes 14% with a drying temperature of 38oC, so the grain drying rate on this machine is 0.17% per minute.

Algorithm-Based Practice Schedule and Task Similarity Enhance Motor Learning in Older Adults

According to the challenge point framework, task difficulty has to be appropriate to learner skill level. The pure blocked or random practice controls the task difficulty during practice monotonically. Therefore, the purpose of this study was to investigate the effect of algorithm-based practice schedule and task similarity on motor learning in older adults. For this purpose, 60 older adults were randomly assigned into six groups of blocked-similar, algorithm-similar, random-similar, blocked-dissimilar, algorithm-dissimilar, and random-dissimilar. Sequential motor tasks were used for learning. Participants practiced absolute timing goals in similar (1350, 1500, 1650 ms) or dissimilar (1050, 1500, 1950 ms) conditions according to their practice schedule. Twenty-four hours after the acquisition phase, retention, and transfer tests were performed. Algorithm-practice was a hybrid practice schedule (blocked, serial, and random practice in forward/backward switching) that switching the schedules was according to error trial number (n ≤ 33%) in each block based on error range of absolute timing goals (± 5%). The results showed that the blocked-practice outperforms the other groups during the acquisition phase, whereas the algorithm-practice outperforms the other groups in retention and transfer in both similar and dissimilar conditions. These findings were discussed according to the challenge point framework.

Time to Start Asking the Right Question or at Least Admit We Do Not Have the Answer—Indications for Elective Neck Dissection in Early-Stage Oral Cavity Cancer

One of my great professional privileges has been to cocreate a Clinical Trial Methods course for the American and International Associations of Oral and Maxillofacial Surgeons. A critical segment of these courses is entitled “Errors in Clinical Trials.” The instructor uses examples of randomized perspective clinical trials (RCTs) where outcomes were broadly adopted but that because of methodological error were later proved “dead wrong,” a term I use with intent. Trial design is a complicated process.

Effects of Cerebellar tDCS on Inhibitory Control: Evidence from a Go/NoGo Task

Response inhibition as an executive function refers to the ability to suppress inappropriate but prepotent responses. Several brain regions have been implicated in the process underlying inhibitory control, including the cerebellum. The aim of the present study was to explore the role of the cerebellum in executive functioning, particularly in response inhibition. For this purpose, we transitorily inhibited cerebellar activity by means of cathodal tDCS and studied the effects of this inhibition on ERP components elicited during a Go/NoGo task in healthy subjects. Sixteen healthy subjects underwent a Go/NoGo task prior to and after cathodal and sham cerebellar tDCS in separate sessions. A reduction in N2-NoGo amplitude and a prolongation in N2-NoGo latency emerged after cathodal tDCS whereas no differences were detected after sham stimulation. Moreover, commission errors in NoGo trials were significantly higher after cathodal tDCS than at the basal evaluation. No differences emerged between performances in Go trials and those after sham stimulation. These data indicate that cerebellar inhibition following cathodal stimulation alters the ability to allocate attentional resources to stimuli containing conflict information and the inhibitory control. The cerebellum may regulate the attentional mechanisms of stimulus orientation and inhibitory control both directly, by making predictions of errors or behaviors related to errors, and indirectly, by controlling the functioning of the cerebral cortical areas involved in the perception of conflict signals and of the basal ganglia involved in the inhibitory control of movement.

Electronic practicum assessment system based on android at politeknik ATI makassar

The Practicum assessment conducted conventionally is gradually replaced with an Android-based system. It aims to support the government program of Making Indonesia 4.0. In this research, the electronics practicum assessment is designed using the App Inventor application. The attendance assessment and initial assignment are designed to obtain an objective grade. Attendance assessment is conducted by making a standard assessment form, determining points obtained by looking at the time of arrival. Assessing the initial task was done by making ten multiple-choice questions for each experiment. The initial assignment assessment form was created in Microsoft Excel to make it easier to import, export data to .csv (comma separated values) to enter the database system. The results obtained from 6 types of initial assignment assessment experiments conducted using the application. There were 5 trials that were successfully run, and there was still one error trial.