Actual Conditions Of Use Research Articles

Immune response to GeneVac-B® (rDNA I.P. hepatitis B vaccine) in vaccinated persons with a standard schedule in Bobo-Dioulasso, Burkina Faso

Background: GeneVac-B® was recently licensed in Burkina Faso and is widely used for population vaccination. This study aimed to evaluate the immune response in people fully vaccinated against hepatitis B with the GeneVac-B® vaccine in Burkina Faso under actual conditions of use. Material and Methods: This cross-sectional study included individuals fully vaccinated with GeneVac-B®. For each consenting participant, sociodemographic and clinical data were collected using a structured questionnaire. Approximately 4 mL of whole blood was collected for immunological (anti-HBs, HBsAg, anti-HCV and anti-HIV) and biochemical (blood glucose, total cholesterol, and triglycerides) testing. The anti-HBs titer was used to determine the immune response. Results: A total of 392 participants were included in the study. The mean age was 35.5±15.3 years. Approximately 56% had been previously exposed to HBV. Three hundred eighty (380) participants had an anti-HBs titer ≥ 12 mIU/mL indicating a seroprotection rate of 96.9%, and 12 had a titer < 12 mIU/mL, a nonresponse rate of 3.1%. Among the nonresponders, 11 (11/12; 91.7%) had high total cholesterol levels (> 240 mg/dL), and 8 (8/12; 66.7%) were older than 40 years of age. Conclusions: The results showed an excellent immune response to GeneVac-B® in our study population. However, age > 40 and high total cholesterol appear to be factors associated with nonresponse.

Representative volume element model for quantitatively predicting the influence of 3D polycrystalline morphology on Coble creep deformation

To evaluate creep in materials under actual-use conditions, it is necessary to consider the polycrystalline morphology. Herein, we propose the first model for quantitatively predicting the influence of 3D polycrystalline morphology on Coble creep deformation. This model was developed using a representative volume element (RVE). Two grain growth mechanisms, namely, grain boundary migration and grain boundary diffusion, were formulated considering the 3D data structure of a polycrystal and then superposed to simulate RVE deformation. The model was validated by comparison with the theoretical solution for Coble creep deformation under uniaxial loading conditions. The proposed model accurately reproduced the influences of grain size, applied stress, and temperature, thus demonstrating its validity. In addition, the influence of polycrystalline morphology was investigated by performing systematic numerical simulations. The model directly provided quantitative predictions of the performance of materials with arbitrary polycrystalline morphologies under any loading or temperature condition. Consequently, the proposed RVE model has the potential to serve as a basis for designing novel materials with resistance against high-temperature creep.

Large Air-to-Water Heat Pumps for Fuel-Boiler Substitution in Non-Retrofitted Multi-Family Buildings—Energy Performance, CO2 Savings, and Lessons Learned in Actual Conditions of Use

The use of air source heat pumps (ASHP) in the specific context of existing multi-family buildings (MFB) represents an important challenge, especially in terms of performance and technical constraints in real conditions of use. This study concerns the actual performance of two non-retrofitted MFB (4047 and 7563 m2), whose original fossil heat supply was replaced by a centralized monovalent (2 × 156 kW) and hybrid (6 × 34 kW) ASHP system for space heating and domestic hot water. Based on a detailed monitoring campaign covering two years of operation, it can be concluded that both systems are able to supply the required temperature and cover the entire heat demand. By closely following up these pilot projects, constraints linked to integration and operation were identified. Optimization measures allowed us to increase the COP of the monovalent system (from 1.3 up to 3.4, with an optimized SPF of 2.3) and to raise the HP share of the hybrid system (from 50% to 67%, with an optimized SPF of 2.3). Both systems offer major progress in terms of CO2 savings (92% and 68%) and increased renewable energy share (75% and 43%), considering the hourly CO2 content of the Swiss electricity mix.

Improving Comfort and Air Conditioner Performance by Optimizing Controllers under Actual Usage Conditions

This study is to increase the efficiency of the air conditioning system under actual conditions of use. In order to improve the increase in energy consumption due to control without considering indoor cooling load fluctuations, we review it compared to conventional control methods in two respects. First, we examined the control method to reduce energy consumption by varying the evaporative pressure of the system according to the cooling load, and secondly, further reducing energy consumption by controlling the revolutions per minute (RPM) of the fan of the indoor unit at the same time as the pressure fluctuation under the cooling load. We found that changing the target pressure depending on the difference between the target temperature and room temperature can control temperature more efficiently and save energy than using fixed target pressure, and that the effect increases when applying the control of the air volume of the indoor air. Cleaning up the resulting values, the fan-load-control condition of the cooling-load-estimation control method showed an energy savings effect of 16.1–48.7% compared with the fixed-pressure control method and 1.2–37.7% compared with the cooling-load-estimation control method.

METHOD OF TESTING THE READINESS OF MEANS OF TRANSPORT WITH THE USE OF SEMI-MARKOV PROCESSES

In the analysis of the readiness of means of transport, the Markov and semi-Markov processes are particularly applicable, allowing for the description of the usage process over long periods of time, determination of indicators of the exploitability and readiness of the used set of objects, as well as simulation of long-term forecasts of the usage process results. The studies presented in the literature usually concern the theoretical side of the matter, mainly the construction of formal models of the process of changing the operating states of a vehicle. Less attention is paid to the empirical side, especially with regard to the actual conditions of use. Examples of experimental observations presented in the literature most often concern individual cases. This paper lists selected irregularities and presents an example of a study of a real transport system based on semi-Markov processes.

Estimating the number of usability problems affecting medical devices: modelling the discovery matrix

BackgroundUsability testing of medical devices are mandatory for market access. The testings’ goal is to identify usability problems that could cause harm to the user or limit the device’s effectiveness. In practice, human factor engineers study participants under actual conditions of use and list the problems encountered. This results in a binary discovery matrix in which each row corresponds to a participant, and each column corresponds to a usability problem. One of the main challenges in usability testing is estimating the total number of problems, in order to assess the completeness of the discovery process. Today’s margin-based methods fit the column sums to a binomial model of problem detection. However, the discovery matrix actually observed is truncated because of undiscovered problems, which corresponds to fitting the marginal sums without the zeros. Margin-based methods fail to overcome the bias related to truncation of the matrix. The objective of the present study was to develop and test a matrix-based method for estimating the total number of usability problems.MethodsThe matrix-based model was based on the full discovery matrix (including unobserved columns) and not solely on a summary of the data (e.g. the margins). This model also circumvents a drawback of margin-based methods by simultaneously estimating the model’s parameters and the total number of problems. Furthermore, the matrix-based method takes account of a heterogeneous probability of detection, which reflects a real-life setting. As suggested in the usability literature, we assumed that the probability of detection had a logit-normal distribution.ResultsWe assessed the matrix-based method’s performance in a range of settings reflecting real-life usability testing and with heterogeneous probabilities of problem detection. In our simulations, the matrix-based method improved the estimation of the number of problems (in terms of bias, consistency, and coverage probability) in a wide range of settings. We also applied our method to five real datasets from usability testing.ConclusionsEstimation models (and particularly matrix-based models) are of value in estimating and monitoring the detection process during usability testing. Matrix-based models have a solid mathematical grounding and, with a view to facilitating the decision-making process for both regulators and device manufacturers, should be incorporated into current standards.

Surgical Simulation: Simulating Realistic Use in Human Factors Validation Testing Using Study Models

When conducting simulated use human factors validation testing, the U.S. FDA requires that test conditions are sufficiently realistic to represent actual conditions of use. As part of this realistic simulation, a simulated patient, also called a “study model,” may be developed or acquired specifically for human factors validation testing of the device. The authors present a recommended process for choosing or developing a study model, using examples from past surgical device studies, and they provide a sample of study model design requirements as well as a summary of study model development considerations. This paper is meant to encourage discussion amongst medical device developers, human factors practitioners, and regulatory agencies regarding the development of study models that are sufficiently realistic for human factors validation testing.

Volatile Organic Compound (VOC) Emissions from a Personal Care Polymer-Based Item: Simulation of the Inhalation Exposure Scenario Indoors under Actual Conditions of Use

Polymer-based items may release Volatile Organic Compounds (VOCs) and odors indoors, contributing to the overall VOC inhalation exposure for end users and building occupants. The main objective of the present study is the evaluation of short-term inhalation exposure to VOCs due to the use of a personal care polymer-based item, namely, one of three electric heating bags, through a strategic methodological approach and the simulation of a ‘near-to-real’ exposure scenario. Seventy two-hour test chamber experiments were first performed to characterize VOC emissions with the items on ‘not-heating mode’ and to derive related emission rates. The polyester bag was revealed to be responsible for the highest emissions both in terms of total VOC and naphthalene emissions (437 and 360 µg/m3, respectively), compared with the other two bags under investigation. Complementary investigations on ‘heating mode’ and the simulation of the exposure scenario inside a 30 m3 reference room allowed us to highlight that the use of the polyester bag in the first life-cycle period could determine a naphthalene concentration (42 µg/m3) higher than the reference Lowest Concentration of Interest (LCI) value (10 µg/m3) reported in European evaluation schemes. The present study proposes a strategic methodological approach highlighting the need for the simulation of a realistic scenario when potential hazards for human health need to be assessed.

Compendial Methods: Suitability Verification, Challenges and Recommendations for Proteins

Compendial testing methods are not required to be fully validated, but their suitability for testing should be verified under actual conditions of use. This requirement is established in 21 CFR 211.194(a)(2) of the current Good Manufacturing Practice regulations in the United States. ANVISA (Agência Nacional de Vigilância Sanitária) also requires that compendial analytical methods shall have their suitability demonstrated for the intended use by a partial validation study. Suitability verifications or partial validation can be divided into two major categories: visual and instrumental methods. For visual methods, the color and opalescence of interferences should be checked. If the color or clarity/opalescence of the sample is outside of the range of the Pharmacopeia standards/reference solutions, the validity of the test results should be evaluated. Specificity is usually waived because the methods are not specific to products, and accuracy/precision can be addressed by comparing results from analyst to analyst. For instrument methods, specificity can also be waived for certain assays. Accuracy is addressed by implementation of instrument calibration and/or method control. Precision is required either in suitability verification or when testing the samples. Here, we present approaches for suitability verification and the scientific rationale supporting compendial methods: visible particulates, subvisible particles, pH, osmolality, color and clarity/opalescence. Current challenges and recommendations are also discussed specifically for the analysis of protein products.

Calculation of Effective Dose on Domestic Chest PA X-ray Examinations

Research on effective dose analysis of actual conditions of use based on large data is scarce. In this study, the exposure conditions of Chest X-Ray examinations used by 324 medical institutions in Korea were calculated and evaluated using computer simulations. As a result of the experiment, the effective dose in the low energy parameter bands was 0.024 mSv, followed by spleen, adrenal glands, and lung. The effective dose in the high-energy exposure parameter band was 0.123 mSv, followed by height, spleen and adrenal glands. The effective dose was 0.017 mSv when the optimal conditions considered the quality and exposure proposed in Park's study were used. The results of the study will be a reference for chest X-rays and will help reduce patient exposure.

Lessons from Randomised Clinical Trials for Triiodothyronine Treatment of Hypothyroidism: Have They Achieved Their Objectives?

Randomised controlled trials are deemed to be the strongest class of evidence in evidence-based medicine. Failure of trials to prove superiority of T3/T4 combination therapy over standard LT4 monotherapy has greatly influenced guidelines, while not resolving the ongoing debate. Novel studies have recently produced more evidence from the examination of homeostatic equilibria in humans and experimental treatment protocols in animals. This has exacerbated a serious disagreement with evidence from the clinical trials. We contrasted the weight of statistical evidence against strong physiological counterarguments. Revisiting this controversy, we identify areas of improvement for trial design related to validation and sensitivity of QoL instruments, patient selection, statistical power, collider stratification bias, and response heterogeneity to treatment. Given the high individuality expressed by thyroid hormones, their interrelationships, and shifted comfort zones, the response to LT4 treatment produces a statistical amalgamation bias (Simpson's paradox), which has a key influence on interpretation. In addition to drug efficacy, as tested by RCTs, efficiency in clinical practice and safety profiles requires reevaluation. Accordingly, results from RCTs remain ambiguous and should therefore not prevail over physiologically based counterarguments. In giving more weight to other forms of valid evidence which contradict key assumptions of historic trials, current treatment options should remain open and rely on personalised biochemical treatment targets. Optimal treatment choices should be guided by strict requirements of organizations such as the FDA, demanding treatment effects to be estimated under actual conditions of use. Various improvements in design and analysis are recommended for future randomised controlled T3/T4 combination trials.

Randomization to randomization probability: Estimating treatment effects under actual conditions of use.

Blinded randomized controlled trials (RCT) require participants to be uncertain if they are receiving a treatment or placebo. Although uncertainty is ideal for isolating the treatment effect from all other potential effects, it is poorly suited for estimating the treatment effect under actual conditions of intended use-when individuals are certain that they are receiving a treatment. We propose an experimental design, randomization to randomization probabilities (R2R), which significantly improves estimates of treatment effects under actual conditions of use by manipulating participant expectations about receiving treatment. In the R2R design, participants are first randomized to a value, π, denoting their probability of receiving treatment (vs. placebo). Subjects are then told their value of π and randomized to either treatment or placebo with probabilities π and 1-π, respectively. Analysis of the treatment effect includes statistical controls for π (necessary for causal inference) and typically a π-by-treatment interaction. Random assignment of subjects to π and disclosure of its value to subjects manipulates subject expectations about receiving the treatment without deception. This method offers a better treatment effect estimate under actual conditions of use than does a conventional RCT. Design properties, guidelines for power analyses, and limitations of the approach are discussed. We illustrate the design by implementing an RCT of caffeine effects on mood and vigilance and show that some of the actual effects of caffeine differ by the expectation that one is receiving the active drug. (PsycINFO Database Record

Selective delivery of adapalene to the human hair follicle under finite dose conditions using polymeric micelle nanocarriers.

Drug delivery systems that target the pilosebaceous unit (PSU) selectively could improve the clinical management of diseases that originate in the hair follicle. The aims of this study were (i) to prepare polymeric micelles using d-α-tocopheryl polyethylene glycol succinate diblock copolymer that incorporated adapalene (ADA), a retinoid indicated for Acne vulgaris, and (ii) to investigate the feasibility of delivering ADA preferentially to the PSU under finite dose conditions - thereby better approximating actual conditions of use by patients. Incorporation of ADA into spherical micelles (dn <20 nm) increased aqueous solubility by ∼50 000-fold (from <4 ng mL-1 to 0.2 mg mL-1). Optimized micelle solution and gel formulations (0.02% ADA) were stable after storage for 4 weeks at 4 °C. Finite dose experiments using full-thickness porcine and human skin revealed that ADA delivery efficiency from micelle solution and gel formulations was equivalent and was >2- and 10-fold higher than that from Differin® gel and Differin® cream (products containing ADA at 0.1% (w/w)). Follicular delivery studies in human skin, using a punch biopsy technique to extract the intact PSU, demonstrated that the micelle solution and gel formulations did indeed enable preferential delivery of ADA to the PSU (4.5- and 3.3-fold higher, respectively, than that to PSU-free skin biopsies). Confocal laser scanning microscopy provided visual corroboration that ADA was uniformly distributed in the hair follicles. In conclusion, the results confirmed that polymeric micelle nanocarriers enabled selective, targeted drug delivery to the PSU under finite dose conditions and so might improve therapy of follicular diseases and decrease off-site side-effects.

Contribution of Technical and Human Factors to “No Fault Found” Events

Multicomponent products that combine hardware and software (cars, airplanes, and telephones, to name a few) are everywhere in our lives. The commercial release of such products is a compromise between performance capabilities, competitive pricing, and time to market (Challa, Rundle, &amp; Pecht, 2013). As product performance increases, system complexity and the number of failure modes also increase. Of particular importance are “No Fault Found” (NFF) events that occur when a user records a system error and subsequent investigations fail to uncover the reason for the system malfunction – the root cause is unknown (Jones &amp; Hayes, 2001). NFF can result in high warranty costs, product recalls, and diminished reputation (Challa et al., 2013). Surprisingly, most organizations do not explicitly calculate the costs of NFF or use a framework to estimate them (Erkoyuncu, Khan, Hussain, &amp; Roy, 2016). A defining aspect of NFF is the discrepancy between actual and anticipated use conditions (Challa et al., 2013). Anticipated use is often defined by qualification, the passing of tests that demonstrate when a product meets nominal design and manufacturing specifications (Challa et al., 2013). A popular form of qualification is standards-based testing due to its speed, low cost, and applicability to many products (Challa et al., 2013). Standards such as Military Standard (MIL-STD) meet these criteria, but are often inappropriate for specific, actual-use conditions in the field. For example, the Ford Motor Company designed thick film integrated (TFI) ignition modules based on a set of laboratory standards. Cars used in hot climates experienced numerous failures that were initially classified as NFF (because these failures could not be reproduced under the milder laboratory conditions) (Thomas et al., 2002). One remedy to this problem would be to adopt more stringent engineering specifications for qualification. In this research, we analyzed NFF across four industries – automotive electronics, aerospace, medical equipment, and consumer electronics. The analysis is based on four contributors to NFF: testing procedures, intermittent failures, environmental factors, and human factors. Intermittent failures are the re-appearance of equipment failure after remedial actions have taken place (Thomas et al., 2002). Environmental factors (also referred to as environmental monitoring) are the context (or “background”) conditions in which the NFF event occurs. These factors can take on a variety of forms, from vibration and humidity in an aircraft to the diverse demographics of users of a consumer electronic product (Kim &amp; Christiaans, 2016; Moffat, Abraham, Desmulliez, Koltsov, &amp; Richardson, 2008). Case studies (representing each of the four industries) demonstrate that the existing strategies for reducing the occurrence of NFF events are limited. Addressing the four contributors to NFF (testing procedures, intermittent failures, environmental factors, and human factors) allows for the development of a systematic approach to reduce these events. First, one must distinguish between “hard” and “soft” failures. Hard failures are technical or equipment reliability failures (den Ouden, Yuan, Sonnemans, &amp; Brombacher, 2006; Kushniruk &amp; Patel, 2004). Soft failures occur when products fail to meet usability expectations, despite functioning from a technical, reliability standpoint (den Ouden et al., 2006). Hard failures are relevant to the aerospace and automotive electronics industry case studies, while soft failures pertain to medical equipment and consumer electronics. Analysis reveals a number of key insights, including the impact of proper failure classification (what is or is not a NFF event). Proper classification enables organizations to quantify how products perform in the field and which corrective actions are needed to improve reliability and usability.

Supplemental Material for Randomization to Randomization Probability: Estimating Treatment Effects Under Actual Conditions of Use

Supplemental Material for Randomization to Randomization Probability: Estimating Treatment Effects Under Actual Conditions of Use

응력완화를 이용한 고무시편의 가속수명시험 연구

Rubber parts are widely used in many applications such as dampers, shock absorbers, and seals used in railway and automotive industries. Much research has thus far been conducted on property estimation and life prediction of rubber parts. To predict the service life of rubber parts at room temperature, most prior work adopts the well-known Arrhenius model that needs the accelerated life test in high-temperature conditions. However, they may not reflect the actual conditions of use that rubber parts are usually used under a specific strain condition during long period of time. In this context, we propose a method for the life prediction of rubber parts in actual conditions of use. The proposed method is based on the accelerated life test using stress relaxation during which three relatively high elongation percentages (100%, 200%, and 300%) are applied to the rubber specimens. Rubber specimens were prepared in accordance with KS M 6518 standard and three stress relaxation testers were fabricated for actual experiments. Finally, a inverse power model for life prediction was derived from experimental results. The predicted life was compared with the actual test life for validation.

A Study on the Actual Conditions of Use and Alternatives of Teaching &amp; Learning Materials Based on a Teacher Survey

A Study on the Actual Conditions of Use and Alternatives of Teaching &amp; Learning Materials Based on a Teacher Survey

Contribution and limits of a non‐intrusive Raman spectroscopic method compared with HPLC for routine application to pre‐delivery analytical control of two major camptothecin analogs: irinotecan and topotecan

The purpose of this study was to develop a Raman spectroscopy (RS) method as an effective tool for the non‐intrusive pre‐delivery analytical quality control (AQC) of two camptothecin analogs, i.e. irinotecan (IRI) and topotecan (TPT), which are prescribed and compounded at the hospital. Following a phase of analytical pre‐validation, based on the actual conditions of use of the analogs, the protocol was validated and compared with the reference high‐performance liquid chromatography (HPLC) method. For IRI, AQC by RS has been validated in ranges from 0.94 to 3.27 mg/ml in saline solutions and from 0.89 to 3.30 mg/ml in dextrose solutions. These ranges recover the entire therapeutic concentrations encountered in clinical practice, i.e. 1.08–2.8 mg/ml. The RS and HPLC methods were validated by calculating the accuracy profile and provided excellent results for the analytical validation key criteria. The Spearman and Kendall correlation tests (p‐value &lt; 1.10−11) and the statistical studies performed on the Bland and Altman graphs confirm a strong correlation between RS and HPLC results. However, we show that a routine apparatus is unable to quantify TPT therapeutic concentrations ranging between 25 and 50 µg/ml but that a sufficiently powerful RS bench is able to detect and quantify TPT. Overall, these results confirm the potential of the RS option for future innovative applications. Owing to its analytical and practical qualities, this promising method contributes to the improvement of the safety of the medication circuit at the hospital and to the protection of caregivers and their working environment. Copyright © 2015 John Wiley &amp; Sons, Ltd.

The use of adalimumab, etanercept, golimumab and infliximab in rheumatic pathologies: variation between label dosage and real-world use

Rheumatoid arthritis (AR), psoriatic arthritis (PSA) and ankylosing spondylitis (AS) are autoimmune systemic diseases characterized by inflammation, pain and joint degeneration. The objective of this study is to evaluate, under the actual conditions of use, dosing patterns of adalimumab, etanercept, golimumab and infliximab in these pathologies, and compare them with the label regimens recommended, as well as evaluating the financial implications of these regimen modifications. The study population included all adult patients diagnosed with RA, PSA or AS who had been treated with adalimumab, etanercept, golimumab and infliximab for at least 6 months between 1 January 2011 and 31 December 2013. The main variable of this study was to assess the dose dispensed for drugs administered subcutaneously and the dose prepared/administered for drugs administered intravenously, and the annual costs of the treatment. A total of 5,428 episodes were included. The mean weekly dose was lower than the standard dose in the three pathologies studied in the patients treated with adalimumab and etanercept (84.3% vs 81.2% for RA, 85.0% vs 78.0% for PSA and 87.8% vs 81.6% for AS). The drugs with highest dose optimization in RA are etanercept (46.3%) followed by adalimumab (46%); however, the highest percentage of patients with major dose optimization corresponds to etanercept (11.6%). Both in the PA and the AS group, we also observed that etanercept is the drug more optimized, corresponding to 53.9 and 43% of patients, respectively. By contrast, 48.5% of patients with RA treated with infliximab required dose intensification; however, infliximab dose intensification in PSA and AS is not so pronounced. The practice of optimization of dose regimens in patients with rheumatic diseases under treatment with anti-TNFα is spreading among professionals, resulting in annual cost reduction in the treatment of rheumatic arthropathies. However, long term follow-up will be necessary to assess the influence of this optimization on health outcomes.

Fault tree analysis of proton exchange membrane fuel cell system safety

Proton exchange membrane fuel cells (PEMFC) system is considered as a solution for electric vehicle autonomy. Hydrogen must be mastered to preserve safety. The risk associated with hydrogen is a consequence of these properties. This study proposes a model of explosion for reliability analysis by fault trees. Details of the PEMFC system architecture are taken into account. The data used are from professional database. Adaptation of these data is proposed to reflect the actual conditions of use of a PEMFC system and a model of degradation mechanism which is realistic. The probability calculation is performed in relation to a reference time of use. The probability of explosion of the system is thus evaluated and critical failure sequences are identified. For these minimum critical cut that are dependent on degradation due to the use of the system, inverse calculation are proposed to define the targets of the design by reliability.