Effects Of Cumulative Doses Research Articles

Dose and Single-Event Effects on a Color CMOS Camera for Space Exploration

This paper focuses on the radiation-induced dose and single-event effects (SEEs) on a color CMOS camera designed for space missions. The γ -ray and proton tests are used to evaluate the tolerance against cumulative dose effects. The dark current of the image sensor is the main parameter impacted by dose effects. Heavy ions testing is performed to evaluate SEEs. single-event upset, single-event functional interrupt, and single-event latchup have been observed and mitigation techniques were proposed for specific space missions.

Evaluation of Radiation Effects in RRAM-Based Neuromorphic Computing System for Inference

Neuromorphic computing systems built with resistive random access memory (RRAM) are attractive solutions for implementing deep learning on-chip. In this paper, the single event and cumulative radiation damage susceptibility of a 1-transistor-1-resistor synaptic array architecture is investigated for the inference stage of a neuromorphic system. A physics-based SPICE RRAM model is developed to simulate the analog switching behavior of HfO x -based RRAM devices. SPICE simulations using the RRAM model are performed to capture the effects of transient heavy-ion strikes and experimental results obtained on GeSe-based RRAM devices are used to model the effects of cumulative radiation dose. Error patterns are fed into the software simulation of a multilayer perceptron, a representative artificial neural network for MNIST handwritten digit recognition. Radiation effects on the inference accuracy are analyzed. The results of the analysis indicate that the RRAM-based neuromorphic computing system is highly resistant to transient single-event effects due to the low cross section. The system is also shown to be tolerant to multi-Mrad levels of total ionizing and displacement damage dose.

Impact of Cumulative Dose of Carfilzomib in Combination with Lenalidomide and Desamethasone in Relapsed Refractory Myeloma Patients: A Retrospective Real Life Survey of the Sicilian Myeloma Network

Background: Triplet-based lenalidomide plus dexamethasone (Rd) combinations have become the new standard of care for early relapse and refractory multiple myeloma (RRMM). Carfilzomib is a novel selective proteasome inhibitor (PI) with high efficacy in RRMM. The ASPIRE phase 3 trial showed the superiority of carfilzomib-based triplet (KRd compared to Rd), leading to approval of K for RRMM. However, little is known about safety and efficacy of KRd outside a clinical trial context.Experimental design and aims: In 11 Sicilian Centers belonging to the Sicilian Myeloma Network, from November 2016, when KRd regimen was approved in Italy, to June 2018, 103 consecutive RRMM patients (previous lines 1-10) have received KRd regimen, according to ASPIRE schedule. Lenalidomide dosage was reduced in patients with a low count of platelet and/or renal failure according to manufacturer guidelines.Since previous studies have demonstrated that increased cumulative dose of first generation PI bortezomib significantly improved overall survival of patients treated with VMP regimen, we studied the effect of cumulative dose of Carfilzomib in RRMM patients receiving KRd.Results: Clinical and demographic characteristics of patients included in the study are summarized in Table 1.Median age was 65 years (range 33-86), most patients were males (54%). About half of the patients included in the survey were refractory to previous treatment (54%); Sixty-five (63%) patients received at least 5 cycles of KRd and 38 (36%) received at least 10 cycles.Overall response rate was 34% (35 patients); 18 patients (17%) achieved a complete response (CR), 6 patients minimal response (MR), 13 (12%) patients achieved PR, 16 patients achieved MR and then progressed; progression occurred in 20 patients, among them 3 did not reached any response.Delays due to adverse events were 33%, mainly due to febrile neutropenia (22%), thromboembolic events (4.5%), heart failure (3%), or thrombocytopenia (4.5%). To prevent hematological toxicities, 24% of patients received granulocyte growth factors, 15% erythropoietin.In 30 patients treatment was reduced (mainly due to lenalidomide toxicity) and in 5 patients discontinued for toxicity. Thus, median cumulative carfizomib doses at 2, 3, 4 and 6 cycles were respectively 480 mg (282 mg/m2), 735 mg (435 mg/m2), 995 mg (589 mg/m2) and 1522mg (890 mg/m2).After a median follow up of 16.2 months, PFS at 12 months was 67.3%. We found that median PFS was significantly longer in patients who received at least 480 mg (282 mg/m2) within first two months of treatment compared to those that could not receive full-dose KRd (respectively, undefined vs 11 months p=0.04).To identify patients that could obtain the most advantage by KRd treatment, 65 patients who had received at least six cycles were distinguished in two groups, based on previous treatments. In group A, 27 patients were heavily pretreated (median previous lines 4, range 2-10) and had previously received lenalidomide while 38 patients included in group B were less pretreated (median previous lines 3, range 1-5) and lenalidomide- naïve. We found that group A had lower PFS than group B although duration of PFS from the previous treatment was similar in both groups.Conclusions: In our cohort of patients rate of VGPR or better obtained with KRd combination was high with an overall response rate of 34%, with an acceptable safety profile. It is therefore reasonable that approaches to achieve a higher cumulative dose, such as continuing therapy in responding patients and/or proactive adverse events management, influence efficacy. In addition, it is likely that patients not previously exposed to several lines of treatment including lenalidomide are the best candidate for a favorable outcome with KRd regimen. DisclosuresDi Raimondo:Celgene: Honoraria; Takeda: Honoraria, Research Funding.

Cancer and mTOR inhibitors in kidney transplantation recipients.

BackgroundPrevious studies show that mTOR inhibitors decrease the risk of cancer development after kidney transplantation. However, the effect of cumulative doses of mTOR inhibitors on cancer after kidney transplantation is not well known.MethodsIn the current study, patients were registered into a national database in Taiwan. Between year 2000 and 2013, 4,563 patients received kidney transplantation. They were divided into two groups, according to mTOR inhibitors usage. The cumulative dose of mTOR inhibitors was recorded. Patients were followed-up until de novo cancer development, death, or the end of 2014.ResultsPatients were divided into two groups: mTOR inhibitors users (study group, n = 828) and mTOR inhibitors non-users (control group, n = 3,735). The median follow-up duration was 7.8 years. The risk of de novo cancer (hazards ratio (HR) 0.80, 95% CI [0.60–1.09], p = 0.16) and risk of death (HR 1.14, 95% CI [0.82–1.60], p = 0.43) was not different between mTOR inhibitor user and non-user groups. Neither high- nor low-dose exposure to mTOR inhibitors was associated with increased risk of cancer or mortality. Analysis of cancer subtypes showed no influence by mTOR inhibitors. In addition, the cause of mortality was not significantly different between the two groups.DiscussionWe could not find the association of mTOR inhibitors use and risk of de novo cancer development or mortality in patients with kidney transplantation in Chinese patients. Cumulative exposure to mTOR inhibitors did not change the results.

Chloroethene. Documentation of proposed values of occupational exposure limits (OELs)

Chloroethene. Documentation of proposed values of occupational exposure limits (OELs)

Effect of Cumulative Intravenous Voriconazole Dose on Renal Function in Hematological Patients.

Intravenous voriconazole (VRC) is formulated by the incorporation of sulfobutylether-β-cyclodextrin (SBECD), which may accumulate to adversely affect renal function. However, the effect of long-term use of intravenous VRC on renal function is unclear. Our retrospective analysis of data confirmed that worsening of renal function was significantly associated with a cumulative dose of intravenous VRC (≥400 mg/kg), suggesting that a higher cumulative dose of intravenous VRC is a risk factor for renal dysfunction.

A facility for the study of Single Event Effects in the TANDAR accelerator

Abstract Semiconductor devices used in space applications suffer degradation due to the space radiation environment, which affects their electric parameters, eventually reducing the in-orbit lifetime. This relatively slow behavior is due to cumulative total dose effects. On the other hand, radiation can destroy information or even damage electronic parts of the device in a sudden way. These processes are known as Single Event Effects (SEE). Heavy ion beams from electrostatic tandem or other accelerators can be used to test and characterize the response of the electronics to SEE. Two conditions are necessary for this purpose: to use very low fluxes of only a few hundred to hundreds of thousand particles/(cm2·s), and to browse over a wide Linear Energy Transfer (LET) interval by changing the energy and/or the type of the impinging particles. In this work we describe the facility developed at the Argentine tandem accelerator (Tandar) to study SEE, and especially the fabrication and use of a perforated Ta foil to reduce the beam current to the required values. The determination of the resulting beam uniformity over the area of irradiation is also reported. The system has been tested by a SEE experiment on a webcam sensor.

Cumulative smoking dose affects the clinical outcomes of EGFR-mutated lung adenocarcinoma patients treated with EGFR-TKIs: a retrospective study

BackgroundAlthough lung adenocarcinoma with activating epidermal growth factor receptor (EGFR) mutations is common in never smokers, one-third of the patients are ever-smokers. We aimed to investigate the effect of cumulative smoking dose(CSD) on clinical outcomes, including progression-free survival (PFS) and overall survival (OS), in patients with EGFR-mutated lung adenocarcinoma receiving EGFR-tyrosine kinase inhibitors (TKIs).MethodsWe retrospectively analyzed 142 patients with EGFR-mutation positive advanced or recurrent lung adenocarcinoma who were administered gefitinib, erlotinib, afatinib, and osimertinib. These patients were classified based on their CSD as never smokers, light smokers (≤10 pack-years [PYs]), moderate smokers (11–30 PYs), and heavy smokers (> 30 PYs). PFS and OS were analyzed according to smoking subgroups via Kaplan-Meier curves.ResultsAmong the 142 patients, 91 (64.1%), 12 (8.5%), 22 (15.5%), and 17 (12%) were never, light, moderate, and heavy smokers, respectively. CSD was inversely associated with median PFS in a statistically significant dose-dependent manner (11.8 months (mo), 11.0 mo, 7.4 mo, and 3.9 mo; p < 0.001). Statistically significant negative association was observed between CSD and median OS (33.6 mo, 26.3 mo, 20 mo, and 8.9 mo; p < 0.001). In the multivariate analysis adjusted for age, sex, performance status, stage, and timing of EGFR-TKIs, CSD was an independent predictive factor for disease progression (hazard ratio [HR], 4.00; 95% confidence interval [CI], 1.95–8.23; p = 0.012) and OS (HR, 3.9; 95% CI, 1.84–8.28; p < 0.001).ConclusionCSD is an important predictive and prognostic factor in patients with EGFR-mutated lung adenocarcinoma, and associated smoking-related gene signatures might affect the outcomes.

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30-16.73), 0.58 (95% CI 0.36-0.81) and 2.66 (95% CI 1.42-4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

Association between Allopurinol and Cardiovascular Events and All-Cause Mortality in Diabetes—A Population-Based Cohort Study

Higher uric acid (UA) is associated with cardiovascular events and mortality. Allopurinol, a UA-lowering therapy, may reduce risk of these outcomes. Despite the high prevalence of elevated UA in diabetes, the association between allopurinol and cardiovascular events and mortality in diabetes is unclear. A population-based cohort was constructed using administrative data in Ontario, Canada. Subjects with diabetes entered on receipt of a new prescription for allopurinol after age 66 (April 1/2002-March 31/2012) and were followed until a composite of all-cause mortality, stroke, myocardial infarction or revascularization. A Cox proportional hazards model was used for each sex, with time-varying allopurinol exposure modeled as yes/no, dose categories and cumulative dose. Over a median [IQR] follow-up time of 4.7[1.8-7.8] years, the composite outcome occurred in 16,262/23,103 males and 10,566/15,313 females. Allopurinol exposure was associated with a reduction in the composite outcome in a dose-response manner but there was no cumulative dose effect (Table 1). Any allopurinol exposure and higher allopurinol doses were associated with reduced cardiovascular events and mortality in a large diabetes cohort. Potential mechanisms include an acute reduction of oxidative stress and endothelial dysfunction. Table 1: Hazard Ratios by Sex.Males (n=23,103)Females (n=15,313)Allopurinol ExposureUnadjusted HRAdjusted HRUnadjusted HRAdjusted HRExposed time v. unexposed time0.82 (0.79, 0.84)0.77 (0.75, 0.80)0.88 (0.85, 0.92)0.81 (0.78, 0.84)Dose categories0mg----&amp;gt;0 and ≤100mg1.03 (0.99, 1.08)0.84 (0.80, 0.88)1.(1.01, 1.12)0.86 (0.81, 0.90)&amp;gt;100 and ≤200mg0.82 (0.78, 0.85)0.75 (0.72, 0.78)0.83 (0.79, 0.87)0.76 (0.72, 0.80)&amp;gt;200mg0.71 (0.68, 0.74)0.75 (0.72, 0.78)0.78 (0.73, 0.82)0.81 (0.77, 0.86)Cumulative Dose (per 100g increase)0.99 (0.98, 1.00)1.00 (0.99, 1.01)0.99 (0.98, 1.01)0.99 (0.98, 1.00) Disclosure A. Weisman: None. G.A. Tomlinson: None. L. Lipscombe: None. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc.. G.A. Hawker: None.

Statins increase the risk of herpes zoster: A propensity score-matched analysis.

ObjectivesStatins, which are lipid-lowering agents, have anti-inflammatory and immunomodulatory properties that may affect the occurrence of various infectious diseases. We assessed whether statins increase the risk of herpes zoster (HZ) with propensity score-matching.MethodsThe study was based on the National Health Insurance database and its subset database of the “medical check-up” population of South Korea. These cohorts consist of about one million and 570,000 people, respectively, representative of the entire population of South Korea. We identified 103,930 statin users and 430,685 non-statin users. After propensity score-matching, 25,726 statin users and the same number of non-statin users were finally analyzed. The development of HZ was monitored in these matched pairs over the 11 years from 2003 to 2013.ResultsStatin users had a significantly higher risk of HZ than non-statin users: hazard ratio (HR) 1.25 (95% CI, 1.15 to 1.37) (p < .0001). The risk of HZ associated with statins was especially high in the elderly: HR 1.39 (95% CI, 1.12 to 1.73) in the over 70-year-olds (p = 0.003) and HR 1.18 (95% CI, 1.00 to 1.39) in the 60-to-69-year-olds (p = 0.056). Furthermore, there was a significant p for trend in terms of cumulative dose effect between the risk of HZ and the duration of statin use (p < .0001).ConclusionsThese epidemiologic findings provide strong evidence for an association between HZ and statin use, and suggest that unnecessary statins should be avoided.

A Systematic Review and Meta-Analysis of the Risk of Dementia Associated with Benzodiazepine Use, After Controlling for Protopathic Bias

Benzodiazepine use is highly prevalent in elderly and late middle-aged populations and may be associated with an increased risk of dementia. Observational studies have suggested that benzodiazepine use may increase the risk of dementia, however there have been significant concerns regarding protopathic bias in these studies, precluding conclusive findings. The aim of our study was to investigate the risk of dementia associated with the use of benzodiazepines in elderly patients, after controlling for protopathic bias. We identified observational studies with more than 50cases, adequate assessment of benzodiazepine exposure, and reliable dementia diagnosis ascertainment, from the MEDLINE, PubMed, EMBASE, CINAHL, LILACS and CENTRAL electronic databases through to 5 June 2018, with no language limits. The association of any current or former use of short- or long-acting benzodiazepines with incident dementia was analysed. A subgroup analysis was performed by the introduction of lag time to assess the effect of protopathic bias. We also performed analyses considering the effect of higher benzodiazepine cumulative doses and adjustment for psychiatric covariates. Study quality was investigated using the Newcastle-Ottawa Scale. We identified 15 studies reported in 14 articles, involving 159,090 cases. Ever use of benzodiazepines was associated with a significantly increased risk of dementia [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.21-1.59]. Those studies that implemented the longest lag times of ≥ 5years, and hence most likely to overcome protopathic bias, found a risk estimate that was marginally attenuated, but still significant (OR 1.30, 95% CI 1.14-1.48). Long-acting benzodiazepines were associated with a marginally higher magnitude risk (OR 1.21, 95% CI 0.99-1.49) than short-acting benzodiazepines (OR 1.13, 95% CI 1.02-1.26), although the former failed to reach statistical significance (p = 0.059). Our findings indicate that the association between benzodiazepine use and dementia incidence is not purely an artefact due to protopathic bias. Reduction of inappropriate benzodiazepine prescription is likely to attenuate dementia risk.

Temporally dissociable effects of ketamine on neuronal discharge and gamma oscillations in rat thalamo-cortical networks

BackgroundSub-anesthetic doses of the non-competitive N-methyl-d-aspartate receptor (NMDA-R) antagonist ketamine evoke transient psychotomimetic effects, followed by persistent antidepressant effects in treatment-resistant depressed patients and rodents through still poorly understood mechanisms. Since phencyclidine (PCP) disinhibits thalamo-cortical networks by blocking NMDA-Rs on GABAergic neurons of the reticular thalamic nucleus (RtN), we examined ketamine's actions in the same areas. MethodsSingle units and local field potentials were recorded in chloral hydrate anesthetized male Wistar rats. The effects of cumulative ketamine doses (0.25–5 mg/kg, i.v.) on neuronal discharge and oscillatory activity were examined in RtN, mediodorsal and centromedial (MD/CM) thalamic nuclei, and layer VI of the medial prefrontal cortex (mPFC). ResultsKetamine (1, 2 and 5 mg/kg, i.v.) significantly decreased the discharge of MD/CM, RtN and layer VI mPFC pyramidal neurons. Simultaneously, ketamine decreased the power of low frequency oscillations in all areas examined and increased gamma oscillations in mPFC and MD/CM. Lower ketamine doses (0.25 and 0.5 mg/kg, i.v.) were ineffective. ConclusionsAs observed for PCP, ketamine markedly inhibited the activity of RtN neurons. However, unlike PCP, this effect did not translate into a disinhibition of MD/CM and mPFC excitatory neurons, possibly due to a more potent and simultaneous blockade of NMDA-Rs by ketamine in MD/CM and mPFC neurons. Hence, the present in vivo results show that ketamine evokes an early transient inhibition of neuronal discharge in thalamo-cortical networks, following its rapid pharmacokinetics, which is likely associated to its psychotomimetic effects. The prolonged increase in gamma oscillations may underlie its antidepressant action.

Statistical methods for elimination of guarantee-time bias in cohort studies: a simulation study

BackgroundAspirin has been considered to be beneficial in preventing cardiovascular diseases and cancer. Several pharmaco-epidemiology cohort studies have shown protective effects of aspirin on diseases using various statistical methods, with the Cox regression model being the most commonly used approach. However, there are some inherent limitations to the conventional Cox regression approach such as guarantee-time bias, resulting in an overestimation of the drug effect. To overcome such limitations, alternative approaches, such as the time-dependent Cox model and landmark methods have been proposed. This study aimed to compare the performance of three methods: Cox regression, time-dependent Cox model and landmark method with different landmark times in order to address the problem of guarantee-time bias.MethodsThrough statistical modeling and simulation studies, the performance of the above three methods were assessed in terms of type I error, bias, power, and mean squared error (MSE). In addition, the three statistical approaches were applied to a real data example from the Korean National Health Insurance Database. Effect of cumulative rosiglitazone dose on the risk of hepatocellular carcinoma was used as an example for illustration.ResultsIn the simulated data, time-dependent Cox regression outperformed the landmark method in terms of bias and mean squared error but the type I error rates were similar. The results from real-data example showed the same patterns as the simulation findings.ConclusionsWhile both time-dependent Cox regression model and landmark analysis are useful in resolving the problem of guarantee-time bias, time-dependent Cox regression is the most appropriate method for analyzing cumulative dose effects in pharmaco-epidemiological studies.

Relationships between iron dose, hospitalizations and mortality in incident haemodialysis patients: a propensity-score matched approach.

Intravenous iron management is common in the haemodialysis population. However, the safest dosing strategy remains uncertain, in terms of the risk of hospitalization and mortality. We aimed to determine the effects of cumulative monthly iron doses on mortality and hospitalization. This multicentre observational retrospective propensity-matched score study included 1679 incident haemodialysis patients. We measured baseline demographic variables, haemodialysis clinical parameters and laboratory analytical values. We compared outcomes among quartiles of cumulative iron dose (mg/kg/month). We implemented propensity-score matching (PSM) to reduce confounding due to indication. In the PSM cohort (330 patients), we compared outcomes between groups that received cumulative iron doses above and below 5.66 mg/kg/month. Kaplan-Meier analyses showed that the high iron dose group had significantly worse survival than the low iron dose group. A univariate analysis indicated that the monthly iron dose could significantly predict mortality. However, a multivariate regression did not confirm that finding. The multivariate regression analysis revealed that iron doses >5.58 mg/kg/month were not associated with elevated mortality risk, but they were associated with elevated risks of all-cause and cardiovascular-related hospitalizations. These results were ratified in the PSM population. Intravenous iron administration is advisable for maintaining haemoglobin levels in patients that receive haemodialysis. Our data suggested that large monthly iron doses, adjusted for body weight, were associated with more hospitalizations, but not with mortality or infection-related hospitalizations.

Cumulative receipt of an anti-poverty tax credit for families did not impact tobacco smoking among parents

The effect of anti-poverty tax credit interventions on tobacco consumption is unclear. Previous studies have estimated short-term effects, did not isolate the effects of cumulative dose of tax credits, produced conflicting results, and used methods with limited control for some time-varying confounders (e.g., those affected by prior treatment) and treatment regimen (i.e., study participants' tax credit receipt pattern over time). We estimated the longer-term, cumulative effect of New Zealand's Family Tax Credit (FTC) on tobacco consumption, using a natural experiment (administrative errors leading to exogenous variation in FTC receipt) and methods specifically for controlling confounding, reverse causation, and treatment regimen. We extracted seven waves (2002–2009) of the nationally representative Survey of Family, Income and Employment including 4404 working-age (18–65 years) parents in families. The exposure was the total numbers of years of receiving FTC. The outcomes were regular smoking and the average daily number of cigarettes usually smoked at wave 7. We estimated average treatment effects using inverse probability of treatment weighting and marginal structural modelling. Each additional year of receiving FTC affected neither the odds of regular tobacco smoking among all parents (odds ratio 1.02, 95% confidence interval 0.94–1.11), nor the number of cigarettes smoked among parents who smoked regularly (rate ratio 1.01, 95% confidence interval 0.99–1.03). We found no evidence for an association between the cumulative number of years of receiving an anti-poverty tax credit and tobacco smoking or consumption among parents. The assumptions of marginal structural modelling are quite demanding, and we therefore cannot rule out residual confounding. Nonetheless, our results suggest that tax credit programme participation will not increase tobacco consumption among poor parents, at least in this high-income country.

High-energy Electron Induced SEUs and Jovian Environment Impact

We present experimental evidence of electron-induced upsets in a reference European Space Agency (ESA) single event upset (SEU) monitor, induced by a 200-MeV electron beam at the Very energetic Electronic facility for Space Planetary Exploration in harsh Radiation environments facility at CERN. Comparison of experimental cross sections and simulated cross sections is shown and the differences are analyzed. Possible secondary contributions to the upset rate by neutrons, flash effects, and cumulative dose effects are discussed, showing that electronuclear reactions are the expected SEU mechanism. The ESA Jupiter Icy Moons Explorer mission, to be launched in 2022, presents a challenging radiation environment due to the intense high-energy electron flux in the trapped radiation belts. Insight is given to the possible contribution of electrons to the overall upset rates in the Jovian radiation environment. Relative contributions of both typical electron and proton spectra created when the environmental spectra are transported through a typical spacecraft shielding are shown and the different mission phases are discussed.

Radiation Effects in Pinned Photodiode CMOS Image Sensors: Variation of Epitaxial Layer Thickness

This paper focuses on radiation effects on process optimized CMOS image sensors. Several technological parameters are varying, especially the epitaxial layer thickness, to reach the best electro-optical performances of the image sensors. The goal of the study is to show how radiation damages the gain brought by these parameters. Proton irradiations were used to study cumulative dose effects. As previously observed, the dark current is the main electrical parameter affected by these ionizing and displacement damage doses. The damage sources are investigated and mitigation techniques are provided to optimize CMOS image sensors dedicated to observation satellites.

Physiologic kinetic profile of glycemic response in a single dose of clonidine

Background: Clonidine activates peripheral α-2 adrenoreceptors and influences glycemic levels. Aim and Objective: The aim and objective of the study was to determine the physiologic kinetic profile of glycemic response in a single dose of clonidine. Materials and Methods: Experimental data on fasting glycemic levels of Sprague-Dawley rats in a single dose intraperitoneal administration of clonidine were used to describe the rate mechanisms behind the physiologic response. Parameters of the kinetic models including zero-order, first-order, and second-order were estimated and compared using nonlinear regression analysis. Results: Clonidine administration resulted to a dose-dependent fasting glycemic level with maximal cumulative dose effect at 4 μg/kg. The overall physiologic glycemic response behaved under zero-order and first-order kinetic models on the first 3 h, while second-order kinetic model captures the fasting glycemic levels on the 3rd-8th h after drug administration. Conclusion: A 4 μg/kg optimal dose accentuates glycemic response behaving under a zero-order or first-order rate mechanism with maximal effect on the first 3 h after clonidine administration.

Effects of Reflexology on Pain in Patients With Fibromyalgia.

The aim of this study was to investigate the effect of reflexology on pain intensity in patients with fibromyalgia, using an experimental repeated-measures design, and a convenience sample of 30 fibromyalgia inpatients. Thirty patients aged 18 to 70 years with fibromyalgia and hospitalized in the algology clinic were taken as a convenience sample. Patients received a total of 12 60-minute sessions of reflexology over a period of 6 consecutive weeks. Reflexology was carried out bilaterally on the hands and feet of patients at the reflex points relating to their pain at a suitable intensity and angle. Subjects had pain scores taken immediately before the intervention (0 minute), and at the 60th minute of the intervention. Data were collected over a 10-month period in 2012. The patients' mean pain intensity scores were reduced by reflexology, and this decrease improved progressively in the first and sixth weeks of the intervention, indicating a cumulative dose effect. The results of this study implied that the inclusion of reflexology in the routine care of patients with fibromyalgia could provide nurses with an effective practice for reducing pain intensity in these patients.