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Objective Serum neurofilament light (sNfL) is a promising new biomarker in multiple sclerosis (MS). We explored the relationship between sNfL and health outcomes and resource use in MS patients. Methods MS patients with serum samples and health‐outcome measurements collected longitudinally between 2011 and 2016 were analyzed. sNfL values were evaluated across age and gender. Data were analyzed using correlation with log‐transformed sNfL values. Results A total of 304 MS patients with a mean age of 32.9 years, average EDSS of 1.6 (SD = 1.5) and baseline sNfL of 8.8 (range 1.23–78.3) pg/mL were studied. Baseline sNFL values increased with age and were higher in females. Baseline sNfL correlated with baseline Multiple Sclerosis Quality of Life physical composite (mean = 49.4 (9.1), P = 0.035) and baseline EDSS (P = 0.002). Other PRO measures at baseline did not show a significant relationship with baseline sNfL. Average of baseline and follow‐up sNfL correlated with MSQoL physical‐role limitations (mean = 48.9 (10.8), P = 0.043) and social‐functioning (mean = 52.3 (7), P = 0.034) at 24‐month follow‐up. We found a trend for numerically higher sNfL levels in nonpersistent patients compared to those who were persistent to treatment (11.13 vs. 8.53 pg/mL, P = 0.093) measured as average of baseline and 24‐month values. Baseline NfL was associated with number of intravenous steroid infusions (mean = 0.2; SD = 3.0, P = 0.013), whereas the average of baseline and 12 months NfL values related to inpatient stays at 12 months (mean = 0.2; SD = 3.0 P = 0.053). Conclusion Serum NfL is a patient‐centric biomarker that correlated with MS patient health‐outcomes and healthcare utilization measures in a real‐world cohort.

Background: The current landscape and treatment patterns of disease-modifying therapy (DMT) use in pediatric patients with multiple sclerosis (MS) are not yet well understood. This study examined DMT utilization and treatment patterns in pediatric patients newly diagnosed as having MS. Methods: Pediatric patients ( Results: Of 182,057 patients newly diagnosed as having MS, 288 pediatric patients (mean age, 14 years; 61% female) were identified. Within the first year of diagnosis, 188 patients (65.3%) did not receive any DMT. The most common first-initiated treatments were interferons and glatiramer acetate (83%), but 28% of patients switched or discontinued from first-initiated treatment within 6 months of treatment initiation. Conclusions: This study suggests that a considerable proportion of pediatric patients with MS remain untreated within 1 year of diagnosis. Patients most commonly initiated injectables as their first DMT. Overall, therapy failed early in approximately one in three patients. Thus, the study warrants urgency in treating these patients with currently approved treatment options.

Background Migraine is associated with debilitating symptoms that can affect daily functioning. "My Migraine Voice" was a large, cross-sectional, multi-country online survey aimed at understanding disease burden directly from people with migraine. Objective This study reports on the social and economic impacts of migraine, specifically the impact on activities of daily living and the costs of migraine, from the point of view of people with migraine in the United States. Methods The online survey was administered to adults with a self-reported diagnosis of migraine who experienced 4 or more monthly migraine days each month for the previous 3 months. Prespecified screening quotas were used so that 90% of respondents reported current or past use of preventive migraine medication, 80% of whom switched treatment (ie, changed their prescribed preventive medication at least once). The remaining 10% were preventive treatment naive (ie, never used any prescribed preventive medication). Burden of migraine on activities of daily living and caregivers (eg, functional limitations, fear of next migraine attack, sleep problems) and economic burden (eg, out-of-pocket costs, impact on work productivity using the validated work productivity and activity impairment questionnaire) reported by respondents from the United States are presented. Results are stratified by employment status, migraine frequency (chronic vs episodic migraine), and history of preventive treatment. Results Thousand hundred and one individuals with migraine from the United States responded to the survey. Respondents reported limitations completing daily activities during all migraine phases, including during the premonitory/aura and postdrome phases. Most (761/1101 (69%)) relied on family, friends, or others for help with daily tasks and reported being helped a median of 9 days (25th percentile 5 days, 75th percentile 15 days) within the last 3 months. Respondents with chronic migraine reported being helped for more days (median 10 days, 25th percentile 5 days, 75th percentile 23 days) in the last 3 months. Almost all (962/1101 (87%)) experienced sleep difficulties and 41% (448/1101) (48% (336/697) of those with 2 or more preventive treatment failures) were very or extremely fearful of a next migraine attack. Median (25th percentile, 75th percentile) monthly out-of-pocket costs of $90.00 ($30.00, $144.00) in doctor's fees (n = 504), $124.00 ($60.00, $234.00) in health insurance (n = 450), $40.00 ($20.00, $100.00) for prescriptions (n = 630), and $50.00 ($0.00, $100.00) for complementary therapies (n = 255) were reported. Those with 2 or more preventive treatment failures reported higher monthly out-of-pocket doctor fees (median $99.00 ($30.00, $150.00), n = 388). Among employed respondents (n = 661), migraine resulted in 22% absenteeism, 60% presenteeism, 65% work productivity loss, and 64% activity impairment. Conclusions Migraine impacts individuals' activities of daily living, work-life, and financial status, especially individuals with high needs, namely those with 4 or more monthly migraine days and prior treatment failures. People with migraine are impaired during all migraine phases, experience fear of their next migraine attack and sleep difficulties, and pay substantial monthly out-of-pocket costs for migraine. Burden is even greater among those who have had 2 or more preventive treatment failures. Impacts of migraine extend beyond probands to caregivers who help people with migraine with daily tasks, employers who are affected by employee absenteeism, presenteeism, and reduced productivity, and society which is burdened by lost and reduced economic productivity and healthcare costs.

Aims: The current study examined the association between insufficient major depressive disorder (MDD) care and healthcare resource use (HCRU) and costs among patients with prior myocardial ...

Purpose: The Treatment Effectiveness Assessment (TEA) is a patient-centered instrument for evaluating treatment progress and recovery from substance use disorders, including opioid use disorder (OUD). We assessed the TEA's reliability and validity and determined minimal clinically important differences (MIDs) in participants with moderate to severe OUD. Patients and methods: The TEA measures change in four single-item domains (substance use, health, lifestyle, community involvement) from treatment initiation across the duration of a treatment program. Self-reported responses range from 1 ("none or not much") to 10 ("much better") with items summed to a total score ranging from 4-40. We assessed floor and ceiling effects, internal consistency, test-retest reliability, known-groups validity (ANOVA stratified by current health status [36-Item Short Form Health Survey item 1]), convergent/divergent validity, and MIDs using data from a phase 3, open-label clinical trial of buprenorphine extended-release monthly injection for subcutaneous use (BUP-XR). Participants with OUD completed the TEA at screening and before monthly injections for up to 12 months. Results: Among 410 participants (mean age 38 years; 64% male), the mean baseline (pre-injection 1) TEA total score was 25.4 (SD 9.7), with

Fault attacks are a known threat to secure embedded implementations. We propose a generic technique to detect and react to fault attacks on embedded software. The countermeasure combines a micro-architecture extension in hardware with a secure trap in software. The combined extension leads to a secure exception mode to handle fault attacks. The microprocessor hardware uses a low-level hardware checkpointing mechanism to recover from fault injection. A high-level secure trap in software then enables an application-specific response. The trap is user-defined and can be co-developed with the application. The combination of hardware fault detection and recovery, with a high-level fault response policy in software leads to significantly lower overhead when compared to traditional redundancy-based techniques in hardware or software. We demonstrate a prototype implementation of the proposed secure exception mode. The prototype is based on a modified LEON3 processor and it is able to detect and respond to setup-time violation attacks. We have realized the design in a 180 nm standard cell ASIC with integrated memory. Using several driver application examples, we characterize the software and hardware overhead of the proposed solution, and we compare it to the conventional redundancy-based solutions. In our understanding this is the first proof-in-silicon processor to offer a comprehensive secure exception mode against fault-injection attacks.

This work will demonstrate how the Energy Recovery Inc. (ERI) engineering team improved the efficiency of a multistage pump by about 10% at the first stage, which translated into a 3% increase in the overall multistage pump efficiency; according to a set of engineering calculations and review of the archived in-house test data for the legacy multistage pumps, it was hypothesized that the performance pain-point of the pump was inefficient performance of the first stage, due to the formation of a strong pre-swirl right before its inlet. The validity of this hypothesis then was confirmed via RANS CFD simulations of the flow field inside the inlet suction housing and pump impeller. Same CFD methodology was used to evaluate multiple engineering solutions to reduce the strength of the inflow pre-swirl by modifying the inlet suction housing geometry. The obtained RANS CFD solutions guided the engineering team towards the most promising hardware modification proposal. The proposed geometrical modification of the inlet suction housing was implemented and tested on different multistage pumps. All of the test results validated the obtained RANS CFD numerical solution. The state of the art in this successful performance improvement process was first the on-point hypothesis development based on fundamentals of engineering and archived test data. Second, the proper RANS CFD methodology development to model/confirm the initial hypothesis and vet all possible engineering solutions to maximize the multistage pump efficiently and accurately. This can be a great example for various relevant turbomachinery industrial applications.

Background Multiple sclerosis (MS) is a chronic neurodegenerative disease. Current monitoring practices predominantly rely on brief and infrequent assessments, which may not be representative of the real-world patient experience. Smartphone technology provides an opportunity to assess people’s daily-lived experience of MS on a frequent, regular basis outside of episodic clinical evaluations. Objective The objectives of this study were to evaluate the feasibility and utility of capturing real-world MS-related health data remotely using a smartphone app, “elevateMS,” to investigate the associations between self-reported MS severity and sensor-based active functional tests measurements, and the impact of local weather conditions on disease burden. Methods This was a 12-week, observational, digital health study involving 3 cohorts: self-referred participants who reported an MS diagnosis, clinic-referred participants with neurologist-confirmed MS, and participants without MS (controls). Participants downloaded the elevateMS app and completed baseline assessments, including self-reported physical ability (Patient-Determined Disease Steps [PDDS]), as well as longitudinal assessments of quality of life (Quality of Life in Neurological Disorders [Neuro-QoL] Cognitive, Upper Extremity, and Lower Extremity Function) and daily health (MS symptoms, triggers, health, mobility, pain). Participants also completed functional tests (finger-tapping, walk and balance, voice-based Digit Symbol Substitution Test [DSST], and finger-to-nose) as an independent assessment of MS-related cognition and motor activity. Local weather data were collected each time participants completed an active task. Associations between self-reported baseline/longitudinal assessments, functional tests, and weather were evaluated using linear (for cross-sectional data) and mixed-effects (for longitudinal data) regression models. Results A total of 660 individuals enrolled in the study; 31 withdrew, 495 had MS (n=359 self-referred, n=136 clinic-referred), and 134 were controls. Participation was highest in clinic-referred versus self-referred participants (median retention: 25.5 vs 7.0 days). The top 5 most common MS symptoms, reported at least once by participants with MS, were fatigue (310/495, 62.6%), weakness (222/495, 44.8%), memory/attention issues (209/495, 42.2%), and difficulty walking (205/495, 41.4%), and the most common triggers were high ambient temperature (259/495, 52.3%), stress (250/495, 50.5%), and late bedtime (221/495, 44.6%). Baseline PDDS was significantly associated with functional test performance in participants with MS (mixed model–based estimate of most significant feature across functional tests [β]: finger-tapping: β=–43.64, P Conclusions The elevateMS study app captured the real-world experience of MS, characterized some MS symptoms, and assessed the impact of environmental factors on symptom severity. Our study provides further evidence that supports smartphone app use to monitor MS with both active assessments and patient-reported measures of disease burden. App-based tracking may provide unique and timely real-world data for clinicians and patients, resulting in improved disease insights and management.

Aims To present the development of the International Consultation on Incontinence Questionnaire-underactive bladder (ICIQ-UAB) as the first patient reported outcome measure for the assessment of the symptoms and impact on the health-related quality of life of UAB developed in-line with the Food and Drug Administration Guidance for Industry. Methods Draft items were developed following 44 semi-structured concept elicitation interviews in the UK and refined using 36 cognitive interviews. A pilot study was designed to assess the draft ICIQ-UAB's initial psychometric properties with 54 patients recruited from European hospitals. Further concept elicitation interviews were also carried out with 11 patients in the US and 10 patients in Japan. All participants had a prior urodynamic diagnosis of detrusor underactivity. Results The cognitive interviews confirmed the initial items to be understood and interpreted as intended. Pilot testing showed that both internal consistency (Cronbach's alpha >= 0.85) and test-retest reliability (stable patients; intraclass correlation coefficient >= 0.88) were high. The interviews in the US and Japan elicited symptoms and impacts that support previous findings in the UK and provided further insight into the experiences of patients in those countries. The developmental ICIQ-UAB was refined using the evidence from all substudies. Conclusions The validity and reliability of the ICIQ-UAB were supported in a pilot study setting and the wider cultural applicability by the additional interviews in the US and Japan. Following further validation in future clinical trials, the developmental ICIQ-UAB is envisaged as an important tool for the monitoring of future UAB treatment strategies.

Aims The association between depression care adequacy and the risk of subsequent adverse cardiovascular disease (CVD) outcomes among patients with a previous diagnosis of myocardial infarction (MI) or stroke is not well defined. Methods and results This retrospective cohort study used commercial claims data (2010-2015) and included adults with newly diagnosed and treated major depressive disorder (MDD) following an initial MI or stroke diagnosis. Depression care adequacy was assessed during the 3-month period following the MDD diagnosis index date using two measures: antidepressant dosage adequacy and duration adequacy. Cox models adjusted for the propensity of receiving adequate depression care were used to compare the risk of a composite CVD outcome (MI, stroke, congestive heart failure, and angina) as well as each individual CVD event between patients receiving adequate vs. inadequate depression care. A total of 1568 patients were included in the final cohort. Of these, 937 (59.8%) were categorized as receiving inadequate depression care based on at least one of the two treatment adequacy criteria. Propensity score adjusted Cox models showed that depression care inadequacy was associated with a significantly higher risk of the composite CVD endpoint [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.04-1.39], stroke (HR 1.20, 95% CI 1.02-1.42), and angina (HR 1.95, 95% CI 1.21-3.16) with no significant interaction based on cohort included (MI vs. stroke) or the definition of inadequate depression (dose vs. duration inadequacy) (Pinteraction > 0.05). Conclusion Inadequate MDD care was associated with a higher risk of adverse CVD events. These findings reveal a significant unmet clinical need in patients with post-MI or post-stroke MDD that may impact CVD outcomes.

Our study examined the impact of adherence to novel oral anticoagulants [NOACs - dabigatran and rivaroxaban] on ischemic-stroke (IS), major-bleeding (MB), deep-vein-thrombosis and pulmonary-embolism (DVTPE) risk in a large, nationwide, propensity-matched sample.A retrospective cohort study utilized data from a US commercial managed-care database (2010-2012). Adult patients with ≥1 diagnosis of atrial fibrillation/flutter (ICD-9 427.31/32),1 prescription of NOACs and CHAA total of 3,629 and 1,946 patients with at least 6 and 12 months of NOAC use were included. Based on a PDC threshold of ≥80%, adherence rates at 6 and 12 month usage were 77% and 76%, respectively. Patients with lowest adherence were from the South, had low stroke risk and EPO/HMO insurance. Using Cox models with matched cohorts, nonadherence within the first 6 months' use was significantly associated with higher risk of IS and DVTPE (IS: hazard ratio [HR] = 1.82, p = .002; DVTPE: HR = 2.12, p = .010) and the risk increased with nonadherence for the prolonged period of 12 months' use (IS: HR = 2.08, p = .022; DVTPE: HR = 5.39, p = .003). The risk of MB was not different (p .05) between adherent and nonadherent groups for both 6 month and 12 month cohorts.Adherence to NOACs for both 6 months and prolonged use (up to 12 months) was associated with a reduction in IS and DVTPE risk, but did not substantially increase risk of MB. Further studies on newer, individual NOACs and older populations are warranted.

Fault attacks on cryptographic software use faulty ciphertext to reverse engineer the secret encryption key. Although modern fault analysis algorithms are quite efficient, their practical implementation is complicated because of the uncertainty that comes with the fault injection process. First, the intended fault effect may not match the actual fault obtained after fault injection. Second, the logic target of the fault attack, the cryptographic software, is above the abstraction level of physical faults. The resulting uncertainty with respect to the fault effects in the software may degrade the efficiency of the fault attack, resulting in many more trial fault injections than the amount predicted by the theoretical fault attack. In this contribution, we highlight the important role played by the processor microarchitecture in the development of a fault attack. We introduce the microprocessor fault sensitivity model to systematically capture the fault response of a microprocessor pipeline. We also propose Microarchitecture-Aware Fault Injection Attack (MAFIA). MAFIA uses the fault sensitivity model to guide the fault injection and to predict the fault response. We describe two applications for MAFIA. First, we demonstrate a biased fault attack on an unprotected Advanced Encryption Standard (AES) software program executing on a seven-stage pipelined Reduced Instruction Set Computer (RISC) processor. The use of the microprocessor fault sensitivity model to guide the attack leads to an order of magnitude fewer fault injections compared to a traditional, blind fault injection method. Second, MAFIA can be used to break known software countermeasures against fault injection. We demonstrate this by systematically breaking a collection of state-of-the-art software fault countermeasures. These two examples lead to the key conclusion of this work, namely that software fault attacks become much more harmful and effective when an appropriate microprocessor fault sensitivity model is used. This, in turn, highlights the need for better fault countermeasures for software.

Caitlyn T Solem,1 Ahmed Shelbaya,2,3 Yin Wan,1 Chinmay G Deshpande,1 Jose Alvir,2 Elizabeth Pappadopulos2 1Pharmerit International, Real World Evidence/Data Analytics, Bethesda, MD, 2Pfizer, Inc., Global Health Outcomes, New York, NY, 3Epidemiology Department of Mailman’s School of Public Health, Columbia University Mailman School of Public Health, New York, NY, USA Background: In major depressive disorder (MDD), treatment persistence is critical to optimize symptom remission, functional recovery, and health care costs. Desvenlafaxine tends to have fewer drug interactions and better tolerability than other MDD drugs; however, its use has not been assessed in the real world.Objective: The aim of the present study is to compare medication persistence and concomitant MDD drug use with branded desvenlafaxine (Pristiq®) compared with antidepressant drug groups classified as 1) branded selective serotonin reuptake inhibitors (SSRIs; ie, escitalopram [Lexapro™]) and selective serotonin–norepinephrine reuptake inhibitors (SNRIs; ie, venlafaxine [Effexor®], duloxetine [Cymbalta®]) and 2) generic SSRIs/SNRIs (ie, escitalopram, citalopram, venlafaxine, fluvoxamine, fluoxetine, sertraline, paroxetine, and duloxetine).Patients and methods: MDD patients (ICD-9-CM codes 296.2, 296.3), with ≥2 prescription fills for study drugs and 12-month preindex continuous enrollment from the MarketScan Commercial Claims and Encounters Database (2009–2013), were included. Time-to-treatment discontinuation (prescription gap ≥45days) was assessed using the Kaplan–Meier curve and Cox model. Concomitant MDD drug use was compared.Results: Of the 273,514 patients included, 14,379 patients were initiated with branded desvenlafaxine, 50,937 patients with other branded SSRIs/SNRIs, and 208,198 patients with generic SSRIs/SNRIs. The number of weeks for treatment discontinuation for branded desvenlafaxine were longer (40.7 [95% CI: 39.3, 42.0]) compared with other branded SSRIs/SNRIs (28.9 [95% CI: 28.4, 29.1]) and generic SSRIs/SNRIs (33.4 [95% CI: 33.1, 33.7]). Adjusting for baseline characteristics, patients who were prescribed with other branded SSRIs/SNRIs were 31% and generic SSRIs/SNRIs were 11% more likely to discontinue treatment compared with branded desvenlafaxine. In sensitivity analysis, the risk of discontinuation was within 10% of branded desvenlafaxine for branded duloxetine, generic escitalopram, and generic venlafaxine. Concomitant MDD drug use was higher among branded desvenlafaxine patients (43.8%) compared with other branded SSRIs/SNRIs (39.8%) and generic SSRIs/SNRIs (36.4%).Conclusion: MDD patients on branded desvenlafaxine were more persistent with treatment compared with those on other branded or generic SSRI/SNRI therapies. Future research should include assessments of underlying factors on the treatment persistence in MDD patients. Keywords: selective serotonin reuptake inhibitors, selective serotonin–norepinephrine re-uptake inhibitors

BACKGROUND: With lack of real-world evidence, the challenge for the drug reimbursement policy decision makers is to understand medication adherence behavior among Novel Oral Anticoagulants [NOAC] users and its impact on overall cost savings. Furthermore, no study has examined and quantified the burden of cost in high-risk patients taking NOAC therapy. OBJECTIVE: To examine an association of cost with adherence, co-morbidity, stroke and bleeding risk in patients taking NOAC [rivaroxaban, dabigatran]. METHODS: A retrospective cohort study utilized de-identified data from a commercial managed care database by Optum® Clinformatics™ Data Mart (OptumInsight, Eden Prairie, MN) (Jan 1, 2010 and Dec 31, 2012). Patients (aged 18+), with ≥1 diagnosis of atrial fibrillation/flutter (ICD-9 427.31/32), >1 prescription of NOACs, 6-month pre-index and 12-month post-index continuous enrollment and CHA(2)DS(2)-VASc score ≥1 were included. Adherence was calculated using Proportion of Days Covered (PDC ≥80%) over 3, 6, 12-month period and compared based on the patient’s level of co-morbidity, stroke and bleeding risk. The adjusted annual healthcare costs per patient (drug, medical and total) were calculated using multivariable gamma regression controlling for demographic and clinical characteristics and compared across groups based on adherence over 12 months, baseline level of co-morbidity, stroke and bleeding risk. RESULTS: Out of 25,120 NOAC patients, a total of 2981 patients were included in the final cohort. Based on a PDC threshold of ≥80%, adherence rates over 3, 6 and 12 months were 72%, 65%, and 54%, respectively. For all time periods (3, 6, 12-months), the level of adherence significantly (P

Electromagnetic Fault Injection (EMFI) is a powerful class of fault attacks that can break hardware and software security mechanisms. The main advantage of EMFI over the other fault injection methods is being able to create local faults without depackaging the target chip. Therefore, designing low-cost and efficient detection mechanisms to sense EMFI is a challenging task. In this work, we propose a low-cost, fully-digital, and cycle-accurate mechanism to detect EMFI. We also present a framework to integrate the proposed detector into any logic core. We implemented the proposed detection mechanism on an Altera Cyclone-IV FPGA and integrated it with a round-serial hardware implementation of AES-128. The area overhead of this design is 14.6% and 81.5% in the number of LUTs and registers, respectively. We also experimentally demonstrated the efficiency of the implemented design under actual EM fault injection. In our experiments, we applied 20000 EM pulses with different parameters (i.e, timing, location, pulse width, energy). In total, 7% of the applied pulses causes faults in the output of the AES. The proposed mechanism successfully detected all of the injected faults without any false alarms.

Introduction: Dabigatran and Rivaroxaban have shown better or similar efficacy to lower stroke risk compared to warfarin in clinical trials. Evidence suggests adherence to cardiac drugs tend to reduce outcomes and cost. Our study is the first to examine the impact of atleast 6 to 12 month adherence to NOACs on ischemic stroke, major bleeding, Deep Vein Thrombosis and Pulmonary Embolism (DVTPE) risk in a propensity score based matched sample. Methods: A retrospective cohort study utilized de-identified data from Optum® Clinformatics™ Data Mart database (OptumInsight, Eden Prairie, MN) (Jan 1, 2010 and Dec 31, 2012). Adult patients with ≥ 1 diagnosis of atrial fibrillation or flutter (ICD9 427.31/32), >1 prescription of NOACs, 6 months pre-index continuous enrollment and CHA2DS2VASC score >1 were included. Adherence was calculated using Proportion of Days Covered (PDC ≥80%) for atleast 6 and 12 months of NOAC use and cohorts (adherent vs. non adherent) were matched on propensity score using Inverse Probability Treatment Weighting (IPTW) controlling for demographic and clinical characteristics at baseline. The risk of ischemic stroke, major bleeding (primary outcomes) and DVTPE (exploratory outcome) was evaluated for the matched cohorts post adherence assessment using Cox regression. Results: Out of 25,150 NOAC patients, a total of 3,629 and 1,946 patients with atleast 6 and 12 months of NOAC use were included. Across 2 cohorts, the mean age of the sample was 65 years, 65% were males and >60% had a moderate-high risk of stroke (CHA2DS2VASC>2). Adherence (PDC ≥80%) was 77% and 76% for patients with 6 and 12 month drug use. Post 12 months of drug use, the overall incidence of bleeding, stroke, and DVTPE in the follow-up period was 4.42%, 1.80%, and 0.82% respectively. Each outcome was analyzed separately to avoid calculation of competing risks. Using Cox models with IPTW balanced cohorts, non-adherence was significantly (p ≤0.05) associated with an increase in stroke (≥ 1.5 fold) and DVTPE (≥ 2 fold) risk in both 6 and 12 month users. The risk of bleeding was not significantly different across adherent vs. non adherent users (Table). Conclusion: In our sample, adherence to NOACs was associated with a reduction in stroke and DVTPE risk but did not substantially increase bleeding risk. Further studies with newer NOACs are warranted.

In this paper, we propose a cycle-accurate monitor that can efficiently detect timing violation based fault attacks. The proposed monitor detects clock or voltage manipulations by monitoring the external clock using an internal Ring Oscillator. The monitor is low cost in terms of area and power consumption and can be easily implemented using the standard cell based VLSI design flow. In addition to the architecture of the timing monitor, we present a detailed analysis on the design considerations that affect the cost and accuracy of the monitor. To validate the functionality of the monitor, we implemented it on Spartan-6 FPGA. We also synthesized our monitor onto IBM 90nm ASIC technology to examine the effects of process variation and aging. We show that the proposed method brings 0.23% area and 1.4% power overhead on a reference AES-128 hardware implementation.

Fault attacks are a known serious threat to embedded software security. We propose FAME, a low-cost and flexible approach to defend embedded software against fault attacks.FAME offers a combination of fault detection in hardware and fault response in software. A hardware fault detection unit continuously monitors the system status. When a fault injection is detected, an alarm signal triggers a secure trap mechanism that passes the control to a software trap handler. The trap handler applies a suitable fault response policy, which may include a broad variety of responses such as clearing sensitive data or issuing system-wide alerts. This enables a targeted, fast fault detection as well as an application-dependent, user-defined fault response.FAME requires much lower overhead than traditional countermeasure techniques in software or hardware. We demonstrate a prototype implementation of FAME using a modified LEON3 processor, and we analyze the hardware and software overhead to thwart setup-time violation attacks. The hardware area overhead is 7.4% and 14.2% in the number of LUTs and registers, respectively. The overhead of the software trap handler on top of an AES-128 program is 0.59%--0.71% in footprint and 1.01%--2.35% in performance, depending on the security policy. In contrast, traditional countermeasures that use redundant hardware or software against similar faults have at least double overhead.

Cardiovascular disease (CVD) patients with major depressive disorder (MDD) have worse outcomes than those without, but few are adequately treated for MDD. Our study examined depression care adequacy among patients with an initial diagnosis of myocardial infarction (MI) or stroke and assessed the

Due to advancement of technology and mainly Internet, the concept of marketing and selling of product has reached to a new level. Now-a-days, lots of companies rely on user reviews for launching their product. These reviews play an important role or companies to know how their product has been accepted in the market. But, today, thousands of reviews are generated for a product. Companies have to process each of these reviews to get user opinion as well as ideas, which is a very tedious and time-consuming. This paper discourses about extracting opinions from the user reviews is semi-automatic, in the sense that it requires some amount of expert assistance. Expert assistance is required for building the domain knowledge for the system, so as to make the system learn about the domain specific words]. The proposed system, using domain knowledge, identifies and extracts the opinions for a given product. These extracted opinions include the opinion words, their polarity in from of weights and for which feature these opinions was provided and system aggregates the extracted opinions them for better display.

487 Background: The humanistic burden of aRCC is not well understood. We describe HRQoL, functional status, treatment satisfaction, and work productivity reported by pts treated with ≥2 lines of treatment (LOT) for aRCC in 6 countries. Methods: Retrospective, observational medical chart review of adults with stage IIIB/IV aRCC who completed the EuroQoL-5D-3L (EQ-5D), Functional Assessment of Cancer Therapy – General (FACT-G)/FACT-Kidney Symptom Index (FKSI-19), Cancer Therapy Satisfaction Questionnaire (CTSQ), and Work Productivity and Activity Impairment (WPAI) questionnaires. FACT-G scores were examined with regression analysis. Results: All measures were impacted by aRCC (Table). Dimensions affected: EQ-5D, pain/discomfort; FACT-G and FKSI-19, functional/emotional; CTSQ, feelings about side effects; WPAI, activity impairment. EQ-5D, FACT-G, FKSI-19 scores were higher (by minimal important difference) in France and Canada vs. other countries. FACT-G scores differed by region, and were higher in Canada and France vs. the USA. Female sex and 2nd LOT were predictors of lower FACT-G score. Conclusions: This study showed a high humanistic burden on aRCC pts across countries. New treatments with reduced side effects and improved effectiveness can help yield improvements in HRQoL, treatment satisfaction, and work productivity. [Table: see text]