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As the COVID-19 pandemic is an emerging healthcare concern, there has been swift vaccine development with minimal clinical trials questioning its protective efficacy outside of clinical trial conditions. The study aims to analyze the adverse events following immunization (AEFI) with COVID-19 vaccines among the domestic Indian population. It also aimed to evaluate the association between AEFI and demographic characteristics, comorbidities, and type of vaccine. This cross-sectional survey included participants ≥ 18 years of Indian origin for passive reporting of AEFI with COVID-19 vaccination using a questionnaire. The incidence of AEFI was calculated in percentage; the Chi-square test was used to determine associations between AEFI and independent variables. The incidence of reported AEFI was 76.4%. The most frequently reported AEFI was redness [74.38% (n = 328)], followed by pain [52.83% (n = 233)], swelling [52.83% (n = 233)], and fever [50.34% (n = 222)]. The majority of AEFIs were mild to moderate and resolved spontaneously. Females had significantly more AEFI with longer duration than males. The type of vaccine received had no significant effect on the number or duration of AEFI; 3.63% tested positive for COVID-19 after the first dose and 3.11% after the second dose of the vaccine, with no significant correlation between comorbidities and the presence of AEFI. More than three-fourths of the vaccines resulted in one or more forms of adverse events, but most events were self-limiting. Females were more prone to develop AEFI. Knowledge about what to expect after vaccination will help educate the public, allay misconceptions and reduce vaccine hesitancy.

Introduction: The Coronavirus Disease-2019 (COVID-19) pandemic, being an emerging world health issue, has led to the swift development of vaccines. Various lifestyles, health conditions, and behaviours affect the body’s reaction to immunisation. Aim: To evaluate the association of Adverse Effects Following Immunisation (AEFI) with different lifestyles and health patterns. Materials and Methods: A cross-sectional online epidemiological analytical survey in study population across India was carried out in Mumbai, India, from 1st June 2021 to 21st June 2021, using Google form survey. It included a sample of 586 responders. A questionnaire consisting of 26 questions regarding lifestyle habits and AEFIs following COVID-19 vaccine administration was distributed. Questions about lifestyle were obtained using Simple Lifestyle Indicator Questionnaire (SLIQ) which includes questions regarding diet, activity/exercise, alcohol consumption, smoking, and stress. Association between the SLIQ score and number and duration of AEFI was determined. Measurement data was presented as means with standard deviation. The SLIQ scores and age were compared between the different groups (AEFI present/absent, no. of AEFI, duration of AEFI) using one-way analysis of variance (ANOVA). Results: The incidence of reported AEFI was n=577 (76.4%). The most frequently reported AEFI was redness, n=328 (74.38%) followed by pain, n=233 (52.83%), swelling n=233 (52.83%) and fever n=222 (50.34%). It was observed that those with a higher SLIQ score, had an increased number and duration of AEFI (p=0.001, ANOVA). With increase in age, number and duration of AEFI experienced decreased (p

Both anti-angiogenesis and immunotherapy are well-established therapeutic options in solid tumors. Here, we review the rationale as well as clinical evidence of combining these two approaches. There is strong rationale and substantial preclinical and clinical evidence that anti-angiogenesis plays a pivotal role in overcoming immunotherapy resistance. The combination of an anti-angiogenic agent and a checkpoint inhibitor offers a more robust treatment option in many clinical trials in a wide variety of solid tumor types. Combination of anti-angiogenesis and immunotherapy has emerged as a standard of care in some tumor types and the indication is expected to expand to more tumor types in the years to come.

SUMMARYWe study the rise of the so-called ‘gig economy’ through the lens of Uber and its drivers in the United Kingdom. Using administrative data from Uber and a new representative survey of London drivers, we explore their backgrounds, earnings, and subjective well-being. We find that the vast majority of Uber drivers are male immigrants, primarily drawn from the bottom half of the London income distribution. Most transitioned out of permanent part- or full-time jobs and about half of drivers’ report that their incomes increased after partnering with Uber. After covering vehicle operation costs and Uber’s service fee, we estimate that the median London driver earns about £11 per hour spent logged into the app. But while Uber drivers remain at the lower end of the London income distribution, they report higher levels of life satisfaction than other workers. Consistent with a trade-off between evaluative and emotional well-being observed among the self-employed, they also report higher anxiety levels. We hypothesize that the higher life satisfaction among Uber drivers partly reflects their preferences for flexibility and the autonomy that the platform offers. We provide suggestive evidence showing that drivers who emphasize flexibility as an important motivation to join Uber also report higher levels of subjective well-being. However, a minority of drivers who report that they would prefer work as an employee report lower levels of life satisfaction and higher levels of anxiety. Overall, our findings highlight the importance of non-monetary factors in shaping the welfare of workers in the gig economy.

In June 2019, a meeting was held in Paris in which experts from different countries (Israel, Spain, Belgium, Italy, USA, and France) met to discuss a selection of topics in integrative oncology (IO). The objectives were to draw on the delegates’ experience and expertise to begin an international collaboration, sharing details of differing existing models and discussing future perspectives to help define and guide practice in IO and define unmet needs. This report presents a summary of the meeting’s main presentations, and also reports on the experts’ responses to a questionnaire examining different aspects of IO service delivery, infrastructure, and utilization.

Background: Fetal autopsy has been an indispensable tool in evaluating the cause of death. The most common cause for fetal deaths is associated with respiratory disorders accounting for around 60%. This study was undertaken to evaluate the gross and microscopic features of lungs in fetal autopsies and estimate the incidence of deaths attributable to pulmonary causes. Materials and Methods: All fetuses received for autopsy at our institute were included in the study with prior consent. Gross and microscopic findings along with relevant clinical data were recorded. Results: A total of 426 autopsies were conducted from January 2011 to August 2016. Of those, 184 had abnormal pulmonary findings constituting 43.19%. Aspiration pneumonia was the most common finding with 67 cases (36.4%), followed by atelectasis 54 cases (29.3%), congenital cystic adenomatoid malformation in 13 cases (7.1%), lung hypoplasia 12 cases (6.5%), pulmonary hemorrhage 21 (11.4%), 15 cases (8.15%) of hyaline membrane disease, one case (0.5%) of heterotaxy, and one case of extralobar pulmonary sequestration (0.5%). Congenital malformations of lungs were seen in 27 (14.67%) cases and 38 cases (20.65%) had other associated anomalies. Conclusion: Pulmonary pathology is the most common finding in fetal deaths with aspiration pneumonitis being the most common avoidable cause. Accurate fetal autopsy along with clinical data are important in evaluating fetal deaths and can help in reduction of unexplained stillbirths.

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) degrades tryptophan to kynurenine, suppressing T cell effector activity and increasing T regulatory cell activity. IDO1 expression is induced in some cancer cells and has been associated with suppression of effector T cell responses toward tumors. In nonclinical studies, IDO1 inhibition combined with other clinically established immune modulating agents (eg, anti-CTLA-4 or anti-PD-1 antibodies) showed a significant improvement in tumor growth suppression. KHK2455 is a long acting and selective IDO1 inhibitor under development as a new approach to enhance anti-tumor immunity. KHK2455 is being combined with different anti-cancer therapies to explore its ability to enhance anti-tumor immunity and overcome tumor immune evasion. Avelumab is a PD-L1 checkpoint inhibitor approved for treatment of urothelial carcinoma. This study represents an opportunity to assess the complementary action of KHK2455 IDO1 inhibition and avelumab checkpoint inhibition in the treatment of urothelial carcinoma. Methods: Study 2455-002 is a two-part, multicenter, open-label Phase 1 study of KHK2455 in combination with avelumab in adult subjects with locally advanced or metastatic urothelial carcinoma (including bladder, urethra, ureters, and renal pelvis), who are checkpoint inhibitor naїve and previously treated with platinum-based therapy. Part 1 (dose-escalation) has a 3+3 design to evaluate safety and tolerability and identify the maximum tolerated dose (MTD). Dose de-escalation based on dose limiting toxicities is permitted. Part 2 (cohort expansion) further explores the safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity for the combination regimen at the MTD or highest tested dose. All subjects will receive oral KHK2455 at their assigned dose and avelumab IV. The primary study endpoints are safety and tolerability, and the secondary endpoints are efficacy (based on RECIST v1.1 criteria), pharmacokinetics, and immunogenicity. Exploratory endpoints include examination of pre and post treatment biopsies for intratumoral suppression of IDO1 activity to correlate peripheral and intratumoral suppression, along with pre and post treatment serum markers including, but not limited to, immune mediators and related cytokines. Descriptive statistics (n, mean, standard deviation, median, minimum, and maximum) for continuous variables and frequency distributions and percentages for discrete variables will be utilized. Approximately 44 subjects are planned for enrollment (12 subjects in Part 1 and 32 subjects in Part 2). Clinical trial information: NCT03915405 (sponsor: Kyowa Kirin Pharmaceutical Development, Inc.) Citation Format: Pratibha Desai, Santosh Rao, Yuta Ikawa, Barbara Kapelan, Sergey Efuni, Robert Latek, Takashi Sato, Denis Healy, Yousef Zakharia. An open-label, phase 1 study of IDO inhibitor KHK2455 in combination with avelumab in adult subjects with locally advanced or metastatic urothelial carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT238.

The value of travel time savings is often the largest benefit from transportation projects and has been studied extensively. Recently, additional attention has been paid to the fact that travelers also benefit from reliable travel times. The value of reliability (VOR) has usually been estimated through stated-preference data or survey-based revealed-preference data. In this research, empirical data were used to estimate VOR. One concern about estimating VOR from empirical data was the lack of a definitive measurement for reliability. Should it be the standard deviation (SD) of travel time, the 95th percentile, or another measure? Data from Katy Freeway in Texas, where travelers chose between tolled but generally more-reliable lanes and free but generally less-reliable lanes, were used in an attempt to find the best measurement of reliability that could lead to the best explanation of travelers’ lane choice. Multinomial logit models were used to estimate travelers’ lane choice on the basis of trip attributes, including travel time, many measures of travel time reliability, and tolls. Models including only travel time and tolls yielded reasonable results and values of time ($2.78/h, $9.09/h, and $10.52/h for off-peak, shoulder, and peak periods, respectively). However, adding reliability to the models caused many of them to have counterintuitive results, and concluding which measure was the best was impossible. In addition, the results of this research suggested that reliability might not be an influential factor in the lane choice decision on managed lanes, at least when travelers had reasonable knowledge of their potential travel time.

The implementation of the I-85 express lanes in Atlanta, Georgia, was the first conversion of a high-occupancy vehicle lane to a high-occupancy toll lane that simultaneously increased the occupancy requirement (from two or more persons to three or more persons) and implemented tolls without the creation of additional lanes. This paper presents the findings of an analysis of tolling data collected during the first year of operation as part of the National Evaluation of Urban Partnership Agreement and Congestion Reduction Demonstration programs sponsored by the U.S. Department of Transportation. This analysis found the median willingness to pay for express lane travel time savings to be $19.45 per hour across all time periods and $33.17 per hour for southbound a.m. peak travel. There was little difference in the willingness to pay between frequent and infrequent travelers of the express lanes. This analysis was based on actual tolls paid by travelers and therefore represents the minimum these travelers were willing to pay.

The aim was to present a rare case of recurrent craniopharyngioma remote from the primary site of origin. A young girl was operated for sellar region craniopharyngioma. For a small residual tumor, she underwent radiotherapy. Follow-up imaging did not reveal any residual tumor or recurrence. Surveillance magnetic resonance imaging after 5 years revealed a recurrence in the right Sylvian fissure. This tumor was totally excised. Recurrence of craniopharyngioma is well-known, but recurrence at a site remote from the original site after radiotherapy is extremely rare. One such case is being presented.

The purpose of this study was to evaluate in vivo the biocompatibility of BioMedFlex (BMF), a new resilient, hard-carbon, thin-film coating, as a blood journal bearing material in Cleveland Heart's (Charlotte, NC, USA) continuous-flow right and left ventricular assist devices (RVADs and LVADs). BMF was applied to RVAD rotating assemblies or both rotating and stator assemblies in three chronic bovine studies. In one case, an LVAD with a BMF-coated stator was also implanted. Cases 1 and 3 were electively terminated at 18 and 29 days, respectively, with average measured pump flows of 4.9 L/min (RVAD) in Case 1 and 5.7 L/min (RVAD) plus 5.7 L/min (LVAD) in Case 3. Case 2 was terminated prematurely after 9 days because of sepsis. The sepsis, combined with running the pump at minimum speed (2000 rpm), presented a worst-case biocompatibility challenge. Postexplant evaluation of the blood-contacting journal bearing surfaces showed no biologic deposition in any of the four pumps. Thrombus inside the RVAD inlet cannula in Case 3 is believed to be the origin of a nonadherent thrombus wrapped around one of the primary impeller blades. In conclusion, we demonstrated that BMF coatings can provide good biocompatibility in the journal bearing for ventricular assist devices.

BACKGROUND The aim of this study was to evaluate the feasibility and efficacy of the injection of a nonabsorbable substance into the base of the left ventricle (LV) to treat functional mitral regurgitation (MR). METHODS Tyramine-based hyaluronan hydrogel was injected into the base of the LV of the beating heart in a canine model of rapid ventricular pacing-induced functional MR (n = 4). The severity of MR was evaluated by epicardial echocardiography before and after hydrogel injection. RESULTS The injection improved MR grade from 3.4 +/- 0.8 to 1.3 +/- 0.5 (P = .006) without inducing hemodynamic instability or any evidence of myocardial ischemia. We noted significant decreases in the septal-lateral dimension at the mitral annulus (3.4 +/- 0.4 cm to 2.9 +/- 0.3 cm; P = .039) and MR volume (20.6 +/- 7.3 mm3 to 5.2 +/- 2.2 mm3; P = .044). CONCLUSIONS A novel treatment consisting of hydrogel injection into the base of the LV between the 2 papillary muscles was found to be feasible and effective for reducing functional MR in a canine model.

Objective The purpose of this study was to evaluate the implantability of a novel epicardial mitral annuloplasty device and its ability to reduce the septal-lateral (S-L) dimension of the mitral annulus. Methods The devices were implanted on the beating heart in 2 healthy dogs (the 24-mm long device in dog A and the 27-mm and 24-mm standard devices in dog B) by sliding the anterior arm onto the floor of the transverse sinus and positioning the posterior arm just apical to the atrioventricular groove on the left ventricular posterolateral wall. The devices were secured with titanium helical tacks driven through the device into the ventricular wall. Two-dimensional epicardial echocardiograms were performed before and after device implantation to evaluate the degree of mitral regurgitation (MR) and the S-L dimension. Results Device implantation was uneventful, taking only ~30 seconds to deploy. MR (1 +) in both dogs at baseline was reduced to zero after implant. The reductions in S-L dimension in systole for the 24-mm device were 7.5% in dog A and 30.5% in dog B. For the 27-mm device in dog B, S-L reduction in systole was 29.9%. The leaflet coaptation length was increased in both cases. Conclusions The new device was effective in reducing S-L dimension and 1 + MR without requiring the use of cardiopulmonary bypass. We are currently evaluating this device for the treatment of MR in a rapid-pacing canine heart failure model.

This is a case study of a forensic geotechnical investigation to assess the possible causes which prevented the satisfactory construction of large-diameter bored piles using the bailer technique. The investigation involved first identifying the possible causes, carrying out field and laboratory tests where necessary to assess the same, analysis of the test results, and finally arriving at the conclusion.

A method of controlling size of a congestion window, includes, at a transmitting device, transmitting a plurality of data packets over a communication channel from the transmitting device to a receiver, determining a queuing delay and a loss rate of the transmission, comparing the queuing delay to a threshold queuing delay, comparing the loss rate to a threshold loss rate, and in response to a determination that the queuing delay is greater than the threshold queuing delay and the loss rate is greater than the threshold loss rate, resetting the size of the congestion window in accordance with a function of the current size of the congestion window, the queuing delay, and the loss rate, wherein at equilibrium the function generates a value inversely proportional to a weighted sum of an excess queuing delay and an excess loss rate.

Emerging evidence suggests that short sleep is associated with an increased risk of cancer; however, little has been done to study the role of sleep on tumor characteristics. In this study, we evaluated the relationship between sleep duration and tumor phenotype in 972 breast cancer patients. Sleep duration was inversely associated with tumor grade (univariateP=0.032), particularly in postmenopausal women (univariateP=0.018). This association did not reach statistical significance after adjustments for age, race, body mass index, hormone replacement therapy use, alcohol consumption, smoking, and physical activity in the entire study sample (P=0.052), but it remained statistically significant (P=0.049) among post-menopausal patients. We did not observe a statistically significant association between sleep duration and stage at diagnosis, ER, or HER2 receptor status. These results present a modest association between short duration of sleep and higher grade breast cancer in post-menopausal women. Further work needs to be done to validate these findings.

There are no FDA-approved pharmacotherapies for cannabis dependence. Cannabis is the most widely used illicit drug in the world, and patients seeking treatment for primary cannabis dependence represent 25% of all substance use admissions. We conducted a phase IIa proof-of-concept pilot study to examine the safety and efficacy of a calcium channel/GABA modulating drug, gabapentin, for the treatment of cannabis dependence. A 12-week, randomized, double-blind, placebo-controlled clinical trial was conducted in 50 unpaid treatment-seeking male and female outpatients, aged 18–65 years, diagnosed with current cannabis dependence. Subjects received either gabapentin (1200 mg/day) or matched placebo. Manual-guided, abstinence-oriented individual counseling was provided weekly to all participants. Cannabis use was measured by weekly urine toxicology and by self-report using the Timeline Followback Interview. Cannabis withdrawal symptoms were assessed using the Marijuana Withdrawal Checklist. Executive function was measured using subtests from the Delis–Kaplan Executive Function System. Relative to placebo, gabapentin significantly reduced cannabis use as measured both by urine toxicology (p=0.001) and by the Timeline Followback Interview (p=0.004), and significantly decreased withdrawal symptoms as measured by the Marijuana Withdrawal Checklist (p

Right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation is associated with morbidity and mortality. Our purpose is to validate the right ventricular failure risk score (RVFRS) proposed by University of Michigan in a large cohort of patients supported with an LVAD

The purpose of the current study was to demonstrate that a proprietary surfactant polymer coating does not adversely affect the hemodynamic performance of cardiopulmonary bypass (CPB) or gas exchange in oxygenators. The new coating was applied to a CPB circuit including cannulae, reservoir, oxygenator, and blood pump implanted into 12 pigs, divided into groups with either coated or noncoated pumps. CPB flow was maintained at a fixed level of approximately 2.4 L/min for 6 hrs with full heparinization. Hemodynamic data and pump performance were recorded every hour, and blood samples were taken every 2 hrs. After sacrifice, the CPB circuit and major organs were macroscopically examined. There was no significant difference in the oxygen transfer rate between the two groups. The coating did not adversely affect oxygenator inlet or outlet pressures. There was no significant difference between the two groups in microthrombi seen in the oxygenators. No thromboemboli were noted in the major organs on gross or histologic examination. In conclusion, this new surfactant polymer coating did not decrease gas exchange performance and its biocompatibility evaluations revealed no differences between coated and noncoated groups under aggressive heparin use.

The purpose of this study was to evaluate in vivo the biocompatibility of BioMedFlex (BMF), a new resilient, hard-carbon, thin-film coating, as a blood journal bearing material in Cleveland Heart's (Charlotte, NC, USA) continuous-flow right and left ventricular assist devices (RVADs and LVADs). BMF was applied to RVAD rotating assemblies or both rotating and stator assemblies in three chronic bovine studies. In one case, an LVAD with a BMF-coated stator was also implanted. Cases 1 and 3 were electively terminated at 18 and 29 days, respectively, with average measured pump flows of 4.9 L/min (RVAD) in Case 1 and 5.7 L/min (RVAD) plus 5.7 L/min (LVAD) in Case 3. Case 2 was terminated prematurely after 9 days because of sepsis. The sepsis, combined with running the pump at minimum speed (2000 rpm), presented a worst-case biocompatibility challenge. Postexplant evaluation of the blood-contacting journal bearing surfaces showed no biologic deposition in any of the four pumps. Thrombus inside the RVAD inlet cannula in Case 3 is believed to be the origin of a nonadherent thrombus wrapped around one of the primary impeller blades. In conclusion, we demonstrated that BMF coatings can provide good biocompatibility in the journal bearing for ventricular assist devices.

The clinical use of left ventricular assist devices (LVADs) is becoming more widely accepted, due in large part to the introduction of continuous-flow blood pumps.1-6 These newer devices show significant improvements in size, simplicity, reliability, durability, and clinical results. However, 20-50% of patients undergoing LVAD implantation also have significant right ventricular failure, which limits the utility of implantable LVAD therapy.7-11 Existing total artificial hearts (TAHs) are either a temporary pneumatic system (CardioWest™, SynCardia, Tucson, AZ) with an externalized pneumatic driver or a permanent pulsatile implantable system (AbioCor™, Abiomed®, Danvers, MA). To date, they have demonstrated significant limitations in initial clinical trials because of their large size, limited durability, and incidence of thrombus formation and embolization.12 The inherent design characteristics of these pulsatile systems prevent significant reductions in size. The feasibility of native heart replacement with two separate continuous-flow pumps has recently been demonstrated at the Texas Heart Institute (Houston, TX)13 and Tohoku University (Sendai, Japan).14 These systems require duplication of pump components, increasing the potential for component failure and necessitating the development of complex algorithms to appropriately coordinate the outputs of the two pumps. We are developing a continuous-flow TAH (CFTAH) that is extremely innovative, exploring radical new concepts in TAH design. The proposed concept involves the use of a valveless, sensorless, continuous-flow pump and automatic control system. This double-pump concept comprises a single, continuously rotating, brushless DC motor and a pump assembly with a centrifugal pump on both ends. Pump speed will be modulated to create pulsatile flow and pressure. This report details the CFTAH design concept and our initial in vitro data in a mock circulatory loop.

Results: A total of 199 (47.3%) had RV failure following LVAD implantation. The area under the curve (AUC) for the RVFRS was 0.675 (0.623, 0.726). Post-operative RVF was present in 26 (49%) of patients with a continuous low pump and 173 (47%) in patients supported with a pulsatile device (p=0.9). Conclusions: The RVFRS may be used to estimate the risk of RVF following LVAD implantation. There was no difference in post-operative RVF in patients supported with a continuous low vs. pulsatile low LVAD. These indings may have important implications on patient selection regarding mechanical circulatory support for end-stage heart failure patients. RVFRS N (%) RVF, N(%) No RVF, N(%) OR(95%CI) vs. ≤ 3.0 OR(95%CI) vs. 4.0-5.0 Sensitivity (%) Speciicity (%) ≤3.0 248(59) 91(37) 157(63) 54 71