To mitigate air traffic demand-capacity imbalances, large European airports implement strategic flight schedules, where flights are assigned arrival/departure slots several months prior to execution. ...We propose a generic assessment of such strategic schedules using predictions about arrival/departure flight delays and cancellations. We demonstrate our approach for strategic flight schedules in the period 2013–2018 at London Heathrow Airport. Together with the development of dedicated strategic flight schedule optimization models, our proposed approach supports an integrated strategic flight schedule assessment, where schedules are evaluated with respect to flight delays and cancellations.
With the unprecedented morbidity and mortality associated with the COVID-19 pandemic, a vaccine against COVID-19 is urgently needed. We investigated CoronaVac (Sinovac Life Sciences, Beijing, China), ...an inactivated vaccine candidate against COVID-19, containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for its safety, tolerability and immunogenicity.
In this randomised, double-blind, placebo-controlled, phase 1/2 clinical trial, healthy adults aged 18–59 years were recruited from the community in Suining County of Jiangsu province, China. Adults with SARS-CoV-2 exposure or infection history, with axillary temperature above 37·0°C, or an allergic reaction to any vaccine component were excluded. The experimental vaccine for the phase 1 trial was manufactured using a cell factory process (CellSTACK Cell Culture Chamber 10, Corning, Wujiang, China), whereas those for the phase 2 trial were produced through a bioreactor process (ReadyToProcess WAVE 25, GE, Umea, Sweden). The phase 1 trial was done in a dose-escalating manner. At screening, participants were initially separated (1:1), with no specific randomisation, into two vaccination schedule cohorts, the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and within each cohort the first 36 participants were assigned to block 1 (low dose CoronaVac 3 μg per 0·5 mL of aluminium hydroxide diluent per dose) then another 36 were assigned to block 2 (high-dose Coronavc 6 μg per 0·5 mL of aluminium hydroxide diluent per dse). Within each block, participants were randomly assigned (2:1), using block randomisation with a block size of six, to either two doses of CoronaVac or two doses of placebo. In the phase 2 trial, at screening, participants were initially separated (1:1), with no specific randomisation, into the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and participants were randomly assigned (2:2:1), using block randomisation with a block size of five, to receive two doses of either low-dose CoronaVac, high-dose CoronaVac, or placebo. Participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after injection in all participants who were given at least one dose of study drug (safety population). The primary immunogenic outcome was seroconversion rates of neutralising antibodies to live SARS-CoV-2 at day 14 after the last dose in the days 0 and 14 cohort, and at day 28 after the last dose in the days 0 and 28 cohort in participants who completed their allocated two-dose vaccination schedule (per-protocol population). This trial is registered with ClinicalTrials.gov, NCT04352608, and is closed to accrual.
Between April 16 and April 25, 2020, 144 participants were enrolled in the phase 1 trial, and between May 3 and May 5, 2020, 600 participants were enrolled in the phase 2 trial. 743 participants received at least one dose of investigational product (n=143 for phase 1 and n=600 for phase 2; safety population). In the phase 1 trial, the incidence of adverse reactions for the days 0 and 14 cohort was seven (29%) of 24 participants in the 3 ug group, nine (38%) of 24 in the 6 μg group, and two (8%) of 24 in the placebo group, and for the days 0 and 28 cohort was three (13%) of 24 in the 3 μg group, four (17%) of 24 in the 6 μg group, and three (13%) of 23 in the placebo group. The seroconversion of neutralising antibodies on day 14 after the days 0 and 14 vaccination schedule was seen in 11 (46%) of 24 participants in the 3 μg group, 12 (50%) of 24 in the 6 μg group, and none (0%) of 24 in the placebo group; whereas at day 28 after the days 0 and 28 vaccination schedule, seroconversion was seen in 20 (83%) of 24 in the 3 μg group, 19 (79%) of 24 in the 6 μg group, and one (4%) of 24 in the placebo group. In the phase 2 trial, the incidence of adverse reactions for the days 0 and 14 cohort was 40 (33%) of 120 participants in the 3 μg group, 42 (35%) of 120 in the 6 μg group, and 13 (22%) of 60 in the placebo group, and for the days 0 and 28 cohort was 23 (19%) of 120 in the 3 μg group, 23 (19%) of 120 in the 6 μg group, and 11 (18%) of 60 for the placebo group. Seroconversion of neutralising antibodies was seen for 109 (92%) of 118 participants in the 3 μg group, 117 (98%) of 119 in the 6 μg group, and two (3%) of 60 in the placebo group at day 14 after the days 0 and 14 schedule; whereas at day 28 after the days 0 and 28 schedule, seroconversion was seen in 114 (97%) of 117 in the 3 μg group, 118 (100%) of 118 in the 6 μg group, and none (0%) of 59 in the placebo group.
Taking safety, immunogenicity, and production capacity into account, the 3 μg dose of CoronaVac is the suggested dose for efficacy assessment in future phase 3 trials.
Chinese National Key Research and Development Program and Beijing Science and Technology Program.
Abstract
STUDY QUESTION
How are rotating night shift schedules associated with age at menopause among a large, national cohort of shift working nurses?
SUMMARY ANSWER
Our findings suggest that ...working rotating night shifts with sufficient frequency may modestly accelerate reproductive senescence among women who may already be predisposed to earlier menopause.
WHAT IS KNOWN ALREADY
Younger age at menopause has been associated with increased risk of adverse health outcomes, particularly those linked to reproduction. Night work has been associated with reproductive dysfunction, including disruption of menstrual cycle patterns.
STUDY DESIGN, SIZE, DURATION
This cohort study was conducted among 80 840 women of the Nurses’ Health Study 2 (NHS2), with prospective follow-up from 1991 through 2013. Loss-to-follow-up of the NHS2 is estimated to be <10%.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We assessed the association between cumulative and current rotating night shift work and age at natural menopause over 22 years of follow-up (1991–2013). Cox proportional hazards models were used to estimate hazard ratios (HR) for menopause, adjusted for age, smoking status, body mass index, physical activity, alcohol consumption, reproductive factors and exogenous hormone use.
MAIN RESULTS AND THE ROLE OF CHANCE
Over follow-up, 27 456 women (34%) reached natural menopause. Women who worked 20 or more months of rotating night shifts in the prior 2-year had an increased risk of earlier menopause (multivariable-adjusted (MV)-HR = 1.09, 95% CI: 1.02–1.16) compared to women without rotating night shift work. This risk was stronger among women undergoing menopause or otherwise censored under age 45 years (MV-HR = 1.25, 95% CI: 1.08–1.46), than it was for those continuing in the study when >45 years old (MV-HR = 1.05, 95% CI: 0.99–1.13). Working 10 or more years of cumulative rotating night work was also associated with higher risk of menopause among women reaching menopause under age 45 (MV-HR10–19 years = 1.22, 95% CI: 1.03–1.44; MV-HR≥20 years = 1.73, 95% CI: 0.90–3.35), though not over the age of 45 years (MV-HR10–19 years = 1.04, 95% CI: 0.99–1.10; MV-HR≥20 years = 1.01, 95% CI: 0.89–1.15).
LIMITATIONS, REASONS FOR CAUTION
The degree to which observed effects of rotating night shifts on age at natural menopause are due to circadian disruption, rather than fatigue and stress associated with working more demanding schedules, is uncertain due to potential residual confounding by these factors.
WIDER IMPLICATIONS OF THE FINDINGS
This is the first study to assess the effects of night work on menopausal timing among a larger national cohort of shift working women. Women already prone to earlier menopause may further truncate their reproductive lifetime by working schedules comprising day as well as night shifts.
STUDY FUNDING/COMPETING INTEREST(s)
This study was supported by Center for Disease Control and Prevention/The National Institute for Occupational Safety and Health Grant 5R01OH009803 (PI: Schernhammer E), as well as UM1 CA176726 from the National Institute of Health. The funding sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the article; and decision to submit the article for publication. The authors have no conflicts of interest.
Functional communication training is a well‐established treatment for socially reinforced destructive behavior that typically includes differential reinforcement of the functional communication ...response (FCR) in combination with extinction of destructive behavior. However, when the schedule of reinforcement for the FCR is thinned, destructive behavior may resurge (e.g., Greer, Fisher, Saini, Owen, & Jones, 2016). Currently, data are unavailable on the prevalence and characteristics of resurgence during reinforcement schedule thinning. In this study, we evaluated the prevalence of resurgence during reinforcement schedule thinning on a per‐case and per‐schedule‐step basis and also evaluated the magnitude of resurgence in relation to the functions of destructive behavior. We observed resurgence in 19 of the 25 (76%) applications of reinforcement schedule thinning. In some cases, the magnitude of resurgence exceeded the mean levels of destructive behavior observed in baseline. We discuss these results relative to prior translational and applied research on resurgence.
Functional communication training (FCT) is used to reduce rates of problem behavior by teaching communicative responses that access functionally equivalent reinforcers. During FCT, the communicative ...response is typically placed on a dense schedule of reinforcement that is unlikely to be maintained in the natural environment. Experiment 1 evaluated the effects of two schedule-thinning procedures (chained schedules and multiple schedules) on problem behavior maintained by escape from demands for three participants following FCT. The chained and multiple-schedule procedures were effective in reducing rates of problem behavior. Compliance increased under both schedules, but the chained schedule resulted in higher levels of compliance with two participants. In Experiment 2, participants’ preference for the chained or multiple-schedule procedure was evaluated using a modified concurrent-chain procedure. One participant preferred the chained schedule. One participant preferred the multiple schedule. One participant did not appear to discriminate between conditions.
•The use of multiple childcare arrangements is higher when mothers have an irregular work schedule.•The use of center-based childcare is lower when mothers work a shift schedule and an irregular ...schedule.•Families’ financial resources are related to the use of center-based childcare.
Mothers with a nonstandard work schedule may be more likely to use multiple childcare arrangements to accommodate their childcare needs and find it difficult to use center-based care that typically operates during daytime hours. Using the framework that working mothers’ workplace demands influence their childcare needs, while families’ relational and financial resources enable them to satisfy the needs, this study examined the association between mothers’ nonstandard work schedules and their use of multiple and center-based childcare. Using a sample of 2566 young children of working mothers from the Survey of Income and Program Participation of 2008, we found that the odds of multiple childcare arrangements were 36% higher when mothers worked an irregular schedule. The odds that one of the arrangements was a childcare center were 54% and 30% lower when mothers had a shift schedule and an irregular schedule. Families’ relational resource, the presence of non-mother adults in the family, was associated with the use of both multiple and center-based care arrangements, but financial resources were related only to the use of center-based care. Potential policy efforts are discussed to help low-wage working mothers better achieve a work-family balance.
Cyclophosphamide and ifosfamide are major alkylating agents but their therapeutics uses are limiting by the toxicity due to several toxicities. Indeed conventional chemotherapies are generally used ...with the maximum tolerated dose. In contrast, metronomic schedule aims to get a minimum dose for efficacy with a good safety. Depending on the dose, their mechanisms of action are different and offer a dual activity: at high dose, cyclophosphamide is mainly used in graft conditioning for its immunosuppressive properties, while at metronomic dose it is used as an immunoactive agent. Currently, at metronomic dose, cyclophosphamide is studied in clinic against various types of cancer, alone or in combination with others anticancer drugs (anti-angiogenic, immune-modulating agents, immune checkpoints blockers, vaccines, radiotherapy, others conventional anticancer agents), as a nth-line or first-line treatment. More than three quarters of clinical studies show promising results, mostly in breast, ovarian and prostate cancers. Taking advantage of the immune system, use dual antitumor action's chemotherapy is clearly a therapeutic strategy that deserves to be confirmed in order to improve the efficacy/toxicity balance of anticancer treatments, and to use CPM or analogues as a standard of care.
Variable work hours are an understudied source of work-to-family conflict (WFC). We examine the relationships between the magnitude and direction of work hour variability and WFC and whether work ...hour control and schedule predictability moderate these relationships. We estimate a series of linear regressions using the 2016 US General Social Survey, examining women and men workers separately and together. Findings indicate that as the magnitude of work hour variability increases, so does WFC, controlling for the usual number of hours worked. Work hour control helps to protect workers, especially women, from WFC when work hour variability is high and hours surge. Although schedule predictability tempers the relationship between work hour variability and WFC, its potency diminishes as variability increases. Our study emphasizes the potential benefit to workers and families of government policies and employer practices that promote work hour stability, schedule predictability, and equity in employee work hour control.
Soiling on solar modules stands as a primary source of energy yield loss, causing reflection of radiation. This paper presents a novel cleaning scheduling model for the maintenance strategy of ...photovoltaic plants, focused on adequately representing the soiling and cleaning processes. We employ a novel methodology based on cleaning sectors to make the model scalable in real-world applications. Computational experiments in a case study of three operating solar power plants in Chile, on three different scales of energy generation, show that the proposed methodology can achieve better results than traditional maintenance models in the literature, increasing revenue an average of 0.8% with respect to an optimized baseline. Additional experiments also show that the proposed model allows for a more efficient use of cleaning resources and makes possible the coordination of multiple large scale power plants, where conventional strategies result on infeasible policies.
•A novel derivation of the cleaning dynamics equations in photovoltaic power plants.•A linearization of cleaning constraints is presented.•The main source of cost reduction in large scale cleaning policies is co-optimization.•The proposed optimization framework allows complex and personalized cleaning policies.•Computational experiments show better performance in three different scales.
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