The Geometry of Most Probable Trajectories in Noise-Driven Dynamical Systems

This paper presents a heuristic derivation of a geometric minimum action method that can be used to determine most-probable transition paths in noise-driven dynamical systems. Particular attention is focused on systems that violate detailed balance, and the role of the stochastic vorticity tensor is emphasized. The general method is explored through a detailed study of a two-dimensional quadratic shear flow which exhibits bifurcating most-probable transition pathways.Comment: 8 pages, 7 figure

Fragmented health systems in COVID-19: rectifying the misalignment between global health security and universal health coverage

The COVID-19 pandemic has placed enormous strain on countries around the world, exposing long-standing gaps in public health and exacerbating chronic inequities. Although research and analyses have attempted to draw important lessons on how to strengthen pandemic preparedness and response, few have examined the effect that fragmented governance for health has had on effectively mitigating the crisis. By assessing the ability of health systems to manage COVID-19 from the perspective of two key approaches to global health policy—global health security and universal health coverage—important lessons can be drawn for how to align varied priorities and objectives in strengthening health systems. This Health Policy paper compares three types of health systems (ie, with stronger investments in global health security, stronger investments in universal health coverage, and integrated investments in global health security and universal health coverage) in their response to the ongoing COVID-19 pandemic and synthesises four essential recommendations (ie, integration, financing, resilience, and equity) to reimagine governance, policies, and investments for better health towards a more sustainable future

Determinants of Length of Stay After Vaginal Deliveries in the Friuli Venezia Giulia Region (NorthEastern Italy), 2005\u20132015

Although length of stay (LoS) after childbirth has been diminishing in several high-income countries in recent decades, the evidence on the impact of early discharge (ED) on healthy mothers and term newborns after vaginal deliveries (VD) is still inconclusive and little is known on the characteristics of those discharged early. We conducted a population-based study in Friuli Venezia Giulia (FVG) during 2005\u20132015, to investigate the mean LoS and the percentage of LoS longer than our proposed ED benchmarks following VD: 2 days after spontaneous vaginal deliveries (SVD) and 3 days post instrumental vaginal deliveries (IVD). We employed a multivariable logistic as well as a linear regression model, adjusting for a considerable number of factors pertaining to health-care setting and timeframe, maternal health factors, newborn clinical factors, obstetric history factors, socio-demographic background and present obstetric conditions. Results were expressed as odds ratios (OR) and regression coefcients (RC) with 95% confdence interval (95%CI). The adjusted mean LoS was calculated by level of pregnancy risk (high vs. low). Due to a very high number of multiple tests performed we employed the procedure proposed by Benjamini-Hochberg (BH) as a further selection criterion to calculate the BH p-value for the respective estimates. During 2005\u20132015, the average LoS in FVG was 2.9 and 3.3 days after SVD and IVD respectively, and the pooled regional proportion of LoS>ED was 64.4% for SVD and 32.0% for IVD. The variation of LoS across calendar years was marginal for both vaginal delivery modes (VDM). The adjusted mean LoS was higher in IVD than SVD, and although a decline of LoS>\u2009ED and mean LoS over time was observed for both VDM, there was little variation of the adjusted mean LoS by nationality of the woman and by level of pregnancy risk (high vs. low). By contrast, the adjusted fgures for hospitals with shortest (centres A and G) and longest (centre B) mean LoS were 2.3 and 3.4 days respectively, among \u201clow risk\u201d pregnancies. The corresponding fgures for \u201chigh risk\u201d pregnancies were 2.5 days for centre A/G and 3.6 days for centre B. Therefore, the shift from \u201clow\u201d to \u201chigh\u201d risk pregnancies in all three latter centres (A, B and G) increased the mean adjusted LoS just by 0.2 days. By contrast, the discrepancy between maternity centres with highest and lowest adjusted mean LoS post SVD (hospital B vs. A/G) was 1.1 days both among \u201clow risk\u201d (1.1 = 3.4\u20132.3 days) and \u201chigh risk\u201d (1.1 = 3.6\u20132.5) pregnanices. Similar patterns were obseved also for IVD. Our adjusted regression models confrmed that maternity centres were the main explanatory factor for LoS after childbirth in both VDM. Therefore, health and clinical factors were less infuential than practice patterns in determining LoS after VD. Hospitalization and discharge policies following childbirth in FVG should follow standardized guidelines, to be enforced at hospital level. Any prolonged LoS post VD (LoS>\u2009ED) should be reviewed and audited if need be. Primary care services within the catchment areas of the maternity centres of FVG should be improved to implement the follow up of puerperae undergoing ED after VD. At the beginning of the 20th century home births were the norm and hospital deliveries very rare. Women started to deliver in hospital during World War 2 (WW2), in facilities near the military areas where their respective partners were training. Tis trend continued in the decades following WW2, with standard length of stay afer childbirth (LoS) increasing up to 10 days. In the 70 ies some USA hospitals started to assess the health of mothers and newborn for eligibility to returnhome within 12\u201324 hours afer childbirth, with a midwife on call for domiciliary care up to 3 days for 2 weekspost discharge. In 1992 the American Academy of Pediatrics (AAP) and the American College of Obstetricians and Gynecologists (ACOG) formalized the most frequently shared defnition of early discharge (ED) afer childbirth worldwide as a LoS less than 48 h post spontaneous vaginal deliveries (SVD) and less than 96 h post cesarean section (CS). Tereafer the reduction of LoS expanded to other high-income countries, with increasing applications of ED. LoS afer childbirth remained however a controversial aspect of obstetric care, creating an open debate not only on its impact on the health of mothers and babies but also on health policies, state legislations and functioning of the respective health care systems. Nevertheless, ED of mothers and newborn has in fact increased dramatically in several high-income countries over the past 10\u201315 years. However, the evidence on the impact of ED on healthy mothers and term newborns ( 6537 weeks) afer a vaginal delivery (VD) is still inconclusive and little is known of the characteristics of those discharged early. Since LoS has become a critical indicator of efciency of health care delivery, understanding its associated factors could provide information helpful in the reduction of health care costs, improvement in the delivery of obstetric care, containment of untoward events associated with comorbidities and complications requiring readmission. For instance, in Canada (excluding Quebec) from 2003 to 2010, neonatal readmission rates were lowest for LoS of 1\u20132 days following VD and 2\u20134 days afer CS. Several factors are reportedly associated with LoS in the open literature, including readiness for discharge (clinical and perceived) of the mother8,17\u201319. However, information on the impact of medical/obstetrical conditions associated with pregnancies is scarce or totally lacking. Using a comprehensive database with information on a considerable number of factors, we previously reviewed the case mix of hospital performance by LoS post SVD as well as instrumental vaginal deliveries (IVD) during 2005\u20132015 in Friuli Venezia Giulia (FVG), a region of North-Eastern Italy. In this study we present the impact of the outstanding determinants on LoS following SVD and IVD, with the aim of inforing health care policy makers

Understanding Factors Leading to Primary Cesarean Section and Vaginal Birth After Cesarean Delivery in the Friuli-Venezia Giulia Region (North-Eastern Italy), 2005\u20132015

Although there is no evidence that elevated rates of cesarean sections (CS) translate into reduced maternal/child perinatal morbidity or mortality, CS have been increasingly overused almost everywhere, both in high and low-income countries. The primary cesarean section (PC S) has become a major driver of the overall CS (OCS) rate, since it carries intrinsic risk of repeat CS (RCS) in future pregnancies. In our study we examined patterns of PCS, pl compared with planned TO LAC anned PCS (PPCS), vaginal birth after 1 previous CS (VBAC-1) and associated factors in Friuli Venezia Giulia (FVG), a region of North-Eastern Italy, collecting data from its 11 maternity centres (coded from A to K) during 2005\u20132015. By fitting three multiple logistic regression models (one for each delivery mode), we calculated the adjusted rates of PCS and PPCS among women without history of CS, whilst the calculation of the VBAC rate was restricted to women with just one previous CS (VBAC-1). Results, expressed as odds ratio (OR) with 95% confidence interval (95%CI), were controlled for the effect of hospital, calendar year as well as several factors related to the clinical and obstetric conditions of the mothers and the newborn, the obstetric history and socio-demographic background. In FVG during 2005\u20132015 there were 24,467 OCS (rate of 24.2%), 19,565 PCS (19.6%), 7,736 PPCS (7.7%) and 2,303 VBAC-1 (28.4%). We found high variability of delivery mode (DM) at hospital level, especially for PCS and PPCS. Breech presentation was the strongest determinant for PCS as well as PPCS. Leaving aside placenta previa/abuptio placenta/ante-partum hemorrhage, further significant factors, more importantly associated with PCS than PPCS were non-reassuring fetal status and obstructed labour, followed by (in order of statistical significance): multiple birth; eclampsia/pre-eclampsia; maternal age 40\u201344 years; placental weight 600-99 g; oligohydramios; pre-delivery LoS 3\u20135 days; maternal age 35\u201339 years; placenta weight 1,000\u20131,500 g; birthweight < 2,000 g; maternal age 65 45 years; pre-delivery LoS 65 6 days; mother\u2019s age 30\u201334 years; low birthweight (2,000\u20132,500 g); polyhydramnions; cord prolaspe; 656 US scas performed during pregnancy and pre-term gestations (33\u201336 weeks). Significant factors for PPCS were (in order of statistical significance): breech presentation; placenta previa/abruptio placenta/ante-partum haemorrhage; multiple birth; pre-delivery LoS 65 3 days; placental weight 65 600 g; maternal age 40\u201344 years; 656 US scans performed in pregnancy; maternal age 65 45 and 35\u201339 years; oligohydramnios; eclampsia/pre-eclampsia; mother\u2019s age 30\u201334 years; birthweight <2,000 g; polyhydramnios and pre-term gestation (33\u201336 weeks). VBAC-1 were more likely with gestation 65 41 weeks, placental weight <500 g and especially labour analgesia. During 2005\u20132015 the overall rate of PCS in FVG (19.6%) was substantially lower than the corresponding figure reported in 2010 for the entire Italy (29%) and still slightly under the most recent national PCS rate for 2017 (22.2%). The VBAC-1 rate on women with history of one previous CS in FVG was 28.4% (25.3% considering VBAC on all women with at least 1 previous CS), roughly three times the Italian national rate of 9% reported for 2017. The discrepancy between the OCS rate at country level (38.1%) and FVG\u2019s (24.2%) is therefore mainly attributable to RCS. Although there was a marginal decrease of PCS and PPCS crudes rates over time in the whole region, accompained by a progressive enhancement of the crude VBAC rate, we found remarkable variability of DM across hospitals. To further contain the number of unnecessary PCS and promote VBAC where appropriate, standardized obstetric protocols should be introduced and enforced at hospital level. Decision-making on PCS should be carefully scrutinized, introducing a diagnostic second opinion for all PCS, particularly for term singleton pregancies with cephalic presentation and in case of obstructed labour as well as non-reassuring fetal status, grey areas potentially affected by subjective clinical assessment. This process of change could be facilitated with education of staff/ patients by opinion leaders and prenatal counseling for women and partners, although clinical audits, financial penalties and rewards to efficient maternity centres could also be considered

Impact of brief prewarming on anesthesia-related core-temperature drop, hemodynamics, microperfusion and postoperative ventilation in cytoreductive surgery of ovarian cancer: a randomized trial

Background: General (GA)- and epidural-anesthesia may cause a drop in body-core-temperature (BCT(drop)), and hypothermia, which may alter tissue oxygenation (StO(2)) and microperfusion after cytoreductive surgery for ovarian cancer. Cell metabolism of subcutaneous fat- or skeletal muscle cells, measured in microdialysis, may be affected. We hypothesized that forced-air prewarming during epidural catheter placement and induction of GA maintains normothermia and improves microperfusion. Methods: After ethics approval 47 women scheduled for cytoreductive surgery were prospectively enrolled. Women in the study group were treated with a prewarming of 43 °C during epidural catheter placement. BCT (Spot on®, 3 M) was measured before (T(1)), after induction of GA (T(2)) at 15 min (T(3)) after start of surgery, and until 2 h after ICU admission (T(ICU2h)). Primary endpoint was BCT(drop) between T(1) and T(2). Microperfusion-, hemodynamic- and clinical outcomes were defined as secondary outcomes. Statistical analysis used the Mann-Whitney-U- and non-parametric-longitudinal tests. Results: BCT(drop) was 0.35 °C with prewarming and 0.9 °C without prewarming (p < 0.005) and BCT remained higher over the observation period (ΔT(4) = 0.9 °C up to ΔT(7) = 0.95 °C, p < 0.001). No significant differences in hemodynamic parameters, transfusion, arterial lactate and dCO(2) were measured. In microdialysis the ethanol ratio was temporarily, but not significantly, reduced after prewarming. Lactate, glucose and glycerol after PW tended to be more constant over the entire period. Postoperatively, six women without prewarming, but none after prewarming were mechanical ventilated (p < 0.001). Conclusion: Prewarming at 43 °C reduces the BCT(drop) and maintains normothermia without impeding the perioperative routine patient flow. Microdialysis indicate better preserved parameters of microperfusion. Trial registration: ClinicalTrials.gov; ID: NCT02364219; Date of registration: 18-febr-2015

A cascaded laser acceleration scheme for the generation of spectrally controlled proton beams

We present a novel, cascaded acceleration scheme for the generation of spectrally controlled ion beams using a laser-based accelerator in a 'double-stage' setup. An MeV proton beam produced during a relativistic laser–plasma interaction on a thin foil target is spectrally shaped by a secondary laser–plasma interaction on a separate foil, reliably creating well-separated quasi-monoenergetic features in the energy spectrum. The observed modulations are fully explained by a one-dimensional (1D) model supported by numerical simulations. These findings demonstrate that laser acceleration can, in principle, be applied in an additive manner.Deutsche Forschungsgemeinschaft (DFG contract no. TR18)Deutsche Forschungsgemeinschaft (contract no. 03ZIK052)European Union (Laserlab Europe

Rumors of disease in the global village: outbreak verification.

Emerging infectious diseases and the growth of information technology have produced new demands and possibilities for disease surveillance and response. Increasing numbers of outbreak reports must be assessed rapidly so that control efforts can be initiated and unsubstantiated reports can be identified to protect countries from unnecessary economic damage. The World Health Organization has set up a process for timely outbreak verification to convert large amounts of data into accurate information for suitable action. We describe the context and processes of outbreak verification and information dissemination

Lessons From the West Africa Ebola Epidemic: A Systematic Review of Epidemiological and Social and Behavioral Science Research Priorities.

This systematic literature review compared the epidemiological (EPI) research and the qualitative social and behavioral science (SBS) research published during the West Africa Ebola virus disease (EVD) epidemic. Beginning with an initial capture of over 2000 articles, we extracted 236 EPI and 171 SBS studies to examine how disciplinary priorities affected research conducted during the EVD response, with implications for epidemic response effectiveness. Building on this research, we set forth a roadmap for the closer integration of EPI and SBS research in all aspects of epidemic preparedness and response that incorporates the lessons of the West Africa EVD outbreak. Key priorities include the following: (1) developing the capacity to systematically quantify qualitative sociocultural variables; (2) establishing interdisciplinary collaborations to improve "risk segmentation" practices; (3) creating and prepositioning qualitative indicators and composite sociocultural indexes for rapid deployment in outbreaks; (4) integrating novel systems with community resources; (5) developing new techniques for modeling social mobilization and community engagement; (6) prioritizing good data and complex analyses early in emergencies; and (7) learning from past experiences. Our findings support a program of action that situates data collection and analysis in real-time, recursive, integrated efforts to move community attitudes, behaviors, and responses into epidemiological research. We offer recommendations to improve coordinated, multidisciplinary approaches to health emergencies