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

Effects of Extended Grape Ripening With or Without Must and Wine Alcohol Manipulations on Cabernet Sauvignon Wine Sensory Characteristics

This study attempts to clarify the consequences for wine flavour that result from harvesting fruit atdifferent maturities. The grapes were harvested from a single vineyard in Paso Robles, and the samplesspanned maturity levels from what would be considered early harvest (about 21 °Brix) to late harvest(about 30 °Brix). The wines made from these grapes were analysed using descriptive analysis to investigatethe relationships between fruit maturity and wine sensory attributes. In addition, musts and/or wines werechaptalised and/or fortified or watered back to determine the effect of these manipulations on wine sensoryproperties. This research showed that the sensory attributes of wines made from grapes at different stagesof maturation, from about 20 to 30 °Brix, varied in a systematic fashion. Specifically, the wines made fromthe grapes with a lower Brix were more sour and had more fresh vegetative flavours, while the wines madefrom the fruit with a high Brix were more hot and bitter and in some cases had more dark fruit flavoursand sweetness. Fortifying wines made from lower Brix musts changed the perceptions of the wine sensoryprofiles more than chaptalising the musts. On the other hand, adding water to higher °Brix musts to mimic24 °Brix musts resulted in wines with similar sensory profiles to wines made from grapes picked at a sugarcontent of close to 24 °Brix. This study shows that wine sensory attributes differ more when grapes arepicked early in ripening rather than after 24 °Brix

Tc-99m-NTP 15-5 assessment of the early therapeutic response of chondrosarcoma to zoledronic acid in the Swarm rat orthotopic model

Background: Since proteoglycans (PGs) appear as key partners in chondrosarcoma biology, PG-targeted imaging using the radiotracer 99mTc-N-(triethylammonium)-3-propyl-[15]ane-N5 (99mTc-NTP 15-5) developed by our group was previously demonstrated to be a good single-photon emission computed tomography tracer for cartilage neoplasms. We therefore initiated this new preclinical study to evaluate the relevance of 99mTc-NTP 15-5 imaging for the in vivo monitoring and quantitative assessment of chondrosarcoma response to zoledronic acid (ZOL) in the Swarm rat orthotopic model. Findings: Rats bearing chondrosarcoma in the orthotopic paratibial location were treated by ZOL (100 μg/kg, subcutaneously) or phosphate-buffered saline, twice a week, from day 4 to day 48 post-tumor implantation. 99mTc-NTP 15-5 imaging was performed at regular intervals with the target-to-background ratio (TBR) determined. Tumor volume was monitored using a calliper, and histology was performed at the end of the study. From day 11 to day 48, mean TBR values ranged from 1.7 ± 0.6 to 2.3 ± 0.6 in ZOL-treated rats and from 2.1 ± 1.0 to 4.9 ± 0.9 in controls. Tumor growth inhibition was evidenced using a calliper from day 24 and associated to a decrease in PG content in treated tumor tissues (confirmed by histology). Conclusions: This work demonstrated two proofs of concept: (1) biphosphonate therapy could be a promising therapeutic approach for chondrosarcoma; (2) 99mTc-NTP 15-5 is expected to offer a novel imaging modality for the in vivo evaluation of the extracellular matrix features of chondrosarcoma, which could be useful for the follow-up and quantitative assessment of proteoglycan ‘downregulation’ associated to the response to therapeutic attempts

Unstable Attractors: Existence and Robustness in Networks of Oscillators With Delayed Pulse Coupling

We consider unstable attractors; Milnor attractors $A$ such that, for some neighbourhood $U$ of $A$, almost all initial conditions leave $U$. Previous research strongly suggests that unstable attractors exist and even occur robustly (i.e. for open sets of parameter values) in a system modelling biological phenomena, namely in globally coupled oscillators with delayed pulse interactions. In the first part of this paper we give a rigorous definition of unstable attractors for general dynamical systems. We classify unstable attractors into two types, depending on whether or not there is a neighbourhood of the attractor that intersects the basin in a set of positive measure. We give examples of both types of unstable attractor; these examples have non-invertible dynamics that collapse certain open sets onto stable manifolds of saddle orbits. In the second part we give the first rigorous demonstration of existence and robust occurrence of unstable attractors in a network of oscillators with delayed pulse coupling. Although such systems are technically hybrid systems of delay differential equations with discontinuous `firing' events, we show that their dynamics reduces to a finite dimensional hybrid system system after a finite time and hence we can discuss Milnor attractors for this reduced finite dimensional system. We prove that for an open set of phase resetting functions there are saddle periodic orbits that are unstable attractors.Comment: 29 pages, 8 figures,submitted to Nonlinearit

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

IL-1 beta and TNF alpha Promote Monocyte Viability through the Induction of GM-CSF Expression by Rheumatoid Arthritis Synovial Fibroblasts

Background. Macrophages and synovial fibroblasts (SF) are two major cells implicated in the pathogenesis of rheumatoid arthritis (RA). SF could be a source of cytokines and growth factors driving macrophages survival and activation. Here, we studied the effect of SF on monocyte viability and phenotype. Methods. SF were isolated from synovial tissue of RA patients and CD14+ cells were isolated from peripheral blood of healthy donors. SF conditioned media were collected after 24 hours of culture with or without stimulation with TNFα or IL-1β. Macrophages polarisation was studied by flow cytometry. Results. Conditioned medium from SF significantly increased monocytes viability by 60% compared to CD14+ cells cultured in medium alone . This effect was enhanced using conditioned media from IL-1β and TNFα stimulated SF. GM-CSF but not M-CSF nor IL34 blocking antibodies was able to significantly decrease monocyte viability by 30% when added to the conditioned media from IL-1β and TNFα stimulated SF . Finally, monocyte cultured in presence of SF conditioned media did not exhibit a specific M1 or M2 phenotype. Conclusion. Overall, rheumatoid arthritis synovial fibroblasts stimulated with proinflammatory cytokines (IL-1β and TNFα) promote monocyte viability via GM-CSF but do not induce a specific macrophage polarization

Atmospheric greenhouse gases retrieved from SCIAMACHY: comparison to ground-based FTS measurements and model results

SCIAMACHY onboard ENVISAT (launched in 2002) enables the retrieval of global long-term column-averaged dry air mole fractions of the two most important anthropogenic greenhouse gases carbon dioxide and methane (denoted XCO_2 and XCH_4). In order to assess the quality of the greenhouse gas data obtained with the recently introduced v2 of the scientific retrieval algorithm WFM-DOAS, we present validations with ground-based Fourier Transform Spectrometer (FTS) measurements and comparisons with model results at eight Total Carbon Column Observing Network (TCCON) sites providing realistic error estimates of the satellite data. Such validation is a prerequisite to assess the suitability of data sets for their use in inverse modelling. It is shown that there are generally no significant differences between the carbon dioxide annual increases of SCIAMACHY and the assimilation system CarbonTracker (2.00 ± 0.16 ppm yr^(−1) compared to 1.94 ± 0.03 ppm yr−1 on global average). The XCO_2 seasonal cycle amplitudes derived from SCIAMACHY are typically larger than those from TCCON which are in turn larger than those from CarbonTracker. The absolute values of the northern hemispheric TCCON seasonal cycle amplitudes are closer to SCIAMACHY than to CarbonTracker and the corresponding differences are not significant when compared with SCIAMACHY, whereas they can be significant for a subset of the analysed TCCON sites when compared with CarbonTracker. At Darwin we find discrepancies of the seasonal cycle derived from SCIAMACHY compared to the other data sets which can probably be ascribed to occurrences of undetected thin clouds. Based on the comparison with the reference data, we conclude that the carbon dioxide data set can be characterised by a regional relative precision (mean standard deviation of the differences) of about 2.2 ppm and a relative accuracy (standard deviation of the mean differences) of 1.1–1.2 ppm for monthly average composites within a radius of 500 km. For methane, prior to November 2005, the regional relative precision amounts to 12 ppb and the relative accuracy is about 3 ppb for monthly composite averages within the same radius. The loss of some spectral detector pixels results in a degradation of performance thereafter in the spectral range currently used for the methane column retrieval. This leads to larger scatter and lower XCH_4 values are retrieved in the tropics for the subsequent time period degrading the relative accuracy. As a result, the overall relative precision is estimated to be 17 ppb and the relative accuracy is in the range of about 10–20 ppb for monthly averages within a radius of 500 km. The derived estimates show that the SCIAMACHY XCH_4 data set before November 2005 is suitable for regional source/sink determination and regional-scale flux uncertainty reduction via inverse modelling worldwide. In addition, the XCO2 monthly data potentially provide valuable information in continental regions, where there is sparse sampling by surface flask measurements

Towards space based verification of CO₂ emissions from strong localized sources: fossil fuel power plant emissions as seen by a CarbonSat constellation

Carbon dioxide (CO₂) is the most important man-made greenhouse gas (GHG) that cause global warming. With electricity generation through fossil-fuel power plants now being the economic sector with the largest source of CO₂, power plant emissions monitoring has become more important than ever in the fight against global warming. In a previous study done by Bovensmann et al. (2010), random and systematic errors of power plant CO₂ emissions have been quantified using a single overpass from a proposed CarbonSat instrument. In this study, we quantify errors of power plant annual emission estimates from a hypothetical CarbonSat and constellations of several CarbonSats while taking into account that power plant CO₂ emissions are time-dependent. Our focus is on estimating systematic errors arising from the sparse temporal sampling as well as random errors that are primarily dependent on wind speeds. We used hourly emissions data from the US Environmental Protection Agency (EPA) combined with assimilated and re-analyzed meteorological fields from the National Centers of Environmental Prediction (NCEP). CarbonSat orbits were simulated as a sun-synchronous low-earth orbiting satellite (LEO) with an 828-km orbit height, local time ascending node (LTAN) of 13:30 (01:30 p.m. LT) and achieves global coverage after 5 days. We show, that despite the variability of the power plant emissions and the limited satellite overpasses, one CarbonSat has the potential to verify reported US annual CO₂ emissions from large power plants (≥5 Mt CO₂ yr⁻¹) with a systematic error of less than ~4.9% and a random error of less than ~6.7% for 50% of all the power plants. For 90% of all the power plants, the systematic error was less than ~12.4% and the random error was less than ~13%. We additionally investigated two different satellite configurations using a combination of 5 CarbonSats. One achieves global coverage everyday but only samples the targets at fixed local times. The other configuration samples the targets five times at two-hour intervals approximately every 6th day but only achieves global coverage after 5 days. From the statistical analyses, we found, as expected, that the random errors improve by approximately a factor of two if 5 satellites are used. On the other hand, more satellites do not result in a large reduction of the systematic error. The systematic error is somewhat smaller for the CarbonSat constellation configuration achieving global coverage everyday. Therefore, we recommend the CarbonSat constellation configuration that achieves daily global coverage

First reported foodborne outbreak associated with microsporidia, Sweden, October 2009

Microsporidia are spore-forming intracellular parasites that infrequently cause disease in immunocompetent persons. This study describes the first report of a foodborne microsporidiosis outbreak which affected persons visiting a hotel in Sweden. Enterocytozoon bieneusi was identified in stool samples from 7/11 case-patients, all six sequenced samples were genotype C. To confirm that this was not a chance finding, 19 stool samples submitted by healthy persons from a comparable group who did not visit the hotel on that day were tested; all were negative for microsporidia. A retrospective cohort study identified 135 case-patients (attack rate 30%). The median incubation period was 9 days. Consumption of cheese sandwiches [relative risk (RR) 4·1, 95% confidence interval (CI) 1·4–12·2] and salad (RR 2·1, 95% CI 1·1–4) were associated with illness. Both items contained pre-washed, ready-to-eat cucumber slices. Microsporidia may be an under-reported cause of gastrointestinal outbreaks; we recommend that microsporidia be explored as potential causative agents in food- and waterborne outbreaks, especially when no other organisms are identified

The Greenhouse Gas Climate Change Initiative (GHG-CCI): comparative validation of GHG-CCI SCIAMACHY/ENVISAT and TANSO-FTS/GOSAT CO₂ and CH₄ retrieval algorithm products with measurements from the TCCON

Column-averaged dry-air mole fractions of carbon dioxide and methane have been retrieved from spectra acquired by the TANSO-FTS (Thermal And Near-infrared Sensor for carbon Observations-Fourier Transform Spectrometer) and SCIAMACHY (Scanning Imaging Absorption Spectrometer for Atmospheric Cartography) instruments on board GOSAT (Greenhouse gases Observing SATellite) and ENVISAT (ENVIronmental SATellite), respectively, using a range of European retrieval algorithms. These retrievals have been compared with data from ground-based high-resolution Fourier transform spectrometers (FTSs) from the Total Carbon Column Observing Network (TCCON). The participating algorithms are the weighting function modified differential optical absorption spectroscopy (DOAS) algorithm (WFMD, University of Bremen), the Bremen optimal estimation DOAS algorithm (BESD, University of Bremen), the iterative maximum a posteriori DOAS (IMAP, Jet Propulsion Laboratory (JPL) and Netherlands Institute for Space Research algorithm (SRON)), the proxy and full-physics versions of SRON's RemoTeC algorithm (SRPR and SRFP, respectively) and the proxy and full-physics versions of the University of Leicester's adaptation of the OCO (Orbiting Carbon Observatory) algorithm (OCPR and OCFP, respectively). The goal of this algorithm inter-comparison was to identify strengths and weaknesses of the various so-called round- robin data sets generated with the various algorithms so as to determine which of the competing algorithms would proceed to the next round of the European Space Agency's (ESA) Greenhouse Gas Climate Change Initiative (GHG-CCI) project, which is the generation of the so-called Climate Research Data Package (CRDP), which is the first version of the Essential Climate Variable (ECV) "greenhouse gases" (GHGs). For XCO₂, all algorithms reach the precision requirements for inverse modelling (< 8 ppm), with only WFMD having a lower precision (4.7 ppm) than the other algorithm products (2.4–2.5 ppm). When looking at the seasonal relative accuracy (SRA, variability of the bias in space and time), none of the algorithms have reached the demanding < 0.5 ppm threshold. For XCH₄, the precision for both SCIAMACHY products (50.2 ppb for IMAP and 76.4 ppb for WFMD) fails to meet the < 34 ppb threshold for inverse modelling, but note that this work focusses on the period after the 2005 SCIAMACHY detector degradation. The GOSAT XCH₄ precision ranges between 18.1 and 14.0 ppb. Looking at the SRA, all GOSAT algorithm products reach the < 10 ppm threshold (values ranging between 5.4 and 6.2 ppb). For SCIAMACHY, IMAP and WFMD have a SRA of 17.2 and 10.5 ppb, respectively