Effects of tidal-forcing variations on tidal properties along a narrow convergent estuary

A 1D analytical framework is implemented in a narrow convergent estuary that is 78 km in length (the Guadiana, Southern Iberia) to evaluate the tidal dynamics along the channel, including the effects of neap-spring amplitude variations at the mouth. The close match between the observations (damping from the mouth to ∼ 30 km, shoaling upstream) and outputs from semi-closed channel solutions indicates that the M2 tide is reflected at the estuary head. The model is used to determine the contribution of reflection to the dynamics of the propagating wave. This contribution is mainly confined to the upper one third of the estuary. The relatively constant mean wave height along the channel (< 10% variations) partly results from reflection effects that also modify significantly the wave celerity and the phase difference between tidal velocity and elevation (contradicting the definition of an “ideal” estuary). Furthermore, from the mouth to ∼ 50 km, the variable friction experienced by the incident wave at neap and spring tides produces wave shoaling and damping, respectively. As a result, the wave celerity is largest at neap tide along this lower reach, although the mean water level is highest in spring. Overall, the presented analytical framework is useful for describing the main tidal properties along estuaries considering various forcings (amplitude, period) at the estuary mouth and the proposed method could be applicable to other estuaries with small tidal amplitude to depth ratio and negligible river discharge.info:eu-repo/semantics/publishedVersio

Burden of diseases and injuries attributable to alcohol consumption in the Middle East and North Africa region, 1990–2019

Alcohol consumption is associated with a number of diseases and injuries, including cardiovascular diseases, cancers, mental and neurological disorders, as well as transport-related injuries. This article reports the alcohol-attributable burden of diseases and injuries at the regional and national levels in the Middle East and North Africa (MENA) region between 1990 and 2019, by sex, age, underlying cause, and Socio-demographic Index (SDI). The regional deaths and disability-adjusted life-years (DALYs) attributable to alcohol consumption were reported for the MENA region, between 1990 and 2019, using the methodological framework and analytical strategies adopted by the Global Burden of Disease (GBD) study 2019. The estimates were all reported as counts, population-attributable fractions, and age-standardised rates per 100,000 population, along with their corresponding 95% uncertainty intervals (UIs). Also, the average annual percentage changes were used to represent the trends of age-standardised rates. In 2019, there were an estimated 22.0 thousand deaths (95% UI: 16.1–29.4) and 1.1 million DALYs (0.8–1.3) attributable to alcohol consumption in the MENA region. The number of DALYs attributable to alcohol consumption were much higher in men (878.0 thousand, 691.4–1104.8) than among women (181.8, 138.6–232.0). The overall age-standardised death and DALY rates attributable to alcohol consumption decreased by 34.5% (13.2–48.3) and 31.9% (16.9–42.5), respectively, over the study period. Egypt (10.1 [5.7–16.6]) and Kuwait (1.1 [0.8–1.5]) had the highest and lowest age-standardised death rates attributable to alcohol consumption, respectively. In 2019, the number of deaths and DALYs in the MENA region were highest in those aged 60–64 and 50–54 years, respectively. A negative association was observed between a country’s SDI and their corresponding age-standardised DALY rates over the period 1990 to 2019. Digestive diseases were the main contributor to the alcohol-attributable burden. Over 1990–2019, the regional deaths and DALYs of diseases and injuries attributable to alcohol consumption decreased with AAPC of − 1.45 (− 1.78 to − 1.12) and − 1.31 (− 1.46 to − 1.15), respectively. The death and DALY rates attributable to alcohol consumption in the MENA region have decreased over the past three decades. Further decreases can be facilitated by implementing country-level policies and increasing public awareness

The transcriptional programme of Salmonella enterica serovar Typhimurium reveals a key role for tryptophan metabolism in biofilms

<p>Abstract</p> <p>Background</p> <p>Biofilm formation enhances the capacity of pathogenic <it>Salmonella </it>bacteria to survive stresses that are commonly encountered within food processing and during host infection. The persistence of <it>Salmonella </it>within the food chain has become a major health concern, as biofilms can serve as a reservoir for the contamination of food products. While the molecular mechanisms required for the survival of bacteria on surfaces are not fully understood, transcriptional studies of other bacteria have demonstrated that biofilm growth triggers the expression of specific sets of genes, compared with planktonic cells. Until now, most gene expression studies of <it>Salmonella </it>have focused on the effect of infection-relevant stressors on virulence or the comparison of mutant and wild-type bacteria. However little is known about the physiological responses taking place inside a <it>Salmonella </it>biofilm.</p> <p>Results</p> <p>We have determined the transcriptomic and proteomic profiles of biofilms of <it>Salmonella enterica </it>serovar Typhimurium. We discovered that 124 detectable proteins were differentially expressed in the biofilm compared with planktonic cells, and that 10% of the <it>S</it>. Typhimurium genome (433 genes) showed a 2-fold or more change in the biofilm compared with planktonic cells. The genes that were significantly up-regulated implicated certain cellular processes in biofilm development including amino acid metabolism, cell motility, global regulation and tolerance to stress. We found that the most highly down-regulated genes in the biofilm were located on <it>Salmonella </it>Pathogenicity Island 2 (SPI2), and that a functional SPI2 secretion system regulator (<it>ssrA</it>) was required for <it>S</it>. Typhimurium biofilm formation. We identified STM0341 as a gene of unknown function that was needed for biofilm growth. Genes involved in tryptophan (<it>trp</it>) biosynthesis and transport were up-regulated in the biofilm. Deletion of <it>trpE </it>led to decreased bacterial attachment and this biofilm defect was restored by exogenous tryptophan or indole.</p> <p>Conclusions</p> <p>Biofilm growth of <it>S</it>. Typhimurium causes distinct changes in gene and protein expression. Our results show that aromatic amino acids make an important contribution to biofilm formation and reveal a link between SPI2 expression and surface-associated growth in <it>S</it>. Typhimurium.</p

Tissue Localization and Extracellular Matrix Degradation by PI, PII and PIII Snake Venom Metalloproteinases: Clues on the Mechanisms of Venom-Induced Hemorrhage

20 páginas, 4 figuras, 3 tablas y 7 tablas en material suplementario.Snake venom hemorrhagic metalloproteinases (SVMPs) of the PI, PII and PIII classes were compared in terms of tissue localization and their ability to hydrolyze basement membrane components in vivo, as well as by a proteomics analysis of exudates collected in tissue injected with these enzymes. Immunohistochemical analyses of co-localization of these SVMPs with type IV collagen revealed that PII and PIII enzymes co-localized with type IV collagen in capillaries, arterioles and post-capillary venules to a higher extent than PI SVMP, which showed a more widespread distribution in the tissue. The patterns of hydrolysis by these three SVMPs of laminin, type VI collagen and nidogen in vivo greatly differ, whereas the three enzymes showed a similar pattern of degradation of type IV collagen, supporting the concept that hydrolysis of this component is critical for the destabilization of microvessel structure leading to hemorrhage. Proteomic analysis of wound exudate revealed similarities and differences between the action of the three SVMPs. Higher extent of proteolysis was observed for the PI enzyme regarding several extracellular matrix components and fibrinogen, whereas exudates from mice injected with PII and PIII SVMPs had higher amounts of some intracellular proteins. Our results provide novel clues for understanding the mechanisms by which SVMPs induce damage to the microvasculature and generate hemorrhage.This work was performed in partial fulfillment of the requirements for the PhD degree for Cristina Herrera at Universidad de Costa Rica.Peer reviewe

An observational study of patient characteristics associated with the mode of admission to acute stroke services in North East, England

Objective Effective provision of urgent stroke care relies upon admission to hospital by emergency ambulance and may involve pre-hospital redirection. The proportion and characteristics of patients who do not arrive by emergency ambulance and their impact on service efficiency is unclear. To assist in the planning of regional stroke services we examined the volume, characteristics and prognosis of patients according to the mode of presentation to local services. Study design and setting A prospective regional database of consecutive acute stroke admissions was conducted in North East, England between 01/09/10-30/09/11. Case ascertainment and transport mode were checked against hospital coding and ambulance dispatch databases. Results Twelve acute stroke units contributed data for a mean of 10.7 months. 2792/3131 (89%) patients received a diagnosis of stroke within 24 hours of admission: 2002 arrivals by emergency ambulance; 538 by private transport or non-emergency ambulance; 252 unknown mode. Emergency ambulance patients were older (76 vs 69 years), more likely to be from institutional care (10% vs 1%) and experiencing total anterior circulation symptoms (27% vs 6%). Thrombolysis treatment was commoner following emergency admission (11% vs 4%). However patients attending without emergency ambulance had lower inpatient mortality (2% vs 18%), a lower rate of institutionalisation (1% vs 6%) and less need for daily carers (7% vs 16%). 149/155 (96%) of highly dependent patients were admitted by emergency ambulance, but none received thrombolysis. Conclusion Presentations of new stroke without emergency ambulance involvement were not unusual but were associated with a better outcome due to younger age, milder neurological impairment and lower levels of pre-stroke dependency. Most patients with a high level of pre-stroke dependency arrived by emergency ambulance but did not receive thrombolysis. It is important to be aware of easily identifiable demographic groups that differ in their potential to gain from different service configurations

The burden of rheumatoid arthritis in the Middle East and North Africa region, 1990–2019

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. The present study reported the burden of RA in the Middle East and North Africa (MENA) region from 1990 to 2019 by age, sex, and socio-demographic index (SDI). Publicly available data from the Global Burden of Disease (GBD) 2019 study was used to report the modelled point prevalence, annual incidence, and disability-adjusted life-years (DALYs) of RA, as counts and age-standardised rates with their corresponding 95% uncertainty intervals (UIs). In 2019, RA had an age-standardised point prevalence of 120.6 per 100,000 population (107.0–135.7) and an annual incidence rate of 5.9 (5.2–6.6) in MENA, which have increased 28.3% and 25.2%, respectively, since 1990. In 2019, the number of DALYs due to RA in the region was 103.6 thousand (74.2–136.7), with an age-standardised rate of 19.0 (13.9–24.9) DALYs per 100,000 population, which has increased by 18.6% since 1990 (6.7–28.2). The highest point prevalence was found in females aged 50–54, and in males aged 45–49. The highest number of DALYs was observed in the 50–54 age group. The MENA DALY rate was lower than the global rate (19.0 vs. 39.6 per 100,000), but the rate was higher in all age groups in 2019, when compared with 1990. In addition, from 1990 to 2019 an increased burden from RA was associated with an increase in SDI. In line with global trends, the burden of RA in the MENA region showed a steady increase from 1990 to 2019. This highlights the increasing need for updating the available health data to design more accurate guidelines to enable the early detection and treatment of RA in the MENA countries

The burden of low back pain and its association with socio-demographic variables in the Middle East and North Africa region, 1990–2019

Background Low back pain (LBP) is the most common musculoskeletal disorder globally. Providing region- and national-specific information on the burden of low back pain is critical for local healthcare policy makers. The present study aimed to report, compare, and contextualize the prevalence, incidence and years lived with disability (YLDs) of low back pain in the Middle East and North Africa (MENA) region by age, sex and sociodemographic index (SDI), from 1990 to 2019. Methods Publicly available data were obtained from the Global Burden of Disease (GBD) study 2019. The burden of LBP was reported for the 21 countries located in the MENA region, from 1990 to 2019. All estimates were reported as counts and age-standardised rates per 100,000 population, together with their corresponding 95% uncertainty intervals (UIs). Results In 2019, the age-standardised point prevalence and incidence rate per 100,000 in MENA were 7668.2 (95% UI 6798.0 to 8363.3) and 3215.9 (95%CI 2838.8 to 3638.3), which were 5.8% (4.3 to 7.4) and 4.4% (3.4 to 5.5) lower than in 1990, respectively. Furthermore, the regional age-standardised YLD rate in 2019 was 862.0 (605.5 to 1153.3) per 100,000, which was 6.0% (4.2 to 7.7) lower than in 1990. In 2019, Turkey [953.6 (671.3 to 1283.5)] and Lebanon [727.2 (511.5 to 966.0)] had the highest and lowest age-standardised YLD rates, respectively. There was no country in the MENA region that showed increases in the age-standardised prevalence, incidence or YLD rates of LBP over the measurement period. Furthermore, in 2019 the number of prevalent cases were highest in the 35–39 age group, with males having a higher number of cases in all age groups. In addition, the age-standardised YLD rates for males in the MENA region were higher than the global estimates in almost all age groups, in both 1990 and 2019. Furthermore, the burden of LBP was not associated with the level of socio-economic development during the measurement period. Conclusion The burden attributable to LBP in the MENA region decreased slightly from 1990 to 2019. Furthermore, the burden among males was higher than the global average. Consequently, more integrated healthcare interventions are needed to more effectively alleviate the burden of low back pain in this region

Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

Background: A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. &lt;p/&gt;Methods: Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK) profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs). &lt;p/&gt;Results: 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients) and 10 mg/m2 (3/12) included thrombocytopenia and febrile neutropenia; diarrhea was uncommon. Six patients (five had received irinotecan), had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1--10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. &lt;p/&gt;Conclusions: TP300 had predictable hematologic toxicity, and diarrhea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage

Jet Dipolarity: Top Tagging with Color Flow

A new jet observable, dipolarity, is introduced that can distinguish whether a pair of subjets arises from a color singlet source. This observable is incorporated into the HEPTopTagger and is shown to improve discrimination between top jets and QCD jets for moderate to high pT.Comment: 8 pages, 6 figures (updated to JHEP version

Mechanical Systems with Symmetry, Variational Principles, and Integration Algorithms

This paper studies variational principles for mechanical systems with symmetry and their applications to integration algorithms. We recall some general features of how to reduce variational principles in the presence of a symmetry group along with general features of integration algorithms for mechanical systems. Then we describe some integration algorithms based directly on variational principles using a discretization technique of Veselov. The general idea for these variational integrators is to directly discretize Hamilton’s principle rather than the equations of motion in a way that preserves the original systems invariants, notably the symplectic form and, via a discrete version of Noether’s theorem, the momentum map. The resulting mechanical integrators are second-order accurate, implicit, symplectic-momentum algorithms. We apply these integrators to the rigid body and the double spherical pendulum to show that the techniques are competitive with existing integrators