To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
High dietary phosphorus (P), particularly soluble salts, may contribute to chronic kidney disease development in cats. The aim of this study was to assess the safety of P supplied at 1g/1000kcal from a highly soluble P salt in P-rich dry format feline diets. Seventy-five healthy adult cats (n=25/group) were fed either a low P control (1.4g/1000 kcal; calcium:phosphorus ratio, Ca:P 0.97) or one of two test diets with 4g/1000 kcal (4184kJ); Ca:P 1.04 or 5g/1000kcal; Ca:P 1.27, both incorporating 1g/1000kcal (4184kJ) sodium tripolyphosphate (STPP) ‒ for a period of 30 weeks in a randomised parallel-group study. Health markers in blood and urine, glomerular filtration rate, renal ultrasound and bone density were assessed at baseline and at regular time points. At the end of the test period, responses following transition to a commercial diet (total P – 2.34g/1000kcal, Ca:P 1.3) for a 4-week washout period were also assessed. No adverse effects on general, kidney or bone (skeletal) function and health were observed. P and Ca balance, some serum biochemistry parameters and regulatory hormones were increased in cats fed test diets from week 2 onwards (p≤0.05). Data from the washout period suggest that increased serum creatinine and urea values observed in the two test diet groups were influenced by dietary differences during the test period, and not indicative of changes in renal function. The present data suggest NOAELs for feline diets containing 1g P/1000kcal (4184kJ) from STPP and total phosphorus level of up to 5g/1000kcal (4184kJ) when fed for 30 weeks.
Around 8150 BP, the Storegga tsunami struck North-west Europe. The size of this wave has led many to assume that it had a devastating impact upon contemporaneous Mesolithic communities, including the final inundation of Doggerland, the now submerged Mesolithic North Sea landscape. Here, the authors present the first evidence of the tsunami from the southern North Sea, and suggest that traditional notions of a catastrophically destructive event may need rethinking. In providing a more nuanced interpretation by incorporating the role of local topographic variation within the study of the Storegga event, we are better placed to understand the impact of such dramatic occurrences and their larger significance in settlement studies.
Background: When control mechanisms such as water temperature and biocide level are insufficient, Legionella, the causative bacteria of Legionnaires’ disease, can proliferate in water distribution systems in buildings. Guidance and oversight bodies are increasingly prioritizing water safety programs in healthcare facilities to limit Legionella growth. However, ensuring optimal implementation in large buildings is challenging. Much is unknown, and sometimes assumed, about whether building and campus characteristics influence Legionella growth. We used an extensive real-world environmental Legionella data set in the Veterans Health Administration (VHA) healthcare system to examine infrastructure characteristics and Legionella positivity. Methods: VHA medical facilities across the country perform quarterly potable water sampling of healthcare buildings for Legionella detection as part of a comprehensive water safety program. Results are reported to a standardized national database. We did an exploratory univariate analysis of facility-reported Legionella data from routine potable water samples taken in 2015 to 2018, in conjunction with infrastructure characteristics available in a separate national data set. This review examined the following characteristics: building height (number of floors), building age (reported construction year), and campus acreage. Results: The final data set included 201,936 water samples from 819 buildings. Buildings with 1–5 floors (n = 634) had a Legionella positivity rate of 5.3%, 6–10 floors (n = 104) had a rate of 6.4%, 11–15 floors (n = 36) had a rate of 8.1%, and 16–22 floors (n = 9) had a rate of 8.8%. All rates were significantly different from each other except 11–15 floors and 16–22 floors (P < .05, χ2). The oldest buildings (1800s) had significantly less (P < .05, χ2) Legionella positivity than those built between 1900 and 1939 and between 1940 and 1979, but they were no different than the newest buildings (Fig. 1). In newer buildings (1980–2019), all decades had buildings with Legionella positivity (Fig. 1 inset). Campus acreage varied from ~3 acres to almost 500 acres. Although significant differences were found in Legionella positivity for different campus sizes, there was no clear trend and campus acreage may not be a suitable proxy for the extent or complexity of water systems feeding buildings. Conclusions: The analysis of this large, real-world data set supports an assumption that taller buildings are more likely to be associated with Legionella detection, perhaps a result of more extensive piping. In contrast, the assumption that newer buildings are less associated with Legionella was not fully supported. These results demonstrate the variability in Legionella positivity in buildings, and they also provide evidence that can inform implementation of water safety programs.
Disclosures: Chetan Jinadatha, principal Investigator/Co-I: Research: NIH/NINR, AHRQ, NSF principal investigator: Research: Xenex Healthcare Services. Funds provided to institution. Inventor: Methods for organizing the disinfection of one or more items contaminated with biological agents. Owner: Department of Veterans Affairs. Licensed to Xenex Disinfection System, San Antonio, TX.
The seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) IgG antibody was evaluated among employees of a Veterans Affairs healthcare system to assess potential risk factors for transmission and infection.
All employees were invited to participate in a questionnaire and serological survey to detect antibodies to SARS-CoV-2 as part of a facility-wide quality improvement and infection prevention initiative regardless of clinical or nonclinical duties. The initiative was conducted from June 8 to July 8, 2020.
Of the 2,900 employees, 51% participated in the study, revealing a positive SARS-CoV-2 seroprevalence of 4.9% (72 of 1,476; 95% CI, 3.8%–6.1%). There were no statistically significant differences in the presence of antibody based on gender, age, frontline worker status, job title, performance of aerosol-generating procedures, or exposure to known patients with coronavirus infectious disease 2019 (COVID-19) within the hospital. Employees who reported exposure to a known COVID-19 case outside work had a significantly higher seroprevalence at 14.8% (23 of 155) compared to those who did not 3.7% (48 of 1,296; OR, 4.53; 95% CI, 2.67–7.68; P < .0001). Notably, 29% of seropositive employees reported no history of symptoms for SARS-CoV-2 infection.
The seroprevalence of SARS-CoV-2 among employees was not significantly different among those who provided direct patient care and those who did not, suggesting that facility-wide infection control measures were effective. Employees who reported direct personal contact with COVID-19–positive persons outside work were more likely to have SARS-CoV-2 antibodies. Employee exposure to SARS-CoV-2 outside work may introduce infection into hospitals.
On 4 July 2017, the European Parliament adopted a resolution “with recommendations to the Commission on common minimum standards of civil procedure in the European Union“. This project is a proposal for a directive and contains 28 articles on diverse aspects of civil procedure. The proposal deserves some attention because it represents the latest step towards procedural harmonisation in the EU. Procedural harmonisation in Europe has come a long way since the famous “Storme Commission‘s report“ of 1993. This report is, nowadays, widely known among European procedural comparatists but, in 1993, it went largely unnoticed, especially by the EU legislator. This “delayed glory“ can be explained by the fact that, in 1993, the European Union had no direct competence to legislate on civil procedure and the Member States ‘governments did not consider the field of civil justice as a political priority.
Both factors changed with the signature of the Amsterdam Treaty in 1997 and the Tampere Council conclusions of October 1999, where the Council expressed its wish to set up a “Genuine European Area of Justice“ with “greater convergence in civil law“. With this political mandate, the European Commission started to work intensively in the field of civil and commercial disputes. The first step was the “communautarisation“ of the Brussels Convention of 1968 with the Brussels Regulation, followed by the adoption of the Insolvency Regulation and several other instruments, mostly focusing on international competence and enforcement of foreign judgments. In the meantime, the Commission proposed to adopt genuine European procedures and published a green paper in 2002 on a European order for payment procedure. In this document, the Commission mentions the Storme Commission‘s report and describes it as a “ valuable point of reference and source of inspiration ”.
Since 2002, the European agenda on civil procedure has been well fulfilled and many instruments have been adopted, enhancing judicial cooperation and facilitating cross-border disputes. 10 Yet, European Union law has barely affected domestic procedures because of the absence of general legislative competence on this matter. EU procedural law also lacks a holistic regulation of civil procedure, at least nothing that comes close to the initial “European Judicial Code“ idea that was the basis for the Storme Commission‘s report.
Obesity rates are increasing worldwide. Potential reasons include excessive consumption of sugary beverages and energy-dense foods instead of more nutrient-rich options. On a per kJ basis, energy-dense grains, added sugars and fats cost less, whereas lean meats, seafood, leafy greens and whole fruit generally cost more. Given that consumer food choices are often driven by price, the observed social inequities in diet quality and health can be explained, in part, by nutrition economics. Achieving a nutrient-rich diet at an affordable cost has become progressively more difficult within the constraints of global food supply. However, given the necessary metrics and educational tools, it may be possible to eat better for less. New metrics of nutrient density help consumers identify foods, processed and unprocessed, that are nutrient-rich, affordable and appealing. Affordability metrics, created by adding food prices to food composition data, permit calculations of both kJ and nutrients per penny, allowing for new studies on the economic drivers of food choice. Merging dietary intake data with local or national food prices permits the estimation of individual-level diet costs. New metrics of nutrient balance can help identify those food patterns that provide optimal nutritional value. Behavioural factors, including cooking at home, have been associated with nutrition resilience, defined as healthier diets at lower cost. Studies of the energy and nutrient costs of the global food supply and diverse food patterns will permit a better understanding of the socioeconomic determinants of health. Dietary advice ought to be accompanied by economic feasibility studies.
First promulgated in 1959, the 3Rs of Replacement, Reduction and Refinement have evolved as fundamental principles underlying the use of animals and alternatives in science throughout the modern world. This review describes a contemporary approach to delivering the 3Rs through acknowledging the contribution of new technologies and emphasising that applying the 3Rs can be beneficial to good science as well as to animal welfare. This science-led approach moves the concept of the 3Rs out of an ethical silo where they were often considered by scientists to be an inconvenient obligation. On the contrary, relevant examples demonstrate the opportunity to practise better science using 3Rs technologies which deliver faster, more reproducible and more cost-effective results. Indeed, methods harnessing Replacement approaches may permit discoveries which are simply not feasible using animals and frequently are more flexible and agile since compliance with regulatory oversight requirements is simplified. Although the necessity for rigorous oversight is well recognised, it is important that the associated bureaucracy is not allowed to become prohibitive, causing scientists to avoid pursuing justifiable and important research involving animals. Public support for research is conditional – animals should not suffer unnecessarily and sufficient potential benefit should accrue from the research. However, society also actively seeks pioneering medical and scientific advances which can only be achieved through research. Therefore, a balance must be struck between safeguarding animal welfare whilst enabling high-quality science. It is this balance which promotes and sustains public confidence that animal based research is acceptable and being appropriately managed.
OBJECTIVES/SPECIFIC AIMS: Alcohol consumption perturbs the normal intestinal microbial communities (alcohol dysbiosis). To begin to investigate the relationship between alcohol-mediated dysbiosis and host defense we developed an alcohol dysbiosis fecal adoptive transfer model, which allows us to isolate the host immune response to a pathogenic challenge at a distal organ (ie, the lung). This model system allowed us to determine whether the host immune responses to Klebsiella pneumoniae are altered by ethanol-associated dysbiosis, independent of alcohol use. We hypothesized that alcohol-induced changes in intestinal microbial communities would impair pulmonary host defenses against K. pneumoniae. METHODS/STUDY POPULATION: Mice were treated with a cocktail of antibiotics daily for 2 weeks. Microbiota-depleted mice were then recolonized by gavage for 3-days with intestinal microbiota from ethanol-fed or pair-fed animals. Following recolonization groups of mice were sacrificed prior to and 48 hours post respiratory infection with K. pneumoniae. We then assessed susceptibility to Klebsiella infection by determining colony counts for pathogen burden in the lungs. We also determined lung and intestinal immunology, intestinal permeability, as well as, liver damage and inflammation. RESULTS/ANTICIPATED RESULTS: We found that increased susceptibility to K. pneumoniae is, in part, mediated by the intestinal microbiota, as animals recolonized with an alcohol-induced dysbiotic intestinal microbial community have significantly higher lung burdens of K. pneumoniae (5×104 CFU vs. 1×103 CFU) independent of EtOH. We also found that increased susceptibility in alcohol-dysbiosis recolonized animals was associated with a decrease in the recruitment and/or proliferation of CD4+ and CD8+ T-cells (1.5×109 cells vs. 2.5×109 cells) in the lung following Klebsiella infection. However, there were increased numbers of T-cells in the intestinal tract following Klebsiella infection, which may suggest that T cells are being sequestered in the intestinal tract to the detriment of host defense in the lung. Interestingly, mice recolonized with an alcohol-dysbiotic microbiota had increased intestinal permeability as measured by increased levels of serum intestinal fatty acid binding protein (55 vs. 30 ng/mL). Alcohol-dysbiotic microbiota also increased liver steatosis (Oil Red-O staining) and liver inflammation (>2-fold expression of IL-17 and IL-23). DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest that the commensal intestinal microbiota support mucosal host defenses against infectious agents by facilitating normal immune responses to pulmonary pathogens. Our data also suggest that increased intestinal permeability coupled with increased liver inflammation may impair the recruitment/proliferation of immune cells in the respiratory tract following infection. The role of the microbiota during host defense will be important areas of future research directed at understanding the effects of microbial dysbiosis in patients with AUDs.
We describe in detail the speed of `coming down from infinity' for birth-and-death processes which eventually become extinct. Under general assumptions on the birth-and-death rates, we firstly determine the behavior of the successive hitting times of large integers. We identify two different regimes depending on whether the mean time for the process to go from n+1 to n is negligible or not compared to the mean time to reach n from ∞. In the first regime, the coming down from infinity is very fast and the convergence is weak. In the second regime, the coming down from infinity is gradual and a law of large numbers and a central limit theorem for the hitting times sequence hold. By an inversion procedure, we deduce that the process is almost surely equivalent to a nonincreasing function when the time goes to 0. Our results are illustrated by several examples including applications to population dynamics and population genetics. The particular case where the death rate varies regularly is studied in detail.
We build a model of search and matching in which agents trade using coins that are imperfectly recognizable, but have access to a coin inspection technology—known as coin assaying—that reveals the intrinsic content of coins for a fee. We consider two sources of imperfect information: counterfeit coins and clipping. With counterfeits, coin assaying reduces the extent of inefficiencies associated with imperfect recognizability of coins (namely lower traded quantities and lower trading frequencies). Yet coin assaying does not necessarily increase welfare, because it unmasks counterfeits that then trade at a discount, reducing total output. With clipping, we show that agents clip for two reasons: in the hope of passing an inferior coin for a superior one, and to reduce the purchasing power of coins that are too valuable. Although coin assaying could remove the first type of clipping, it had no effect on the second.
The objective of this study was to report procedural characteristics and adverse events on the data collected in the IMproving Paediatric and Adult Congenital Treatment registry.
The IMproving Paediatric and Adult Congenital Treatment– registry is a catheterisation registry focussed on paediatric and adult patients with congenital heart disease who are undergoing diagnostic catheterisations and catheter-based interventions. This study reports procedural characteristics and adverse events of patients who have undergone selected catheterisation procedures from January, 2011 to June, 2013.
Demographic, clinical, procedural, and institutional data elements were collected at participating centres and entered via either a web-based platform or software provided by the American College of Cardiology-certified vendors, and were collected in a secure, centralised database. For the purpose of this study, procedures that were not classified as one of the ‘core’ IMproving Paediatric and Adult Congenital Treatment procedures originally chosen for additional data collection were identified and selected for further data analysis.
During the time frame of data collection, a total of 8021 cases were classified as other procedures and/or multiple procedures. The most commonly performed case types – isolated or in combination with other procedures – were right ventricular biopsy in 3433 (42.8%), conduit/MPA interventions in 979 (12.3%), and systemic pulmonary artery collateral occlusion in 601 (7.5%). For the whole cohort, adverse events of any severity occurred in 957 (12.0%) cases, whereas major adverse events occurred in 113 (1.4%) cases; six patients (0.1%) died in the catheterisation laboratory.
The IMproving Paediatric and Adult Congenital Treatment registry has provided important data on the frequency and spectrum of cardiac catheterisation procedures performed in the present era. For many procedures, more data and work are needed to identify more subtle differences between case categories, especially as it relates to the incidence of major adverse events, and to further develop a risk-adjustment methodology to allow equitable comparisons among institutions.
To report procedural characteristics and adverse events on data collected in the registry.
The IMPACT – IMproving Paediatric and Adult Congenital Treatment – Registry is a catheterisation registry of paediatric and adult patients with CHD undergoing diagnostic and interventional cardiac catheterisation. We are reporting the procedural characteristics and adverse events of patients undergoing diagnostic and interventional catheterisation procedures from January, 2011 to March, 2013.
Demographic, clinical, procedural, and institutional data elements were collected at the participating centres and entered via either a web-based platform or software provided by American College of Cardiology-certified vendors, and were collected in a secure, centralised database. Centre participation was voluntary.
During the time frame of data collection, 19,797 procedures were entered into the IMPACT Registry. Procedures were classified as diagnostic only (35.4%); one of six specific interventions (23.8%); other or multiple interventions (40.7%); and were further broken down into four age groups. Anaesthesia was used in 84.1% of diagnostic procedures and 87.8% of interventional ones. Adverse events occurred in 10.0% of diagnostic and 11.1% of interventional procedures.
The IMPACT Registry is gathering data to set national benchmarks for diagnostic and certain specific interventional procedures. We are seeing little differences in procedural characteristics or adverse events in diagnostic procedures compared with interventional procedures overall, but there is significant variation in adverse events amongst age categories. Risk stratification and patient acuity scores will be required for further analysis of these differences.