Furosemide-induced vasodilation: Importance of the state of hydration and filtration

Furosemide-induced vasodilation: Importance of the state of hydration and filtration. The circumstances under which furose-mide increases renal blood flow was examined in mongrel dogs as it may relate to a tubuloglomerular feedback mechanism. Two maneuvers, desoxycorticosterone (DOCA) plus salt treatment and inhibition of tubular fluid flow, were used in the dogs to evaluate the renal vascular effects of furosemide because these maneuvers have been reported to blunt the tubuloglomerular feedback in micropuncture studies. In addition, we also used two structurally different nonsteroidal antiinflammatory drugs to assess the importance of prostaglandins to achieve furosemide's renal vasodilation. Furosemide (5 mg/kg, i.v.) increased renal blood flow in volume-depleted animals from a baseline flow of 141 ± 28ml/min to a maximum of 176 ± 35ml/min at 6min after furosemide administration. If the animals were pretreated with a high-salt diet and i.m. DOCA for 5 days, furosemide administration produced no renal vascular effects but still caused a large diuresis, and these dogs still had a responsive renal vascular bed to infused prostaglandin E2. In addition, kidneys rendered non-filtering in volume-depleted animals had no renal vascular response to furosemide. Volume-depleted animals, pretreated with either indomethacin or sodium meclofenamate, did not have a renal vascular response to furosemide although they did have a diuretic response and a responsive renal vasculature to prostaglandin E2. From our data, we hypothesize that the renal vascular response to furosemide is secondary to a tubular mechanism mediated by a vasodilatory prostaglandin. Because furosemide has been shown to disrupt the tubuloglomerular feedback mechanism, and the two maneuvers, DOCA plus salt treatment and lack of filtration, blunt the tubuloglomerular feedback response as well as inhibit the renal vascular response to furosemide, we further hypothesize that furosemide-induced renal vasodilation may be secondary to the disruption of an active tubuloglomerular feedback mechanism.Vasodilatation induite par le furosémide: Importance de l'état d'hydratation et de filtration. Les circonstances où le furosémide augmente le débit sanguin rénal ont été étudiées chez des chiens bâtards en fonction d'un mécanisme possible de rétro-contrôle tubulo-glomérulaire. Deux manoeuvres, le traitement par la désoxycorticosterone (DOCA) et le sel et l'inhibition du débit tubulaire, ont été utilisées chez des chiens pour évaluer les effets vasculaires rénaux du furosemide, puisque ces deux manoeuvres sont réputées effacer le rétro-contrôle tubulo-glomérulaire dans les études par microponction. De plus, nous avons employé deux drogues anti-inflammatoires, non stéroïdiennes, de structures différentes pour évaluer l'importance des prostaglandines dans le déterminisme d'une vasodilatation rénale. Le furosemide (5 mg/kg, i.v.) augmente le débit sanguin rénal chez les animaux déshydratés à partir d'une ligne de base de 141 ± 28ml/min jusqu'à un maximum de 176 ± 35ml/min 6 minutes après l'administration de furosémide. Quand les animaux ont été prétraités par une alimentation riche en sel et de la DOCA i.m. pendant 5 jours l'administration de furosémide n'a pas produit d'effets vasculaires rénaux mais a cependant déterminé une diurèse importante et le lit vasculaire rénal de ces chiens pouvait encore répondre à la perfusion de prostaglandines E2. De plus, des reins devenus non filtrants chez des animaux déshydratés n'avaient pas de réponse vasculaire rénale au furosémide. Les animaux déshydratés et pré-traités soit par l'indométhacine, soit par le méclofénamate de sodium, n'avaient pas de réponse vasculaire rénale au furosémide quoiqu'ils avaient une réponse diurétique et une réponse vasculaire rénale à la prostaglandin E2. De ces résultats nous tirons l'hypothèse que la réponse vasculaire rénale au furosémide est secondaire à un mécanisme tubulaire dont la vasodilatation par la prostaglandine est un médiateur. Puisqu'il a été montré que le furosemide supprime le rétro-contrôle tubulo-glomérulaire et que les deux manoeuvres, DOCA et sel, d'une part, absence de filtration, d'autre part, annulent le rétro-contrôle tubulo-glomérulaire de même qu'elles inhibent la réponse vasculaire rénale au furosémide, nous faisons l'hypothèse supplémentaire que la vasodilatation rénale induite par le furosémide peut être secondaire à l'interruption d'un mécanisme actif de rétro-contrôle tubulo-glomérulaire

Stratosphere‐troposphere coupling and annular mode variability in chemistry‐climate models

The internal variability and coupling between the stratosphere and troposphere in CCMVal‐2 chemistry‐climate models are evaluated through analysis of the annular mode patterns of variability. Computation of the annular modes in long data sets with secular trends requires refinement of the standard definition of the annular mode, and a more robust procedure that allows for slowly varying trends is established and verified. The spatial and temporal structure of the models’ annular modes is then compared with that of reanalyses. As a whole, the models capture the key features of observed intraseasonal variability, including the sharp vertical gradients in structure between stratosphere and troposphere, the asymmetries in the seasonal cycle between the Northern and Southern hemispheres, and the coupling between the polar stratospheric vortices and tropospheric midlatitude jets. It is also found that the annular mode variability changes little in time throughout simulations of the 21st century. There are, however, both common biases and significant differences in performance in the models. In the troposphere, the annular mode in models is generally too persistent, particularly in the Southern Hemisphere summer, a bias similar to that found in CMIP3 coupled climate models. In the stratosphere, the periods of peak variance and coupling with the troposphere are delayed by about a month in both hemispheres. The relationship between increased variability of the stratosphere and increased persistence in the troposphere suggests that some tropospheric biases may be related to stratospheric biases and that a well‐simulated stratosphere can improve simulation of tropospheric intraseasonal variability

Agricultural climate change mitigation : Carbon calculators as a guide for decision making

This is an Accepted Manuscript of an article published by Taylor & Francis Group in International Journal of Agricultural Sustainability on 9 November 2017, available online: https://doi.org/10.1080/14735903.2017.1398628. Under embargo. Embargo end date: 9 November 2018.The dairy industry is receiving considerable attention in relation to both its significant greenhouse gas (GHG) emissions, and it’s potential for reducing those emissions, contributing towards meeting national targets and driving the industry towards sustainable intensification. However, the extent to which improvements can be made is dependent on the decision making processes of individual producers, so there has been a proliferation of carbon accounting tools seeking to influence those processes. This paper evaluates the suitability of such tools for driving environmental change by influencing on-farm management decisions. Seven tools suitable for the European dairy industry were identified, their characteristics evaluated, and used to process data relating to six scenario farms, emulating process undertaken in real farm management situations. As a result of the range of approaches taken by the tools, there was limited agreement between them as to GHG emissions magnitude, and no consistent pattern as to which tools resulted in the highest/lowest results. Despite this it is argued, that as there was agreement as to the farm activities responsible for the greatest emissions, the more complex tools were still capable of performing a ‘decision support’ role, and guiding management decisions, whilst others could merely focus attention on key issues.Peer reviewe

Voting Technology, Vote-by-Mail, and Residual Votes in California, 1990-2010

This paper examines how the growth in vote-by-mail and changes in voting technologies led to changes in the residual vote rate in California from 1990 to 2010. We find that in California’s presidential elections, counties that abandoned punch cards in favor of optical scanning enjoyed a significant improvement in the residual vote rate. However, these findings do not always translate to other races. For instance, find that the InkaVote system in Los Angeles has been a mixed success, performing very well in presidential and gubernatorial races, fairly well for ballot propositions, and poorly in Senate races. We also conduct the first analysis of the effects of the rise of vote-by-mail on residual votes. Regardless of the race, increased use of the mails to cast ballots is robustly associated with a rise in the residual vote rate. The effect is so strong that the rise of voting by mail in California has mostly wiped out all the reductions in residual votes that were due to improved voting technologies since the early 1990s

Tests of the Equivalence Principle with Neutral Kaons

We test the Principle of Equivalence for particles and antiparticles, using CPLEAR data on tagged K0 and K0bar decays into pi^+ pi^-. For the first time, we search for possible annual, monthly and diurnal modulations of the observables |eta_{+-}| and phi_{+-}, that could be correlated with variations in astrophysical potentials. Within the accuracy of CPLEAR, the measured values of |eta_{+-}| and phi_{+-} are found not to be correlated with changes of the gravitational potential. We analyze data assuming effective scalar, vector and tensor interactions, and we conclude that the Principle of Equivalence between particles and antiparticles holds to a level of 6.5, 4.3 and 1.8 x 10^{-9}, respectively, for scalar, vector and tensor potentials originating from the Sun with a range much greater than the distance Earth-Sun. We also study energy-dependent effects that might arise from vector or tensor interactions. Finally, we compile upper limits on the gravitational coupling difference between K0 and K0bar as a function of the scalar, vector and tensor interaction range.Comment: 15 pages latex 2e, five figures, one style file (cernart.csl) incorporate

Systematic review of communication technologies to promote access and engagement of young people with diabetes into healthcare

Background: Research has investigated whether communication technologies (e.g. mobile telephony, forums, email) can be used to transfer digital information between healthcare professionals and young people who live with diabetes. The systematic review evaluates the effectiveness and impact of these technologies on communication. Methods: Nine electronic databases were searched. Technologies were described and a narrative synthesis of all studies was undertaken. Results: Of 20,925 publications identified, 19 met the inclusion criteria, with 18 technologies assessed. Five categories of communication technologies were identified: video-and tele-conferencing (n = 2); mobile telephony (n = 3); telephone support (n = 3); novel electronic communication devices for transferring clinical information (n = 10); and web-based discussion boards (n = 1). Ten studies showed a positive improvement in HbA1c following the intervention with four studies reporting detrimental increases in HbA1c levels. In fifteen studies communication technologies increased the frequency of contact between patient and healthcare professional. Findings were inconsistent of an association between improvements in HbA1c and increased contact. Limited evidence was available concerning behavioural and care coordination outcomes, although improvement in quality of life, patientcaregiver interaction, self-care and metabolic transmission were reported for some communication technologies. Conclusions: The breadth of study design and types of technologies reported make the magnitude of benefit and their effects on health difficult to determine. While communication technologies may increase the frequency of contact between patient and health care professional, it remains unclear whether this results in improved outcomes and is often the basis of the intervention itself. Further research is needed to explore the effectiveness and cost effectiveness of increasing the use of communication technologies between young people and healthcare professionals

Participatory Epidemiology: Use of Mobile Phones for Community-Based Health Reporting

Clark Freifeld and colleagues discuss mobile applications, including their own smartphone application, that show promise for health monitoring and information sharing

Evaluation of serological cross-reactivity and cross-neutralization between the United States porcine epidemic diarrhea virus prototype and S-INDEL-variant strains

BACKGROUND: At least two genetically different porcine epidemic diarrhea virus (PEDV) strains have been identified in the United States (U.S. PEDV prototype and S-INDEL-variant strains). The current serological assays offered at veterinary diagnostic laboratories for detection of PEDV-specific antibody are based on the U.S. PEDV prototype strain. The objectives of this study were: 1) isolate the U.S. PEDV S-INDEL-variant strain in cell culture; 2) generate antisera against the U.S. PEDV prototype and S-INDEL-variant strains by experimentally infecting weaned pigs; 3) determine if the various PEDV serological assays could detect antibodies against the U.S. PEDV S-INDEL-variant strain and vice versa. RESULTS: A U.S. PEDV S-INDEL-variant strain was isolated in cell culture in this study. Three groups of PEDV-negative, 3-week-old pigs (five pigs per group) were inoculated orally with a U.S. PEDV prototype isolate (previously isolated in our lab), an S-INDEL-variant isolate or virus-negative culture medium. Serum samples collected at 0, 7, 14, 21 and 28 days post inoculation were evaluated by the following PEDV serological assays: 1) indirect fluorescent antibody (IFA) assays using the prototype and S-INDEL-variant strains as indicator viruses; 2) virus neutralization (VN) tests against the prototype and S-INDEL-variant viruses; 3) PEDV prototype strain whole virus based ELISA; 4) PEDV prototype strain S1-based ELISA; and 5) PEDV S-INDEL-variant strain S1-based ELISA. The positive antisera against the prototype strain reacted to and neutralized both prototype and S-INDEL-variant viruses, and the positive antisera against the S-INDEL-variant strain also reacted to and neutralized both prototype and S-INDEL-variant viruses, as examined by IFA antibody assays and VN tests. Antibodies against the two PEDV strains could be detected by all three ELISAs although detection rates varied to some degree. CONCLUSIONS: These data indicate that the antibodies against U.S. PEDV prototype and S-INDEL-variant strains cross-reacted and cross-neutralized both strains in vitro. The current serological assays based on U.S. PEDV prototype strain can detect antibodies against both U.S. PEDV strains