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IntroductionSynthesis of evidence provided check by randomised controlled trials (RCTs) is commonly used to develop clinical guidelines and make reimbursement decision for pharmacological interventions can you buy lasix. While the dose of a drug is of central importance, meta-analyses that examine their efficacy and safety often focus on comparing only agents can you buy lasix or classes of drugs, ignoring potential variability due to different doses. As different dose schedules may result in considerable heterogeneity in efficacy and safety, one common approach is to restrict the database at certain dose range (e.g., the therapeutic dose), discard all studies outside that range and then examine the role of dose in a subgroup analysis for the lowest and the highest dose categories.1 This approach fails, however, to synthesise the whole relevant evidence. Alternatively, researchers might opt to perform many meta-analyses, each restricted to studies that can you buy lasix examine a particular drug-dose combination. This will inevitably result in many underpowered meta-analyses.In this paper, we present a recently developed evidence synthesis method of a doseâeffect meta-analysis can you buy lasix (DE-MA) approach that offers a middle ground between âlumpingâ all doses together into a single meta-analysis and âsplittingâ them to many dose-specific meta-analyses.
In DE-MA, we model the changes in the drug effect along the range of all studied dosages. There are can you buy lasix two common approaches to conduct DE-MA. Two-stage and one-stage models. In the two-stage model, the doseâeffect curve is estimated within each study and then synthesised across studies.2 3 These two steps are performed simultaneously in the one-stage model.4We first provide the statistical explanations of the two models, can you buy lasix and then illustrate the models by using a collection of RCTs examining the efficacy of selective serotonin reuptake inhibitors (SSRI) antidepressants.5The analysis is implemented in R6 and is made available along with dataset and the results on GitHub (https://github.com/htx-r/Dose-effect-MA-EBMH-article-).MethodsIn this section, we describe the two-stage DE-MA model with summarised data. Then we present briefly the one-stage can you buy lasix model.
Finally, we discuss other issues related to this topic, namely. Statistical testing of doseâeffect coefficients and can you buy lasix how to assess heterogeneity and make predictions. The models which are illustrated here to conduct DE-MA have been implemented in various software packages, for example, the drmeta command (in Stata7) and the dosresmeta package8 (in R).6Doseâeffect shape within a studyLet us consider the case of an RCT where several doses are examined (one dose per arm) denoted by where the index j enumerates the dose levels starting with zero. The outcome is measured in each arm can you buy lasix on an additive scale (e.g., a mean, a log-odds). The doseâeffect model within a study associates the change in the outcome (ie, the treatment effect) to the change in the dose can you buy lasix.
Let us assume a trial like the one presented in table 1 that has a placebo arm, a dichotomous outcome and the changes in the outcome are measured using the odds ratio (logOR) of each dose level j relevant to a reference dose. Using the placebo arm as a reference (at dose , and assuming a linear association between logOR and dose, the doseâeffect model isView this table:Table 1 We present the data of Feighner et al study on the observed five can you buy lasix dose levels. The data consist of the observed dose, the number of responses, the total number of participants, the odds ratio (OR) and its 95% CI, log transformations of OR and its standard error (SE) The estimated coefficient β shows how much an increase in the dose will impact on the change in logOR.Typically, the referent dose is assigned can you buy lasix to the zero or the minimal dose to make interpretation easier. The doses are centred around the referent dose so the relationship quantifies the change in relative effects. However, this centralisation induces correlation between the logORs in each study (as they are all estimated relative to the outcome of can you buy lasix the.
Such correlations should be estimated and accounted for using the Longnecker and Greenland method.2 9In practice, multiple changes in the doseâeffect shape are expected so that the linear model is not often a realistic assumption. More flexible models are needed to account for those changes10 such as can you buy lasix restricted cubic spline (RCS). RCS is can you buy lasix a piecewise function. The dose spectrum is split into intervals (using some changepoints, called knots) and in each interval a cubic polynomial is fitted.11 Restrictions in the estimation of the polynomial coefficients are then imposed to ensure that they are connected and forming a smooth function which is linear in the two tails. The location and the number of those knots determine can you buy lasix the shape of the RCS.
The locations indicate intervals where changes in the shape might occur, and the number reflects how many such changes are anticipated. In general, setting k can you buy lasix knots creates a RCS model with regression coefficients. For identifiability, the minimum number of knots can you buy lasix is three and the doseâeffect shape is. This function is a combination of linear and non linear transformations.11Of note, a two-stage approach requires that the study examines at least three dose-level data including the referent level and that enables estimating the two regression coefficients in the linear and spline (nonlinear, ) parts of the equation.Any type of function could be used in the doseâeffect association. For study indicator i, the general form of the doseâeffect model can can you buy lasix be written.
The term refers to the p doseâeffect parameter and f denotes the doseâeffect shape.Synthesis of doseâeffect shapes across studiesConsider that we have fit the RCS model in k studies and we have obtained k sets of estimates ( ). Each pair of coefficients represents the shape of the doseâeffect within each study can you buy lasix. Now, we synthesise can you buy lasix the shapes across studies by combining their coefficients. We may set a common underlying coefficient for all studies, for example, and (common-effect model). Alternatively, the underlying study-specific coefficients can be assigned a two-dimensional normal distribution with mean and a varianceâcovariance can you buy lasix matrix to reflect the heterogeneity across the studies (random-effects model).
In the general can you buy lasix case, the doseâeffect shape f involving p coefficients which are similarly synthesised using a multivariate normal distribution.What we describe above is the two-stage approach. The doseâeffect curves are estimated within each study and then synthesised across studies in two separate steps. This requires can you buy lasix each study to report non-referent doses at least as many as the number of the doseâeffect coefficients. Otherwise, the coefficients will be non-identifiable and the study should be excluded from the analysis. For example, to estimate a doseâeffect quadratic shape or a RCS with three knots, two coefficients need to be estimated and hence each study needs to report at least two logORs (which means can you buy lasix at least three dose levels).
Studies that report less dose levels, shall be excluded from the synthesis.In the one-stage approach, within and across study estimation of the shape are performed simultaneously.4 This allows for borrowing information across studies and the study-specific coefficients can can you buy lasix be estimated even if the study itself does not report the required number of doses. This means that, with the one-stage approach, we can include in the synthesis studies that report only one logOR (two dose levels) even if we want to estimate RCS.There are different ways to present the results from the DE-MAs. The doseâeffect shape as a function of any dose can be presented in graphical or can you buy lasix tabular form by plugging-in the dose values and the estimated coefficients in the assumed function (see figures 1 and 2). Another useful presentation of the results could be to show absolute estimates of the outcome, such as estimates of probability for efficacy at any given dose, see figure 3. This can be done in can you buy lasix two simple steps.
First, we estimate the absolute probability of the response at the reference dose (e.g., can you buy lasix zero) and then we combine this with the estimated relative treatment effect at each dose (e.g., with the estimated logOR) to obtain the absolute outcome (e.g., the probability to respond at an active dose level).The estimated doseâeffect curves of citalopram in Feighner et al study. The fluoxetine-equivalent doses are presented versus the odds ratio with two different doseâeffect shapes. The linear model in grey (dashed) and the restricted cubic spline can you buy lasix (with knots at 20.0, 23.6 and 44.4) in red (solid). The 95% confidence bands are shaded around each curve." data-icon-position data-hide-link-title="0">Figure 1 The estimated doseâeffect curves of citalopram in Feighner et can you buy lasix al study. The fluoxetine-equivalent doses are presented versus the odds ratio with two different doseâeffect shapes.
The linear model in grey (dashed) and the restricted cubic spline (with can you buy lasix knots at 20.0, 23.6 and 44.4) in red (solid). The 95% confidence bands are shaded around each curve.Dose-effect curves for selective serotonin reuptake inhibitors. These curves are estimated using the restricted cubic spline function where knots are set at doses 20.0, 23.6 and 44.4 can you buy lasix mg/day. For data synthesis, we apply a one-stage (grey, solid) and two-stage (red, dashed) approaches.The 95% confidence bands are shaded around can you buy lasix each curve. SSRI, selective serotonin reuptake inhibitor." data-icon-position data-hide-link-title="0">Figure 2 Dose-effect curves for selective serotonin reuptake inhibitors.
These curves are estimated using can you buy lasix the restricted cubic spline function where knots are set at doses 20.0, 23.6 and 44.4 mg/day. For data synthesis, we apply a one-stage (grey, solid) and two-stage (red, dashed) approaches.The 95% confidence bands are shaded around each curve. SSRI, selective serotonin reuptake inhibitor.The synthesised doseâeffect curves across studies can you buy lasix of SSRI. The fluoxetine-equivalent doses are presented versus the predicted absolute can you buy lasix effect. The doseâeffect function is the restricted cubic spline (with knots at 20.0, 23.6 and 44.4).
The solid line represents can you buy lasix the mean absolute effect and the shaded area is its 95% confidence bands. The dashed (horizontal) line represents can you buy lasix the placebo absolute effect at 37.7%. SSRI, selective serotonin reuptake inhibitor." data-icon-position data-hide-link-title="0">Figure 3 The synthesised doseâeffect curves across studies of SSRI. The fluoxetine-equivalent can you buy lasix doses are presented versus the predicted absolute effect. The doseâeffect function is the restricted cubic spline (with knots at 20.0, 23.6 and 44.4).
The solid line represents the can you buy lasix mean absolute effect and the shaded area is its 95% confidence bands. The dashed (horizontal) line represents can you buy lasix the placebo absolute effect at 37.7%. SSRI, selective serotonin reuptake inhibitor.HeterogeneityHeterogeneity in the study-specific coefficients introduces heterogeneity in the relative treatment effects, which is what we will call heterogeneity from now on. It is a function of the dose and can be measured by the variance partition coefficient (VPC).4 The VPC is a study-specific and dose-specific which shows the can you buy lasix percentage of heterogeneity out of the total variability specific to the study. VPC can be computed for each non-referent dose in each study.
An average of the study-specific VPCs can you buy lasix by dose level could be seen as a dose-specific I2. It is can you buy lasix useful to plot the study-specific VPCs (as %) against the dose levels to gauge the level of heterogeneity.ResultsWe illustrate the models by re-analysing a dataset about the role of dose in the efficacy of SSRIs. Drug-specific doses are converted into fluoxetine-equivalents (mg/day) using a validated formula.5 The outcome is response to treatment defined as 50% reduction in symptoms. The data include 60 RCTs, which recruited 15 174 participants in 145 different dose arms can you buy lasix (see online supplemental appendix figure 1, 2 and table 1).Supplemental materialDoseâeffect model within a studyTo exemplify the process, we consider the study by Feighner et al.13 Table 1 presents the data at the five examined dose arms. The four logORs are estimated as the odds of each non-referent category (10, 20, 40, 60 mg/day) relative to the odds in the referent dose (Placebo, 0 mg/day).
The study-specific estimated logORs and their SEs can be used to fit a linear doseâeffect model.A log linear trend is then estimated based on the aggregate data presented by Feighner can you buy lasix et al (figure 1).13 The Greenland and Longnecker method is used to back estimate the covariance of these four empirical logORs used as dependent variable of the linear doseâeffect model.The linear doseâeffect coefficient is estimated at 0.0156 (95% CI 0.0083 to 0.0230) on the log scale. The OR at dose 10 to be which means OR increases by for a 10-unit increase in dose.Biologically, it is quite unrealistic can you buy lasix to assume a constant effect of fluoxetine-equivalents on the relative odds of the outcome. We expect the shape to increase up to a dose level and then flatten out. The exact can you buy lasix value of the dose, at which the doseâeffect model is levelling out, is unknown. And it would be good to specify a doseâeffect can you buy lasix model that is able to capture this plausible mechanism.For this reason, we use a RCS function, rather than a linear function, for fluoxetine-equivalents.
RCSs are generated using three knots at 20, 23.6 and 44.4 dose levels which represent the 10%, 50% and 90% percentiles, of the observed non-zero dose distribution. A Wald-test indicates large can you buy lasix incompatibility between this study and the hypothesis of a linear function ( , p =0.033). Figure 1 indicates a large positive doseâeffect up to 30 mg/day of fluoxetine-equivalents and no increase in the effect beyond that value.The fact that the shape is estimated from just a single study results in a large uncertainty around the RCS curve.Synthesis of doseâeffect shapes across studiesWe first synthesise the doseâeffect coefficients from all studies assuming a random-effects two-stage model. For RCS in the two-stage model, can you buy lasix only 17 studies can be synthesised (those with at least three dose levels). The results are depicted in figure 2 can you buy lasix.
The estimated linear coefficient at 0.0186 (95% CI 0.0118 to 0.0253) and the spline coefficient is â0.0628 (95% CI â0.0876 to â0.0379).The random-effects one-stage model can include all 60 studies. The estimated linear and spline coefficients are very close to those from the two-stage model ( 0.0189 (95% CI 0.0146 to 0.0232) and â0.0621 (95% CI can you buy lasix â0.0814 to â0.0428)) which is also shown in the agreement of the two shapes in figure 2. The important difference between the results from the two approaches is that the confidence bands are tighter from the one-stage due to including double as many studies as the two-stage approach does.In figure 3, we show the probability of response as a function of the dose as estimated from the meta-analysis. After meta-analysing all placebo arms, the probability of response to placebo is estimated at can you buy lasix 37.7% (dashed line in figure 3). Then, increase of the dose up to can you buy lasix 30 mg/day of fluoxetine-equivalent results in 50% probability to respond.
Beyond 40 mg/day, the probability of response flattens out.For the two-stage and the one-stage models, the statistical hypothesis can be rejected with estimated p-values less than 0.001 for both the linear and spline coefficients. This can be seen as a can you buy lasix statistical evidence that the linear model hypothesis is rejected, and the RCS is preferable with both the linear and the spline part. The hypothesis of no dose-effect association is not also accepted (p-value<0.001).Figure 4 shows the variance partition component along with the observed doses. At dose 20 mg/day, the total variability that is attributed solely to heterogeneity ranges between 4% and 40%, which is considered can you buy lasix to be moderate. Overall, the majority of VPC can you buy lasix values does not exceed 60%.The variance partition component of each observed dose (non-referent doses in each study) presented in circles.
Each circle represents a study. The fitted line is LOWESS curve." data-icon-position data-hide-link-title="0">Figure 4 The variance can you buy lasix partition component of each observed dose (non-referent doses in each study) presented in circles. Each circle can you buy lasix represents a study. The fitted line is LOWESS curve.DiscussionResearchers can conduct a DE-MA by following two steps. The first can you buy lasix step is to estimate a doseâeffect curve within each study.
The second step is to synthesise those curves across studies. These two steps can be performed either separately (two-stage model)2 3 or simultaneously (one-stage model).4 In this article, we detail these two models, alongside considerations for statistical testing of the doseâeffect parameters, estimation of heterogeneity and presentation of the can you buy lasix results. We use the presented models to re-analyse RCT data comparing various can you buy lasix SSRIs in terms of response .We describe the models for a dichotomous outcome and the effect size we used as odds ratio. However, the model can be adapted easily to other measures like risk ratio and hazard ratio. Likewise, the model can be employed with other data types such as continuous outcome with (standardised) mean differences.14Recently, two extensions of the presented models have been introduced in the can you buy lasix literature.
The one-stage and two-stage models have been extended to a Bayesian setting15 to take advantage of its great flexibility. One of these advantages is to can you buy lasix implement the exact binomial distribution for binary data, instead of the approximate normal distribution for the relative treatment effect in the frequentist settings. The assumption of a normal distribution can can you buy lasix be hard to meet when the sample size is small as shown in recent simulations.15 The doseâeffect model has been also extended to network meta-analysis which allows for modelling the doseâeffect relationship simultaneously to more than two agents.16 17Researchers should be careful when they report the findings of DE-MA and follow the existing reporting guidelines. Xu et al proposed a checklist with 33 reporting items for such analysis.18 The majority of these items (27) come from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement after some modifications.19 The other six items are added from Meta-analyses Of Observational Studies in Epidemiology checklist to cover key considerations of observational studies.20 They used the proposed checklist to assess quality of reporting in the published DE-MAs. They found that while reporting in the introduction and results was on average good, further improvements are can you buy lasix required in reporting methods.
Xu and colleagues also studied can you buy lasix the association between reporting quality and study characteristics. They observed that studies including more authors or methodologist have a better reporting quality. They conclude that while the quality of reporting has improved over the years, further refinement in the can you buy lasix reporting checklists is required.The main challenge in DE-MA is how to define the doseâeffect shape. The shape selection can be guided by previous studies (such as dose-finding studies), clinical experience and biological plausibility informed by pharmacodynamic and pharmacokinetic studies. Additional evidence could be provided by considering the goodness of fitness measures of various shapes21 or via graphical inspection can you buy lasix of the data.
Yet, the RCS model has sufficient flexibility to can you buy lasix capture different shapes. In our case study, using only three knots was sufficient to capture the expected drug behaviour SSRIs while requires only three dose levels to be reported in at least one study. This makes RCS an attractive choice for the majority of analyses.18 However, the number and location of knots should be chosen carefully based on the anticipated drug behaviour and the clinical knowledge.Researchers may encounter additional challenges if observational studies are synthesised instead of RCTs as it was the case in can you buy lasix this paper. First, defining the dependent and independent variables in observational studies could be difficult. For example, if we want to evaluate the association between the alcohol consumption and the use of tobacco, can you buy lasix the shape will depend on whether alcohol is set as a dependent or independent variable.
Second, categorisation can you buy lasix of non-pharmacological exposures (such as environmental exposure, diet and so on), which are often the focus of observational studies, is often difficult. There might be open-ended categories to which assignment of a specific dose is not obvious (e.g., smoking two packages per day and above) and exposure categories might be differently defined across studies.22 23 These challenges could induce additional uncertainty in the analysis. In such cases, sensitivity analysis is recommended to investigate the robustness of the DE-MA results.In conclusion, the DE-MA enables clinicians to understand how the effect of a drug changes as a function of its dose can you buy lasix. Such analysis should be conducted in practice using the one-stage model that incorporates evidence from all available studies.Research-active clinical services have lower mortality rates and produce higher quality care outcomes, however, recruiting participants to clinical research in the National Health System (NHS) remains challenging.1 A recent study, assessing the feasibility of clinical staff electronically documenting patient consent to discuss research participation, indicated very low patient uptake, limiting its effectiveness as a strategy for improving access to research.2 A follow-on study comparing this âopt-inâ approach with an âopt-outâ approach, whereby patients are informed about research opportunities unless they indicate otherwise, found that patients and staff favoured an âopt-outâ approach and wanted research to be more accessible.3Subsequently, in August 2021, Count me In was developed and launched within Oxford Health â¦.
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TTE, transthoracic echocardiogram." data-icon-position this hyperlink data-hide-link-title="0">Figure 1 hydrochlorothiazide lasix Potential interactions between primary and secondary care. AECG, ambulatory ECG. CP, chest pain.
CTCA, CT coronary hydrochlorothiazide lasix angiography. EHR, electronic health records. EOL, end of life.
EP, electrophysiology hydrochlorothiazide lasix. GP, general practitioner. GPwSI, general practitioner with specialist interest.
GUCH, grown-up hydrochlorothiazide lasix congenital heart disease. HF, heart failure. NT-pro BNP, N terminal pro B-type natriuretic peptide.
OOH, out of hours hydrochlorothiazide lasix. OPD, out patient department. QI, quality improvement.
RAAC, rapid access arrhythmia clinic hydrochlorothiazide lasix. RACP, rapid access chest pain clinic. RAHF, rapid access heart failure.
TLOC, transient loss of hydrochlorothiazide lasix consciousness. TTE, transthoracic echocardiogram.The association of low-income levels with adverse outcomes in patients with heart failure (HF) and the effects of universal health coverage on reducing those differences has not been well documented. In this issue of Heart, Hung and colleagues3 used nationwide data in Taiwan on 633â098 patients hospitalised for HF spanning the years from 1996 (just after implementation of a nationwide health insurance programme) to 2013.
Overall, low-income patients, compared with high-income patients, had hydrochlorothiazide lasix higher in-hospital mortality rates (5.07% vs 2.51%), higher HF readmission rates, and lower utilisation of guideline-directed medical therapy. However, the disparities in outcomes between low-income versus high-income patients appeared to dissipate over time (figure 2).Temporal trends of heart failure (HF) readmission (A) and all-cause mortality (B) by three income groups over time (1996â2013). A marked decrease in the incidence of HF readmission and all-cause mortality was observed over time for the low-income group (expressed as HR, reference.
High-income group) hydrochlorothiazide lasix. A linear trend analysis was used for adjusted HR for low-income versus high-income HF group (as reference) across observation time (per year as ordinal category)." data-icon-position data-hide-link-title="0">Figure 2 Temporal trends of heart failure (HF) readmission (A) and all-cause mortality (B) by three income groups over time (1996â2013). A marked decrease in the incidence of HF readmission and all-cause mortality was observed over time for the low-income group (expressed as HR, reference.
High-income group) hydrochlorothiazide lasix. A linear trend analysis was used for adjusted HR for low-income versus high-income HF group (as reference) across observation time (per year as ordinal category).In an editorial, Zimerman and Rohde4 suggest three possible explanations for the worse outcomes in low-income patients with HF. (1) poverty may be a marker of poor prognosis related to factors such as geographic barriers to access to healthcare, education levels, racial/ethnic biases, unemployment and stress levels.
(2) poverty might cause adverse outcomes indirectly due to issues such as lack of expensive medications, inadequate hydrochlorothiazide lasix nutrition and exercise. And (3) poverty might lead directly to poor health outcomes. The reasons for the improvement over time in income inequities in Taiwan are more difficult to explain.
As the hydrochlorothiazide lasix authors conclude. ÂHealthcare professionals should understand how poverty is an indicator and a cause of poor healthcare and strive to explore alternatives to patients.âAnother interesting article in this issue by Almorad and colleagues5 prospectively evaluated the accuracy of serum D-dimer levels for exclusion of left atrial (LA) thrombus in 142 patients with atrial fibrillation (AF) undergoing transoesophageal echocardiography (TOE) prior to planned cardioversions. Overall, D-dimer levels were lower in the 91% of patients with no LA thrombus compared with the 9% with an LA thrombus (729±611 vs 2376±1081âng/L.
P<0.05). Specificity of a D-dimer level less than 10 times the patient age had a specificity of 66% and sensitivity of 100% for detection of LA thrombus, suggesting that about 60% of the study group could have safely undergone cardioversion without TOE (figure 3).Evolution of D-dimer levels according to age category in the two groups with or without left atrial (LA) thrombus. Above 60âyears, difference between the two groups becomes significant (pFigure 4 Schematic for employing genetic testing in the proband (index patient) and family.
ACC, American College of Cardiology. AHA, American Heart Association. ESC, European Society of Cardiology.
EOL, end can you buy lasix of life. EP, electrophysiology. GP, general practitioner. GPwSI, general practitioner with specialist interest can you buy lasix. GUCH, grown-up congenital heart disease.
HF, heart failure. NT-pro BNP, N terminal pro B-type can you buy lasix natriuretic peptide. OOH, out of hours. OPD, out patient department. QI, quality improvement can you buy lasix.
RAAC, rapid access arrhythmia clinic. RACP, rapid access chest pain clinic. RAHF, rapid access heart failure can you buy lasix. TLOC, transient loss of consciousness. TTE, transthoracic echocardiogram." data-icon-position data-hide-link-title="0">Figure 1 Potential interactions between primary and secondary care.
AECG, ambulatory can you buy lasix ECG. CP, chest pain. CTCA, CT coronary angiography. EHR, electronic health can you buy lasix records. EOL, end of life.
EP, electrophysiology. GP, general can you buy lasix practitioner. GPwSI, general practitioner with specialist interest. GUCH, grown-up congenital heart disease. HF, heart failure can you buy lasix.
NT-pro BNP, N terminal pro B-type natriuretic peptide. OOH, out of hours. OPD, out can you buy lasix patient department. QI, quality improvement. RAAC, rapid access arrhythmia clinic.
RACP, rapid can you buy lasix access chest pain clinic. RAHF, rapid access heart failure. TLOC, transient loss of consciousness. TTE, transthoracic echocardiogram.The association of low-income levels with adverse outcomes in patients with heart failure (HF) and the effects of can you buy lasix universal health coverage on reducing those differences has not been well documented. In this issue of Heart, Hung and colleagues3 used nationwide data in Taiwan on 633â098 patients hospitalised for HF spanning the years from 1996 (just after implementation of a nationwide health insurance programme) to 2013.
Overall, low-income patients, compared with high-income patients, had higher in-hospital mortality rates (5.07% vs 2.51%), higher HF readmission rates, and lower utilisation of guideline-directed medical therapy. However, the disparities in outcomes between low-income versus can you buy lasix high-income patients appeared to dissipate over time (figure 2).Temporal trends of heart failure (HF) readmission (A) and all-cause mortality (B) by three income groups over time (1996â2013). A marked decrease in the incidence of HF readmission and all-cause mortality was observed over time for the low-income group (expressed as HR, reference. High-income group). A linear trend analysis was used for adjusted HR for low-income versus high-income HF group (as reference) across observation time (per year as ordinal category)." data-icon-position data-hide-link-title="0">Figure 2 Temporal trends of heart failure (HF) readmission (A) and all-cause mortality (B) by three income groups over time (1996â2013) can you buy lasix.
A marked decrease in the incidence of HF readmission and all-cause mortality was observed over time for the low-income group (expressed as HR, reference. High-income group).
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In recent years, states have made considerable strides in shifting bumex to lasix conversion iv long-term services and supports (LTSS) systems can you buy lasix away from institutional care and toward home and community-based services (HCBS). In Federal Fiscal Year (FY) 2019, the proportion of Medicaid LTSS expenditures allocated to HCBS was at an bumex to lasix conversion iv all-time high both nationally and for many states. This followed years of steady gains and, for some states, uneven progress, according to a new report documenting Medicaid LTSS expenditures in FY 2019 prepared by Mathematica for the Centers for Medicare &. Medicaid Services (CMS) bumex to lasix conversion iv.
Nationally, HCBS made up 58.6 percent of Medicaid LTSS expenditures in FY 2019, an increase of 2.5 percentage points over FY 2018. At the state level, expenditures ranged bumex to lasix conversion iv from 33.4 percent in Mississippi to 83.3 percent in Oregon. Thirty states spent at least 50 percent of Medicaid dollars on HCBS in FY 2019. This finding showed an improvement over FY 2018, when 27 states met this bumex to lasix conversion iv benchmark.Although nearly all states saw increases in total HCBS expenditures in FY 2019 compared with FY 2018, the goal of rebalancing initiatives is not simply to increase HCBS spending but to shift expenditures away from services provided in institutional settings to HCBS.
Hawaii, Iowa, Kansas, Maine, Massachusetts, Nebraska, North Dakota, South Dakota, Texas, Washington, and Wyoming saw simultaneous increases in HCBS spending in FY 2019 while seeing declines in total institutional spending. The new report also looked at bumex to lasix conversion iv broader trends browse this site in LTSS expenditures. National Medicaid LTSS expenditures totaled $162.1 billion in FY 2019, with $95.0 billion spent on HCBS and $67.1 billion spent on institutional services. In recent years, LTSS expenditures have declined as a proportion of total Medicaid spending, from 47 percent in FY 1988 to bumex to lasix conversion iv 34 percent in FY 2019.
Several factors have led to this decline, including state initiatives to rebalance spending on LTSS systems that promote the use of more cost-effective HCBS and increased spending for Medicaid populations that do not use LTSS. However, spending on managed LTSS (MLTSS) programs continued to grow in recent years, from $6.7 billion in FY 2008 to $47.5 billion in bumex to lasix conversion iv FY 2019. This growth reflects more states using MLTSS and more people receiving LTSS through these programs.Because the report covers FY 2019, it is not clear how the public health emergency might impact LTSS expenditure and rebalancing trends. ÂOne key bumex to lasix conversion iv unknown for FY 2020 is whether upward rebalancing trends will continue, given the major disruptions to Medicaid LTSS delivery during the lasix and the major impact the lasix has had on people living in nursing homes,â said Andrea Wysocki, a lead researcher on this work.
ÂIt is also not clear how these trends will change as states take advantage of new opportunities to expand HCBS through increased funding from CMS. As states focus on increasing home and bumex to lasix conversion iv community-based options and accelerating rebalancing, it will be critical for CMS to continue monitoring Medicaid LTSS expenditures, users, and other measures that reflect LTSS access and quality of care to better understand how the LTSS system meets the needs of Medicaid beneficiaries.â You can read the full report on Medicaid LTSS expenditures here. A companion report on section 1915(c) waiver programs is available here..
In recent years, states have made considerable strides in shifting long-term services and supports can you buy lasix (LTSS) systems away where can you get lasix from institutional care and toward home and community-based services (HCBS). In Federal Fiscal Year (FY) 2019, the proportion of Medicaid LTSS expenditures allocated to HCBS was at an can you buy lasix all-time high both nationally and for many states. This followed years of steady gains and, for some states, uneven progress, according to a new report documenting Medicaid LTSS expenditures in FY 2019 prepared by Mathematica for the Centers for Medicare &. Medicaid Services (CMS) can you buy lasix.
Nationally, HCBS made up 58.6 percent of Medicaid LTSS expenditures in FY 2019, an increase of 2.5 percentage points over FY 2018. At the state level, expenditures ranged from 33.4 can you buy lasix percent in Mississippi to 83.3 percent in Oregon. Thirty states spent at least 50 percent of Medicaid dollars on HCBS in FY 2019. This finding showed an improvement over FY 2018, when 27 states met this benchmark.Although nearly all states saw increases in total HCBS expenditures in FY 2019 compared can you buy lasix with FY 2018, the goal of rebalancing initiatives is not simply to increase HCBS spending but to shift expenditures away from services provided in institutional settings to HCBS.
Hawaii, Iowa, Kansas, Maine, Massachusetts, Nebraska, North Dakota, South Dakota, Texas, Washington, and Wyoming saw simultaneous increases in HCBS spending in FY 2019 while seeing declines in total institutional spending. The new report also looked can you buy lasix at http://rabbitsunlimited.org/?p=318 broader trends in LTSS expenditures. National Medicaid LTSS expenditures totaled $162.1 billion in FY 2019, with $95.0 billion spent on HCBS and $67.1 billion spent on institutional services. In recent years, LTSS expenditures have declined as a proportion of total Medicaid can you buy lasix spending, from 47 percent in FY 1988 to 34 percent in FY 2019.
Several factors have led to this decline, including state initiatives to rebalance spending on LTSS systems that promote the use of more cost-effective HCBS and increased spending for Medicaid populations that do not use LTSS. However, spending on managed LTSS (MLTSS) programs continued to grow in recent can you buy lasix years, from $6.7 billion in FY 2008 to $47.5 billion in FY 2019. This growth reflects more states using MLTSS and more people receiving LTSS through these programs.Because the report covers FY 2019, it is not clear how the public health emergency might impact LTSS expenditure and rebalancing trends. ÂOne key unknown for FY 2020 is whether upward rebalancing trends will continue, given the major disruptions to Medicaid LTSS delivery during the lasix and the major impact the lasix has had on people living can you buy lasix in nursing homes,â said Andrea Wysocki, a lead researcher on this work.
ÂIt is also not clear how these trends will change as states take advantage of new opportunities to expand HCBS through increased funding from CMS. As states focus on increasing home and community-based options and accelerating rebalancing, it will be critical for CMS to continue monitoring Medicaid LTSS expenditures, users, and other measures that reflect LTSS access and quality of care to better understand how the LTSS can you buy lasix system meets the needs of Medicaid beneficiaries.â You can read the full report on Medicaid LTSS expenditures here. A companion report on section 1915(c) waiver programs is available here..
Cheap lasix online
For thousands of years, people looked into the cheap lasix online night sky with their naked eyes -- and told stories about the few visible stars. Then we invented telescopes. In 1840, the philosopher Thomas Carlyle claimed that "the history of the world is but the biography of great men." Then cheap lasix online we started posting on Twitter.Now scientists have invented an instrument to peer deeply into the billions and billions of posts made on Twitter since 2008 -- and have begun to uncover the vast galaxy of stories that they contain."We call it the Storywrangler," says Thayer Alshaabi, a doctoral student at the University of Vermont who co-led the new research.
"It's like a telescope to look -- in real time -- at all this data that people share on social media. We hope people will use it themselves, in the same way you might look up at the stars and ask your own questions."The new tool can give an unprecedented, minute-by-minute view of popularity, from rising political movements to box office flops. From the staggering success of K-pop to signals of emerging new diseases.The story of the Storywrangler -- a curation and analysis of over 150 billion tweets -- and some of its key findings were published on July 16 in the journal Science cheap lasix online Advances.EXPRESSIONS OF THE MANY The team of eight scientists who invented Storywrangler -- from the University of Vermont, Charles River Analytics, and MassMutual Data Science -- gather about ten percent of all the tweets made every day, around the globe.
For each day, they break these tweets into single bits, as well as pairs and triplets, generating frequencies from more than a trillion words, hashtags, handles, symbols and emoji, like "Super Bowl," "Black Lives Matter," "gravitational waves," "#metoo," "hypertension," and "keto diet." advertisement "This is the first visualization tool that allows you to look at one-, two-, and three-word phrases, across 150 different languages, from the inception of Twitter to the present," says Jane Adams, a co-author on the new study who recently finished a three-year position as a data-visualization artist-in-residence at UVM's Complex Systems Center.The online tool, powered by UVM's supercomputer at the Vermont Advanced Computing Core, provides a powerful lens for viewing and analyzing the rise and fall of words, ideas, and stories each day among people around the world. "It's important because it shows major discourses as they're happening," Adams says. "It's quantifying collective attention." Though Twitter does not represent the whole of humanity, it is used by a very large and diverse group of people, which means cheap lasix online that it "encodes popularity and spreading," the scientists write, giving a novel view of discourse not just of famous people, like political figures and celebrities, but also the daily "expressions of the many," the team notes.In one striking test of the vast dataset on the Storywrangler, the team showed that it could be used to potentially predict political and financial turmoil.
They examined the percent change in the use of the words "rebellion" and "crackdown" in various regions of the world. They found that the rise cheap lasix online and fall of these terms was significantly associated with change in a well-established index of geopolitical risk for those same places.WHAT'S HAPPENING?. The global story now being written on social media brings billions of voices -- commenting and sharing, complaining and attacking -- and, in all cases, recording -- about world wars, weird cats, political movements, new music, what's for dinner, deadly diseases, favorite soccer stars, religious hopes and dirty jokes.
advertisement "The Storywrangler gives us a data-driven way to index what regular people are talking about in everyday conversations, not just what reporters or authors have chosen. It's not just the educated or the wealthy or cultural elites," says applied mathematician Chris Danforth, a professor at the University of Vermont who cheap lasix online co-led the creation of the StoryWrangler with his colleague Peter Dodds. Together, they run UVM's Computational Story Lab."This is part of the evolution of science," says Dodds, an expert on complex systems and professor in UVM's Department of Computer Science.
"This tool can enable new approaches in journalism, powerful ways to look at natural language processing, and the development of computational history."How much a few powerful people shape the course of events has been debated for centuries. But, certainly, if we knew what every peasant, soldier, shopkeeper, nurse, and teenager was saying during the French Revolution, we'd have a richly different set of stories about the rise cheap lasix online and reign of Napoleon. "Here's the deep question," says Dodds, "what happened?.
Like, what actually happened?. "GLOBAL SENSOR The UVM team, with support from the National Science Foundation, is using Twitter to demonstrate how chatter on distributed social media can act as a kind of global sensor system -- of what happened, how people reacted, and what might come cheap lasix online next. But other social media streams, from Reddit to 4chan to Weibo, could, in theory, also be used to feed Storywrangler or similar devices.
Tracing the reaction to cheap lasix online major news events and natural disasters. Following the fame and fate of political leaders and sports stars. And opening a view of casual conversation that can provide insights into dynamics ranging from racism to employment, emerging health threats to new memes.In the new Science Advances study, the team presents a sample from the Storywrangler's online viewer, with three global events highlighted.
The death cheap lasix online of Iranian general Qasem Soleimani. The beginning of the hypertension medications lasix. And the Black Lives Matter protests following the murder of George Floyd by Minneapolis police.
The Storywrangler dataset records a sudden spike of tweets cheap lasix online and retweets using the term "Soleimani" on January 3, 2020, when the United States assassinated the general. The strong rise of "hypertension" and the lasix emoji over the spring of 2020 as the disease spread. And a burst of use of the hashtag "#BlackLivesMatter" on and after May 25, 2020, the day George Floyd was murdered."There's a hashtag that's being invented while I'm talking right now," says UVM's cheap lasix online Chris Danforth.
"We didn't know to look for that yesterday, but it will show up in the data and become part of the story."A new method developed by Institute for Systems Biology (ISB) and University of California, Riverside provides new insights into cancer biology by allowing researchers to show how fatty acids are absorbed by single cells.Fatty acids, along with glucose and amino acids, are a major energy source for cellular growth and proliferation, and abnormal fatty acid metabolism is often seen in cancer. Dr. Wei Wei's cheap lasix online lab at ISB and Dr.
Min Xue's lab at UC Riverside have been collaborating for years to develop a series of chemical probes and analytical approaches for quantifying cellular glucose uptake, lactate production, amino acid uptake, and other cancer-related metabolites.Unlike glucose and amino acids, however, the mechanisms underlying the uptake of fatty acids into cells have been lesser known and difficult to discern. The technical tools for measuring fatty acid uptake at the single-cell level are extremely limited."This work is the first example of profiling fatty acid uptake in conjunction with aberrant protein signaling in cancer cells at single-cell resolution and represents an important advance in the single-cell metabolic assay," said ISB Assistant Professor Dr. Wei Wei, co-corresponding author of a just-published paper in the Journal of the American Chemical Society.To profile the fatty acid uptake, the researchers chose a surrogate molecule that cheap lasix online was structurally similar to natural fatty acids.
This similarity tricked the cells into taking up these surrogates like the native ones. Then, using a unique dendrimer molecule -- a tree-like polymer -- the researchers achieved precise quantitation of those surrogates from single cells.Applying this new single-cell tool to a brain cancer model, the researchers identified that fatty acid uptake was differentially regulated by two downstream effectors of the Mammalian Target of Rapamycin (mTOR) -- a critical regulator of cell proliferation and protein synthesis. The results revealed a compensatory activation of fatty acid metabolism upon oncogene inhibition or attenuation of glucose metabolism in these brain cancer cells and cheap lasix online uncovered a novel combination therapy that targets this bioenergetic flexibility to synergistically block the tumor growth."This novel tool opens new avenues for studying how fatty acid metabolism affects biological systems.
It has also inspired us to develop more metabolic probes for single-cell analysis," said UC Riverside Assistant Professor Dr. Min Xue, co-corresponding cheap lasix online author on the paper. Story Source.
Materials provided by Institute for Systems Biology. Note. Content may be edited for style and length.A UC San Francisco study has found that the antibiotic azithromycin was no more effective than a placebo in preventing symptoms of hypertension medications among non-hospitalized patients, and may increase their chance of hospitalization, despite widespread prescription of the antibiotic for the disease."These findings do not support the routine use of azithromycin for outpatient hypertension ," said lead author Catherine E.
Oldenburg, ScD, MPH, an assistant professor with the UCSF Proctor Foundation. hypertension is the lasix that causes hypertension medications.Azithromycin, a broad-spectrum antibiotic, is widely prescribed as a treatment for hypertension medications in the United States and the rest of the world. "The hypothesis is that it has anti-inflammatory properties that may help prevent progression if treated early in the disease," said Oldenburg.
"We did not find this to be the case."The study, which was conducted in collaboration with Stanford University, appears July 16, 2021, in the Journal of the American Medical Association.The study included 263 participants who all tested positive for hypertension within seven days before entering the study. None were hospitalized at the time of enrollment. In a random selection process, 171 participants received a single, 1.2 gram oral dose of azithromycin and 92 received an identical placebo.At day 14 of the study, 50 percent of the participants remained symptom free in both groups.
By day 21, five of the participants who received azithromycin had been hospitalized with severe symptoms of hypertension medications and none of the placebo group had been hospitalized.The researchers concluded that treatment with a single dose of azithromycin compared to placebo did not result in greater likelihood of being symptom-free."Most of the trials done so far with azithromycin have focused on hospitalized patients with pretty severe disease," said Oldenburg. "Our paper is one of the first placebo-controlled studies showing no role for azithromycin in outpatients."Co-authors included Jessica Brogdon, MPH&TM. Cindi Chen, MS.
Catherine A. Cook, MPH. Armin Hinterwirth, PhD.
Elodie Lebas, RN. Travis Redd, MD, MPH. Travis C.
And Benjamin F. Arnold, PhD, MPH, all of UCSF. Senior investigator Thuy Doan, MD, PhD, with the UCSF Proctor Foundation, and Benjamin A.
Pinsky, MD, PhD, of Stanford University.The trial was supported by the Bill and Melinda Gates Foundation (INV-017026). Azithromycin and matching placebo were donated by Pfizer, Inc. (New York, NY).
Thuy Doan was supported in part by a Research to Prevent Blindness Career Development Award. The authors had no conflicts of interest. Story Source.
Materials provided by University of California - San Francisco. Original written by Elizabeth Fernandez. Note.
Content may be edited for style and length.Messenger RNA treatments against hypertension medications were not detected in human milk, according to a small study by UC San Francisco, providing early evidence that the treatment mRNA is not transferred to the infant.The study, which analyzed the breast milk of seven women after they received the mRNA treatments and found no trace of the treatment, offers the first direct data of treatment safety during breastfeeding and could allay concerns among those who have declined vaccination or discontinued breastfeeding due to concern that vaccination might alter human milk. The paper appears in JAMA Pediatrics.Research has demonstrated that treatments with mRNA inhibit transmission of the lasix that causes hypertension medications. The study analyzed the Pfizer and Moderna treatments, both of which contain mRNA.The World Health Organization recommends that breastfeeding people be vaccinated, and the Academy of Breastfeeding Medicine has said there is little risk of treatment nanoparticles or mRNA entering breast tissue or being transferred to milk, which theoretically could affect infant immunity."The results strengthen current recommendations that the mRNA treatments are safe in lactation, and that lactating individuals who receive the hypertension medications treatment should not stop breastfeeding," said corresponding author Stephanie L.
Gaw, MD, PhD, assistant professor of Maternal-Fetal Medicine at UCSF."We didn't detect the treatment associated mRNA in any of the milk samples tested," said lead author Yarden Golan, PhD, a postdoctoral fellow at UCSF. "These findings provide an experimental evidence regarding the safety of the use of mRNA-based treatments during lactation."The study was conducted from December 2020 to February 2021. The mothers' mean age was 37.8 years and their children ranged in age from one month to three years.
Milk samples were collected prior to vaccination and at various times up to 48 hours after vaccination.Researchers found that none of the samples showed detectable levels of treatment mRNA in any component of the milk.The authors noted that the study was limited by the small sample size and said that further clinical data from larger populations were needed to better estimate the effect of the treatments on lactation outcomes.Co-authors are Mary Prahl, MD. Arianna Cassidy, MD. Christine Y.
Flaherman, MD, MPH, all of UCSF.The study was supported by the Marino Family Foundation. The National Institutes of Health (grant numbers K23AI127886 and K08AI141728). The Weizmann Institute of Science-National Postdoctoral Award Program for Advancing Women in Science.
The International Society for Research in Human Milk and Lactation Trainee Bridge Fund. And the Human Frontier Science Program. Disclosures can be found in the paper.
Story Source. Materials provided by University of California - San Francisco. Original written by Elizabeth Fernandez.
Note. Content may be edited for style and length.Primary immunodeficiencies, such as severe combined immunodeficiency disease (SCID), occur when the immune system does not work properly, leading to increased susceptibility to various s, autoimmunity, and cancers. Most of these are inherited and have an underlying genetic causes.
A team at TMDU has identified a novel disorder resulting from a mutation in a protein called AIOLOS, which functions through a previously unknown pathogenic mechanism called heterodimeric interference.The gene family known as IKAROS zinc finger proteins (IKZFs) is associated with the development of lymphocyte, a type of white blood cell involved in the immune response -- meaning that mutations in this family can be involved in immune system deficiencies. Most research so far has focused on IKAROS protein, encoded by the gene IKZF1, although the underlying mechanism by which IKAROS mutations cause the deficiencies is not yet fully understood. A mutation in AIOLOS -- another member of the IKZF family that is encoded by the gene IKZF3 -- has now also been revealed to cause a hereditary immune deficiency.
In addition to not functioning properly itself, the resultant mutant protein interferes with the functioning of IKAROS protein.TMDU researchers uncovered this new mechanism while investigating the cause of a previously undescribed inherited B cell deficiency observed in a family of patients. After sequencing all of the protein-coding genes, the team focused their research on AIOLOS as IKAROS is known to be the cause of B cell deficiency. They showed that the mutant form of AIOLOS that was present in this family did not just fail to function, but actively bound to a different DNA sequence than the normal version of the protein.They went on to use a mouse model that harbors equivalent AIOLOS mutation identified in the patients to outline the underlying pathogenic mechanism.
AIOLOS and IKAROS bind together to form a "heterodimer." The mutant form of AIOLOS retained the ability to bind IKAROS but then interfered with the normal function of IKAROS, and led to the heterodimer being recruited to the incorrect regions of the genome."This is a novel pathogenic mechanism that we termed heterodimeric interference," says lead author Motoi Yamashita, "where a mutant protein in a heterodimer hijacks the function of the normal partner protein."The team were then able to rescue some of the immune function in the mouse model by deleting the dimerization domain of the mutant AIOLOS."The fact we could rescue the phenotype in our mouse model indicates a potential therapeutic approach," says Tomohiro Morio, senior author. "The deletion of the domain responsible for binding IKAROS in the mutant AIOLOS protein could ameliorate the immunodeficiency observed in the patients."The discovery of this new pathogenic mechanism, heterodimeric interference, may well help to shed light on many other disease processes such as autoimmunity and cancer development where mutant proteins act in the same way. Story Source.
Materials provided by Tokyo Medical and Dental University. Note. Content may be edited for style and length..
For thousands Buy zithromax online next day delivery of years, people can you buy lasix looked into the night sky with their naked eyes -- and told stories about the few visible stars. Then we invented telescopes. In 1840, the philosopher Thomas Carlyle claimed that "the history of the world is but the biography of great men." Then we started posting on Twitter.Now scientists have invented an instrument to peer deeply into the billions and billions of posts made on Twitter since 2008 -- and have begun to uncover can you buy lasix the vast galaxy of stories that they contain."We call it the Storywrangler," says Thayer Alshaabi, a doctoral student at the University of Vermont who co-led the new research.
"It's like a telescope to look -- in real time -- at all this data that people share on social media. We hope people will use it themselves, in the same way you might look up at the stars and ask your own questions."The new tool can give an unprecedented, minute-by-minute view of popularity, from rising political movements to box office flops. From the staggering success of K-pop to signals of emerging new diseases.The story of the Storywrangler -- a curation and analysis of over 150 billion tweets -- and some of its key findings were published on July 16 in the journal Science Advances.EXPRESSIONS OF THE MANY The team of eight scientists who invented Storywrangler -- from the University of Vermont, Charles River Analytics, and MassMutual Data Science -- gather about ten percent of all the can you buy lasix tweets made every day, around the globe.
For each day, they break these tweets into single bits, as well as pairs and triplets, generating frequencies from more than a trillion words, hashtags, handles, symbols and emoji, like "Super Bowl," "Black Lives Matter," "gravitational waves," "#metoo," "hypertension," and "keto diet." advertisement "This is the first visualization tool that allows you to look at one-, two-, and three-word phrases, across 150 different languages, from the inception of Twitter to the present," says Jane Adams, a co-author on the new study who recently finished a three-year position as a data-visualization artist-in-residence at UVM's Complex Systems Center.The online tool, powered by UVM's supercomputer at the Vermont Advanced Computing Core, provides a powerful lens for viewing and analyzing the rise and fall of words, ideas, and stories each day among people around the world. "It's important because it shows major discourses as they're happening," Adams says. "It's quantifying collective attention." Though Twitter does not represent the whole of humanity, it is used by a very large and diverse group of people, which means that it "encodes popularity and spreading," the scientists write, giving a novel view of discourse not just of famous people, like political figures and can you buy lasix celebrities, but also the daily "expressions of the many," the team notes.In one striking test of the vast dataset on the Storywrangler, the team showed that it could be used to potentially predict political and financial turmoil.
They examined the percent change in the use of the words "rebellion" and "crackdown" in various regions of the world. They found that the rise and fall of these terms was significantly associated with change in a well-established index of geopolitical can you buy lasix risk for those same places.WHAT'S HAPPENING?. The global story now being written on social media brings billions of voices -- commenting and sharing, complaining and attacking -- and, in all cases, recording -- about world wars, weird cats, political movements, new music, what's for dinner, deadly diseases, favorite soccer stars, religious hopes and dirty jokes.
advertisement "The Storywrangler gives us a data-driven way to index what regular people are talking about in everyday conversations, not just what reporters or authors have chosen. It's not just the educated or the wealthy or cultural elites," can you buy lasix says applied mathematician Chris Danforth, a professor at the University of Vermont who co-led the creation of the StoryWrangler with his colleague Peter Dodds. Together, they run UVM's Computational Story Lab."This is part of the evolution of science," says Dodds, an expert on complex systems and professor in UVM's Department of Computer Science.
"This tool can enable new approaches in journalism, powerful ways to look at natural language processing, and the development of computational history."How much a few powerful people shape the course of events has been debated for centuries. But, certainly, can you buy lasix if we knew what every peasant, soldier, shopkeeper, nurse, and teenager was saying during the French Revolution, we'd have a richly different set of stories about the rise and reign of Napoleon. "Here's the deep question," says Dodds, "what happened?.
Like, what actually happened?. "GLOBAL SENSOR The UVM team, with support from the National Science Foundation, is using Twitter to demonstrate how chatter on distributed can you buy lasix social media can act as a kind of global sensor system -- of what happened, how people reacted, and what might come next. But other social media streams, from Reddit to 4chan to Weibo, could, in theory, also be used to feed Storywrangler or similar devices.
Tracing the reaction to major news can you buy lasix events and natural disasters. Following the fame and fate of political leaders and sports stars. And opening a view of casual conversation that can provide insights into dynamics ranging from racism to employment, emerging health threats to new memes.In the new Science Advances study, the team presents a sample from the Storywrangler's online viewer, with three global events highlighted.
The death of Iranian general Qasem Soleimani can you buy lasix. The beginning of the hypertension medications lasix. And the Black Lives Matter protests following the murder of George Floyd by Minneapolis police.
The Storywrangler dataset records can you buy lasix a sudden spike of tweets and retweets using the term "Soleimani" on January 3, 2020, when the United States assassinated the general. The strong rise of "hypertension" and the lasix emoji over the spring of 2020 as the disease spread. And a burst of can you buy lasix use of the hashtag "#BlackLivesMatter" on and after May 25, 2020, the day George Floyd was murdered."There's a hashtag that's being invented while I'm talking right now," says UVM's Chris Danforth.
"We didn't know to look for that yesterday, but it will show up in the data and become part of the story."A new method developed by Institute for Systems Biology (ISB) and University of California, Riverside provides new insights into cancer biology by allowing researchers to show how fatty acids are absorbed by single cells.Fatty acids, along with glucose and amino acids, are a major energy source for cellular growth and proliferation, and abnormal fatty acid metabolism is often seen in cancer. Dr. Wei Wei's lab at can you buy lasix ISB and Dr.
Min Xue's lab at UC Riverside have been collaborating for years to develop a series of chemical probes and analytical approaches for quantifying cellular glucose uptake, lactate production, amino acid uptake, and other cancer-related metabolites.Unlike glucose and amino acids, however, the mechanisms underlying the uptake of fatty acids into cells have been lesser known and difficult to discern. The technical tools for measuring fatty acid uptake at the single-cell level are extremely limited."This work is the first example of profiling fatty acid uptake in conjunction with aberrant protein signaling in cancer cells at single-cell resolution and represents an important advance in the single-cell metabolic assay," said ISB Assistant Professor Dr. Wei Wei, co-corresponding author can you buy lasix of a just-published paper in the Journal of the American Chemical Society.To profile the fatty acid uptake, the researchers chose a surrogate molecule that was structurally similar to natural fatty acids.
This similarity tricked the cells into taking up these surrogates like the native ones. Then, using a unique dendrimer molecule -- a tree-like polymer -- the researchers achieved precise quantitation of those surrogates from single cells.Applying this new single-cell tool to a brain cancer model, the researchers identified that fatty acid uptake was differentially regulated by two downstream effectors of the Mammalian Target of Rapamycin (mTOR) -- a critical regulator of cell proliferation and protein synthesis. The results revealed a compensatory activation of fatty acid metabolism upon oncogene inhibition or attenuation of glucose metabolism in these brain cancer cells and uncovered a novel combination therapy that targets this bioenergetic flexibility to synergistically block the tumor growth."This can you buy lasix novel tool opens new avenues for studying how fatty acid metabolism affects biological systems.
It has also inspired us to develop more metabolic probes for single-cell analysis," said UC Riverside Assistant Professor Dr. Min Xue, co-corresponding author on can you buy lasix the paper. Story Source.
Materials provided by Institute for Systems Biology. Note. Content may be edited for style and length.A UC San Francisco study has found that the antibiotic azithromycin was no more effective than a placebo in preventing symptoms of hypertension medications among non-hospitalized patients, and may increase their chance of hospitalization, despite widespread prescription of the antibiotic for the disease."These findings do not support the routine use of azithromycin for outpatient hypertension ," said lead author Catherine E.
Oldenburg, ScD, MPH, an assistant professor with the UCSF Proctor Foundation. hypertension is the lasix that causes hypertension medications.Azithromycin, a broad-spectrum antibiotic, is widely prescribed as a treatment for hypertension medications in the United States and the rest of the world. "The hypothesis is that it has anti-inflammatory properties that may help prevent progression if treated early in the disease," said Oldenburg.
"We did not find this to be the case."The study, which was conducted in collaboration with Stanford University, appears July 16, 2021, in the Journal of the American Medical Association.The study included 263 participants who all tested positive for hypertension within seven days before entering the study. None were hospitalized at the time of enrollment. In a random selection process, 171 participants received a single, 1.2 gram oral dose of azithromycin and 92 received an identical placebo.At day 14 of the study, 50 percent of the participants remained symptom free in both groups.
By day 21, five of the participants who received azithromycin had been hospitalized with severe symptoms of hypertension medications and none of the placebo group had been hospitalized.The researchers concluded that treatment with a single dose of azithromycin compared to placebo did not result in greater likelihood of being symptom-free."Most of the trials done so far with azithromycin have focused on hospitalized patients with pretty severe disease," said Oldenburg. "Our paper is one of the first placebo-controlled studies showing no role for azithromycin in outpatients."Co-authors included Jessica Brogdon, MPH&TM. Cindi Chen, MS.
Catherine A. Cook, MPH. Armin Hinterwirth, PhD.
Elodie Lebas, RN. Travis Redd, MD, MPH. Travis C.
And Benjamin F. Arnold, PhD, MPH, all of UCSF. Senior investigator Thuy Doan, MD, PhD, with the UCSF Proctor Foundation, and Benjamin A.
Pinsky, MD, PhD, of Stanford University.The trial was supported by the Bill and Melinda Gates Foundation (INV-017026). Azithromycin and matching placebo were donated by Pfizer, Inc. (New York, NY).
Thuy Doan was supported in part by a Research to Prevent Blindness Career Development Award. The authors had no conflicts of interest. Story Source.
Materials provided by University of California - San Francisco. Original written by Elizabeth Fernandez. Note.
Content may be edited for style and length.Messenger RNA treatments against hypertension medications were not detected in human milk, according to a small study by UC San Francisco, providing early evidence that the treatment mRNA is not transferred to the infant.The study, which analyzed the breast milk of seven women after they received the mRNA treatments and found no trace of the treatment, offers the first direct data of treatment safety during breastfeeding and could allay concerns among those who have declined vaccination or discontinued breastfeeding due to concern that vaccination might alter human milk. The paper appears in JAMA Pediatrics.Research has demonstrated that treatments with mRNA inhibit transmission of the lasix that causes hypertension medications. The study analyzed the Pfizer and Moderna treatments, both of which contain mRNA.The World Health Organization recommends that breastfeeding people be vaccinated, and the Academy of Breastfeeding Medicine has said there is little risk of treatment nanoparticles or mRNA entering breast tissue or being transferred to milk, which theoretically could affect infant immunity."The results strengthen current recommendations that the mRNA treatments are safe in lactation, and that lactating individuals who receive the hypertension medications treatment should not stop breastfeeding," said corresponding author Stephanie L.
Gaw, MD, PhD, assistant professor of Maternal-Fetal Medicine at UCSF."We didn't detect the treatment associated mRNA in any of the milk samples tested," said lead author Yarden Golan, PhD, a postdoctoral fellow at UCSF. "These findings provide an experimental evidence regarding the safety of the use of mRNA-based treatments during lactation."The study was conducted from December 2020 to February 2021. The mothers' mean age was 37.8 years and their children ranged in age from one month to three years.
Milk samples were collected prior to vaccination and at various times up to 48 hours after vaccination.Researchers found that none of the samples showed detectable levels of treatment mRNA in any component of the milk.The authors noted that the study was limited by the small sample size and said that further clinical data from larger populations were needed to better estimate the effect of the treatments on lactation outcomes.Co-authors are Mary Prahl, MD. Arianna Cassidy, MD. Christine Y.
Flaherman, MD, MPH, all of UCSF.The study was supported by the Marino Family Foundation. The National Institutes of Health (grant numbers K23AI127886 and K08AI141728). The Weizmann Institute of Science-National Postdoctoral Award Program for Advancing Women in Science.
The International Society for Research in Human Milk and Lactation Trainee Bridge Fund. And the Human Frontier Science Program. Disclosures can be found in the paper.
Story Source. Materials provided by University of California - San Francisco. Original written by Elizabeth Fernandez.
Note. Content may be edited for style and length.Primary immunodeficiencies, such as severe combined immunodeficiency disease (SCID), occur when the immune system does not work properly, leading to increased susceptibility to various s, autoimmunity, and cancers. Most of these are inherited and have an underlying genetic causes.
A team at TMDU has identified a novel disorder resulting from a mutation in a protein called AIOLOS, which functions through a previously unknown pathogenic mechanism called heterodimeric interference.The gene family known as IKAROS zinc finger proteins (IKZFs) is associated with the development of lymphocyte, a type of white blood cell involved in the immune response -- meaning that mutations in this family can be involved in immune system deficiencies. Most research so far has focused on IKAROS protein, encoded by the gene IKZF1, although the underlying mechanism by which IKAROS mutations cause the deficiencies is not yet fully understood. A mutation in AIOLOS -- another member of the IKZF family that is encoded by the gene IKZF3 -- has now also been revealed to cause a hereditary immune deficiency.
In addition to not functioning properly itself, the resultant mutant protein interferes with the functioning of IKAROS protein.TMDU researchers uncovered this new mechanism while investigating the cause of a previously undescribed inherited B cell deficiency observed in a family of patients. After sequencing all of the protein-coding genes, the team focused their research on AIOLOS as IKAROS is known to be the cause of B cell deficiency. They showed that the mutant form of AIOLOS that was present in this family did not just fail to function, but actively bound to a different DNA sequence than the normal version of the protein.They went on to use a mouse model that harbors equivalent AIOLOS mutation identified in the patients to outline the underlying pathogenic mechanism.
AIOLOS and IKAROS bind together to form a "heterodimer." The mutant form of AIOLOS retained the ability to bind IKAROS but then interfered with the normal function of IKAROS, and led to the heterodimer being recruited to the incorrect regions of the genome."This is a novel pathogenic mechanism that we termed heterodimeric interference," says lead author Motoi Yamashita, "where a mutant protein in a heterodimer hijacks the function of the normal partner protein."The team were then able to rescue some of the immune function in the mouse model by deleting the dimerization domain of the mutant AIOLOS."The fact we could rescue the phenotype in our mouse model indicates a potential therapeutic approach," says Tomohiro Morio, senior author. "The deletion of the domain responsible for binding IKAROS in the mutant AIOLOS protein could ameliorate the immunodeficiency observed in the patients."The discovery of this new pathogenic mechanism, heterodimeric interference, may well help to shed light on many other disease processes such as autoimmunity and cancer development where mutant proteins act in the same way. Story Source.
Materials provided by Tokyo Medical and Dental University. Note. Content may be edited for style and length..