Prognostic utility of blood pressure-adjusted global and basal systolic longitudinal strain

Assessment of global longitudinal systolic strain (GLS) and longitudinal systolic strain of the basal segments (BLS) has shown prognostic value in cardiac disorders. However, strain is reduced with increased afterload. We assessed the prognostic value of GLS and BLS adjusted for afterload. GLS and BLS were determined in 272 subjects with normal ejection fraction and no known coronary disease, or significant valve disease. Systolic blood pressure (SP) and diastolic blood pressure (DP) obtained at the time of echocardiography were used to adjust GLS and BLS as follows: strain×SP (mmHg)/120 mmHg and strain×DP (mmHg)/80 mmHg. Patients were followed for cardiac events and mortality. The mean age was 53±15 years and 53% had hypertension. There were 19 cardiac events and 70 deaths over a mean follow-up of 26±14 months. Cox analysis showed that left ventricular mass index (P=0.001), BLS (P<0.001), and DP-adjusted BLS (P<0.001) were independent predictors of cardiac events. DP-adjusted BLS added incremental value (P<0.001) to the other two predictors and had an area under the curve of 0.838 for events. DP (P=0.001), age (P=0.001), ACE inhibitor use (P=0.017), and SP-adjusted BLS (P=0.012) were independent predictors of mortality. SP-adjusted BLS added incremental value (P=0.014) to the other independent predictors. In conclusion, DP-adjusted BLS and SP-adjusted BLS were independent predictors of cardiac events and mortality, respectively. Blood pressure-adjusted strain added incremental prognostic value to other predictors of outcome

Markers of Maternal and Infant Metabolism are Associated with Ventricular Dysfunction in Infants of Obese Women with Type 2 Diabetes

BACKGROUND To test the hypothesis that infants born to obese women with pregestational type 2 diabetes mellitus (IBDM) have ventricular dysfunction at one month that is associated with markers of maternal lipid and glucose metabolism. METHODS In a prospective observational study of IBDM (OB+DM, n=25), echocardiography measures of septal, left (LV) and right ventricular (RV) function and structure were compared at one month of age to infants born to OB mothers without DM (OB, n=24), and non-OB without DM (Lean, n=23). Basal maternal lipid and glucose kinetics and maternal plasma and infant (cord) plasma were collected for hormone and cytokine analyses. RESULTS RV, LV, and septal strain measures were lower in the OB+DM infants vs. other groups, without evidence of septal hypertrophy. Maternal hepatic insulin sensitivity, maternal plasma free fatty acid concentration, and cord plasma insulin and leptin most strongly predicted decreased septal strain in the OB+DM infants. CONCLUSION IBDM’s have reduced septal function at one month in the absence of septal hypertrophy, which is associated with altered maternal and infant lipid and glucose metabolism. These findings suggest that maternal obesity and DM may have a prolonged impact on the cardiovascular health of their offspring, despite resolution of cardiac hypertrophy

PCA-Correlated SNPs for Structure Identification in Worldwide Human Populations

Existing methods to ascertain small sets of markers for the identification of human population structure require prior knowledge of individual ancestry. Based on Principal Components Analysis (PCA), and recent results in theoretical computer science, we present a novel algorithm that, applied on genomewide data, selects small subsets of SNPs (PCA-correlated SNPs) to reproduce the structure found by PCA on the complete dataset, without use of ancestry information. Evaluating our method on a previously described dataset (10,805 SNPs, 11 populations), we demonstrate that a very small set of PCA-correlated SNPs can be effectively employed to assign individuals to particular continents or populations, using a simple clustering algorithm. We validate our methods on the HapMap populations and achieve perfect intercontinental differentiation with 14 PCA-correlated SNPs. The Chinese and Japanese populations can be easily differentiated using less than 100 PCA-correlated SNPs ascertained after evaluating 1.7 million SNPs from HapMap. We show that, in general, structure informative SNPs are not portable across geographic regions. However, we manage to identify a general set of 50 PCA-correlated SNPs that effectively assigns individuals to one of nine different populations. Compared to analysis with the measure of informativeness, our methods, although unsupervised, achieved similar results. We proceed to demonstrate that our algorithm can be effectively used for the analysis of admixed populations without having to trace the origin of individuals. Analyzing a Puerto Rican dataset (192 individuals, 7,257 SNPs), we show that PCA-correlated SNPs can be used to successfully predict structure and ancestry proportions. We subsequently validate these SNPs for structure identification in an independent Puerto Rican dataset. The algorithm that we introduce runs in seconds and can be easily applied on large genome-wide datasets, facilitating the identification of population substructure, stratification assessment in multi-stage whole-genome association studies, and the study of demographic history in human populations

Bounds for Lepton Flavor Violation and the Pseudoscalar Higgs in the General Two Higgs Doublet Model using g−2g-2 muon factor

Current experimental data from the $g-2$ muon factor, seems to show the necessity of physics beyond the Standard Model (SM), since the difference between SM and experimental predictions is 2.6$\sigma$. In the framework of the General Two Higgs Doublet Model (2HDM), we calculate the muon anomalous magnetic moment to get lower and upper bounds for the Flavour Changing (FC) Yukawa couplings in the leptonic sector. We also obtain lower bounds for the mass of the pseudoscalar Higgs ($m_{A^0}$) as a function of the parameters of the model.Comment: 12 pages, RevTex4, 5 figures. Improved presentation, updated experimental data, amplified analysis, new figures added. Subbmited to Phys. Rev.

Stock price reaction to profit warnings: The role of time-varying betas

This study investigates the role of time-varying betas, event-induced variance and conditional heteroskedasticity in the estimation of abnormal returns around important news announcements. Our analysis is based on the stock price reaction to profit warnings issued by a sample of firms listed on the Hong Kong Stock Exchange. The standard event study methodology indicates the presence of price reversal patterns following both positive and negative warnings. However, incorporating time-varying betas, event-induced variance and conditional heteroskedasticity in the modelling process results in post-negative-warning price patterns that are consistent with the predictions of the efficient market hypothesis. These adjustments also cause the statistical significance of some post-positive-warning cumulative abnormal returns to disappear and their magnitude to drop to an extent that minor transaction costs would eliminate the profitability of the contrarian strategy

Why do UK banks securitize?

Working paper seriesThe eight years from 2000 to 2008 saw a rapid growth in the use of securitization by UK banks. We aim to identify the reasons that contributed to this rapid growth. The time period (2000 to 2010) covered by our study is noteworthy as it covers the pre- nancial crisis credit- boom, the peak of the nancial crisis and its aftermath. In the wake of the nancial crisis, many governments, regulators and political commentators have pointed an accusing nger at the securitization market - even in the absence of a detailed statistical and economic analysis. We contribute to the extant literature by performing such an analysis on UK banks, fo- cussing principally on whether it is the need for liquidity (i.e. the funding of their balance sheets), or the desire to engage in regulatory capital arbitrage or the need for credit risk trans- fer that has led to UK banks securitizing their assets. We show that securitization has been signi cantly driven by liquidity reasons. In addition, we observe a positive link between securitization and banks credit risk. We interpret these latter ndings as evidence that UK banks which engaged in securitization did so, in part, to transfer credit risk and that, in comparison to UK banks which did not use securitization, they had more credit risk to transfer in the sense that they originated lower quality loans and held lower quality assets. We show that banks which issued more asset-backed securities before the nancial crisis su¤ered more defaults after the nancial crisis.The eight years from 2000 to 2008 saw a rapid growth in the use of securitization by UK banks. We aim to identify the reasons that contributed to this rapid growth. The time period (2000 to 2010) covered by our study is noteworthy as it covers the pre-financial crisis credit- boom, the peak of the financial crisis and its aftermath. In the wake of the financial crisis, many governments, regulators and political commentators have pointed an accusing finger at the securitization market - even in the absence of a detailed statistical and economic analysis. We contribute to the extant literature by performing such an analysis on UK banks, fo- cussing principally on whether it is the need for liquidity (i.e. the funding of their balance sheets), or the desire to engage in regulatory capital arbitrage or the need for credit risk trans- fer that has led to UK banks securitizing their assets. We show that securitization has been significantly driven by liquidity reasons. In addition, we observe a positive link between securitization and banks credit risk. We interpret these latter findings as evidence that UK banks which engaged in securitization did so, in part, to transfer credit risk and that, in comparison to UK banks which did not use securitization, they had more credit risk to transfer in the sense that they originated lower quality loans and held lower quality assets. We show that banks which issued more asset-backed securities before the financial crisis suffered more defaults after the financial crisis

The systematic guideline review: method, rationale, and test on chronic heart failure

Background: Evidence-based guidelines have the potential to improve healthcare. However, their de-novo-development requires substantial resources-especially for complex conditions, and adaptation may be biased by contextually influenced recommendations in source guidelines. In this paper we describe a new approach to guideline development-the systematic guideline review method (SGR), and its application in the development of an evidence-based guideline for family physicians on chronic heart failure (CHF). Methods: A systematic search for guidelines was carried out. Evidence-based guidelines on CHF management in adults in ambulatory care published in English or German between the years 2000 and 2004 were included. Guidelines on acute or right heart failure were excluded. Eligibility was assessed by two reviewers, methodological quality of selected guidelines was appraised using the AGREE instrument, and a framework of relevant clinical questions for diagnostics and treatment was derived. Data were extracted into evidence tables, systematically compared by means of a consistency analysis and synthesized in a preliminary draft. Most relevant primary sources were re-assessed to verify the cited evidence. Evidence and recommendations were summarized in a draft guideline. Results: Of 16 included guidelines five were of good quality. A total of 35 recommendations were systematically compared: 25/35 were consistent, 9/35 inconsistent, and 1/35 un-rateable (derived from a single guideline). Of the 25 consistencies, 14 were based on consensus, seven on evidence and four differed in grading. Major inconsistencies were found in 3/9 of the inconsistent recommendations. We re-evaluated the evidence for 17 recommendations (evidence-based, differing evidence levels and minor inconsistencies) - the majority was congruent. Incongruity was found where the stated evidence could not be verified in the cited primary sources, or where the evaluation in the source guidelines focused on treatment benefits and underestimated the risks. The draft guideline was completed in 8.5 man-months. The main limitation to this study was the lack of a second reviewer. Conclusion: The systematic guideline review including framework development, consistency analysis and validation is an effective, valid, and resource saving-approach to the development of evidence-based guidelines

Management of patients with biliary sphincter of Oddi disorder without sphincter of Oddi manometry

<p>Abstract</p> <p>Background</p> <p>The paucity of controlled data for the treatment of most biliary sphincter of Oddi disorder (SOD) types and the incomplete response to therapy seen in clinical practice and several trials has generated controversy as to the best course of management of these patients. In this observational study we aimed to assess the outcome of patients with biliary SOD managed without sphincter of Oddi manometry.</p> <p>Methods</p> <p>Fifty-nine patients with biliary SOD (14% type I, 51% type II, 35% type III) were prospectively enrolled. All patients with a dilated common bile duct were offered endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy whereas all others were offered medical treatment alone. Patients were followed up for a median of 15 months and were assessed clinically for response to treatment.</p> <p>Results</p> <p>At follow-up 15.3% of patients reported complete symptom resolution, 59.3% improvement, 22% unchanged symptoms, and 3.4% deterioration. Fifty-one percent experienced symptom resolution/improvement on medical treatment only, 12% after sphincterotomy, and 10% after both medical treatment/sphincterotomy. Twenty percent experienced at least one recurrence of symptoms after initial response to medical and/or endoscopic treatment. Fifty ERCP procedures were performed in 24 patients with an 18% complication rate (16% post-ERCP pancreatitis). The majority of complications occurred in the first ERCP these patients had. Most complications were mild and treated conservatively. Age, gender, comorbidity, SOD type, dilated common bile duct, presence of intact gallbladder, or opiate use were not related to the effect of treatment at the end of follow-up (p > 0.05 for all).</p> <p>Conclusions</p> <p>Patients with biliary SOD may be managed with a combination of endoscopic sphincterotomy (performed in those with dilated common bile duct) and medical therapy without manometry. The results of this approach with regards to symptomatic relief and ERCP complication rate are comparable to those previously published in the literature in cohorts of patients assessed by manometry.</p

Decision or No Decision: How Do Patient–Physician Interactions End and What Matters?

BACKGROUND: A clearly stated clinical decision can induce a cognitive closure in patients and is an important investment in the end of patient–physician communications. Little is known about how often explicit decisions are made in primary care visits. OBJECTIVE: To use an innovative videotape analysis approach to assess physicians’ propensity to state decisions explicitly, and to examine the factors influencing decision patterns. DESIGN: We coded topics discussed in 395 videotapes of primary care visits, noting the number of instances and the length of discussions on each topic, and how discussions ended. A regression analysis tested the relationship between explicit decisions and visit factors such as the nature of topics under discussion, instances of discussion, the amount of time the patient spoke, and competing demands from other topics. RESULTS: About 77% of topics ended with explicit decisions. Patients spoke for an average of 58 seconds total per topic. Patients spoke more during topics that ended with an explicit decision, (67 seconds), compared with 36 seconds otherwise. The number of instances of a topic was associated with higher odds of having an explicit decision (OR = 1.73, p < 0.01). Increases in the number of topics discussed in visits (OR = 0.95, p < .05), and topics on lifestyle and habits (OR = 0.60, p < .01) were associated with lower odds of explicit decisions. CONCLUSIONS: Although discussions often ended with explicit decisions, there were variations related to the content and dynamics of interactions. We recommend strengthening patients’ voice and developing clinical tools, e.g., an “exit prescription,” to improving decision making

Deciding Together?:Best Interests and Shared Decision-Making in Paediatric Intensive Care

In the western healthcare, shared decision making has become the orthodox approach to making healthcare choices as a way of promoting patient autonomy. Despite the fact that the autonomy paradigm is poorly suited to paediatric decision making, such an approach is enshrined in English common law. When reaching moral decisions, for instance when it is unclear whether treatment or non-treatment will serve a child’s best interests, shared decision making is particularly questionable because agreement does not ensure moral validity. With reference to current common law and focusing on intensive care practice, this paper investigates what claims shared decision making may have to legitimacy in a paediatric intensive care setting. Drawing on key texts, I suggest these identify advantages to parents and clinicians but not to the child who is the subject of the decision. Without evidence that shared decision making increases the quality of the decision that is being made, it appears that a focus on the shared nature of a decision does not cohere with the principle that the best interests of the child should remain paramount. In the face of significant pressures toward the displacement of the child’s interests in a shared decision, advantages of a shared decision to decisional quality require elucidation. Although a number of arguments of this nature may have potential, should no such advantages be demonstrable we have cause to revise our commitment to either shared decision making or the paramountcy of the child in these circumstances