Preponderance Of Evidence Research Articles

Cardioprotection by Metformin: Beneficial Effects Beyond Glucose Reduction.

Metformin is a biguanide that is widely used as an insulin-sparing agent to treat diabetes. When compared with the general population, diabetics are twice as likely to die from fatal myocardial infarction and congestive heart failure (CHF). There has been a significant concern regarding the use of metformin in patients with CHF because of their higher tendency to develop lactic acidosis. However, large epidemiological trials have reported better cardiovascular prognosis with metformin compared to other glucose-lowering agents among diabetics. Additionally, metformin has reduced the risk of reinfarction and all-cause mortality in patients with coronary artery disease and CHF, respectively. The protection against cardiovascular diseases appears to be independent of the anti-hyperglycemic effects of metformin. These effects are mediated through an increase in 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and by increased phosphorylation of endothelial nitric oxide synthase (eNOS) in cardiomyocytes with an increased production of nitric oxide (NO). Metformin preconditions the heart against ischemia-reperfusion injury and may improve myocardial remodeling after an ischemic insult. The preponderance of evidence currently suggests that metformin is safe in patients with CHF, prompting the Food and Drug Administration to remove CHF as a contraindication from the package insert of all generic metformin preparations. In this narrative, along with a limited meta-analysis of available studies, we have reviewed the pleiotropic (non-glucose-lowering) effects of metformin that potentially contribute to its cardioprotective properties. Additionally, we have reviewed issues surrounding the safety of metformin in patients with cardiac diseases.

Role of fractional flow reserve in the evaluation and management of patients with acute coronary syndrome.

The aim of this review is to appraise the clinical and prognostic value and pitfalls of FFR across different spectra of ACS presentations and lesion subsets. Preponderance of evidence on this subject is from observational nonrandomized studies with conflicting results and short-term outcomes. Multiple recent studies evaluating the role of FFR-based deferral in non-STE ACS from a potentially culprit lesion have demonstrated poor long-term prognosis as related to future risk of target vessel failure (myocardial infarction/revascularization). The prognostic power of nonischemic FFR seems favorable in clear nonculprit ACS lesions. Fractional flow reserve evaluation can be helpful in clinical decision-making for certain subsets of ACS patients and lesions. Definite ACS-producing lesions should not be evaluated using FFR due to altered pathophysiology and distinct mechanisms underlying the disease process. In uncertain culprit lesions, FFR may be useful with complementary intracoronary imaging.

Challenges and opportunities in the use of low‐energy sugar replacers

Challenges and opportunities in the use of low‐energy sugar replacers

What additional treatment is indicated for oral cavity cancer with isolated perineural invasion?

What additional treatment is indicated for oral cavity cancer with isolated perineural invasion?

Abstract WP3: Occluded Vessel Location is a Predictor of Clinical Outcome in the Natural History of Acute Ischemic Stroke From Large Vessel Occlusion Eligible for Mechanical Thrombectomy

Purpose: The preponderance of evidence suggests that target vessel locations (TVL) are important predictors of outcomes in acute ischemic stroke (AIS). However, few studies have examined in detail their correlation in the natural history of a cohort of patients with ICA, M1 and M2 vessel occlusions who are eligible for, but untreated with, mechanical thrombectomy. Hypothesis: We hypothesize that, similar to the broader stroke cohort, there is a correlation between TVL and outcomes. Methods: The SOS and FIRST trials were prospective, multicenter studies evaluating the natural history of a stroke cohort eligible for mechanical thrombectomy but did not receive the treatment. Enrolled patients presented with symptoms of AIS due to LVO and were refractory or ineligible for rtPA treatment. Functional independence was defined as a mRS score 0-2 at 90 days. Incidence of death, intracranial hemorrhage (ICH), serious adverse events (SAEs), and mortality were assessed for association with TVL. Results: A total of 238 patients (median age: 71) met study criteria. Occlusions were reported in the ICA (32.5%), M1 (54.4%), M2 (8.9%), and basilar artery (1.7%). At 90 days, 9.2% of ICA, 12.1% of MCA M1, 25.0% of MCA M2, and 0.0% of basilar artery patients achieved functional independence as defined by a mRS score of 0-2. Although the rate of SAEs was similar between ICA (83.3%), M1 (81.4%), and basilar artery (75%), the rate was lowered in patients with M2 occlusion (61.9%, p<0.05). There were also significantly fewer mortalities associated with occlusion of the M1 (27.4%, p<0.01) and M2 (10.0%, p<0.01) when compared to ICA occlusions (40.8%). Conclusion: Similar to the broader patients with AIS, there is a significant correlation between TVL and outcomes in patients with LVO eligible for mechanical thrombectomy. Although occlusion of smaller vessels (i.e. M2) predicts better functional outcome, 75% of patients will not reach functional independence.

Carotenoid glycosides from cyanobacteria are teratogenic in the zebrafish (Danio rerio) embryo model

Toxigenicity of cyanobacteria is widely associated with production of several well-described toxins that pose recognized threats to human and ecosystem health as part of both freshwater eutrophication, and episodic blooms in freshwater and coastal habitats. However, a preponderance of evidence indicates contribution of additional bioactive, and potentially toxic, metabolites. In the present study, the zebrafish (Danio rerio) embryo was used as a model of vertebrate development to identify, and subsequently isolate and characterize, teratogenic metabolites from two representative strains of C. raciborskii. Using this approach, three chemically related carotenoids - and specifically the xanthophyll glycosides, myxol 2′-glycoside (1), 4-ketomyxol 2′-glycoside (2) and 4-hydroxymyxol 2′-glycoside (3) - which are, otherwise, well known pigment molecules from cyanobacteria were isolated as potently teratogenic compounds. Carotenoids are recognized “pro-retinoids” with retinoic acid, as a metabolic product of the oxidative cleavage of carotenoids, established as both key mediator of embryo development and, consequently, a potent teratogen. Accordingly, a comparative toxicological study of chemically diverse carotenoids, as well as apocarotenoids and retinoids, was undertaken. Based on this, a working model of the developmental toxicity of carotenoids as pro-retinoids is proposed, and the teratogenicity of these widespread metabolites is discussed in relation to possible impacts on aquatic vertebrate populations.

Vancomycin and the Risk of AKI: A Systematic Review and Meta-Analysis.

Vancomycin has been in use for more than half a century, but whether it is truly nephrotoxic and to what extent are still highly controversial. The objective of this study was to determine the risk of AKI attributable to intravenous vancomycin. We conducted a systematic review of randomized, controlled trials and cohort studies that compared patients treated with intravenous vancomycin with a control group of patients given a comparator nonglycopeptide antibiotic and in which kidney function or kidney injury outcomes were reported. PubMed and Cochrane Library were searched from 1990 to September of 2015. Two reviewers extracted data and assessed study risk of bias, and one reviewer adjudicated the assessments. A meta-analysis was conducted on seven randomized, controlled trials (total of 4033 patients). Moderate quality evidence suggested that vancomycin treatment is associated with a higher risk of AKI, with a relative risk of 2.45 (95% confidence interval, 1.69 to 3.55). The risk of kidney injury was similar in patients treated for skin and soft tissue infections compared with those treated for nosocomial pneumonia and other complicated infections. There was an uncertain risk of reporting bias, because kidney function was not a prespecified outcome in any of the trials. The preponderance of evidence was judged to be indirect, because the majority of studies compared vancomycin specifically with linezolid. Our findings suggest that there is a measurable risk of AKI associated with vancomycin, but the strength of the evidence is moderate. A randomized, controlled trial designed to study kidney function as an outcome would be needed to draw unequivocal conclusions.

Review of the Empirical Business Services Sourcing Literature: An Update and Future Directions

The 2010 Journal of Information Technology (JIT) article, ‘A Review of the IT Outsourcing Empirical Literature and Future Research Directions,’ analyzed 741 findings on the determinants of Information Technology Outsourcing (ITO) decisions and outcomes from 164 empirical articles published between 1992 and 2010. Using the same coding method, the 2011 JIT article, ‘Business Process Outsourcing Studies: A Critical Review and Research Directions,’ analyzed 615 findings on the determinants of Business Process Outsourcing (BPO) decisions and outcomes from 67 empirical articles published between 1996 and 2011. Taken together, these two reviews found that the preponderance of evidence from both ITO and BPO research streams produced largely consistent results pertaining to the categories of independent variables that affected outsourcing decisions and outcomes. To investigate the most current research findings on business services, which comprise ITO and BPO, and to compare the results with the prior JIT reviews, we replicated the method used in the prior JIT reviews. In this update, we examined 174 newly published articles across 78 academic journals published between 2010 and 2014. We found that researchers have significantly expanded the variables of interest in the last 4 years. In all, researchers investigated 69 new variables. Compared with earlier research, this review of recent articles found a deeper exploration of the direct effects of transaction attributes, sourcing motivations, client and provider capabilities, and governance on sourcing decisions and outcomes. Researchers have also studied a broader variety of sourcing decisions, including shared services, captive centers, rural sourcing and backsourcing. This update also found a more nuanced understanding of relational governance and its interaction with contractual governance. We assessed the research progress that has been made on ten previously identified gaps in knowledge. We proposed a future research agenda that includes continued, incremental progress on ‘normal science’ research questions, as well as more ambitious research goals. We challenged researchers to investigate how sourcing clients, providers, and advisors can protect jobs, protect the environment, and ensure security in an increasingly automated world.

A Review of the Evidence Supporting the Taste of Non‐esterified Fatty Acids in Humans

AbstractDietary fats contribute to the flavor of foods by multiple mechanisms. A role for their taste has only recently gained credence. Current evidence indicates non‐esterified fatty acids (NEFA) are the effective stimuli for the taste component. CD36 and GPR120 are putative receptors, but may not fully account for the totality of the range of sensations elicited by fatty acids. The sensory quality of long‐chain NEFA is not adequately characterized by commonly accepted taste primary qualities and has been termed oleogustus. There is marked individual variability in sensitivity to the taste of NEFA prompting hypotheses of genetic and environmental determinants. Though an association with BMI has been proposed, the preponderance of evidence is not supportive. The importance of oleogustus has not been fully established, but likely contributes to flavor, which influences food choice as well as lipid metabolism and chronic disease risk. A better understanding of oleogustus may provide insights useful for product formulation.

The Strange Case of Smoking and Schizophrenia—The Epidemiology Detectives Are on the Trail

The Strange Case of Smoking and Schizophrenia—The Epidemiology Detectives Are on the Trail

Heterogeneous effects of old age on human muscle oxidative capacity in vivo: a systematic review and meta-analysis.

Despite intensive efforts to understand the extent to which skeletal muscle mitochondrial capacity changes in older humans, the answer to this important question remains unclear. To determine what the preponderance of evidence from in vivo studies suggests, we conducted a systematic review and meta-analysis of the effects of age on muscle oxidative capacity as measured noninvasively by magnetic resonance spectroscopy. A secondary aim was to examine potential moderators contributing to differences in results across studies, including muscle group, physical activity status, and sex. Candidate papers were identified from PubMed searches (n = 3561 papers) and the reference lists of relevant papers. Standardized effects (Hedges' g) were calculated for age and each moderator using data from the 22 studies that met the inclusion criteria (n = 28 effects). Effects were coded as positive when older (age, ≥55 years) adults had higher muscle oxidative capacity than younger (age, 20-45 years) adults. The overall effect of age on oxidative capacity was positive (g = 0.171, p < 0.001), indicating modestly greater oxidative capacity in old. Notably, there was significant heterogeneity in this result (Q = 245.8, p < 0.001; I2 = ∼70%-90%). Muscle group, physical activity, and sex were all significant moderators of oxidative capacity (p ≤ 0.029). This analysis indicates that the current body of literature does not support a de facto decrease of in vivo muscle oxidative capacity in old age. The heterogeneity of study results and identification of significant moderators provide clarity regarding apparent discrepancies in the literature, and indicate the importance of accounting for these variables when examining purported age-related differences in muscle oxidative capacity.

Perceptions of Quality School Facilities – Implications for the School Administrator

The elements that comprise a school’s climate are extensive and complex. There is a preponderance of evidence in the literature that suggest a strong relationship between school climate and academic achievement at the school level. However, there is insufficient research on the elements of school facilities and its relationship to student academic achievement. This paper presents the survey results of 3453 elementary and middle school teacher respondents to the 2010 Administration of the Measures of Effective Teaching Working Conditions Survey on their perceptions of school facilities and its relationship to reading and math on the 2010 Tennessee Comprehensive Achievement Program (TCAP) assessment. Results indicated there were no significant differences between elementary and middle school teachers’ perceptions about quality school facilities. However, there was a difference in teachers’ perceptions of those who worked in schools with proficient reading and math scores on standardized test.

Attention-Deficit Hyperactivity Disorder Status and Baseline Neurocognitive Performance in High School Athletes

Approximately 136,000 concussions occur annually in American high school sports. Neuropsychological data indicate that children with preexisting cognitive difficulties, such as attention-deficit hyperactivity disorder (ADHD), may have protracted recovery from concussion. ADHD, with an estimated prevalence of 11% in youth, may increase an athlete's vulnerability to sustaining sports-related traumatic brain injury (TBI). The preponderance of evidence focusing on TBI and ADHD has derived from motor vehicle accidents rather than sports-related incidents. Thus, it is paramount to explore how ADHD may relate to injury in the sports concussion context, as well as to assess how ADHD may affect baseline neurocognitive testing. Adolescent athletes with ADHD (n = 256) demonstrated significantly reduced Verbal Memory, Visual Motor, and Impulse Control index scores compared with their peers without ADHD (n = 256). Athletes with ADHD were nearly twice as likely to have sustained a prior concussion (ADHD, 14.1%; non-ADHD, 7.8%). Knowledge regarding the unique neurocognitive profile of athletes with ADHD may enhance clinical management decisions.

National Comprehensive Cancer Network petitions: Submissions and outcomes.

248 Background: The National Comprehensive Cancer Network (NCCN) invites petitions to its scientific panels. Most ( &gt; 95%) are from the pharmaceutical industry lobbying to include their products in the NCCN Guidelines. Rarely, physicians request scientific scrutiny of the guidelines. We report the experience of Oncology Analytics (OA) with petition submissions and the possible impact on guidelines. Methods: From 2011-2015, OA made 7 petitions to NCCN. The content of each was tracked into subsequent NCCN Guidelines to ascertain whether any changes resulted. Results: 1) The Survivorship Panel was petitioned to add liposomal doxorubicin to the list of cardiotoxic anthracyclines: No changes were made. 2-3) The NSCLC Panel was asked in 2014 to remove the category 2A listing for trastuzumab and afatinib as HER-2 targeted drugs, and cabozantinib as a RET rearrangement target based on absence of phase I-III full text scientific literature. This was done, however, cabozantinib was reverted to 2A status late 2015 based on abstract-only data. 4) Per FDA approval, the NSCLC Panel was asked to recommend bevacizumab only in combination with carboplatin/paclitaxel for 1st line non-squamous NSCLC based on a survival advantage in ECOG 4599: No changes were made. 5) Given the FDA-approval, the Ovarian Cancer Panel was requested to add doxorubicin: This was done. 6) A 2012 Supportive Care Panel petition pointed out the absence of data supporting palonosetron as the preferred 5-HT3 antagonist with aprepitant for moderate or high emetic risk chemotherapy: No change was made upon request; however, preferred status was removed in 2015 from high emetic risk. 7) Based on a preponderance of evidence, a Supportive Care Panel petition requested re-categorization of the febrile neutropenia risk for carboplatin/paclitaxel from intermediate to low except in patients of Japanese ancestry and/or carboplatin AUC &gt; 6: This was done. Conclusions: Majority of NCCN physician petitions came from OA, yet constituted less than 5% of all petitions submitted. NCCN does not provide direct petitioner feedback, so we cannot say for certain that our petitions led to changes in subsequent guidelines. Not all requests resulted in NCCN changes, despite level one supportive data or accentuating an absence of data.

Organizational slack in declining firms and surviving firms

Purpose– There is a preponderance of evidence in the established literature that declining firms have lower levels of organizational slack when compared with surviving firms. To further advance the current literature, the purpose of this paper is to examine whether or not organizational slack in its various forms differ in declining firms and in surviving firms. Additionally, this study examines whether there is a change in the extent of slack in the declining firms in the years immediately preceding bankruptcy filing.Design/methodology/approach–t-tests and panel regressions with random effects are performed.Findings– Available slack, potential slack and total slack of bankrupts significantly differ from that of survivors in each year. However, recoverable slack levels do not differ in bankrupts and survivors. Available slack of bankrupts reduces significantly over the last five years before bankruptcy. Recoverable slack, potential slack and total slack conditions do not drastically deteriorate for the bankrupts over the last few years prior to bankruptcy.Research limitations/implications– Not confirming to prior evidences, the results of this study suggest that not every type of organizational slack is in a worse condition within a declining firm than in a surviving firm.Practical implications– Among all the slack types, what differentiates bankrupts from survivors is the amount of available slack. Decreasing available slack within declining firms should forewarn managers of further likely deteriorations.Originality/value– The results of this study questions the prevailing wisdom that financial resource levels, especially the levels of organizational slack is in a significantly lower level in declining firms than in surviving firms.

Risks and pecularities of the default situations in bank-consumer relationship: A case study

Kubyana and Standard Bank of South Africa, this matter was brought before the North Gauteng High Court sitting in Pretoria, South Africa. The issue to be determine by the Court was to look at the steps that the credit provider ought to take in order to ensure that a notice, notifying the debtor about his/her debt reaches him/her as a consumer before such notice could commence court litigation. This can only happen, in the circumstances where he/she (the defaulter/consumer) failed to comply with his/her obligation. The North Gauteng High Court was required to decide the legal requirements that may be brought in to satisfy the court on preponderance of evidence that the credit provider has satisfied the court that the defaulter or consumer received such notice.

Chapter 50 - Imaging of neurodegenerative cognitive and behavioral disorders: practical considerations for dementia clinical practice

This chapter reviews clinical applications and imaging findings useful in medical practice relating to neurodegenerative cognitive/dementing disorders. The preponderance of evidence and consensus guidelines support an essential role of multitiered neuroimaging in the evaluation and management of neurodegenerative cognitive/dementia syndrome that range in severity from mild impairments to frank dementia. Additionally, imaging features are incorporated in updated clinical and research diagnostic criteria for most dementias, including Alzheimer's disease (AD), Dementia with Lewy bodies (DLB), Frontotemporal Lobar Degenerations/Frontotemporal Dementia (FTD), and Vascular Cognitive Impairment (VCI). Best clinical practices dictate that structural imaging, preferably with magnetic resonance imaging (MRI) when possible and computed tomography when not, be obtained as a first-tier approach during the course of a thorough clinical evaluation to improve diagnostic confidence and assess for nonneurodegenerative treatable conditions that may cause or substantially contribute to cognitive/behavioral symptoms or which may dictate a substantial change in management. These conditions include less common structural (e.g., mass lesions such as tumors and hematomas; normal-pressure hydrocephalus), inflammatory, autoimmune and infectious conditions, and more common comorbid contributing conditions (e.g., vascular cerebral injury causing leukoaraiosis, infarcts, or microhemorrhages) that can produce a mixed dementia syndrome. When, after appropriate clinical, cognitive/neuropsychologic, and structural neuroimaging assessment, a dementia specialist remains in doubt regarding etiology and appropriate management, second-tier imaging with molecular methods, preferably with fluorodexoyglucose positron emission tomography (PET) (or single-photon emission computed tomography if PET is unavailable) can provide more diagnostic specificity (e.g., help differentiate between atypical AD and FTD as the etiology for a frontal/dysexecutive syndrome). The potential clinical utility of other promising methods, whether already approved for use (e.g., amyloid PET) or as yet only used in research (e.g., tau PET, functional MRI, diffusor tensor imaging), remains to be proven for widespread use in community practice. However, these constitute unreimbursed third-tier options that merit further study for clinical and cost-effective utility. In the future, combination use of imaging methods will likely improve diagnostic accuracy.

A Design Theory for Vigilant Online Learning Systems

There is now a preponderance of evidence suggesting that the types of online course management software (OCMS) used in purely online undergraduate college courses, do not meet the needs of younger immature students. These students often lack the learning skills necessary to succeed in such courses, nor do the popular OCMS include the vigilance mechanisms to guide such students to successful course completion in the absence of face-to-face human instruction. This paper explores the literature relevant to design theory, learning theory, decision support, and vigilance, to extend information systems design theory to a design theory of vigilant online learning systems. It is hoped that this research note will help guide software developers and academics studying how to design future online learning systems for the immature student.

Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies.

By reducing energy density, low-energy sweeteners (LES) might be expected to reduce energy intake (EI) and body weight (BW). To assess the totality of the evidence testing the null hypothesis that LES exposure (versus sugars or unsweetened alternatives) has no effect on EI or BW, we conducted a systematic review of relevant studies in animals and humans consuming LES with ad libitum access to food energy. In 62 of 90 animal studies exposure to LES did not affect or decreased BW. Of 28 reporting increased BW, 19 compared LES with glucose exposure using a specific ‘learning' paradigm. Twelve prospective cohort studies in humans reported inconsistent associations between LES use and body mass index (−0.002 kg m−2 per year, 95% confidence interval (CI) −0.009 to 0.005). Meta-analysis of short-term randomized controlled trials (129 comparisons) showed reduced total EI for LES versus sugar-sweetened food or beverage consumption before an ad libitum meal (−94 kcal, 95% CI −122 to −66), with no difference versus water (−2 kcal, 95% CI −30 to 26). This was consistent with EI results from sustained intervention randomized controlled trials (10 comparisons). Meta-analysis of sustained intervention randomized controlled trials (4 weeks to 40 months) showed that consumption of LES versus sugar led to relatively reduced BW (nine comparisons; −1.35 kg, 95% CI –2.28 to −0.42), and a similar relative reduction in BW versus water (three comparisons; −1.24 kg, 95% CI –2.22 to −0.26). Most animal studies did not mimic LES consumption by humans, and reverse causation may influence the results of prospective cohort studies. The preponderance of evidence from all human randomized controlled trials indicates that LES do not increase EI or BW, whether compared with caloric or non-caloric (for example, water) control conditions. Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water.

Depressive symptoms related to low fractional anisotropy of white matter underlying the right ventral anterior cingulate in older adults with atherosclerotic vascular disease.

We sought to characterize the relationship between integrity of the white matter underlying the ventral anterior cingulate (vAC) and depressive symptoms in older adults with atherosclerotic vascular disease (AVD), a condition associated with preferential degeneration of the white matter. The vAC was defined as including white matter underlying ventral Brodmann Area 24 and Brodmann Area 25, corresponding with the “subcallosal” and “subgenual” cingulate respectively. This region of interest was chosen based on the preponderance of evidence that the white matter in the region plays a critical role in the manifestation of depressive symptoms. Participants had current unequivocal diagnoses of AVD and were between 55 and 90 years-old. Fractional anisotropy (FA) was used as an index of white matter integrity and organization. Whole-brain mean diffusivity (MD) was used as an index of global white matter lesion burden. Depressive symptoms were measured using the Symptom Checklist-90-Revised (SCL-90-R) Depression Scale. Depressive symptoms were significantly related to low FA in the right vAC (r = -0.356, df = 30, p = 0.045) but not the left vAC (r = 0.024, df = 30, p = 0.896) after controlling for total brain MD (a statistical control for global white matter lesion burden). Further, depressive symptoms were significantly related to low FA in the right vAC (r = -0.361, df = 31, p = 0.039), but not the left vAC (r = 0.259, df = 31, p = 0.145) when controlled for the contralateral vAC FA. The correlation coefficients for this follow-up analysis were found to be significantly different between left and right vAC (Z = 2.310, p = 0.021). Poor white matter health in the vAC may be a biological mechanism for depressive symptoms in older adults with vascular disease. Further studies may corroborate that the right vAC plays a unique role in depressive symptom manifestation in cases where the white matter is preferentially affected, as is the case in AVD. This could lead to future targeting of the region for somatic antidepressant treatment, as well as the development of a precise approach for patients with white matter damage, which could produce significant improvement in quality of life, medical morbidity, and mortality.