University of Louisville Hospital

The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

The summarizes much of particle physics and cosmology. Using data from previous editions, plus 2,717 new measurements from 869 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. Particle properties and search limits are listed in Summary Tables. We give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Most of the 120 reviews are updated, including many that are heavily revised. The is divided into two volumes. Volume 1 includes the Summary Tables and 97 review articles. Volume 2 consists of the Particle Listings and contains also 23 reviews that address specific aspects of the data presented in the Listings. The complete (both volumes) is published online on the website of the Particle Data Group () and in a journal. Volume 1 is available in print as the . A with the Summary Tables and essential tables, figures, and equations from selected review articles is available in print, as a web version optimized for use on phones, and as an Android app. The 2024 edition of the Review of Particle Physics should be cited as: S. Navas et al. (Particle Data Group), Phys. Rev. D 110, 030001 (2024) © 2024 2024

Practice guidelines are not intended as absolute requirements. The use of these practice guidelines does not in any way project or guarantee any specific benefit in outcome or survival. The judgment of the healthcare professional based on individual circumstances of the patient must always take precedence over the recommendations in these guidelines. The guidelines offer basic recommendations that are supported by review and analysis of the pertinent available current literature, by other national and international guidelines, and by the blend of expert opinion and clinical practicality. The “intensive care unit” (ICU) or “critically ill” patient is not a homogeneous population. Many of the studies on which the guidelines are based are limited by sample size, patient heterogeneity, variability in definition of disease state and severity of illness, lack of baseline nutrition status, and lack of statistical power for analysis. Whenever possible, these factors are taken into account and the grade of statement will reflect the power of the data. One of the major methodological problems with any guideline is defining the exact population to be included. These guidelines may be subject to periodic review and revision based on new peer-reviewed critical care nutrition literature and practice. These guidelines are intended for the adult medical and surgical critically ill patient populations expected to require an ICU stay of > 2 or 3 days and are not intended for those patients in the ICU for temporary monitoring or those who have minimal metabolic or traumatic stress. These guidelines are based on populations, but like any other therapeutic treatment in an ICU patient, nutrition requirements and techniques of access should be tailored to the individual patient. The intended use of these guidelines is for all individuals involved in the nutrition therapy of the critically ill, primarily physicians, nurses, dietitians, pharmacists, and respiratory and physical therapists where indicated. A list of guideline recommendations was compiled by the experts on the Guidelines Committee for the 2 societies, each of which represented clinically applicable definitive statements of care or specific action statements. Prospective randomized controlled trials were used as the primary source to support guideline statements, with each study being evaluated and given a level of evidence. The overall grade for the recommendation was based on the number and level of investigative studies referable to that guideline. Large studies warranting level I evidence were defined as those with ≥100 patients or those which fulfilled endpoint criteria predetermined by power analysis. The level of evidence for uncontrolled studies was determined by whether they included contemporaneous controls (level III), historical controls (level IV), or no controls (level V, equal to expert opinion). See Table 1 . 1 Review papers and consensus statements were considered expert opinion and were designated the appropriate level of evidence. Meta-analyses were used to organize the information and to draw conclusions about an overall treatment effect from multiple studies on a particular subject. The grade of recommendation, however, was based on the level of evidence of the individual studies. An A or B grade recommendation required at least 1 or 2 large positive randomized trials supporting the claim, while a C grade recommendation required only 1 small supportive randomized investigation. The rationale for each guideline statement was used to clarify certain points from the studies, to identify controversies, and to provide clarity in the derivation of the final recommendation. Significant controversies in interpretation of the literature were resolved by consensus of opinion of the committee members, which in some cases led to a downgrade of the recommendation. Following an extensive review process by external reviewers, the final guideline manuscript was reviewed and approved by A.S.P.E.N. Board of Directors and SCCM's Board of Regents and Council. The significance of nutrition in the hospital setting cannot be overstated. This significance is particularly noted in the ICU. Critical illness is typically associated with a catabolic stress state in which patients commonly demonstrate a systemic inflammatory response. This response is coupled with complications of increased infectious morbidity, multi-organ dysfunction, prolonged hospitalization, and disproportionate mortality. Over the past 3 decades, the understanding of the molecular and biological effects of nutrients in maintaining homeostasis in the critically ill population has made exponential advances. Traditionally, nutrition support in the critically ill population was regarded as adjunctive care designed to provide exogenous fuels to support the patient during the stress response. This support had 3 main objectives: to preserve lean body mass, to maintain immune function, and to avert metabolic complications. Recently these goals have become more focused on nutrition therapy, specifically attempting to attenuate the metabolic response to stress, to prevent oxidative cellular injury, and to favorably modulate the immune response. Nutritional modulation of the stress response to critical illness includes early enteral nutrition, appropriate macro- and micronutrient delivery, and meticulous glycemic control. Delivering early nutrition support therapy, primarily using the enteral route, is seen as a proactive therapeutic strategy that may reduce disease severity, diminish complications, decrease length of stay in the ICU, and favorably impact patient outcome. A1. Traditional nutrition assessment tools (albumin, prealbumin, and anthropometry) are not validated in critical care. Before initiation of feedings, assessment should include evaluation of weight loss and previous nutrient intake prior to admission, level of disease severity, comorbid conditions, and function of the gastrointestinal (GI) tract. (Grade: E) Rationale. In the critical care setting, the traditional protein markers (albumin, prealbumin, transferrin, retinol binding protein) are a reflection of the acute phase response (increases in vascular permeability and reprioritization of hepatic protein synthesis) and do not accurately represent nutrition status in the ICU setting. Anthropometrics are not reliable in assessment of nutrition status or adequacy of nutrition therapy.2,3 A2. Nutrition support therapy in the form of enteral nutrition (EN) should be initiated in the critically ill patient who is unable to maintain volitional intake. (Grade: C) Rationale. EN supports the functional integrity of the gut by maintaining tight junctions between the intraepithelial cells, stimulating blood flow, and inducing the release of trophic endogenous agents (such as cholecystokinin, gastrin, bombesin, and bile salts). EN maintains structural integrity by maintaining villous height and supporting the mass of secretory IgA-producing immunocytes which comprise the gut-associated lymphoid tissue (GALT) and in turn contribute to mucosal-associated lymphoid tissue (MALT) at distant sites such as the lungs, liver, and kidneys.4-7 Adverse change in gut permeability from loss of functional integrity is a dynamic phenomenon which is time-dependent (channels opening within hours of the major insult or injury). The consequences of the permeability changes include increased bacterial challenge (engagement of GALT with enteric organisms), risk for systemic infection, and greater likelihood of multi-organ dysfunction syndrome (MODS).4,5 As disease severity worsens, increases in gut permeability are amplified and the enteral route of feeding is more likely to favorably impact outcome parameters of infection, organ failure, and hospital length of stay (compared to the parenteral route).8 The specific reasons for providing early EN are to maintain gut integrity, modulate stress and the systemic immune response, and attenuate disease severity.6,8,9 Additional endpoints of EN therapy include use of the gut as a conduit for the delivery of immune-modulating agents and use of enteral formulations as an effective means for stress ulcer prophylaxis. Nutrition support therapy (also called “specialized” or“ artificial” nutrition therapy) refers to the provision of enteral tube feeding or parenteral nutrition. “Standard therapy” refers to a patient's own volitional intake without provision of specialized nutrition support therapy. The importance of promoting gut integrity with regard to patient outcome is being strengthened by clinical trials comparing critically ill patients fed by EN to those receiving standard (STD) therapy. In a recent meta-analysis10 in elective gastrointestinal surgery and surgical critical care, patients undergoing a major operation who were given early postoperative EN experienced significant reductions in infection (relative risk [RR] = 0.72; 95% confidence interval [CI] 0.54-0.98; P = .03), hospital length of stay (mean 0.84 days; range 0.36-1.33 days; P = .001), and a trend toward reduced anastomotic dehiscence (RR = 0.53; 95% CI 0.26-1.08; P = .08), when compared to similar patients receiving no nutrition support therapy.10-16 In a meta-analysis17 of patients undergoing surgery for complications of severe acute pancreatitis, those placed on EN 1 day postop showed a trend toward reduced mortality compared to controls randomized to STD therapy (RR = 0.26; 95% CI 0.06-1.09; P = .06).17-19 See Table 2 . 11-16,18,19 A3. EN is the preferred route of feeding over parenteral nutrition (PN) for the critically ill patient who requires nutrition support therapy. (Grade: B) Rationale. In the majority of critically ill patients, it is practical and safe to utilize EN instead of PN. The beneficial effects of EN when compared to PN are well documented in numerous prospective randomized controlled trials involving a variety of patient populations in critical illness, including trauma, burns, head injury, major surgery, and acute pancreatitis.8,20-22 While few studies have shown a differential effect on mortality, the most consistent outcome effect from EN is a reduction in infectious morbidity (generally pneumonia and central line infections in most patient populations, and specifically abdominal abscess in trauma patients).20 In many studies, further benefits are seen from significant reductions in hospital length of stay,21 cost of nutrition therapy,21 and even return of cognitive function (in head injury patients).23 All 6 meta-analyses that compared EN to PN showed significant reductions in infectious morbidity with use of EN.21,24-28 Noninfective complications (risk difference = 4.9; 95% CI 0.3-9.5; P =.04) and reduced hospital length of stay (weighted mean difference [WMD] = 1.20 days; 95% CI 0.38-2.03; P = .004) were seen with use of EN compared to PN in 1 metaanalysis by Peter et al.28 Five of the meta-analyses showed no difference in mortality between the 2 routes of nutrition support therapy.21,24,26-28 One meta-analysis by Simpson and Doig25 showed a significantly lower mortality (RR = 0.51; 95% CI 0.27-0.97; P =.04) despite a significantly higher incidence of infectious complications (RR = 1.66; 95% CI 1.09-2.51; P =.02) with use of PN compared to EN.25 See Table 3 . 8,20,22,29-61 A4. Enteral feeding should be started early within the first 24-48 hours following admission. (Grade: C) The feedings should be advanced toward goal over the next 48-72 hours. (Grade: E) Rationale. Attaining access and initiating EN should be considered as soon as fluid resuscitation is completed and the patient is hemodynamically stable. A “window of opportunity” exists in the first 24-72 hours following admission or the onset of a hypermetabolic insult. Feedings started within this time frame (compared to feedings started after 72 hours) are associated with less gut permeability, diminished activation, and release of inflammatory cytokines (ie, tumor necrosis factor [TNF] and reduced systemic endotoxemia).21 One meta-analysis by Heyland et al showed a trend toward reduced infectious morbidity (RR = 0.66; 95% CI 0.36-1.22; P =.08) and mortality (RR = 0.52; 95% CI 0.25-1.08; P = .08),21 while a second by Marik and Zaloga showed significant reductions in infectious morbidity (RR = 0.45; 95% CI 0.30-0.66; P = .00006) and hospital length of stay (mean 2.2 days, 95% CI 0.81-3.63 days; P = .001) with early EN compared to delayed feedings.62 See Table 4 . 63-72 A5. In the setting of hemodynamic compromise (patients requiring significant hemodynamic support including high dose catecholamine agents, alone or in combination with large volume fluid or blood product resuscitation to maintain cellular perfusion), EN should be withheld until the patient is fully resuscitated and/or stable. (Grade: E) Rationale. At the height of critical illness, EN is being provided to patients who are prone to GI dysmotility, sepsis, and hypotension and thus are at increased risk for subclinical ischemia/reperfusion injury involving the intestinal microcirculation. Ischemic bowel is a rare complication of EN, occurring in <1% of cases.73,74 EN-related ischemic bowel has been reported most often in the past with use of surgical jejunostomy tubes. However, more recently, this complication has been described with use of nasojejunal tubes.75 EN intended to be infused into the small bowel should be withheld in patients who are hypotensive (mean arterial blood pressure <60 mm Hg), particularly if clinicians are initiating use of catecholamine agents (eg, norepinephrine, phenylephrine, epinephrine, dopamine) or escalating the dose of such agents to maintain hemodynamic stability. EN may be provided with caution to patients into either the stomach or small bowel on stable low doses of pressor agents,76 but any signs of intolerance (abdominal distention, increasing nasogastric tube output or gastric residual volumes, decreased passage of stool and flatus, hypoactive bowel sounds, increasing metabolic acidosis and/or base deficit) should be closely scrutinized as possible early signs of gut ischemia. A6. In the ICU patient population, neither the presence nor absence of bowel sounds nor evidence of passage of flatus and stool is required for the initiation of enteral feeding. (Grade: B) Rationale. The literature supports the concept that bowel sounds and evidence of bowel function (ie, passing flatus or stool) are not required for initiation of enteral feeding. GI dysfunction in the ICU setting occurs in 30%-70% of patients depending on the diagnosis, premorbid condition, ventilation mode, medications, and metabolic state.77 Proposed mechanisms of ICU and postoperative GI dysfunction can be separated into 3 general categories: mucosal barrier disruption, altered motility and atrophy of the mucosa, and reduced mass of GALT. Bowel sounds are only indicative of contractility and do not necessarily relate to mucosal integrity, barrier function, or absorptive capacity. Success at attaining nutrition goals within the first 72 hours ranges from 30% to 85%. When ICU enteral feeding protocols are followed, rates of GI tolerance in the range of 70%-85% can be achieved.76 Ten randomized clinical trials,63-72 the majority in surgical critically ill patients, have reported feasibility and safety of enteral feeding within the initial 36-48 hours of admission to the ICU. The grade of this recommendation is based on the strength of the literature supporting A3, where patients in the experimental arm of the above mentioned studies were successfully started on EN within the first 36 hours of admission (regardless of clinical signs of stooling, flatus, or borborygmi). See Table 4 . 63-72 A7. Either gastric or small bowel feeding is acceptable in the ICU setting. Critically ill patients should be fed via an enteral access tube placed in the small bowel if at high risk for aspiration or after showing intolerance to gastric feeding. (Grade: C) Withholding of enteral feeding for repeated high gastric residual volumes alone may be sufficient reason to switch to small bowel feeding (the definition for high gastric residual volume is likely to vary from one hospital to the next, as determined by individual institutional protocol). (Grade: E) (See guideline D4 for recommendations on gastric residual volumes, identifying high risk patients, and reducing chances for aspiration.) Rationale. Multiple studies have evaluated gastric vs jejunal feeding in various medical and surgical ICU settings. One level II study comparing gastric vs jejunal feeding showed significantly less gastroesophageal reflux with small bowel feeding.78 In a nonrandomized prospective study using a radioisotope in an enteral formulation, esophageal reflux was reduced significantly with a trend toward reduced aspiration as the level of infusion was moved from the stomach down through the third portion of the duodenum.79 Three meta-analyses have been published comparing gastric with post-pyloric feeding in the ICU setting.80-82 Only 1 of these meta-analyses showed a significant reduction in ventilator-associated pneumonia with post-pyloric feeding (RR = 0.76; 95% CI 0.59-0.99; P = .04),82 an effect heavily influenced by 1 study by Taylor et al.23 With removal of this study from the meta-analysis, the difference was no longer significant. The 2 other meta-analyses (which did not include the Taylor study) showed no difference in pneumonia between gastric and post-pyloric feeding.80,81 While 1 showed no difference in ICU length of stay,80 all 3 meta-analyses showed no significant difference in mortality between gastric and post-pyloric feeding.80-82 See Table 5 . 23,68,78,83-91 B1. If early EN is not feasible or available the first 7 days following admission to the ICU, no nutrition support therapy (ie, STD therapy) should be provided. (Grade: C) In the patient who was previously healthy prior to critical illness with no evidence of protein-calorie malnutrition, use of PN should be reserved and initiated only after the first 7 days of hospitalization EN is not (Grade: E) Rationale. These 2 recommendations are the most in these guidelines, are influenced primarily by 2 and should be in to patient meta-analyses compared use of PN with STD therapy no nutrition support therapy was In critically ill patients in the absence of EN is not et al 7 and showed that use of STD therapy was associated with significantly reduced infectious morbidity (RR = 95% CI P and a trend toward reduced overall complications (RR = 95% CI P not compared to use of In the circumstances ill, no EN and no evidence of Heyland et 4 and showed a significant in mortality with use of PN (RR = 95% CI P and a trend toward greater of complications (RR = 95% CI P not when compared to STD therapy. See Table 6 . With increased of severe illness, between STD therapy and PN become et al first showed that after the first days of hospitalization had to provide no nutrition therapy was associated with significantly greater mortality vs P and longer hospital length of stay days vs days, P when compared to use of The of as to the appropriate length of time initiating PN in a patient on STD therapy who has not to days, Heyland were reported in a study of patients with severe acute In this a significant was seen in each clinical outcome length of infection, overall complications, and when comparing patients randomized to STD therapy vs PN vs PN with parenteral of the to the of this study to of but were The final recommendation was based on the overall treatment effect of PN over the first of hospitalization seen in the 2 the literature PN for days, the Guidelines Committee that to provide STD therapy nutrition support therapy) 7 days to of nutrition status and an effect on clinical outcome. If is evidence of protein-calorie on admission and EN is not it is appropriate to PN as soon as possible following admission and (Grade: C) Rationale. In the where EN is not available and evidence of protein-calorie is defined by recent weight loss of or body weight of body initial are and use of PN has a more outcome STD therapy. See Table 6 . In the Heyland meta-analysis, use of PN in ICU patients was associated with significantly overall complications (RR = 0.52; 95% CI P STD In the meta-analysis, STD therapy in ICU patients was associated with significantly higher risk for mortality (RR = 95% CI P and a trend toward higher of infection (RR = 95% CI P not compared to use of these patients, when EN is not should be in initiating PN after admission to the ICU. If a patient is expected to major GI surgery and EN is not PN should be provided specific If the patient is PN should be initiated days and into the postoperative (Grade: B) PN should not be initiated in the postoperative but should be delayed for days EN not to be (Grade: B) PN therapy provided for a of days be expected to have no outcome effect and may in increased risk to the patient. PN should be initiated only if the of therapy is to be (Grade: B) Rationale. One population of patients that has shown more consistent benefit of PN over STD those patients undergoing major GI surgery or other major abdominal if is evidence of protein-calorie and the PN is provided specific critically ill patients in the Heyland meta-analysis experienced increased mortality with use of PN compared to STD therapy rationale for guideline surgical patients no treatment effect with PN mortality (RR = 95% CI P = Critically ill patients experienced a trend toward increased complications, while surgical patients significant reductions in complications with use of PN mortality (RR = 95% CI P These benefits were noted when PN was provided for a of days and through the In an meta-analysis by et comparing PN with STD therapy, only of provided PN for As a only 1 study showed a treatment and the overall meta-analysis showed no significant benefit from In a meta-analysis by et the from all of which provided PN for of the studies showed significant beneficial treatment effects from use of with the from the overall meta-analysis showing a significant decrease in infectious morbidity compared to STD See Table 6 . is to be that the beneficial effect of PN is if given only of from studies that evaluated postoperative showed a significant in complications compared to STD of the outcome effect from PN initiated in the postoperative et al PN for days following surgery if EN not to be The goal of EN by should be determined and at the time of initiation of nutrition support therapy. (Grade: C) requirements may be by or by should be used with as they provide a less of requirements in the individual patient. In the patient, the are even more without of (Grade: E) Rationale. should identify the goal of EN, as determined by requirements. Over have been published in the requirements may be either through published or the use of provided via infusion of should be considered when the nutrition While it is often to provide of goal by the enteral route, studies in which a was used to delivery of EN have shown that a volume of EN where the level of and protein provided is to goal This recommendation is supported by level II studies in which those patients who by a greater volume of EN experienced significantly complications and less infectious as well as hospital of and a trend toward lower those patients receiving lower to provide of goal should be made in to the clinical benefit of EN over the first of (Grade: C) Rationale. The impact of early EN on patient outcome to be a or trophic defined as may be sufficient to prevent mucosal atrophy but may be to the endpoints from EN therapy. that of goal may be required to prevent increases in intestinal permeability in and patients, to return of cognitive function in head injury patients, and to outcome from immune-modulating enteral formulations in critically ill This recommendation is supported by one level and one level where increases in the goal infused from a range of to clinical outcome. If unable to requirements of goal after days by the enteral route initiating PN. (Grade: E) PN prior to this day in the patient receiving EN does not outcome and may be to the patient. (Grade: C) Rationale. EN is toward maintaining gut integrity, reducing oxidative stress, and systemic In patients receiving some volume of EN, use of PN over the first days and to provide no In 1 small study in patients, EN with PN was associated with a significant in mortality vs P when compared to EN See Table 7 . As in guideline the time to PN in a patient who is receiving some volume of enteral feeding is not The by et al and et al that after the first days, the to provide and protein is increased in to prevent the consequences of of nutrition At this if the provision of EN is to the of PN should be assessment of adequacy of protein provision should be The use of protein is a as standard enteral formulations to have a high In patients with body mass protein requirements should be in the range of body weight and may likely be even higher in or (Grade: E) Rationale. In the critical care setting, protein to be the most for supporting immune function, and maintaining lean body most critically ill patients, protein requirements are higher requirements and are not by provision of enteral The to protein should be based on an assessment of adequacy of protein in the critical care setting, of protein requirements is

(1995). Frame Reflection: Toward the Resolution of Intractable Policy Controversies. Journal of Economic Issues: Vol. 29, No. 3, pp. 965-968.

First Page

In this article, the authors outline methods for using fixed and random effects power analysis in the context of meta-analysis. Like statistical power analysis for primary studies, power analysis for meta-analysis can be done either prospectively or retrospectively and requires assumptions about parameters that are unknown. The authors provide some suggestions for thinking about these parameters, in particular for the random effects variance component. The authors also show how the typically uninformative retrospective power analysis can be made more informative. The authors then discuss the value of confidence intervals, show how they could be used in addition to or instead of retrospective power analysis, and also demonstrate that confidence intervals can convey information more effectively in some situations than power analyses alone. Finally, the authors take up the question “How many studies do you need to do a meta-analysis?” and show that, given the need for a conclusion, the answer is “two studies,” because all other synthesis techniques are less transparent and/or are less likely to be valid. For systematic reviewers who choose not to conduct a quantitative synthesis, the authors provide suggestions for both highlighting the current limitations in the research base and for displaying the characteristics and results of studies that were found to meet inclusion criteria.

A multistage, four sample study was conducted to develop a conceptually consistent and psychometrically sound measure of decision-making style. Construct definitions were developed from prior theory, and items were written to assess rational, avoidant, intuitive, and dependent decision-making styles. A series of principal-axis factor analyses with varimax rotation and subsequent item analyses were conducted to develop four conceptually distinct scales with acceptable internal consistency (alpha ranging from .68 to .94) and a stable factor structure. In the process of scale development, a fifth style (spontaneous) was identified. Tests for independence among the five decision-making style scales and concurrent validity analyses were conducted. Finally, discussion of the new instrument with reference to the extant literature is provided.

(2003). International Standards For Neurological Classification Of Spinal Cord Injury. The Journal of Spinal Cord Medicine: Vol. 26, No. sup1, pp. S50-S56.

BACKGROUND: Impaired endothelium-mediated relaxation contributes to vasospasm and myocardial ischemia in patients with coronary artery disease. We hypothesized that cholesterol-lowering therapy with the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor lovastatin could improve endothelium-mediated responses in patients with coronary atherosclerosis. METHODS: In a randomized, double-blind, placebo-controlled trial, we studied coronary endothelial responses in 23 patients randomly assigned to either lovastatin (40 mg twice daily; 11 patients) or placebo (12 patients) plus a lipid-lowering diet (American Heart Association Step 1 diet). Patients were studied 12 days after randomization and again at 5 1/2 months. These patients had total cholesterol levels ranging from 160 to 300 mg per deciliter (4.1 to 7.8 mmol per liter) and were undergoing coronary angioplasty. At the initial and follow-up studies, patients received serial intracoronary infusions (in a coronary artery not undergoing angioplasty) of acetylcholine to assess endothelium-mediated vasodilatation. The responses of the coronary vessels were analyzed with quantitative angiography. RESULTS: The patients in the placebo and lovastatin groups had similar responses to acetylcholine at a mean of 12 days of therapy (expressed as the percentage of change in diameter in response to acetylcholine doses of 10(-9) M, 10(-8) M, 10(-7) M, and 10(-6) M). In the placebo group, the respective mean (+/- SE) changes were 1 +/- 2, 0 +/- 2, -2 +/- 4, and -19 +/- 4 percent; in the lovastatin group, they were -2 +/- 2, -4 +/- 4, -12 +/- 5, and -16 +/- 7 percent (P = 0.32). (Coronary-artery constriction is reflected by negative numbers). The responses to acetylcholine in the placebo group after a mean of 5.5 months of therapy were -3 +/- 3, -1 +/- 2, -8 +/- 4, and -18 +/- 5 percent, respectively; there was significant improvement in the lovastatin group, which had responses of 3 +/- 3, 3 +/- 3, 0 +/- 2, and 0 +/- 3 percent (P = 0.004). CONCLUSIONS: Cholesterol lowering with lovastatin significantly improved endothelium-mediated responses in the coronary arteries of patients with atherosclerosis. Such improvement in the local regulation of coronary arterial tone could potentially relieve ischemic symptoms and signal the stabilization of the atherosclerotic plaque.

As there are no biological markers for the antemortem diagnosis of degenerative parkinsonian disorders, diagnosis currently relies upon the presence and progression of clinical features and confirmation depends on neuropathology. Clinicopathologic studies have shown significant false-positive and false-negative rates for diagnosing these disorders, and misdiagnosis is especially common during the early stages of these diseases. It is important to establish a set of widely accepted diagnostic criteria for these disorders that may be applied and reproduced in a blinded fashion. This review summarizes the findings of the SIC Task Force for the study of diagnostic criteria for parkinsonian disorders in the areas of Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. In each of these areas, diagnosis continues to rest on clinical findings and the judicious use of ancillary studies.

Although several theories assert that understanding the search for meaning in life is important, empirical research on this construct is sparse. Three studies provide the first extensive effort to understand the correlates of the search for meaning in a multistudy research program. Assessed were relations between search for meaning and well-being, cognitive style, and the Big Five, Big Three, Approach/Avoidance, and Interest models of personality, with a particular emphasis on understanding the correlates of search for meaning that are independent of presence of meaning. Conceptual models of the relation between search and presence were tested. Findings suggest that people lacking meaning search for it; the search for meaning did not appear to lead to its presence. Study 3 found that basic motive dispositions moderated relations between search for meaning and its presence. Results highlight the importance of basic personality dispositions in understanding the search for meaning and its correlates.

BACKGROUND: Idiopathic membranous nephropathy is an autoimmune disease. In approximately 70% of patients, it is associated with autoantibodies against the phospholipase A2 receptor 1 (PLA2R1). Antigenic targets in the remaining patients are unknown. METHODS: Using Western blotting, we screened serum samples from patients with idiopathic membranous nephropathy, patients with other glomerular diseases, and healthy controls for antibodies against human native glomerular proteins. We partially purified a putative new antigen, identified this protein by means of mass spectrometry of digested peptides, and validated the results by analysis of recombinant protein expression, immunoprecipitation, and immunohistochemical analysis. RESULTS: Serum samples from 6 of 44 patients in a European cohort and 9 of 110 patients in a Boston cohort with anti-PLA2R1-negative idiopathic membranous nephropathy recognized a glomerular protein that was 250 kD in size. None of the serum samples from the 74 patients with idiopathic membranous nephropathy who were seropositive for anti-PLA2R1 antibodies, from the 76 patients with other glomerular diseases, and from the 44 healthy controls reacted against this antigen. Although this newly identified antigen is clearly different from PLA2R1, it shares some biochemical features, such as N-glycosylation, membranous location, and reactivity with serum only under nonreducing conditions. Mass spectrometry identified this antigen as thrombospondin type-1 domain-containing 7A (THSD7A). All reactive serum samples recognized recombinant THSD7A and immunoprecipitated THSD7A from glomerular lysates. Moreover, immunohistochemical analyses of biopsy samples from patients revealed localization of THSD7A to podocytes, and IgG eluted from one of these samples was specific for THSD7A. CONCLUSIONS: In our cohort, 15 of 154 patients with idiopathic membranous nephropathy had circulating autoantibodies to THSD7A but not to PLA2R1, a finding that suggests a distinct subgroup of patients with this condition. (Funded by the French National Center for Scientific Research and others.).

BACKGROUND: The results from small clinical studies suggest that therapy with adult bone marrow (BM)-derived cells (BMCs) reduces infarct size and improves left ventricular function and perfusion. However, the effects of BMC transplantation in patients with ischemic heart disease remains unclear. METHODS: We searched MEDLINE, EMBASE, Science Citation Index, CINAHL (Cumulative Index to Nursing and Allied Health), and the Cochrane Central Register of Controlled Trials (CENTRAL) (through July 2006) for randomized controlled trials and cohort studies of BMC transplantation to treat ischemic heart disease. We conducted a random-effects meta-analysis across eligible studies measuring the same outcomes. RESULTS: Eighteen studies (N = 999 patients) were eligible. The adult BMCs included BM mononuclear cells, BM mesenchymal stem cells, and BM-derived circulating progenitor cells. Compared with controls, BMC transplantation improved left ventricular ejection fraction (pooled difference, 3.66%; 95% confidence interval [CI], 1.93% to 5.40%; P<.001); reduced infarct scar size (-5.49%; 95% CI, -9.10% to -1.88%; P = .003); and reduced left ventricular end-systolic volume (-4.80 mL; 95% CI, -8.20 to -1.41 mL; P = .006). CONCLUSIONS: The available evidence suggests that BMC transplantation is associated with modest improvements in physiologic and anatomic parameters in patients with both acute myocardial infarction and chronic ischemic heart disease, above and beyond conventional therapy. Therapy with BMCs seems safe. These results support conducting large randomized trials to evaluate the impact of BMC therapy vs the standard of care on patient-important outcomes.

AbstractThe purpose of this paper is to critically explore the construct of entrepreneurial marketing (EM). This term is used as an integrative conceptualization that reflects such alternative perspectives as guerrilla marketing, radical marketing, expeditionary marketing, disruptive marketing and others. Seven core dimensions of EM are identified, and an underlying theoretical foundation based on resource advantage theory is proposed. A conceptual model is introduced of key factors surrounding the phenomenon of entrepreneurial marketing. Conclusions and implications are drawn for theory and practice, and priorities are proposed for continuing research.Key Words: customer intensityentrepreneurshipentrepreneurial orientationinnovationmarket orientationopportunityresource leveragingresource advantagerisk-taking This article is part of the following collections: Celebrating the Impactful Articles from Journal of Marketing Theory and Practice Additional informationNotes on contributorsMichael H. MorrisMichael H. Morris (Ph.D. Virginia Technical Institute), holds the Writing Chair in Entrepreneurship at Syracuse University, and is the Director of the Program in Entrepreneurship and Emerging Enterprises. Dr. Morris has served as chair of the American Marketing Association’s Task Force on Marketing and Entrepreneurship and is currently the editor of the Journal of Developmental Entrepreneurship. He has received Edwin M. and Gloria W. Appel Prize for for contributions to the field of entrepreneurship, has been inducted as a “21st Centur Entrepreneurship Research Fellow”. He is a former Fulbright Scholar (South Africa, 1993).Minet SchindehutteMinet Schindehutte (Ph.D., University of Pretoria) is assistant professor of Entrepreneurship at Miami University in Ohio. She holds a Post-graduate Diploma in Marketing from the University of South Africa. Dr. Schindehutte has been extensively involved with curriculum development efforts for the nationally recognized Entrepreneurship Program at Miami. Her current research interests include innovation strategies in entrepreneurial firms, the unique challenges of women and ethnic entrepreneurs, and the roles of ethics and values in entrepreneurial companies.Raymond W. LaForgeRaymond W. LaForge (DBA, University of Tennessee) is the Brown-Forman Professor of Marketing at the Univesity of Louisville. The founder and executive editor of the Marketing Education Review, he has championed a number of innovations both in university and professional sales management and sales force training. Dr. LaForge has published extensively in the areas of sales management and professional selling, and is the author of leading textbooks in marketing, sales management, and personal selling.

Unlike the early phase of preconditioning (PC), which lasts 2 to 3 hours and protects against infarction but not against stunning, the late phase of PC lasts 3 to 4 days and protects against both infarction and stunning, suggesting that it may have greater clinical relevance. It is now clear that late PC is a polygenic phenomenon that requires the simultaneous activation of multiple stress-responsive genes. Chemical signals released by a sublethal ischemic stress (such as NO, reactive oxygen species, and adenosine) trigger a complex cascade of signaling events that includes the activation of protein kinase C, Src protein tyrosine kinases, and nuclear factor kappaB and culminates in increased synthesis of inducible NO synthase, cyclooxygenase-2, aldose reductase, Mn superoxide dismutase, and probably other cardioprotective proteins. An analogous sequence of events can be triggered by a variety of stimuli, such as heat stress, exercise, and cytokines. Thus, late PC appears to be a universal response of the heart to stress in general. Importantly, the cardioprotective effects of late PC can be reproduced pharmacologically with clinically relevant agents (eg, NO donors, adenosine receptor agonists, endotoxin derivatives, or opioid receptor agonists), suggesting that this phenomenon might be exploited for therapeutic purposes. The purpose of this review is to summarize current information regarding the pathophysiology and mechanism of late PC.

The teaching of Botany in Basic Education has been characterized as discouraging for students in Brazil, mainly due to the traditional teaching methodologies practiced by the teachers. It discusses the role of pre-class approaches, involving the relationships between the object of study and the daily life of the student, as a strategy to attract student's attention to specific content. In this way, this work had as objective to evaluate the process of "initial sensitization of the student", through the use of methods that aim to stimulate students' interest in Botany, before a class in this area. The first step was to list strategies already described along with the development of new strategies related to the concepts addressed in secondary education in the context of regular education, according to the competences and skills required by the National High School Examination (ENEM) and (Encceja), both offered by the Ministry of Education (MEC). In the second stage, some Sensitivity Strategies were evaluated in a high school class, obtaining qualitative and quantitative data from the comparison with controlled groups. The results showed an increase in students' interest in botanical subjects in the groups that passed through the strategies. From these experiences, the work presents a guide of simple strategies to be used by botany teachers at the beginning of each lesson related to the Botany concepts of the curriculum required by ENEM and Encceja.

We have observed a narrow state near $2.32\text{ }\mathrm{G}\mathrm{e}\mathrm{V}/{c}^{2}$ in the inclusive ${D}_{s}^{+}{\ensuremath{\pi}}^{0}$ invariant mass distribution from ${e}^{+}{e}^{\ensuremath{-}}$ annihilation data at energies near 10.6 GeV. The observed width is consistent with the experimental resolution. The small intrinsic width and the quantum numbers of the final state indicate that the decay violates isospin conservation. The state has natural spin-parity and the low mass suggests a ${J}^{P}={0}^{+}$ assignment. The data sample corresponds to an integrated luminosity of $91\text{ }{\mathrm{f}\mathrm{b}}^{\ensuremath{-}1}$ recorded by the BABAR detector at the SLAC PEP-II asymmetric-energy ${e}^{+}{e}^{\ensuremath{-}}$ storage ring.

Searches for lepton-flavor-violating decays of a $\ensuremath{\tau}$ lepton to a lighter mass lepton and a photon have been performed with the entire data set of $(963\ifmmode\pm\else\textpm\fi{}7)\ifmmode\times\else\texttimes\fi{}{10}^{6}\text{ }\text{ }\ensuremath{\tau}$ decays collected by the BABAR detector near the $\ensuremath{\Upsilon}(4S)$, $\ensuremath{\Upsilon}(3S)$ and $\ensuremath{\Upsilon}(2S)$ resonances. The searches yield no evidence of signals and we set upper limits on the branching fractions of $\mathcal{B}({\ensuremath{\tau}}^{\ifmmode\pm\else\textpm\fi{}}\ensuremath{\rightarrow}{e}^{\ifmmode\pm\else\textpm\fi{}}\ensuremath{\gamma})&lt;3.3\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}8}$ and $\mathcal{B}({\ensuremath{\tau}}^{\ifmmode\pm\else\textpm\fi{}}\ensuremath{\rightarrow}{\ensuremath{\mu}}^{\ifmmode\pm\else\textpm\fi{}}\ensuremath{\gamma})&lt;4.4\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}8}$ at 90% confidence level.

INTRODUCTION: In Appalachia, youth tobacco-use rates remain higher than the U.S. national average. Past research has indicated that several factors are related to high rates of tobacco use among Appalachian youth (e.g. low socioeconomic status, rural lifestyles). Of the Appalachian states, Kentucky has one of the highest rates of youth tobacco use. The aim of this study was to explore views of tobacco among Kentucky youth living in Appalachian counties. METHODS: In Fall 2014 - Spring 2015, focus group interviews were conducted with middle and high school students (N=109) in Appalachian counties in Kentucky. Each focus group session included open-ended questions and was conducted by trained facilitators. Focus group transcriptions and field notes were analyzed for themes. RESULTS: Study participants described an entrenched culture of tobacco. Three themes exemplified this culture. First, adult behavior served to enable youth tobacco use (e.g. teachers ignoring dip use in class, adults smoking with youth). Second, tobacco is easily accessible to youth (e.g. restrictions on youth sales are often ignored, family members provide). Third, symbols of tobacco are prevalent (e.g. festivals celebrating tobacco heritage, tobacco barns, and tobacco marketing logos). CONCLUSIONS: Youth participants described a deeply rooted tobacco culture, which they believed was unlikely to change. Additional studies and health education efforts are needed in these rural communities. Further, stricter enforcement of tobacco sales and marketing restrictions may be helpful in protecting this vulnerable population.

Structural Equation Modeling (SEM) is gaining attention in social work as an analytical method for studying social policy and testing theories for practice. This paper demonstrates a special SEM application to test a theory for research use in the human services. Data from 294 decision-makers in human service organizational units of federal, state, and local governments are used to show the appropriateness of using composites instead of multiple indicators in a SEM model with latent variables. The step-by-step description of a two-stage modeling process is presented. Using a model generation analysis strategy, the results show that a nonrecursive model positing a reciprocal relationship between research use and diffusion could not be confirmed. Instead, a recursive model is uncovered with research use leading to research diffusion. In addition, perceived quality of research, positive interaction between researchers and decision-makers, and transfer intensity of disseminating research results through multiple media, produced direct and indirect effects on research use and diffusion. The limitations and strengths of this study using the special SEM application are discussed.