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Selected AbstractsNON-GYNAECOLOGICAL CYTOLOGY: THE CLINICIAN'S VIEWCYTOPATHOLOGY, Issue 2006I. Penman There is increased recognition of the importance of accurate staging of malignancies of the GI tract and lung, greater use of neoadjuvant therapies and more protocol-driven management. This is particularly important where regional lymph node involvement significantly impacts on curability. Multidetector CT and PET scanning have resulted in greater detection of potential abnormalities which, if positive for malignancy, would change management. There is also a greater recognition that many enlarged nodes may be inflammatory and that size criteria alone are unreliable in determining involvement. In other situations, especially pancreatic masses, not all represent carcinoma as focal chronic pancreatitis, autoimmune pancreatitis etc can catch out the unwary. A preoperative tissue diagnosis is essential and even if unresectable, oncologists are increasingly reluctant to initiate chemotherapy or enroll patients into trials without this. The approach to obtaining tissue is often hampered by the small size or relative inaccessibility of lesions by percutaneous approaches. As such novel techniques such as endoscopic ultrasound (EUS) guided FNA have been developed. A 120cm needle is passed through the instrument and, under real-time visualisation, through the gastrointestinal wall to sample adjacent lymph nodes or masses. Multiple studies have demonstrated the safety and performance of this technique. In oesophageal cancer, confirmation of node positivity by has a major negative influence on curative resection rates and will often lead to a decision to use neoadjuvant chemotherapy or a non-operative approach. Sampling of lymph nodes at the true coeliac axis upstages the patient to M1a status (stage IV) disease and makes the patient incurable. In NSCLC, subcarinal lymph nodes are frequently present but may be inflammatory. If positive these represent N2 (stage IIIA) disease and in most centres again makes the patient inoperable. Access to these lymph nodes would otherwise require mediastinosocopy whereas this can be done simply, safely and quickly by EUS. Overall the sensitivity for EUS , FNA of mediastinal or upper abdominal lymph nodes is 83,90% with an accuracy of 80,90%. In pancreatic cancer performance is less good but pooled analysis of published studies indicates a sensitivity of 85% and accuracy of 88%. In a recent spin-off from EUS, endobronchial ultrasound (EBUS) instruments have been developed and the ability to sample anterior mediastinal nodes has been demonstrated. It is likely that this EBUS , FNA technique will become increasingly utilised and may replace mediastinoscopy. The development of techniques such as EUS and EBUS to allow FNA sampling of lesions has increased the role of non-gynaecological cytology significantly in recent years. Cytology therefore remains important for a broad range of specialties and there is ongoing need for careful and close co-operation between cytologists and clinicians in these specialties. References:, 1. Williams DB, Sahai AV, Aabakken L, Penman ID, van Velse A, Webb J et al. Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre experience. Gut. 1999; 44: 720,6. 2. Silvestri GA, Hoffman BJ, Bhutani MS et al. Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer. Ann Thorac Surg 1996; 61: 1441,6. 3. Rintoul RC, Skwarski KM, Murchison JT, Wallace WA, Walker WS, Penman ID. Endobronchial and endoscopic ultrasound real-time fine-needle aspiration staging of the mediastinum ). Eur Resp J 2005; 25: 1,6. [source] The Multicenter Study of Epilepsy Surgery: Recruitment and Selection for SurgeryEPILEPSIA, Issue 11 2003Anne T. Berg Summary:,Purpose: Multiple studies have examined predictors of seizure outcomes after epilepsy surgery. Most are single-center series with limited sample size. Little information is available about the selection process for surgery and, in particular, the proportion of patients who ultimately have surgery and the characteristics that identify those who do versus those who do not. Such information is necessary for providing the epidemiologic and clinical context in which epilepsy surgery is currently performed in the United States and in other developed countries. Methods: An observational cohort of 565 surgical candidates was prospectively recruited from June 1996 through January 2001 at six Northeastern and one Midwestern surgical centers. Standardized eligibility criteria and protocol for presurgical evaluations were used at all seven sites. Results: Three hundred ninety-six (70%) study subjects had resective surgery. Clinical factors such as a well-localized magnetic resonance imaging (MRI) abnormality and consistently localized EEG findings were most strongly associated with having surgery. Of those who underwent intracranial monitoring (189, 34%), 85% went on to have surgery. Race/ethnicity and marital status were marginally associated with having surgery. Age, education, and employment status were not. Demographic factors had little influence over the surgical decision. More than half of the patients had intractable epilepsy for ,10 years and five or more drugs had failed by the time they initiated their surgical evaluation. During the recruitment period, eight new antiepileptic drugs were approved by the Food and Drug Administration for use in the United States and came into increasing use in this study's surgical candidates. Despite the increased availability of new therapeutic options, the proportion that had surgery each year did not fluctuate significantly from year to year. This suggests that, in this group of patients, the new drugs did not provide a substantial therapeutic benefit. Conclusions: Up to 30% of patients who undergo presurgical evaluations for resective epilepsy surgery ultimately do not have this form of surgery. This is a group whose needs are not currently met by available therapies and procedures. Lack of clear localizing evidence appears to be the main reason for not having surgery. To the extent that these data can address the question, they suggest that repeated attempts to control intractable epilepsy with new drugs will not result in sustained seizure control, and eligible patients will proceed to surgery eventually. This is consistent with recent arguments to consider surgery earlier rather than later in the course of epilepsy. Postsurgical follow-up of this group will permit a detailed analysis of presurgical factors that predict the best and worst seizure outcomes. [source] Mechanisms and consequences of bladder cell invasion by uropathogenic Escherichia coliEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2008B. K. Dhakal ABSTRACT Strains of uropathogenic Escherichia coli (UPEC) are the major cause of urinary tract infections worldwide. Multiple studies over the past decade have called into question the dogmatic view that UPEC strains act as strictly extracellular pathogens. Rather, bacterial expression of filamentous adhesive organelles known as type 1 pili and Afa/Dr fibrils enable UPEC to invade host epithelial cells within the urinary tract. Entry into bladder epithelial cells provides UPEC with a protected niche where the bacteria can persist quiescently for long periods, unperturbed by host defences and protected from many antibiotic treatments. Alternately, internalized UPEC can rapidly multiply, forming large intracellular inclusions that can contain several thousand bacteria. Initial work aimed at defining the host and bacterial factors that modulate the entry, intracellular trafficking, and eventual resurgence of UPEC suggests a high degree of host-pathogen crosstalk. Targeted disruption of these processes may provide a novel means to prevent and treat recurrent, relapsing and chronic infections within the urinary tract. [source] IL23R haplotypes provide a large population attributable risk for Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 9 2008Kent D. Taylor PhD Abstract Background: The IL-23 pathway plays a pivotal role in the development of chronic mucosal inflammation seen in the inflammatory bowel diseases. Multiple studies have now established the contribution of the interleukin 23 receptor gene (IL23R) to Crohn's disease (CD) risk in general and of the IL23R R381Q variant in particular. The aim of this work was to estimate the total contribution of this gene to CD risk test using a haplotype approach. Methods: In all, 763 CD subjects and 254 controls were genotyped for single nucleotide polymorphisms in the IL23R gene using Illumina and ABI methods. Haplotypes were assigned using PHASEv2 and tested for association with CD by chi-square and permutation. Results: Haplotypes with both increased and decreased risk for CD were observed in 2 of the 4 observed blocks (Block 2 H1: 55.4% control, 64% CD, P = 0.019; H2: 64.5% control, 54.4% CD, P = 0.006; Block 3 H1: 55.8% control, 64.4% CD, P = 0.013; H2: 47.0% control, 36.6% CD, P = 0.001). The population attributable risk for these haplotypes was substantially larger than that estimated for the IL23R R381Q variant (Block 2 H1 and block 3 H1 ,20%, compared with ,4% for Block 3 H6, containing the variant). Conclusions: These observations suggest that IL23R makes a substantial contribution to CD susceptibility, larger than that estimated from the population frequency of the R381Q variant. These observations also support the expectation that finding "hits" from genomewide association studies will be but an important chapter in the story of unraveling the genetic contribution to CD, rather than the final chapter that brings clarity to all the plot twists of a complicated story. (Inflamm Bowel Dis 2008) [source] Clinical (Nonforensic) Application of Ethyl Glucuronide Measurement: Are We Ready?ALCOHOLISM, Issue 6 2010Peter Jatlow Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are minor metabolites of ethanol. Multiple studies have documented that, depending upon the amount of alcohol consumed, they can be measured in biological fluids for hours to days after the parent compound can no longer be detected. Testing for the presence of EtG, in a manner analogous to urinary drug abuse screening, has largely been restricted to forensic and law enforcement situations. Despite a real need for an objective and possibly quantitative marker of ethanol exposure for use in conjunction with outpatient clinical trials and treatment programs, measurement of these metabolites has seen only limited clinical application. The barriers to more extensive clinical use of EtG/EtS testing, particularly misleading assay results that can occur as a consequence of inadvertent exposure to nonbeverage ethanol-containing substances, are reviewed and put into perspective. Additional information needed to develop guidelines for optimal clinical utilization of EtG/EtS measurements is discussed. [source] Aesthetic effects of topical photodynamic therapyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 11 2010E Kohl Abstract Topical photodynamic therapy has shown to be effective for the treatment of several aspects of skin ageing. Multiple studies have demonstrated improvement of fine wrinkles, mottled hyperpigmentation, tactile roughness and sallowness. These results are supported by immunohistochemical analysis that revealed both upregulation of collagen production and increased epidermal proliferation. Neocollagenesis as an indirect dermal effect of photodynamic therapy is stimulated through cytokine induction. This article reviews the available literature for photodynamic rejuvenation while discussing cosmetic effects, light sources, adverse effects and the mechanism of action. [source] Thoracic Aortic Aneurysms and Dissections: Endovascular TreatmentMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 3 2010Donald T. Baril MD Abstract The treatment of thoracic aortic disease has changed radically with the advances made in endovascular therapy since the concept of thoracic endovascular aortic repair was first described 15 years ago. Currently, there is a diverse array of endografts that are commercially available to treat the thoracic aorta. Multiple studies, including industry-sponsored and single-institution reports, have demonstrated excellent outcomes of thoracic endovascular aortic repair for the treatment of thoracic aortic aneurysms, with less reported perioperative morbidity and mortality in comparison with conventional open repair. Additionally, similar outcomes have been demonstrated for the treatment of type B dissections. However, the technology remains relatively novel, and larger studies with longer term outcomes are necessary to more fully evaluate the role of endovascular therapy for the treatment of thoracic aortic disease. This review examines the currently available thoracic endografts, preoperative planning for thoracic endovascular aortic repair, and outcomes of thoracic endovascular aortic repair for the treatment of both thoracic aortic aneurysms and type B aortic dissections. Mt Sinai J Med 77:256,269, 2010. © 2010 Mount Sinai School of Medicine [source] The Utility of Simulation in Medical Education: What Is the Evidence?MOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 4 2009Yasuharu Okuda MD Abstract Medical schools and residencies are currently facing a shift in their teaching paradigm. The increasing amount of medical information and research makes it difficult for medical education to stay current in its curriculum. As patients become increasingly concerned that students and residents are "practicing" on them, clinical medicine is becoming focused more on patient safety and quality than on bedside teaching and education. Educators have faced these challenges by restructuring curricula, developing small-group sessions, and increasing self-directed learning and independent research. Nevertheless, a disconnect still exists between the classroom and the clinical environment. Many students feel that they are inadequately trained in history taking, physical examination, diagnosis, and management. Medical simulation has been proposed as a technique to bridge this educational gap. This article reviews the evidence for the utility of simulation in medical education. We conducted a MEDLINE search of original articles and review articles related to simulation in education with key words such as simulation, mannequin simulator, partial task simulator, graduate medical education, undergraduate medical education, and continuing medical education. Articles, related to undergraduate medical education, graduate medical education, and continuing medical education were used in the review. One hundred thirteen articles were included in this review. Simulation-based training was demonstrated to lead to clinical improvement in 2 areas of simulation research. Residents trained on laparoscopic surgery simulators showed improvement in procedural performance in the operating room. The other study showed that residents trained on simulators were more likely to adhere to the advanced cardiac life support protocol than those who received standard training for cardiac arrest patients. In other areas of medical training, simulation has been demonstrated to lead to improvements in medical knowledge, comfort in procedures, and improvements in performance during retesting in simulated scenarios. Simulation has also been shown to be a reliable tool for assessing learners and for teaching topics such as teamwork and communication. Only a few studies have shown direct improvements in clinical outcomes from the use of simulation for training. Multiple studies have demonstrated the effectiveness of simulation in the teaching of basic science and clinical knowledge, procedural skills, teamwork, and communication as well as assessment at the undergraduate and graduate medical education levels. As simulation becomes increasingly prevalent in medical school and resident education, more studies are needed to see if simulation training improves patient outcomes. Mt Sinai J Med 76:330,343, 2009. © 2008 Mount Sinai School of Medicine [source] Folic acid and orofacial clefts: a review of the evidenceORAL DISEASES, Issue 1 2010GL Wehby Orofacial clefts are common and burdensome birth defects with a complex genetic and environmental etiology. The contribution of nutritional factors and supplements to the etiology of orofacial clefts has long been theorized and studied. Multiple studies have evaluated the role of folic acid in the occurrence and recurrence of orofacial clefts, using observational and non-randomized interventional designs. While preventive effects of folic acid on orofacial clefts are commonly reported, the evidence remains generally inconsistent. This paper reviews the findings of the main studies of the effects of folic acid on orofacial clefts, summarizes study limitations, and discusses research needs with a focus on studying the effects of high dosage folic acid on the recurrence of oral clefts using a randomized clinical trial design. The role of folic acid in the prevention of neural tube defects is also briefly summarized and discussed as a reference model for orofacial clefts. [source] The Safety and Efficacy of Tacrolimus Ointment in Pediatric Patients with Atopic DermatitisPEDIATRIC DERMATOLOGY, Issue 5 2010Alexandra D. McCollum M.D. It is a chronic disorder, characterized by intermittent flares and phases of remission. Treatment regimens often require multiple therapies. These can vary between patients, and in an individual patient, depending on the state of disease. The traditional treatment for AD flares is topical corticosteroids, which are fast acting and effective for relief of symptoms, but may cause adverse effects, including those resulting from systemic absorption, particularly in children. Topical calcineurin inhibitors (TCIs) are alternative treatments for AD. Tacrolimus ointment, a TCI, is approved for patients aged 2 years and older. Multiple studies have shown that tacrolimus is effective for short-term relief of symptoms in pediatric patients with AD. Long-term trials have demonstrated that the effectiveness of tacrolimus is maintained for up to 4 years in children. Additional studies have revealed that long-term intermittent use of tacrolimus as part of maintenance therapy can prevent AD flares. Tacrolimus has a low potential for systemic accumulation, and analysis of long-term studies indicates that it has a good safety profile. Treatment with tacrolimus, alone or in combination with topical corticosteroids for acute flares, may be a useful option for long-term management of AD in pediatric patients. [source] An evaluation of PCR primer sets used for detection of Propionibacterium acnes in prostate tissue samplesTHE PROSTATE, Issue 14 2008Karen S. Sfanos Abstract BACKGROUND Multiple studies have now shown that Propionibacterium acnes can be cultured from post-prostatectomy derived prostate tissue samples. In contrast, both universal eubacterial 16S rDNA PCR and P. acnes -specific 16S rDNA PCR have failed to detect this organism at a frequency similar to that of bacterial culture. A potential explanation for this discrepancy, proposed by Cohen et al., involves mismatches in 16S rDNA primer sets used for bacterial detection. METHODS The sensitivity of both a previously published P. acnes -specific primer set containing a potential mismatch and a new primer set with no mismatches was determined. Both primer sets were used to interrogate two sets of DNA samples derived from post-prostatectomy prostate tissues that differed in the level of sterile precautions maintained during tissue collection. RESULTS The number of P. acnes positive samples was associated with the sterility of the sample collection process. In all instances, positive samples were determined to reflect low cell numbers (<10 CFU). CONCLUSIONS Although the results of previous studies have shown that P. acnes is not the only organism potentially present in the prostates of prostate cancer patients, mismatches in PCR primer sets may have also influenced the sensitivity of P. acnes detection. When using PCR in determining the presence of P. acnes in the human prostate, care should be taken to establish the potential influence of exogenous contamination and, due to the sensitivity of the assay, samples exposed to the urethra during the collection process (prostatic secretions, TURP specimens) should not be used. Prostate 68: 1492,1495, 2008. © 2008 Wiley-Liss, Inc. [source] Epidemiology of recurrent respiratory papillomatosisAPMIS, Issue 6-7 2010DANIEL A. LARSON Larson DA, Derkay CS. Epidemiology of recurrent respiratory papillomatosis. APMIS 2010; 118: 450,454. Recurrent respiratory papillomatosis (RRP) was first described in the 1800s, but it was not until the 1980s when it was convincingly attributed to human papilloma virus (HPV). RRP is categorized into juvenile onset and adult onset depending on presentation before or after the age of 12 years, respectively. The prevalence of this disease is likely variable depending on the age of presentation, country and socioeconomic status of the population being studied, but is generally accepted to be between 1 and 4 per 100 000. Despite the low prevalence, the economic burden of RRP is high given the multiple procedures required by patients. Multiple studies have shown that the most likely route of transmission of HPV in RRP is from mother to child during labor. Exceptions to this may include patients with congenital RRP who have been exposed in utero and adult patients who may have been exposed during sexual contact. Although cesarean section may prevent the exposure of children to the HPV virus during childbirth, its effectiveness in preventing RRP is debatable and the procedure itself carries an increased risk of complications. The quadrivalent HPV vaccine holds the most promise for the prevention of RRP by eliminating the maternal reservoir for HPV. [source] Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity,ARTHRITIS & RHEUMATISM, Issue 8 2010Vitaly Napadow Objective Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. The objective of this study was to investigate the degree of connectivity between multiple brain networks in patients with FM, as well as how activity in these networks correlates with the level of spontaneous pain. Methods Resting-state functional magnetic resonance imaging (FMRI) data from 18 patients with FM and 18 age-matched healthy control subjects were analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic, or resting-state, connectivity was evaluated in multiple brain networks: the default mode network (DMN), the executive attention network (EAN), and the medial visual network (MVN), with the MVN serving as a negative control. Spontaneous pain levels were also analyzed for covariance with intrinsic connectivity. Results Patients with FM had greater connectivity within the DMN and right EAN (corrected P [Pcorr] < 0.05 versus controls), and greater connectivity between the DMN and the insular cortex, which is a brain region known to process evoked pain. Furthermore, greater intensity of spontaneous pain at the time of the FMRI scan correlated with greater intrinsic connectivity between the insula and both the DMN and right EAN (Pcorr < 0.05). Conclusion These findings indicate that resting brain activity within multiple networks is associated with spontaneous clinical pain in patients with FM. These findings may also have broader implications for how subjective experiences such as pain arise from a complex interplay among multiple brain networks. [source] Clinical trials and statistical analyses: what should dermatologists look for in a report?DERMATOLOGIC THERAPY, Issue 3 2009Mohamed Alosh ABSTRACT Clinicians need to evaluate the quality of individual clinical studies and synthesize the information from multiple clinical studies to provide insights in selecting appropriate therapies for patients. Understanding the key statistical principles that underlie a clinical trial and how they may be implemented can help clinicians properly interpret the efficacy and safety findings of clinical trials. Several factors should be considered when evaluating clinical studies reported in the literature, as important differences might exist among reported studies, thereby impacting the reliability of their findings. Studies vary in terms of study design, conduct, analysis, and presentation of findings. The key features to consider when evaluating clinical trials are inferential intent (exploratory versus confirmatory), choice of control group, randomization, extent of blinding, prespecification of analyses, appropriate handling of missing data, and multiple end points. Making comparisons across studies is extremely difficult and rarely statistically justified. However, this article will point out issues to keep in mind when evaluating multiple studies, such as variations in design and study populations. [source] The role of renin,angiotensin,aldosterone system-based therapy in diabetes prevention and cardiovascular and renal protectionDIABETES OBESITY & METABOLISM, Issue 12 2008Hussam Abuissa Hypertension increases the risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease. In addition to lowering blood pressure, blockade of the renin,angiotensin,aldosterone system (RAAS) reduces the risk of new-onset T2DM and offers renal protection. Using a MEDLINE search, we identified multiple trials that reported the incidence of T2DM in patients taking inhibitors of RAAS. In this review, we will discuss the RAAS as a potential target in diabetes prevention and the mechanisms through which inhibitors of this system achieve such an important effect. We will also shed light on the beneficial cardiovascular and renal effects of RAAS blockade. Although multiple studies have demonstrated that inhibitors of RAAS, especially angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, can reduce the incidence of T2DM, randomized controlled studies are still needed to further elucidate their exact role in diabetes prevention. [source] Genetics of Type 2 diabetesDIABETIC MEDICINE, Issue 5 2005I. Barroso Abstract Type 2 diabetes (T2D) has become a health-care problem worldwide, with the rise in disease prevalence being all the more worrying as it not only affects the developed world but also developing nations with fewer resources to cope with yet another major disease burden. Furthermore, the problem is no longer restricted to the ageing population, as young adults and children are also being diagnosed with T2D. In recent years, there has been a surge in the number of genetic studies of T2D in attempts to identify some of the underlying risk factors. In this review, I highlight the main genes known to cause uncommon monogenic forms of diabetes (e.g. maturity-onset diabetes of the young,MODY,and insulin resistance syndromes), as well as describe some of the main approaches used to identify genes involved in the more common forms of T2D that result from the interaction between environmental risk factors and predisposing genotypes. Linkage and candidate gene studies have been highly successful in the identification of genes that cause the monogenic variants of diabetes and, although progress in the more common forms of T2D has been slow, a number of genes have now been reproducibly associated with T2D risk in multiple studies. These are discussed, as well as the main implications that the diabetes gene discoveries will have in diabetes treatment and prevention. [source] SYNTHESIS: Life history change in commercially exploited fish stocks: an analysis of trends across studiesEVOLUTIONARY APPLICATIONS (ELECTRONIC), Issue 3 2009Diana M. T. Sharpe Abstract Age and size at maturation have declined dramatically in many commercial fish stocks over the past few decades , changes that have been widely attributed to fishing pressure. We performed an analysis of such trends across multiple studies, to test for the consistency of life history changes under fishing, and for their association with the intensity of exploitation (fishing mortality rate). We analyzed 143 time series from 37 commercial fish stocks, the majority of which originated from the North Atlantic. Rates of phenotypic change were calculated for two traditional maturation indices (length and age at 50% maturity), as well as for probabilistic maturation reaction norms (PMRNs). We found that all three indices declined in heavily exploited populations, and at a rate that was strongly correlated with the intensity of fishing (for length at 50% maturity and PMRNs). These results support previous assertions that fishing pressure is playing a major role in the life history changes observed in commercial fish stocks. Rates of change were as strong for PMRNs as for age and size at 50% maturity, which is consistent with the hypothesis that fishing-induced phenotypic changes can sometimes have a genetic basis. [source] Enabling regional management in a changing climate through Bayesian meta-analysis of a large-scale disturbanceGLOBAL ECOLOGY, Issue 3 2010M Aaron MacNeil ABSTRACT Aim, Quantifying and predicting change in large ecosystems is an important research objective for applied ecologists as human disturbance effects become increasingly evident at regional and global scales. However, studies used to make inferences about large-scale change are frequently of uneven quality and few in number, having been undertaken to study local, rather than global, change. Our aim is to improve the quality of inferences that can be made in meta-analyses of large-scale disturbance by integrating studies of varying quality in a unified modelling framework that is informative for both local and regional management. Innovation, Here we improve conventionally structured meta-analysis methods by including imputation of unknown study variances and the use of Bayesian factor potentials. The approach is a coherent framework for integrating data of varying quality across multiple studies while facilitating belief statements about the uncertainty in parameter estimates and the probable outcome of future events. The approach is applied to a regional meta-analysis of the effects of loss of coral cover on species richness and the abundance of coral-dependent fishes in the western Indian Ocean (WIO) before and after a mass bleaching event in 1998. Main conclusions, Our Bayesian approach to meta-analysis provided greater precision of parameter estimates than conventional weighted linear regression meta-analytical techniques, allowing us to integrate all available data from 66 available study locations in the WIO across multiple scales. The approach thereby: (1) estimated uncertainty in site-level estimates of change, (2) provided a regional estimate for future change at any given site in the WIO, and (3) provided a probabilistic belief framework for future management of reef resources at both local and regional scales. [source] A comparison of label-based review and ALE meta-analysis in the Stroop taskHUMAN BRAIN MAPPING, Issue 1 2005Angela R. Laird Abstract Meta-analysis is an important tool for interpreting results of functional neuroimaging studies and is highly influential in predicting and testing new outcomes. Although traditional label-based review can be used to search for agreement across multiple studies, a new function-location meta-analysis technique called activation likelihood estimation (ALE) offers great improvements over conventional methods. In ALE, reported foci are modeled as Gaussian functions and pooled to create a statistical whole-brain image. ALE meta-analysis and the label-based review were used to investigate the Stroop task in normal subjects, a paradigm known for its effect of producing conflict and response inhibition due to subjects' tendency to perform word reading as opposed to color naming. Both methods yielded similar activation patterns that were dominated by response in the anterior cingulate and the inferior frontal gyrus. ALE showed greater involvement of the anterior cingulate as compared to that in the label-based technique; however, this was likely due to the increased spatial level of distinction allowed with the ALE method. With ALE, further analysis of the anterior cingulate revealed evidence for somatotopic mapping within the rostral and caudal cingulate zones, an issue that has been the source of some conflict in previous reviews of the anterior cingulate cortex. Hum Brain Mapp 25:6,21, 2005. © 2005 Wiley-Liss, Inc. [source] Generalizability in Communication ResearchHUMAN COMMUNICATION RESEARCH, Issue 4 2002Michael A. Shapiro In communication research, attempts to enhance external validity usually focus on techniques to enhance the surface representativeness attained in a particular study. Such surface representativeness is a useful tool. However, a larger ability to generalize emerges from a constantly evolving scientific discourse across multiple studies about how social meanings and social behaviors impact outcomes. The resulting conceptual knowledge enables us to generalize about communication across a much wider range of persons, settings, times, and messages than does surface similarity. The findings of a study should be examined in light of its contribution to theory. The surface representativeness of a study is usually not a good indicator of contribution to theory. The discipline of communication, particularly journal editors and reviewers, bears a heavy responsibility to think about generalizability in the complex ways the topic requires. [source] Safety and tolerability of duloxetine in the treatment of major depressive disorder: analysis of pooled data from eight placebo-controlled clinical trialsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2005James I. Hudson Abstract Objective To examine the safety and tolerability of the antidepressant duloxetine across multiple studies for major depressive disorder (MDD). Method Safety data were integrated from the acute phases of eight double-blind, placebo-controlled trials in which patients were randomized to duloxetine (40,120,mg/d; n,=,1139) or placebo (n,=,777) for up to 9 weeks. This data set included all acute-phase clinical trials that formed the basis of the New Drug Application (United States) or European Union submission package for duloxetine in the treatment of MDD. Two studies included continuation phases in which acute treatment responders received duloxetine or placebo for an additional 26 weeks. Safety assessments included serious adverse event reports, rates of discontinuation, spontaneously reported treatment-emergent adverse events, changes in vital signs and laboratory values, and electrocardiograms. Results The rates of serious adverse events for duloxetine- and placebo-treated patients were 0.3% and 0.6%, respectively (p,=,0.282). Adverse events led to discontinuation in 9.7% of duloxetine-treated patients, compared with 4.2% of patients receiving placebo (p,<,0.001). Treatment-emergent adverse events with an incidence for duloxetine ,,5.0% and significantly greater than placebo were nausea, dry mouth, constipation, insomnia, dizziness, fatigue, somnolence, increased sweating and decreased appetite. Mean changes in blood pressure and heart rate were small, and the incidence of increases above normal ranges was low. Duloxetine-treated patients had a mean decrease in weight of 0.5,kg compared with an increase of 0.2,kg for patients receiving placebo (p,<,0.001). No significant differences were found between duloxetine and placebo in the incidence of potentially clinically significant laboratory values at anytime while on treatment. Conclusion These results are consistent with those obtained previously from smaller pooled data sets, and suggest that duloxetine is safe and well tolerated in patients with MDD. Copyright © 2005 John Wiley & Sons, Ltd. [source] Postoperative therapy for Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2009Eric Blum MD Abstract Prevention of the postoperative recurrence of Crohn's disease (CD) remains a challenging clinical problem. The majority of patients with CD will need surgery for treatment of the disease, most of these patients will develop recurrent symptoms within 5 years postoperatively, and many patients will need reoperation within 10 years. In patients with an ileocolic anastomosis, endoscopic recurrence precedes clinical recurrence and the severity of endoscopic recurrence correlates with the risk of clinical recurrence. Despite multiple studies, the best postoperative prophylactic therapy remains uncertain. Numerous randomized controlled trials of 5-aminosalicylates have shown only modest effect. Antibiotics, including metronidazole and ornidazole, decrease short-term, but not long-term endoscopic recurrence and are limited by side effects. Immunomodulators have yet to be extensively evaluated, although limited data suggest possible efficacy in preventing postoperative recurrence, particularly in high-risk patients. This review will evaluate the current state of the art therapy for postoperative prophylaxis in CD, with an emphasis on critical analysis of the available randomized controlled trials. (Inflamm Bowel Dis 2008) [source] Learning sobriety together: behavioural couples therapy for alcoholism and drug abuseJOURNAL OF FAMILY THERAPY, Issue 2 2009William Fals-Stewart Among the various types of partner- and family-involved interventions used to treat adults with substance use disorders, Behavioural Couples Therapy (BCT) has garnered the strongest empirical support for its efficacy. During the past thirty years, multiple studies have consistently found married or cohabiting substance-abusing patients who engage in BCT, compared to traditional individual-based counselling or partner-involved attention control treatments, report significantly greater (1) reductions in substance use, (2) levels of relationship satisfaction, and (3) greater improvements in other areas of relationship and family adjustment (e.g. reductions in partner violence, improvements in custodial children's adjustment). In addition to discussing the theoretical rationale for BCT as a treatment of substance abuse, this article describes specific therapeutic techniques used as part of this intervention and summarizes the relevant evaluative empirical literature. [source] Ultrastructure of spermiogenesis in the Cottonmouth, Agkistrodon piscivorus (Squamata: Viperidae: Crotalinae)JOURNAL OF MORPHOLOGY, Issue 3 2010Kevin M. Gribbins Abstract To date multiple studies exist that examine the morphology of spermatozoa. However, there are limited numbers of data detailing the ontogenic characters of spermiogenesis within squamates. Testicular tissues were collected from Cottonmouths (Agkistrodon piscivorus) and tissues from spermiogenically active months were analyzed ultrastructurally to detail the cellular changes that occur during spermiogenesis. The major events of spermiogenesis (acrosome formation, nuclear elongation/DNA condensation, and flagellar development) resemble that of other squamates; however, specific ultrastructural differences can be observed between Cottonmouths and other squamates studied to date. During acrosome formation vesicles from the Golgi apparatus fuse at the apical surface of the nuclear membrane prior to making nuclear contact. At this stage, the acrosome granule can be observed in a centralized location within the vesicle. As elongation commences the acrosome complex becomes highly compartmentalized and migrates laterally along the nucleus. Parallel and circum-cylindrical microtubules (components of the manchette) are observed with parallel microtubules outnumbering the circum-cylindrical microtubules. Flagella, displaying the conserved 9 + 2 microtubule arrangement, sit in nuclear fossae that have electron lucent shoulders juxtaposed on either side of the spermatids basal plates. This study aims to provide developmental characters for squamates in the subfamily Crotalinae, family Viperidae, which may be useful for histopathological studies on spermatogenesis in semi-aquatic species exposed to pesticides. Furthermore, these data in the near future may provide morphological characters for spermiogenesis that can be added to morphological data matrices that may be used in phylogenetic analyses. J. Morphol. 2010. © 2009 Wiley-Liss, Inc. [source] Local recurrence rate of fine-needle aspiration biopsy in primary high-grade sarcomasJOURNAL OF SURGICAL ONCOLOGY, Issue 7 2010Benjamin H. Kaffenberger BS Abstract Background Fine-needle aspiration biopsy (FNAB) is an emerging technique for diagnosis of bone and soft tissue lesions. While multiple studies have demonstrated efficacy, cost-effectiveness, and convenience, none have attempted to determine if the modality leads to an increased rate of local recurrence. Our objective was to determine whether FNAB could be linked to an increased rate of local recurrence. Methods We reviewed a database containing records of 388 patients who underwent FNAB without surgical biopsy tract excision between September 2002 and December 2006 in the orthopedics department at our institution. After application of rigid criteria to minimize confounding variables, 20 patients were retrospectively examined for local recurrence and distant metastasis. Results In this cohort, no local recurrences were seen over a mean follow-up of 45 months. Fifteen percent of our patients developed one or more distant metastases over the same time interval. Our experience offers preliminary evidence for the safety of this method. Conclusions While further studies are needed, our data combined with already reported studies on efficacy, cost-effectiveness, and convenience are encouraging for expanding the use of FNAB in the diagnosis of bone and soft tissue tumors. J. Surg. Oncol. 2010; 101:618,621. © 2010 Wiley-Liss, Inc. [source] Phase I study on sentinel lymph node mapping in colon cancer: A preliminary report,JOURNAL OF SURGICAL ONCOLOGY, Issue 2 2002Yves Bendavid Abstract Background and Objectives Lymph node (LN) metastasis is one of the most significant prognostic factor in colorectal cancer. In fact, therapeutic decisions are based on LN status. However, multiple studies have reported on the limitations of the conventional pathological LN examination techniques, and therefore, the actual number of patients with LN positive colorectal cancer is probably underestimated. We assume that lymphatic tumor dissemination follows an orderly sequential route. We report here a simple and harmless coloration technique that was recently elaborated, and that allows us to identify the sentinel LN(s) (SLN) or first relay LNs in colorectal cancer patients. The main endpoint of this clinical trial is the feasibility of the technique. Methods Twenty patients treated by surgery for a colic cancer were admitted in this protocol. A subserosal peritumoral injection of lymphazurin 1% was performed 10 min before completing the colic resection. A pathologist immediately examined the specimens, harvested the colored SLN, and examined them by serial cuts (200 ,m) with H&E staining, followed by immunohistochemical staining (AE1-AE3 cytokeratin markers), when serial sections were classified as cancer free. Results The preoperative identification of the SLN was impossible in at least 50 of the cases, however, SLNs were identified by the pathologist in 90% of cases. In two patients (10%) SLN was never identified. The average number of SLN was 3.9. Immunohistochemical analysis of the SLN has potentially changed the initial staging (from Dukes B to Dukes C) for 5 of the 20 patients (25%). On the other hand, there was one patient (5%) with hepatic metastasis from adenocarcinoma for whom SLN pathology was negative for metastasis (skip metastasis). Conclusions SLN biopsy is readily feasible with identification of SLN in at least 90% of patients with colorectal cancers. Our results indicate that 45% of patients initially staged as Dukes B had tumor cells identified in their SLN when these were subjected to our protocol. This represented a 25% upgrading rate when our complete study population is considered. However, controversy persist about the clinical significance and metastatic potential of these often very small clusters of tumor cells. J. Surg. Oncol. 2002;79:81,84. © 2002 Wiley-Liss, Inc. [source] Nurse Practitioner, Nurse Midwife and Physician Assistant Attitudes and Care Practices Related to Persons with HIV/AIDSJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 2 2000Jane E. Martin RN ABSTRACT Although multiple studies of nurses' attitudes toward people living with HIV/AIDS (PLWAs) can be found in the literature, little is known about the attitudes, beliefs and practices of nurse practitioners (NPs), certified nurse midwives (CNMs), and physician assistants (PAs). A survey including a 21-item AIDS Attitude Scale measuring the constructs of Avoidance and Empathy was sent to 1,291 NPs, CNMs and PAs in Louisiana, Arkansas and Mississippi to describe their attitudes and care practices related to PLWAs. Respondents who were more comfortable treating PLWAs had significantly lower avoidance scores and significantly higher empathy scores than respondents with lower comfort levels in providing care. Greater than 80% of respondents indicated that they would provide health care to HIV-infected individuals. Respondents who referred HIV/AIDS patients for all care did so primarily due to lack of experience with HIV and the availability of more experienced providers. Avoidance and empathy scores were not found to be significantly associated with referral for care. This study suggests that this group of providers has relatively low avoidance and high empathy toward PLWAs and is willing to care for HIV-infected individuals. This study was supported by Grant No. 5U69PE00112-06 from the Department of Health & Human Services, Health Resources and Services Administration, HIV/AIDS Bureau, National AIDS Education and Training Center. [source] Meta-analysis of pharmacokinetic data of veterinary drugs using the Food Animal Residue Avoidance Databank: oxytetracycline and procaine penicillin GJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2004A. L. Craigmill Investigators frequently face the quandary of how to interpret the oftentimes disparate pharmacokinetic parameter values reported in the literature. Combining of data from multiple studies (meta-analysis) is a useful tool in pharmacokinetics. Few studies have explored the use of meta-analysis for veterinary species. Even fewer studies have explored the potential strengths and weaknesses of the various methods of performing a meta-analysis. Therefore, in this study we performed a meta-analysis for oxytetracycline (OTC) and procaine penicillin G (PPG) given intramuscularly to cattle. The analysis included 28 individual data sets from 18 published papers for PPG (288 data points), and 41 individual data sets from 25 published papers for OTC (489 data points). Three methods were used to calculate the parameters. The first was a simple statistical analysis of the parameter values reported in each paper. The second method was a standard Two-Stage Method (TSM) using the mean concentration vs. time data extracted from each paper. The third method was the use of nonlinear mixed effect modeling (NMEM) of the concentration vs. time data reported in the various papers, treating the mean data as if each set came from an individual animal. The results of this evaluation indicate that all three methods generate comparable mean parameter estimates for OTC and PPG. The only significant difference noted was for OTC absorption half-lives taken from the published literature, a difference attributable to the use of an alternative method of parameter calculation. The NMEM procedure offers the possibility of including covariates such as dose, age, and weight. In this study the covariates did not influence the derived parameters. A combination approach to meta-analysis of published mean data is recommended, where the TSM is the first step, followed by the NMEM approach. [source] Association of ERCC1 polymorphisms and susceptibility to nasopharyngeal carcinomaMOLECULAR CARCINOGENESIS, Issue 3 2009Zhi-Hui Yang Abstract The normal function of excision repair cross complementing group 1 (ERCC1) is essential for maintaining genomic integrity and preventing cellular neoplastic transformation, and multiple studies have reported an association between ERCC1 polymorphisms and increased risk of cancers. To test whether the genetic variants of ERCC1 gene modify the risk of nasopharyngeal carcinoma (NPC), we compared the 8092 C,>,A and 19007 C,>,T single nucleotide polymorphisms (SNPs) and the haplotypes of ERCC1 between 267 patients with NPC and 304 healthy controls. Linkage disequilibrium was observed between the two SNPs loci (D,,=,0.861). Significant differences of allele frequencies were found for ERCC1 8092C,>,A between the cases and controls. Individuals with 8092 C allele showed 1.411-fold (OR,=,1.411, 95% CI, 1.076,1.850, P,=,0.014) increased risk of developing NPC, and the CC haplotype was associated with a significantly increased risk of NPC (OR,=,1.712; 95% CI, 1.211,2.421; P,=,0.013). No interactions were found between 8092C,>,A polymorphism and genders, smoking status and alcohol consumption. These results suggested that the polymorphism of ERCC1 8092 C,>,A might be a contributing factor in the development of NPC in Chinese population. © 2008 Wiley-Liss, Inc. [source] Non-therapeutic risk factors for onset of tardive dyskinesia in schizophrenia: A meta-analysis,,MOVEMENT DISORDERS, Issue 16 2009Diederik E. Tenback MD Abstract A meta-analysis of prospective studies with schizophrenia patients was conducted to examine whether the evidence exists for risk factors for the emergence of Tardive Dyskinesia (TD) in schizophrenia. A computer assisted Medline/PubMed and Embase search was conducted in January 2008 for the years 1985,2007. Selected were truly prospective studies of incident cases of TD in a population with at least 80% patients with schizophrenia. Measures of relative risk were collected from the individual studies, either directly or by calculating the relative risk from the cox- or logistic regression coefficient provided in the article. Hazard Ratio's and Odds Ratio's were pooled using fixed and random effect models in case of multiple studies using the same measure of risk and outcome. Only eight studies satisfied the inclusion criteria reporting on 25 different single estimate risk factors. Of 25 risk factors, six concerned replicated estimates suitable for meta-analysis. Of these, non-white ethnic group and early extrapyramidal symptoms qualified as risk factors for the emergence of TD in schizophrenia. The association with older age was suggestive but inconclusive. Despite many reported risk factors for TD in schizophrenia, little conclusive evidence exists to corroborate this. However, the fact that early EPS predicts onset of TD has important clinical and research implications. © 2009 Movement Disorder Society [source] |