Current concepts of the management of dental extractions for patients taking warfarin

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: Controversy has surrounded the correct management of patients therapeutically anticoagulated with warfarin who require dental extractions. The risk of bleeding must be weighed up against the risk of thromboembolism when deciding whether to interfere with a patient's warfarin regimen. An improved understanding of the importance of fibrinolytic mechanisms in the oral cavity has resulted in the development of various local measures to enable these patients to be treated on an outpatient basis. Methods: A review of the literature was undertaken. This was supplemented by the authors' clinical trials and extensive clinical experience with anticoagulated patients. Results: Various protocols for treating patients taking warfarin have been reviewed and summarized and an overview of the haemostatic and fibrinolytic systems is presented. A protocol for management of warfarinized patients requiring dental extractions in the outpatient setting is proposed. Conclusions: Patients therapeutically anticoagulated with warfarin can be treated on an ambulatory basis, without interruption of their warfarin regimen provided appropriate local measures are used.G Carter, AN Goss, JV Lloyd, R Tocchett

Individualism and stock price crash risk

Employing a sample of 26,473 firms across 42 countries from 1990 to 2013, we find that firms located in countries with higher individualism have higher stock price crash risk. Furthermore, individualism can be transmitted by foreign investors from overseas markets to influence local firms’ crash risk, and can exacerbate the impact of firm risk taking and earnings management on crash risk. Moreover, the positive relation between individualism and crash risk is amplified during the global financial crisis and attenuated by enhanced country-level financial information transparency and the adoption of International Financial Reporting Standards

Comparison of gene expression during in vivo and in vitro postnatal retina development

Retina explants are widely used as a model of neural development. To define the molecular basis of differences between the development of retina in vivo and in vitro during the early postnatal period, we carried out a series of microarray comparisons using mouse retinas. About 75% of 8,880 expressed genes from retina explants kept the same expression volume and pattern as the retina in vivo. Fewer than 6% of the total gene population was changed at two consecutive time points, and only about 1% genes showed more than a threefold change at any time point studied. Functional Gene Ontology (GO) mapping for both changed and unchanged genes showed similar distribution patterns, except that more genes were changed in the GO clusters of response to stimuli and carbohydrate metabolism. Three distinct expression patterns of genes preferentially expressed in rod photoreceptors were observed in the retina explants. Some genes showed a lag in increased expression, some showed no change, and some continued to have a reduced level of expression. An early downregulation of cyclin D1 in the explanted retina might explain the reduction in numbers of precursors in explanted retina and suggests that external factors are required for maintenance of cyclin D1. The global view of gene profiles presented in this study will help define the molecular changes in retina explants over time and will provide criteria to define future changes that improve this model system

Patient-reported outcomes in a trial of exenatide and insulin glargine for the treatment of type 2 diabetes

BACKGROUND: Patient-reported measures can be used to examine whether drug differences other than clinical efficacy have an impact on outcomes that may be important to patients. Although exenatide and insulin glargine appear to have similar efficacy for treatment of type 2 diabetes, there are several differences between the two treatments that could influence outcomes from the patient's perspective. The purpose of the current study was to examine whether the two drugs were comparable as assessed by patient-reported outcomes using data from a clinical trial in which these injectable medications were added to pre-existing oral treatment regimens. METHODS: Patients were randomized to either twice daily exenatide or once daily insulin glargine during a 26-week international trial. At baseline and endpoint, five patient-reported outcome measures were administered: the Vitality Scale of the SF-36, The Diabetes Symptom Checklist – Revised (DSC-R), the EuroQol EQ-5D, the Treatment Flexibility Scale (TFS), and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Change from baseline to endpoint was analyzed within each treatment group. Group differences were examined with General linear models (GLMs), controlling for country and baseline scores. RESULTS: A total of 549 patients with type 2 diabetes were enrolled in the trial, and current analyses were conducted with data from the 455 per protocol patients (228 exenatide and 227 insulin glargine). The sample was primarily Caucasian (79.6%), with slightly more men (55.2%) than women, and with a mean age of 58.5 years. Paired t-tests found that both treatment groups demonstrated statistically significant baseline to endpoint change on several of the health outcomes instruments including the DSC-R, DTSQ, and the SF-36 Vitality subscale. GLMs found no statistically significant differences between groups in change on the health outcomes instruments. CONCLUSION: This analysis found that both exenatide and insulin glargine were associated with significant improvements in patient-reported outcomes when added to oral medications among patients with type 2 diabetes. Despite an additional daily injection and a higher rate of gastrointestinal adverse events, treatment satisfaction in the exenatide group was comparable to that of the glargine group, possibly because of weight reduction observed in patients treated with exenatide

Phosphorylation of AMPA Receptors Is Required for Sensory Deprivation-Induced Homeostatic Synaptic Plasticity

Sensory experience, and the lack thereof, can alter the function of excitatory synapses in the primary sensory cortices. Recent evidence suggests that changes in sensory experience can regulate the synaptic level of Ca2+-permeable AMPA receptors (CP-AMPARs). However, the molecular mechanisms underlying such a process have not been determined. We found that binocular visual deprivation, which is a well-established in vivo model to produce multiplicative synaptic scaling in visual cortex of juvenile rodents, is accompanied by an increase in the phosphorylation of AMPAR GluR1 (or GluA1) subunit at the serine 845 (S845) site and the appearance of CP-AMPARs at synapses. To address the role of GluR1-S845 in visual deprivation-induced homeostatic synaptic plasticity, we used mice lacking key phosphorylation sites on the GluR1 subunit. We found that mice specifically lacking the GluR1-S845 site (GluR1-S845A mutants), which is a substrate of cAMP-dependent kinase (PKA), show abnormal basal excitatory synaptic transmission and lack visual deprivation-induced homeostatic synaptic plasticity. We also found evidence that increasing GluR1-S845 phosphorylation alone is not sufficient to produce normal multiplicative synaptic scaling. Our study provides concrete evidence that a GluR1 dependent mechanism, especially S845 phosphorylation, is a necessary pre-requisite step for in vivo homeostatic synaptic plasticity

A deletion and a duplication in distal 22q11.2 deletion syndrome region. Clinical implications and review

<p>Abstract</p> <p>Background</p> <p>Individuals affected with DiGeorge and Velocardiofacial syndromes present with both phenotypic diversity and variable expressivity. The most frequent clinical features include conotruncal congenital heart defects, velopharyngeal insufficiency, hypocalcemia and a characteristic craniofacial dysmorphism. The etiology in most patients is a 3 Mb recurrent deletion in region 22q11.2. However, cases of infrequent deletions and duplications with different sizes and locations have also been reported, generally with a milder, slightly different phenotype for duplications but with no clear genotype-phenotype correlation to date.</p> <p>Methods</p> <p>We present a 7 month-old male patient with surgically corrected ASD and multiple VSDs, and dysmorphic facial features not clearly suggestive of 22q11.2 deletion syndrome, and a newborn male infant with cleft lip and palate and upslanting palpebral fissures. Karyotype, FISH, MLPA, microsatellite markers segregation studies and SNP genotyping by array-CGH were performed in both patients and parents.</p> <p>Results</p> <p>Karyotype and FISH with probe N25 were normal for both patients. MLPA analysis detected a partial <it>de novo </it>1.1 Mb deletion in one patient and a novel partial familial 0.4 Mb duplication in the other. Both of these alterations were located at a distal position within the commonly deleted region in 22q11.2. These rearrangements were confirmed and accurately characterized by microsatellite marker segregation studies and SNP array genotyping.</p> <p>Conclusion</p> <p>The phenotypic diversity found for deletions and duplications supports a lack of genotype-phenotype correlation in the vicinity of the LCRC-LCRD interval of the 22q11.2 chromosomal region, whereas the high presence of duplications in normal individuals supports their role as polymorphisms. We suggest that any hypothetical correlation between the clinical phenotype and the size and location of these alterations may be masked by other genetic and/or epigenetic modifying factors.</p

Search for Top-Quark Partners with Charge 5/3 in the Same-Sign Dilepton Final State

A search for the production of heavy partners of the top quark with charge 5/3 is performed in events with a pair of same-sign leptons. The data sample corresponds to an integrated luminosity of 19.5 fb(-1) and was collected at root s = 8 TeV by the CMS experiment. No significant excess is observed in the data above the expected background, and the existence of top-quark partners with masses below 800 GeV is excluded at a 95% confidence level, assuming they decay exclusively to tW. This is the first limit on these particles from the LHC, and it is significantly more restrictive than previous limits

Measurement of the cross section and angular correlations for associated production of a Z boson with b hadrons in pp collisions at root s=7 TeV

A study of proton-proton collisions in which two b hadrons are produced in association with a Z boson is reported. The collisions were recorded at a centre-of-mass energy of 7 TeVwith the CMS detector at the LHC, for an integrated luminosity of 5.2 fb(-1). The b hadrons are identified by means of displaced secondary vertices, without the use of reconstructed jets, permitting the study of b-hadron pair production at small angular separation. Differential cross sections are presented as a function of the angular separation of the b hadrons and the Z boson. In addition, inclusive measurements are presented. For both the inclusive and differential studies, different ranges of Z boson momentum are considered, and each measurement is compared to the predictions from different event generators at leading-order and next-to-leading-order accuracy

Searches for long-lived charged particles in pp collisions at root s=7 and 8 TeV

Results of searches for heavy stable charged particles produced in pp collisions at root s = 7 and 8 TeV are presented corresponding to an integrated luminosity of 5.0 fb(-1) and 18.8 fb(-1), respectively. Data collected with the CMS detector are used to study the momentum, energy deposition, and time-of-flight of signal candidates. Leptons with an electric charge between e/3 and 8e, as well as bound states that can undergo charge exchange with the detector material, are studied. Analysis results are presented for various combinations of signatures in the inner tracker only, inner tracker and muon detector, and muon detector only. Detector signatures utilized are long time-of-flight to the outer muon system and anomalously high (or low) energy deposition in the inner tracker. The data are consistent with the expected background, and upper limits are set on the production cross section of long-lived gluinos, scalar top quarks, and scalar tau leptons, as well as pair produced long-lived leptons. Corresponding lower mass limits, ranging up to 1322 GeV/c(2) for gluinos, are the most stringent to date