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Background The prevalence of atrial fibrillation ( AF ) continues to increase; however, there are limited data describing the division of care among practitioners in the community and whether care differs depending on provider specialty. Methods and Results Using the Outcomes Registry for Better Informed Treatment of AF ( ORBIT ‐ AF ) Registry, we described patient characteristics and AF management strategies in ambulatory clinic practice settings, including electrophysiology ( EP ), general cardiology, and primary care. A total of 10 097 patients were included; of these, 1544 (15.3%) were cared for by an EP provider, 6584 (65.2%) by a cardiology provider, and 1969 (19.5%) by an internal medicine/primary care provider. Compared with those patients who were cared for by cardiologists or internal medicine/primary care providers, patients cared for by EP providers were younger (median age, 73 years [interquartile range, IQR , 64, 80 years, Q1, Q3] versus 75 years [ IQR , 67, 82 years] for cardiology and versus 76 years [ IQR , 68, 82 years] for primary care). Compared with cardiology and internal medicine/primary care providers, EP providers used rhythm control (versus rate control) management more often (44.2% versus 29.7% and 28.8%, respectively, P <0.0001; adjusted odds ratio [ OR ] EP versus cardiology, 1.66 [95% confidence interval, CI , 1.05 to 2.61]; adjusted OR for internal medicine/primary care versus cardiology, 0.91 [95% CI , 0.65 to 1.26]). Use of oral anticoagulant therapy was high across all providers, although it was higher for cardiology and EP providers (overall, 76.1%; P =0.02 for difference between groups). Conclusions Our data demonstrate important differences between provider specialties, the demographics of the AF patient population treated, and treatment strategies—particularly for rhythm control and anticoagulation therapy.

Abstract The critical role of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by both laboratory and clinical experts, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including Tickborne Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

In vivo assessment of ventricular function in rodents has largely been restricted to transthoracic echocardiography (TTE). However 1.5 T cardiac magnetic resonance (CMR) and transoesophageal echocardiography (TOE) have emerged as possible alternatives. Yet, to date, no study has systematically assessed these three imaging modalities in determining ejection fraction (EF) in rats. Twenty rats underwent imaging four weeks after surgically-induced myocardial infarction. CMR was performed on a 1.5 T scanner, TTE was conducted using a 9.2 MHz transducer and TOE was performed with a 10 MHz intracardiac echo catheter. Correlation between the three techniques for EF determination and analysis reproducibility was assessed. Moderate-strong correlation was observed between the three modalities; the greatest between CMR and TOE (intraclass correlation coefficient (ICC) = 0.89), followed by TOE and TTE (ICC = 0.70) and CMR and TTE (ICC = 0.63). Intra- and inter-observer variations were excellent with CMR (ICC = 0.99 and 0.98 respectively), very good with TTE (0.90 and 0.89) and TOE (0.87 and 0.84). Each modality is a viable option for evaluating ventricular function in rats, however the high image quality and excellent reproducibility of CMR offers distinct advantages even at 1.5 T with conventional coils and software.

SummaryPre‐existing central nervous system (CNS) involvement may influence referral for autologous haematopoietic cell transplantation (AHCT) for patients with non‐Hodgkin lymphoma (NHL). The outcomes of 151 adult patients with NHL with prior secondary CNS involvement (CNS+) receiving an AHCT were compared to 4688 patients without prior CNS lymphoma (CNS−). There were significant baseline differences between the cohorts. CNS+ patients were more likely to be younger, have lower performance scores, higher age‐adjusted international prognostic index scores, more advanced disease stage at diagnosis, more aggressive histology, more sites of extranodal disease, and a shorter interval between diagnosis and AHCT. However, no statistically significant differences were identified between the two groups by analysis of progression‐free survival (PFS) and overall survival (OS) at 5 years. A matched pair comparison of the CNS+ group with a subset of CNS− patients matched on propensity score also showed no differences in outcomes. Patients with active CNS lymphoma at the time of AHCT (n = 55) had a higher relapse rate and diminished PFS and OS compared with patients whose CNS lymphoma was in remission (n = 96) at the time of AHCT. CNS+ patients can achieve excellent long‐term outcomes with AHCT. Active CNS lymphoma at transplant confers a worse prognosis.

The cytochrome P450 2B6 (CYP2B6) is involved in the metabolism of testosterone. Functional changes in this enzyme may influence endogenous hormone exposure, which has been associated with risk of breast cancer. To assess potential associations between two functional polymorphisms CYP2B6_516_G>T (rs3745274) and CYP2B6_785_A>G (rs2279343) and breast cancer risk, we established a specific matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry assay. The GENICA breast cancer case–control study showed associations between the variant genotypes CYP2B6_516_TT and CYP2B6_785_GG and breast cancer risk with odds ratios (ORs) of 1.34 (p = 0.001) and 1.31 (p = 0.002), respectively. A similar effect was observed for carriers of the CYP2B6_516_T allele in a validation study including four independent studies from Germany, Sweden and USA. In a pooled analysis of all five studies involving 4,638 breast cancer cases and 3,594 controls of European ancestry, carriers of the CYP2B6_516_G and the CYP2B6_785_G variant had an increased breast cancer risk with ORs of 1.10 (p = 0.027) and 1.10 (p = 0.031), respectively. We conclude that the genetic variants CYP2B6_516_G and CYP2B6_785_G (designated CYP2B6*6), which are known to decrease activity of the CYP2B6 enzyme, contribute to an increased breast cancer risk.

Human sperm centrosome reconstitution and the parental contributions to the zygotic centrosome are examined in mammalian zygotes and after exposure of spermatozoa to Xenopus laevis cell-free extracts. The presence and inheritance of the conserved centrosomal constituents γ-tubulin, centrin, and MPM-2 (which detects phosphorylated epitopes) are traced, as is the sperm microtubule-nucleating capability on reconstituted centrosomes. γ-Tubulin is biparentally inherited in humans (maternal >> than paternal): Western blots detect the presence of paternal γ-tubulin. Recruitment of maternal γ-tubulin to the sperm centrosome occurs after sperm incorporation in vivo or exposure to cell-free extract, especially after sperm “priming” induced by disulfide bond reduction. Centrin is found in the proximal sperm centrosomal region, demonstrates expected calcium sensitivity, but appears absent from the zygotic centrosome after sperm incorporation or exposure to extracts. Sperm centrosome phosphorylation is detected after exposure of primed sperm to egg extracts as well as during the early stages of sperm incorporation after fertilization. Finally, centrosome reconstitution in cell-free extracts permits sperm aster microtubule assembly in vitro. Collectively, these results support a model of a blended zygotic centrosome composed of maternal constituents attracted to an introduced paternal template after insemination.

Consensus abstract Background The management of primary rectal cancer beyond total mesorectal excision planes (PRC-bTME) and recurrent rectal cancer (RRC) is challenging. There is global variation in standards and no guidelines exist. To achieve cure most patients require extended, multivisceral, exenterative surgery, beyond conventional total mesorectal excision planes. The aim of the Beyond TME Group was to achieve consensus on the definitions and principles of management, and to identify areas of research priority. Methods Delphi methodology was used to achieve consensus. The Group consisted of invited experts from surgery, radiology, oncology and pathology. The process included two international dedicated discussion conferences, formal feedback, three rounds of editing and two rounds of anonymized web-based voting. Consensus was achieved with more than 80 per cent agreement; less than 80 per cent agreement indicated low consensus. During conferences held in September 2011 and March 2012, open discussion took place on areas in which there is a low level of consensus. Results The final consensus document included 51 voted statements, making recommendations on ten key areas of PRC-bTME and RRC. Consensus agreement was achieved on the recommendations of 49 statements, with 34 achieving consensus in over 95 per cent. The lowest level of consensus obtained was 76 per cent. There was clear identification of the need for referral to a specialist multidisciplinary team for diagnosis, assessment and further management. Conclusion The consensus process has provided guidance for the management of patients with PRC-bTME or RRC, taking into account global variations in surgical techniques and technology. It has further identified areas of research priority.

Background— Patients with atrial fibrillation (AF) at the highest stroke risk derive the largest benefit from oral anticoagulation (OAC). Those with the highest stroke risk have been paradoxically less likely to receive OAC. This study assessed the association between stroke and bleeding risk on rates of OAC. Methods and Results— We analyzed OAC use among 10 098 patients with AF from 174 community-based outpatient practices enrolled in 2010–2011 in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). OAC was defined as warfarin or dabigatran use at study enrollment. Stroke and bleeding risk were calculated using congestive heart failure, hypertension, age, diabetes mellitus, prior stroke (CHADS 2 ), and anticoagulation and risk factors in AF (ATRIA) scores, respectively. The mean subject age was 73 years; 58% were men. Overall, 76% of patients received OAC (71% warfarin and 5% dabigatran). The use of OAC increased among those with higher CHADS 2 scores, from 53% for CHADS 2 =0 to 80% for CHADS 2 ≥2 ( P <0.001). OAC use fell slightly with increasing ATRIA bleeding risk score, from 81% for ATRIA=3 to 73% for ATRIA≥5 ( P <0.001). A significant interaction existed between ATRIA and CHADS 2 scores ( P =0.021). Among those with low bleeding risk, use of OAC increased significantly with increasing stroke risk. Among those with high bleeding risk, CHADS 2 stroke risk had a smaller impact on use of OAC. Conclusions— In community-based outpatients with AF, use of OAC was high and driven by not only predominantly stroke but also bleeding risk. Stroke risk significantly affects OAC use among those with low bleeding risk, whereas those with high bleeding risk demonstrate consistently lower use of OAC regardless of stroke risk.