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Background Aortic stenosis (AS) is a common valvular abnormality and transcatheter aortic valve implantation (TAVI) is being increasingly used to treat patients considered too high risk for conventional surgery. We aimed to assess the prevalence of comorbid conditions in patients undergoing TAVI using the Charlson Comorbidity Index (CCI) and to assess their impact on clinical and procedural outcomes. Methods We analysed 158 patients who underwent a TAVI at our institution between June 2009 and September 2015 to define their co-morbid burden as measured with CCI, and study its impact on procedural characteristics and mortality at 30 days. Results One hundred fifty-eight (158) patients with a mean age of 82 ± 8 years and a mean CCI score of 2.67 underwent a TAVI. Only 12/158 patients had a CCI of 0. The commonest cardiovascular comorbidities were previous myocardial infarction (24%), congestive heart failure (15%) and diabetes mellitus (23%) whilst the commonest non-cardiovascular comorbidities were renal disease (46%) and chronic obstructive pulmonary disease (COPD) (29%). After multivariable adjustment, CCI was not independently associated with adverse clinical outcomes. The addition of CCI to scoring systems such as Logistic EuroScore (LES) and Society of Thoracic Surgeons (STS) risk models improved the area under the curve from 0.75 (95%CI: 0.44–1.00) and 0.83 (95%CI: 0.64–1.00) to 0.78 (95%CI: 0.53–1.00) and 0.89 (95%CI: 0.78–1.00) respectively. Conclusions The burden of comorbid conditions in patients undergoing TAVI is significant. The CCI score was not independently associated with a higher risk of death but can be useful in addition to LES and STS risk models in informing decision making on the selection of patients for TAVI.

IgGTo characterise the Royal Adelaide Hospital IgG4RD cohort with biopsy-proven disease.A search of the Frome Road SA Pathology database was performed for all tissue biopsies containing the phrase 'IgGTwenty patients had definite or probable IgG4RD and suggestive clinical features; median age 59 (20-76), male : female 1.5:1. There was considerable delay in diagnosis (median diagnosis at 64 months). Organ involvement included: 11 exocrine gland, seven pancreatobiliary, seven nodal, seven soft tissue, five retro-orbital, three retroperitoneal fibrosis and two renal. Systemic symptoms at diagnosis were seen in eight patients. Seven (35%) had an elevated serum IgGThis is the first characterised Australian cohort with generalised IgG4RD, a rare, relatively indolent and under-recognised multisystem disorder. Diagnosis is difficult given lack of awareness of this rare condition among physicians, its presentation as a great disease mimic, challenges with histopathological assessment and the absence of a suitable serum biomarker.

Background: Transradial access (TRA) for percutaneous coronary intervention (PCI) is associated with a reduced risk of mortality compared with transfemoral access, access site–related bleeding complications, and shorter length of stay. The budget impact from a healthcare system that has largely transitioned to TRA for PCI has not been previously published. Methods and Results: Data from 323 656 patients undergoing PCI between 2010 and 2014 were obtained from the British Cardiovascular Intervention Society database. Costs for TRA and transfemoral access PCI were estimated based on procedure cost, length of stay, and differences in the rates of complications (major bleeding and vascular complications). In the base case, a propensity-matched data set between transfemoral access and TRA was used to directly compare the cost per PCI, whereas in the real-world analysis, the full data set was used. Across all indications and all years, TRA offered an average cost saving of £250.59 per procedure (22% reduction) versus transfemoral access with the majority of cost saving derived from reduced length of stay (£190.43) rather than direct costs of complications (£3.71). In the real-world analysis, adoption of TRA was estimated to have provided cost savings of £13.31 million across England between 2010 and 2014; however, if operators in all regions had adopted TRA at the rate of the region with the highest utilization, cost savings of £33.40 million could have been achieved. Conclusions: The transition to TRA in England has been associated with significant cost savings across the national healthcare system, in addition to the well-established clinical benefits.

Background\ud The radial artery is increasingly used for cardiac procedures, but is a relatively small vessel that is prone to spasm when instrumented. Intra-arterial nitroglycerine has been shown to reduce radial spasm but first requires arterial access. We investigated the effect of pre-procedure sublingual nitroglycerin (NTG) on the diameter of the radial artery in a large cohort of patients.\ud \ud Methods\ud 305 subjects underwent ultrasound measurement of their radial and ulnar arteries in both arms before and after the administration of 800 μg of sublingual NTG. The Allen's test was also performed in the subjects prior to and after NTG.\ud \ud Results\ud Radial artery diameter in this Caucasian study group is larger than that reported for other populations. The administration of sublingual NTG significantly increased the size of the right radial artery from 2.88 ± 0.36 mm to 3.36 ± 0.40 mm in men and from 2.23 ± 0.37 up to 2.74 ± 0.36 mm in women. There were also significant increases in left radial, right and left ulnar artery diameters in males and females with NTG. There was no significant effect of NTG on blood pressure. In all patients with an unfavourable Allen's test, retesting following sublingual NTG resulted in transition to a favourable Allen's.\ud \ud Conclusion\ud Caucasian populations have larger calibre radial arteries compared to other geographic areas. Sublingual NTG is effective at dilating the radial artery in both men and women. This may make radial artery puncture and cannulation less challenging and should be considered in all patients in the absence of contraindications. The results of Allen's testing are dynamic and its usefulness for screening prior to transradial access is undetermined.

Background— Retroperitoneal hemorrhage (RH) is a rare bleeding complication of percutaneous coronary intervention, which can result as a consequence of femoral access or can occur spontaneously. This study aims to evaluate temporal changes in RH, its predictors, and clinical outcomes in a national cohort of patients undergoing percutaneous coronary intervention in the United Kingdom. Methods and Results— We analyzed RH events in patients who underwent percutaneous coronary intervention between 2007 and 2014. Multiple logistic regression models were used to identify factors associated with RH and to quantify the association between RH and 30-day mortality and major adverse cardiovascular events. A total of 511 106 participants were included, and 291 in hospital RH events were recorded (0.06%). Overall, rates of RH declined from 0.09% to 0.03% between 2007 and 2014. The strongest independent predictors of RH events were femoral access (odds ratio [OR], 19.66; 95% confidence interval [CI], 11.22–34.43), glycoprotein IIb/IIIa inhibitor (OR, 2.63; 95% CI, 1.99–3.47), and warfarin use (OR, 2.53; 95% CI, 1.07–5.99). RH was associated with a significant increase in 30-day mortality (OR, 3.59; 95% CI, 2.19–5.90) and in-hospital major adverse cardiovascular events (OR, 5.76; 95% CI, 3.71–8.95). A legacy effect was not observed; patients with RH who survived 30 days did not have higher 1-year mortality compared with those without this complication (hazard ratio, 0.97; 95% CI, 0.49–1.91). Conclusions— Our results suggest that RH is a rare event that is declining in the United Kingdom, related to transition to transradial access site utilization, but remains a clinically important event associated with increased 30-day mortality but no long-term legacy effect.

Purpose\ud Radial artery occlusion flowing cardiac catheterisation has been linked to flow reduction and prolonged compression. We investigate whether these factors can be optimised following transradial cardiac catheterisation by using an accelerated band removal protocol facilitated by a haemostasis promoting pad, in combination with a patent haemostasis technique.\ud \ud Methods\ud In this single centre prospective study, 389 consecutive patients undergoing TRA for coronary angiography or angioplasty were randomised to two haemostasis protocols: use of a Helix™ compression device alone (HC) or in combination with a haemostatic pad (StatSeal® disc) and an accelerated haemostasis protocol (AC). A patent haemostasis technique was employed in both study arms. The primary efficacy endpoint was the time to haemostasis and the secondary safety outcome was access site related complications: re-bleeding, haematoma and radial artery patency assessed within 24 h using reverse Barbeau's Test (BT).\ud \ud Results\ud Between May and Nov 2017, 191 patients were randomised to receive HC and 198 patients to AC. Compression time was significantly higher with HC as compared to AC (165.8 ± 63.1 versus 79.7 ± 41.2 min, p

The cost of inpatient percutaneous coronary interventions (PCI) procedure is related to length of stay (LOS). It is unknown, how LOS may be associated with readmission rates and costs of index PCI and readmissions in elective PCI. This study aims to evaluate rates, predictors, causes, and costs associated with 30-day unplanned readmissions according to lLOS in patients, who underwent elective PCI. We included patients in the Nationwide Readmission Database, who were admitted to hospital from 2010 to 2014, who underwent uncomplicated elective PCI. LOS was defined as 0, 1, 2, and ≥3 days. A total of 324,345 patients were included in the analysis and the 30-day unplanned readmission was 4.75%, 4.67%, 6.44%, and 9.42% in the LOS groups 0, 1, 2, and ≥3 days, respectively. Prolonged LOS was associated with increased average total 30-day cost (index and readmission cost, 0 days $15,063, 1 day $14,693, 2 days $18,136, and ≥3 days $24,336). Compared with 0 days, the odds of readmissions were greater for 2 days (odds ratio 1.41, 95% confidence interval 1.07 to 1.87, p = 0.016) and ≥3 days (odds ratio 1.70, 95% confidence interval 1.28 to 2.24, p

The 1980s and 1990s represented something of a merger wave in US freight rail. A number of major US railroad mergers were proposed, with many subsequently approved by regulators. But in 1999–2000, a (failed) merger attempt between Canadian National and Burlington Northern Santa Fe railways also led to significant new regulations governing future rail mergers. Now, after almost two decades of silence, high-level corporate activity indicates that the likelihood of new mega mergers in North American freight rail is growing. Using a novel dataset of digitized regulatory submissions from the 1999–2000 Surface Transportation Board merger hearings, we employ qualitative textual analysis to assess both the content and focus of the submissions. Mapping these findings onto what is happening today, we highlight several important operational and regulatory issues that are likely to arise in future rail mergers.

Coronary angiography is a widely available diagnostic and therapeutic modality. Radiation exposure is set to increase as a result of greater complexity of coronary and structural cases now being undertaken. Therefore all cardiologists need to be aware of not only the risks of radiation but also strategies to minimize radiation exposure for both patients and catheter laboratory staff.

Background Pseudomonas aeruginosa is a commonly isolated pathogen in adults with cystic fibrosis (CF). Antimicrobial resistance is an escalating problem due to chronic colonization and frequent antimicrobial exposure. Ceftolozane–tazobactam (C/T) and ceftazidime–avibactam (CZA) exhibit promising activity against antimicrobial-resistant organisms, including P. aeruginosa. In this study, we compared in vitro activity of C/T and CZA against P. aeruginosa isolated from respiratory cultures obtained from adult patients with CF. Methods This is a retrospective study of respiratory cultures positive for P. aeruginosa collected from adult CF patients between January 1, 2015 to November 30, 2018. The first isolate per patient per year that underwent susceptibility testing for C/T, CZA, and colistin were included in the study. All isolates underwent in-house susceptibility testing for 9 anti-pseudomonal agents according to the methodology established by the Clinical Laboratory Standards Institute (CLSI). Susceptibility testing of C/T, CZA, and colistin were performed by a reference lab. Isolates were classified into 3 drug-resistant categories using the following definition: multidrug-resistant (MDR) non-susceptible (NS) to ≥1 agent in ≥3 different antimicrobial classes, extensive drug-resistant (XDR) NS to 4 or 5 different classes, and pan drug-resistant (PDR) NS to all 6 classes except colistin. Results Forty-two P. aeruginosa respiratory isolates from 32 patients with CF were included. The overall susceptibility to C/T and CZA was 59.5% and 42.9%, respectively. Thirty-eight (90%) isolates were considered MDR with susceptibility of 55.3% to C/T and 44.7% to CZA. Among the 11 XDR isolates, susceptibility to C/T was 81.8% vs. CZA 72.7%. Susceptibility to C/T vs. CZA was also higher (37.5% vs. 25%) among the 24 PDR isolates. Conclusion Among P. aeruginosa isolated from CF respiratory cultures, C/T appears to have better in vitro activity compared with CZA, and remained true among isolates considered XDR and PDR. These results suggest using C/T while awaiting susceptibilities when standard anti-pseudomonal agents cannot be used. Future studies evaluating clinical outcomes for the treatment of pulmonary CF exacerbations are needed to assess the applicability of in vitro susceptibility data. Disclosures All authors: No reported disclosures.

Background— Rotational atherectomy (RA) is an important interventional tool for heavily calcified coronary lesions. We compared the early clinical outcomes in patients undergoing RA using radial or femoral access. Methods and Results— We identified all patients in England and Wales who underwent RA between January 1, 2005, and March 31, 2014. Eight thousand six hundred twenty-two RA cases (3069 radial and 5553 femoral) were included in the analysis. The study primary outcome was 30-day mortality. Propensity scores were calculated to determine the factors associated with treatment assignment to radial or femoral access. Multivariable logistic regression analysis, using the calculated propensity scores, was performed. Thirty-day mortality was 2.2% in the radial and 2.3% in the femoral group ( P =0.76). Radial access was associated with equivalent 30-day mortality (adjusted odds ratio [OR], 1.06; 95% confidence interval [CI], 0.77–1.46; P =0.71), procedural success (OR, 1.04; 95% CI, 0.84–1.29; P =0.73), major adverse cardiac and cerebrovascular events (OR, 1.05; 95% CI, 0.80–1.38; P =0.72), and net adverse clinical events (OR, 0.90; 95% CI, 0.71–1.15; P =0.41), but lower rates of in-hospital major bleeding (OR, 0.62; 95% CI, 0.40–0.98; P =0.04) and major access site complications (OR, 0.05; 95% CI, 0.01–0.38; P =0.004), compared with femoral access. Conclusions— In this large real-world study of patients undergoing RA, radial access was associated with equivalent 30-day mortality and procedural success, but reduced major bleeding and access site complications, compared with femoral access.

In recent years, there has been an increase in paraeducator supports, in large part because students with low incidence disabilities are being included more frequently in general education settings. As a result, special education teachers have been given additional supervisory responsibilities related to directing the work of paraeducators in special and general education settings. Many teachers, however, feel unprepared for this supervisory role. Therefore, to gain a better understanding of current practices in paraeducator supervision, the authors interviewed 13 special education teachers who were nominated by district special education administrators as exemplary supervisors of paraeducators. From the interviews, three themes emerged: creating effective teams, ensuring appropriate training and evaluation, and recommendations for the field. Practices for paraeducators working with students with low incidence disabilities in general education settings are noted in the first two themes. Implications for policy, practice, teacher preparation, and future research are also discussed.

Transradial access for cardiac catheterisation results in lower bleeding and vascular complications than the traditional transfemoral access route. However, the increased radiation exposure potentially associated with transradial access is a possible drawback of this method. Whether transradial access is associated with a clinically significant increase in radiation exposure that outweighs its benefits is unclear. Our aim was therefore to compare radiation exposure between transradial access and transfemoral access for diagnostic coronary angiograms and percutaneous coronary interventions (PCI).We did a systematic review and meta-analysis of the scientific literature by searching the PubMed, Embase, and Cochrane Library databases with relevant terms, and cross-referencing relevant articles for randomised controlled trials (RCTs) that compared radiation parameters in relation to access site, published from Jan 1, 1989, to June 3, 2014. Three investigators independently sorted the potentially relevant studies, and two others extracted data. We focused on the primary radiation outcomes of fluoroscopy time and kerma-area product, and used meta-regression to assess the changes over time. Secondary outcomes were operator radiation exposure and procedural time. We used both fixed-effects and random-effects models with inverse variance weighting for the main analyses, and we did confirmatory analyses for observational studies.Of 1252 records identified, we obtained data from 24 published RCTs for 19 328 patients. Our primary analyses showed that transradial access was associated with a small but significant increase in fluoroscopy time for diagnostic coronary angiograms (weighted mean difference [WMD], fixed effect: 1·04 min, 95% CI 0·84-1·24; p0·0001) and PCI (1·15 min, 95% CI 0·96-1·33; p0·0001), compared with transfemoral access. Transradial access was also associated with higher kerma-area product for diagnostic coronary angiograms (WMD, fixed effect: 1·72 Gy·cm(2), 95% CI -0·10 to 3·55; p=0·06), and significantly higher kerma-area product for PCI (0·55 Gy·cm(2), 95% CI 0·08-1·02; p=0·02). Mean operator radiation doses for PCI with basic protection were 107 μSv (SD 110) with transradial access and 74 μSv (68) with transfemoral access; with supplementary protection, the doses decreased to 21 μSv (17) with transradial access and 46 μSv (9) with transfemoral. Meta-regression analysis showed that the overall difference in fluoroscopy time between the two procedures has decreased significantly by 75% over the past 20 years from 2 min in 1996 to about 30 s in 2014 (p0·0001). In observational studies, differences and effect sizes remained consistent with RCTs.Transradial access was associated with a small but significant increase in radiation exposure in both diagnostic and interventional procedures compared with transfemoral access. Since differences in radiation exposure narrow over time, the clinical significance of this small increase is uncertain and is unlikely to outweigh the clinical benefits of transradial access.None.

We have just completed 5 years as editors of Journal of Teacher Education (JTE), having published four full volumes (63-66) and part of one (62), and will hand over the privilege and responsibility to a new team from Michigan State University in the next issue. In one of our first editorials (Knight et al., 2012), we reflected on how views of teacher education research from both within and outside the profession influenced our vision for the journal. At that time, we saw our challenge as building on the emerging traditions of diversity and excellence established by previous teams of capable editors with the ultimate goal of further advancing research to establish teacher education as a distinct field with knowledge, histories, research methodologies, and practices that are recognized and recognizable. Furthering the goal would require us to bring together the three dimensions of teacher education--practice, policy, and research--in challenging and productive ways so that considerations of issues or challenges in teacher education would be enriched by careful attention from these multiple frames of reference. We recognized a number of obstacles: the reputation of research in teacher education as lacking rigor and relevance and, relatedly, an incomplete knowledge base that prevents us from connecting findings in meaningful ways to inform practice and policy (e.g., Cochran-Smith & Zeichner, 2005; Feuer, Towne, & Shavelson, 2002; Kaestle, 1993; Moss et al., 2006; National Research Council, 2002; Wilson, Floden, & Ferrini-Mundy, 2001); a lack of a sense of professional identity among teacher educators (Labaree, 2008); and publication of teacher education research in specialized content journals with limited audiences rather than in broader teacher education research journals. In reflecting on our tenure as JTE editors, we see that putting our rhetoric into reality was challenging. The sheer number of manuscripts--more than 700 per year--was overwhelming even for a relatively large editorial team with diverse expertise and interests. We made concerted efforts to address our goal of improving quality; we devoted editorials (e.g., Knight et al., 2012) to the topic of quality and led interactive sessions at the annual meetings of our sponsoring organization, the American Association of Colleges of Teacher Education (AACTE), to discuss what constitutes rigor in teacher education research. To address our goal of improving relevance, we sponsored major forums at AACTE meetings on current topics and solicited recommendations from teacher educators for theme issues focusing on emerging areas of interest. Teacher Education Research Quality Based on our review of manuscripts from the first year of our editorship (Volume 63), we identified four areas that authors could target to improve the quality of their research (Knight et al., 2013). The first area that we identified, appropriateness for JTE, involves an explicit connection to an important topic or issue related to research and scholarship in teacher education. We initially rejected a large number of articles prior to external review for two primary reasons: They focused on teachers, teaching, or K-12 students without a clear connection to teacher education or they used teacher education students or faculty as their sample but did not connect to relevant theory and previous methodological and empirical work in teacher education. The second and third areas involve intertwined issues related to the nature of the research design and the samples used in the studies. We received a large number of manuscripts describing studies where the researchers were also the teacher educators or program developers and implementers and the samples were their own students. Whereas this relationship is not problematic in and of itself, the genre of many of the manuscripts often appeared to be program evaluation with program improvement or validation as the primary purpose. …

Percutaneous coronary intervention (PCI) is the commonest form of revascularization in patients with coronary heart disease. The benefit of early invasive treatment with PCI in patients presenting with acute coronary syndromes are well accepted. Traditionally, PCI has been performed via the femoral access with significant risks for the development of access site-related bleeding complications. Increased international adoption of the transradial access site for PCI procedures has been shown to reduce such major access site-related bleeding complications and mortality, especially in the high-risk patient groups. We provide a brief overview of the historical perspective on transradial approach and the evidence supporting its use. We then discuss the current data supporting transradial access in high-risk populations and factors that have limited its adoption.

At our first Journal Editor's Roundtable for Journal of Teacher Education (JTE) 5 years ago at the American Educational Research Association (AERA) after assuming the editorship in 2010, we engaged in discussion with various attendees about the nature of the journal and our vision for the duration of our term as editors. We received several questions about whether we accepted international manuscripts because we were perceived by many to be a unique "American" journal with a sole interest in research on preservice teacher (PST) education and inservice professional development in the United States. Although we were disturbed by that perception, because attracting more international contributors and readers was one of our major goals, on reflection we were not surprised. The membership of our sponsoring organization, the American Association of Colleges of Teacher Education (AACTE), consists of U.S. institutions and historically has closely aligned itself to matters of national accreditation and policy. Not surprisingly, the SAGE Publisher's Report to AACTE in 2010 indicated that only 1 of over 200 manuscripts submitted from countries outside of the United States to AACTE's flagship research journal had been accepted for publication and that particular manuscript was from a Canadian author. In addition, the first author of this editorial recalled that she and a colleague had conducted a review of literature in the early part of the millennium on professional development for teachers of diverse students that had explicitly restricted the review to publications of research in the United States (Knight & Wiseman, 2006). A National Advisory Team for Professional Development for Diversity established by the Center for Research on Education, Diversity & Excellence (CREDE) guided the review. The reasoning of the group around international research appears in this quotation from one of the publications. Our search for studies for the synthesis focused on research on professional development for in-service teachers in U.S. classrooms populated by diverse students. We recognize that high-quality research on professional development in other countries exists, but our rationale for excluding international studies in this review is similar to that discussed in Richardson and Placier (2002). Studies of professional development for teachers in one country may not generalize to different nations due to differences in political and cultural structures as well as ethnic composition. The reverse would also be true, in particular when the focus is on cultural, ethnic, and socioeconomic diversity. (Knight & Wiseman, 2005, p. 391) The view that generalization of studies across national contexts is limited was prevalent as recently as a decade ago. Perhaps for this reason, although it is difficult to determine the direction of the influence, schools and colleges of education have been the least internationalized units on U.S. university campuses (Longview Foundation, 2008). The consensus that preservice and inservice teacher professional development is specific to the national context influenced the kinds of articles published in JTE for many years. Only relatively recently has interest around issues of internationalization and globalization of teacher education emerged, resulting in a standing committee on Global Diversity and a Topical Action Group on the Internationalization of Teacher Education at AACTE and the establishment of a goal for JTE to attract and publish more international research on teacher education and encourage more readers in international settings. In contrast to previous views, we now consider research on teacher education in international settings as a valuable contribution and tool for improvement of teacher education in U.S. settings and suggest that the reverse is also true. Ironically, the recognition that international research can contribute to U.S. teacher education has occurred at a time when we are questioning whether teacher preparation programs should prepare teachers for multiple settings and types of students or for more specific types of settings and students. …

Aims This study aims to evaluate temporal changes in stroke complications and their association with mortality and MACE outcomes in a national cohort of patients undergoing percutaneous coronary interventions (PCIs) in England and Wales. Methods and results A total of 426 046 patients who underwent PCI in England and Wales between 2007 and 2012 in the British Cardiovascular Intervention Society (BCIS) database were analysed. Statistical analyses were performed evaluating the rates of stroke complications according to the year of PCI and multiple logistic regressions were used to evaluate the odds of 30-day mortality and in-hospital major adverse cardiovascular events (MACE; a composite of in-hospital mortality, myocardial infarction or re-infarction, and revascularization) with stroke complications. Four hundred and thirty-six patients (0.1%) sustained an ischaemic stroke/TIA complication and 107 patients (0.03%) sustained a haemorrhagic stroke complication. Ischaemic stroke/TIA complications increased non-linearly from 0.67 (95% CI 0.47–0.87) to 1.14 (0.94–1.34) per 1000 patients between 2007 and 2012 ( P = 0.006), whilst haemorrhagic stroke rates decreased non-linearly from 0.29 (0.19–0.39) to 0.15 (0.05–0.25) per 1000 patients in 2012 ( P = 0.009). Following adjustment for baseline clinical and procedural demographics, ischaemic stroke was independently associated with both 30-day mortality (OR 4.92, 3.06–7.92) and in-hospital MACE (OR 3.11, 1.83–5.27). An even greater impact on prognosis was observed with haemorrhagic complications (30-day mortality: OR 13.87, 6.37–30.21), in-hospital MACE (OR 13.50, 6.30–28.92). Conclusions Incident ischaemic stroke complications have increased over time, whilst haemorrhagic stroke complications have decreased, driven through changes in clinical, procedural, drug-treatment, and demographic factors. Both ischaemic and haemorrhagic strokes are rare but devastating complications with high 30-day mortality and in-hospital MACE rates.

BACKGROUND: Acute nail gun injuries can be controlled significantly by using tools with sequential triggers and training. Concern has been raised that sequential triggers, which require that the nose piece of the gun be depressed prior to pulling the trigger, could increase risk of musculoskeletal problems. METHODS: We conducted active injury surveillance among union carpenter apprentices to monitor acute injuries and musculoskeletal disorders between 2010 and 2013. RESULTS: Acute injury risk was 70% higher with contact trip rather than sequential triggers. Musculoskeletal risk was comparable (contact trip 0.09/10,000 hr (95% CI, 0.02-0.26); sequential 0.08/ 10,000 hr (95% CI 0.02-0.23)). CONCLUSIONS: Concern about excess risk of musculoskeletal problems from nail guns with sequential triggers is unwarranted. Both actuation systems carry comparable musculoskeletal risk which is far less than the risk of acute injury; there is clearly no justification for failure to prevent acute injuries through use of the safer sequential trigger. Am. J. Ind. Med. © 2015 Wiley Periodicals, Inc. Language: en

We investigate adoption of the TRA in different age groups and study the relationship between age and access site related outcomes in a national cohort of patients undergoing PCI in the UK. Previous studies have reported conflicting data on radial access site adoption between different age groups, with age an independent predictor of failure of procedures undertaken through the radial approach. Age and access site related outcomes (based on transradial (TRA) and transfemoral (TFA) access) were studied in 469,983 PCI procedures undertaken in the UK from 2006 to 2012 in the age groups

This study sought to determine the relationships among access site practice, clinical presentation, and procedural outcomes in a large patient population.Transradial access (TRA) has been associated with improved patient outcomes in selected populations in randomized trials. It is unclear whether these outcomes are achievable in clinical practice.Using the BCIS (British Cardiovascular Intervention Society) database, we investigated outcomes for percutaneous coronary intervention procedures undertaken between 2007 and 2012 according to access site practice. Patients were categorized as stable, non-ST-segment elevation acute coronary syndrome (NSTEACS) and ST-elevation acute coronary syndrome (STEACS). The impact of access site on 30-day mortality, major adverse cardiac events, bleeding, and arterial access site complications was studied.Data from 210,260 TRA and 229,687 transfemoral access procedures were analyzed. Following multivariate analysis, TRA was independently associated with a reduction in bleeding in all presenting syndromes (stable odds ratio [OR]: 0.24, p0.001; NSTEACS OR: 0.35, p0.001; STEACS OR: 0.47, p0.001) as well as access site complications (stable OR: 0.21, p0.001; NSTEACS OR: 0.19; STEACS OR: 0.16, p0.001). TRA was associated with reduced major adverse cardiac events only in patients with unstable syndromes (stable OR: 1.08, p = 0.25; NSTEACS OR: 0.72, p0.001; STEACS OR: 0.70, p0.001). TRA was associated with improved outcomes compared with a transfemoral access (TFA) with a vascular closure device in a propensity matched cohort.In this large study, TRA is associated with reduced percutaneous coronary intervention-related complications in all patient groups and may reduce major adverse cardiac events and mortality in ACS patients. TRA is superior to transfemoral access with closure devices. Use of TRA may lead to important patient benefits in routine practice. TRA should be considered the preferred access site for percutaneous coronary intervention.

With worldwide food security emerging as a major policy issue moving forward, the structure and optimization of key agricultural supply chains is of growing importance. In turn, while many working models of supply chain optimization have been developed to ensure analytic tractability, others are building more precise characterizations of a supply chain as a complex system that may not be amenable to analytic solution. This research examines an important agricultural supply chain from the perspective of developing effective solutions to complex internal optimization issues that could ultimately affect food security. To this end, the Canadian wheat handling system is a complex export oriented supply chain that is currently undergoing extensive changes with respect to quality control. We develop both analytic and simulation models of this supply chain with the ultimate goal of identifying effective wheat quality testing strategies in a complex operational and regulatory environment. While the analytic model is founded on limited assumptions about individual behavior, agent-based simulation allows us to model farmers and handlers as rational and learning individuals who make decisions based on their own experiences as well as the experiences of others around them. We then make explicit comparisons between solutions and policies generated using the simulation approach against those generated by the analytically tractable model of the wheat supply chain. While the two approaches generate somewhat different solutions, in many respects they lead to similar conclusions regarding the overall testing and quality control issue in wheat handling.

In this issue, Marilyn Cochran-Smith provides the first of two Journal of Teacher Education (JTE) articles based on her chapter in the upcoming fifth edition of the Handbook of Research on Teaching (Cochran-Smith, Villegas, Abrams, Chavez Moreno, Mills, & Stern, in press). Her handbook chapter presents the findings from the review of 1,500 teacher education research studies published between 2000 and 2012. JTE is publishing the review in two parts. The first part, the lead article in this issue, describes the procedures and theoretical/analytical framework used in the literature review and outlines three major trends that have influenced the nature of research programs in teacher education: increased attention to teacher quality and accountability, changes in our conceptions of teacher and student learning, and changing demographics. Part 1 also presents the findings from the first of three major research programs in teacher education identified through the search--teacher preparation accountability, effectiveness, and policies. Part 2, to be published in the next issue of JTE, discusses the findings from the remaining two research programs. The first research program includes studies on alternative certification and pathways, analyses of policy trends and discourses, assessment of preservice teachers (PSTs) and/or teacher preparation programs (TPPs), and program evaluation studies. Cochran-Smith's reference in the article to her JTE editorial 10 years prior (Taking Stock in 2005; Cochran-Smith, 2005) prompted us to reflect on the contributions of JTE to advances in teacher education research in the areas identified in the first program described in the study. We comment briefly on research and issues associated with accountability, effectiveness, and policies in relation to the Cochran-Smith article and previous JTE articles published during our tenure as editors. Advances in Research on Teacher Preparation Accountability The theme of accountability has been widespread and persistent over the past 5 years, and JTE has published theme issues and articles related to the use of value-added models to determine the effectiveness of TPPs (Volume 63:5) and to examine the role of performance assessments in accountability (Volume 65:5). The articles on value-added modeling (VAM) for TPPs in the theme issue provide some support for the potential of the approach to provide feedback to policymakers and educators on the achievement of students taught by teachers in different TPPs (Gansle, Noell, & Burns, 2012; Plecki, Elfers, & Nakamura, 2012). However, the potential of using VAM for teacher preparation is diminished by the complexity and limitations of the choice of variables selected for the VAM models; the nature of the accountability criteria; the unidimensional focus on student standardized tests; decisions made about selection, estimation, and reporting; and the unintended consequences of the approach (see Floden, 2012; Goldhaber & Cowan, 2014; Henry, Kershaw, Zulli, & Smith, 2012; Lincove, Osborne, Dillon, & Mills, 2014.) The pitfalls associated with VAM make it less acceptable to educators as a high-stakes accountability measure and appear to outweigh the potential. On the other hand, performance assessment of teacher candidates (TPA) has been suggested as an alternative or addition to VAM to determine TPP effectiveness (Knight et al., 2014) and was the theme of the previous issue of JTE (Volume 65:5). While performance assessments appear to receive more support from educators as they can be used for program improvement as well as evidence for certification and licensure, problems with validity and reliability as well as questions about conceptualization of teaching and accompanying value assumptions have emerged (see Caughlan & Jiang, 2014; Duckor, Castellano, Tellez, Wihardini, & Wilson, 2014; Sato, 2014). More research is needed to address the concerns of both accountability approaches and to determine the feasibility of using a combination of VAM and TPA for high-stakes TPP accountability. …

During the 2008 United States presidential election, political pundits and statisticians worked feverishly to predict who would be elected as the next resident of the White House. While many of their models took into account public polling, other methods relied on more exotic data. One list of

INTRODUCTION Transfemoral access (TFA) is widely used for coronary angiography and percutaneous coronary intervention (PCI). The influence of operator age, gender, experience, and procedural volume on performance of femoral arterial access has not been studied. METHODS A survey instrument was developed and distributed via e-mail from professional societies to interventional cardiologists worldwide from March to December 2016. RESULTS A total of 988 physicians from 88 countries responded to the survey. TFA is the preferred approach for patients with cardiogenic shock, left main or bifurcation PCI, and procedures with mechanical circulatory support. Older (

Using the British Cardiovascular Intervention Society percutaneous coronary intervention (PCI) database, access site choice and outcomes of patients undergoing PCI with previous coronary artery bypass grafting (CABG) were studied.Given the influence of access site on outcomes, use of radial access in PCI-CABG warrants further investigation.Data were analyzed from 58,870 PCI-CABG procedures performed between 2005 and 2014. Multivariate logistic regression was used to identify predictors of access site choice and its association with outcomes.The number of PCI-CABG cases and the percentage of total PCI increased significantly during the study period. Femoral artery (FA) utilization fell from 90.8% in 2005 to 57.6% in 2014 (p 0.001), with no differences in the rate of change of left versus right radial use. In contemporary study years (2012 to 2014), female sex, acute coronary syndrome presentation, chronic total occlusion intervention, and lower operator volume were independently associated with FA access. Length of stay was shortened in the radial cohort. Unadjusted outcomes including an access site complication (1.10% vs. 0.30%; p 0.001), blood transfusion (0.20% vs. 0.04%; p 0.001), major bleeding (1.30% vs. 0.40%; p 0.001), and in-hospital death (1.10% vs. 0.60%; p = 0.001) were more likely to occur with FA access compared with radial access. After adjustment, although arterial complications, transfusion, and major bleeding remained more common with FA use, short- and longer-term mortality and major adverse cardiac event rates were similar.In contemporary practice, FA access remains predominant during PCI-CABG with case complexity associated with it use. FA use was associated with longer length of stay, and higher rates of vascular complications, major bleeding, and transfusion.

This study aimed to examine the 30-day unplanned readmissions rate, predictors of readmission, causes of readmissions, and clinical impact of readmissions after percutaneous coronary intervention (PCI).Unplanned rehospitalizations following PCI carry significant burden to both patients and the local health care economy and are increasingly considered as an indicator of quality of care.Patients undergoing PCI between 2013 and 2014 in the U.S. Nationwide Readmission Database were included. Incidence, predictors, causes, and cost of 30-day unplanned readmissions were determined.A total of 833,344 patients with PCI were included, of whom 77,982 (9.3%) had an unplanned readmission within 30 days. Length of stay for the index PCI was greater (4.7 vs. 3.9 days) and mean total hospital cost ($23,211 vs. $37,524) was higher for patients who were readmitted compared with those not readmitted. The factors strongly independently associated with readmissions were index hospitalization discharge against medical advice (odds ratio [OR]: 1.91; 95% confidence interval [CI]: 1.65 to 2.22), transfer to short-term hospital for inpatient care (OR: 1.62; 95% CI: 1.38 to 1.90), discharge to care home (OR: 1.57; 95% CI: 1.51 to 1.64), and chronic kidney disease (OR: 1.50; 95% CI: 1.44 to 1.55). Charlson Comorbidity Index score (OR: 1.28; 95% CI: 1.27 to 1.29) and number of comorbidities (OR: 1.18; 95% CI: 1.17 to 1.18) were independently associated with unplanned readmission. The majority of readmissions were due to noncardiac causes (56.1%).Thirty-day readmissions after PCI are relatively common and relate to baseline comorbidities and place of discharge. More than one-half of the readmissions were due to noncardiac causes.

The authors sought to determine the relationships between left radial access (LRA) or right radial access (RRA) and clinical outcomes using the British Cardiovascular Intervention Society (BCIS) database.LRA has been shown to offer procedural advantages over RRA in percutaneous coronary intervention (PCI) although few data exist from a national perspective around its use and association with clinical outcomes.The authors investigated the relationship between use of LRA or RRA and clinical outcomes of in-hospital or 30-day mortality, major adverse cardiovascular events (MACE), in-hospital stroke, and major bleeding complications in patients undergoing PCI between 2007 and 2014.Of 342,806 cases identified, 328,495 (96%) were RRA and 14,311 (4%) were LRA. Use of LRA increased from 3.2% to 4.6% from 2007 to 2014. In patients undergoing a repeat PCI procedure, the use of RRA dropped to 72% at the second procedure and was even lower in females (65%) and patients75 years of age (70%). Use of LRA (compared with RRA) was not associated with significant differences in in-hospital mortality (odds ratio [OR]: 1.19, 95% confidence interval [CI]: 0.90 to 1.57; p = 0.20), 30-day mortality (OR: 1.17, 95% CI: 0.93 to 1.74; p = 0.16), MACE (OR: 1.06, 95% CI: 0.86 to 1.32; p = 0.56), or major bleeding (OR: 1.22, 95% CI: 0.87 to 1.77; p = 0.24). In propensity match analysis, LRA was associated with a significant decrease in in-hospital stroke (OR: 0.52, 95% CI: 0.37 to 0.82; p = 0.005).In this large PCI database, use of LRA is limited compared with RRA but conveys no increased risk of adverse outcomes, but may be associated with a reduction in PCI-related stroke complications.

We assess the structure of grain shipping within the Great Lakes and St. Lawrence Seaway system. While U.S. grain exports ship from the port of Duluth, Minnesota, Canadian grain exports ship from several ports located on the Lower St. Lawrence Seaway. While North American grain exports moving from west to east can be transported in several different ways, due to data limitations our focus in this analysis is on the so-called saltie shipping market. While our findings are somewhat unexpected, they give us some unique insight into the nature of this crucial yet understudied transportation market.

Background— The radial artery is increasingly adopted as the primary access site for cardiac catheterization because of patient preference, lower bleeding rates, cost effectiveness, and reduced risk of mortality in high-risk patient groups. Concerns have been expressed that operators/centers have become increasingly unfamiliar with transfemoral access. The aim of this study was to assess whether a change in access site practice toward transradial access nationally has led to worse outcomes in percutaneous coronary intervention procedures performed through the transfemoral access approach. Methods and Results— Using the British Cardiovascular Intervention Society (BCIS) database, a retrospective analysis of 235 250 transfemoral access percutaneous coronary intervention procedures was undertaken in all 92 centers in England and Wales between 2007 and 2013. Recent femoral proportion and recent femoral volume were determined, and in-hospital vascular complications and 30-day mortality were evaluated. After case-mix adjustment, no independent association was observed between 30-day mortality for cases undertaken through the transfemoral access and center femoral proportion, the risk-adjusted odds ratio for recent femoral proportion was nonsignificant (odds ratio, 0.99; 95% confidence interval, 0.97–1.02; P =0.472 per 0.1 increase in proportion), and similarly recent femoral volume (per 100 procedures) was not found to be significant (odds ratio, 1.00; 95% confidence interval, 0.98–1.01; P =0.869). The in-hospital vascular complication rate was 1.0%, and this outcome was not significantly associated with recent femoral proportion after risk-adjustment (odds ratio, 0.97; 95% confidence interval, 0.94–1.00; P =0.060 per 0.1 increase in proportion). Conclusions— The outcome gains achieved by the national adoption of radial access are not associated with a loss of femoral proficiency, and centers should be encouraged to continue to adopt radial access as the default access site for percutaneous coronary intervention wherever possible in line with current best evidence.

AIM\ud To sythesize the available literature on hand dysfunction after transradial catheterization.\ud \ud METHODS\ud We searched MEDLINE and EMBASE. The search results were reviewed by two independent judicators for studies that met the inclusion criteria and relevant reviews. We included studies that evaluated any transradial procedure and evaluated hand function outcomes post transradial procedure. There were no restrictions based on sample size. There was no restriction on method of assessing hand function which included disability, nerve damage, motor or sensory loss. There was no restriction based on language of study. Data was extracted, these results were narratively synthesized.\ud \ud RESULTS\ud Out of 555 total studies 13 studies were finally included in review. A total of 3815 participants with mean age of 62.5 years were included in this review. A variety of methods were used to assess sensory and motor dysfunction of hand. Out of 13 studies included, only 3 studies reported nerve damage with a combined incidence of 0.16%, 5 studies reported sensory loss, tingling and numbness with a pooled incidence of 1.52%. Pain after transradial access was the most common form of hand dysfunction (6.67%) reported in 3 studies. The incidence of hand dysfunction defined as disability, grip strength change, power loss or any other hand complication was incredibly low at 0.26%. Although radial artery occlusion was not our primary end point for this review, it was observed in 2.41% of the participants in total of five studies included.\ud \ud CONCLUSION\ud Hand dysfunction may occur post transradial catheterisation and majority of symptoms resolve without any clinical sequel.

Background Around one third of patients undergoing percutaneous coronary intervention (PCI) have left ventricular (LV) dysfunction. Whilst the prevalence of LV dysfunction is known to increase with age, the prevalence of LV dysfunction in different age groups in the PCI setting is not known and the effect of age on the prognostic value of LV function in the PCI setting has not been examined. Methods The relationship between LV function and 30-day mortality in patients undergoing PCI in different age groups (

Between 10 and 30% of patients undergoing percutaneous coronary intervention (PCI) have left ventricular (LV) dysfunction. We investigate the association between LV function on early and late mortality outcomes in a national 'real-world' cohort undergoing PCI in the elective and acute coronary syndrome setting through analysis of the British Cardiovascular Intervention Society (BCIS) data set.The relationship between LV function and 30-day mortality in patients undergoing PCI for elective, ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) indications was studied in 230 464 patients in the UK between 2006 and 2011. Abnormal LV function was an independent predictor of 30-day mortality outcomes: 30-day mortality risk for patients with moderate LV function (EF: 30-49%) (HR: 2.91; 95% CI: 2.43-3.49, P0.0001) and poor LV function (EF30%) (HR: 7.25; 95% CI: 5.87-8.96, P0.0001) was compared with patients with good LV function (EF50%). The independent prognostic impact of poor LV function on 30-day mortality increased from elective PCI (HR: 3.72: 95% CI: 2.21-6.25, P0.0001) through to the NSTEMI (HR: 5.03: 95% CI: 3.64-6.93, P0.0001) and STEMI (HR: 8.18: 95% CI: 5.62-11.92, P0.0001).Our data suggest a strong relationship between LV function and mortality outcomes following PCI, with worsening LV function independently predicting 30-day and longer-term mortality outcomes across all indications for PCI. We report a differential impact of LV function on mortality outcomes across different indications for PCI, with the greatest adverse prognostic association between worsening LV function and mortality outcomes observed in patients undergoing PCI in the STEMI setting.

The introduction of new generation agricultural products has generated an increased need for efficient and accurate product segregation across a number of Canadian agricultural sectors. As a key component of wheat handling in the Canadian grain industry, grading of wheat for value-added blending has historically been accomplished by visual identification. As of 2008 in Canada, visual identification was eliminated for all primary classes of wheat and replaced by an alternative system of wheat declaration. Given the high costs of testing each truck and railcar for quality assurance, the declaration system must rely on incentives and trust as there is now considerable potential for accidental or opportunistic misrepresentation throughout the grain supply chain. This research attempts to identify cost-effective handling strategies and policies so as to maintain the integrity of the supply chain under the new declaration system. An agent-based simulation model is developed to capture the effects of individual heterogeneity as well as behavioral adaption to the declaration system within the modern wheat supply chain. The simulated results are used to identify superior testing strategies for handlers, along with the relative risks and costs associated with each of the testing strategies. L'introduction de nouvelles generations de produits agricoles a accru le besoin de segregation fiable et efficace des produits issus de certaines activites du secteur agricole canadien. Le classement du ble destine a la preparation de melanges a valeur ajoutee, etape cle de la manutention du ble au sein de l'industrie cerealiere canadienne, s'effectuait par le passe a l'aide d'un systeme d'identification visuelle. Au Canada, l'identification visuelle des principales classes de ble a ete abolie en 2008 et a ete remplacee par un systeme de declaration de la classe de ble au moment de la livraison. Compte tenu des couts substantiels lies a la verification des camions et des wagons pour l'assurance de la qualite, le nouveau systeme de declaration doit reposer sur des mesures incitatives et la confiance etant donne qu'il existe dorenavant un potentiel eleve d'accident ou de fausse declaration accidentelle ou opportuniste de la part des acteurs de la chaine d'approvisionnement des grains. La presente etude tente de determiner des strategies et des politiques de manutention efficaces par rapport au cout afin de maintenir l'integrite de la chaine d'approvisionnement sous le nouveau systeme de declaration. Nous avons mis au point un modele de simulation multi-agent pour cerner les effets de l'heterogeneite individuelle de meme que l'adaptation comportementale au nouveau systeme de declaration en vigueur. Nous avons utilise les resultats du modele pour elaborer des strategies de verification de la qualite pour les manutentionnaires de grains et mesurer les risques et les couts relatifs lies a chacune de ces strategies.

Background The Affordable Care Act provides health care coverage to an increasing segment of the population at Medicaid reimbursement rates. Health care systems currently offset lower Medicaid reimbursement through higher payers. The ability to "cost shift" will be diminished as the Medicaid population increases. Study Design A financial cost and revenue analysis of outpatient laparoscopic cholecystectomy at our institution was performed. Cost was defined as actual expense to the health care institution. Fixed and variable costs were identified to calculate a break-even point. Time spent from check in to dismissal was based on historic averages. When actual costs could not be pinpointed, estimates from industry experts were used. Reimbursement included surgeon and anesthesia professional fees and facility fees. Results A total of 501 laparoscopic cholecystectomies were performed at the main operating room facility in 2012. Annual fixed costs were $252,637. Variable costs were $1,860/case. Personnel and single-use equipment made the largest contribution to variable costs. Reimbursement for professional and facility fees totaled $2,444/case. The break-even point occurred at 454 cases. Based on historic volume, the break-even point for the calendar year would occur on November 27. Conclusions Our analysis demonstrates that laparoscopic cholecystectomy can be performed with a positive margin at Medicaid reimbursement rates with sufficient volume. The minimal margin, however, could substantially limit the ability of lower-volume hospitals to provide these services and negatively impact access to care in this patient population.

Background Up to half of patients undergoing percutaneous coronary intervention have multivessel coronary artery disease ( MVD ) with conflicting data regarding optimal revascularization strategy in such patients. This paper assesses the evidence for complete revascularization ( CR ) versus incomplete revascularization in patients undergoing percutaneous coronary intervention, and its prognostic impact using meta‐analysis. Methods and Results A search of PubMed, EMBASE , MEDLINE , Current Contents Connect, Google Scholar, Cochrane library, Science Direct, and Web of Science was conducted to identify the association of CR in patients with multivessel coronary artery disease undergoing percutaneous coronary intervention with major adverse cardiac events and mortality. Random‐effects meta‐analysis was used to estimate the odds of adverse outcomes. Meta‐regression analysis was conducted to assess the relationship with continuous variables and outcomes. Thirty‐eight publications that included 156 240 patients were identified. Odds of death ( OR 0.69, 95% CI 0.61‐0.78), repeat revascularization ( OR 0.60, 95% CI 0.45‐0.80), myocardial infarction ( OR 0.64, 95% CI 0.50‐0.81), and major adverse cardiac events ( OR 0.63, 95% CI 0.50‐0.79) were significantly lower in the patients who underwent CR . These outcomes were unchanged on subgroup analysis regardless of the definition of CR . Similar findings were recorded when CR was studied in the chronic total occlusion ( CTO ) subgroup ( OR 0.65, 95% CI 0.53‐0.80). A meta‐regression analysis revealed a negative relationship between the OR for mortality and the percentage of CR . Conclusion CR is associated with reduced risk of mortality and major adverse cardiac events, irrespective of whether an anatomical or a score‐based definition of incomplete revascularization is used, and this magnitude of risk relates to degree of CR . These results have important implications for the interventional management of patients with multivessel coronary artery disease.

Transfemoral access (TFA) is widely used for coronary angiography and percutaneous coronary intervention (PCI). The influence of operator experience and PCI volume on adherence to transfemoral access best practices has not been studied. This international survey aimed to examine the influence of

Incorporating a potassium ferrate hemostatic disc (StatSeal Advanced, Biolife, Sarasota, Florida) as an adjunct to a hemostasis band has been shown to reduce time to hemostasis (TTH) with low rates of radial artery occlusion (RAO). Hematoma rates, however, have been variable across previous trials.

Despite the sustained clinical benefit demonstrated by immune checkpoint inhibitors, a majority of patients derive minimal or no appreciable benefit, indicating the urgent need to incorporate novel immunomodulatory targets and therapeutic strategies. Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) catalyze the first and rate-limiting step in the immunosuppressive tryptophan/kynurenine pathway and are both upregulated in a number of tumor types. Although small-molecule IDO1 inhibitors are being clinically evaluated in several tumor types, so far they have not demonstrated significant clinical benefits either as a single agent or in combination with immune checkpoint inhibition. We are developing pegylated kynureninase (Kynase), a kynurenine degrading enzyme, to treat a broader population with IDO1 and/or TDO2 expressing tumors. We believe that a more robust antitumor immune response can be achieved by depleting kynurenine, produced by both IDO1 and TDO2, with Kynase, than by inhibiting only IDO1. The human Kynase (HsKYN) has been successfully engineered to exhibit vastly improved catalytic activity and stability toward kynurenine over the wild-type human enzyme. HsKYN achieved durable and near complete plasma kynurenine depletion in mice, rats and non-human primates. HsKYN demonstrated single agent efficacy in CT26, MC38 and B16-IDO syngeneic mouse models. Tumor gene expression analysis using NanoString revealed that HsKYN treatment upregulated T-cell and NK cell activation signature. More importantly, HsKYN significantly increased the tumor-infiltrating CD8 T-cells and their activation/polyfunctionality, and reduced the Treg population. As a direct comparison, the lead IDO1 inhibitor epacadostat did not impose any meaningful effects on the same immune cell populations. Furthermore, HsKYN showed beneficial combination efficacy with anti-PD-1 that was superior to combined Epacadostat / anti-PD-1. Evidence to date suggest that HsKYN is well tolerated in multiple species. Therefore, immunoprofiling, efficacy and safety results strongly support that Kynase is a more effective therapeutic approach than IDO1 inhibition. HsKYN is moving toward clinical development for treatment of cancers where IDO1 and/or TDO2 pathways play a significant immunosuppressive role. Citation Format: Silvia Coma, Jillian Cavanaugh, James Nolan, Jeremy Tchaicha, Karen McGovern, Everett Stone, John Blazeck, Candice Lamb, George Georgiou, Mark G Manfredi, Michelle Zhang. Treatment of IDO1 and TDO2 positive tumors with a kynurenine-degrading enzyme: A highly differentiated approach from IDO1 inhibition [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B008.

Atypical non HLA antibodies are increasingly recognised as causes of immunological injury in allotransplantation. In this report we describe a non HLA sensitized male renal allograft recipient who developed acute vascular rejection on a “for cause” biopsy (Banff v2, g2, ptc 3) at day 4 post first renal allograft in the presence of elevated angiotensin II type 1 receptor antibodies (AT1R-Ab level 14.1). The acute rejection was treated with pulse corticosteroid therapy, anti-thymocyte globulin (ATG × 6), plasma exchange (1.5 plasma volume replacement x6) and oral candesartan. Serum creatinine improved and follow up biopsy confirmed resolution of rejection following treatment. AT1R-Ab should be considered when rejection is diagnosed in the absence of HLA antibodies.

Objectives This study sought to investigate the influence of access site utilization on mortality, major adverse cardiac and cardiovascular events (MACCE), bleeding, and vascular complications in a large number of patients treated by primary percutaneous coronary intervention (PPCI) in the United Kingdom over a 5-year period, through analysis of the British Cardiovascular Intervention Society database. Background Despite advances in antithrombotic and antiplatelet therapy, bleeding complications remain an important cause of morbidity and mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing PPCI. A significant proportion of such bleeding complications are related to the access site, and adoption of radial access may reduce these complications. These benefits have not previously been studied in a large unselected national population of PPCI patients. Methods Mortality (30-day), MACCE (a composite of 30-day mortality and in-hospital myocardial re-infarction, target vessel revascularization, and cerebrovascular events), and bleeding and access site complications were studied based on transfemoral access (TFA) and transradial access (TRA) site utilization in PPCI STEMI patients. The influence of access site selection was studied in 46,128 PPCI patients; TFA was used in 28,091 patients and TRA in 18,037. Data were adjusted for potential confounders using Cox regression that accounted for the propensity to undergo radial or femoral approach. Results TRA was independently associated with a lower 30-day mortality (hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.52 to 0.97; p Conclusions This analysis of a large number of PPCI procedures demonstrates that utilization of TRA is independently associated with major reductions in mortality, MACCE, major bleeding, and vascular complication rates.

[1] Northern peatlands contain vast amounts of organic carbon. Large-scale datasets have documented spatial patterns of peatland initiation as well as vertical peat accumulation rates. However, the rate, pattern, and timing of lateral expansion across the northern landscape remain largely unknown. As peatland lateral extent is a key boundary condition constraining the dynamics of peatland systems, understanding this process is essential. Here we use ground penetrating radar (GPR) and peat core analysis to study the effect of local slope and topography on peatland development at a site in south-central Alaska. The study site is unique in that a thick tephra (volcanic ash) layer, visible in the GPR data, interrupted the peatland development for about one thousand years during the mid Holocene. In our analysis, this tephra layer serves as a re-initiation point for peatland development. By comparing the initial mineral basin vs. the post-tephra surfaces, the influence of topography and slope on peatland expansion rate and peat-carbon sequestration was analyzed. Our results show that (1) peatland surface slope becomes progressively shallower over the Holocene, (2) slope affects peatland lateral expansion nonlinearly, (3) the relationship between lateral expansion rate and slope follows a power-law behavior, and (4) peatland expansion becomes slope-limited above a threshold (0.5°). Furthermore, we propose a conceptual model linking slope to peatland lateral expansion where slope gradient and basin topography exert deterministic controls on peatland lateral expansion directly or through hydrology and vertical accumulation rates.

Radial access use has been growing steadily but, despite encourag- ing results, still varies greatly among operators, hospitals, countries and continents. Twenty years from its introduction, it was felt that the time had come to develop a common evidence-based view on the technical, clinical and organisational implications of using the radial approach for coronary angiography and interventions. The European Association of Percutaneous Cardiovascular Interven- tions (EAPCI) has, therefore, appointed a core group of European and non-European experts, including pioneers of radial angioplasty and operators with different practices in vascular access supported by experts nominated by the Working Groups on Acute Cardiac Care and Thrombosis of the European Society of Cardiology (ESC). Their goal was to define the role of the radial approach in modern interventional practice and give advice on technique, training needs, and optimal clinical indications.