Quantitative evaluation of diffusion tensor imaging at 3T in the human lumbar intervertebral disc degeneration

Poster presentations: ST4postprintThe 2010 World Forum for Spine Research (WFSR 2010): The Intervertebral Disc, Montreal, Canada, 5-8 July 2010

Colorectal cancer with synchronous liver-limited metastases : the protocol of an Inception Cohort study (CoSMIC)

Introduction Colorectal cancer is the fourth most common cancer in the UK and an important cause of cancer-related death. In 20% of patients, there is metastasis to the liver or beyond at the time of diagnosis. The management of synchronous disease is complex. Conventional surgery removes the colorectal primary first, followed by chemotherapy, with resection of liver metastases as a final step. Advances in the availability and safety of liver surgery, anaesthesia and critical care have made two alternative options feasible. The first is synchronous resection of the primary and liver metastases. The second is resection of the metastatic disease as the first step, termed the reverse or liver-first approach. Currently, evidence is inadequate to inform the selection of care pathway for patients with colorectal cancer and synchronous liver-limited metastases. Specifically, optimal pathways are not defined and there is a dearth of prospectively recorded cohort-defining factors influencing treatment selection or outcome. Methods and analysis Colorectal cancer with Synchronous liver-limited Metastases: an Inception Cohort (CoSMIC) is an inception cohort study of patients with a new diagnosis of colorectal cancer with synchronous liver-limited metastases. The sequence of treatment received, and factors influencing treatment decisions, will be evaluated against European Society of Medical Oncology guidelines. Clinical data will be collected, and quality of life, morbidity, mortality and long-term outcome compared for different treatment sequences adjusted for prognostic factors. Disease-free survival or progression will be measured at 1, 2 and 5 years. A nested qualitative study will ascertain patient experiences and clinician perspectives on delivery of care. Ethics and dissemination The full study protocol was independently peer reviewed by Professor Kees de Jong (University of Maastricht, Holland). CoSMIC has ethical approval from the National Health Service Research Ethics Committee (14/NW/1397). Results will be disseminated to healthcare professionals and patient groups, and may be used to design a definitive trial addressing areas of equipoise in treatment pathways, as well as optimising current pathways to improve outcomes and experiences

How ethnic studies faculty use streaming video: Instructional needs, applications, and challenges

While there have been studies on faculty use of streaming video resources in academic libraries, none have focused on the specific needs of ethnic studies faculty. Using a thematic analysis of semi-structured interviews with 13 ethnic studies faculty from two public university campuses, this study found that faculty engagement with video is based upon a pedagogical strategy that responds to the specific demands and goals of ethnic studies curricula, while centering on student needs by using free resources whenever possible. Within this paradigm, faculty choose from three categories of content: key primary and secondary sources; flexible supporting sources; and current topics of interest. Understanding what motivates ethnic study faculty could be helpful as librarians work with vendors and advocate for the content that best meets instructional needs. Librarians can also help improve faculty\u27s instructional outcomes by communicating about licensing options and streaming media availability through the library

An Antithrombin-Heparin Complex Increases the Anticoagulant Activity of Fibrin Clots

Clotting blood contains fibrin-bound thrombin, which is a major source of procoagulant activity leading to clot extension and further activation of coagulation. When bound to fibrin, thrombin is protected from inhibition by antithrombin (AT) + heparin but is neutralized when AT and heparin are covalently linked (ATH). Here, we report the surprising observation that, rather than yielding an inert complex, thrombin-ATH formation converts clots into anticoagulant surfaces that effectively catalyze inhibition of thrombin in the surrounding environment

Rewiring the Epigenetic Networks in MLL-Rearranged Leukemias: Epigenetic Dysregulation and Pharmacological Interventions

Leukemias driven by chromosomal translocation of the mixed-lineage leukemia gene (MLL or KMT2A) are highly prevalent in pediatric oncology. The poor survival rate and lack of an effective targeted therapy for patients with MLL-rearranged (MLL-r) leukemias emphasize an urgent need for improved knowledge and novel therapeutic approaches for these malignancies. The resulting chimeric products of MLL gene rearrangements, i.e., MLL-fusion proteins (MLL-FPs), are capable of transforming hematopoietic stem/progenitor cells (HSPCs) into leukemic blasts. The ability of MLL-FPs to reprogram HSPCs toward leukemia requires the involvement of multiple chromatin effectors, including the histone 3 lysine 79 methyltransferase DOT1L, the chromatin epigenetic reader BRD4, and the super elongation complex. These epigenetic regulators constitute a complicated network that dictates maintenance of the leukemia program, and therefore represent an important cluster of therapeutic opportunities. In this review, we will discuss the role of MLL and its fusion partners in normal HSPCs and hematopoiesis, including the links between chromatin effectors, epigenetic landscapes, and leukemia development, and summarize current approaches to therapeutic targeting of MLL-r leukemias

Same day HIV diagnosis and antiretroviral therapy initiation affects retention in Option B+ prevention of mother-to-child transmission services at antenatal care in Zomba District, Malawi.

INTRODUCTION: Data from the Option B+ prevention of mother-to-child transmission (PMTCT) program in Malawi show considerable variation between health facilities in retention on antiretroviral therapy (ART). In a programmatic setting, we studied whether the "model of care," based on the degree of integration of antenatal care (ANC), HIV testing and counselling (HTC) and ART service provision-influenced uptake of and retention on ART. METHODS: We conducted a retrospective cohort study of pregnant women seeking ANC at rural primary health facilities in Zomba District, Malawi. Data were extracted from standardized national ANC registers, ART registers and ART master cards. The "model of care" of Option B+ service delivery was determined at each health facility, based on the degree of integration of ANC, HTC and ART. Full integration (Model 1) of HTC and ART initiation at ANC was compared with integration of HTC only into ANC services (Model 2) with subsequent referral to an existing ART clinic for treatment initiation. RESULTS AND DISCUSSION: A total of 10,528 women were newly registered at ANC between October 2011 and March 2012 in 23 rural health facilities (12 were Model 1 and 11 Model 2). HIV status was ascertained in 8,572 (81%) women. Among 914/8,572 (9%) HIV-positive women enrolling at ANC, 101/914 (11%) were already on ART; of those not on treatment, 456/813 (56%) were started on ART. There was significantly higher ART uptake in Model 1 compared with Model 2 sites (63% vs. 51%; p=0.001), but significantly lower ART retention in Model 1 compared with Model 2 sites (79% vs. 87%; p=0.02). Multivariable analysis showed that initiation of ART on the same day as HIV diagnosis, but not model of care, was independently associated with reduced retention in the first six months (adjusted odds ratio 2.27; 95% CI: 1.34-3.85; p=0.002). CONCLUSIONS: HIV diagnosis and treatment on the same day was associated with reduced retention on ART, independent of the level of PMTCT service integration at ANC

ULF wave derived radiation belt radial diffusion coefficients

Waves in the ultra-low-frequency (ULF) band have frequencies which can be drift resonant with electrons in the outer radiation belt, suggesting the potential for strong interactions and enhanced radial diffusion. Previous radial diffusion coefficient models such as those presented by Brautigam and Albert (2000) have typically used semiempirical representations for both the ULF wave’s electric and magnetic field power spectral densities (PSD) in space in the magnetic equatorial plane. In contrast, here we use ground- and space-based observations of ULF wave power to characterize the electric and magnetic diffusion coefficients. Expressions for the electric field power spectral densities are derived from ground-based magnetometer measurements of the magnetic field PSD, and in situ AMPTE and GOES spacecraft measurements are used to derive expressions for the compressional magnetic field PSD as functions of Kp, solar wind speed, and L-shell. Magnetic PSD results measured on the ground are mapped along the field line to give the electric field PSD in the equatorial plane assuming a guided Alfvén wave solution and a thin sheet ionosphere. The ULF wave PSDs are then used to derive a set of new ULF-wave driven diffusion coefficients. These new diffusion coefficients are compared to estimates of the electric and magnetic field diffusion coefficients made by Brautigam and Albert (2000) and Brautigam et al. (2005). Significantly, our results, derived explicitly from ULF wave observations, indicate that electric field diffusion is much more important than magnetic field diffusion in the transport and energization of the radiation belt electrons

Association between antibiotic consumption and colon and rectal cancer development in older individuals: A territory‐wide study

Background: Antibiotics may alter colorectal cancer (CRC) risk due to gut dysbiosis. We aimed to study the specific and temporal effects of various antibiotics on CRC development in older individuals. Methods: This was a territory-wide retrospective cohort study. Subjects aged 60 years and older who did not have CRC diagnosed on screening/diagnostic colonoscopy diagnosed between 2005 and 2013 were recruited. Exclusion criteria were history of CRC, colectomy, inflammatory bowel disease, and CRC diagnosed within 6 months of index colonoscopy. Exposure was use of any antibiotics up to 5 years before colonoscopy. The primary outcomes were CRC diagnosed >6 m after colonoscopy. Covariates were patient demographics, history of colonic polyps/polypectomy, concomitant medication use (NSAIDs, COX-2 inhibitors, aspirin, and statins), and performance of endoscopy centers (colonoscopy volume and polypectomy rate). Stratified analysis was conducted according to nature of antibiotics and location of cancer. Results: Ninety seven thousand one hundred and sixty-two eligible subjects (with 1026 [1.0%] cases of CRC) were identified, 58,704 (60.4%) of whom were exposed to antibiotics before index colonoscopy. Use of antibiotics was associated with a lower risk of cancer in rectum (adjusted hazard ratio [aHR]: 0.64, 95% CI: 0.54–0.76), but a higher risk of cancer in proximal colon (aHR: 1.63, 95%CI: 1.15–2.32). These effects differed as regards the anti-anaerobic/anti-aerobic activity, narrow-/broad-spectrum, and administration route of antibiotics. Conclusions: Antibiotics had divergent effects on CRC development in older subjects, which varied according to the location of cancer, antibiotic class, and administration route