Tylosis with oesophageal cancer: Diagnosis, management and molecular mechanisms

Research on iRHOM2 in the Kelsell group is funded by an MRC project grant, a MRC Clinical Fellowship (to TM) and a Cancer Research UK program grant

Tibial impacts and muscle activation during walking, jogging and running when performed overground, and on motorised and non-motorised treadmills.

Purpose To examine tibial acceleration and muscle activation during overground (OG), motorised treadmill (MT) and non-motorised treadmill conditions (NMT) when walking, jogging and running at matched velocities. Methods An accelerometer recorded acceleration at the mid-tibia and surface EMG electrodes recorded rectus femoris (RF), semitendinosus (ST), tibialis anterior (TA) and soleus (SL) muscle activation during OG, MT and NMT locomotion whilst walking, jogging and running. Results The NMT produced large reductions in tibial acceleration when compared with OG and MT conditions across walking, jogging and running conditions. RF EMG was small-moderately higher in the NMT condition when compared with the OG and MT conditions across walking, jogging and running conditions. ST EMG showed large and very large increases in the NMT when compared to OG and MT conditions during walking whilst SL EMG found large increases on the NMT when compared to OG and MT conditions during running. The NMT condition generated very large increases in step frequency when compared to OG and MT conditions during walking, with large and very large decreases during jogging and very large decreases during running. Conclusions The NMT generates large reductions in tibial acceleration, moderate to very large increases in muscular activation and large to very large decreases in cycle time when compared to OG and MT locomotion. Whilst this may decrease the osteogenic potential of NMT locomotion, there may be uses for NMTs during rehabilitation for lower limb injuries

Cost-effectiveness of adoption strategies for point of care HIV viral load monitoring in South Africa

Background: Viral load (VL) testing is recommended for monitoring people on ART. The National Health Laboratory Service (NHLS) in South Africa conducts >5million laboratory-based VL tests but faces challenges with specimen integrity and results delivery. Point-of-care (POC) VL monitoring may improve VL suppression (VLS). We assessed the cost-effectiveness of different strategies for POC testing in South Africa. Methods: We developed a cost-outcome model utilizing NHLS data, including facility-level annual VL volumes, proportion with VLS, specimen rejection rates, turn-around-time, and the cost/test. We assessed the impact of adopting POC VL technology under 4 strategies: (1) status-quo; (2) targeted POC testing at facilities with high levels of viral failure; (3) targeted POC testing at low-performing facilities; (4) complete POC adoption. For each strategy, we determined the total cost, effectiveness (expected number of virally suppressed people) and incremental cost-effectiveness ratio (ICER) based on expected (>10%) VLS improvement. Findings: Existing laboratory-based VL testing costs $126 m annually and achieves 85.2$40/additional person suppressed, compared to the status-quo. Should resources allow, complete POC adoption may be cost-effective (ICER: $136/additional person suppressed), requiring an additional$49 m annually and achieving 94.5% VLS. All other strategies were dominated in the incremental analysis. Interpretation: Assuming POC VL monitoring confers clinical benefits, the most cost-effective strategy for POC adoption in South Africa is a targeted approach with POC VL technologies placed at facilities with high level of viral failure. Funding: Funding support from the Bill & Melinda Gates Foundation

AML risk stratification models utilizing ELN-2017 guidelines and additional prognostic factors: a SWOG report.

Background: The recently updated European LeukemiaNet risk stratification guidelines combine cytogenetic abnormalities and genetic mutations to provide the means to triage patients with acute myeloid leukemia for optimal therapies. Despite the identification of many prognostic factors, relatively few have made their way into clinical practice. Methods: In order to assess and improve the performance of the European LeukemiaNet guidelines, we developed novel prognostic models using the biomarkers from the guidelines, age, performance status and select transcript biomarkers. The models were developed separately for mononuclear cells and viable leukemic blasts from previously untreated acute myeloid leukemia patients (discovery cohort, Results: Models using European LeukemiaNet guidelines were significantly associated with clinical outcomes and, therefore, utilized as a baseline for comparisons. Models incorporating age and expression of select transcripts with biomarkers from European LeukemiaNet guidelines demonstrated higher area under the curve and C-statistics but did not show a substantial improvement in performance in the validation cohort. Subset analyses demonstrated that models using only the European LeukemiaNet guidelines were a better fit for younger patients (age \u3c 55) than for older patients. Models integrating age and European LeukemiaNet guidelines visually showed more separation between risk groups in older patients. Models excluding results for Conclusions: While European LeukemiaNet guidelines remain a critical tool for triaging patients with acute myeloid leukemia, the findings illustrate the need for additional prognostic factors, including age, to improve risk stratification

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software