Phase I/II trial of concurrent extracranial palliative radiation therapy with Dabrafenib and Trametinib in metastatic BRAF V600E/K mutation-positive cutaneous Melanoma

Background: Concurrent treatment with BRAF inhibitors and palliative radiation therapy (RT) could be associated with increased toxicity, especially skin toxicity. Current Eastern Cooperative Oncology Group (ECOG) consensus guideline recommend ceasing BRAF inhibitors during RT. There is a lack of data regarding concurrent RT with combined BRAF and MEK inhibitors. This single-arm phase I/II trial was designed to assess the safety and tolerability of palliative RT with concurrent Dabrafenib and Trametinib in patients with BRAF-mutant metastatic melanoma. Materials and methods: Patients received Dabrafenib and Trametinib before and during palliative RT to soft tissue, nodal or bony metastases. The RT dose was escalated stepwise during the study period. Toxicity data including clinical photographs of the irradiated area was collected for up to 12 months following completion of RT. Results: Between June 2016 to October 2019, ten patients were enrolled before the study was stopped early due to low accrual rate. Six patients were treated at level 1 (20 Gy in 5 fractions, any location) and 4 patients at level 2a (30 Gy in 10 fractions with no abdominal viscera exposed). All alive patients completed one year of post-RT follow-up. Of the 82 adverse events (AEs) documented, the majority (90%) were grade 1 and 2. Eight grade 3 events (10%) occurred in five patients, only one was treatment-related (grade 3 fever due to Dabrafenib and Trametinib). No patients experienced grade 3 or 4 RT related toxicities, including skin toxicities. One serious AE was documented in relation to a grade 3 fever due to Dabrafenib and Trametinib requiring hospitalisation. Conclusions: The lack of grade 3 and 4 RT-related toxicities in our study suggests that Dabrafenib and Trametinib may be continued concurrently during fractionated non-visceral palliative RT to extracranial sites

The SAMI Galaxy Survey: Spatially resolving the environmental quenching of star formation in GAMA galaxies

We use data from the Sydney-AAO Multi-Object Integral Field Spectrograph (SAMI) Galaxy Survey and the Galaxy And Mass Assembly (GAMA) survey to investigate the spatially-resolved signatures of the environmental quenching of star formation in galaxies. Using dust-corrected measurements of the distribution of Hα emission we measure the radial profiles of star formation in a sample of 201 star-forming galaxies covering three orders of magnitude in stellar mass (M∗M∗; 108.1-1010.95 M⊙) and in 5th nearest neighbour local environment density (Σ5; 10−1.3- 102.1 Mpc−2). We show that star formation rate gradients in galaxies are steeper in dense (log10(Σ5/Mpc2) > 0.5) environments by 0.58 ± 0.29 dex re−1 in galaxies with stellar masses in the range 1010 1.0). These lines of evidence strongly suggest that with increasing local environment density the star formation in galaxies is suppressed, and that this starts in their outskirts such that quenching occurs in an outside-in fashion in dense environments and is not instantaneous

Global data set of long-term summertime vertical temperature profiles in 153 lakes

peer reviewedClimate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change. © 2021, The Author(s)

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

IMMEDIATE AND PROLONGED EFFECTS OF THERAPEUTIC ELASTIC TAPE ON VASTI MUSCLE ACTIVATION

IMMEDIATE AND PROLONGED EFFECTS OF THERAPEUTIC ELASTIC TAPE ON VASTI MUSCLE ACTIVATION S.E. Risso, K.M. Bishop, M.S. Fogarty, A.L. Johanson, A.D. LaGoy, M.M. O’Hollaren, A.E. Zander, R.S. McCulloch Gonzaga University, Spokane, WA Patellofemoral pain syndrome (PFPS) is a common ailment that can cause severe anterior knee pain. Up to 40% of patients seen in orthopedic clinics for knee pain are diagnosed with PFPS. One proposed mechanism of PFPS is lateral tracking of the patella due to imbalance between the vastus medialis (VM) and vastus lateralis (VL) muscles. A low VM: VL activation ratio has been correlated with increased patellar tilt in subjects with PFPS. Despite increased usage of therapeutic elastic tape for injury prevention and rehabilitation for conditions such as knee pain, its effectiveness has not been extensively studied. PURPOSE: To determine if therapeutic elastic tape has a positive effect on the VM: VL activation ratio in healthy subjects, and thus whether further testing should be done to examine its effects in PFPS patients with patellar maltracking. METHODS: Thirteen healthy, active, female undergraduate students participated in four testing sessions. In sessions one and three, therapeutic elastic tape or placebo tape was applied to the subjects’ VM in a randomized and counterbalanced manner. Muscle activation was then tested during a step activity ten minutes post taping to determine the short term effects of therapeutic elastic tape. To determine long term effects, subjects kept the tape on for 3 days, after which time they returned to the lab for session two or four. During each session, subjects performed a warm up followed by a maximum voluntary contraction (MVC) and step up for which electromyography (EMG) data was recorded for VM and VL. The MVC consisted of three knee extensions against resistance. After a two minute rest, subjects performed three step ups onto a 19.6 cm box. Step rate was standardized using a metronome set at 40 bpm. Average EMG values were converted to a percentage of MVC from which the VM: VL activation ratio was calculated. RESULTS: No significance was found for effect of time (F (1, 9) = 0.15, p = 0.704), taping condition (F (2, 18) = 0.32, p = 0.730), or interaction of time and tape (F (2, 18) = 0.67, p = 0.523). CONCLUSIONS: The current study does not support the clinical use of therapeutic elastic tape for improved VM: VL ratio. Further research is suggested to determine the effects of therapeutic elastic tape in other applications

The matrix metalloproteinase-3 (MMP-3) 5A/6A promoter polymorphism is not associated with ischaemic heart disease: Analysis employing a family based approach

Matrix metalloproteinase-3 (MMP-3) has been proposed as an important mediator of the atherosclerotic process. The possible role of the functional -1612 5A/6A polymorphism of the MMP-3 gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family based tests of association. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped. Using the combined transmission disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test (PDT), no association between the MMP-3 -1612 5A/6A polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the MMP-3 -1612 5A/6A polymorphism is not associated with IHD