A pooled long-term follow-up after radiotherapy for prostate cancer with and without a rectal hydrogel spacer: Impact of hydrogel on decline in sexual quality of life

PURPOSE: The purpose of this study was to analyze the impact of prostate rectal spacers on sexual quality of life (QOL) following external beam radiation therapy (RT). METHODS AND MATERIALS: Patient- reported QOL was evaluated using the Expanded Prostate Cancer Index Composite (EPIC). Patients were pooled from two sources: a randomized controlled trial and a non-randomized cohort of patients from a single institution. Both cohorts used the same spacing product and QOL instrument. Analysis was limited to those with good baseline pre-treatment sexual QOL (EPIC \u3e/= 60). Differences in QOL summary score and individual items were assessed compared with baseline and between treatment arms. RESULTS: A total of 128 men had good baseline sexual function and were evaluated (64% with spacer and 36% without) with QOL data available for median 33 months (range: 2.5-69.4 months). Men without spacer were more likely to have declines in sexual function ( CONCLUSION: In this pooled analysis of QOL after prostate RT, the utilization of a hydrogel spacer was associated with better sexual QOL, less men with measurable declines in sexual QOL, and higher rates of adequate erectile function

A pooled long-term follow-up after radiotherapy for prostate cancer with and without a rectal hydrogel spacer: impact of hydrogel on decline in sexual quality of life

PurposeThe purpose of this study was to analyze the impact of prostate rectal spacers on sexual quality of life (QOL) following external beam radiation therapy (RT).Methods and materialsPatient- reported QOL was evaluated using the Expanded Prostate Cancer Index Composite (EPIC). Patients were pooled from two sources: a randomized controlled trial and a non-randomized cohort of patients from a single institution. Both cohorts used the same spacing product and QOL instrument. Analysis was limited to those with good baseline pre-treatment sexual QOL (EPIC >/= 60). Differences in QOL summary score and individual items were assessed compared with baseline and between treatment arms.ResultsA total of 128 men had good baseline sexual function and were evaluated (64% with spacer and 36% without) with QOL data available for median 33 months (range: 2.5–69.4 months). Men without spacer were more likely to have declines in sexual function (p < 0.0001), bother (p = 0.0002), and sexual summary score (p < 0.0001). A minimally important difference of 10 points (1xMID) and 20 point (2xMID) was more likely without rectal spacer [10 points: odds ratio 3.53, (95% confidence interval 1.11–11.2), p = 0.032; 20 points: odds ratio 3.29, (95% confidence interval 1.16–9.33), p = 0.025]. Seven of 13 QOL items were statistically superior with hydrogel (six of nine functional and one of four bother), while no items were statistically superior for control. At baseline, more men treated with hydrogel had erections sufficient for intercourse; however, when analyzed only by the men with best baseline erectile potential and excluding those with worse function, the benefit of rectal spacing was maintained with a higher likelihood of preservation of erections sufficient for intercourse in those treated with hydrogel.ConclusionIn this pooled analysis of QOL after prostate RT, the utilization of a hydrogel spacer was associated with better sexual QOL, less men with measurable declines in sexual QOL, and higher rates of adequate erectile function

Histone H1 Limits DNA Methylation in Neurospora crassa

Histone H1 variants, known as linker histones, are essential chromatin components in higher eukaryotes, yet compared to the core histones relatively little is known about their in vivo functions. The filamentous fungus Neurospora crassa encodes a single H1 protein that is not essential for viability. To investigate the role of N. crassa H1, we constructed a functional FLAG-tagged H1 fusion protein and performed genomic and molecular analyses. Cell fractionation experiments showed that H1-3XFLAG is a chromatin binding protein. Chromatin-immunoprecipitation combined with sequencing (ChIP-seq) revealed that H1-3XFLAG is globally enriched throughout the genome with a subtle preference for promoters of expressed genes. In mammals, the stoichiometry of H1 impacts nucleosome repeat length. To determine if H1 impacts nucleosome occupancy or nucleosome positioning in N. crassa, we performed micrococcal nuclease digestion in the wild-type and the ΔhH1 strain followed by sequencing (MNase-seq). Deletion of hH1 did not significantly impact nucleosome positioning or nucleosome occupancy. Analysis of DNA methylation by whole-genome bisulfite sequencing (MethylC-seq) revealed a modest but global increase in DNA methylation in the ΔhH1 mutant. Together, these data suggest that H1 acts as a nonspecific chromatin binding protein that can limit accessibility of the DNA methylation machinery in N. crassa

RGB2LIDAR: Towards Solving Large-Scale Cross-Modal Visual Localization

We study an important, yet largely unexplored problem of large-scale cross-modal visual localization by matching ground RGB images to a geo-referenced aerial LIDAR 3D point cloud (rendered as depth images). Prior works were demonstrated on small datasets and did not lend themselves to scaling up for large-scale applications. To enable large-scale evaluation, we introduce a new dataset containing over 550K pairs (covering 143 km^2 area) of RGB and aerial LIDAR depth images. We propose a novel joint embedding based method that effectively combines the appearance and semantic cues from both modalities to handle drastic cross-modal variations. Experiments on the proposed dataset show that our model achieves a strong result of a median rank of 5 in matching across a large test set of 50K location pairs collected from a 14km^2 area. This represents a significant advancement over prior works in performance and scale. We conclude with qualitative results to highlight the challenging nature of this task and the benefits of the proposed model. Our work provides a foundation for further research in cross-modal visual localization.Comment: ACM Multimedia 202

Role of drug transporters and drug accumulation in the temporal acquisition of drug resistance

<p>Abstract</p> <p>Background</p> <p>Anthracyclines and taxanes are commonly used in the treatment of breast cancer. However, tumor resistance to these drugs often develops, possibly due to overexpression of drug transporters. It remains unclear whether drug resistance <it>in vitro </it>occurs at clinically relevant doses of chemotherapy drugs and whether both the onset and magnitude of drug resistance can be temporally and causally correlated with the enhanced expression and activity of specific drug transporters. To address these issues, MCF-7 cells were selected for survival in increasing concentrations of doxorubicin (MCF-7_DOX-2), epirubicin (MCF-7_EPI), paclitaxel (MCF-7_TAX-2), or docetaxel (MCF-7_TXT). During selection cells were assessed for drug sensitivity, drug uptake, and the expression of various drug transporters.</p> <p>Results</p> <p>In all cases, resistance was only achieved when selection reached a specific threshold dose, which was well within the clinical range. A reduction in drug uptake was temporally correlated with the acquisition of drug resistance for all cell lines, but further increases in drug resistance at doses above threshold were unrelated to changes in cellular drug uptake. Elevated expression of one or more drug transporters was seen at or above the threshold dose, but the identity, number, and temporal pattern of drug transporter induction varied with the drug used as selection agent. The pan drug transporter inhibitor cyclosporin A was able to partially or completely restore drug accumulation in the drug-resistant cell lines, but had only partial to no effect on drug sensitivity. The inability of cyclosporin A to restore drug sensitivity suggests the presence of additional mechanisms of drug resistance.</p> <p>Conclusion</p> <p>This study indicates that drug resistance is achieved in breast tumour cells only upon exposure to concentrations of drug at or above a specific selection dose. While changes in drug accumulation and the expression of drug transporters does occur at the threshold dose, the magnitude of resistance cannot be attributed solely to changes in drug accumulation or the activity of drug transporters. The identities of these additional drug-transporter-independent mechanisms are discussed, including their likely clinical relevance.</p

Outcomes of hypofractionated stereotactic body radiotherapy boost for intermediate and high-risk prostate cancer

BACKGROUND AND PURPOSE: Treatment of intermediate and high-risk prostate cancer with a high BED has been shown to increase recurrence free survival (RFS). While high dose rate (HDR) brachytherapy, given as a boost is effective in delivering a high BED, many patients are not candidates for the procedure or wish to avoid an invasive procedure. We evaluated the use of stereotactic body radiotherapy (SBRT) as a boost, with dosimetry modeled after HDR-boost. MATERIAL AND METHODS: Fifty patients were treated with two fractions of SBRT (9.5-10.5 Gy/fraction) after 45 Gy external-beam radiotherapy, with 48 eligible for analysis at a median follow-up of 42.7 months. RESULTS: The Kaplan-Meier estimates of biochemical control post-radiation therapy (95 % Confidence Interval) at 3, 4 and 5 years were 95 % (81–99 %), 90 % (72–97 %) and 90 % (72–97 %), respectively (not counting 2 patients with a PSA bounce as failures). RFS (defined as disease recurrence or death) estimates at 3, 4 and 5 years were 92 % (77–97 %), 88 % (69–95 %) and 83 % (62–93 %) if patients with PSA bounces are not counted as failures, and were 90 % (75–96 %), 85 % (67–94 %) and 75 % (53–88 %) if they were. The median time to PSA nadir was 26.2 months (range 5.8–82.9 months), with a median PSA nadir of 0.05 ng/mL (range <0.01–1.99 ng/mL). 2 patients had a “benign PSA bounce”, and 4 patients recurred with radiographic evidence of recurrence beyond the RT fields. Treatment was well tolerated with no acute G3 or higher GI or GU toxicity and only a single G3 late GU toxicity of urinary obstruction. CONCLUSIONS: SBRT boost is well-tolerated for intermediate and high-risk prostate cancer patients with good biochemical outcomes and low toxicity

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe