479 research outputs found

    Choosing appropriate patient‐reported outcome measures for prostate disease

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    Robot-assisted surgery in horseshoe kidneys: A safety and feasibility multi-centre case series

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    OBJECTIVE: We assessed the safety and feasibility of minimally invasive robot-assisted surgery for horseshoe kidney (HSK). METHOD: A prospectively maintained data set for consecutive patients undergoing robotic kidney surgery was reviewed for patients with HSK. Cases were performed by experienced robotic surgeons, across two high-volume centres between 2016 and 2020. RESULTS: A prospectively maintained data set for consecutive patients undergoing robotic kidney surgery was reviewed for patients with HSK. Cases were performed by experienced robotic surgeons, across two high-volume centres between 2016 and 2020. CONCLUSION: We report one the largest series of robot-assisted surgery on HSK. Robotic surgery is safe and feasible for HSK in centralised high-volume centres with acceptable perioperative outcomes. Established benefits of minimally invasive surgery, such as reduced LOS and low complication rates, were demonstrated. LEVEL OF EVIDENCE: 4

    Phylogenetic Beta Diversity Metrics, Trait Evolution and Inferring the Functional Beta Diversity of Communities

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    The beta diversity of communities along gradients has fascinated ecologists for decades. Traditionally such studies have focused on the species composition of communities, but researchers are becoming increasingly interested in analyzing the phylogenetic composition in the hope of achieving mechanistic insights into community structure. To date many metrics of phylogenetic beta diversity have been published, but few empirical studies have been published. Further inferences made from such phylogenetic studies critically rely on the pattern of trait evolution. The present work provides a study of the phylogenetic dissimilarity of 96 tree communities in India. The work compares and contrasts eight metrics of phylogenetic dissimilarity, considers the role of phylogenetic signal in trait data and shows that environmental distance rather than spatial distance is the best correlate of phylogenetic dissimilarity in the study system

    Selective Inhibitors of the JMJD2 Histone Demethylases: Combined Nondenaturing Mass Spectrometric Screening and Crystallographic Approaches†

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    Ferrous ion and 2-oxoglutarate (2OG) oxygenases catalyze the demethylation of N(epsilon)-methylated lysine residues in histones. Here we report studies on the inhibition of the JMJD2 subfamily of histone demethylases, employing binding analyses by nondenaturing mass spectrometry (MS), dynamic combinatorial chemistry coupled to MS, turnover assays, and crystallography. The results of initial binding and inhibition assays directed the production and analysis of a set of N-oxalyl-d-tyrosine derivatives to explore the extent of a subpocket at the JMJD2 active site. Some of the inhibitors were shown to be selective for JMJD2 over the hypoxia-inducible factor prolyl hydroxylase PHD2. A crystal structure of JMJD2A in complex with one of the potent inhibitors was obtained; modeling other inhibitors based on this structure predicts interactions that enable improved inhibition for some compounds

    Paleo-Drainage Basin Connectivity Predicts Evolutionary Relationships across Three Southeast Asian Biodiversity Hotspots

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    Understanding factors driving diversity across biodiversity hotspots is critical for formulating conservation priorities in the face of ongoing and escalating environmental deterioration. While biodiversity hotspots encompass a small fraction of Earth's land surface, more than half the world's plants and two-thirds of terrestrial vertebrate species are endemic to these hotspots. Tropical Southeast (SE) Asia displays extraordinary species richness, encompassing four biodiversity hotspots, though disentangling multiple potential drivers of species richness is confounded by the region's dynamic geological and climatic history. Here, we use multilocus molecular genetic data from dense multispecies sampling of freshwater fishes across three biodiversity hotspots, to test the effect of Quaternary climate change and resulting drainage rearrangements on aquatic faunal diversification. While Cenozoic geological processes have clearly shaped evolutionary history in SE Asian halfbeak fishes, we show that paleo-drainage re-arrangements resulting from Quaternary climate change played a significant role in the spatiotemporal evolution of lowland aquatic taxa, and provide priorities for conservation efforts. [Freshwater; geology; halfbeak; island radiation; Miocene; Pleistocene; river; Southeast Asia.

    Longitudinal MR imaging after unilateral MR-guided focused ultrasound thalamotomy: clinical and radiological correlation

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    IntroductionMagnetic-resonance-guided focused ultrasound (MRgFUS) thalamotomy uses multiple converging high-energy ultrasonic beams to produce thermal lesions in the thalamus. Early postoperative MR imaging demonstrates the location and extent of the lesion, but there is no consensus on the utility or frequency of postoperative imaging. We aimed to evaluate the evolution of MRgFUS lesions and describe the incidence, predictors, and clinical effects of lesion persistence in a large patient cohort.MethodsA total of 215 unilateral MRgFUS thalamotomy procedures for essential tremor (ET) by a single surgeon were retrospectively analyzed. All patients had MR imaging 1 day postoperatively; 106 had imaging at 3 months and 32 had imaging at 1 year. Thin cut (2 mm) axial and coronal T2-weighted MRIs at these timepoints were analyzed visually on a binary scale for lesion presence and when visible, lesion volumes were measured. SWI and DWI sequences were also analyzed when available. Clinical outcomes including tremor scores and side effects were recorded at these same time points. We analyzed if patient characteristics (age, skull density ratio), preoperative tremor score, and sonication parameters influenced lesion evolution and if imaging characteristics correlated with clinical outcomes.ResultsVisible lesions were present in all patients 1 day post- MRgFUS and measured 307.4 ± 128.7 mm3. At 3 months, residual lesions (excluding patients where lesions were not visible) were 83.6% smaller and detectable in only 54.7% of patients (n = 58). At 1 year, residual lesions were detected in 50.0% of patients (n = 16) and were 90.7% smaller than 24 h and 46.5% smaller than 3 months. Lesions were more frequently visible on SWI (100%, n = 17), DWI (n = 38, 97.4%) and ADC (n = 36, 92.3%). At 3 months, fewer treatment sonications, higher maximum power, and greater distance between individual sonications led to larger lesion volumes. Volume at 24 h did not predict if a lesion was visible later. Lesion visibility at 3 months predicted sensory side effects but was not correlated with tremor outcomes.DiscussionOverall, lesions are visible on T2-weighted MRI in about half of patients at both 3 months and 1 year post-MRgFUS thalamotomy. Certain sonication parameters significantly predicted persistent volume, but residual lesions did not correlate with tremor outcomes

    The role of multiple marks in epigenetic silencing and the emergence of a stable bivalent chromatin state

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    We introduce and analyze a minimal model of epigenetic silencing in budding yeast, built upon known biomolecular interactions in the system. Doing so, we identify the epigenetic marks essential for the bistability of epigenetic states. The model explicitly incorporates two key chromatin marks, namely H4K16 acetylation and H3K79 methylation, and explores whether the presence of multiple marks lead to a qualitatively different systems behavior. We find that having both modifications is important for the robustness of epigenetic silencing. Besides the silenced and transcriptionally active fate of chromatin, our model leads to a novel state with bivalent (i.e., both active and silencing) marks under certain perturbations (knock-out mutations, inhibition or enhancement of enzymatic activity). The bivalent state appears under several perturbations and is shown to result in patchy silencing. We also show that the titration effect, owing to a limited supply of silencing proteins, can result in counter-intuitive responses. The design principles of the silencing system is systematically investigated and disparate experimental observations are assessed within a single theoretical framework. Specifically, we discuss the behavior of Sir protein recruitment, spreading and stability of silenced regions in commonly-studied mutants (e.g., sas2, dot1) illuminating the controversial role of Dot1 in the systems biology of yeast silencing.Comment: Supplementary Material, 14 page

    Comparison of three methods for ascertainment of contact information relevant to respiratory pathogen transmission in encounter networks

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    <p>Abstract</p> <p>Background</p> <p>Mathematical models of infection that consider targeted interventions are exquisitely dependent on the assumed mixing patterns of the population. We report on a pilot study designed to assess three different methods (one retrospective, two prospective) for obtaining contact data relevant to the determination of these mixing patterns.</p> <p>Methods</p> <p>65 adults were asked to record their social encounters in each location visited during 6 study days using a novel method whereby a change in physical location of the study participant triggered data entry. Using a cross-over design, all participants recorded encounters on 3 days in a paper diary and 3 days using an electronic recording device (PDA). Participants were randomised to first prospective recording method.</p> <p>Results</p> <p>Both methods captured more contacts than a pre-study questionnaire, but ascertainment using the paper diary was superior to the PDA (mean difference: 4.52 (95% CI 0.28, 8.77). Paper diaries were found more acceptable to the participants compared with the PDA. Statistical analysis confirms that our results are broadly consistent with those reported from large-scale European based surveys. An association between household size (trend 0.14, 95% CI (0.06, 0.22), <it>P </it>< 0.001) and composition (presence of child 0.37, 95% CI (0.17, 0.56), <it>P </it>< 0.001) and the total number of reported contacts was observed, highlighting the importance of sampling study populations based on household characteristics as well as age. New contacts were still being recorded on the third study day, but compliance had declined, indicating that the optimal number of sample days represents a trade-off between completeness and quality of data for an individual.</p> <p>Conclusions</p> <p>The study's location-based reporting design allows greater scope compared to other methods for examining differences in the characteristics of encounters over a range of environments. Improved parameterisation of dynamic transmission models gained from work of this type will aid in the development of more robust decision support tools to assist health policy makers and planners.</p
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