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It has been suggested that a cellularly unstable laminar flame, which is freely propagating in unbounded space, can accelerate and evolve into a turbulent flame with the neighbouring flow exhibiting the basic characteristics of turbulence. Famously known as self-turbulization, this conceptual transition in the flow regime, which arises from local interactions between the propagating wrinkled flamefront and the flow, is critical in extreme events such as the deflagration-to-detonation transition (DDT) leading to supernova explosions. Recognizing that such a transition in the flow regime has not been conclusively demonstrated through experiments, in this work, we present experimental measurements of flow characteristics of flame-generated ‘turbulence’ for expanding cellular laminar flames. The energy spectra of such ‘turbulence’ at different stages of cellular instability are analysed. A subsequent scaling analysis points out that the observed energy spectra are driven by the fractal topology of the cellularly unstable flamefront.
ABSTRACT IMPACT: Urine tumor DNA non-invasively detects minimal residual disease and infers tumor mutational burden in locally advanced bladder cancer prior to radical cystectomy, which may potentially enable the selection of patients for bladder-sparing treatment or facilitate personalized adjuvant immunotherapy. OBJECTIVES/GOALS: Standard-of-care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy. The inability to assess minimal residual disease (MRD) non-invasively limits our ability to offer bladder-sparing treatment. We sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis. METHODS/STUDY POPULATION: We applied uCAPP-Seq, a targeted sequencing method for detecting utDNA, to urine cell-free DNA samples acquired on the day of radical cystectomy from 42 patients with bladder cancer. utDNA variant-calling was performed non-invasively without prior tumor mutational knowledge. The overall utDNA level for each patient was represented by the non-silent mutation with the highest variant allele fraction after removing germline variants. Urine was similarly analyzed from 15 healthy adults. Tumor mutational burden (TMB) was inferred from the number of non-silent mutations detected in urine cell-free DNA by applying a linear relationship derived from TCGA whole exome sequencing of 409 MIBC tumors. RESULTS/ANTICIPATED RESULTS: utDNA levels were significantly higher in patients with residual disease detected in their surgical pathology compared to those who achieved a pathologic complete response (P = 0.002). Using an optimal utDNA threshold to define MRD detection, positive utDNA MRD significantly predicted the absence of pathologic complete response with a sensitivity of 81% and specificity of 81%. Positive utDNA MRD also portended significantly worse progression-free survival (HR = 7.4; P = 0.03) compared to negative utDNA MRD. Furthermore, we applied a linear relationship (Pearson r = 0.84; P < 0.0001) to identify patients with high inferred TMB who may have been candidates for early immune checkpoint blockade. DISCUSSION/SIGNIFICANCE OF FINDINGS: utDNA MRD analysis prior to surgery correlated significantly with pathologic response and progression-free survival, which may help select patients for bladder-sparing treatment. utDNA can also non-invasively infer TMB, which could facilitate personalized adjuvant therapy for patients in the future.
The Scaling-up Health-Arts Programme: Implementation and Effectiveness Research (SHAPER) project is the world's largest hybrid study on the impact of the arts on mental health embedded into a national healthcare system. This programme, funded by the Wellcome Trust, aims to study the impact and the scalability of the arts as an intervention for mental health. The programme will be delivered by a team of clinicians, research scientists, charities, artists, patients and healthcare professionals in the UK's National Health Service (NHS) and the community, spanning academia, the NHS and the charity sector. SHAPER consists of three studies – Melodies for Mums, Dance for Parkinson's, and Stroke Odysseys – which will recruit over 800 participants, deliver the interventions and draw conclusions on their clinical impact, implementation effectiveness and cost-effectiveness. We hope that this work will inspire organisations and commissioners in the NHS and around the world to expand the remit of social prescribing to include evidence-based arts interventions.
This study determines the prevalence of inadequate micronutrient intakes consumed by long-term care (LTC) residents. This cross-sectional study was completed in thirty-two LTC homes in four Canadian provinces. Weighed and estimated food and beverage intake were collected over 3 non-consecutive days from 632 randomly selected residents. Nutrient intakes were adjusted for intra-individual variation and compared with the Dietary Reference Intakes. Proportion of participants, stratified by sex and use of modified (MTF) or regular texture foods, with intakes below the Estimated Average Requirement (EAR) or Adequate Intake (AI), were identified. Numbers of participants that met these adequacy values with use of micronutrient supplements was determined. Mean age of males (n 197) was 85·2 (sd 7·6) years and females (n 435) was 87·4 (sd 7·8) years. In all, 33 % consumed MTF; 78·2 % (males) and 76·1 % (females) took at least one micronutrient pill. Participants on a MTF had lower intake for some nutrients (males=4; females=8), but also consumed a few nutrients in larger amounts than regular texture consumers (males=4; females =1). More than 50 % of participants in both sexes and texture groups consumed inadequate amounts of folate, vitamins B6, Ca, Mg and Zn (males only), with >90 % consuming amounts below the EAR/AI for vitamin D, E, K, Mg (males only) and K. Vitamin D supplements resolved inadequate intakes for 50–70 % of participants. High proportions of LTC residents have intakes for nine of twenty nutrients examined below the EAR or AI. Strategies to improve intake specific to these nutrients are needed.
The aim of the present study was to report the survival outcomes and late toxicity of high-dose-rate brachytherapy (HDRBT) boost for dose escalation in patients with intermediate-to-high-risk prostate cancer.
Materials and methods
Retrospective data were collected from 137 patients who had undergone definitive radiotherapy for prostate cancer between 2006 and 2010. All patients had external-beam radiotherapy (median dose 46Gy) and HDRBT. Brachytherapy dose was 19Gy in two fractions (6 hours apart) with one implant using Ir-192.
There were 94 high-risk and 43 intermediate-risk patients (NCCN classification). The median follow-up period was 60 months. The 5-year biochemical progression-free survival was 92 and 76% for intermediate- and high-risk groups, respectively. Prostate cancer-specific survival for the intermediate-risk group was 100% and for the high-risk group it was 92% at 5 years. For the entire cohort, the 5-year rate of urethral stricture formation was 13%, and the 5-year rate of late grade 2 and grade 3 gastrointestinal toxicity was 4·7 and 4·6%, respectively. There was no grade 3 or greater genitourinary toxicity.
Our data add to the growing body of literature supporting the use of HDRBT in prostate cancer. Late toxicity rates were marginally higher than that expected.
Psychiatric and cognitive changes are common in patients with Parkinson's disease and have key clinical consequences but, despite this, these symptoms are often under-diagnosed and under-treated, leading to increased morbidity and costs. With chapters focused on the major neuropsychiatric features, Neuropsychiatric and Cognitive Changes in Parkinson's Disease and Related Movement Disorders rectifies this deficit. Written by experts in the field, with a consistent focus on relevant clinical knowledge, it provides a comprehensive overview including all the major behavioral changes associated with movement disorders. The book provides broad, in-depth, accurate and up-to-date scientific information as well as crucial understanding and practical tools to help patients. The book is essential reading for clinicians working in neurology, psychiatry and geriatric medicine.
Nitridation of GeO2 interfacial layer (IL) was done using continuous wave (CW) and pulsed wave (PW) decoupled plasma nitridation (DPN) processes. Langmuir probe analysis of the N2 plasma demonstrates that at the same effective power and pressure, PW plasma has similar electron density (Ne) with lower electron temperature (kTe) and plasma potential (Vp) as compared to CW plasma. This results in softer plasma conditions using a PW process leading to lower plasma-related damage in the IL, but without reducing the overall nitrogen concentration. The plasma parameters were further correlated to mobility (μ) and interface trap density (Dit) extracted from fabricated Ge n-MOSFETs. As expected from the plasma analysis, at the same effective power and pressure, the PW DPN process shows 1.2X higher electron mobility as compared to a CW process. This improvement can enable GeON as an IL for future Ge CMOS gate stack technology.
High resolution Schottky barrier detectors for alpha particles have been fabricated on 20 μm n-type 4H-SiC epitaxial layers. Schottky barrier contact structure was accomplished by deposition of 10 nm nickel on the Si face of the epilayers. The detectors were characterized for structural, electrical, and spectroscopic properties. Scanning electron microscopy and Nomarski optical microscopy revealed a micropipe density lower than 1 cm-2. The current-voltage (I-V) characteristics of the device exhibited very low leakage current of the order of 6.5 pA at an operating bias of 90 V. C-V measurements revealed a typical effective doping concentrations of 2.4 × 1014 cm-3 in these epilayers. The detectors were evaluated for alpha particles detection using a 241Am source. An energy resolution of ∼0.98% for 5.48 MeV alpha particles was observed. The separate contribution of charge carrier drift and diffusion to the total charge collection efficiency has been calculated in these detectors following a drift-diffusion model. Detailed electronic noise analysis in terms of equivalent noise charge (ENC) was carried out to study the effect of various noise components that contribute to the total electronic noise in the detection system. Effect of shaping time, presence of source and bias on the ENC has been studied in details.