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Temperature-activated dislocation avalanches signaling brittle-to-ductile transition in BCC micropillars
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We carry out strain-controlled in-situ compression experiments of micron-sized tungsten (W) micropillars in the temperature range 300–900 K, together with simulations of three-dimensional discrete dislocation dynamics (DDD) at the same scale. Two distinct regimes are observed. At low temperatures, plastic deformation appears smooth, both temporally and spatially. Stress fluctuations are consistent with a Wiener stochastic process resulting from uncorrelated dislocation activity within the pillars. However, high-temperature stress fluctuations are highly correlated and exhibit features of self-organized criticality (SOC), with deformation located within well-defined slip bands. The high-temperature stress relaxation statistics are consistent with a thermally activated nucleation process from the surface. The nature of the transition between the two regimes is a manifestation of the brittle to ductile transition in BCC metals
Building a framework for adolescent and young adult transition of care for patients with neurofibromatosis type 1 and neurofibromatosis type 2-related schwannomatosis syndromes
No full textNeurofibromatosis type 1 (NF1) and Neurofibromatosis Type 2-Related Schwannomatosis (NF2-SWN) are the two most common genetic disorders that present with Central nervous system(CNS) tumors. Patients with NF1 and NF2-SWN typically present in childhood and are initially managed by pediatric subspecialties. As CNS tumors are the leading cause of pediatric cancer related death, managing these tumors in NF1 and NF2-SWN patients requires coordinated multidisciplinary life-long care. Adolescent and young adult (AYA) transition of care is a major opportunity for improvement in NF2 and NF2-SWN outcomes. While few small studies have focused on the NF1 population, there is minimal literature covering NF2-SWN AYA transition of care. Healthcare transition (HCT) is extremely complex for all chronic patients; however, these complexities are magnified in patients with NF1 and NF2-SWN. Having an AYA HCT model can decrease gaps in care and improve survival. We review the literature on NF1 and NF2-SWN transition of care and describe the necessary framework to establish a system to improve patient outcomes
Prevalence of treatment-acquired homozygous losses (homozygous deletions) of PTEN from androgen receptor pathway inhibitors (ARPI) in metastatic prostate cancer
No full text27Background: Validated homozygous loss detection is becoming increasingly important in clinical practice, with prostate NCCN guideline inclusion of BRCA1/2 loss (often portending durable PARP inhibitor benefit) and multi-tumor trials of PRMT5 and MAT2A inhibitors ongoing (biomarker: MTAP loss). Homozygous losses are challenging to detect and require intentional NGS assay design and validations. Using an FDA-approved NGS assay, we evaluated the most frequent losses identified in metastatic prostate cancer, evaluated prognostic associations on ARPI, and prevalence before and after ARPI treatments. Methods: This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine Prostate Cancer clinico-genomic database (FH-FMI CGDB), originating from approximately 280 US cancer clinics (~800 sites of care). Patients with metastatic prostate cancer and tissue tumor genomic testing by FoundationOne CDx were eligible for analysis. Alteration prevalence was compared between non-sequential groups of specimens obtained from patients naïve to ADT and ARPI, naïve to ARPI but not ADT, or exposed to any ARPI. Outcome analyses adjusted for: ECOG performance score, age, baseline PSA, and socioeconomic status. To limit immortal time confounding, outcome analyses were restricted to patients with specimens tested prior to initiation of ARPI. Results: 1990 specimens from 1984 unique patients met criteria for assessment. The most common losses and respective ADT & ARPI naïve vs ADT exposed & ARPI-naïve vs ARPI-exposed prevalence were PTEN (17.1% vs 24.8% vs. 33.5%, p < 0.001), FAS (2.4% vs 5.0% vs 5.8%, p = 0.003), BRCA2 (4.2% vs 3.2% vs. 2.8%, p = 0.36), RB1 (1.6% vs 3.0% vs 3.5%, p = 0.062), and TP53 (2.3% vs 2.3% vs 4.4%, p = 0.064). 227 patients had tissue specimens obtained and NGS results reported prior to initiation of ARPI. Sufficient patients with PTEN loss were present for nominal outcome associations, observing less favorable time to next treatment (HR: 1.81, 95%CI: 1.24 – 2.65, p = 0.002) and overall survival (HR: 1.65, 95%CI: 1.02 – 2.65, p = 0.040) from the initiation of ARPI. In the mHSPC (ADT and ARPI naïve) setting, 17.1% had PTEN loss, 32.8% had an HRR gene alteration, and 2.8% had both. Conclusions: Our results are consistent with homozygous losses of certain genes, notably PTEN, potentially being acquired resistance alterations to ARPI. Prostate cancer trials often do not specify timing of specimen acquisition relative to treatment initiation. For trials like IPATential-150 or CAPItello-280 that evaluate AKT inhibitors in post-ARPI setting, patients with PTEN status determined by archival tissue could be false negatives and reduce power of analysis in biomarker(+) group. Our results underscore the importance of clinical context, especially prior treatment exposures, when interpreting biomarker prevalence
ASO Visual Abstract: Commission on Cancer Quality Measure for Omission of Sentinel Lymph Node Biopsy (SNB) in Women Aged 70 Years or Older with Hormone Receptor-Positive (HR + ) Invasive Breast Cancer (IBC) Undergoing Breast-Conserving Surgery (BCS): Review of Historical Performance
No full textStudy design considerations in clinical trials testing transcutaneous stimulation for spinal cord injury
No full textMethodological review and expert perspective.
To examine the methodological challenges in designing rigorous clinical trials for transcutaneous spinal cord stimulation (tSCS) in chronic spinal cord injury (SCI), with particular focus on challenges of sham control implementation, and to propose alternative trial design approaches that balance scientific rigor with practical feasibility and ethical considerations.
United States.
We analyzed the design considerations that influenced the Up-LIFT pivotal trial, examining three critical constraints: the technical limitations of creating safe and convincing sham stimulation for extended protocols; the participant burden associated with traditional sham-controlled designs; and the heightened risks during the COVID-19 pandemic. We reviewed existing literature on placebo effects in neuromodulation, technical challenges of sham tSCS implementation, and ethical considerations specific to the SCI population. Alternative methodological approaches were evaluated, including sequential self-controlled designs, biomarker-guided approaches, and adaptive trial designs.
Traditional sham controls for tSCS face serious technical challenges because participants readily detect stimulation parameters, minimal currents produce detectable neuromodulatory effects, and extended protocols amplify these issues through knowledge sharing and functional feedback. Ethical concerns include substantial participant burden, potential for lessebo effects when a sham is suspected, and erosion of therapeutic relationships through prolonged deception. The COVID-19 pandemic added critical safety considerations for the vulnerable SCI population. Alternative designs, such as sequential self-controlled approaches, as implemented in Up-LIFT, can maintain scientific validity while addressing these constraints.
The unique challenges of tSCS clinical trials necessitate innovative methodological approaches beyond traditional placebo-controlled designs. Sequential self-controlled designs, biomarker-guided studies, and adaptive trial methodologies offer scientifically sound alternatives that respect participant welfare while generating robust evidence. Future research should pursue dual paths: developing improved sham paradigms while advancing alternative trial methodologies suitable for neuromodulation-enhanced rehabilitation interventions
Patterns of Care and Clinical Outcomes in Systemic Peripheral T-cell Lymphoma: The LEO-MER Prospective Cohort Study
No full text•LEO-MER real-world prospective cohort study shows that systemic PTCLs remain highly heterogeneous, with poor outcomes in most subtypes.•Minimal change in survival rates over the last two decades emphasizes the unmet clinical need for novel therapeutic approaches in PTCL.
Few prospective benchmark studies exist to characterize the evolving contemporary real-world practice for PTCL. We report the patterns of first-line care and outcomes for 720 patients with systemic PTCL enrolled in two related prospective cohort studies, LEO from 2015-2020 (ClinicalTrials.gov NCT02736357) and MER from 2002-2015, both followed through 2024. The primary endpoints were EFS and OS using Kaplan-Meier estimator and Cox regression model. Secondary endpoints included correlations of clinical and treatment factors with survival. The most common induction regimens were CHOP-based (70%), given as CHOP (36%), CHOP plus etoposide (23%), or CHOP-like plus novel agents (11.5%, including 5% BV-CHP). Consolidative autologous stem cell transplant was performed in 102 patients (14%). Within nodal PTCL, EFS and OS were adversely associated with IPI 2-5 (HR=2.00, 95%CI: 1.59–2.52 for EFS; HR=2.44, 95%CI: 1.86–3.19 for OS), PIT 1-4 (HR=3.02, 95%CI 2.07-4.39 for EFS; HR=5.10, 95%CI 3.01-8.63 for OS), and non-ALCL subtypes (HR=2.97, 95%CI: 2.26–3.91 for EFS; HR=3.71, 95%CI: 2.65–5.20 for OS). Within LEO, which captured increasing first-line etoposide and BV, adding etoposide to CHOP was associated with better OS in ALK-negative ALCL (HR=0.14, 95%CI: 0.03-0.69, p=0.015). BV-CHP showed a trend toward OS improvement in ALCL (HR=0.15, 95%CI 0.02-1.19, p=0.073). Patients failing EFS6 and EFS24 had 5-year subsequent OS of 12% (95% CI: 7.8%, 19%) and 17% (95% CI: 13%, 22%), respectively. The inferior outcomes in non-ALCL subtypes and patients failing EFS6 and EFS24 highlight unmet needs with CHOP-based induction, where clinical trials with targeted therapy should be prioritized
In Search of Wool(s): Rethinking the Future of Materials and Craft Communities
No full textSustainable and circular production has been highlighting the importance of material extraction, processing, and disposal. In order to reduce the negative environmental and social impact of design products, relying on regenerative resources that are biodegradable and non-hazardous have become important assets. Developing novel materials with such properties is one of the strategies for minimizing material-based impact. This paper explores possibilities of reviving existing materials in industrial and local production for bettering the conditions. The paper introduces a project titled “In Search of Wool(s)” to identify the challenges of growing and using local wool, specifically in North Carolina, USA. The project examines the potential of existing natural materials to be reintroduced as sustainable solutions for overcoming environmental problems that stem from material generation and disposal. By building on the findings developed from interviews and a workshop with sheep farmers, artisans, and educators, the paper proposes developing and strengthening material communities as a method of reviving the use of existing natural materials. Findings show that expanding people and things involved in material communities is a crucial first step to bringing innovative thinking back to local practices. These initiatives can also help small communities develop in socially sustainable ways
Factors Associated with a Higher Risk of Conversion from Radiation-Free Percutaneous Nephrolithotomy (PCNL) to Fluoroscopy-Guided Percutaneous nephrolithotomy
No full textIntroduction and Objective: Percutaneous nephrolithotomy percutaneous nephrostomy (PCNL) is a minimally invasive procedure for kidney stone removal traditionally guided by fluoroscopy. This study aimed to evaluate the feasibility and outcomes of radiation-free PCNL using ultrasonography alone compared with standard fluoroscopy-guided PCNL.Methods: A total of 63 PCNL cases were eligible for radiation-free PCNL, but 27 were excluded (intraoperatively aborted, ureteroscopy performed instead, preoperative complex anatomy). Of the remaining 36 cases eligible for radiation-free PCNL, 11 were converted intraoperatively to fluoroscopic-based PCNL. Postoperative computed tomography (CT) imaging was available for only 16 of the 25 radiation-free PCNL cases and 4 of the 11 converted cases. We designated these 16 prospective radiation-free PCNL cases (2024-2025) as Group A. For comparison purposes, we identified a historical case-matched cohort of 150 PCNLs. Of these, 67 were excluded (similar reasons), leaving 83 retrospective fluoroscopy-guided PCNL cases (2022-2024) called Group B. A subset of Group A cases was converted from radiation-free intraoperatively to fluoroscopy and were designated as Group C. The primary outcome was stone-free rate (SFR), assessed postoperatively by noncontrast CT (2-3 mm slices). Secondary outcomes included estimated blood loss, complication rates (Clavien-Dindo), and postoperative stone events.Results: The median preoperative stone burden was 35 mm in Group A and 27 mm in Groups B and C [p = 0.3]. SFR (Grade A) was comparable across Groups A, B, and C [38%, 30%, and 25%, respectively (p = 0.8)]. No differences were observed in complications or secondary outcomes.Conclusions: Radiation-free PCNL is feasible and yields comparable outcomes to standard fluoroscopy-guided PCNL, offering a promising method to reduce radiation exposure without compromising surgical success. However, we identified a consistent theme of poor visualization that prompted conversion to fluoroscopy for some of the cases. Innovation directed toward improving tool echogenicity is key to diffusing this technique
"No BLT": The Rise and Risk of Acronyms in the Medical Record
No full textBLT, SSCP, WHOL-the use of acronyms has expanded, comprising large portions of most clinicians' notes. We present examples of acronyms found in medical records at our institutions and collected as part of an initiative among three ethics committees to demonstrate not only their widespread use, but also the breadth of the types of acronyms used in the medical record. Acronyms have traditionally been used in medical charting to increase efficiency. However, acronyms can impede patient care because they are prone to misinterpretations and misunderstandings between medical professionals. Such misunderstandings have led to incorrect pharmaceutical dosage administration and misdiagnoses. With patients gaining access to their medical records under the Cures Act in 2020, clinicians must also consider the readability of their notes not only for colleagues, but also patients. We provide four different solutions to help mitigate the use of acronyms in medical records while balancing clinician interests in efficiency: creating and implementing "do not use" lists for commonly misunderstood acronyms, leading educational sessions and audits to ensure clinical care team members adhere to "do not use" lists and "approved acronyms" lists, implementing an Electronic Health Record with functionality to create "user dictionaries" in which typed acronyms automatically become full phrases, and seeking feedback from care team members and patients on whether notes have become more "readable" after implementation of initial strategies. Though the use of acronyms may continue to be a feature of medical communication, we hope to encourage the reduction and then judicious use of acronyms.</p
Empowering the Community Health Worker Role in the Stroke Continuum of Care: Development of the Florida Stroke Registry CHW Stroke Training Program
No full textObjectives Community health workers (CHWs) help patients navigate community resources and support healthier lifestyles. Although stroke transitions of care require navigating complex clinical services and behavioral changes, there is no established formal training for CHWs in stroke care across Florida. We describe the impact of a comprehensive stroke training course designed and tailored for community health workers. Methods We developed a CHW stroke care curriculum with input from the Florida CHW Coalition, vascular neurologists, epidemiologists, and Florida Stroke Registry stakeholders. The course, featuring a 12-credit continuing medical education curriculum, was a hybrid of live and recorded lectures, modules, and community engagement exercises. Free registrations were promoted via the Florida CHW Coalition advertisements, Florida Stroke Registry Web site and listserv, and stakeholder meetings. Results Three separate cohorts accomplished the course. Across 3 years (2022-2024), a total of 75 participants (54 of whom completed the course) were included in this analysis. The median age was 44 years (interquartile range 35-54), with 74% of participants aged 54 years or younger. The racial/ethnic distribution was 33% Hispanic, 30% White, and 26% Black. The majority were female (n = 50, 93%). The mean pretraining score was 72% (standard deviation 15.2%), which increased to 91% (standard deviation 6.2%) posttraining. Due to the nonnormal distribution of score differences, we used the Wilcoxon signed-rank test (S) which confirmed a statistically significant improvement in scores post training (S = 735.5, p < 0.001) indicating higher post-training scores and reduced variability, indicating both effectiveness and consistency of learning gains. Conclusions The formal training of CHWs to recognize stroke risk factors, promote self-management, and support stroke care equipped CHWs with the essential skills and knowledge to confidently foster meaningful partnerships with the community aimed at improving stroke outcomes.</p