Evidence of in-situ Cu clustering as a function of laser power during laser powder bed fusion of 17–4 PH stainless steel

The use of intrinsic heat treatments to control the microstructural evolution during additive manufacturing could eliminate the need for costly post-build processing. Using atom probe microscopy and cluster search algorithms, this study investigates the degree of Cu clustering and precipitation in 17–4 precipitate hardening (PH) stainless steel fabricated by laser powder bed fusion (LPBF). It was found that LPBF samples exhibit a greater than random degree of Cu clustering, irrespective of the laser power during fabrication. It is further shown that using a higher laser power (161.5 W rather than 127.5 W) led to a higher number density of Cu clusters, Cu precipitates, and higher hardness due to the greater heat input. The observations of Cu-rich clusters and precipitates within as-printed LPBF samples and its laser power dependence are novel and show potential for inducing desired strengthening phases directly during LPBF, mitigating the need for post-fabrication heat treatments

Feasibility of right-sided total extraperitoneal procedure for inguinal hernia repair after appendectomy: a prospective cohort study

Contains fulltext : 80682.pdf (publisher's version ) (Open Access)BACKGROUND: Totally extraperitoneal (TEP) endoscopic hernia surgery is increasingly popular since it is associated with little postoperative pain and with early return to work. Previous appendectomy may preclude preperitoneal dissection in patients with right-sided hernias. The feasibility of TEP surgery in these patients was the subject of the present study. METHODS: Between January 2005 and February 2007 all consecutive patients undergoing TEP surgery were included in a prospective cohort study. The study group consisted of patients with right-sided and bilateral hernias. Operative times, conversions, complication rates, and return to daily activities were recorded. Patients were divided into two groups according to previous appendectomy. RESULTS: A total of 462 patients with right-sided hernias underwent TEP surgery: 421 patients without previous abdominal surgery (group 1) and 41 patients with previous appendectomy (group 2). The conversion rate was significantly higher in group 2: four patients (10%) were converted to open Lichtenstein repair versus five (1%) in group 1 (p = 0.005). However, we found no significant differences in complication rate, operative time, and return to daily activities. CONCLUSIONS: A right-sided (or bilateral) TEP procedure may be performed safely in patients after previous appendectomy. Despite a higher conversion rate, the vast majority of patients can be operated endoscopically

Review for the generalist: evaluation of anterior knee pain

Anterior knee pain is common in children and adolescents. Evaluation and management is challenging and requires a thorough history and physical exam, and understanding of the pediatric skeleton. This article will review common causes of chronic anterior knee pain in the pediatric population with a focus on patellofemoral pain

Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process

Protein S-palmitoylation, a hydrophobic post-translational modification, is performed by protein acyltransferases that have a common DHHC Cys-rich domain (DHHC proteins), and provides a regulatory switch for protein membrane association. In this work, we analyzed the presence of DHHC proteins in the protozoa parasite Giardia lamblia and the function of the reversible S-palmitoylation of proteins during parasite differentiation into cyst. Two specific events were observed: encysting cells displayed a larger amount of palmitoylated proteins, and parasites treated with palmitoylation inhibitors produced a reduced number of mature cysts. With bioinformatics tools, we found nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome. These proteins displayed a conserved structure when compared to different organisms and are distributed in different monophyletic clades. Although all Giardia DHHC proteins were found to be present in trophozoites and encysting cells, these proteins showed a different intracellular localization in trophozoites and seemed to be differently involved in the encystation process when they were overexpressed. dhhc transgenic parasites showed a different pattern of cyst wall protein expression and yielded different amounts of mature cysts when they were induced to encyst. Our findings disclosed some important issues regarding the role of DHHC proteins and palmitoylation during Giardia encystation.Fil: Merino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Vranych, Cecilia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

Treatment Discontinuation Patterns for Patients With Chronic Lymphocytic Leukemia in Real-World Settings: Results From a Multi-Center International Study

Introduction: This study assessed treatment discontinuation patterns and reasons among chronic lymphocytic leukemia (CLL) patients initiating first-line (1L) and second-line (2L) treatments in real-world settings. Materials and / Methods: Using deidentified electronic medical records from the CLL Collaborative Study of Real-World Evidence, premature treatment discontinuation was assessed among FCR, BR, BTKi-based, and BCL-2-based regimen cohorts. / Results: Of 1364 1L patients (initiated in 1997-2021), 190/13.9% received FCR (23.7% discontinued prematurely); 255/18.7% received BR (34.5% discontinued prematurely); 473/34.7% received BTKi-based regimens, of whom 28.1% discontinued prematurely; and 43/3.2% received venetoclax-based regimens, of whom 16.3% discontinued prematurely (venetoclax monotherapy: 7/0.5%, of whom 42.9% discontinued; VG/VR: 36/2.6%, of whom 11.1% discontinued). The most common reasons for treatment discontinuation were adverse events (FCR: 25/13.2%; BR: 36/14.1%; BTKi-based regimens: 75/15.9%) and disease progression (venetoclax-based: 3/7.0%). Of 626 2L patients, 20/3.2% received FCR (50.0% discontinued); 62/9.9% received BR (35.5% discontinued); 303/48.4% received BTKi-based regimens, of whom 38.0% discontinued; and 73/11.7% received venetoclax-based regimens, of whom 30.1% discontinued (venetoclax monotherapy: 27/4.3%, of whom 29.6% discontinued; VG/VR: 43/6.9%, of whom 27.9% discontinued). The most common reasons for treatment discontinuation were adverse events (FCR: 6/30.0%; BR: 11/17.7%; BTKi-based regimens: 60/19.8%; venetoclax-based: 6/8.2%). / Conclusion: The findings of this study highlight the continued need for tolerable therapies in CLL, with finite therapy offering a better tolerated option for patients who are newly diagnosed or relapsed/refractory to prior treatments

Coordination in climbing: effect of skill, practice and constraints manipulation

BACKGROUND: Climbing is a physical activity and sport involving many subdisciplines. Minimization of prolonged pauses, use of a relatively simple path through a route and smooth transitions between movements broadly define skilled coordination in climbing. OBJECTIVES: To provide an overview of the constraints on skilled coordination in climbing and to explore future directions in this emerging field. METHODS: A systematic literature review was conducted in 2014 and retrieved studies reporting perceptual and movement data during climbing tasks. To be eligible for the qualitative synthesis, studies were required to report perceptual or movement data during climbing tasks graded for difficulty. RESULTS: Qualitative synthesis of 42 studies was carried out, showing that skilled coordination in climbing is underpinned by superior perception of climbing opportunities; optimization of spatial-temporal features pertaining to body-to-wall coordination, the climb trajectory and hand-to-hold surface contact; and minimization of exploratory behaviour. Improvements in skilled coordination due to practice are related to task novelty and the difficulty of the climbing route relative to the individual's ability level. CONCLUSION: Perceptual and motor adaptations that improve skilled coordination are highly significant for improving the climbing ability level. Elite climbers exhibit advantages in detection and use of climbing opportunities when visually inspecting a route from the ground and when physically moving though a route. However, the need to provide clear guidelines on how to improve climbing skill arises from uncertainties regarding the impacts of different practice interventions on learning and transfer

Efficacy and Safety of Duvelisib Following Disease Progression on Ofatumumab in Patients with Relapsed/Refractory CLL or SLL in the DUO Crossover Extension Study

Purpose: In the phase 3 DUO trial, duvelisib, an oral dual PI3K-δ,γ inhibitor, demonstrated significantly improved efficacy vs ofatumumab (median [m]PFS, 13.3 vs 9.9 months [HR, 0.52; P < .0001]; ORR, 74% vs 45% [P < .0001]), with a manageable safety profile in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). We report results from patients with progressive disease (PD) after ofatumumab who crossed over to duvelisib in the DUO trial. Experimental Design: Patients with radiographically confirmed PD after ofatumumab received duvelisib 25 mg twice daily in 28-day cycles until PD, intolerance, death, or study withdrawal. The primary endpoint was ORR per investigator. Secondary endpoints included duration of response (DOR), PFS, and safety. Results: As of December 14, 2018, 90 ofatumumab-treated patients in the DUO trial prior to crossover had an ORR of 29%, mDOR of 10.4 months, and mPFS of 9.4 months. After crossover, 77% of patients (69/90) achieved a response, with an mDOR of 14.9 months and mPFS of 15.7 months. Patients with del(17p) and/or TP53 mutations had similar outcomes (ORR, 77% [20/26]; mPFS, 14.7 months). Notably, 73% of patients (47/64) with disease previously refractory to ofatumumab achieved a response. The most frequent any-grade/grade 3/4 treatment-emergent adverse events were diarrhea (47%/23%), neutropenia (26%/23%), pyrexia (24%/4%), cutaneous reactions (23%/4%), and thrombocytopenia (10%/6%). Conclusions: Duvelisib demonstrated high response rates with good durability and a manageable safety profile in patients with R/R CLL/SLL who progressed on ofatumumab, including patients with high-risk disease and disease previously refractory to ofatumumab

Rationale and design of a proof-of-concept trial investigating the effect of uninterrupted perioperative (par)enteral nutrition on amino acid profile, cardiomyocytes structure, and cardiac perfusion and metabolism of patients undergoing coronary artery bypass grafting

<p>Abstract</p> <p>Background</p> <p>Malnutrition is very common in patients undergoing cardiac surgery. Malnutrition can change myocardial substrate utilization which can induce adverse effects on myocardial metabolism and function. We aim to investigate the hypothesis that there is a disturbed amino acids profile in the cardiac surgical patient which can be normalized by (par)enteral nutrition before, during and after surgery, subsequently improving cardiomyocyte structure, cardiac perfusion and glucose metabolism.</p> <p>Methods/Design</p> <p>This randomized controlled intervention study investigates the effect of uninterrupted perioperative (par)enteral nutrition on cardiac function in 48 patients undergoing coronary artery bypass grafting. Patients are given enteral nutrition (n = 16) or parenteral nutrition (n = 16), at least two days before, during, and two days after coronary artery bypass grafting, or are treated according to the standard guidelines (control) (n = 16). We will illustrate the effect of (par)enteral nutrition on differences in concentrations of amino acids and asymmetric dimethylarginine and in activity of dimethylarginine dimethylaminohydrolase and arginase in cardiac tissue and blood plasma. In addition, cardiomyocyte structure by histological, immuno-histochemical and ultrastructural analysis will be compared between the (par)enteral and control group. Furthermore, differences in cardiac perfusion and global left ventricular function and glucose metabolism, and their changes after coronary artery bypass grafting are evaluated by electrocardiography-gated myocardial perfusion scintigraphy and ¹⁸F-fluorodeoxy-glucose positron emission tomography respectively. Finally, fat free mass is measured before and after intervention with bioelectrical impedance spectrometry in order to evaluate nutritional status.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2183">NTR2183</a></p

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO