“No Wash” Albumin-Dextran Dilution for Double-Unit Cord Blood Transplantation is Safe with High Rates of Sustained Donor Engraftment

AbstractWashing cord blood (CB) grafts involves product manipulation and may result in cell loss. We investigated double-unit CB transplantation (CBT) using red blood cell (RBC)–depleted units diluted with albumin-dextran in patients with hematologic malignancies. One-hundred thirty-six patients (median age, 43 years; range, 4 to 71; median weight, 69 kilograms (kg); range, 24 to 111) underwent transplantation with a 4/6 to 6/6 HLA-matched graft. Patients ≤ 20 kg were excluded, as they only received washed units. Units were diluted a median of 8 fold to a median volume of 200 mL/unit. The median infused total nucleated cell doses were 2.7 (larger unit) and 2.0 (smaller unit) x 107/kg, respectively, and the median post-thaw recovery was 86%. Units were infused consecutively (median, 45 minutes/unit). While only 17 patients (13%) had no infusion reactions, reactions in the remaining 119 patients were almost exclusively mild-moderate (by CTCAE v4 criteria 12 grade 1, 43 grade 2, 63 grade 3) with only 1 patient (< 1%) having a severe (grade 4) reaction. Moreover, most were easily treated. Grade 2 to 3 hypertension was the most common in 101 (74%) patients. The cumulative incidence of sustained donor-derived neutrophil engraftment was high: 95% in myeloablative and 94% in nonmyeloablative CBT recipients. With appropriate supportive care, double-unit CBT with RBC-depleted grafts infused after albumin-dextran dilution is safe with high rates of engraftment in patients > 20 kg

Long-term prognosis for 1-year relapse-free survivors of CD34 cell-selected allogeneic hematopoietic stem cell transplantation : a landmark analysis

Altres ajuts: This research was supported in part by National Institutes of Health award number P01 CA23766 and NIH/NCI Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.CD34 selection significantly improves GVHD-free survival in allogeneic hematopoietic cell transplantation (allo-HSCT). Specific information regarding long-term prognosis and risk factors for late mortality after CD34-selected allo-HSCT is lacking, however. We conducted a single-center landmark analysis in 276 patients alive without relapse 1 year after CD34-selected allo-HSCT for AML (n=164), ALL (n=33), or MDS (n=79). At 5 years' follow-up after the 1-year landmark (range 0.03-13 years), estimated RFS was 73% and OS 76%. The 5-year cumulative incidence of relapse and NRM were 11% and 16%, respectively. In multivariate analysis, HCT-CI score ≥ 3 correlated with marginally worse RFS (HR 1.78, 95% CI 0.97-3.28, p=0.06) and significantly worse OS (HR 2.53, 95% CI 1.26-5.08, p=0.004). Despite only 24% of patients with acute GVHD within 1 year, this also significantly correlated with worse RFS and OS, with increasing grades of acute GVHD associating with increasingly poorer survival on multivariate analysis (p<0.0001). Of 63 deaths after the landmark, GVHD accounted for 27% of deaths and was the most common cause of late mortality, followed by relapse and infection. While prognosis is excellent for patients alive without relapse 1 year after CD34-selected allo-HSCT, risks of late relapse and NRM persist, particularly due to GVHD

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI