Explore the vast range of titles available.

Consolidation therapies for children with intermediate- or high-risk acute myeloid leukemia (AML) are urgently needed to achieve higher cure rates while limiting therapy-related toxicities. We determined if adoptive transfer of natural killer (NK) cells from haploidentical killer immunoglobulin–like receptor (KIR)–human leukocyte antigen (HLA)-mismatched donors may prolong event-free survival in children with intermediate-risk AML who were in first complete remission after chemotherapy. Patients received cyclophosphamide (Day − 7), fludarabine (Days − 6 through − 2), and subcutaneous interleukin-2 (Days − 1, 1, 3, 5, 7, and 9). Purified, unmanipulated NK cells were infused on Day 0, and NK cell chimerism and phenotyping from peripheral blood were performed on Days 7, 14, 21, and 28. As primary endpoint, the event-free survival was compared to a cohort of 55 patients who completed chemotherapy and were in first complete remission but did not receive NK cells. Donor NK cell kinetics were determined as secondary endpoints. Twenty-one patients (median age at diagnosis, 6.0 years [range, 0.1–15.3 years]) received a median of 12.5 × 10 6 NK cells/kg (range, 3.6–62.2 × 10 6 cells/kg) without major side effects. All but 3 demonstrated transient engraftment with donor NK cells (median peak donor chimerism, 4% [range, 0–43%]). KIR–HLA-mismatched NK cells expanded in 17 patients (81%) and contracted in 4 (19%). However, adoptive transfer of NK cells did not decrease the cumulative incidence of relapse (0.393 [95% confidence interval: 0.182–0.599] vs. 0.35 [0.209–0.495]; P =  .556) and did not improve event-free (60.7 ± 10.9% vs. 69.1 ± 6.8%; P  = .553) or overall survival (84.2 ± 8.5% vs. 79.1 ± 6.6%; P  = .663) over chemotherapy alone. The lack of benefit may result from insufficient numbers and limited persistence of alloreactive donor NK cells but does not preclude its potential usefulness during other phases of therapy, or in combination with other immunotherapeutic agents. Trial registration www.clinicaltrials.gov , NCT00703820 . Registered 24 June 2008.

BackgroundNatural killer (NK) cells are one of the main effector populations of immunotherapy with monoclonal antibody and cytokines, used in combination with chemotherapy to treat children with high-risk neuroblastoma on this phase II trial. However, the impact of chemoimmunotherapy on NK cell kinetics, phenotype, and function is understudied.MethodsWe prospectively examined NK cell properties from 63 children with newly diagnosed neuroblastoma enrolled in a phase II trial (NCT01857934) and correlated our findings with tumor volume reduction after 2 courses of chemoimmunotherapy. NK cell studies were conducted longitudinally during chemoimmunotherapy and autologous hematopoietic cell transplantation (autoHCT) with optional haploidentical NK cell infusion and additional immunotherapy.ResultsChemoimmunotherapy led to significant NK cytopenia, but complete NK cell recovery reliably occurred by day 21 of each therapy course as well as after autoHCT. Haploidentical NK cell infusion elevated the NK cell count transiently during autoHCT. NK cell cytotoxicity increased significantly during treatment compared with diagnosis. In addition, NK cells maintained their ability to respond to cytokine stimulation in culture longitudinally. Unsupervised cluster analysis of CD56bright NK cell count and tumor volume at diagnosis and after two courses of chemoimmunotherapy identified two patient groups with distinct primary tumor sizes and therapy responses.ConclusionAfter profound NK cytopenia due to chemoimmunotherapy, endogenously reconstituted NK cells exhibit enhanced NK cytotoxicity compared with pretherapy measurements. Our data suggest a relationship between CD56bright expression and tumor size before and after two courses of chemoimmunotherapy; however, future studies are necessary to confirm this relationship and its predictive significance.Trial registration number NCT01857934.

Recent reports have demonstrated that trans-splicing ribozymes can be employed to repair mutant RNAs. One key factor that influences RNA repair efficiency is the accessibility of the substrate RNA for ribozyme binding, which is complicated by the fact that RNAs may assume multiple conformations and have proteins bound to them in vivo. Here we describe a strategy to map accessible sites on sickle β-globin (βs-globin) transcripts in vitro and in vivo and to use this information to enhance RNA repair efficiency. Two sites upstream of the sickle mutation were identified as accessible in some fraction of the β-globin RNA by mapping with a ribozyme library and the accessibility of those sites was assessed by in vitro cleavage analyses. Ribozymes targeting either site could only convert a certain fraction of the βs-globin RNA to product but not drive the reaction to completion. However, cleavage and splicing reactions were driven further toward completion when the two ribozymes were both added to the reactions, suggesting that the substrate RNA is present in multiple conformations in vitro. These two ribozymes were each able to repair βs-globin transcripts in erythrocyte precursors derived from peripheral blood from individuals with sickle cell disease. Moreover, the relative accessibility of the targeted sites in vivo is as predicted by mapping and in vitro analyses. These results demonstrate that this novel RNA mapping strategy represents an effective means to determine the accessible regions of target RNAs and that combinations of trans-splicing ribozymes can be employed to enhance RNA repair efficiency of clinically relevant transcripts such as βs-globin RNA.

To help address the disability burden and growing financial impact of chronic diseases, interagency group programmes targeting a socio-economically deprived population offer opportunities to exercise in a gym and receive education on healthier lifestyle matters. Set up to engage and support people with persistent lower back pain (LBP) and multimorbidity (2 or more chronic diseases) to become more active, they are implemented by Health Service Executive (HSE) primary care physiotherapy and Dublin City Council (DCC) fitness instructor services. Based on a bio-psycho-social model and motivational interviewing, the programmes support experiential learning to improve self efficacy.Existing Interagency services have been reconfigured without additional resources. An interagency vision has facilitated sharing of facilities, knowledge and manpower.Both programmes offered participants six free 60 minute sessions in a gym led by a fitness instructor using equipment that suit preferences and needs, followed by a 30 minute education session led by a physiotherapist encouraging healthier lifestyle choices and goal setting around 8 key areas. These are exercise, pacing, pain, stress, sleep, nutrition, medications and signposting to relevant psychological and physical supports. Ongoing participant feedback has led to the introduction of discounted memberships similar to the DCC 'passport for leisure' scheme on programme completion and free swimming pool access after each session. A texting system between participants and physiotherapist facilitates group time reminders and rescheduling.Outcomes: In 2013 the 'Back on Track' programme started for adults with persistent LBP, and in 2016 this model was adapted as the ‘Activ8’ programme to suit people with multimorbidity. In its first three years the ‘Back on Track’ programme received 203 referrals, 164 started and 101 completed the 6 weeks. 90% showed reduced fear avoidance behaviours and 98% showed improved physical function. Withdrawal reasons included family commitments, pain 'flare up' and 'not for me' attitude. 39 'graduates' availed of discounted memberships.A self directed peer support group commenced in 2015. With interagency trust, alliances and good communication channels it is envisaged both programmes are transferable to other community based sports and recreation facilities. A feasibility study was conducted in late 2016 on ‘Activ8’ and in early 2017 it will be replicated in a different socio-economic area.Lessons learnt include better engagement when physical activities are less prescriptive and more self directed. Internet sites offer opportunities for online learning. The Back on Track programme is enhanced by a physiotherapist with specialist skills in pain management or with direct psychologist input. Using a community based state supported leisure centre for the programmes promotes accessibility, sustainability and is a cost effective model for an overstretched healthcare system.

Objectives. To investigate the extent to which compliance with treatment is related to outcome, and factors associated with compliance in a group of treatment‐resistant eating‐disordered in‐patients. Design. A retrospective case study design was employed where clinic staff made expert ratings of eating behaviours, attitudes and outcome of former in‐patients. Method. Ten health‐care staff at a specialist eating disorders clinic rated overall success of treatment outcome at discharge, as well as compliance, severity of disordered eating behaviours and body‐image disturbance at both admission and discharge for 46 anorexic and 14 bulimic patients. Results. For all participants, high compliance at admission was associated with lower levels of body image disturbance, less disordered eating behaviours and higher ratings of overall treatment success at discharge. Compliance at admission predicted the body mass index (BMI) at discharge for anorexic participants and predicted higher ratings of overall treatment success at discharge for all participants. In all participants, compliance at admission was related to the extent of eating‐disordered behaviours at admission. Conclusions. Results suggest the importance of compliance in facilitating recovery and treatment success among treatment‐resistant eating‐disordered in‐patients. The promotion of strategies to improve compliance in this population should be considered. A role for motivational interviewing is discussed.

First, there is the social barrier. This is decreasing, thanks to the movements for equal rights and equal pay, but the ideas that \"women should stay home and keep house,\" that \"it's not suitable work for women,\" that \"the good-paying jobs should be kept for men with families to support,\" are still there, and believe me, I've heard them all -- and a few more. Add in a few men who make things harder with daily, petty pinpricks, and the work environment can be pretty difficult.

Secondly, to say that trade unions pursuing union ends is \"an activity not usually associated with dignity\" is a revolting lie. What are union ends? Fair wages, decent working conditions, safety and justice in employment -- what is better associated with dignity?

More by good luck than good management I have accumulated a fair amount of wealth, most of which my children will inherit when I die.