681 research outputs found

    Evidence-Based Interventions and Strategies for the Grand Challenges Approach: The Need for Judgement

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    What is the value of evidence-based interventions in addressing “Grand Challenges”? Building upon the EPOS Grand Challenges work (Sakhrani et al., 2017), this paper explores whether evidence-based approaches developed for management and policy are relevant to addressing Grand Challenges. It discusses the criticisms of the Evidence-based Management approach and argues that evidence is a necessary, but not sufficient input in the decisionmaking process of addressing Grand Challenges

    The effects of continued azacitidine treatment cycles on response in higher risk patients with myelodysplastic syndromes: an update

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    The international, phase III, multi-centre AZA-001 trial demonstrated azacitidine (AZA) is the first treatment to significantly extend overall survival (OS) in higher risk myelodysplastic syndromes (MDS) patients (Fenaux (2007) Blood 110 817). The current treatment paradigm, which is based on a relationship between complete remission (CR) and survival, is increasingly being questioned (Cheson (2006) Blood 108 419). Results of AZA-001 show CR is sufficient but not necessary to prolong OS (List (2008) Clin Oncol 26 7006). Indeed, the AZA CR rate in AZA-001 was modest (17%), while partial remission (PR, 12%) and haematological improvement (HI, 49%) were also predictive of prolonged survival. This analysis was conducted to assess the median number of AZA treatment cycles associated with achievement of first response, as measured by IWG 2000-defined CR, PR or HI (major + minor). The number of treatment cycles from first response to best response was also measured

    Pirfenidone in idiopathic pulmonary fibrosis:expert panel discussion on the management of drug-related adverse events

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    Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.Correction in: Advances in Therapy, Volume 31, Issue 5, pp 575-576 , doi: 10.1007/s12325-014-0118-8</p

    Azacitidine prolongs overall survival and reduces infections and hospitalizations in patients with WHO-defined acute myeloid leukaemia compared with conventional care regimens: an update

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    Azacitidine (AZA), as demonstrated in the phase III trial (AZA-001), is the first MDS treatment to significantly prolong overall survival (OS) in higher risk MDS pts ((2007) Blood 110 817). Approximately, one-third of the patients (pts) enrolled in AZA-001 were FAB RAEB-T (≥20–30% blasts) and now meet the WHO criteria for acute myeloid leukaemia (AML) ((1999) Blood 17 3835). Considering the poor prognosis (median survival <1 year) and the poor response to chemotherapy in these pts, this sub-group analysis evaluated the effects of AZA versus conventional care regimens (CCR) on OS and on response rates in pts with WHO AML

    A Measurement of the Coulomb Dissociation of 8B at 254 MeV/nucleon and the 8B Solar Neutrino Flux

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    We have measured the Coulomb dissociation of 8B into 7Be and proton at 254 MeV/nucleon using a large-acceptance focusing spectrometer. The astrophysical S17 factor for the 7Be(p,gamma)8B reaction at E{c.m.} = 0.25-2.78 MeV is deduced yielding S17(0)=20.6 \pm 1.2 (exp.) \pm 1.0 (theo.) eV-b. This result agrees with the presently adopted zero-energy S17 factor obtained in direct-reaction measurements and with the results of other Coulomb-dissociation studies performed at 46.5 and 51.2 MeV/nucleon.Comment: paper to be published in Phys. Rev. Lett. 3 figures. New Version fixes formatting problems with the figures only. There are no other change

    Neuromonitoring in neonatal critical care part II: extremely premature infants and critically ill neonates

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    Abstract: Neonatal intensive care has expanded from cardiorespiratory care to a holistic approach emphasizing brain health. To best understand and monitor brain function and physiology in the neonatal intensive care unit (NICU), the most commonly used tools are amplitude-integrated EEG, full multichannel continuous EEG, and near-infrared spectroscopy. Each of these modalities has unique characteristics and functions. While some of these tools have been the subject of expert consensus statements or guidelines, there is no overarching agreement on the optimal approach to neuromonitoring in the NICU. This work reviews current evidence to assist decision making for the best utilization of these neuromonitoring tools to promote neuroprotective care in extremely premature infants and in critically ill neonates. Neuromonitoring approaches in neonatal encephalopathy and neonates with possible seizures are discussed separately in the companion paper. Impact: For extremely premature infants, NIRS monitoring has a potential role in individualized brain-oriented care, and selective use of aEEG and cEEG can assist in seizure detection and prognostication.For critically ill neonates, NIRS can monitor cerebral perfusion, oxygen delivery, and extraction associated with disease processes as well as respiratory and hypodynamic management. Selective use of aEEG and cEEG is important in those with a high risk of seizures and brain injury.Continuous multimodal monitoring as well as monitoring of sleep, sleep–wake cycling, and autonomic nervous system have a promising role in neonatal neurocritical care

    Mutational Spectrum of the ABCA12 Gene and Genotype-Phenotype Correlation in a Cohort of 64 Patients with Autosomal Recessive Congenital Ichthyosis

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    Autosomal recessive congenital ichthyosis (ARCI) is a non-syndromic congenital disorder of cornification characterized by abnormal scaling of the skin. The three major phenotypes are lamellar ichthyosis, congenital ichthyosiform erythroderma, and harlequin ichthyosis. ARCI is caused by biallelic mutations in ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, NIPAL4, PNPLA1, SDR9C7, SULT2B1, and TGM1. The most severe form of ARCI, harlequin ichthyosis, is caused by mutations in ABCA12. Mutations in this gene can also lead to congenital ichthyosiform erythroderma or lamellar ichthyosis. We present a large cohort of 64 patients affected with ARCI carrying biallelic mutations in ABCA12. Our study comprises 34 novel mutations in ABCA12, expanding the mutational spectrum of ABCA12-associated ARCI up to 217 mutations. Within these we found the possible mutational hotspots c.4541G>A, p.(Arg1514His) and c.4139A>G, p.(Asn1380Ser). A correlation of the phenotype with the effect of the genetic mutation on protein function is demonstrated. Loss-of-function mutations on both alleles generally result in harlequin ichthyosis, whereas biallelic missense mutations mainly lead to CIE or LI

    Observations of the Gamow-Teller resonance in the rare-earth nuclei above Gd 146 populated in β decay

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    13 págs.; 11 figs. ; 1 tab.The rare-earth region of the nuclear table around the quasi-doubly magic nucleus Gd146 is one of the very few places in which the Gamow-Teller (GT) resonance can be populated in β decay. The appropriate technique to study such a phenomenon is total absorption spectroscopy, thanks to which one can measure the B(GT) distribution in β-decay experiments even when it is very fragmented and lies at high excitation energy in the daughter nucleus. Results on the GT resonance measured in the β decay of the odd-Z, N=83 nuclei Tb148, Ho150, and Tm152 are presented in this work and compared with shell-model calculations. The tail of the resonance is clearly observed up to the limit imposed by the Q value. This observation is important in the context of the understanding of the >quenching> of the GT strength. ©2016 American Physical SocietyThe authors would like to thank the GSI accelerator crew and the MSEP group for their support. This work has been partially supported by the Spanish Ministry (Grants No. FPA2005-03993, No. FPA200806419-C02-01, No. FPA2011- 24553, No. FPA2012-32443, No. FPA2014-57196-C5, and No. FPA2014-52823-C2-1-P) and the Generalitat Valenciana (PROMETEOII/2014/019).Peer Reviewe

    Micronutrient intakes affect early growth in extremely preterm infants : preliminary results from a Swedish cohort

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    Background: Extremely preterm infants generally experience postnatal growth failure. It is still unclear if this is related to micronutrient intakes.Aim: To investigate the effect of micronutrient intakes (calcium, zinc, iron, phosphorus, sodium, potassium, chloride, magnesium, vitamin A, vitamin D, vitamin E, folate and vitamin B12) on growth during the first 28 days of life in extremely preterm infants.Method: From the EXPRESS cohort (all infants born &lt; 27 gestational weeks between 2004-2007 in Sweden), those who survived the first 28 days were included (n=524). Daily parenteral and enteral intakes and anthropometric measurements were retrieved from hospital records.Results: Preliminary analyses of data from 333 infants (mean&plusmn;SD gestational age 25.2&plusmn;1.0 weeks, birth weight 753&plusmn;168g) showed that macronutrient intakes were lower than recommended (energy 98&plusmn;13kcal/kg/day, protein 2.9&plusmn;0.4g/kg/day). Infants showed postnatal growth failure: mean standard deviation scores decreased by 2.2 for weight, 2.3 for length and 1.4 for head circumference. Intakes of micronutrients were generally low, e.g. adjusted enteral intakes of calcium were 66.6&plusmn;21.4 mg/kg/day. The exception was iron, with a high parenteral intake of 2.7&plusmn;1.6 mg/kg/day, mainly from blood transfusions. Adjusting for protein intake and other confounders, calcium intakes were positively correlated with head growth (r=+0.19, p=0.006) and iron intakes were negatively correlated with length gain (r=-0.18, p=0.009).Conclusions: Low calcium intakes and high iron intakes were associated with poor growth with regard to head circumference and length, respectively. If these results are confirmed, optimized micronutrient intakes may improve early growth in extremely preterm infants
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