3,086 research outputs found
SUPPLY RESPONSE TO TECHNOLOGICAL CHANGE AND REGULATION: THE CASE OF MECHANICALLY DEBONED POULTRY
Research and Development/Tech Change/Emerging Technologies,
RASSF1A and the rs2073498 Cancer Associated SNP
RASSF1A is one of the most frequently inactivated tumor suppressors yet identified in human cancer. It is pro-apoptotic and appears to function as a scaffolding protein that interacts with a variety of other tumor suppressors to modulate their function. It can also complex with the Ras oncoprotein and may serve to integrate pro-growth and pro-death signaling pathways. A SNP has been identified that is present in approximately 29% of European populations [rs2073498, A(133)S]. Several studies have now presented evidence that this SNP is associated with an enhanced risk of developing breast cancer. We have used a proteomics based approach to identify multiple differences in the pattern of protein/protein interactions mediated by the wild type compared to the SNP variant protein. We have also identified a significant difference in biological activity between wild type and SNP variant protein. However, we have found only a very modest association of the SNP with breast cancer predisposition
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Programmable Thermostat Module Upgrade for the Multipurpose Logistics Module
The STS-121/ULF 1.1 mission was the maiden flight of the programmable thermostat module (PTM) system used to control the 28 V shell heaters on the multi-purpose logistics module (MPLM). These PTMs, in conjunction with a data recorder module (DRM), provide continuous closed loop temperature control and data recording of MPLM on-orbit heater operations. This Technical Memorandum discusses the hardware design, development, test, and verification (DDT&V) activities performed at the Marshall Space Flight Center as well as the operational implementation and mission performance
Marine seismic surveys and ocean noise : time for coordinated and prudent planning
Marine seismic surveys use intense (eg >= 230 decibel [dB] root mean square [RMS]) sound impulses to explore the ocean bottom for hydrocarbon deposits, conduct geophysical research, and establish resource claims under the United Nations Convention on the Law of the Sea. The expansion of seismic surveys necessitates greater regional and international dialogue, partnerships, and planning to manage potential environmental risks. Data indicate several reasons for concern about the negative impacts of anthropogenic noise on numerous marine species, including habitat displacement, disruption of biologically important behaviors, masking of communication signals, chronic stress, and potential auditory damage. The sound impulses from seismic surveys - spanning temporal and spatial scales broader than those typically considered in environmental assessments - may have acute, cumulative, and chronic effects on marine organisms. Given the international and transboundary nature of noise from marine seismic surveys, we suggest the creation of an international regulatory instrument, potentially an annex to the existing International Convention on the Prevention of Pollution from Ships, to address the issue.Publisher PDFPeer reviewe
Success of blinding a procedural intervention in a randomised controlled trial in preterm infants receiving respiratory support
Background:
Blinding of treatment allocation from treating clinicians in neonatal randomised controlled trials can minimise performance bias, but its effectiveness is rarely assessed.
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Methods:
To examine the effectiveness of blinding a procedural intervention from treating clinicians in a multicentre randomised controlled trial of minimally invasive surfactant therapy versus sham treatment in preterm infants of gestation 25–28 weeks with respiratory distress syndrome. The intervention (minimally invasive surfactant therapy or sham) was performed behind a screen within the first 6 h of life by a ‘study team’ uninvolved in clinical care including decision-making. Procedure duration and the study team’s words and actions during the sham treatment mimicked those of the minimally invasive surfactant therapy procedure. Post-intervention, three clinicians completed a questionnaire regarding perceived group allocation, with the responses matched against actual intervention and categorised as correct, incorrect, or unsure. Success of blinding was calculated using validated blinding indices applied to the data overall (James index, successful blinding defined as > 0.50), or to the two treatment allocation groups (Bang index, successful blinding: −0.30 to 0.30). Blinding success was measured within staff role, and the associations between blinding success and procedural duration and oxygenation improvement post-procedure were estimated.
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Results:
From 1345 questionnaires in relation to a procedural intervention in 485 participants, responses were categorised as correct in 441 (33%), incorrect in 142 (11%), and unsure in 762 (57%), with similar proportions for each of the response categories in the two treatment arms. The James index indicated successful blinding overall 0.67 (95% confidence interval (CI) 0.65–0.70). The Bang index was 0.28 (95% CI 0.23–0.32) in the minimally invasive surfactant therapy group and 0.17 (95% CI 0.12–0.21) in the sham arm. Neonatologists more frequently guessed the correct intervention (47%) than bedside nurses (36%), neonatal trainees (31%), and other nurses (24%). For the minimally invasive surfactant therapy intervention, the Bang index was linearly related to procedural duration and oxygenation improvement post-procedure. No evidence of such relationships was seen in the sham arm.
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Conclusion:
Blinding of a procedural intervention from clinicians is both achievable and measurable in neonatal randomised controlled trials
High-Dose Ipilimumab and High-Dose Interleukin-2 for Patients With Advanced Melanoma.
High-dose ipilimumab (IPI) and high-dose interleukin-2 (IL-2) are approved agents for metastatic melanoma, but the efficacy and safety of the combination are unknown. The objective of this study was to evaluate the feasibility, safety, and efficacy of combination high-dose IPI and high-dose IL-2 in patients with histologically confirmed advanced unresectable stage III and IV melanoma. This Phase II, multicenter, open-label, single-arm trial was conducted in nine patients enrolled between 12/2014 and 12/2015. Subjects were treated with high-dose IPI 10 mg/kg intravenous (IV) every 3 weeks for four doses starting at week 1 and high-dose IL-2 (600,000 IU/kg IV bolus every 8 h for up to 14 doses) concurrently with IPI at weeks 4 and 7. After the first 12 weeks of combination therapy, maintenance IPI (10 mg/kg IV) monotherapy was administered every 12 weeks for up to 1 year. No patient had received prior PD-1 blockade, and only one received prior vemurafenib. Confirmed partial response was achieved in one (11%), stable disease in four (44%), and progressive disease in four (44%) of nine patients. Two patients achieved durable disease control of 44+ and 50+ months at the most recent follow-up without subsequent therapy. The median overall survival was not reached after a minimum 24 months of follow-up time. One-year and 2-year survival rates were 89 and 67%, respectively. Seven patients (78%) experienced grade 3 or 4 adverse events related to the study therapy, three of which were attributed to both agents. One patient discontinued the treatment due to liver and kidney toxicity. While toxicity was significant, all events were reversible, and there was no treatment-related mortality. In peripheral blood of patients with decreasing tumor burden, the ratio of the non-classical MHC-II proteins HLA-DM to HLA-DO increased 2-fold, raising the possibility of the ratio of HLA-DM:HLA-DO as a novel biomarker of response to treatment. Although the sample size was limited, combination therapy with high-dose IPI and high-dose IL-2 was feasible and associated with clinical benefit. IL-2-based compounds in combination with CTLA-4 blockade should be studied in advanced melanoma patients who fail to benefit from first-line PD-1 blockade
Successfully implementing and embedding guidelines to improve the nutrition and growth of preterm infants in neonatal intensive care: a prospective interventional study.
OBJECTIVES: We aimed to improve the nutritional care of preterm infants by developing a complex (multifaceted) intervention intended to translate current evidence into practice. We used the sociological framework of Normalization Process Theory (NPT), to guide implementation in order to embed the new practices into routine care. DESIGN: A prospective interventional study with a before and after methodology. PARTICIPANTS: Infants <30 weeks gestation or <1500 g at birth. SETTING: Tertiary neonatal intensive care unit. INTERVENTIONS: The intervention was introduced in phases: phase A (control period, January-August 2011); phase B (partial implementation; improved parenteral and enteral nutrition solutions, nutrition team, education, August-December 2011); phase C (full implementation; guidelines, screening tool, 'nurse champions', January-December 2012); phase D (postimplementation; January-June 2013). Bimonthly audits and staff NPT questionnaires were used to measure guideline compliance and 'normalisation', respectively. NPT Scores were used to guide implementation in real time. Data on nutrient intakes and growth were collected continuously. RESULTS: There were 52, 36, 75 and 35 infants in phases A, B, C and D, respectively. Mean guideline compliance exceeded 75% throughout the intervention period, peaking at 85%. Guideline compliance and NPT scores both increased over time, (r=0.92 and 0.15, p<0.03 for both), with a significant linear association between the two (r=0.21, p<0.01). There were significant improvements in daily protein intake and weight gain between birth and discharge in phases B and Ccompared with phase A (p<0.01 for all), which were sustained into phase D. CONCLUSIONS: NPT and audit results suggest that the intervention was rapidly incorporated into practice, with high guideline compliance and accompanying improvements in protein intake and weight gain. NPT appears to offer an effective way of implementing new practices such that they lead to sustained changes in care. Complex interventions based on current evidence can improve both practice and clinical outcomes
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