Redundant actuator development program

Two concepts of redundant secondary actuator mechanization, applicable to future advanced flight control systems, were studied to quantitatively assess their design applicability to an AST. The two actuator concepts, a four-channel, force summed system and a three-channel, active/standby system have been developed and evaluated through analysis, analog computer simulation, and piloted motion simulation. The quantitative comparison of the two concepts indicates that the force summed concept better meet performance requirements, although the active/standby is superior in other respects. Both concepts are viable candidates for advanced control application dependent on the specific performance requirements

Older people’s experiences of living with, responding to and managing sensory loss

(1) Background: Ageing is associated with a decline in sensory function (sight, hearing, taste, touch and smell), which play an important role in the maintenance of an older person’s health, independence and well-being. (2) Methods: This qualitative study obtained data through face-to-face semi-structured interviews with a convenience sample of thirteen community-dwelling adults 65 years and older. Themes were derived inductively, guided by semi-structured interviews. (3) Results: Twelve participants had two or more sensory impairments, mainly concurrent hearing and vision, which became apparent when a situation/individual alerted them to change/s occurring. They were less aware of impaired smell, taste and touch. Sensory changes impacted on important life functions, prompting many participants to take measured risks in maintaining their independence. Half (seven) of the participants lacked motivation to manage sensory function through goal-directed behaviour, taking remedial actions only when this was relevant to lifestyle preferences. (4) Con-clusions: Internal and/or external triggers of sensory changes did not generally motivate remedial action. Health professionals can help to improve older people’s attention to sensory impairment by routinely discussing sensory function with them, screening for sensory changes and facilitating early intervention and support

The health of women and girls determines the health and well-being of our modern world: A White Paper From the International Council on Women's Health Issues

The International Council on Women's Health Issues (ICOWHI) is an international nonprofit association dedicated to the goal of promoting health, health care, and well-being of women and girls throughout the world through participation, empowerment, advocacy, education, and research. We are a multidisciplinary network of women's health providers, planners, and advocates from all over the globe. We constitute an international professional and lay network of those committed to improving women and girl's health and quality of life. This document provides a description of our organization mission, vision, and commitment to improving the health and well-being of women and girls globally

The challenges of applying planetary boundaries as a basis for strategic decision-making in companies with global supply chains

The Planetary Boundaries (PB) framework represents a significant advance in specifying the ecological constraints on human development. However, to enable decision-makers in business and public policy to respect these constraints in strategic planning, the PB framework needs to be developed to generate practical tools. With this objective in mind, we analyse the recent literature and highlight three major scientific and technical challenges in operationalizing the PB approach in decision-making: first, identification of thresholds or boundaries with associated metrics for different geographical scales; second, the need to frame approaches to allocate fair shares in the 'safe operating space' bounded by the PBs across the value chain and; third, the need for international bodies to co-ordinate the implementation of the measures needed to respect the Planetary Boundaries. For the first two of these challenges, we consider how they might be addressed for four PBs: climate change, freshwater use, biosphere integrity and chemical pollution and other novel entities. Four key opportunities are identified: (1) development of a common system of metrics that can be applied consistently at and across different scales; (2) setting 'distance from boundary' measures that can be applied at different scales; (3) development of global, preferably open-source, databases and models; and (4) advancing understanding of the interactions between the different PBs. Addressing the scientific and technical challenges in operationalizing the planetary boundaries needs be complemented with progress in addressing the equity and ethical issues in allocating the safe operating space between companies and sectors

Dementia Care Mapping™ to reduce agitation in care home residents with dementia: the EPIC cluster RCT

Background The quality of care for people with dementia in care homes is of concern. Interventions that can improve care outcomes are required. Objective To investigate the clinical effectiveness and cost-effectiveness of Dementia Care Mapping™ (DCM) for reducing agitation and improving care outcomes for people living with dementia in care homes, versus usual care. Design A pragmatic, cluster randomised controlled trial with an open-cohort design, follow-up at 6 and 16 months, integrated cost-effectiveness analysis and process evaluation. Clusters were not blinded to allocation. The primary end point was completed by staff proxy and independent assessors. Setting Stratified randomisation of 50 care homes to the intervention and control groups on a 3 : 2 ratio by type, size, staff exposure to dementia training and recruiting hub. Participants Fifty care homes were randomised (intervention, n = 31; control, n = 19), with 726 residents recruited at baseline and a further 261 recruited after 16 months. Care homes were eligible if they recruited a minimum of 10 residents, were not subject to improvement notices, had not used DCM in the previous 18 months and were not participating in conflicting research. Residents were eligible if they lived there permanently, had a formal diagnosis of dementia or a score of 4+ on the Functional Assessment Staging Test of Alzheimer’s Disease, were proficient in English and were not terminally ill or permanently cared for in bed. All homes were audited on the delivery of dementia and person-centred care awareness training. Those not reaching a minimum standard were provided training ahead of randomisation. Eighteen homes took part in the process evaluation. Intervention Two staff members from each intervention home were trained to use DCM and were asked to carry out three DCM cycles; the first was supported by an external expert. Main outcome measures The primary outcome was agitation (Cohen-Mansfield Agitation Inventory), measured at 16 months. Secondary outcomes included resident behaviours and quality of life. Results There were 675 residents in the final analysis (intervention, n = 388; control, n = 287). There was no evidence of a difference in agitation levels between the treatment arms. The adjusted mean difference in Cohen-Mansfield Agitation Inventory score was –2.11 points, being lower in the intervention group than in the control (95% confidence interval –4.66 to 0.44; p = 0.104; adjusted intracluster correlation coefficient: control = 0, intervention = 0.001). The sensitivity analyses results supported the primary analysis. No differences were detected in any of the secondary outcomes. The health economic analyses indicated that DCM was not cost-effective. Intervention adherence was problematic; only 26% of homes completed more than their first DCM cycle. Impacts, barriers to and facilitators of DCM implementation were identified. Limitations The primary completion of resident outcomes was by staff proxy, owing to self-report difficulties for residents with advanced dementia. Clusters were not blinded to allocation, although supportive analyses suggested that any reporting bias was not clinically important. Conclusions There was no benefit of DCM over control for any outcomes. The implementation of DCM by care home staff was suboptimal compared with the protocol in the majority of homes. Future work Alternative models of DCM implementation should be considered that do not rely solely on leadership by care home staff. Trial registration Current Controlled Trials ISRCTN82288852. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 16. See the NIHR Journals Library website for further project information

Guiding the Design of Synthetic DNA-Binding Molecules with Massively Parallel Sequencing

Genomic applications of DNA-binding molecules require an unbiased knowledge of their high affinity sites. We report the high-throughput analysis of pyrrole-imidazole polyamide DNA-binding specificity in a 10^(12)-member DNA sequence library using affinity purification coupled with massively parallel sequencing. We find that even within this broad context, the canonical pairing rules are remarkably predictive of polyamide DNA-binding specificity. However, this approach also allows identification of unanticipated high affinity DNA-binding sites in the reverse orientation for polyamides containing β/Im pairs. These insights allow the redesign of hairpin polyamides with different turn units capable of distinguishing 5′-WCGCGW-3′ from 5′-WGCGCW-3′. Overall, this study displays the power of high-throughput methods to aid the optimal targeting of sequence-specific minor groove binding molecules, an essential underpinning for biological and nanotechnological applications

Antioxidant activity and hepatoprotective potential of agaro-oligosaccharides in vitro and in vivo

BACKGROUND: Agaro-oligosaccharides derived from red seaweed polysaccharide have been reported to possess antioxidant activity. In order to assess the live protective effects of agar-oligosaccharides, we did both in vitro and in vivo studies based on own-made agaro-oligosaccharides, and the structural information of this oligosaccharide was also determined. METHOD: Structure of agaro-oligosaccharides prepared with acid hydrolysis on agar was confirmed by matrix-assisted ultraviolet laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) and NMR. The antioxidant effect of agaro-oligosaccharides on intracellular reactive oxygen species (ROS) was assessed by 2', 7'-dichlorofluorescin diacetate. Carbon tetrachloride was used to induce liver injury, some index including SOD, GSH-Px, MDA, AST, ALT were examined to determine the hepatoprotective effect of agaro-oligosaccharides. RESULTS: Agaro-oligosaccharides we got were composed of odd polymerizations with molecular weights ranged from 500 to 2500. Results from intracellular test indicated that agaro-oligosaccharides could significantly scavenge the level of oxidants in the hepatocytes, more beneficially, also associated with the improvement of cell viability In vivo studies of the antioxidant effects on tissue peroxidative damage induced by carbon tetrachloride in rat model indicated that agaro-oligosaccharides could elevate the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and decrease the level of malondialdehyde (MDA), glutamate oxaloacetate transaminase (AST), glutamic pyruvic transaminase (ALT) significantly. At 400 mg/kg, MDA level reduced 44 % and 21 % in liver and heart, SOD and GSH-Px increased to highest in liver and serum, while ALT level decreased 22.16 % in serum. CONCLUSION: Overall, the results of the present study indicate that agaro-oligosaccharides can exert their in vitro and in vivo hepatoprotective effect through scavenging oxidative damage induced by ROS

Efficacy and safety of telithromycin 800 mg once daily for 7 days in community-acquired pneumonia: an open-label, multicenter study

BACKGROUND: Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality throughout the world. Telithromycin (a new ketolide) has shown good in vitro activity against the key causative pathogens of CAP, including S pneumoniae resistant to penicillin and/or macrolides. METHODS: The efficacy and safety of telithromycin 800 mg orally once daily for 7 days in the treatment of CAP were assessed in an open-label, multicenter study of 442 adults. RESULTS: Of 149 microbiologically evaluable patients, 57 (9 bacteremic) had Streptococcus pneumoniae. Of the 57 S pneumoniae pathogens isolated in these patients, 9 (2 bacteremic) were penicillin- or erythromycin-resistant; all 57 were susceptible to telithromycin and were eradicated. Other pathogens and their eradication rates were: Haemophilus influenzae (96%), Moraxella catarrhalis (100%), Staphylococcus aureus (80%), and Legionella spp. (100%). The overall bacteriologic eradication rate was 91.9%. Of the 357 clinically evaluable patients, clinical cure was achieved in 332 (93%). In the 430 patients evaluable for safety, the most common drug-related adverse events were diarrhea (8.1%) and nausea (5.8%). CONCLUSION: Telithromycin 800 mg once daily for 7 days is an effective and well-tolerated oral monotherapy and offers a new treatment option for CAP patients, including those with resistant S pneumoniae

Allosteric Analysis of Glucocorticoid Receptor-DNA Interface Induced by Cyclic Py-Im Polyamide: A Molecular Dynamics Simulation Study

Background: It has been extensively developed in recent years that cell-permeable small molecules, such as polyamide, can be programmed to disrupt transcription factor-DNA interfaces and can silence aberrant gene expression. For example, cyclic pyrrole-imidazole polyamide that competes with glucocorticoid receptor (GR) for binding to glucocorticoid response elements could be expected to affect the DNA dependent binding by interfering with the protein-DNA interface. However, how such small molecules affect the transcription factor-DNA interfaces and gene regulatory pathways through DNA structure distortion is not fully understood so far. Methodology/Principal Findings: In the present work, we have constructed some models, especially the ternary model of polyamides+DNA+GR DNA-binding domain (GRDBD) dimer, and carried out molecular dynamics simulations and free energy calculations for them to address how polyamide molecules disrupt the GRDBD and DNA interface when polyamide and protein bind at the same sites on opposite grooves of DNA. Conclusions/Significance: We found that the cyclic polyamide binding in minor groove of DNA can induce a large structural perturbation of DNA, i.e. a.4 A ˚ widening of the DNA minor groove and a compression of the major groove by more than 4A ˚ as compared with the DNA molecule in the GRDBD dimer+DNA complex. Further investigations for the ternary system of polyamides+DNA+GRDBD dimer and the binary system of allosteric DNA+GRDBD dimer revealed that the compression o