Initial Investigation of Reaction Control System Design on Spacecraft Handling Qualities for Earth Orbit Docking

A program of research, development, test, and evaluation is planned for the development of Spacecraft Handling Qualities guidelines. In this first experiment, the effects of Reaction Control System design characteristics and rotational control laws were evaluated during simulated proximity operations and docking. Also, the influence of piloting demands resulting from varying closure rates was assessed. The pilot-in-the-loop simulation results showed that significantly different spacecraft handling qualities result from the design of the Reaction Control System. In particular, cross-coupling between translational and rotational motions significantly affected handling qualities as reflected by Cooper-Harper pilot ratings and pilot workload, as reflected by Task-Load Index ratings. This influence is masked but only slightly by the rotational control system mode. While rotational control augmentation using Rate Command Attitude Hold can reduce the workload (principally, physical workload) created by cross-coupling, the handling qualities are not significantly improved. The attitude and rate deadbands of the RCAH introduced significant mental workload and control compensation to evaluate when deadband firings would occur, assess their impact on docking performance, and apply control inputs to mitigate that impact

Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.

The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease

Inclusion of carer health-related quality of life in national institute for health and care excellence appraisals

Objectives Health interventions for patients can have effects on their carers too. For consistency, decision makers may wish to specify whether carer outcomes should be included. One example is the National Institute for Health and Care Excellence (NICE), whose reference case specifies that economic evaluations should include direct health effects for patients and carers where relevant. We aimed to review the methods used in including carer health-related quality of life (HRQL) in NICE appraisals. Methods We reviewed all published technology appraisals (TAs) and highly specialized technologies (HSTs) to identify those that included carer HRQL and discussed the methods and data sources. Results Twelve of 414 TAs (3%) and 4 of 8 HSTs (50%) included carer HRQL in cost-utility analyses. Eight were for multiple sclerosis, the remainder were each in a unique disease area. Twelve of the 16 appraisals modeled carer HRQL as a function of the patient’s health state, 3 modeled carer HRQL as a function of the patient’s treatment, and 1 included family quality-adjusted life year (QALY) loss. They used 5 source studies: 2 compared carer EQ-5D scores with controls, 2 measured carer utility only (1 health utilities index and 1 EQ-5D), and 1 estimated family QALY loss from a child’s death. Two used disutility estimates not from the literature. Including carer HRQL increased the incremental QALYs and decreased incremental cost-effectiveness ratios in all cases. Conclusions The inclusion of carer HRQL in NICE appraisals is relatively uncommon and has been limited by data availability

Measuring Health Spillovers for Economic Evaluation:A Case Study in Meningitis

The health of carers and others close to the patient will often be relevant to economic evaluation, but it is very rarely considered in practice. This may reflect a lack of understanding of how the spillover effect of illness can be appropriately quantified. In this study we used three different approaches to quantify health spillovers resulting from meningitis. We conducted a survey of 1218 family networks affected by meningitis and used regression modelling to estimate spillover effects. The findings show that meningitis had long-term effects on family members' health, particularly affecting the likelihood of family members reporting anxiety and depression. These effects extended beyond a single close family member. These findings suggest that vaccinating against meningitis will bring significant health benefits not just to those that might have contracted the illness but also to their family networks. In methodological terms, different approaches for quantifying health spillovers provided broadly consistent results. The choice of method will be influenced by the ease of collecting primary data from family members in intervention contexts

Burying the 'refuse revolution': the rise of controlled tipping in Britain 1920-1960

The definitive, peer-reviewed and edited version of this article is published in Environment and Planning A, 42, 5, 1033-1048, 2010, 10.1068/a42120.This paper investigates the emergence of ‘controlled tipping’ as the dominant method of municipal waste disposal in Britain between 1920 and 1960. The triumph of controlled tipping, despite the availability of alternative disposal technologies, needs to be understood in the context of the contested meanings of ‘waste’ and ‘wasteland’, which helped to determine attitudes and approaches to disposal. Following the conclusion of the First World War there was an urgent requirement for a cheap means of disposing of increasing amounts of urban municipal waste. The obvious choice was tipping. Before the war, however, refuse tipping had been rejected as insanitary by the emerging waste disposal profession. Public cleansing professionals therefore had to recuperate tipping as a medically and environmentally benign mode of disposal that was reconcilable with the needs of sanitary science and landscape preservation. Controlled tipping, with its combined claims to scientific progress and the revalorization of refuse, enabled dumping to be successfully re-produced as the dominant mode of municipal refuse disposal in Britain. However, tipping faced further challenges after 1945 from changing popular understandings of the value of ‘derelict’ landscapes and from the politics of amenity. The ‘refuse revolution’ was a work in progress

Incorporating Hydrologic Data and Ecohydrologic Relationships into Ecological Site Descriptions

The purpose of this paper is to recommend a framework and methodology for incorporating hydrologic data and ecohydrologic relationships in Ecological Site Descriptions (ESDs) and thereby enhance the utility of ESDs for assessing rangelands and guiding resilience-based management strategies. Resilience-based strategies assess and manage ecological state dynamics that affect state vulnerability and, therefore, provide opportunities to adapt management. Many rangelands are spatially heterogeneous or sparsely vegetated where the vegetation structure strongly influences infiltration and soil retention. Infiltration and soil retention further influence soil water recharge, nutrient availability, and overall plant productivity. These key ecohydrologic relationships govern the ecologic resilience of the various states and community phases on many rangeland ecological sites (ESs) and are strongly affected by management practices, land use, and disturbances. However, ecohydrologic data and relationships are often missing in ESDs and state-and-transition models (STMs). To address this void, we used literature to determine the data required for inclusion of key ecohydrologic feedbacks into ESDs, developed a framework and methodology for data integration within the current ESD structure, and applied the framework to a select ES for demonstrative purposes. We also evaluated the utility of the Rangeland Hydrology and Erosion Model (RHEM) for assessment and enhancement of ESDs based in part on hydrologic function. We present the framework as a broadly applicable methodology for integrating ecohydrologic relationships and feedbacks into ESDs and resilience-based management strategies. Our proposed framework increases the utility of ESDs to assess rangelands, target conservation and restoration practices, and predict ecosystem responses to management. The integration of RHEM technology and our suggested framework on ecohydrologic relations expands the ecological foundation of the overall ESD concept for rangeland management and is well aligned with resilience-based, adaptive management of US rangelands. The proposed enhancement of ESDs will improve communication between private land owners and resource managers and researchers across multiple disciplines in the field of rangeland management

The Team Keck Treasury Redshift Survey of the GOODS-North Field

We report the results of an extensive imaging and spectroscopic survey in the GOODS-North field completed using DEIMOS on the Keck II telescope. Observations of 2018 targets in a magnitude-limited sample of 2911 objects to R=24.4 yield secure redshifts for a sample of 1440 galaxies and AGN plus 96 stars. In addition to redshifts and associated quality assessments, our catalog also includes photometric and astrometric measurements for all targets detected in our R-band imaging survey of the GOODS-North region. We investigate various sources of incompleteness and find the redshift catalog to be 53% complete at its limiting magnitude. The median redshift of z=0.65 is lower than in similar deep surveys because we did not select against low-redshift targets. Comparison with other redshift surveys in the same field, including a complementary Hawaii-led DEIMOS survey, establishes that our velocity uncertainties are as low as 40 km/s for red galaxies and that our redshift confidence assessments are accurate. The distributions of rest-frame magnitudes and colors among the sample agree well with model predictions out to and beyond z=1. We will release all survey data, including extracted 1-D and sky-subtracted 2-D spectra, thus providing a sizable and homogeneous database for the GOODS-North field which will enable studies of large scale structure, spectral indices, internal galaxy kinematics, and the predictive capabilities of photometric redshifts.Comment: 17 pages, 18 figures, submitted to AJ; v2 minor changes; see survey database at http://www2.keck.hawaii.edu/realpublic/science/tksurvey

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Carer social care-related quality of life outcomes: estimating English preference weights for the Adult Social Care Outcomes Toolkit for Carers (ASCOT-Carer)

Objective: To estimate preference-based index values for the English version of the ASCOT-Carer, a measure assessing social care-related quality of life (SCRQoL) in informal carers, from the general population in England. Methods: The ASCOT-Carer consists of seven domains, each reflecting aspects of SCRQoL in informal carers. Preferences for the ASCOT-Carer SCRQoL states were estimated using a Best-Worst Scaling exercise (BWS) in an online survey. The survey was administered to a sample of the general adult population in England (n=1,000). Participants were asked to put themselves into the hypothetical state of being an informal carer and indicate which attribute they thought was the best (first and second) and worst (first and second) from a profile list of seven attributes reflecting the seven domains, each ranging at a different level (1-4). Multinomial logistic regression was used to analyse the data and estimate preference weights for the ASCOT-Carer measure. Results: The most valued aspect by English participants was the ‘occupation’ attribute at its highest level. Results further showed participants rated having ‘no control over their daily life’ as the lowest attribute-level of all those presented. The position of the seven attributes influenced participants’ best and worst choices, and there was evidence of both scale and taste heterogeneity on preferences. Conclusions: This study has established a set of preference-based index values for the ASCOT-Carer in England derived from the BWS exercise that can be used for economic evaluation of interventions on older individuals and their informal carers