221 research outputs found
Mammalian copper homeostasis requires retromer-dependent recycling of the high-affinity copper transporter
Technology to encourage meaningful activities following brain injury
Background: Cognitive and behavioural difficulties after acquired brain injury (ABI) may lead to reduced engagement in leisure and social activities. Increasing participation is a goal of neuropsychological rehabilitation and assistive and behaviour change technology can play an important role in this. Focus groups and interviews were conductive with brain injury rehabilitation stakeholders (n = 24): people with ABI (n = 9), family members (n = 3) and care providers (n = 12) in order to understand the barriers to engaging in meaningful activities and what helps to overcome these barriers. A collaborative thematic analysis was performed by a multi-disciplinary research team using an approach based on Grounded Theory.
Results: Four central, interlinked, barriers were found: Access, Cognitive Difficulties, Anticipation (of Physical or Cognitive Difficulties) and Motivation. To overcome these barriers, participants cited themes such as External Motivation from both Other People and Technology, Maintaining Momentum and different aspects of Being Planful.
Conclusions: The results point to future directions for the purposeful development of effective assistive technology for this user group. Technology that is social, persuasive, adapts to individual needs and supports people to plan activities are likely to be particularly useful within neuropsychological rehabilitation.
Implications For Rehabilitation:
Adults with ABI and their carers describe problems accessing activities, cognitive difficulties, anticipationof physical or cognitive difficulties and low motivation as the key barriers to undertaking meaningfulactivities.
Current solutions are external prompting, maintaining momentum and being planful.
This detailed qualitative analysis of a diverse group of carers and service users allows insight into theassistive technologies that could aid rehabilitation
Systematic errors in weak lensing: application to SDSS galaxy-galaxy weak lensing
Weak lensing is emerging as a powerful observational tool to constrain
cosmological models, but is at present limited by an incomplete understanding
of many sources of systematic error. Many of these errors are multiplicative
and depend on the population of background galaxies. We show how the commonly
cited geometric test, which is rather insensitive to cosmology, can be used as
a ratio test of systematics in the lensing signal at the 1 per cent level. We
apply this test to the galaxy-galaxy lensing analysis of the Sloan Digital Sky
Survey (SDSS), which at present is the sample with the highest weak lensing
signal to noise and has the additional advantage of spectroscopic redshifts for
lenses. This allows one to perform meaningful geometric tests of systematics
for different subsamples of galaxies at different mean redshifts, such as
brighter galaxies, fainter galaxies and high-redshift luminous red galaxies,
both with and without photometric redshift estimates. We use overlapping
objects between SDSS and the DEEP2 and 2SLAQ spectroscopic surveys to establish
accurate calibration of photometric redshifts and to determine the redshift
distributions for SDSS. We use these redshift results to compute the projected
surface density contrast DeltaSigma around 259 609 spectroscopic galaxies in
the SDSS; by measuring DeltaSigma with different source samples we establish
consistency of the results at the 10 per cent level (1-sigma). We also use the
ratio test to constrain shear calibration biases and other systematics in the
SDSS survey data to determine the overall galaxy-galaxy weak lensing signal
calibration uncertainty. We find no evidence of any inconsistency among many
subsamples of the data.Comment: 39 pages, 19 figure
EpsteināBarr Virus MicroRNAs Are Evolutionarily Conserved and Differentially Expressed
The pathogenic lymphocryptovirus EpsteināBarr virus (EBV) is shown to express at least 17 distinct microRNAs (miRNAs) in latently infected cells. These are arranged in two clusters: 14 miRNAs are located in the introns of the viral BART gene while three are located adjacent to BHRF1. The BART miRNAs are expressed at high levels in latently infected epithelial cells and at lower, albeit detectable, levels in B cells. In contrast to the tissue-specific expression pattern of the BART miRNAs, the BHRF1 miRNAs are found at high levels in B cells undergoing stage III latency but are essentially undetectable in B cells or epithelial cells undergoing stage I or II latency. Induction of lytic EBV replication was found to enhance the expression of many, but not all, of these viral miRNAs. Rhesus lymphocryptovirus, which is separated from EBV by ā„13 million years of evolution, expresses at least 16 distinct miRNAs, seven of which are closely related to EBV miRNAs. Thus, lymphocryptovirus miRNAs are under positive selection and are likely to play important roles in the viral life cycle. Moreover, the differential regulation of EBV miRNA expression implies distinct roles during infection of different human tissues
Multispecies Livelihoods: A Posthumanist Approach to Wildlife Ecotourism That Promotes Animal Ethics
Research on animal ethics in tourism has gained traction but posthumanist approaches to wildlife (eco)tourism remain sparse. There has never been a more urgent need to redress this paucity in theory and practice. More than 60% of the worldās wildlife has died-off in the last 50āyears, 100 million-plus nonhuman animals are used for entertainment in wildlife tourist attractions (WTAs), more than one billion āwildlifeā live in captivity, and some scholars argue that earth has entered its sixth mass extinction event known as the Anthropocene. This paper presents a posthumanist multispecies livelihoods framework (MLF) based on an applied ethnographic study of 47 wildlife ecotourism (WE) operators and wildlife researchers in protected area WTAs across four countries. Like any framework, it is a snapshot of the authorsā thinking at a particular time and must be improved upon. The MLF does not purport to solve the negative treatment of nonhumans that can occur in tourism settings, but rather responds to calls in the tourism literature to acknowledge our effects on other species and advocates for equitable human-nonhuman livelihoods. This paper argues that we have a moral responsibility to nonhumans and the environment, and the authors hope to generate reflexive discourse concerning the role tourism can play in redressing the ecological crisis and improving the treatment of individual nonhumans to foster wildlife-human coexistence
Surveillance after initial surgery for pediatric and adolescent girls with stage I ovarian germ cell tumors: report from the Children's Oncology Group
PURPOSE:
To determine whether overall survival (OS) can be preserved for patients with stage I pediatric malignant ovarian germ cell tumor (MOGCT) with an initial strategy of surveillance after surgical resection.
PATIENTS AND METHODS:
Between November 2003 and July 2011, girls age 0 to 16 years with stage I MOGCT were enrolled onto Children's Oncology Group study AGCT0132. Required histology included yolk sac, embryonal carcinoma, or choriocarcinoma. Surveillance included measurement of serum tumor markers and radiologic imaging at defined intervals. In those with residual or recurrent disease, chemotherapy with compressed PEB (cisplatin, etoposide, and bleomycin) was initiated every 3 weeks for three cycles (cisplatin 33 mg/m(2) on days 1 to 3, etoposide 167 mg/m(2) on days 1 to 3, bleomycin 15 U/m(2) on day 1). Survivor functions for event-free survival (EFS) and OS were estimated using the Kaplan-Meier method.
RESULTS:
Twenty-five girls (median age, 12 years) with stage I MOGCT were enrolled onto AGCT0132. Twenty-three patients had elevated alpha-fetoprotein (AFP) at diagnosis. Predominant histology was yolk sac. After a median follow-up of 42 months, 12 patients had evidence of persistent or recurrent disease (4-year EFS, 52%; 95% CI, 31% to 69%). Median time to recurrence was 2 months. All patients had elevated AFP at recurrence; six had localized disease, two had metastatic disease, and four had tumor marker elevation only. Eleven of 12 patients experiencing relapse received successful salvage chemotherapy (4-year OS, 96%; 95% CI, 74% to 99%).
CONCLUSION:
Fifty percent of patients with stage I pediatric MOGCT can be spared chemotherapy; treatment for those who experience recurrence preserves OS. Further study is needed to identify the factors that predict recurrence and whether this strategy can be extended successfully to older adolescents and young adults
Spatio-temporal modelling of climate-sensitive disease risk: Towards an early warning system for dengue in Brazil
NOTICE: this is the authorās version of a work that was accepted for publication in Computers and Geosciences. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Computers and Geosciences, Vol. 37, Issue 3, (2011), DOI: 10.1016/j.cageo.2010.01.008This paper considers the potential for using seasonal climate forecasts in developing an early warning system for dengue fever epidemics in Brazil. In the first instance, a generalised linear model (GLM) is used to select climate and other covariates which are both readily available and prove significant in prediction of confirmed monthly dengue cases based on data collected across the whole of Brazil for the period January 2001 to December 2008 at the microregion level (typically consisting of one large city and several smaller municipalities). The covariates explored include temperature and precipitation data on a 2.5Ā°Ć2.5Ā°2.5Ā°Ć2.5Ā° longitudeālatitude grid with time lags relevant to dengue transmission, an El NiƱo Southern Oscillation index and other relevant socio-economic and environmental variables. A negative binomial model formulation is adopted in this model selection to allow for extra-Poisson variation (overdispersion) in the observed dengue counts caused by unknown/unobserved confounding factors and possible correlations in these effects in both time and space. Subsequently, the selected global model is refined in the context of the South East region of Brazil, where dengue predominates, by reverting to a Poisson framework and explicitly modelling the overdispersion through a combination of unstructured and spatio-temporal structured random effects. The resulting spatio-temporal hierarchical model (or GLMMāgeneralised linear mixed model) is implemented via a Bayesian framework using Markov Chain Monte Carlo (MCMC). Dengue predictions are found to be enhanced both spatially and temporally when using the GLMM and the Bayesian framework allows posterior predictive distributions for dengue cases to be derived, which can be useful for developing a dengue alert system. Using this model, we conclude that seasonal climate forecasts could have potential value in helping to predict dengue incidence months in advance of an epidemic in South East Brazil
The microtubule catastrophe promoter Sentin delays stable kinetochore-microtubule attachment in oocytes
The critical step in meiosis is to attach homologous chromosomes to the opposite poles. In mouse oocytes, stable microtubule end-on attachments to kinetochores are not established until hours after spindle assembly, and phosphorylation of kinetochore proteins by Aurora B/C is responsible for the delay. Here we demonstrated that microtubule ends are actively prevented from stable attachment to kinetochores until well after spindle formation in Drosophila melanogaster oocytes. We identified the microtubule catastrophe-promoting complex Sentin-EB1 as a major factor responsible for this delay. Without this activity, microtubule ends precociously form robust attachments to kinetochores in oocytes, leading to a high proportion of homologous kinetochores stably attached to the same pole. Therefore, regulation of microtubule ends provides an alternative novel mechanism to delay stable kinetochoreāmicrotubule attachment in oocytes
Novel homozygous missense mutation in GAN associated with Charcot-Marie-Tooth disease type 2 in a large consanguineous family from Israel.
BACKGROUND: CMT-2 is a clinically and genetically heterogeneous group of peripheral axonal neuropathies characterized by slowly progressive weakness and atrophy of distal limb muscles resulting from length-dependent motor and sensory neurodegeneration. Classical giant axonal neuropathy (GAN) is an autosomal recessively inherited progressive neurodegenerative disorder of the peripheral and central nervous systems, typically diagnosed in early childhood and resulting in death by the end of the third decade. Distinctive phenotypic features are the presence of "kinky" hair and long eyelashes. The genetic basis of the disease has been well established, with over 40 associated mutations identified in the gene GAN, encoding the BTB-KELCH protein gigaxonin, involved in intermediate filament regulation. METHODS: An Illumina Human CytoSNP-12 array followed by whole exome sequence analysis was used to identify the disease associated gene mutation in a large consanguineous family diagnosed with Charcot-Marie-Tooth disease type 2 (CMT-2) from which all but one affected member had straight hair. RESULTS: Here we report the identification of a novel GAN missense mutation underlying the CMT-2 phenotype observed in this family. Although milder forms of GAN, with and without the presence of kinky hair have been reported previously, a phenotype distinct from that was investigated in this study. All family members lacked common features of GAN, including ataxia, nystagmus, intellectual disability, seizures, and central nervous system involvement. CONCLUSIONS: Our findings broaden the spectrum of phenotypes associated with GAN mutations and emphasize a need to proceed with caution when providing families with diagnostic or prognostic information based on either clinical or genetic findings alone
Planetary science and exploration in the deep subsurface: results from the MINAR Program, Boulby Mine, UK
The subsurface exploration of other planetary bodies can be used to unravel their geological history and assess their habitability. On Mars in particular, present-day habitable conditions may be restricted to the subsurface. Using a deep subsurface mine, we carried out a program of extraterrestrial analog research ā MINe Analog Research (MINAR). MINAR aims to carry out the scientific study of the deep subsurface and test instrumentation designed for planetary surface exploration by investigating deep subsurface geology, whilst establishing the potential this technology has to be transferred into the mining industry. An integrated multi-instrument suite was used to investigate samples of representative evaporite minerals from a subsurface Permian evaporite sequence, in particular to assess mineral and elemental variations which provide small-scale regions of enhanced habitability. The instruments used were the Panoramic Camera emulator, Close-Up Imager, Raman spectrometer, Small Planetary Linear Impulse Tool, Ultrasonic drill and handheld X-ray diffraction (XRD). We present science results from the analog research and show that these instruments can be used to investigate in situ the geological context and mineralogical variations of a deep subsurface environment, and thus habitability, from millimetre to metre scales. We also show that these instruments are complementary. For example, the identification of primary evaporite minerals such as NaCl and KCl, which are difficult to detect by portable Raman spectrometers, can be accomplished with XRD. By contrast, Raman is highly effective at locating and detecting mineral inclusions in primary evaporite minerals. MINAR demonstrates the effective use of a deep subsurface environment for planetary instrument development, understanding the habitability of extreme deep subsurface environments on Earth and other planetary bodies, and advancing the use of space technology in economic mining
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