277 research outputs found
Mixed Mimetic Spectral Element Method for Stokes Flow: A Pointwise Divergence-Free Solution
In this paper we apply the recently developed mimetic discretization method
to the mixed formulation of the Stokes problem in terms of vorticity, velocity
and pressure. The mimetic discretization presented in this paper and in [50] is
a higher-order method for curvilinear quadrilaterals and hexahedrals.
Fundamental is the underlying structure of oriented geometric objects, the
relation between these objects through the boundary operator and how this
defines the exterior derivative, representing the grad, curl and div, through
the generalized Stokes theorem. The mimetic method presented here uses the
language of differential -forms with -cochains as their discrete
counterpart, and the relations between them in terms of the mimetic operators:
reduction, reconstruction and projection. The reconstruction consists of the
recently developed mimetic spectral interpolation functions. The most important
result of the mimetic framework is the commutation between differentiation at
the continuous level with that on the finite dimensional and discrete level. As
a result operators like gradient, curl and divergence are discretized exactly.
For Stokes flow, this implies a pointwise divergence-free solution. This is
confirmed using a set of test cases on both Cartesian and curvilinear meshes.
It will be shown that the method converges optimally for all admissible
boundary conditions
Both the Caspase CSP-1 and a Caspase-Independent Pathway Promote Programmed Cell Death in Parallel to the Canonical Pathway for Apoptosis in Caenorhabditis elegans
Caspases are cysteine proteases that can drive apoptosis in metazoans and have critical functions in the elimination of cells during development, the maintenance of tissue homeostasis, and responses to cellular damage. Although a growing body of research suggests that programmed cell death can occur in the absence of caspases, mammalian studies of caspase-independent apoptosis are confounded by the existence of at least seven caspase homologs that can function redundantly to promote cell death. Caspase-independent programmed cell death is also thought to occur in the invertebrate nematode Caenorhabditis elegans. The C. elegans genome contains four caspase genes (ced-3, csp-1, csp-2, and csp-3), of which only ced-3 has been demonstrated to promote apoptosis. Here, we show that CSP-1 is a pro-apoptotic caspase that promotes programmed cell death in a subset of cells fated to die during C. elegans embryogenesis. csp-1 is expressed robustly in late pachytene nuclei of the germline and is required maternally for its role in embryonic programmed cell deaths. Unlike CED-3, CSP-1 is not regulated by the APAF-1 homolog CED-4 or the BCL-2 homolog CED-9, revealing that csp-1 functions independently of the canonical genetic pathway for apoptosis. Previously we demonstrated that embryos lacking all four caspases can eliminate cells through an extrusion mechanism and that these cells are apoptotic. Extruded cells differ from cells that normally undergo programmed cell death not only by being extruded but also by not being engulfed by neighboring cells. In this study, we identify in csp-3; csp-1; csp-2 ced-3 quadruple mutants apoptotic cell corpses that fully resemble wild-type cell corpses: these caspase-deficient cell corpses are morphologically apoptotic, are not extruded, and are internalized by engulfing cells. We conclude that both caspase-dependent and caspase-independent pathways promote apoptotic programmed cell death and the phagocytosis of cell corpses in parallel to the canonical apoptosis pathway involving CED-3 activation.Howard Hughes Medical InstituteDamon Runyon Cancer Research FoundationCharles A. King Trus
An association between polymorphism of the heme oxygenase-1 and -2 genes and age-related macular degeneration
Iron may be implicated in the generation of oxidative stress by the catalyzing the Haber–Weiss or Fenton reaction. On the other hand, oxidative stress has been implicated in the pathogenesis of age-related macular degeneration (AMD) and heme oxygenase-1 (HO-1), encoded by the HMOX1 gene and heme oxygenase-2 (HO-2), encoded by the HMOX2 gene are important markers of iron-related oxidative stress and its consequences. Therefore, variability of the HMOX1 and HMOX2 genes might be implicated in the pathogenesis of AMD through the modulation of the cellular reaction to oxidative stress. In the present work, we investigated the association between AMD and a G → C transversion at the 19 position in the HMOX1 gene (the 19G>C-HMOX1 polymorphism, rs2071747) and a A → G transition at the −42 + 1444 position in the HMOX2 gene (the −42 + 1444A>G-HMOX2 polymorphism, rs2270363) and its modulation by some environmental factors. 279 patients with AMD and 105 controls were recruited in this study and the polymorphisms were typed by restriction fragment length polymorphism and allele-specific polymerase chain reaction (PCR). We observed an association between the occurrence of dry AMD and the G/A genotype of the −42 + 1444A>G-HMOX2 polymorphism (odds ratio (OR) 2.72), whereas the G/G genotype reduced the risk of dry AMD (OR 0.41). The G/C genotype and the C allele of the 19 G>C-HMOX1 polymorphism and the G/G genotype and the G allele of the −42 + 1444A>G-HMOX2 polymorphism were associated with progression of AMD from dry to wet form (OR 4.83, 5.20, 2.55, 1.69, respectively). On the other hand, the G/G genotype and the G allele of the 19 G>C-HMOX1 polymorphism and the A/G genotype and the A allele of the −42 + 1444A>G-HMOX2 polymorphism protected against AMD progression (OR 0.19, 0.19, 0.34, 0.59, respectively). Therefore, the 19G>C-HMOX1 and the −42 + 1444A>G-HMOX2 polymorphisms may be associated with the occurrence and progression of AMD
Investigating variation in replicability
Although replication is a central tenet of science, direct replications are rare in psychology. This research tested variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants. In the aggregate, 10 effects replicated consistently. One effect – imagined contact reducing prejudice – showed weak support for replicability. And two effects – flag priming influencing conservatism and currency priming influencing system justification – did not replicate. We compared whether the conditions such as lab versus online or US versus international sample predicted effect magnitudes. By and large they did not. The results of this small sample of effects suggest that replicability is more dependent on the effect itself than on the sample and setting used to investigate the effect
Language endangerment and language documentation in Africa
Non peer reviewe
Automated telephone communication systems for preventive healthcare and management of long-term conditions
Background
Automated telephone communication systems (ATCS) can deliver voice messages and collect health-related information from patients
using either their telephone’s touch-tone keypad or voice recognition software. ATCS can supplement or replace telephone contact
between health professionals and patients. There are four different types of ATCS: unidirectional (one-way, non-interactive voice
communication), interactive voice response (IVR) systems, ATCS with additional functions such as access to an expert to request advice
(ATCS Plus) and multimodal ATCS, where the calls are delivered as part of a multicomponent intervention.
Objectives
To assess the effects of ATCS for preventing disease and managing long-term conditions on behavioural change, clinical, process,
cognitive, patient-centred and adverse outcomes.
Search methods
We searched 10 electronic databases (the Cochrane Central Register of Controlled Trials; MEDLINE; Embase; PsycINFO; CINAHL;
Global Health; WHOLIS; LILACS; Web of Science; and ASSIA); three grey literature sources (Dissertation Abstracts, Index to Theses,
Australasian Digital Theses); and two trial registries (www.controlled-trials.com; www.clinicaltrials.gov) for papers published between
1980 and June 2015.
Selection criteria
Randomised, cluster- and quasi-randomised trials, interrupted time series and controlled before-and-after studies comparing ATCS
interventions, with any control or another ATCS type were eligible for inclusion. Studies in all settings, for all consumers/carers, in any
preventive healthcare or long term condition management role were eligible.
Data collection and analysis
We used standard Cochrane methods to select and extract data and to appraise eligible studies.
Main results
We included 132 trials (N = 4,669,689). Studies spanned across several clinical areas, assessing many comparisons based on evaluation
of different ATCS types and variable comparison groups. Forty-one studies evaluated ATCS for delivering preventive healthcare, 84 for
managing long-term conditions, and seven studies for appointment reminders. We downgraded our certainty in the evidence primarily
because of the risk of bias for many outcomes. We judged the risk of bias arising from allocation processes to be low for just over half
the studies and unclear for the remainder. We considered most studies to be at unclear risk of performance or detection bias due to
blinding, while only 16% of studies were at low risk. We generally judged the risk of bias due to missing data and selective outcome
reporting to be unclear.
For preventive healthcare, ATCS (ATCS Plus, IVR, unidirectional) probably increase immunisation uptake in children (risk ratio (RR)
1.25, 95% confidence interval (CI) 1.18 to 1.32; 5 studies, N = 10,454; moderate certainty) and to a lesser extent in adolescents (RR
1.06, 95% CI 1.02 to 1.11; 2 studies, N = 5725; moderate certainty). The effects of ATCS in adults are unclear (RR 2.18, 95% CI
0.53 to 9.02; 2 studies, N = 1743; very low certainty).
For screening, multimodal ATCS increase uptake of screening for breast cancer (RR 2.17, 95% CI 1.55 to 3.04; 2 studies, N = 462;
high certainty) and colorectal cancer (CRC) (RR 2.19, 95% CI 1.88 to 2.55; 3 studies, N = 1013; high certainty) versus usual care.
It may also increase osteoporosis screening. ATCS Plus interventions probably slightly increase cervical cancer screening (moderate
certainty), but effects on osteoporosis screening are uncertain. IVR systems probably increase CRC screening at 6 months (RR 1.36,
95% CI 1.25 to 1.48; 2 studies, N = 16,915; moderate certainty) but not at 9 to 12 months, with probably little or no effect of IVR
(RR 1.05, 95% CI 0.99, 1.11; 2 studies, 2599 participants; moderate certainty) or unidirectional ATCS on breast cancer screening.
Appointment reminders delivered through IVR or unidirectional ATCS may improve attendance rates compared with no calls (low
certainty). For long-term management, medication or laboratory test adherence provided the most general evidence across conditions
(25 studies, data not combined). Multimodal ATCS versus usual care showed conflicting effects (positive and uncertain) on medication
adherence. ATCS Plus probably slightly (versus control; moderate certainty) or probably (versus usual care; moderate certainty) improves
medication adherence but may have little effect on adherence to tests (versus control). IVR probably slightly improves medication
adherence versus control (moderate certainty). Compared with usual care, IVR probably improves test adherence and slightly increases
medication adherence up to six months but has little or no effect at longer time points (moderate certainty). Unidirectional ATCS,
compared with control, may have little effect or slightly improve medication adherence (low certainty). The evidence suggested little or
no consistent effect of any ATCS type on clinical outcomes (blood pressure control, blood lipids, asthma control, therapeutic coverage)
related to adherence, but only a small number of studies contributed clinical outcome data.
The above results focus on areas with the most general findings across conditions. In condition-specific areas, the effects of ATCS
varied, including by the type of ATCS intervention in use.
Multimodal ATCS probably decrease both cancer pain and chronic pain as well as depression (moderate certainty), but other ATCS
types were less effective. Depending on the type of intervention, ATCS may have small effects on outcomes for physical activity,
weight management, alcohol consumption, and diabetes mellitus. ATCS have little or no effect on outcomes related to heart failure,
hypertension, mental health or smoking cessation, and there is insufficient evidence to determine their effects for preventing alcohol/
substance misuse or managing illicit drug addiction, asthma, chronic obstructive pulmonary disease, HIV/AIDS, hypercholesterolaemia,
obstructive sleep apnoea, spinal cord dysfunction or psychological stress in carers.
Only four trials (3%) reported adverse events, and it was unclear whether these were related to the intervention
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