We present a general treatment of the variational multiscale method in the context of an abstract Dirichlet problem. We show how the exact theory represents a paradigm for subgrid-scale models and a ...posteriori error estimation. We examine hierarchical
p-methods and bubbles in order to understand and, ultimately, approximate the ‘fine-scale Green's function’ which appears in the theory. We review relationships between residual-free bubbles, element Green's functions and stabilized methods. These suggest the applicability of the methodology to physically interesting problems in fluid mechanics, acoustics and electromagnetics.
Patients with acute abdominal pathology requiring emergency laparotomy who experience a delay to theatre have an increased risk of morbidity, mortality and complications. The timeline between symptom ...onset and operation is ill defined with international variance in assessment and management. This systematic review aims to define where delays to surgery occur and assess the evidence for interventions trialled across Europe.
A systematic review was performed searching MEDLINE and EMBASE databases (1 January 2005 to 6 May 2020). All studies assessing the impact of time to theatre in patients with acute abdominal pathology requiring emergency laparotomy were considered.
Sixteen papers, involving 50 653 patients, were included in the analysis. Fifteen unique timepoints were identified in the patient pathway between symptom onset and operation which are classified into four distinct phases. Time from admission to theatre (1-72 hours) and mortality rate (10.6-74.5 per cent) varied greatly between studies. Mean time to surgery was significantly higher in deceased patients compared with that in survivors. Delays were related to imaging, diagnosis, decision making, theatre availability and staffing. Four of five interventional studies showed a reduced mortality rate following introduction of an acute laparotomy pathway.
Given the heterogeneous nature of the patient population and pathologies, an assessment and management framework from onset of symptoms to operation is proposed. This could be incorporated into mortality prediction and audit tools and assist in the assessment of interventions.
Quantum key distribution (QKD) enables unconditional physical layer security for the distribution of cryptographic key material. However, most experimental demonstrations have relied on simple ...point-to-point optical links. In this paper we investigate the compatibility of QKD with reconfigurable optical networks. By performing the first tests of QKD transmission through optical switches, we study if there are impairment mechanisms other than switch insertion loss that impact the sifted and error corrected secret bit yield. Three types of transparent optical switch elements are investigated including lithium niobate (LiNbO/sub 3/), microelectromechanical systems (MEMS), and optomechanical. We show that QKD can be extended beyond point-to-point links to switched multinode architectures including protected ring networks to enhance quantum channel availability.
We present the first dynamical mass estimates and scaling relations for a sample of Sunyaev-Zel'dovich effect (SZE) selected galaxy clusters. The sample consists of 16 massive clusters detected with ...the Atacama Cosmology Telescope (ACT) over a 455 deg super(2) area of the southern sky. The dynamical masses M sub(200)c of the clusters have been calculated using simulation-based scaling relations between velocity dispersion and mass. These masses are compared to the ACT SZE properties of the sample, specifically, the match-filtered central SZE amplitude y sub(0), the central Compton parameter y sub(0), and the integrated Compton signal Y sub(200)c, which we use to derive SZE-mass scaling relations. All SZE estimators correlate with dynamical mass with low intrinsic scatter (lap20%), in agreement with numerical simulations. There are hints that disturbed systems might bias the scaling relations, but given the current sample sizes, these differences are not significant; further studies including more clusters are required to assess the impact of these clusters on the scaling relations.
Summary Background A severe form of encephalitis associated with antibodies against NR1–NR2 heteromers of the NMDA receptor was recently identified. We aimed to analyse the clinical and immunological ...features of patients with the disorder and examine the effects of antibodies against NMDA receptors in neuronal cultures. Methods We describe the clinical characteristics of 100 patients with encephalitis and NR1–NR2 antibodies. HEK293 cells ectopically expressing single or assembled NR1–NR2 subunits were used to determine the epitope targeted by the antibodies. Antibody titres were measured with ELISA. The effect of antibodies on neuronal cultures was determined by quantitative analysis of NMDA-receptor clusters. Findings Median age of patients was 23 years (range 5–76 years); 91 were women. All patients presented with psychiatric symptoms or memory problems; 76 had seizures, 88 unresponsiveness (decreased conciousness), 86 dyskinesias, 69 autonomic instability, and 66 hypoventilation. 58 (59%) of 98 patients for whom results of oncological assessments were available had tumours, most commonly ovarian teratoma. Patients who received early tumour treatment (usually with immunotherapy) had better outcome (p=0·004) and fewer neurological relapses (p=0·009) than the rest of the patients. 75 patients recovered or had mild deficits and 25 had severe deficits or died. Improvement was associated with a decrease of serum antibody titres. The main epitope targeted by the antibodies is in the extracellular N-terminal domain of the NR1 subunit. Patients' antibodies decreased the numbers of cell-surface NMDA receptors and NMDA-receptor clusters in postsynaptic dendrites, an effect that could be reversed by antibody removal. Interpretation A well-defined set of clinical characteristics are associated with anti-NMDA-receptor encephalitis. The pathogenesis of the disorder seems to be mediated by antibodies. Funding National Institutes for Health, University of Pennsylvania Institute for Translational Medicine, Lankenau Institute for Medical Research, Foederer Foundation of the Children's Hospital of Philadelphia.
This study investigates the association of CRP (C-reactive protein) single-nucleotide polymorphisms (SNPs) with plasma CRP levels and radiographic severity in African Americans with early and ...established rheumatoid arthritis (RA). Using a cross-sectional case-only design, CRP SNPs were genotyped in two independent sets of African Americans with RA: Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR 1) and CLEAR 2. Radiographic data and CRP measurements were available for 294 individuals from CLEAR 1 (median (interquartile range (IQR) 25-75) disease duration of 1 (0.6-1.6) year) and in 407 persons from CLEAR 2 (median (IQR 25-75) disease duration of 8.9 (3.5-17.7) years). In CLEAR 1, in adjusted models, the minor allele of rs2808630 was associated with total radiographic score (incident rate ratio 0.37 (95% confidence interval (CI) 0.19-0.74), P-value=0.0051). In CLEAR 2, the minor allele of rs3093062 was associated with increased plasma CRP levels (P-value=0.002). For each rs3093062 minor allele, the plasma CRP increased by 1.51 (95% CI 1.15-1.95) mg dl(-1) when all the other covariates remained constant. These findings have important implications for assessment of the risk of joint damage in African Americans with RA.
There is growing interest in the use of the ketogenic diet (KD) to treat inherited metabolic diseases including mitochondrial disorders. However, neither the mechanism whereby the diet may be ...working, nor if it could benefit all patients with mitochondrial disease, is known. This study focusses on decanoic acid (C10), a component of the medium chain triglyceride KD, and a ligand for the nuclear receptor PPAR-γ known to be involved in mitochondrial biogenesis. The effects of C10 were investigated in primary fibroblasts from a cohort of patients with Leigh syndrome (LS) caused by nuclear-encoded defects of respiratory chain complex I, using mitochondrial respiratory chain enzyme assays, gene expression microarray, qPCR and flow cytometry. Treatment with C10 increased citrate synthase activity, a marker of cellular mitochondrial content, in 50 % of fibroblasts obtained from individuals diagnosed with LS in a PPAR-γ-mediated manner. Gene expression analysis and qPCR studies suggested that treating cells with C10 supports fatty acid metabolism, through increasing
ACADVL
and
CPT1
expression, whilst downregulating genes involved in glucose metabolism (
PDK3
,
PDK4
).
PCK2
, involved in blocking glucose metabolism, was upregulated, as was
CAT
, encoding catalase. Moreover, treatment with C10 also decreased oxidative stress in complex I deficient (rotenone treated) cells. However, since not all cells from subjects with LS appeared to respond to C10, prior cellular testing in vitro could be employed as a means for selecting individuals for subsequent clinical studies involving C10 preparations.
Recent observations show that human-induced climate change (CC) and land transformation (LT) are threatening wildlife globally. Thus, there is a need to assess the sensitivity of wildlife on large ...spatial scales and evaluate whether national parks (NPs), a key conservation tools used to protect species, will meet their mandate under future CC and LT conditions. Here, we assess the sensitivity of 277 mammals at African scale to CC at 10prime resolution, using static LT assumptions in a 'first-cut' estimate, in the absence of credible future LT trends. We examine the relationship between species' current distribution and macroclimatic variables using generalized additive models, and include LT indirectly as a filter. Future projections are derived using two CC scenarios (for 2050 and 2080) to estimate the spatial patterns of loss and gain in species richness that might ultimately result. We then apply the IUCN Red List criteria A3(c) of potential range loss to evaluate species sensitivity. We finally estimate the sensitivity of 141 NPs in terms of both species richness and turnover. Assuming no spread of species, 10-15% of the species are projected to fall within the critically endangered or extinct categories by 2050 and between 25% and 40% by 2080. Assuming unlimited species spread, less extreme results show proportions dropping to approximately 10-20% by 2080. Spatial patterns of richness loss and gain show contrasting latitudinal patterns with a westward range shift of species around the species-rich equatorial zone in central Africa, and an eastward shift in southern Africa, mainly because of latitudinal aridity gradients across these ecological transition zones. Xeric shrubland NPs may face significant richness losses not compensated by species influxes. Other NPs might expect substantial losses and influxes of species. On balance, the NPs might ultimately realize a substantial shift in the mammalian species composition of a magnitude unprecedented in recent geological time. To conclude, the effects of global CC and LT on wildlife communities may be most noticeable not as a loss of species from their current ranges, but instead as a fundamental change in community composition.
Intrapulmonary vascular dilations (IPVD) are common in patients with cirrhosis, but the majority do not have hepatopulmonary syndrome (HPS). The clinical significance of IPVD is unknown. Our aim was ...to determine the clinical impact due to the entire spectrum of IPVD in liver transplant (LT) candidates. A total of 122 evaluees for LT underwent contrast transthoracic echocardiography (cTTE). The degree of shunting was graded 1–3 (severe). HPS was defined as PaO2 < 70 mmHg in the presence of IPVD and exclusion of other causes of hypoxemia. IPVD were detected in 57/122 (47%), and of these HPS was found in 5. IPVD were associated with higher Alveolar‐arterial (A‐a) gradients, with the highest occurring in patients with HPS (IPVD vs. no IPVD: p = 0.003; HPS vs. no IPVD: p = 0.004). All patients with HPS had grade 3 shunting, and had significantly widened A‐a gradient and lower PaO2 compared with grade 1 or 2 IPVDs. Presence of IPVD did not affect survival measured from evaluation or after LT. Other clinical outcomes were also similar among patients with and without IPVD. IPVD are common among LT candidates. HPS is unlikely in presence of only mild to moderate shunting. Clinical outcomes are similar among patients with and without IPVD.
Resource managers and scientists from disparate disciplines are rising to the challenge of understanding and moderating human impacts on marine ecosystems. Traditional barriers to communication ...between marine ecologists, fisheries biologists, social scientists and economists are beginning to break down, and the distinction between applied and basic research is fading. These ongoing trends arise, in part, from an increasing awareness of the profound influence of people on the functioning of all marine ecosystems, an increased focus on spatial and temporal scale, and a renewed assessment of the role of biodiversity in the sustainability of ecosystem goods and services upon which human societies depend. Here, we highlight the emergence of a complex systems approach for sustaining and repairing marine ecosystems, linking ecological resilience to governance structures, economics and society.
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