218 research outputs found

    Wavenumber-explicit analysis for the Helmholtz h-BEM: error estimates and iteration counts for the Dirichlet problem

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    We consider solving the exterior Dirichlet problem for the Helmholtz equation with the h-version of the boundary element method (BEM) using the standard second-kind combined-field integral equations. We prove a new, sharp bound on how the number of GMRES iterations must grow with the wavenumber k to have the error in the iterative solution bounded independently of k as k→∞ when the boundary of the obstacle is analytic and has strictly positive curvature. To our knowledge, this result is the first-ever sharp bound on how the number of GMRES iterations depends on the wavenumber for an integral equation used to solve a scattering problem. We also prove new bounds on how h must decrease with k to maintain k-independent quasi-optimality of the Galerkin solutions as k→∞ when the obstacle is nontrapping

    Congenital scoliosis associated with agenesis of the uterine cervix. Case report

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    BACKGROUND: Alterations in the normal sequence of development of müllerian ducts lead to a wide spectrum of reproductive tract abnormalities. A rare form of lack of development, regarding a short tract of the müllerian ducts, leads to the isolated agenesis of the uterine cervix. Anomalies identified among patients with müllerian agenesis include skeletal deformities (i.e., scoliosis of the spine and Klippel-Feil anomaly). CASE PRESENTATION: A 46 years old woman presenting cyphoscoliosis and very low stature (120 cm – 3,93 feet), came to our observation for acute pelvic pain; she also reported primary amenorrhoea associated with cyclic pelvic pain. Clinical and imaging evaluation, evidenced a blind vaginal duct of normal length, left cystic adnexal mass, and enlarged uterus with hematometra. FSH, LH, 17β estradiol and CA-125, karyotype and radiographic study of limbs and vertebral column were also evaluated. At laparotomy, a left ovarian cyst was found. Uterus ended at the isthmus; under this level a thin fibrous tissue band was found, joining the uterus to the vagina. Uterine cervix was replaced by fibrous tissue containing some dilated glands lined with müllerian epithelium. Karyotype resulted 46, XX. The described skeletal deformity, were consistent with Klippel-Feil syndrome. CONCLUSION: We report a case of congenital scoliosis associated with müllerian agenesis limited to uterine cervix, association thus far seen only among patients with Mayer-Rokitansky-Kuster-Hauser syndrome (utero-vaginal agenesis). This case report supports the necessity to evaluate, for accompanying müllerian anomalies, all cases of congenital structural scoliosis in view of the possibility for many müllerian development abnormalities, if timely diagnosed, to be surgically corrected

    The impact of parenthood on environmental attitudes and behaviour: a longitudinal investigation of the legacy hypothesis

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    Willingness to engage in sustainable actions may be limited by the psychological distance of climate change. In this study, we test the legacy hypothesis, which holds that having children leads parents to consider the legacy left to offspring in respect of environmental quality. Using the Understanding Society dataset, a longitudinal survey representative of the UK population (n = 18,176), we assess how having children may change people’s individual environmental attitudes and behaviour. Results indicate that having a new child is associated with a small decrease in the frequency of a few environmental behaviours. Only parents with already high environmental concern show a small increase in the desire to act more sustainably after the birth of their first child. Overall, the results do not provide evidence in support of the legacy hypothesis in terms of individual-level environmental attitudes and behaviours. We argue that the transition to parenthood is a time where concern is prioritised on the immediate wellbeing of the child and not on the future environmental threats

    Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

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    Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

    Social Intelligence and Academic Achievement as Predictors of Adolescent Popularity

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    This study compared the effects of social intelligence and cognitive intelligence, as measured by academic achievement, on adolescent popularity in two school contexts. A distinction was made between sociometric popularity, a measure of acceptance, and perceived popularity, a measure of social dominance. Participants were 512, 14–15 year-old adolescents (56% girls, 44% boys) in vocational and college preparatory schools in Northwestern Europe. Perceived popularity was significantly related to social intelligence, but not to academic achievement, in both contexts. Sociometric popularity was predicted by an interaction between academic achievement and social intelligence, further qualified by school context. Whereas college bound students gained sociometric popularity by excelling both socially and academically, vocational students benefited from doing well either socially or academically, but not in combination. The implications of these findings were discussed

    Retrograde trafficking of β-dystroglycan from the plasma membrane to the nucleus

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    β-Dystroglycan (β-DG) is a transmembrane protein with critical roles in cell adhesion, cytoskeleton remodeling and nuclear architecture. This functional diversity is attributed to the ability of β-DG to target to, and conform specific protein assemblies at the plasma membrane (PM) and nuclear envelope (NE). Although a classical NLS and importin α/β mediated nuclear import pathway has already been described for β-DG, the intracellular trafficking route by which β-DG reaches the nucleus is unknown. In this study, we demonstrated that β-DG undergoes retrograde intracellular trafficking from the PM to the nucleus via the endosome-ER network. Furthermore, we provided evidence indicating that the translocon complex Sec61 mediates the release of β-DG from the ER membrane, making it accessible for importins and nuclear import. Finally, we show that phosphorylation of β-DG at Tyr890 is a key stimulus for β-DG nuclear translocation. Collectively our data describe the retrograde intracellular trafficking route that β-DG follows from PM to the nucleus. This dual role for a cell adhesion receptor permits the cell to functionally connect the PM with the nucleus and represents to our knowledge the first example of a cell adhesion receptor exhibiting retrograde nuclear trafficking and having dual roles in PM and NE

    Use of social audits to examine unofficial payments in government health services: experience in South Asia, Africa, and Europe

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    <p>Abstract</p> <p>Background</p> <p>Unofficial payments in health services around the world are widespread and as varied as the health systems in which they occur. We reviewed the main lessons from social audits of petty corruption in health services in South Asia (Bangladesh, Pakistan), Africa (Uganda and South Africa) and Europe (Baltic States).</p> <p>Methods</p> <p>The social audits varied in purpose and scope. All covered representative sample communities and involved household interviews, focus group discussions, institutional reviews of health facilities, interviews with service providers and discussions with health authorities. Most audits questioned households about views on health services, perceived corruption in the services, and use of government and other health services. Questions to service users asked about making official and unofficial payments, amounts paid, service delivery indicators, and satisfaction with the service.</p> <p>Results</p> <p>Contextual differences between the countries affected the forms of petty corruption and factors related to it. Most households in all countries held negative views about government health services and many perceived these services as corrupt. There was little evidence that better off service users were more likely to make an unofficial payment, or that making such a payment was associated with better or quicker service; those who paid unofficially to health care workers were not more satisfied with the service. In South Asia, where we conducted repeated social audits, only a minority of households chose to use government health services and their use declined over time in favour of other providers. Focus groups indicated that reasons for avoiding government health services included the need to pay for supposedly free services and the non-availability of medicines in facilities, often perceived as due to diversion of the supplied medicines.</p> <p>Conclusions</p> <p>Unofficial expenses for medical care represent a disproportionate cost for vulnerable families; the very people who need to make use of supposedly free government services, and are a barrier to the use of these services. Patient dissatisfaction due to petty corruption may contribute to abandonment of government health services. The social audits informed plans for tackling corruption in health services.</p

    Exploratory study of plasma total homocysteine and its relationship to short-term outcome in acute ischaemic stroke in Nigerians

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    <p>Abstract</p> <p>Background</p> <p>Hyperhomocysteinemia is a potentially modifiable risk factor for stroke, and may have a negative impact on the course of ischaemic stroke. The role of hyperhomocysteinemia as it relates to stroke in Africans is still uncertain. The objective of this study was to determine the prevalence and short-term impact of hyperhomocysteinemia in Nigerians with acute ischaemic stroke. We hypothesized that Hcy levels are significantly higher than in normal controls, worsen stroke severity, and increase short-term case fatality rates following acute ischaemic stroke.</p> <p>Methods</p> <p>The study employed both a case-control and prospective follow-up design to study hospitalized adults with first – ever acute ischaemic stroke presenting within 48 hours of onset. Clinical histories, neurological evaluation (including National Institutes of Health Stroke Scale (NIHSS) scores on admission) were documented. Total plasma Hcy was determined on fasting samples drawn from controls and stroke cases (within 24 hours of hospitalization). Outcome at 4 weeks was assessed in stroke patients using the Glasgow Outcome Scale (GOS).</p> <p>Results</p> <p>We evaluated 155 persons (69 acute ischaemic stroke and 86 healthy controls). The mean age ± SD of the cases was 58.8 ± 9.8 years, comparable to that of controls which was 58.3 ± 9.9 years (T = 0.32; P = 0.75). The mean duration of stroke (SD) prior to hospitalization was 43.5 ± 38.8 hours, and mean admission NIHSS score was 10.1 ± 7.7. Total fasting Hcy in stroke patients was 10.2 ± 4.6 umol/L and did not differ significantly from controls (10.1 ± 3.6 umol/L; P = 0.88). Hyperhomocysteinemia, defined by plasma Hcy levels > 90<sup>th </sup>percentile of controls (>14.2 umol/L in women and >14.6 umol/L in men), was present in 7 (10.1%) stroke cases and 11 (12.8%) controls (odds ratio 0.86, 95% confidence interval 0.31 – 2.39; P > 0.05). In multiple regression analysis admission NIHSS score (but not plasma Hcy) was a significant determinant of 4 week outcome measured by GOS score (P < 0.0001).</p> <p>Conclusion</p> <p>This exploratory study found that homocysteine levels are not significantly elevated in Nigerians with acute ischaemic stroke, and admission Hcy level is not a determinant of short-term (4 week) stroke outcome.</p

    A case of autism with an interstitial deletion on 4q leading to hemizygosity for genes encoding for glutamine and glycine neurotransmitter receptor sub-units (AMPA 2, GLRA3, GLRB) and neuropeptide receptors NPY1R, NPY5R

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    BACKGROUND: Autism is a pervasive developmental disorder characterized by a triad of deficits: qualitative impairments in social interactions, communication deficits, and repetitive and stereotyped patterns of behavior. Although autism is etiologically heterogeneous, family and twin studies have established a definite genetic basis. The inheritance of idiopathic autism is presumed to be complex, with many genes involved; environmental factors are also possibly contributory. The analysis of chromosome abnormalities associated with autism contributes greatly to the identification of autism candidate genes. CASE PRESENTATION: We describe a child with autistic disorder and an interstitial deletion on chromosome 4q. This child first presented at 12 months of age with developmental delay and minor dysmorphic features. At 4 years of age a diagnosis of Pervasive Developmental Disorder was made. At 11 years of age he met diagnostic criteria for autism. Cytogenetic studies revealed a chromosome 4q deletion. The karyotype was 46, XY del 4 (q31.3-q33). Here we report the clinical phenotype of the child and the molecular characterization of the deletion using molecular cytogenetic techniques and analysis of polymorphic markers. These studies revealed a 19 megabase deletion spanning 4q32 to 4q34. Analysis of existing polymorphic markers and new markers developed in this study revealed that the deletion arose on a paternally derived chromosome. To date 33 genes of known or inferred function are deleted as a consequence of the deletion. Among these are the AMPA 2 gene that encodes the glutamate receptor GluR2 sub-unit, GLRA3 and GLRB genes that encode glycine receptor subunits and neuropeptide Y receptor genes NPY1R and NPY5R. CONCLUSIONS: The deletion in this autistic subject serves to highlight specific autism candidate genes. He is hemizygous for AMPA 2, GLRA3, GLRB, NPY1R and NPY5R. GluR2 is the major determinant of AMPA receptor structure. Glutamate receptors maintain structural and functional plasticity of synapses. Neuropeptide Y and its receptors NPY1R and NPY5R play a role in hippocampal learning and memory. Glycine receptors are expressed in very early cortical development. Molecular cytogenetic studies and DNA sequence analysis in other patients with autism will be necessary to confirm that these genes are involved in autism
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