In this article, we review the PET neuroimaging literature, which indicates peculiarities of brain networks involved in speech restoration after cochlear implantation. We consider data on implanted ...patients during stimulation as well as during resting state, which indicates basic long-term reorganisation of brain functional architecture. On the basis of our analysis of neuroimaging literature and considering our own studies, we indicate that auditory recovery in deaf patients after cochlear implantation partly relies on visual cues. The brain develops mechanisms of audio-visual integration as a strategy to achieve high levels of speech recognition. It turns out that this neuroimaging evidence is in line with behavioural findings of better audiovisual integration in these patients. Thus, strong visually and audio-visually based rehabilitation during the first months after cochlear implantation would significantly improve and fasten the functional recovery of speech intelligibility and other auditory functions in these patients. We provide perspectives for further neuroimaging studies in cochlear implanted patients, which would help understand brain organisation to restore auditory cognitive processing in the implanted patients and would potentially suggest novel approaches for their rehabilitation.
This article is part of a Special Issue entitled <Lasker Award>.
•We review the PET data of brain activity post-implantation.•Brain plasticity is important for auditory recovery after cochlear implantation.•The degraded auditory signal requires the support of the visual channel.•Audio-visual brain plasticity constitutes a key element of brain reorganisation.
Abstract INTRODUCTION Despite a two‐fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts. METHODS Genome‐wide association studies (GWAS) ...of 2,903 AD cases and 6,265 controls of African ancestry. Within‐dataset results were meta‐analyzed, followed by functional genomics analyses. RESULTS A novel AD‐risk locus was identified in MPDZ on chromosome (chr) 9p23 (rs141610415, MAF = 0.002, P = 3.68×10 −9 ). Two additional novel common and nine rare loci were identified with suggestive associations ( P < 9×10 −7 ). Comparison of association and linkage disequilibrium (LD) patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 ( ASCL1 ), suggesting that this association is modulated by regional origin of local African ancestry. DISCUSSION These analyses identified novel AD‐associated loci in individuals of African ancestry and suggest that degree of African ancestry modulates some associations. Increased sample sets covering as much African genetic diversity as possible will be critical to identify additional loci and deconvolute local genetic ancestry effects. Highlights Genetic ancestry significantly impacts risk of Alzheimer's Disease (AD). Although individuals of African ancestry are twice as likely to develop AD, they are vastly underrepresented in AD genomics studies. The Alzheimer's Disease Genetics Consortium has previously identified 16 common and rare genetic loci associated with AD in African American individuals. The current analyses significantly expand this effort by increasing the sample size and extending ancestral diversity by including populations from continental Africa. Single variant meta‐analysis identified a novel genome‐wide significant AD‐risk locus in individuals of African ancestry at the MPDZ gene, and 11 additional novel loci with suggestive genome‐wide significance at P < 9×10−7. Comparison of African American datasets with samples of higher degree of African ancestry demonstrated differing patterns of association and linkage disequilibrium at one of these loci, suggesting that degree and/or geographic origin of African ancestry modulates the effect at this locus. These findings illustrate the importance of increasing number and ancestral diversity of African ancestry samples in AD genomics studies to fully disentangle the genetic architecture underlying AD, and yield more effective ancestry‐informed genetic screening tools and therapeutic interventions.
The high-temperature oxidation tests were carried out for the regular fuel rod claddings specimens made of sponge-based zirconium alloy (E110G) and for the accident tolerant fuel (ATF) ones - pure ...vacuum melted molybdenum (VCPM) and niobium alloy (Nb-1%Zr). The tests were carried out under the ambient pressure p ∼ 0.1 MPa in pure water steam. The experimental data on the oxidation characteristics were obtained for E110G specimens in the temperature range T = 1100 − 1500 °C, that for VCPM and Nb-1%Zr are investigated under extended temperature-duration range (more than 1 hour). The thermal effects of molybdenum (QSMR) and niobium (QSNR) interactions with steam were defined and the derived oxidation rate constants for refractory metals were compared with the known ones. Based on the computations performed with PARAM-TG code the high-temperature oxidation characteristics of model fuel assemblies of large-scale facilities under LOCA conditions with regular and ATF claddings were compared. It was shown that Zr-steam interaction of fuel rod cladding (QSZR) is more intensive compared with VCPM and Nb-1%Zr ones under investigated conditions.
Seventeen patients with advanced prostate cancer were studied to evaluate the pharmacokinetics and pharmacodynamics of a hydrogel implant designed to deliver histrelin at a constant rate (50 ...microg/d) for 1 year. Serum histrelin levels were collected during the 52-week implantation period and after a second implant. Testosterone suppression was the primary pharmacodynamic endpoint, with treatment success defined as serum testosterone less than 50 ng/dL. The histrelin subdermal implant delivered constant histrelin levels, with mean serum histrelin of approximately 0.265 ng/mL over 52 weeks. At the end of 52 weeks, mean histrelin concentrations were 0.128 +/- 0.0652 ng/mL. Patients achieved chemical castration (testosterone less than 50 ng/mL) by week 4. In patients who had the first implant removed and received a new implant at the end of the first 52 weeks, testosterone suppression was not interrupted. The hydrogel implant provided consistent delivery of histrelin over 1 year and effectively suppressed testosterone in men with prostate cancer.
A moderate number of oval-shaped, 114.7 × 61.3 μm in size, amber-colored, arthropod-like eggs that had chitinous, smooth, semi-thickened outer wall and 2-4 short appendages armed with 2 terminal ...hook-like structures were detected in multiple fecal samples from an approximately 9-month-old, intact female, collie-mixed dog that had been recently imported from Ethiopia to Oklahoma, United States. Initially the unusual arthropod-like eggs were considered to be a pseudoparasite, most likely mite eggs. However, based on the history of the dog, morphology of the eggs, and presence of the eggs in repetitive fecal flotations, a pentastomid, Linguatula serrata, was suspected. DNA extraction and PCR analysis of the partial 18S rRNA gene were performed on the eggs, and nucleic acid sequence showed 100% homology to L. serrata, a parasite of dogs, and L. arctica, a parasite of Norwegian reindeers. Rhinoscopy and head CT scan on the dog failed to demonstrate adult parasites or detect any pathologic changes. At this time, pentastomid eggs were no longer observed on fecal flotation. Due to the possibility of juvenile stages of the parasite still migrating in the dog, fluralaner (Bravecto®, Merck) was administered and continuing treatment recommended for at least 6 months. A follow-up fecal examination conducted a month after the treatment did not reveal any parasites or eggs. This is a case report of canine linguatuliasis diagnosed in Oklahoma, United States.
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Background: Currently, low molecular weight heparin is the guideline endorsed treatment of patients with cancer associated venous thromboembolism (VTE). While apixaban is approved for the treatment ...of acute VTE, there are limited data supporting its use in cancer patients.
Methods: Patients with cancer associated acute VTE were randomly assigned to receive either apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily or subcutaneous dalteparin (200 IU/kg for 1 month followed by 150 IU/kg once daily) for 6 months. The primary outcome was major bleeding. Secondary outcomes included VTE recurrence and a composite of major plus clinically relevant non-major bleeding.
Results: Of the 300 patients who underwent randomization, 287 were included in the primary analysis. Of these, metastatic disease was present in 65.5% of subjects and 74% were receiving concurrent systemic cancer therapy. Colorectal, lung, pancreas, and breast cancers were the four most prevalent cancer types. Major bleeding occurred in 0 of the 142 patients (0%) in the apixaban group as compared with 3 of the 145 patients (2.1%) in the dalteparin group (p=0.9956). Recurrent VTE occurred in 5 patients (3.4%) in the apixaban group and 20 patients (14.1%) in the dalteparin group (difference in risk -10.7 percentage points) with a Hazard Ratio (HR) 0.26, (95% CI, 0.09 - 0.80, p = 0.0182). Major plus clinically relevant non-major bleeding were similar at 9% for both groups. There were no mortality differences comparing apixaban (15.9%) and dalteparin (10.6%) groups at 6 months (HR 1.36, 95% CI 0.79 - 2.35). Monthly quality of life surveys favored apixaban therapy for many measures including: concern for excess bruising, stress, irritation, burden of delivery, and overall satisfaction with anticoagulant therapy (p<0.05). Monthly bruising questionnaire favored apixaban at each interval (p<0.002).
Conclusions: Oral apixaban therapy was associated with very low rates of bleeding and significantly lower VTE recurrence with superior quality of life outcome measures compared to parenteral dalteparin in the treatment of cancer associated VTE. These data support the clinical utility of apixaban for the acute treatment of VTE in this patient population.
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No relevant conflicts of interest to declare.
The Alzheimer's Disease Sequencing Project (ADSP) performed whole genome sequencing (WGS) of 584 subjects from 111 multiplex families at three sequencing centers. Genotype calling of single ...nucleotide variants (SNVs) and insertion-deletion variants (indels) was performed centrally using GATK-HaplotypeCaller and Atlas V2. The ADSP Quality Control (QC) Working Group applied QC protocols to project-level variant call format files (VCFs) from each pipeline, and developed and implemented a novel protocol, termed “consensus calling,” to combine genotype calls from both pipelines into a single high-quality set. QC was applied to autosomal bi-allelic SNVs and indels, and included pipeline-recommended QC filters, variant-level QC, and sample-level QC. Low-quality variants or genotypes were excluded, and sample outliers were noted. Quality was assessed by examining Mendelian inconsistencies (MIs) among 67 parent-offspring pairs, and MIs were used to establish additional genotype-specific filters for GATK calls. After QC, 578 subjects remained. Pipeline-specific QC excluded ~12.0% of GATK and 14.5% of Atlas SNVs. Between pipelines, ~91% of SNV genotypes across all QCed variants were concordant; 4.23% and 4.56% of genotypes were exclusive to Atlas or GATK, respectively; the remaining ~0.01% of discordant genotypes were excluded. For indels, variant-level QC excluded ~36.8% of GATK and 35.3% of Atlas indels. Between pipelines, ~55.6% of indel genotypes were concordant; while 10.3% and 28.3% were exclusive to Atlas or GATK, respectively; and ~0.29% of discordant genotypes were. The final WGS consensus dataset contains 27,896,774 SNVs and 3,133,926 indels and is publicly available.
•The ADSP performed quality control of whole genome sequencing from 584 samples called on two pipelines, AtlasV2 and GATK-HC.•QC filtered at genotype, variant, and sample levels; QCed calls from each pipeline were integrated with “consensus calling.”•This novel QC protocol added in 4.3% more SNVs and 28.8% more indels than QC on genotypes from one calling pipeline.
Sedentary behavior is associated with an attenuated thermogenic response to beta-adrenergic receptor (beta-AR) stimulation, an important regulator of energy expenditure (EE) in humans. Chronic ...stimulation of beta-ARs, via heightened activity of the sympathoadrenal system, leads to diminished beta-AR function. We have investigated the hypothesis that the thermogenic response of sedentary adults to beta-AR stimulation will be increased during short-term sympathoadrenal inhibition. Using a randomly ordered, repeated measures study design, resting EE (REE; indirect calorimetry, ventilated hood technique) and the % increase in EE above REE (%DeltaEE) during acute i.v. isoproterenol administration (nonselective beta-AR agonist; 6, 12, and 24 ng/kg fat-free mass per min) were determined in 16 sedentary adults (nine females and seven males, 25+/-1 years, body mass index: 26.1+/-0.9 kg/m(2), maximal oxygen uptake: 40+/-2 ml/kg per min (mean+/-s.e.m.)) in the basal state and on the 6th day of transdermal clonidine administration (centrally acting alpha2-AR agonist; 0.2 mg/day). Relative to baseline, clonidine inhibited sympathoadrenal activity, as evidenced by decreased plasma norepinephrine concentration (1.04+/-0.13 vs 0.34+/-0.03 nmol/l; P<0.001), skeletal muscle sympathetic nerve activity (22.5+/-3.8 vs 8.5+/-1.9 bursts/min; P=0.003), and resting heart rate (63+/-2 vs 49+/-1 beats/min; P<0.001). Sympathoadrenal inhibition decreased REE (6510+/-243 vs 5857+/-218 kJ/day; P<0.001), increased respiratory exchange ratio (0.84+/-0.01 vs 0.86+/-0.01; P=0.03), and augmented the thermogenic response to beta-AR stimulation (%DeltaEE: 11+/-2, 16+/-2, and 24+/-2 vs 14+/-1, 20+/-2, and 31+/-2; P=0.04). These data demonstrate that in sedentary humans, short-term inhibition of sympathoadrenal activity increases the thermogenic response to beta-AR stimulation, an important determinant of EE and hence energy balance.
Changes in the nanohardness
H
and Young’s modulus
E
of Ge
x
As
y
Se
100 −
x
−
y
films have been studied as a function of the penetration depth of the Berkovich indenter. The values of
H
and
E
have ...been measured in the regime of harmonic modulation of a linearly increasing indenter load. It has been shown that the changes in
E
and
H
of the films under study during nanoindentation arise due to the peculiarities of their elastoplastic behavior, the formation of deformation zones near the nanocontact, and also size effects.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease mainly affecting upper and lower motor neurons in the brain and spinal cord. Pathogenesis of ALS is still unclear, and a ...multifactorial etiology is presumed. The remarkable clinical heterogeneity between different phenotypes of ALS patients suggests that environmental and lifestyle factors could play a role in onset and progression of ALS. We analyzed a cohort of 117 ALS patients and 93 controls. ALS patients and controls were compared regarding physical activity, dietary habits, smoking, residential environment, potentially toxic environmental factors and profession before symptom onset and throughout the disease course. Data were collected by a personal interview. For statistical analysis descriptive statistics, statistical tests and analysis of variance were used. ALS patients and controls did not differ regarding smoking, diet and extent of physical training. No higher frequency of toxic influences could be detected in the ALS group. ALS patients lived in rural environment considerably more often than the control persons, but this was not associated with a higher percentage of occupation in agriculture. There was also a higher percentage of university graduates in the ALS group. Patients with bulbar onset were considerably more often born in an urban environment as compared to spinal onset. Apart from education and environment, ALS phenotypes did not differ in any investigated environmental or life-style factor. The rate of disease progression was not influenced by any of the investigated environmental and life-style factors. The present study could not identify any dietary habit, smoking, physical activity, occupational factor as well as toxic influences as risk factor or protective factor for onset or progression of ALS. Living in rural environment and higher education might be associated with higher incidence of ALS.
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