Ratings of Overall Olfactory Function

The aim of this study was to investigate the accuracy of self-reported ratings of olfactory function in 83 healthy subjects. Such ratings were compared with quantitative measures of olfactory function, as well as with ratings of nasal patency. In experiment 1 subjects rated olfactory function and nasal patency before olfactory testing, whereas in experiment 2 the reverse was the case. No feedback regarding test results were provided until after completion of the testing. The principal findings were: (i) when ratings preceded measurements of olfactory function, there was no significant correlation between the two parameters. However, ratings of olfactory function correlated significantly with ratings of nasal airway patency. (ii) In contrast, when measurements of olfactory function preceded the ratings, this constellation switched. Now ratings of olfactory function correlated significantly with measured olfactory function, whereas there was no significant correlation between ratings of nasal airway patency and ratings of olfactory function. In conclusion, these data suggest that ratings of olfactory function are unreliable in healthy, untrained subjects. The ratings seem to reflect changes of nasal airway patency to a larger degree than measurable olfactory function. The results further indicate that this is mainly due to the limited attention the sense of smell receives in daily lif

EHBP1L1 Frameshift Deletion in English Springer Spaniel Dogs with Dyserythropoietic Anemia and Myopathy Syndrome (DAMS) or Neonatal Losses

Hereditary myopathies are well documented in dogs, whereas hereditary dyserythropoietic anemias are rarely seen. The aim of this study was to further characterize the clinical and clinicopathological features of and to identify the causative genetic variant for a dyserythropoietic anemia and myopathy syndrome (DAMS) in English springer spaniel dogs (ESSPs). Twenty-six ESSPs, including five dogs with DAMS and two puppies that died perinatally, were studied. Progressive weakness, muscle atrophy-particularly of the temporal and pelvic muscles-trismus, dysphagia, and regurgitation due to megaesophagus were observed at all ages. Affected dogs had a non-regenerative, microcytic hypochromic anemia with metarubricytosis, target cells, and acanthocytes. Marked erythroid hyperplasia and dyserythropoiesis with non-orderly maturation of erythrocytes and inappropriate microcytic metarubricytosis were present. Muscle biopsies showed centralized nuclei, central pallor, lipocyte infiltrates, and fibrosis, which was consistent with centronuclear myopathy. The genome sequencing of two affected dogs was compared to 782 genomes of different canine breeds. A homozygous frameshift single-base deletion in EHBP1L1 was identified; this gene was not previously associated with DAMS. Pedigree analysis confirmed that the affected ESSPs were related. Variant genotyping showed appropriate complete segregation in the family, which was consistent with an autosomal recessive mode of inheritance. This study expands the known genotype-phenotype correlation of EHBP1L1 and the list of potential causative genes in dyserythropoietic anemias and myopathies in humans. EHBP1L1 deficiency was previously reported as perinatally lethal in humans and knockout mice. Our findings enable the genetic testing of ESSP dogs for early diagnosis and disease prevention through targeted breeding strategies

EHBP1L1 Frameshift Deletion in English Springer Spaniel Dogs with Dyserythropoietic Anemia and Myopathy Syndrome (DAMS) or Neonatal Losses

Hereditary myopathies are well documented in dogs, whereas hereditary dyserythropoietic anemias are rarely seen. The aim of this study was to further characterize the clinical and clinicopathological features of and to identify the causative genetic variant for a dyserythropoietic anemia and myopathy syndrome (DAMS) in English springer spaniel dogs (ESSPs). Twenty-six ESSPs, including five dogs with DAMS and two puppies that died perinatally, were studied. Progressive weakness, muscle atrophy—particularly of the temporal and pelvic muscles—trismus, dysphagia, and regurgitation due to megaesophagus were observed at all ages. Affected dogs had a non-regenerative, microcytic hypochromic anemia with metarubricytosis, target cells, and acanthocytes. Marked erythroid hyperplasia and dyserythropoiesis with non-orderly maturation of erythrocytes and inappropriate microcytic metarubricytosis were present. Muscle biopsies showed centralized nuclei, central pallor, lipocyte infiltrates, and fibrosis, which was consistent with centronuclear myopathy. The genome sequencing of two affected dogs was compared to 782 genomes of different canine breeds. A homozygous frameshift single-base deletion in EHBP1L1 was identified; this gene was not previously associated with DAMS. Pedigree analysis confirmed that the affected ESSPs were related. Variant genotyping showed appropriate complete segregation in the family, which was consistent with an autosomal recessive mode of inheritance. This study expands the known genotype–phenotype correlation of EHBP1L1 and the list of potential causative genes in dyserythropoietic anemias and myopathies in humans. EHBP1L1 deficiency was previously reported as perinatally lethal in humans and knockout mice. Our findings enable the genetic testing of ESSP dogs for early diagnosis and disease prevention through targeted breeding strategies

Preferential MGMT hypermethylation in SDH-deficient wild-type GIST

AIMS: Wild-type gastrointestinal stromal tumours (wtGIST) are frequently caused by inherited pathogenic variants, or somatic alterations in the succinate dehydrogenase subunit genes (SDHx). Succinate dehydrogenase is a key enzyme in the citric acid cycle. SDH deficiency caused by SDHx inactivation leads to an accumulation of succinate, which inhibits DNA and histone demethylase enzymes, resulting in global hypermethylation. Epigenetic silencing of the DNA repair gene MGMT has proven utility as a positive predictor of the therapeutic efficacy of the alklyating drug temozolomide (TMZ) in tumours such as glioblastoma multiforme. The aim of this study was to examine MGMT promoter methylation status in a large cohort of GIST. METHODS: MGMT methylation analysis was performed on 65 tumour samples including 47 wtGIST (33 SDH-deficient wtGIST and 11 SDH preserved wtGIST) and 21 tyrosine kinase (TK) mutant GIST. RESULTS: MGMT promoter methylation was detected in 8 cases of SDH-deficient (dSDH) GIST but in none of the 14 SDH preserved wild-type GIST or 21 TK mutant GIST samples analysed. Mean MGMT methylation was significantly higher (p 0.0449) and MGMT expression significantly lower (p<0.0001) in dSDH wtGIST compared with TK mutant or SDH preserved GIST. No correlation was identified between SDHx subunit gene mutations or SDHC epimutation status and mean MGMT methylation levels. CONCLUSION: MGMT promoter hypermethylation occurs exclusively in a subset of dSDH wtGIST. Data from this study support testing of tumour MGMT promoter methylation in patients with dSDH wtGIST to identify those patients who may benefit from most from TMZ therapy

The new green grabbing frontier and participation: conserving drylands with or without people

Drylands have been affected by so-called green grabbing—that is, the dispossession or displacement of local communities in order to expand areas devoted to conservation, as well as the signifcant curtailment of access to natural resources by non-displaced groups (Fairhead et al. 2012). Green grabbing can take different forms, such as the removal of people from offcially protected areas (PAs), the concession of communal lands to outside investors that will develop conservationrelated activities, and the negative side-effects of community conservation (CC) programmes.info:eu-repo/semantics/publishedVersio

A Real-time System for In-home Activity Monitoring of Elders

In this paper, we propose a real-time system for in-home activity monitoring and functional assessment for elder care. We describe the development of the whole system which could be used to assist the independent living of elders and improve the efficiency of eldercare practice. With this system, data is collected, silhouettes extracted, features further analyzed and visualized into graphs from which eldercare professionals are able to understand massive video monitoring data within a short period of time. Our experimental results demonstrate that the proposed system is efficient in indoor elder activities monitoring and easily utilized by eldercare professionals.This work was supported in part by National Institutes of Health under grant 1R21AG026412-01A2

Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts

The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1–4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2–4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC

Insights from an extensive triaxial testing campaign on a shale for comparative site characterization of a deep geological repository

Several boreholes were drilled for site comparison of a deep geological repository (DGR) in Northern Switzerland. The main target of the exploration program was the >100m thick Opalinus Clay, the designated host rock encountered at approximately 450 to 1000 m depth in three different sites. This contribution focuses on the evaluation of geomechanical properties and the deformation behavior from the triaxial testing campaign, both aspects relevant to construction and the assessment of the long-term safety of a DGR. Some 140 triaxial tests were performed on cores from seven different boreholes to evaluate potential differences in material properties by depth and geographic location. Core sampling, preparation chain, and testing protocols were validated before the campaign, and three laboratories were commissioned to perform the tests. A comparison of basic properties from cores used for triaxial testing with a much larger database of complementary core analyses and geophysical logging demonstrates that the performed tests cover the range of expected material properties. Limited to no differences in strength and stiffness are detected from cores at different depths and sites. Despite a relatively large variation in bulk mineralogy of the formation (e.g. clay-mineral content varying between 35 and 75 wt%), the strength values of Opalinus Clay vary only moderately, with equivalent (calculated) unconfined compressive strengths of 21 ± 5 MPa, for loading directions parallel or perpendicular to bedding. This contrasts with the results of Opalinus Clay from the Rock Laboratory at Mont Terri, where the effect of material composition was more relevant. Assuming a Mohr-Coulomb-type failure law, the transition from peak to post-peak strength comes at the expense of cohesion, and only a small reduction of the shear strength angle. Hence the burial history, tectonic overprint, and current depth mainly control the intact properties by additional cohesion, whereas the post-peak behavior is mainly controlled by bulk mineralogy.publishedVersio

Stress field sensitivity analysis in a sedimentary sequence of the Alpine foreland, Northern Switzerland

The stress field at depth is a relevant parameter for the design of subsurface constructions and reservoir management. Yet the distortion of the regional stress field due to local-scale features such as sedimentary and tectonic structures or topography is often poorly constrained. We conduct a stress sensitivity analysis using 3-D numerical geomechanical modelling with an elasto-plastic material law to explore the impact of such site specific features on the stress field in a sedimentary sequence of the Swiss Alpine foreland. The model\u27s dimensions are 14 km × 14 km × 3 km and it contains ten units with different mechanical properties, intersected by two regional fault zones. An initial stress state is established involving a semi-empirical relationship between the ratio of horizontal to vertical stress and the overconsolidation ratio of argillaceous sediments. The model results indicate that local topography can affect the stress field significantly to depths greater than the relief contrasts at the surface, especially in conjunction with horizontal tectonic loading. The complexity and frictional properties of faults are also relevant. The greatest variability of the stress field arises across the different sedimentary units. Stress magnitudes and stress anisotropy are much larger in stiffer formations such as massive limestones than in softer argillaceous formations. The stiffer formations essentially carry the load of the far-field forces and are therefore more sensitive to changes of the boundary conditions. This general characteristic of stress distribution in the stiff and soft formations is broadly maintained also with progressive loading towards the plastic limit. The stress field in argillaceous sediments within a stack of formations with strongly contrasting mechanical properties like in the Alpine foreland appears to be relatively insensitive to changes in the tectonic boundary conditions and is largely controlled by the maximum stiffness contrast with respect to the load-bearing formations

Burden of postinfectious symptoms after acute Dengue, Vietnam.

We assessed predominantly pediatric patients in Vietnam with dengue and other febrile illness 3 months after acute illness. Among dengue patients, 47% reported >1 postacute symptom. Most resolved by 3 months, but alopecia and vision problems often persisted. Our findings provide additional evidence on postacute dengue burden and confirm children are affected