Weighted Sobolev spaces of radially symmetric functions

We prove dilation invariant inequalities involving radial functions, poliharmonic operators and weights that are powers of the distance from the origin. Then we discuss the existence of extremals and in some cases we compute the best constants.Comment: 38 page

Multiple Promoters and Alternative Splicing: Hoxa5 Transcriptional Complexity in the Mouse Embryo

The genomic organization of Hox clusters is fundamental for the precise spatio-temporal regulation and the function of each Hox gene, and hence for correct embryo patterning. Multiple overlapping transcriptional units exist at the Hoxa5 locus reflecting the complexity of Hox clustering: a major form of 1.8 kb corresponding to the two characterized exons of the gene and polyadenylated RNA species of 5.0, 9.5 and 11.0 kb. This transcriptional intricacy raises the question of the involvement of the larger transcripts in Hox function and regulation.We have undertaken the molecular characterization of the Hoxa5 larger transcripts. They initiate from two highly conserved distal promoters, one corresponding to the putative Hoxa6 promoter, and a second located nearby Hoxa7. Alternative splicing is also involved in the generation of the different transcripts. No functional polyadenylation sequence was found at the Hoxa6 locus and all larger transcripts use the polyadenylation site of the Hoxa5 gene. Some larger transcripts are potential Hoxa6/Hoxa5 bicistronic units. However, even though all transcripts could produce the genuine 270 a.a. HOXA5 protein, only the 1.8 kb form is translated into the protein, indicative of its essential role in Hoxa5 gene function. The Hoxa6 mutation disrupts the larger transcripts without major phenotypic impact on axial specification in their expression domain. However, Hoxa5-like skeletal anomalies are observed in Hoxa6 mutants and these defects can be explained by the loss of expression of the 1.8 kb transcript. Our data raise the possibility that the larger transcripts may be involved in Hoxa5 gene regulation.Our observation that the Hoxa5 larger transcripts possess a developmentally-regulated expression combined to the increasing sum of data on the role of long noncoding RNAs in transcriptional regulation suggest that the Hoxa5 larger transcripts may participate in the control of Hox gene expression

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass X-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the $\mathcal{J}$-statistic, and by analysing data from Advanced LIGO's second observing run. In the frequency range searched, from $60$ to $650\,\mathrm{Hz}$, we find no evidence of gravitational radiation. At $194.6\,\mathrm{Hz}$, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95\% confidence) of $h_0^{95\%} = 3.47 \times 10^{-25}$ when marginalising over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering

Magnetic resonance imaging of the erector spinae muscles in Duchenne muscular dystrophy: implication for scoliotic deformities

<p>Abstract</p> <p>Background</p> <p>In Duchenne muscular dystrophy (DMD), the muscular degeneration often leads to the development of scoliosis. Our objective was to investigate how anatomical changes in back muscles can lead to scoliosis. Muscular volume and the level of fat infiltration in those muscles were thus evaluated, in non-scoliotic, pre-scoliotic and scoliotic patients. The overlying skin thickness over the apex level of scoliotic deformations was also measured to facilitate the interpretation of electromyographic signals when recorded on the skin surface.</p> <p>Methods</p> <p>In 8 DMD patients and two healthy controls with no known muscular deficiencies, magnetic resonance imaging (MRI) was used to measure continuously at 3 mm intervals the distribution of the erector spinae (ES) muscle in the T8-L4 region as well as fat infiltration in the muscle and overlying skin thickness: four patients were non-scoliotic (NS), two were pre-scoliotic (PS, Cobb angle < 15°) and two were scoliotic (S, Cobb angle ≥ 15°). For each subject, 63 images 3 mm thick of the ES muscle were obtained in the T8-L4 region on both sides of the spine. The pixel dimension was 0.39 × 0.39 mm. With a commercial software, on each 12 bits image, the ES contour on the left and on the right sides of the spine were manually determined as well as those of its constituents i.e., the iliocostalis (IL), the longissimus (LO) and the spinalis (SP) muscles. Following this segmentation, the surfaces within the contours were determined, the muscles volume were obtained, the amount of fat infiltration inside each muscle was evaluated and the overlying skin thickness measured.</p> <p>Findings</p> <p>The volume of the ES muscle of our S and PS patients was found smaller on the convex side relative to the concave one by 5.3 ± 0.7% and 2.8 ± 0.2% respectively. For the 4 NS patients, the volume difference of this muscle between right and left sides was 2.1 ± 1.5% and for the 2 controls, it was 1.4 ± 1.2%. Fat infiltration for the S and the PS patients was larger on the convex side than on the concave one (4.4 ± 1.6% and 4.5 ± 0.7% respectively) and the difference was more important near the apex. Infiltration was more important in the lateral IL muscle than in the medial SP and it was always larger near L2 than at any other spinal level. Fat infiltration was much more important in the ES for the DMD patients (49.9% ± 1.6%) than for the two controls (2.6 ± 0.8%). As for the overlying skin thickness measured near the deformity of the patients, it was larger on the concave than on the convex side: 14.8 ± 6.1 vs 13.5 ± 5.7 mm for the S and 10.3 ± 6.3 vs 9.8 ± 5.6 mm for the PS.</p> <p>Interpretation</p> <p>In DMD patients, our results indicate that a larger replacement of muscles fibers by fat infiltration on one side of the spine is a factor that can lead to the development of scoliosis. Efforts to slow such an infiltration on the most affected side of the spine could thus be beneficial to those patients by delaying the apparition of the scoliotic deformation. In addition to anatomical considerations, results obtained from the same patients but in experiments dealing with electromyography recordings, point to differences in the muscular contraction mechanisms and/or of the neural input to back muscles. This is similar to the adolescent idiopathic scoliosis (AIS) where a role of the nervous system in the development of the deformation has also been suggested.</p

Set optimization - a rather short introduction

Recent developments in set optimization are surveyed and extended including various set relations as well as fundamental constructions of a convex analysis for set- and vector-valued functions, and duality for set optimization problems. Extensive sections with bibliographical comments summarize the state of the art. Applications to vector optimization and financial risk measures are discussed along with algorithmic approaches to set optimization problems

Overt is no better than covert when rehearsing visuo-spatial information in working memory

In the present study, we examined whether eye movements facilitate retention of visuo-spatial information in working memory. In two experiments, participants memorised the sequence of the spatial locations of six digits across a retention interval. In some conditions, participants were free to move their eyes during the retention interval, but in others they either were required to remain fixated or were instructed to move their eyes exclusively to a selection of the memorised locations. Memory performance was no better when participants were free to move their eyes during the memory interval than when they fixated a single location. Furthermore, the results demonstrated a primacy effect in the eye movement behaviour that corresponded with the memory performance. We conclude that overt eye movements do not provide a benefit over covert attention for rehearsing visuo-spatial information in working memory

Biomechanical analysis and modeling of different vertebral growth patterns in adolescent idiopathic scoliosis and healthy subjects

<p>Abstract</p> <p>Background</p> <p>The etiology of AIS remains unclear, thus various hypotheses concerning its pathomechanism have been proposed. To date, biomechanical modeling has not been used to thoroughly study the influence of the abnormal growth profile (i.e., the growth rate of the vertebral body during the growth period) on the pathomechanism of curve progression in AIS. This study investigated the hypothesis that AIS progression is associated with the abnormal growth profiles of the anterior column of the spine.</p> <p>Methods</p> <p>A finite element model of the spinal column including growth dynamics was utilized. The initial geometric models were constructed from the bi-planar radiographs of a normal subject. Based on this model, five other geometric models were generated to emulate different coronal and sagittal curves. The detailed modeling integrated vertebral body growth plates and growth modulation spinal biomechanics. Ten years of spinal growth was simulated using AIS and normal growth profiles. Sequential measures of spinal alignments were compared.</p> <p>Results</p> <p>(1) Given the initial lateral deformity, the AIS growth profile induced a significant Cobb angle increase, which was roughly between three to five times larger compared to measures utilizing a normal growth profile. (2) Lateral deformities were absent in the models containing no initial coronal curvature. (3) The presence of a smaller kyphosis did not produce an increase lateral deformity on its own. (4) Significant reduction of the kyphosis was found in simulation results of AIS but not when using the growth profile of normal subjects.</p> <p>Conclusion</p> <p>Results from this analysis suggest that accelerated growth profiles may encourage supplementary scoliotic progression and, thus, may pose as a progressive risk factor.</p

WHEDA study: Effectiveness of occupational therapy at home for older people with dementia and their caregivers - the design of a pragmatic randomised controlled trial evaluating a Dutch programme in seven German centres

Contains fulltext : 80941.pdf (publisher's version ) (Open Access)BACKGROUND: A recent Dutch mono-centre randomised controlled trial has shown that occupational therapy improves daily functioning in dementia. The aim of this present study is to compare the effects of the Dutch community occupational therapy programme with a community occupational therapy consultation on daily functioning in older people with mild or moderate dementia and their primary caregivers in a German multi-centre context. METHODS/DESIGN: A multi-centre single blind randomised controlled trial design is being used in seven health care centres (neurological, psychiatric and for older people) in urban regions. Patients are 1:1 randomised to treatment or control group. Assessors are blind to group assignment and perform measurements on both groups at baseline, directly after intervention at 6 weeks and at 16, 26 and 52 weeks follow-up. A sample of 140 community dwelling older people (aged >65 years) with mild or moderate dementia and their primary caregivers is planned. The experimental intervention consists of an evidence-based community occupational therapy programme including 10 sessions occupational therapy at home. The control intervention consists of one community occupational therapy consultation based on information material of the Alzheimer Society. Providers of both interventions are occupational therapists experienced in treatment of cognitively impaired older people and trained in both programmes. 'Community' indicates that occupational therapy intervention occurs in the person's own home. The primary outcome is patients' daily functioning assessed with the performance scale of the Interview for Deterioration in Daily Living Activities in Dementia and video tapes of daily activities rated by external raters blind to group assignment using the Perceive, Recall, Plan and Perform System of Task Analysis. Secondary outcomes are patients' and caregivers' quality of life, mood and satisfaction with treatment; the caregiver's sense of competence, caregiver's diary (medication, resource utilisation, time of informal care); and the incidence of long-term institutionalisation. Process evaluation is performed by questionnaires and focus group discussion. DISCUSSION: The transfer from the Dutch mono-centre design to the pragmatic multi-site trial in a German context implicates several changes in design issues including differences in recruitment time, training of interventionists and active control group treatment.The study is registered under DRKS00000053 at the German register of clinical trials, which is connected to the International Clinical Trials Registry Platform

Targeted therapies in colorectal cancer: an integrative view by PPPM

In developed countries, colorectal cancer (CRC) is the third most common malignancy, but it is the second most frequent cause of cancer-related death. Clinicians are still faced with numerous challenges in the treatment of this disease, and future approaches which target the molecular features of the disorder will be critical for success in this disease setting. Genetic analyses of many solid tumours have shown that up to 100 protein-encoding genes are mutated. Within CRC, numerous genetic alterations have been identified in a number of pathways. Therefore, understanding the molecular pathology of CRC may present information on potential routes for treatment and may also provide valuable prognostic information. This will be particularly pertinent for molecularly targeted treatments, such as anti-vascular endothelial growth factor therapies and anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy. KRAS and BRAF mutations have been shown to predict response to anti-EGFR therapy. As EGFR can also signal via the phosphatidylinositol 3-kinase (PI3K) kinase pathway, there is considerable interest in the potential roles of members of this pathway (such as PI3K and PTEN) in predicting treatment response. Therefore, a combined approach of new techniques that allow identification of these biomarkers alongside interdisciplinary approaches to the treatment of advanced CRC will aid in the treatment decision-making process and may also serve to guide future therapeutic approaches