Colored Non-Crossing Euclidean Steiner Forest

Given a set of $k$-colored points in the plane, we consider the problem of finding $k$ trees such that each tree connects all points of one color class, no two trees cross, and the total edge length of the trees is minimized. For $k=1$, this is the well-known Euclidean Steiner tree problem. For general $k$, a $k\rho$-approximation algorithm is known, where $\rho \le 1.21$ is the Steiner ratio. We present a PTAS for $k=2$, a $(5/3+\varepsilon)$-approximation algorithm for $k=3$, and two approximation algorithms for general~$k$, with ratios $O(\sqrt n \log k)$ and $k+\varepsilon$

Management of Spastic Paresis and Cervical Dystonia: access to Therapeutic Innovations Through an International Program of Practical Courses

Purpose: Our purpose was to determine satisfaction and confidence of the Ixcellence Network training program on health care practitioners using botulinum toxin A (BoNT-A) for neurologic disorders, including spastic paresis and cervical dystonia. / Methods: The Ixcellence Network training program was designed by a scientific committee of 6 experts and then tested at centers in Europe, and Latin America. The training, provided by 16 experienced neurologists and rehabilitation specialists, consisted of theoretic and practical sessions that covered the different stages of the patient's journey from diagnosis to tailored treatment and rehabilitation. Trainees' feedback and the impact on participants' practice were evaluated by 2 individual questionnaires, at the end of the session (T0) and at 6 months (T6). Trainers' feedback was also collected through an individual questionnaire. / Findings: Between September 2012 and December 2017, 728 trained physicians participated in training programs with 48%, 23%, and 29% of attendees participating in training sessions dedicated to adult spastic paresis, child spastic paresis, and cervical dystonia, respectively. At T0, 93% of attendees thought that they had been given new information and 90% thought that the training would change their daily practice. This was confirmed at T6 by 93% of respondents. Trainees were highly satisfied with the program, in particular with the practical sessions. Trainers expectations were met for attendees' level of expertise, motivation, language, and participation. / Implications: In this descriptive study, we show that the Ixcellence Network program represents a new educational approach to promote consistency in care practices and dissemination of expertise on the use of BoNT-A for neurologic disorders.

Atomic Layer Deposition of Ni Thin Films and Application to Area-Selective Deposition

Ni thin films were deposited by atomic layer deposition (ALD) using bis(dimethylamino-2-methyl-2-butoxo)nickel [Ni(dmamb)(2)] as a precursor and NH3 gas as a reactant. The growth characteristics and film properties of ALD Ni were investigated. Low-resistivity films were deposited on Si and SiO2 substrates, producing high-purity Ni films with a small amount of oxygen and negligible amounts of nitrogen and carbon. Additionally, ALD Ni showed excellent conformality in nanoscale via holes. Utilizing this conformality, Ni/Si core/shell nanowires with uniform diameters were fabricated. By combining ALD Ni with octadecyltrichlorosilane (OTS) self-assembled monolayer as a blocking layer, area-selective ALD was conducted for selective deposition of Ni films. When performed on the prepatterned OTS substrate, the Ni films were selectively coated only on OTS-free regions, building up Ni line patterns with 3 mu m width. Electrical measurement results showed that all of the Ni lines were electrically isolated, also indicating the selective Ni deposition. (C) 2010 The Electrochemical Society. [DOI: 10.1149/1.3504196] All rights reserved.ope

Identification of hip fracture patients from radiographs using Fourier analysis of the trabecular structure: a cross-sectional study

Peer reviewedPublisher PD

Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)

A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Interference of H-bonding and substituent effects in nitro- and hydroxy-substituted salicylaldehydes

Two intramolecular interactions, i.e., (1) hydrogen bond and (2) substituent effect, were analyzed and compared. For this purpose, the geometry of 4- and 5-X-substituted salicylaldehyde derivatives (X = NO2, H or OH) was optimized by means of B3LYP/6-311 + G(d,p) and MP2/aug-cc-pVDZ methods. The results obtained allowed us to show that substituents (NO2 or OH) in the para or meta position with respect to either OH or CHO in H-bonded systems interact more strongly than in the case of di-substituted species: 4- and 3-nitrophenol or 4- and 3-hydroxybenzaldehyde by ∼31%. The substituent effect due to the intramolecular charge transfer from the para-counter substituent (NO2) to the proton-donating group (OH) is ∼35% greater than for the interaction of para-OH with the proton-accepting group (CHO). The total energy of H-bonding for salicylaldehyde, and its derivatives, is composed of two contributions: ∼80% from the energy of H-bond formation and ∼20% from the energy associated with reorganization of the electron structure of the systems in question

Complexity of case mix in a regional allergy service

<p>Abstract</p> <p>Background</p> <p>Currently in the United Kingdom (UK), there is a mismatch between limited financial resources and the large proportion of patients with suspected allergies actually being referred to specialist allergy clinics. To better understand the case mix of patients being referred, we audited referrals to a regional allergy service over an 8 year period.</p> <p>The main source of data was consultant letters to General Practitioners (GP) summarising the diagnosis of patients, archived from January 2002 to September 2009. Letters were reviewed, extracting the clinic date, doctor seen, gender, date of birth, postcode, GP, and diagnoses. Diagnoses were classified into seven groups and illustrative cases for each group noted.</p> <p>Findings</p> <p>Data from 2,028 new referrals with suspected allergy were analysed. The largest group of patients (43%) were diagnosed with a type I hypersensitivity. The other diagnostic groups were chronic idiopathic (spontaneous) urticaria (35%), suspected type I hypersensitivity but no allergen identified (8%), idiopathic (spontaneous) angioedema (8%), physical urticaria (2.5%), non-allergic symptoms (1.6%), type IV hypersensitivity (0.8%) and ACE inhibitor sensitivity (0.5%). Two thirds of patients seen were female with a higher percentage of female patients in the non type-I hypersensitivity group (71%) than the type 1 hypersensitivity (66%) (χ²= 5.1, 1df, <it>p = 0.024</it>). The type 1 hypersensitivity patients were younger than other patients (38 Vs 46 years, t = -10.8, <it>p < 0.001</it>)</p> <p>Conclusions</p> <p>This study highlights the complexity of specialist allergy practice and the large proportion of patients referred with non-type I hypersensitivities, chronic idiopathic (spontaneous) urticaria being by far the largest group. Such information is critical to inform commissioning decisions, define referral pathways and in primary care education.</p

The psychiatric phenotypes of 1q21 distal deletion and duplication

Copy number variants are amongst the most highly penetrant risk factors for psychopathology and neurodevelopmental deficits, but little information about the detailed clinical phenotype associated with particular variants is available. We present the largest study of the microdeletion and -duplication at the distal 1q21 locus, which has been associated with schizophrenia and intellectual disability, in order to investigate the range of psychiatric phenotypes. Clinical and cognitive data from 68 deletion and 55 duplication carriers were analysed with logistic regression analysis to compare frequencies of mental disorders between carrier groups and controls, and linear mixed models to compare quantitative phenotypes. Both children and adults with copy number variants at 1q21 had high frequencies of psychopathology. In the children, neurodevelopmental disorders were most prominent (56% for deletion, 68% for duplication carriers). Adults had increased prevalence of mood (35% for deletion [OR = 6.6 (95% CI: 1.4-40.1)], 55% for duplication carriers [8.3 (1.4-55.5)]) and anxiety disorders (24% [1.8 (0.4-8.4)] and 55% [10.0 (1.9-71.2)]). The adult group, which included mainly genetically affected parents of probands, had an IQ in the normal range. These results confirm high prevalence of neurodevelopmental disorders associated with CNVs at 1q21 but also reveal high prevalence of mood and anxiety disorders in a high-functioning adult group with these CNVs. Because carriers of neurodevelopmental CNVs who show relevant psychopathology but no major cognitive impairment are not currently routinely receiving clinical genetic services widening of genetic testing in psychiatry may be considered

A homozygous ATAD1 mutation impairs postsynaptic AMPA receptor trafficking and causes a lethal encephalopathy

Members of the AAA+ superfamily of ATPases are involved in the unfolding of proteins and disassembly of protein complexes and aggregates. ATAD1 encoding the ATPase family, AAA+ domain containing 1-protein Thorase plays an important role in the function and integrity of mitochondria and peroxisomes. Postsynaptically, Thorase controls the internalization of excitatory, glutamatergic AMPA receptors by disassembling complexes between the AMPA receptor-binding protein, GRIP1, and the AMPA receptor subunit GluA2. Using whole-exome sequencing, we identified a homozygous frameshift mutation in the last exon of ATAD1 [c.1070_1071delAT; p.(His357Argfs*15)] in three siblings who presented with a severe, lethal encephalopathy associated with stiffness and arthrogryposis. Biochemical and cellular analyses show that the C-terminal end of Thorase mutant gained a novel function that strongly impacts its oligomeric state, reduces stability or expression of a set of Golgi, peroxisomal and mitochondrial proteins and affects disassembly of GluA2 and Thorase oligomer complexes. Atad1−/− neurons expressing Thorase mutantHis357Argfs*15 display reduced amount of GluA2 at the cell surface suggesting that the Thorase mutant may inhibit the recycling back and/or reinsertion of AMPA receptors to the plasma membrane. Taken together, our molecular and functional analyses identify an activating ATAD1 mutation as a new cause of severe encephalopathy and congenital stiffness