Subsquares Approach - Simple Scheme for Solving Overdetermined Interval Linear Systems

In this work we present a new simple but efficient scheme - Subsquares approach - for development of algorithms for enclosing the solution set of overdetermined interval linear systems. We are going to show two algorithms based on this scheme and discuss their features. We start with a simple algorithm as a motivation, then we continue with a sequential algorithm. Both algorithms can be easily parallelized. The features of both algorithms will be discussed and numerically tested.Comment: submitted to PPAM 201

Long survival of primary diffuse leptomeningeal gliomatosis following radiotherapy and temozolomide: case report and literature review

<p>Abstract</p> <p>Objective</p> <p>Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare neoplasm with a short survival time of a few months. there is currently no standardized therapeutic approach for PDLG.</p> <p>Materials and methods</p> <p>We report on a 53-year-old male patient who presented with epileptic seizures, gait disturbance, paraparesis and sensory deficits in the dermatomes T8-10.</p> <p>Results</p> <p>Magnetic resonance imaging (MRI) revealing numerous spinal and cranial gadolinium-enhancing nodules in the meninges and histopathology led us to diagnose primary diffuse leptomeningeal gliomatosis with WHO grade III astrocytic cells. Consecutively, the patient underwent craniospinal radiotherapy (30 Gy) and 11 sequential cycles of temozolomide. This regimen led to partial tumor regression. Thirteen months later, spinal MRI revealed tumor progression. Second-line chemotherapy with 5 cycles of irinotecan and bevacizumab did not prevent further clinical deterioration. The patient died twenty-two months after diagnosis, being the longest survival time described thus far with respect to PDLG consisting of astrocytic tumor cells.</p> <p>Conclusions</p> <p>Radiochemotherapy including temozolomide, as established standard therapy for brain malignant astrocytomas, might be valid as a basic therapeutic strategy for this PDLG subtype.</p

Novel Characteristics of Valveless Pumping

This study investigates the occurrence of valveless pumping in a fluidfilled system consisting of two open tanks connected by an elastic tube. We show that directional flow can be achieved by introducing a periodic pinching applied at an asymmetrical location along the tube, and that the flow direction depends on the pumping frequency. We propose a relation between wave propagation velocity, tube length, and resonance frequencies associated with shifts in the pumping direction using numerical simulations. The eigenfrequencies of the system are estimated from the linearized system, and we show that these eigenfrequencies constitute the resonance frequencies and the horizontal slope frequencies of the system; 'horizontal slope frequency' being a new concept. A simple model is suggested, explaining the effect of the gravity driven part of the oscillation observed in response to the tank and tube diameter changes. Results are partly compared with experimental findings.Art. no. 22450

Ubp43 gene expression is required for normal Isg15 expression and fetal development

BACKGROUND: Isg15 covalently modifies murine endometrial proteins in response to early pregnancy. Isg15 can also be severed from targeted proteins by a specific protease called Ubp43 (Usp18). Mice lacking Ubp43 (null) form increased conjugated Isg15 in response to interferon. The Isg15 system has not been examined in chorioallantoic placenta (CP) or mesometrial (MM) components of implantation sites beyond 9.5 days post coitum (dpc). It was hypothesized that deletion of Ubp43 would cause disregulation of Isg15 in implantation sites, and that this would affect pregnancy rates. METHODS: Heterozygous (het) Ubp43 mice were mated and MM and CP implantation sites were collected on 12.5 and 17.5 days post-coitum (dpc). RESULTS: Free and conjugated Isg15 were greater on 12.5 versus 17.5 dpc in MM. Free and conjugated Isg15 were also present in CP, but did not differ due to genotype on 12.5 dpc. However, null CP had greater free and conjugated Isg15 when compared to het/wt on 17.5 dpc. Null progeny died in utero with fetal genotype ratios (wt:het:null) of 2:5:1 on 12.5 and 2:2:1 on 17.5 dpc. Implantation sites were disrupted within the junctional zone and spongiotrophoblast, contained less vasculature based on lectin B4 staining and contained greater Isg15 mRNA and VEGF protein in Ubp43 null when compared to wt placenta. CONCLUSION: It is concluded that Isg15 and its conjugates are present in implantation sites during mid to late gestation and that deletion of Ubp43 causes an increase in free and conjugated Isg15 at the feto-maternal interface. Also, under mixed genetic background, deletion of Ubp43 results in fetal death

Measurement of migration of a humeral head resurfacing prosthesis using radiostereometry without implant marking: An experimental study

Today, the shoulder joint is the third most commonly replaced joint after the hip and knee joints and the incidence is increasing. In Sweden, 1863 primary Shoulder Arthroplasties and 195 revisions were performed in 2017. The most common diagnoses are Osteoarthritis and irreparable tears of the rotator cuff, with or without arthropathy, often referred to as cuff tear arthropathy. Different Shoulder Arthroplasty (SA) concepts include anatomical total shoulder arthroplasty (TSA), hemiarthroplasty (HSA) and reversed shoulder arthroplasty, but also humeral head resurfacing (HHR) and stemless arthroplasties. All concepts offer pain relief, improvement of function and in quality of life for the different diagnoses. Unfortunately, there are sometimes complications after SA. They involve periprosthetic joint infection, humeral and glenoid fractures, stress shielding, loosening of the glenoid and humeral component but also glenoid erosion and cuff rupture. Some of these complications are most common within 1 year after operation, some after several years, both may lead to a revision. This, together with the fact that new designs of implants and methods of fixation of SA continues to develop, stresses the importance of continuous monitoring of implant survival and follow-up. The overall aim of this thesis was to describe clinical examples of different methods to assess the outcome after Shoulder Arthroplasty. The most common methods are clinical examination, radiographic assessment, Patient Reported Outcome Measure (PROM), National Joint registries, where revisions are an important outcome, but also Clinical Trials. All of these methods are used in one or more of the 4 papers in this thesis and shows the complexity of the topic and the practical work. In paper I we used Radio Stereometric Analysis (RSA) in an experimental set-up and concluded that marker-free RSA can be used for a humeral head resurfacing arthroplasty. In paper II we used data from the Swedish Shoulder Arthroplasty Registry (SSAR) with PROM and revisions to conclude that age is the only factor that affects revision when comparing HSA and HHR. Paper III is a long-time follow-up of a Randomized controlled study where we used radiological assessment, PROM and revisions. The conclusion was that both TSA and HSA develop severe radiological changes 10 year after primary operation. Paper IV is a prospective RSA cohort study where we also evaluated PROM and revisions. The conclusion is that HHR seems to obtain a secure fixation in the humerus, after an initial migration. But also that the prostheses shows continuous glenoid wear. The main conclusion of this thesis is that patient’s operated with SA needs continuous monitoring and several methods may be used to evaluate the outcome

Positive Semidefiniteness and Positive Definiteness of a Linear Parametric Interval Matrix

We consider a symmetric matrix, the entries of which depend linearly on some parameters. The domains of the parameters are compact real intervals. We investigate the problem of checking whether for each (or some) setting of the parameters, the matrix is positive definite (or positive semidefinite). We state a characterization in the form of equivalent conditions, and also propose some computationally cheap sufficient\,/\,necessary conditions. Our results extend the classical results on positive (semi-)definiteness of interval matrices. They may be useful for checking convexity or non-convexity in global optimization methods based on branch and bound framework and using interval techniques

Next-generation sequencing of AV nodal reentrant tachycardia patients identifies broad spectrum of variants in ion channel genes.

Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often diagnosed in patients <40 years of age. Familial clustering, early onset of symptoms and lack of structural anomaly indicate involvement of genetic factors in AVNRT pathophysiology. We hypothesized that AVNRT patients have a high prevalence of variants in genes that are highly expressed in the atrioventricular conduction axis of the heart and potentially involved in arrhythmic diseases. Next-generation sequencing of 67 genes was applied to the DNA profile of 298 AVNRT patients and 10 AVNRT family members using HaloPlex Target Enrichment System. In total, we identified 229 variants in 60 genes; 215 missenses, four frame shifts, four codon deletions, three missense and splice sites, two stop-gain variants, and one start-lost variant. Sixty-five of these were not present in the Exome Aggregation Consortium (ExAC) database. Furthermore, we report two AVNRT families with co-segregating variants. Seventy-five of 284 AVNRT patients (26.4%) and three family members to different AVNRT probands had one or more variants in genes affecting the sodium handling. Fifty-four out of 284 AVNRT patients (19.0%) had variants in genes affecting the calcium handling of the heart. We furthermore find a large proportion of variants in the HCN1-4 genes. We did not detect a significant enrichment of rare variants in the tested genes. This could be an indication that AVNRT might be an electrical arrhythmic disease with abnormal sodium and calcium handling

Lack of association of CTLA-4 +49 A/G polymorphism with predisposition to type 1 diabetes in a cohort of Egyptian families

Background: Type 1 diabetes is one of the most common chronic childhood illnesses. Interplay between genetic susceptibility and environmental factors is thought to provide the fundamental element for the disease. Apart from the Major Histocompatibility locus which is the main contributor to risk susceptibility, more than 40 loci are recognized. One among these is the CTLA-4, however data from the literature are controversial. The aim of our study was to investigate the role of CTLA4 49 A/G as a risk susceptibility factor for the development of type 1 diabetes in a cohort of Egyptian families.Subjects and methods: This is a case control study including 88 Egyptian families with one or more index cases (&lt;18 years). The control group comprised 369 healthy unrelated subjects with no family history of diabetes or autoimmune disease. Using PCR-RFLP methodology, CTLA4 49 A/G was analyzed in 738 samples representing 88 families (88 patients, 125 siblings and 156 parents) and 369 control.Results: The age of onset was 6 days-12.5 years with a mean of 5.3± 3.6 and a median of 5 years. The mode of presentation was classic symptoms in 51 and diabetic ketoacidosis in 37 cases. Twenty-two cases had a history of viral infection or exanthematous disease and four had associated autoimmune diseases. No significant differences were encountered between the different groups with regard to CTLA4 +49 A/G genotype or allele frequencies. Neither was there a relation between the various genotypes and age of onset or the mode of presentation.Conclusions: CTLA4 49 A/G polymorphism was not recognized as a risk susceptibility factor in our cohort. This may be attributed to the low co-incidence of autoimmune diseases. Up to our best knowledge, this is the first study involving families. We recommend that all studies performed on risk susceptibility to type 1 diabetes should include proper investigation for other autoimmune diseases to exclude their confounding effect on data analysis.Keywords: Type 1 diabetes; CTLA-4; Risk susceptibilit

Big-Data-Driven Materials Science and its FAIR Data Infrastructure

This chapter addresses the forth paradigm of materials research -- big-data driven materials science. Its concepts and state-of-the-art are described, and its challenges and chances are discussed. For furthering the field, Open Data and an all-embracing sharing, an efficient data infrastructure, and the rich ecosystem of computer codes used in the community are of critical importance. For shaping this forth paradigm and contributing to the development or discovery of improved and novel materials, data must be what is now called FAIR -- Findable, Accessible, Interoperable and Re-purposable/Re-usable. This sets the stage for advances of methods from artificial intelligence that operate on large data sets to find trends and patterns that cannot be obtained from individual calculations and not even directly from high-throughput studies. Recent progress is reviewed and demonstrated, and the chapter is concluded by a forward-looking perspective, addressing important not yet solved challenges.Comment: submitted to the Handbook of Materials Modeling (eds. S. Yip and W. Andreoni), Springer 2018/201

Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young

Member of the EMQN MODY group: Gisela GasparAIMS/HYPOTHESIS: Mutations in the GCK and HNF1A genes are the most common cause of the monogenic forms of diabetes known as 'maturity-onset diabetes of the young'. GCK encodes the glucokinase enzyme, which acts as the pancreatic glucose sensor, and mutations result in stable, mild fasting hyperglycaemia. A progressive insulin secretory defect is seen in patients with mutations in the HNF1A and HNF4A genes encoding the transcription factors hepatocyte nuclear factor-1 alpha and -4 alpha. A molecular genetic diagnosis often changes management, since patients with GCK mutations rarely require pharmacological treatment and HNF1A/4A mutation carriers are sensitive to sulfonylureas. These monogenic forms of diabetes are often misdiagnosed as type 1 or 2 diabetes. Best practice guidelines for genetic testing were developed to guide testing and reporting of results