A Clinical Decision Support System for the Diagnosis, Fracture Risks and Treatment of Osteoporosis

Expanding medical knowledge increases the potential risk of medical errors in clinical practice. We present, OPAD, a clinical decision support system in the field of the medical care of osteoporosis. We utilize clinical information from international guidelines and experts in the field of osteoporosis. Physicians are provided with user interface to insert standard patient data, from which OPAD provides instant diagnostic comments, 10-year risk of fragility fracture, treatment options for the given case, and when to offer a follow-up DXA-evaluation. Thus, the medical decision making is standardized according to the best expert knowledge at any given time. OPAD was evaluated in a set of 308 randomly selected individuals. OPAD’s ten-year fracture risk computation is nearly identical to FRAX (r = 0.988). In 58% of cases OPAD recommended DXA evaluation at the present time. Following a DXA measurement in all individuals, 71% of those that were recommended to have DXA at the present time received recommendation for further investigation or specific treatment by the OPAD. In only 5.9% of individuals in which DXA was not recommended, the result of the BMD measurement changed the recommendations given by OPAD

Insertion of an SVA-E retrotransposon into the CASP8 gene is associated with protection against prostate cancer

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Transcriptional and splicing anomalies have been observed in intron 8 of the CASP8 gene (encoding procaspase-8) in association with cutaneous basal-cell carcinoma (BCC) and linked to a germline SNP rs700635. Here, we show that the rs700635[C] allele, which is associated with increased risk of BCC and breast cancer, is protective against prostate cancer [odds ratio (OR) = 0.91, P = 1.0 × 10(-6)]. rs700635[C] is also associated with failures to correctly splice out CASP8 intron 8 in breast and prostate tumours and in corresponding normal tissues. Investigation of rs700635[C] carriers revealed that they have a human-specific short interspersed element-variable number of tandem repeat-Alu (SINE-VNTR-Alu), subfamily-E retrotransposon (SVA-E) inserted into CASP8 intron 8. The SVA-E shows evidence of prior activity, because it has transduced some CASP8 sequences during subsequent retrotransposition events. Whole-genome sequence (WGS) data were used to tag the SVA-E with a surrogate SNP rs1035142[T] (r(2) = 0.999), which showed associations with both the splicing anomalies (P = 6.5 × 10(-32)) and with protection against prostate cancer (OR = 0.91, P = 3.8 × 10(-7)).National Cancer Research Institute (NCRI) G0500966/75466 Department of Health, Medical Research Council Cancer Research UK University of Cambridge NIHR Department of Health Anniversary Fund of the Austrian National Bank 15079 Medical and Scientific Fund of the Mayor of the City of Vienna 10077 Common Fund of the Office of the Director of the National Institutes of Health NCI NHGRI NHLBI NIDA NIMH NINDS NCI\SAIC-Frederick, Inc. (SAIC-F) 10XS170 Roswell Park Cancer Institute 10XS171 Science Care, Inc. X10S172 SAIC-F 10ST1035 HHSN261200800001E deCODE genetics/AMGEN HHSN268201000029C DA006227 DA033684 N01MH000028 MH090941 MH101814 MH090951 MH090937 MH101820 MH101825 MH090936 MH101819 MH090948 MH101782 MH101810 MH10182

New basal cell carcinoma susceptibility loci.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10(-12)), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10(-9)), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10(-12)) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10(-16)). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained.NCI\SAIC-Frederick, Inc. (SAIC-F) 10XS170 Roswell Park Cancer Institute 10XS171 Science Care Inc. X10S172 Laboratory, Data Analysis and Coordinating Center (LDACC) HHSN268201000029C SAIC-F 10ST1035 HHSN261200800001E Brain Bank DA006227 DA033684 N01MH000028 University of Geneva MH090941 MH101814 University of Chicago MH090951 MH090937 MH101820 MH101825 University of North Carolina-Chapel Hill MH090936 MH101819 Harvard University MH090948 Stanford University MH101782 Washington University St Louis MH101810 University of Pennsylvania MH10182

Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadPelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P 5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.UCL Hospitals NIHR Biomedical Research Centr

Genetic correction of PSA values using sequence variants associated with PSA levels

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldMeasuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 × 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.info:eu-repo/grantAgreement/EC/FP7/202059/ 218071 Urological Research Foundation P50 CA90386-05S2 Robert H. Lurie Comprehensive Cancer Center p30 CA60553 Health Technology Assessment Programme 96/20/06 96/20/99 Department of Health, England Cancer Research UK C522/A8649 Medical Research Council of England G0500966 ID 75466 National Cancer Research Institute (NCRI), UK Southwest National Health Service Research and Development NCRI National Institute for Health Resear

Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study

© 2023. The Author(s).BACKGROUND: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. METHODS: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection. RESULTS: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. CONCLUSIONS: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.Peer reviewe

Integration of a Folding Electric Two-wheeler Vehicle for a Future Commuting Transportation

The paper issues the development, building and testing of a Folding Electric Motorbike, a lightweight, low cost and all-electric two-wheeler vehicle taking full advantage on today’s city infrastructure. The technology offers drivers to combine transportation methods, lowering cost, and greenhouse gas emission. The paper documents innovative studies on how the technology can be used to explode the today’s transportation system and be used to bridge the gap of today’s challenges and future solutions. The optimum components to be used in the small, lightweight vehicles are selected based on the technology’s functional requirements. The selection of motorbike’s drivetrain components is based on the latest available technology, with respect to economic viability. The technologies first two development stages are described. In the first development stage the vehicle’s functional requirements are defined. This is followed by a feasibility study and a realization on technologies capabilities. The feasibility study is performed by developing, building and evaluating an alpha-prototype vehicle. The research indicate that the possibility of developing a powerful , light-weight, low cost and all-electric two-wheeler vehicle taking full advantage on today’s city infrastructure is very prospective. The alpha-prototype was successfully constructed and is considered to be ready for further laboratory testing and test driving before continuations on a fully designed beta-prototype

Addressing intersection artifacts on textured, geometrically rendered vector data in 3D applications

There exist various methods to render vector data in 3D applications. One such method is to render the data geometrically, where polyline data is tessellated into some geometry that is rendered on top of the 3D terrain. Having explicit access to the line geometry is valuable to applications that demand high visual quality, as it enables applying various effects to the line data. However, a prominent visual artifact in geometrically rendered line data occurs around intersections, where it is hard to render lines seamlessly. In this thesis paper I present a method that is aimed to address this issue. By generating explicit geometry for line intersections, and by enforcing several restrictions on the design of the applied textures, the proposed method ensures seamless rendering of textures over complex intersections, including intersections that adjoin lines with different textures assigned to them. To ensure minimal performance overhead at runtime the proposed method computes all the required geometry offline, and stores it in a static vertex buffer on the GPU. At runtime a separate index buffer is generated, which is used to reference the vertices required to generate the appropriate geometry. Finally, the proposed method supports interactively assigning textures to line data at runtime, which could for example enable filtering and focusing of vector data. Empirical measurements are provided for runtime performance, these measurements show that the performance overhead introduced by the method is reasonably small, making the proposed method a feasible addition to interactive systems. A qualitative comparison is used to validate the visual results, where examples show successful rendering of several intersections that include a variety of textures. The proposed method paves the way for possible future work, for example in defining a taxonomy of textures, along with a set of rules describing how each group of textures should be drawn at intersections.Det finns olika metoder för att rendera vektordata i 3D-applikationer. En sådan metod är att rendera datan geometriskt, där polylinje data är tessellerade till geometri som renderas ovanpå en 3D-terräng. Att ha explicit tillgång till linjens geometri är viktigt för applikationer som kräver hög visuell kvalité, eftersom det möjliggör tillämpning av olika effekter på linjedatan. En framträdande visuell artefakt i geometriskt renderad vektordata sker runt korsningar, där det är svårt att göra linjerna sömlösa. I den här uppsatsen presenterar jag en metod som syftar till att ta itu med denna fråga. Genom att skapa specifik geometri för linjekorsningar, och genom att tillämpa flera begränsningar på utformningen av de applicerade texturerna, säkerställer den föreslagna metoden smidig rendering av texturer över komplexa korsningar, inklusive korsningar som angränsar linjer med olika texturer tilldelade dem. För att säkerställa minimal påverkan prestanda vid körning beräknar den föreslagna metoden all nödvändig geometri offline och lagrar den i en statisk vertexbuffer på GPU:n. Vid körningen genereras en separat indexbuffer som används för att referera till de vertricer som krävs för att generera lämplig geometri. Den nämnda metoden stödjer interaktiv tilldelning av texturer till linjedata vid körning, vilket exempelvis kan möjliggöra filtrering och fokusering av vektordata. Empiriska mätningar ges för prestanda, och dessa mätningar visar att metodens påverkan på prestanda är relativt liten, vilket gör den föreslagna metoden till ett genomförbart tillägg till interaktiva system. En kvalitativ jämförelse används för att validera de visuella resultaten, där exempel visar en lyckad rendering av flera korsningar som innehåller en mängd olika texturer. Denna metod banar vägen för eventuellt framtida arbeten, till exempel vid definitioner av texturernas taxonomi, tillsammans med en uppsättning regler som beskriver hur varje grupp av texturer ska dras vid korsningar

Prevalence of symptomatic Charcot-Marie-Tooth disease in Iceland: a study of a well-defined population

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND/AIM: To determine the prevalence and clinical spectrum of Charcot-Marie-Tooth disease (CMT) in Iceland. METHODS: We identified all individuals with symptomatic CMT, based on information from all practicing neurologists, both neurophysiology laboratories and the only neurology department in the country. The diagnosis was based on clinical features and neurophysiological testing. DNA testing was regarded as confirmatory. RESULTS: We identified 37 individuals in 18 families, which were not linked by identifying 5 generations of ancestors. The point prevalence (January 1, 2007) for all CMT subtypes in Iceland was 12.0/10(5), 10.1/10(5) for CMT1 and 2.0/10(5) for CMT2. The clinical features include lower limb weakness (95%), impaired gait (68%), decreased or absent deep tendon reflexes (86%), pes cavus (70%) and hammer toes (46%). Clinical symptoms were similar for the 2 main CMT subtypes. CONCLUSION: We report the prevalence and clinical spectrum of CMT, which is comparable to the results of other prevalence studies, in a well-defined, total population sample