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Uterine leiomyomas are common benign tumors. Here, a meta-analysis of two European leiomyoma GWAS uncovers 21 leiomyoma risk variants at 16 loci, providing evidence of genetic overlap between leiomyoma and various benign and malignant tumors and highlighting the role of estrogen in tumor growth.

The prosthetic feet that are most often prescribed to individuals with K3/K4 levels of ambulation are the ESR feet. ESR stands for energy-storing and -releasing. The elastic energy is stored by the elastic elements in composite materials (carbon fiber or glass fiber). ESR feet must be developed and optimized in terms of stiffness, taking into account the loads that a healthy human foot undergoes and its kinematics while walking. So far, state-of-the-art analyses show that the literature approaches for prosthetic foot design are not based on a systematic methodology. With the aim of optimizing the stiffness of ESR feet following a methodological procedure, a methodology based on finite element structural analysis, standard static testing (ISO 10328) and functional verification was optimized and it is presented in this paper. During the path of optimization of the foot prototypes, this methodology was validated experimentally. It includes the following: (i) geometry optimization through two-dimensional finite element analysis; (ii) material properties optimization through three-dimensional finite element analysis; (iii) validation test on physical prototypes; (iv) functionality verification through dynamic finite element analysis. The design and functional verification of MyFlex-γ, a three-blade ESR foot prosthesis, is presented to describe the methodology and demonstrate its usability.

In 2018, Iceland had Europe's second-fewest police officers per capita and had experienced the continent's biggest reduction in officers since 2009—after suffering the biggest financial crisis in modern economic history. Fewer officers, a growing, more diverse population, and a tourist boom fuelled a police staffing crisis peaking in the mid-2010s. In this case study, we document, using secondary data and interrupted time-series analysis, how moving basic police education to the university level in 2016 and shifting from face-to-face to flexible learning—a form of blended learning—helped Iceland accommodate more students, reverse the downward trend of police staffing, improve female representation, and raise the education level. Moreover, public trust in the police remained high after reform. The case of Iceland demonstrates that blended learning can facilitate police–university partnerships, accommodate more students by expanding access, capacity, and capability, help address staffing challenges, and optimize resources. [ABSTRACT FROM AUTHOR]

This research attempted to find and define holistic systems that affect the productivity of the knowledge worker (KW), using the soft systems methodology (SSM). It is not enough to look at the management and improvement of knowledge worker productivity (KWP) from the viewpoint of the organization. The viewpoint of the individual KW needs to be considered as well. The KW owns the means of production; they carry their knowledge in their heads and take it with them when changing jobs. This paper proposes a conceptual framework that describes the process in which the KW uses resources to execute actions to create tangible or intangible artifacts with the intention of generating value. It was based on interpretations and inferences made from an extensive literature review using the snowballing method. This paper highlights what implications the lessons learned from the conceptual framework have on managing and improving KWP and delves deeper into four key concepts: value in knowledge work, knowledge, personal resources, and competencies.

Abstract Background Rare missense mutations in the gene encoding coatomer subunit alpha (COPA) have recently been shown to cause autoimmune interstitial lung, joint and kidney disease, also known as COPA syndrome, under a dominant mode of inheritance. Case presentation Here we describe an Icelandic family with three affected individuals over two generations with a rare clinical presentation of lung and joint disease and a histological diagnosis of follicular bronchiolitis. We performed whole-genome sequencing (WGS) of the three affected as well as three unaffected members of the family, and searched for rare genotypes associated with disease using 30,067 sequenced Icelanders as a reference population. We assessed all coding and splicing variants, prioritizing variants in genes known to cause interstitial lung disease. We detected a heterozygous missense mutation, p.Glu241Lys, in the COPA gene, private to the affected family members. The mutation occurred de novo in the paternal germline of the index case and was absent from 30,067 Icelandic genomes and 141,353 individuals from the genome Aggregation Database (gnomAD). The mutation occurs within the conserved and functionally important WD40 domain of the COPA protein. Conclusions This is the second report of the p.Glu241Lys mutation in COPA, indicating the recurrent nature of the mutation. The mutation was reported to co-segregate with COPA syndrome in a large family from the USA with five affected members, and classified as pathogenic. The two separate occurrences of the p.Glu241Lys mutation in cases and its absence from a large number of sequenced genomes confirms its role in the pathogenesis of the COPA syndrome.

Abstract Background Epileptic encephalopathies are a group of childhood epilepsies that display high phenotypic and genetic heterogeneity. The recent, extensive use of next-generation sequencing has identified a large number of genes in epileptic encephalopathies, including UBA5 in which biallelic mutations were first described as pathogenic in 2016 (Colin E et al., Am J Hum Genet 99(3):695-703, 2016. Muona M et al., Am J Hum Genet 99(3):683-694, 2016). UBA5 encodes an activating enzyme for a post-translational modification mechanism known as ufmylation, and is the first gene from the ufmylation pathway that is linked to disease. Case presentation We sequenced the genomes of two sisters with early-onset epileptic encephalopathy along with their unaffected parents in an attempt to find a genetic cause for their condition. The sisters, born in 2004 and 2006, presented with infantile spasms at six months of age, which later progressed to recurrent, treatment-resistant seizures. We detected a compound heterozygous genotype in UBA5 in the sisters, a genotype not seen elsewhere in an Icelandic reference set of 30,067 individuals nor in public databases. One of the mutations, c.684G > A, is a paternally inherited exonic splicing mutation, occuring at the last nucleotide of exon 7 of UBA5. The mutation is predicted to disrupt the splice site, resulting in loss-of-function of one allele of UBA5. The second mutation is a maternally inherited missense mutation, p.Ala371Thr, previously reported as pathogenic when in compound heterozygosity with a loss-of-function mutation in UBA5 and is believed to produce a hypomorphic allele. Supportive of this, we have identified three adult Icelanders homozygous for the p.Ala371Thr mutation who show no signs of neurological disease. Conclusions We describe compound heterozygous mutations in the UBA5 gene in two sisters with early-onset epileptic encephalopathy. To our knowledge, this is the first description of mutations in UBA5 since the initial discovery that pathogenic biallelic variants in the gene cause early-onset epileptic encephalopathy. We further provide confirmatory evidence that p.Ala371Thr is a hypomorphic mutation, by presenting three adult homozygotes who show no signs of neurological disease.

Abstract Appendicitis is one of the most common conditions requiring acute surgery and can pose a threat to the lives of affected individuals. We performed a genome-wide association study of appendicitis in 7,276 Icelandic and 1,139 Dutch cases and large groups of controls. In a combined analysis of the Icelandic and Dutch data, we detected a single signal represented by an intergenic variant rs2129979 [G] close to the gene PITX2 associating with increased risk of appendicitis (OR = 1.15, P = 1.8 × 10−11). We only observe the association in patients diagnosed in adulthood. The marker is close to, but distinct from, a set of markers reported to associate with atrial fibrillation, which have been linked to PITX2. PITX2 has been implicated in determination of right-left symmetry during development. Anomalies in organ arrangement have been linked to increased prevalence of gastrointestinal and intra-abdominal complications, which may explain the effect of rs2129979 on appendicitis risk.

Lumbar disc herniation (LDH) can cause persistent sciatica, and in some cases surgery is required to relieve symptoms. Here, the authors carry out a genome-wide association study using microdiscectomy as an indicator of severe LDH, and find a locus on chromosome 8 associated with this condition.

We report how data from satellite and aerial synthetic aperture radar (SAR) observations were integrated into monitoring of the 2014–2015 Holuhraun eruption in the Bárðarbunga volcanic system, the largest effusive eruption in Iceland since the 1783–84 Laki eruption. A lava field formed in one of the most remote areas in Iceland, after the propagation of a ∼50 km-long dyke beneath the Vatnajökull ice cap, where the Bárðarbunga caldera is located. Due to the 6 month duration of the eruption, mainly in wintertime, daily monitoring was particularly challenging. During the eruption, the European volcanological project FutureVolc was ongoing, allowing collaboration of many European experts on volcano monitoring activities. Icelandic volcanoes are also a permanent Supersite within the Geohazard Supersites and Natural Laboratories (GSNL) initiative, with support from the Committee on Earth Observation Satellite (CEOS) in the form of a large collection of SAR images. SAR data were acquired by Cosmo-SkyMed (CSK) and TerraSAR-X (TSX) satellites and complemented by aerial SAR images. The large set of SAR satellite data significantly contributed to the daily monitoring during the unrest at Bárðarbunga caldera, the Holuhraun eruption and the year following the eruption. Detection of surface changes using both SAR amplitude and phase information was conducted throughout the whole duration of the volcano-tectonic event, and in the following months, to quantify and track the evolution of volcanic processes at Holuhraun and geothermal activity at Bárðarbunga volcano. Combination of SAR data with other data sets, e.g., satellite optical images and geodetic Global Positioning System (GPS) measurements, was essential for the evaluation of the volcanic hazard in the whole area. International collaboration within the FutureVolc project formed the basis for successful analyses and interpretation of the large SAR data set. Information was provided at Scientific Advisory Board meetings of the Icelandic Civil Protection and used in decision-making, as well as for supporting field-deployment and air-based surveys.

Fairness issues within food systems are of increasing concern for policy makers and other stakeholders. Given the topicality and policy relevance of fairness within food systems, there is value in exploring the subject further. Simulation modelling has been successfully used to develop and test policy interventions. However, the subjectivity and intangibleness of fairness perceptions make them difficult to operationalize in a quantitative model. The objective of this study is to facilitate research on fairness in food systems using simulation modelling by defining the social construct of fairness in model operational terms. The operationalization is conducted in two steps. First, the construct of fairness is conceptually defined in terms of its dimensions, antecedents, and consequences using the literature on interorganizational fairness. Then, by focusing specifically on fairness issues within food systems, the conceptual definition is used as a basis for the identification of proxy indicators of fairness. Seven groups of factors related to fairness perceptions were identified during the conceptualization phase: financial outcomes, operational outcomes, power, environmental stability, information sharing, relationship quality, and controls. From these factor groups, five indicators of fairness that are operational in a quantitative model were identified: profit margin as an indicator of distributive fairness and four indicators of procedural fairness related to market power and bargaining power.

Adult height has a strong genetic component and is highly heritable. Here the authors whole-genome sequence 8,453 Icelanders and find novel parent-of-origin derived associations in IGF2-H19 and DLK1-MEG3.

Creatine kinase (CK) and lactate dehydrogenase (LDH) are biomarkers of tissue damages including myopathy and myocardial infarction. Here, Patrick Sulem and colleagues perform a genome-wide association study to identify common and rare genetic variants that associates with serum CK or LDH levels.

Despite extensive efforts in the development of drugs for complex neurodegenerative diseases, treatment often remains challenging or ineffective, and hence new treatment strategies are necessary. One approach is the design of multi-target drugs, which can potentially address the complex nature of disorders such as Alzheimer’s disease. We report a method for high throughput virtual screening aimed at identifying new dual target hit molecules. One of the identified hits, N,N-dimethyl-1-(4-(3-methyl-[1,2,4]triazolo[4,3-a]pyrimidin-6-yl)phenyl)ethan-1-amine (Ýmir-2), has dual-activity as an acetylcholinesterase (AChE) inhibitor and as an α7 nicotinic acetylcholine receptor (α7 nAChR) agonist. Using computational chemistry methods, parallel and independent screening of a virtual compound library consisting of 3,848,234 drug-like and commercially available molecules from the ZINC15 database, resulted in an intersecting set of 57 compounds, that potentially possess activity at both of the two protein targets. Based on ligand efficiency as well as scaffold and molecular diversity, 16 of these compounds were purchased for in vitro validation by Ellman’s method and two-electrode voltage-clamp electrophysiology. Ýmir-2 was shown to exhibit the desired activity profile (AChE IC50 = 2.58 ± 0.96 µM; α7 nAChR activation = 7.0 ± 0.9% at 200 µM) making it the first reported compound with this particular profile and providing further evidence of the feasibility of in silico methods for the identification of novel multi-target hit molecules.

Aquaculture intensity has been used for years as a means to gauge how much production a site makes using three terms: extensive, semi-intensive and intensive aquaculture production systems. The industry has a relatively coordinated understanding of these terms, but an explicit general definition does not seem to exist. This paper aims to use three kinds of production function groups; the input, treatment and output functions to describe and define the terms extensive, semi-intensive and intensive explicitly. This is done with extensive literature review to find the meaning of the terms. The terms are then mapped onto the three production function groups. The resulting framework accomplishes two things. Firstly, it defines extensive, semi-intensive and intensive aquaculture in terms of production functions. Secondly, it creates an eight level scale, the aquaculture production intensity scale (APIS), that provides three levels of extensive systems, two level of semi-intensive systems and three level of intensive systems. APIS allows mapping of all uses of the terms in current literature to an APIS score, though some results might differ from current usage.

Following publication of the original article Witham et al., 2020, it was noticed a mistake of copyright holder name.