Finnish new variant of Chlamydia trachomatis escaping detection in the Aptima Combo 2 assay also present in Orebro County, Sweden, May 2019

We identified the first two cases of the Finnish new variant of Chlamydia trachomatis (F-nvCT) beyond Finland in two clinical urogenital specimens in Orebro County, Sweden. These Aptima Combo 2 assay-negative specimens were Aptima Chlamydia trachomatis (CT) assay positive and had the characteristic C1515T mutation in the 23S rRNA gene. From 22 March to 31 May 2019, 1.3% (2/158) of the CT-positive cases in Orebro County were missed because of the F-nvCT. International awareness, investigations and actions are essential.Peer reviewe

Potential drivers of human tick-borne encephalitis in the orebro region of Sweden, 2010-2021

Incidence of tick-borne encephalitis (TBE) has increased during the last years in Scandinavia, but the underlying mechanism is not understood. TBE human case data reported between 2010 and 2021 were aggregated into postal codes within orebro County, south-central Sweden, along with tick abundance and environmental data to analyse spatial patterns and identify drivers of TBE. We identified a substantial and continuing increase of TBE incidence in orebro County during the study period. Spatial cluster analyses showed significant hotspots (higher number of cases than expected) in the southern and northern parts of orebro County, whereas a cold spot (lower number of cases than expected) was found in the central part comprising orebro municipality. Generalised linear models showed that the risk of acquiring TBE increased by 12.5% and 72.3% for every percent increase in relative humidity and proportion of wetland forest, respectively, whereas the risk decreased by 52.8% for every degree Celsius increase in annual temperature range. However, models had relatively low goodness of fit (R-2 < 0.27). Results suggest that TBE in orebro County is spatially clustered, however variables used in this study, i.e., climatic variables, forest cover, water, tick abundance, sheep as indicator species, alone do not explain this pattern

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

A More Accurate Semantics for Distributed Erlang

In order to formally reason about distributed Erlang systems, it isnecessary to have a formal semantics. In a previous paper we haveproposed such a semantics for distributed Erlang. However, recent workwith a model checker for Erlang revealed that the previous attempt wasnot good enough. In this paper we present a more accurate semanticsfor distributed Erlang. The more accurate semantics includes severalmodifications and additions to the semantics for distributed Erlangproposed by Claessen and Svensson in 2005, which in turn is anextension to Fredlund\u27s formal single-node semantics for Erlang. Themost distinct addition to the previous semantics is the possibility tocorrectly model disconnected nodes

McErlang: A Model Checker for a Distributed Functional Programming Language

We present a model checker for verifying distributed programs written in the Erlang programming language. Providing a model checker for Erlang is especially rewarding since the language is by now being seen as a very capable platform for developing industrial strength distributed applications with excellent failure tolerance characteristics. In contrast to most other Erlang verification attempts, we provide support for a very substantial part of the language. The model checker has full Erlang data type support, support for general process communication, node semantics (inter-process behave subtly different from intra-process communication), fault detection and fault tolerance through process linking, and can verify programs written using the OTP Erlang component library (used by most modern Erlang programs). As the model checking tool is itself implemented in Erlang we benefit from the advantages that a (dynamically typed) functional programming language offers: easy prototyping and experimentation with new verification algorithms, rich executable models that use complex data structures directly programmed in Erlang, the ability to treat executable models interchangeably as programs (to be executed directly by the Erlang interpreter) and data, and not least the possibility to cleanly structure and to cleanly combine various verification sub-tasks. In the paper we discuss the design of the tool and provide early indications on its performance

A More Accurate Semantics for Distributed Erlang

In order to formally reason about distributed Erlang systems, it is necessary to have a formal semantics. In a previous paper we have proposed such a semantics for distributed Erlang. However, recent work with a model checker for Erlang revealed that the previous attempt was not good enough. In this paper we present a more accurate semantics for distributed Erlang. The more accurate semantics includes several modifications and additions to the semantics for distributed Erlang proposed by Claessen and Svensson in 2005, which in turn is an extension to Fredlund's formal single-node semantics for Erlang. The most distinct addition to the previous semantics is the possibility to correctly model disconnected nodes

Programming Distributed Erlang Applications: Pitfalls and Recipes

We investigate the distributed part of the Erlang programminglanguage, with an aim to develop robust distributed systems andalgorithms running on top of Erlang runtime systems. Although the stepto convert an application running on a single node to a fullydistributed (multi-node) application is deceptively simple (changingcalls to spawn so that processes are spawned on differentnodes), there are some corner cases in the Erlang language and APIwhere the introduction of distribution can cause problems. In thispaper we discuss a number of such pitfalls, where the semantics ofcommunicating processes differs significantly depending if theprocesses reside on the same node or not, we also provide someguidelines for safe programming of distributed systems

Comparison of Serologic and Genetic porB-Based Typing of Neisseria gonorrhoeae: Consequences for Future Characterization

Due to temporal changes in the epidemiology of gonorrhea, a precise characterization of Neisseria gonorrhoeae is essential. In the present study genetic heterogeneity in the porB genes of N. gonorrhoeae was examined, and serovar determination was compared to porB gene sequencing. Among 108 N. gonorrhoeae isolates, phylogenetic analysis of the entire porB alleles (924 to 993 bp) identified 87 unique sequences. By analyzing only the four to six most heterogeneous porB gene regions (174 to 363 bp), 86 out of these 87 genetic variants were identified. Consequently, analysis of shorter highly variable regions of the porB gene generates high-level discriminatory ability as well as fast, objective, reproducible, and portable data for epidemiological characterization of N. gonorrhoeae. Regarding putative antigenic epitopes of PorB for Genetic Systems monoclonal antibodies (MAbs), some of the previous findings were confirmed, but new findings were also observed. For several of the MAbs, however, the precise amino acid residues of PorB critical for single-MAb reactivity were difficult to identify. In addition, repeated serovar determination of 108 N. gonorrhoeae isolates revealed discrepancies for 34 isolates, mostly due to nonreproducible reactivity with single MAbs. Thus, the prospects of a genetic typing system with congruent translation of the serovar determination seem to be limited. In conclusion, analysis of short highly variable regions of the porB gene could form the basis for a fast molecular epidemiological tool for the examination of emergence and transmission of N. gonorrhoeae strains within the community