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International policy recently adopted commitments to maintain genetic diversity in wild populations to secure their adaptive potential, including metrics to monitor temporal trends in genetic diversity - so-called indicators. A national programme for assessing trends in genetic diversity was recently initiated in Sweden. Relating to this effort, we systematically assess contemporary genome-wide temporal trends (40 years) in wild populations using the newly adopted indicators and whole genome sequencing (WGS). We use pooled and individual WGS data from brown trout (Salmo trutta) in eight alpine lakes in protected areas. Observed temporal trends in diversity metrics (nucleotide diversity, Watterson's ϴ and heterozygosity) lie within proposed acceptable threshold values for six of the lakes, but with consistently low values in lakes above the tree line and declines observed in these northern-most lakes. Local effective population size is low in all lakes, highlighting the importance of continued protection of interconnected systems to allow genetic connectivity for long-term viability of these populations. Inbreeding (F ROH ) spans 10%-30% and is mostly represented by ancient (<1 Mb) runs of homozygosity, with observations of little change in mutational load. We also investigate adaptive dynamics over evolutionarily short time frames (a few generations); identifying putative parallel selection across all lakes within a gene pertaining to skin pigmentation as well as candidates of selection unique to specific lakes and lake systems involved in reproduction and immunity. We demonstrate the utility of WGS for systematic monitoring of natural populations, a priority concern if genetic diversity is to be protected., (© 2023 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Ungulate species have experienced severe declines over the past centuries through overharvesting and habitat loss. Even if many game species have recovered thanks to strict hunting regulation, the genome-wide impacts of overharvesting are still unclear. Here, we examine the temporal and geographical differences in genome-wide diversity in moose (Alces alces) over its whole range in Sweden by sequencing 87 modern and historical genomes. We found limited impact of the 1900s near-extinction event but local variation in inbreeding and load in modern populations, as well as suggestion of a risk of future reduction in genetic diversity and gene flow. Furthermore, we found candidate genes for local adaptation, and rapid temporal allele frequency shifts involving coding genes since the 1980s, possibly due to selective harvesting. Our results highlight that genomic changes potentially impacting fitness can occur over short time scales and underline the need to track both deleterious and selectively advantageous genomic variation., (© 2023. Springer Nature Limited.)

Population translocations occur for a variety of reasons, from displacement due to climate change to human-induced transfers. Such actions have adverse effects on genetic variation and understanding their microevolutionary consequences requires monitoring. Here, we return to an experimental release of brown trout ( Salmo trutta ) in order to monitor the genomic effects of population translocations. In 1979, fish from each of two genetically ( F ST  = 0.16) and ecologically separate populations were simultaneously released, at one point in time, to a lake system previously void of brown trout. Here, whole-genome sequencing of pooled DNA (Pool-seq) is used to characterize diversity within and divergence between the introduced populations and fish inhabiting two lakes downstream of the release sites, sampled 30 years later (c. 5 generations). Present results suggest that while extensive hybridization has occurred, the two introduced populations are unequally represented in the lakes downstream of the release sites. One population, which is ecologically resident in its original habitat, mainly contributes to the lake closest to the release site. The other population, migratory in its natal habitat, is genetically more represented in the lake further downstream. Genomic regions putatively under directional selection in the new habitat are identified, where allele frequencies in both established populations are more similar to the introduced population stemming from a resident population than the migratory one. Results suggest that the microevolutionary consequences of population translocations, for example, hybridization and adaptation, can be rapid and that Pool-seq can be used as an initial tool to monitor genome-wide effects., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Recent studies have shown low caspofungin concentrations in critically ill patients. In some patients, the therapeutic target, area under the total plasma concentration curve in relation to the minimal inhibition concentration (AUC tot /MIC), seems not to be achieved and therapeutic drug monitoring (TDM) has been proposed. Caspofungin is highly protein-bound and the effect of reduced plasma protein levels on pharmacodynamics has not been investigated., Objectives: Fungal killing activity of caspofungin in vitro was investigated under varying levels of human plasma protein., Methods: Time-kill studies were performed with clinically relevant caspofungin concentrations of 1-9 mg/L on four blood isolates of C. glabrata, three susceptible and one strain with reduced susceptibility, in human plasma and plasma diluted to 50% and 25% using Ringer's acetate., Results: Enhanced fungal killing of the three susceptible strains was observed in plasma with lower protein content (p < .001). AUC tot /MIC required for a 1 log 10 CFU/ml kill at 24 h in 50% and 25% plasma was reduced with 36 + 12 and 80 + 9%, respectively. The maximum effect was seen at total caspofungin concentrations of 4-9 × MIC. For the strain with reduced susceptibility, growth was significantly decreased at lower protein levels., Conclusions: Reduced human plasma protein levels increase the antifungal activity of caspofungin in vitro, most likely by increasing the free concentration. Low plasma protein levels in critically ill patients with candidemia might explain a better response to caspofungin than expected from generally accepted target attainment and should be taken into consideration when assessing TDM based on total plasma concentrations., (© 2021 The Authors. Mycoses published by Wiley-VCH GmbH.)

The sympatric existence of genetically distinguishable populations of the same species remains a puzzle in ecology. Coexisting salmonid fish populations are known from over 100 freshwater lakes. Most studies of sympatric populations have used limited numbers of genetic markers making it unclear if genetic divergence involves certain parts of the genome. We returned to the first reported case of salmonid sympatry, initially detected through contrasting homozygosity at a single allozyme locus (coding for lactate dehydrogenase A) in brown trout in the small Lakes Bunnersjöarna, Sweden. First, we verified the existence of the two coexisting demes using a 96-SNP fluidigm array. We then applied whole-genome resequencing of pooled DNA to explore genome-wide diversity within and between these demes; nucleotide diversity was higher in deme I than in deme II. Strong genetic divergence is observed with genome-wide F ST  ≈ 0.2. Compared with data from populations of similar small lakes, this divergence is of similar magnitude as that between reproductively isolated populations. Individual whole-genome resequencing of two individuals per deme suggests higher inbreeding in deme II versus deme I, indicating different degree of isolation. We located two gene-copies for LDH-A and found divergence between demes in a regulatory section of one of these genes. However, we did not find a perfect fit between the sequence data and previous allozyme results, and this will require further research. Our data demonstrates genome-wide divergence governed mostly by genetic drift but also by diversifying selection in coexisting populations. This type of hidden biodiversity needs consideration in conservation management., (© 2021 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Background: The implantation rates of cardiac implantable electronic devices have steadily increased, accompanied by a steeper rise of device related infections (DRI)., Hypothesis: The prevalence of DRI for cardiac resynchronization therapy (CRT) is higher in clinical practice than reported previously, even at a university hospital, and likely higher than reported to the national device registry., Methods: Electronic medical records of consecutive patients undergoing a CRT procedure between January 2016 and December 2017 were analyzed. Clinical history, procedure related variables and complications were reviewed by specialists in cardiology and infectious diseases., Results: A total of 171 patients, mean aged 74 years, 138 males (80.7%) were included. Twelve DRI occurred in 10 patients during mean 2.5 years follow-up, giving a prevalence of 7% (incidence of 29/1000 person-years). Reoperation, pocket haematoma, ≥3 procedures, previous device infection and indwelling central venous line were the strongest predictive factors according to univariate analysis. Out of 63/171 (36.8%) major complications, 31(49.2%) were lead-related. There were 49/171 (28.7%) reoperations and 15/171 (8.8%) minor complications. The number major complications and DRI reported to the national device registry were 7/171 (4.1%) and 2/171 (0.6%), respectively, reflecting a 5-fold underreporting., Conclusions: The high rate of CRT device infections is in sharp contrast to those reported by others and to the national device registry. Although a center specific explanation cannot be excluded, the high rates highlight a major issue with registries, reinforcing the need for better surveillance and automatic reporting of device related complications., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Multisystem inflammatory syndrome in adults, MIS-A, is a rare but severe post-covid-19 immunologic complication. The presentation is similar to Multisystem inflammatory syndrome in children, MIS-C. Both MIS-A/C are life-threatening immunologic syndromes characterized by hypotension, skin rashes, myocardial affection, coagulopathy and GI symptoms.  Here we describe a case of MIS-A in a 35-year-old previously healthy female who, five weeks after a mild covid-19 infection, presented with a life-threatening immunological reaction. The patient made a swift recovery upon treatment with immunoglobulins, corticosteroids and an interleukin-1 receptor antagonist. We want to highlight the importance of immunological derangements following covid-19 infections in adults. We also present a treatment suggestion for MIS-A based on the management routine for MIS-C, which has been developed from international discussions and collaborations by pediatric rheumatologists in Sweden and around the world.

Developing genomic insights is challenging in nonmodel species for which resources are often scarce and prohibitively costly. Here, we explore the potential of a recently established approach using Pool-seq data to generate a de novo genome assembly for mining exons, upon which Pool-seq data are used to estimate population divergence and diversity. We do this for two pairs of sympatric populations of brown trout ( Salmo trutta ): one naturally sympatric set of populations and another pair of populations introduced to a common environment. We validate our approach by comparing the results to those from markers previously used to describe the populations (allozymes and individual-based single nucleotide polymorphisms [SNPs]) and from mapping the Pool-seq data to a reference genome of the closely related Atlantic salmon ( Salmo salar ). We find that genomic differentiation ( F ST ) between the two introduced populations exceeds that of the naturally sympatric populations ( F ST  = 0.13 and 0.03 between the introduced and the naturally sympatric populations, respectively), in concordance with estimates from the previously used SNPs. The same level of population divergence is found for the two genome assemblies, but estimates of average nucleotide diversity differ ( π ¯  ≈ 0.002 and π ¯  ≈ 0.001 when mapping to S. trutta and S. salar , respectively), although the relationships between population values are largely consistent. This discrepancy might be attributed to biases when mapping to a haploid condensed assembly made of highly fragmented read data compared to using a high-quality reference assembly from a divergent species. We conclude that the Pool-seq-only approach can be suitable for detecting and quantifying genome-wide population differentiation, and for comparing genomic diversity in populations of nonmodel species where reference genomes are lacking., Competing Interests: None declared., (© 2019 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Coastal global oceans are expected to undergo drastic changes driven by climate change and increasing anthropogenic pressures in coming decades. Predicting specific future conditions and assessing the best management strategies to maintain ecosystem integrity and sustainable resource use are difficult, because of multiple interacting pressures, uncertain projections, and a lack of test cases for management. We argue that the Baltic Sea can serve as a time machine to study consequences and mitigation of future coastal perturbations, due to its unique combination of an early history of multistressor disturbance and ecosystem deterioration and early implementation of cross-border environmental management to address these problems. The Baltic Sea also stands out in providing a strong scientific foundation and accessibility to long-term data series that provide a unique opportunity to assess the efficacy of management actions to address the breakdown of ecosystem functions. Trend reversals such as the return of top predators, recovering fish stocks, and reduced input of nutrient and harmful substances could be achieved only by implementing an international, cooperative governance structure transcending its complex multistate policy setting, with integrated management of watershed and sea. The Baltic Sea also demonstrates how rapidly progressing global pressures, particularly warming of Baltic waters and the surrounding catchment area, can offset the efficacy of current management approaches. This situation calls for management that is (i) conservative to provide a buffer against regionally unmanageable global perturbations, (ii) adaptive to react to new management challenges, and, ultimately, (iii) multisectorial and integrative to address conflicts associated with economic trade-offs.

The evolutionary consequences of temporal variation in selection remain hotly debated. We explored these consequences by studying threespine stickleback in a set of bar-built estuaries along the central California coast. In most years, heavy rains induce water flow strong enough to break through isolating sand bars, connecting streams to the ocean. New sand bars typically re-form within a few weeks or months, thereby re-isolating populations within the estuaries. These breaching events cause severe and often extremely rapid changes in abiotic and biotic conditions, including shifts in predator abundance. We investigated whether this strong temporal environmental variation can maintain within-population variation while eroding adaptive divergence among populations that would be caused by spatial variation in selection. We used neutral genetic markers to explore population structure and then analysed how stickleback armor traits, the associated genes Eda and Pitx1 and elemental composition (%P) varies within and among populations. Despite strong gene flow, we detected evidence for divergence in stickleback defensive traits and Eda genotypes associated with predation regime. However, this among-population variation was lower than that observed among other stickleback populations exposed to divergent predator regimes. In addition, within-population variation was very high as compared to populations from environmentally stable locations. Elemental composition was strongly associated with armor traits, Eda genotype and the presence of predators, thus suggesting that spatiotemporal variation in armor traits generates corresponding variation in elemental phenotypes. We conclude that gene flow, and especially temporal environmental variation, can maintain high levels of within-population variation while reducing, but not eliminating, among-population variation driven by spatial environmental variation., (© 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.)

Background: Interprofessional collaboration (IPC) is essential for quality care. Understanding residents' level of competence is a critical first step to designing targeted curricula and workplace learning activities. In this needs assessment, we measured residents' IPC competence using specifically designed Objective Structured Clinical Exam (OSCE) cases and surveyed residents regarding training needs., Methods: We developed three cases to capture IPC competence in the context of physician-nurse collaboration. A trained actor played the role of the nurse (Standardized Nurse - SN). The Interprofessional Education Collaborative (IPEC) framework was used to create a ten-item behaviorally anchored IPC performance checklist (scored on a three-point scale: done, partially done, well done) measuring four generic domains: values/ethics; roles/responsibilities; interprofessional communication; and teamwork. Specific skills required for each scenario were also assessed, including teamwork communication (SBAR and CUS) and patient-care-focused tasks. In addition to evaluating IPC skills, the SN assessed communication, history-taking and physical exam skills. IPC scores were computed as percent of items rated well done in each domain (Cronbach's alpha > 0.77). Analyses include item frequencies, comparison of mean domain scores, correlation between IPC and other skills, and content analysis of SN comments and resident training needs., Results: One hundred and seventy-eight residents (of 199 total) completed an IPC case and results are reported for the 162 who participated in our medical education research registry. IPC domain scores were: Roles/responsibilities mean = 37 % well done (SD 37 %); Values/ethics mean = 49 % (SD 40 %); Interprofessional communication mean = 27 % (SD 36 %); Teamwork mean = 47 % (SD 29 %). IPC was not significantly correlated with other core clinical skills. SNs' comments focused on respect and IPC as a distinct skill set. Residents described needs for greater clarification of roles and more workplace-based opportunities structured to support interprofessional education/learning., Conclusions: The IPC cases and competence checklist are a practical method for conducting needs assessments and evaluating IPC training/curriculum that provides rich and actionable data at both the individual and program levels.

Streptococcus spp. are important causes of infective endocarditis but challenging in species identification. This study compared identification based on sequence determination of the rnpB gene with 2 systems of matrix-assisted laser desorption ionization-time of flight mass spectrometry, MALDI Biotyper (Bruker) and VITEK MS IVD (bioMérieux). Blood culture isolates of viridans streptococci from 63 patients with infective endocarditis were tested. The 3 methods showed full agreement for all 36 isolates identified in the Anginosus, Bovis, and Mutans groups or identified as Streptococcus cristatus, Streptococcus gordonii, or Streptococcus sanguinis. None of the methods could reliably identify the 23 isolates to the species level when designated as Streptococcus mitis, Streptococcus oralis, or Streptococcus tigurinus. In 7 isolates classified to the Mitis group, the rnpB sequences deviated strikingly from all reference sequences, and additional analysis of sodA and groEL genes indicated the occurrence of yet unidentified Streptococcus spp., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A total of 154 episodes of infective endocarditis (IE) in 149 patients were studied retrospectively with special regard to the major aetiological groups and the surgical evaluation. There were 136 episodes of native valve endocarditis (NVE) (88%) and 18 episodes of prosthetic valve endocarditis (PVE) (12%). Three major groups of NVE crystallized: Streptococcus viridans in 37 (27%), Staphylococcus aureus in 39 (29%) and culture negative IE in 28 (21%) episodes. In these groups surgery during the active phase was required in 41, 28 and 18%, respectively. At the operation myocardial abscess was found in as many as 7/15 cases with S. viridans, but in only in 3/11 cases with S. aureus and 1/5 cases with culture negative IE. The mean duration of preoperative antibiotic treatment was 34 d. This long period of unsuccessful pharmacotherapy, preceded by a mean of 47 d from start of symptoms to admission to hospital, has probably resulted in the high frequency of myocardial abscess in S. viridans NVE. Surgical evaluation should be considered when fever persists beyond 10 d of adequate treatment, even in the absence of clinically apparent complications. Among the PVE episodes, 11/18 were managed with pharmacological treatment alone. Uncomplicated PVE may thus often be successfully treated with antibiotics alone.

A mouse platelet-derived growth factor A chain (PDGF-A) null allele is shown to be homozygous lethal, with two distinct restriction points, one prenatally before E10 and one postnatally. Postnatally surviving PDGF-A-deficient mice develop lung emphysema secondary to the failure of alveolar septation. This is apparently caused by the loss of alveolar myofibroblasts and associated elastin fiber deposits. PDGF alpha receptor-positive cells in the lung having the location of putative alveolar myofibroblast progenitors were specifically absent in PDGF-A null mutants. We conclude that PDGF-A is crucial for alveolar myofibroblast ontogeny. We have previously shown that PDGF-B is required in the ontogeny of kidney mesangial cells. The PDGFs therefore appear to regulate the generation of specific populations of myofibroblasts during mammalian development. The two PDGF null phenotypes also reveal analogous morphogenetic functions for myofibroblast-type cells in lung and kidney organogenesis.

A considerable body of literature advocates and defines treatment of vocal cord cancer with posterior extension by hemilaryngectomy. The present study was carried out to determine the feasibility of using a newly devised pedicle flap, composed of thyroid cartilage and inferior constrictor muscle, to replace the ablated arytenoid cartilage. Animal investigation revealed satisfactory viability of the pedicle flap in canines, and in humans, five patients with T2 glottic carcinoma demonstrated excellent postoperative deglutition and return of voice. The results of the study indicate that this surgical technique merits consideration for its use in minimizing protracted glottic incompetence following hemilaryngectomy. The thyroid cartilage-inferior constrictor muscle pedicle flap may also prove useful as partial cricoid replacement in selected cases of subglottic extension and in cricoid reconstruction following trauma.