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Mandana Fallahpour,1,2 Heather Fritz,3 Charlotta Thunborg,2,4 Ulrika Akenine,2 Miia Kivipelto2,5,6 1Department of Neurobiology, Care Sciences and Society, Division of Occupational Therapy, Karolinska Institutet, Stockholm, Sweden; 2Department of Neurobiology, Care Sciences and Society, Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; 3School of Occupational Therapy, Pacific Northwest University of Health Sciences, Yakima, WA, USA; 4School of Health, Care and Social Welfare, Department of Physiotherapy, Mälardalen University, Västerås, Sweden; 5Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; 6Stockholms Sjukhem, Research & Development Unit, Stockholm, SwedenCorrespondence: Mandana Fallahpour, Department of Neurobiology, Care Sciences and Society, Division of Occupational Therapy, Karolinska Institutet, Stockholm, Sweden, Email mandana.fallahpour@ki.seIntroduction: Identifying strategies to prevent or delay cognitive decline among the rising numbers of elderly is acknowledged as a global public health priority. Research suggests that an active lifestyle in terms of participation in activities has the potential to reduce the risk of later-life cognitive decline. The concept of “active everyday life”, however, needs to be further explored.Aim: The study aimed to explore and describe the active everyday lives of persons with prodromal Alzheimer’s disease (AD) in terms of quality of participation in activities and perceived restrictions.Methods: This qualitative study was part of a larger project, the MIND-ADMINI trial. Nine in-depth interviews were conducted with seven participants (2 males, 5 females; mean age of 72.3) at baseline before the intervention. The data were collected from January to October 2018 and analyzed using the grounded theory approach.Results: Four categories emerged from the analysis: (i) active body and mind; (ii) doing desired meaningful activities to feel engaged, contented, and satisfied; (iii) doing in the context of being connected to others; (iv) ability in making decisions and taking actions. From these categories, which presented the key elements of an active everyday life, a core category was identified: Living a complete life in flow.Conclusion: The findings suggest key elements of participation quality that contribute to an active life. The identified elements are important to be considered in rehabilitation to provide opportunities and possibilities for participation to enable and improve the quality of participation among persons with cognitive impairments.Keywords: Alzheimer’s disease, everyday life, activity, participation, prevention, qualitative method

The global effort to sequence millions of SARS-CoV-2 genomes has provided an unprecedented view of viral evolution. Characterizing how selection acts on SARS-CoV-2 is critical to developing effective, long-lasting vaccines and other treatments, but the scale and complexity of genomic surveillance data make rigorous analysis challenging. To meet this challenge, we develop Bayesian Viral Allele Selection (BVAS), a principled and scalable probabilistic method for inferring the genetic determinants of differential viral fitness and the relative growth rates of viral lineages, including newly emergent lineages. After demonstrating the accuracy and efficacy of our method through simulation, we apply BVAS to 6.9 million SARS-CoV-2 genomes. We identify numerous mutations that increase fitness, including previously identified mutations in the SARS-CoV-2 Spike and Nucleocapsid proteins, as well as mutations in non-structural proteins whose contribution to fitness is less well characterized. In addition, we extend our baseline model to identify mutations whose fitness exhibits strong dependence on vaccination status as well as pairwise interaction effects, i.e. epistasis. Strikingly, both these analyses point to the pivotal role played by the N501 residue in the Spike protein. Our method, which couples Bayesian variable selection with a diffusion approximation in allele frequency space, lays a foundation for identifying fitness-associated mutations under the assumption that most alleles are neutral.

Abstract Introduction The aim of our analysis was to compare the effectiveness of the XEN45 gel stent implantation in patients without and with prior glaucoma intervention. Methods Retrospective analysis including 148 medical records of consecutive glaucoma eyes without prior glaucoma intervention (group A, n = 45) or with prior glaucoma intervention (group B, n = 103). Follow-up data up to 12 months after XEN45 gel implantation were available for all eyes. Results At 12 months, qualified success (IOP reduction of ≥ 20% and IOP

Abstract Purpose To compare efficacy and safety results of an ab interno gel implant in patients with pseudoexfoliation glaucoma (PXG) and primary open angle glaucoma (POAG). Methods Retrospective analysis of the medical records of 110 consecutive eyes with open angle glaucoma who had received a XEN45 gel implant between March 2014 and June 2015. Intraocular pressure course, number of glaucoma medications, the need for additional intervention (including needling) and complications were evaluated until 12 months postoperatively. Results Data of 67 eyes with POAG and 43 eyes with PXG were analyzed. At 12 months postoperatively, the mean IOP had significantly decreased by 54.0% from preoperatively 31.85 ± 8.5 mmHg to 13.99 ± 2.6 mmHg in the POAG group, (p = 0.000; Wilcoxon test), and by 55.2% from 31.63 ± 9.0 mmHg to 13.28 ± 3.1 mmHg in the PXG group (p = 0.000; Wilcoxon test). The mean number of anti-glaucoma medications had significantly decreased from 3.25 ± 0.8 at baseline to 0.3 ± 0.7 medications at 12 months postoperatively in POAG eyes (p = 0.000; Wilcoxon test), and from 3.05 ± 1.0 to 0.3 ± 0.6 medications in PXG eyes (p = 0.000; Wilcoxon test). Hypotony (IOP ≤ 6 mmHg) was observed in 2 POAG eyes (3.0%) and in 5 PXG eyes (11.7%) at 1 month but normalized in all eyes at 12 months postoperatively. Severe complications were not observed. No statistically significant differences were found between PXG eyes and POAG eyes. Conclusion Our data indicate that the XEN45 gel implant provides significant and comparable reduction in IOP and anti-glaucoma medication during the one-year follow-up period in POAG as well as PXG eyes. This suggests that it may be a noteworthy alternative to traditional filtering procedures in patients with POAG and PXG respectively.

Abstract Introduction The aim of this study was to assess 36-month outcomes after cataract surgery and implantation of two second-generation trabecular micro-bypass stents (iStent inject, Glaukos Corporation, San Clemente, CA, USA) into eyes with predominantly primary open-angle glaucoma (POAG) or pseudoexfoliative glaucoma (PEX). Methods This prospective, non-randomized, consecutive cohort study included eyes with POAG (n = 60), PEX (n = 15), appositional narrow-angle (n = 4), pigmentary (n = 1), or neovascular (secondary) (n = 1) glaucoma and cataract requiring surgery. All eyes (n = 81) underwent ab interno iStent inject implantation following cataract surgery. Effectiveness endpoints through 36 months included intraocular pressure (IOP), number of medications, and proportion of eyes with ≥ 20% IOP reduction, IOP ≤ 18 mmHg, and IOP ≤ 15 mmHg. Safety measures included corrected distance visual acuity (CDVA), adverse events, and secondary surgeries. Outcomes were evaluated for the overall cohort, and for the POAG and PEX subgroups. Results Preoperatively, 32.1% of eyes had undergone prior glaucoma surgery, 56% were on 3–4 medications, and 1 eye (1%) was medication-free. At 36 months postoperatively, mean IOP reduced by 37% (14.3 ± 1.7 mmHg versus 22.6 ± 6.2 mmHg preoperatively), and mean medication burden decreased by 68% (0.8 ± 0.9 versus 2.5 ± 1.1 medications preoperatively). IOP reduced by ≥ 20% in 78% of eyes; 100% of eyes reached IOP ≤ 18 mmHg and 71% reached ≤ 15 mmHg. Medication burden reduced considerably: 22 eyes (54%) were medication-free compared to 1 eye (1%) preoperatively; 1 eye (2%) required ≥ 3 medications compared to 45 eyes (56%) preoperatively; and 92.7% of eyes required reduced medications postoperatively. From 3 through 36 months, mean IOP remained ≤ 15.0 mmHg, and mean number of medications remained ≤ 0.9. Outcomes in the POAG and PEX subgroups included 33% and 32% lower IOP, and 68% and 64% fewer medications, respectively. iStent inject showed a favorable safety profile, including no intraoperative complications, minimal adverse events, and a stable CDVA. Conclusion This real-world cohort of eyes with various types of glaucoma and considerable disease burden exhibited durable and safe IOP and medication reductions through 36 months following iStent inject implantation with cataract surgery. Outcomes were similarly beneficial in eyes with POAG and PEX. Funding Article processing charges were funded by Glaukos Corporation (San Clemente, CA, USA).

Despite their extensive use, the absolute dating of tree-ring chronologies has not hitherto been independently validated at the global scale. Here, the identification of distinct 14C excursions in 484 individual tree rings, enable the authors to confirm the dating of 44 dendrochronologies from five continents.

Fine-root lifetimes and carbon inputs from roots into soil impact carbon cycle-climate feedbacks yet remain poorly constrained. Here, using annual-growth rings and radiocarbon dating, the authors show that the chronological age of fine roots is substantially younger than that of the carbon used for their growth.

The original version of this Article contained an error in the Data Availability section, which incorrectly read ‘All data will be freely available via https://www.ams.ethz.ch/research.html.’ The correct version states ‘http://www.ams.ethz.ch/research/published-data.html’ in place of ‘https://www.ams.ethz.ch/research.html’. This has been corrected in both the PDF and HTML versions of the Article.

The flow behavior of two commercial liquid crystalline polymers (LCPs), trade name Vectra B 950 and Vectra L 950 supplied by Ticona, was investigated using a capillary rheometer with a special double slit die. The pressure drops in convergent and divergent wedge passage between the two slit sections, which are influenced by the curvature strains in nematic melts, were determined and compared with the pressure drops of a conventional polystyrene (PS) with flexible polymer chains. Furthermore the extensional viscositiy was determined from the pressure drop in convergent wedge passage. The development of the shear induced texture as a function of shear rate was investigated by use of a rapidly coolable double slit die with the same gap design as the double slit die used for viscosity measurement. The structural analysis was performed using polarized light microscopy.

The area covered by boreal forests accounts for ∼16% of the global and 22% of the Northern Hemisphere landmass. Changes in the productivity and functioning of this circumpolar biome not only have strong effects on species composition and diversity at regional to larger scales, but also on the Earth’s carbon cycle. Although temporal inconsistency in the response of tree growth to temperature has been reported from some locations at the higher northern latitudes, a systematic dendroecological network assessment is still missing for most of the boreal zone. Here, we analyze the geographical patterns of changes in summer temperature and precipitation across northern Eurasia >60 °N since 1951 AD, as well as the growth trends and climate responses of 445 Pinus , Larix and Picea ring width chronologies in the same area and period. In contrast to widespread summer warming, fluctuations in precipitation and tree growth are spatially more diverse and overall less distinct. Although the influence of summer temperature on ring formation is increasing with latitude and distinct moisture effects are restricted to a few southern locations, growth sensitivity to June–July temperature variability is only significant at 16.6% of all sites ( p ≤ 0.01). By revealing complex climate constraints on the productivity of Eurasia’s northern forests, our results question the a priori suitability of boreal tree-ring width chronologies for reconstructing summer temperatures. This study further emphasizes regional climate differences and their role on the dynamics of boreal ecosystems, and also underlines the importance of free data access to facilitate the compilation and evaluation of massively replicated and updated dendroecological networks.

Exposing donor mice to carbon monoxide (CO) protects transplanted islet allografts from immune rejection after transplantation (referred as the “donor” effect). In an attempt to understand the mechanisms of the donor effect of CO, we found that donor treatment with CO upregulates expression of peroxisome proliferatoractivated receptor γ (PPARγ), a transcriptional regulator, in isolated islets. In this study, we evaluated whether PPARγ contributes to the survival and function of transplanted islets and whether PPARγ mediates the protective effect of CO in a major mismatch islet allogeneic transplantation model. BALB/c (H-2 d ) islets in which PPARγ activity was induced by its agonists, 15-deoxy-Δ 12–14 -prostaglandin J 2 (15d-PGJ 2 ) or troglitazone were transplanted into C57BL/6 (H-2 b ) recipients that had been rendered diabetic by streptozotocin (STZ). Blood glucose levels of recipients were monitored to determine the function of transplanted islets. Our data indicated that PPARγ activation in islets led to a high percentage of BALB/c islets survived long-term in C57BL/6 recipients. Activation of PPARγ in the donor suppresses expressions of proinflammatory cytokines including tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) in transplanted islets. Blocking PPARγ activity by its antagonist, GW9662, abrogated the donor effect of CO in vivo and in vitro. Our data demonstrate that PPARγ plays a critical role in the survival and function of transplanted islets after transplantation in the recipient. The protective effects of CO are at least in part mediated by PPARγ.

We have previously demonstrated that bilirubin administration to the recipient induces tolerance towards islet cell transplants across a complete MHC mismatch in a mouse model. Here we assess the mechanisms of such protection. Bilirubin treatment of recipients improved function of islet allografts by suppressing expressions of proinflammatory and proapoptotic genes in those islets and by increasing Foxp3 + T regulatory (Treg) cells at the site of transplanted islets at various days after transplantation. No prolongation of graft survival was observed in recipients treated with bilirubin when CD4 + CD25 + T cells were predepleted from those recipients, indicating that Treg cells are necessary for the protective effect of bilirubin. Adoptive transfer of Treg cells from tolerant mice into Rag1 -/- recipients resulted in long-term acceptance of skin allografts in an alloantigen-specific manner, suggesting that Treg cells are sufficient to induce tolerance. In addition, bilirubin treatment promoted de novo generation of Treg cells in Rag1 -/- recipients. Thus, bilirubin treatment to the recipients prolongs islet allograft survival via a Treg-dependent manner in which CD4 + CD25 + Treg cells are both necessary and sufficient for tolerance induction and graft acceptance. Bilirubin treatment promotes de novo generation of Treg cells that might account for the protective effects of bilirubin given to recipients.

A 7-month-old female mixed breed foal with a 2-day history of recumbency and inability to open its mouth convulsed acutely and died and was submitted for necropsy examination. The foal was thin and large patches of haemorrhage were present throughout the peritoneal wall, the diaphragmatic surfaces and the retroperitoneum. Numerous nematode larvae were visible on the serosal surfaces and penetrated and embedded into the subserosa associated with the haemorrhages. The dorsal portion of the abdominal diaphragm had a partial tear and large numbers of nematodes were within the muscle fibres. Histologically, the larvae had a smooth cuticle, polymyarian/coelomyarian musculature and multinucleated intestinal cells, and were typically surrounded by haemorrhage, neutrophils, dense fibrovascular connective tissue and rare multinucleated giant cells. Parasitological examination identified the larvae as Strongylus edentatus based on the morphology of the buccal capsule. Additionally, there was severe muscle necrosis of the tongue and liver tissue analysis detected selenium deficiency. S. edentatus infections are uncommon in California, USA, and are typically non-lethal. In this case, the selenium deficiency may have led to immunosuppression, resulting in the hyperinfection with S. edentatus, and to the muscle damage and tear of the diaphragm. Although ivermectin treatment was indicated in the history, inadequate deworming or anthelmintic resistance may have played a role in the severity of infection.

Toxoplasma gondii is a global, zoonotic parasite capable of infecting any warm-blooded host. Toxoplasmosis can cause a variety of illnesses including abortions and congenital defects in humans, sheep, and goats. Congenital toxoplasmosis is considered to have the highest global disease burden of any foodborne illness in humans. This study examined the potential role of milk as a route of T. gondii transmission between livestock and humans within Mongolian herders, a little-studied population which relies heavily on animals. Milk of Mongolian sheep, goats and Bactrian camels was tested for the presence of T. gondii DNA, and a survey was conducted to ascertain what behavioral and environmental factors were present that might potentiate T. gondii infection within these Mongolian communities. T. gondii DNA was detected in samples from one sheep and five camels. Sequence analysis of DNA from camel milk revealed that two were from potentially virulent T. gondii genotypes. This has implications for public health in the region, as milk is an extremely important source of nutrition and our survey results imply that some people believe consumption of raw camel milk carries health benefits. This is the first report of T. gondii DNA in Bactrian camel milk as well as the first genotypic characterization of T. gondii within Mongolia.

Fine roots support the water and nutrient demands of plants and supply carbon to soils. Quantifying turnover times of fine roots is crucial for modeling soil organic matter dynamics and constraining carbon cycle-climate feedbacks. Here we challenge widely used isotope-based estimates suggesting the turnover of fine roots of trees to be as slow as a decade. By recording annual growth rings of roots from woody plant species, we show that mean chronological ages of fine roots vary from