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Abstract Background Rapamycin is an inhibitor of the mechanistic target of rapamycin (mTOR) protein kinase, and preclinical data demonstrate that it is a promising candidate for a general gero- and neuroprotective treatment in humans. Results from mouse models of Alzheimer’s disease have shown beneficial effects of rapamycin, including preventing or reversing cognitive deficits, reducing amyloid oligomers and tauopathies and normalizing synaptic plasticity and cerebral glucose uptake. The “Evaluating Rapamycin Treatment in Alzheimer’s Disease using Positron Emission Tomography” (ERAP) trial aims to test if these results translate to humans through evaluating the change in cerebral glucose uptake following six months of rapamycin treatment in participants with early-stage Alzheimer’s disease. Methods ERAP is a six-month-long, single-arm, open-label, phase IIa biomarker-driven study evaluating if the drug rapamycin can be repurposed to treat Alzheimer’s disease. Fifteen patients will be included and treated with a weekly dose of 7 mg rapamycin for six months. The primary endpoint will be change in cerebral glucose uptake, measured using [18F]FDG positron emission tomography. Secondary endpoints include changes in cognitive measures, markers in cerebrospinal fluid as well as cerebral blood flow measured using magnetic resonance imaging. As exploratory outcomes, the study will assess change in multiple age-related pathological processes, such as periodontal inflammation, retinal degeneration, bone mineral density loss, atherosclerosis and decreased cardiac function. Discussion The ERAP study is a clinical trial using in vivo imaging biomarkers to assess the repurposing of rapamycin for the treatment of Alzheimer’s disease. If successful, the study would provide a strong rationale for large-scale evaluation of mTOR-inhibitors as a potential disease-modifying treatment in Alzheimer’s disease. Trial registration ClinicalTrials.gov ID NCT06022068, date of registration 2023–08-30.

Abstract Purpose To evaluate if satisfactory post-therapeutic image-based dosimetry can be achieved for Lu-177-DOTATATE treatments using a reduced number of image acquisitions to improve patient comfort and reduce economical costs. Methods 39 patients who underwent 147 treatment cycles of Lu-177-DOTATATE for neuroendocrine tumors were included in the study. A total of 291 and 284 absorbed doses were calculated to kidneys and tumors, respectively. Single-point dosimetry was performed using one SPECT/CT image acquired at 1 d or 7 d post-treatment using a fixed effective half-life (T eff) or using a patient-specific T eff determined for the initial cycle. Also, dose-per-activity values, (D/A)1, were determined from the first cycle and used to calculate doses for subsequent cycles. All absorbed doses were evaluated against “true” doses calculated using both the 1 d and 7 d images. The relation between tumor grade and absorbed doses was also investigated. All dosimetry was performed on SPECT images. Results Absorbed doses to kidneys were most accurate when single-point dosimetry was performed using 1 d images with median ratios in relation to “true” doses in total dose of 1.00 (IQR: 0.97–1.03) when using fixed T eff and 1.01 (IQR: 0.98–1.04) when using T eff from the initial cycle. Calculations based on the 7 d image were most accurate for tumors with corresponding ratios in total absorbed dose of 0.98 (IQR: 0.96–1.00) and 1.00 (IQR: 0.99–1.01) when using a fixed T eff or T eff from the first cycle, respectively. The (D/A)1 approach performed worse, as 2 of 77 total absorbed doses to the kidneys deviated with > 30%, and tumor-absorbed doses were increasingly overestimated with every cycle. Absorbed doses, T eff and 1 d uptake were higher for G1 tumors than G2 tumors. Conclusion Dosimetry can be performed with satisfactory accuracy when using single SPECT/CT images acquired at 1 d for kidneys or at 7 d for tumors.

Abstract Background Hyperthyroidism has been treated with radioiodine therapy for eight decades, with known benefits and side-effects. No consensus exists on which activity dosage and pre-therapeutic measurements are required for optimal treatment, balancing risk of incomplete response, therapy-induced hypothyroidism and radiation exposure. A retrospective analysis was performed to assess these questions. Methods Data was collected on radioiodine treatment outcomes for 904 patients treated for Graves' disease or toxic nodular goitres at our institution during 2016–2020. The prescribed absorbed doses were 120 Gy (Graves’ disease), 200 Gy (toxic multinodular goitre) and 300 Gy (solitary toxic adenoma). Univariate analysis and multivariate regression modelling were used to find factors linked to treatment outcome. Results The cure rate of hyperthyroidism after one administration of radioiodine was 79% for Graves' disease, 94% for toxic multinodular goitre and 98% for solitary toxic adenoma. Thyroid mass, uptake and effective half-life were all significantly associated with cure in Graves’ disease, but not in toxic multinodular goitre. The rates of therapy-induced hypothyroidism were 20% and 29% for toxic multinodular goitre and solitary toxic adenoma. Neither the cure rate nor the hypothyroidism rate was found to be superior among patients with individualised effective half-life measurements in toxic nodular goitres. Poor renal function was associated with dubious iodine uptake measurements but was not found to correlate with worse outcome. Conclusions Multiple measurements of individual iodine uptake for kinetics estimation may be unnecessary, and a population-based value can be used instead. Patients with renal impairment had similar outcome as other patients, but with a higher risk of dubious uptake measurements.

This study reports findings on Internet gambling and problem gambling among Icelandic youth. Participants were 1.537 13-18 year-old students, 786 boys and 747 girls. Results revealed that 56.6% had gambled at least once in the past 12 months and 24.3% on the Internet. Gender and developmental differences were found for Internet gambling, as boys and older age-groups were more likely to gamble on the Internet than girls or younger age groups. Problem gambling for the total sample was 2.2%, but Internet gamblers were more likely to be classified as problem gamblers (7.7%) than non-Internet gamblers (1.1%). A comparison of the findings of this study to earlier studies on adolescents conducted in 2003 and 2004 reveals that Icelandic adolescents are gambling less in land-based types of gambling and more on the Internet. In general, the results of this study thus suggest that the gambling habits of Icelandic youth are changing.

This article explores the way in which love is understood and expressed through the original English lyrics of songs by New Creation Church Singapore (NCC) in comparison to the original songs from Hillsong Church Australia (Hillsong) through the period of 2014–2020. While NCC has a multilingual congregation, reflective of the larger Singaporean society, it composes and releases original contemporary congregational songs (CCS) with English lyrics. English is the primary language in Singapore; however, it is shaped by the languages spoken in homes (e.g., Mandarin, Malay, Tamil). Combined with the theological emphases of NCC, its CCS provide a unique lens into English as a common language of worship. This article demonstrates that while the use of English lyrics is a unifying force for multilingual congregational worship, it is also not benign, but actively shaping Christian confession and associated theology and being shaped by wider multilingual contexts.

The hot Neptune desert is one of the most sparsely populated regions of the exoplanet parameter space, and atmosphere observations of its few residents can provide insights into how such planets have managed to survive in such an inhospitable environment. Here, we present transmission observations of LTT 9779 b, the only known hot Neptune to have retained a significant H/He-dominated atmosphere, taken with JWST NIRISS/SOSS. The 0.6–2.85 μ m transmission spectrum shows evidence for muted spectral features, rejecting a perfectly flat line at >5 σ . We explore water- and methane-dominated atmosphere scenarios for LTT 9779 b’s terminator, and retrieval analyses reveal a continuum of potential combinations of metallicity and cloudiness. Through comparisons to previous population synthesis works and our own interior structure modeling, we are able to constrain LTT 9779 b’s atmosphere metallicity to 20–850× solar. Within this range of metallicity, our retrieval analyses prefer solutions with clouds at millibar pressures, regardless of whether the atmosphere is water or methane dominated—though cloud-free atmospheres with metallicities >500× solar cannot be entirely ruled out. By comparing self-consistent atmosphere temperature profiles with cloud condensation curves, we find that silicate clouds can readily condense in the terminator region of LTT 9779 b. Advection of these clouds onto the dayside could explain the high dayside albedo previously inferred for this planet and be part of a feedback loop aiding the survival of LTT 9779 b’s atmosphere in the hot Neptune desert.

Direct imaging observations are biased toward wide-separation, massive companions that have degenerate formation histories. Although the majority of exoplanets are expected to form via core accretion, most directly imaged exoplanets have not been convincingly demonstrated to follow this formation pathway. We obtained new interferometric observations of the directly imaged giant planet AF Lep b with the VLTI/GRAVITY instrument. We present three epochs of ∼50 μ as relative astrometry and the K -band spectrum of the planet for the first time at a resolution of R = 500. Using only these measurements, spanning less than 2 months, and the Hipparcos-Gaia Catalogue of Accelerations, we are able to significantly constrain the planet’s orbit; this bodes well for interferometric observations of planets discovered by Gaia DR4. Including all available measurements of the planet, we infer an effectively circular orbit ( e < 0.02, 0.07, and 0.13 at 1 σ , 2 σ , and 3 σ , respectively) in spin–orbit alignment with the host and measure a dynamical mass of M _p = 3.75 M _Jup ± 0.5 M _Jup . Models of the spectrum of the planet show that it is metal-rich ([M/H] = 0.75 ± 0.25), with a C/O abundance encompassing the solar value. This ensemble of results shows that the planet is consistent with core accretion formation.

The characterization of young planets (

We present a new grid of cloudy atmosphere and evolution models for substellar objects. These models include the effect of refractory cloud species, including silicate clouds, on the spectra and evolution. We include effective temperatures from 900 to 2400 K and surface gravities from log g = 3.5 to 5.5, appropriate for a broad range of objects with masses between 1 and 84 M _J . Model pressure–temperature structures are calculated assuming radiative–convective and chemical equilibrium. We consider the effect of both clouds and metallicity on the atmospheric structure, resulting spectra, and thermal evolution of substellar worlds. We parameterize clouds using the A. S. Ackerman & M. S. Marley cloud model, including cloud parameter f _sed values from 1 to 8; we include three metallicities (−0.5, 0.0, and +0.5). Refractory clouds and metallicity both alter the evolution of substellar objects, changing the inferred temperature at a given age by up to 100–200 K. For solar-metallicity evolution models including clouds in warm objects, we find a hydrogen-burning minimum mass of 70.2 M _J , close to empirical measurements; we find a deuterium-burning minimum mass of 12.05 M _J (50% of initial D burned). We compare to the observed photometry of brown dwarfs, finding broad agreement with the measured photometry. We publish the spectra, evolution, and other data products online with open access on Zenodo (doi: https://doi.org/10.5281/zenodo.12735103 ).

The recent discoveries of Neptune-sized ultra-short-period planets (USPs) challenge existing planet formation theories. It is unclear whether these residents of the Hot Neptune Desert have similar origins to smaller, rocky USPs, or if this discrete population is evidence of a different formation pathway altogether. We report the discovery of TOI-3261b, an ultrahot Neptune with an orbital period P = 0.88 day. The host star is a V = 13.2 mag, slightly supersolar metallicity ([Fe/H] ≃0.15), inactive K1.5 main-sequence star at d = 300 pc. Using data from the Transiting Exoplanet Survey Satellite and the Las Cumbres Observatory Global Telescope, we find that TOI-3261b has a radius of ${3.82}_{-0.35}^{+0.42}$ R _⊕ . Moreover, radial velocities from ESPRESSO and HARPS reveal a mass of ${30.3}_{-2.4}^{+2.2}$ M _⊕ , more than twice the median mass of Neptune-sized planets on longer orbits. We investigate multiple mechanisms of mass loss that can reproduce the current-day properties of TOI-3261b, simulating the evolution of the planet via tidal stripping and photoevaporation. Thermal evolution models suggest that TOI-3261b should retain an envelope potentially enriched with volatiles constituting ∼5% of its total mass. This is the second highest envelope mass fraction among ultrahot Neptunes discovered to date, making TOI-3261b an ideal candidate for atmospheric follow-up observations.

Hot Neptunes, gaseous planets smaller than Saturn (∼3–8 R _⊕ ) with orbital periods less than 10 days, are rare. Models predict this is due to high-energy stellar irradiation stripping planetary atmospheres over time, often leaving behind only rocky planetary cores. Using our TESS full-frame-image pipeline giants in conjunction with Keck/HIRES radial velocity measurements, we present the discovery of TIC365102760 b, a 6.2 R _⊕ (0.55 R _J ), 19.2 M _⊕ (0.060 M _J ) planet transiting a red giant star every 4.21285 days. The old age and high equilibrium temperature yet remarkably low density of this planet ( ${\rho }_{p}={0.58}_{-0.20}^{+0.30}{\rho }_{{\rm{J}}}$ ) suggest that its gaseous envelope should have been stripped by high-energy stellar irradiation billions of years ago. The present-day planet mass and radius suggest the atmospheric stripping was slower than predicted. Unexpectedly low stellar activity and/or late-stage planet inflation could be responsible for the observed properties of this system. Further studies of this system with more precise photometry in multiple passbands will be capable of revealing more details of this planet’s atmosphere.

Abstract The application of species distribution models (SDMs) to areas outside of where a model was created allows informed decisions across large spatial scales, yet transferability remains a challenge in ecological modeling. We examined how regional variation in animal‐environment relationships influenced model transferability for Canada lynx (Lynx canadensis), with an additional conservation aim of modeling lynx habitat across the northwestern United States. Simultaneously, we explored the effect of sample size from GPS data on SDM model performance and transferability. We used data from three geographically distinct Canada lynx populations in Washington (n = 17 individuals), Montana (n = 66), and Wyoming (n = 10) from 1996 to 2015. We assessed regional variation in lynx‐environment relationships between these three populations using principal components analysis (PCA). We used ensemble modeling to develop SDMs for each population and all populations combined and assessed model prediction and transferability for each model scenario using withheld data and an extensive independent dataset (n = 650). Finally, we examined GPS data efficiency by testing models created with sample sizes of 5%–100% of the original datasets. PCA results indicated some differences in environmental characteristics between populations; models created from individual populations showed differential transferability based on the populations' similarity in PCA space. Despite population differences, a single model created from all populations performed as well, or better, than each individual population. Model performance was mostly insensitive to GPS sample size, with a plateau in predictive ability reached at ~30% of the total GPS dataset when initial sample size was large. Based on these results, we generated well‐validated spatial predictions of Canada lynx distribution across a large portion of the species' southern range, with precipitation and temperature the primary environmental predictors in the model. We also demonstrated substantial redundancy in our large GPS dataset, with predictive performance insensitive to sample sizes above 30% of the original.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease and smooth muscle cells are the most affected cells in HGPS individuals. Here, the authors report a microfluidics platform with HGPS induced pluripotent stem cells and show that inhibition of metalloprotease 13 may reduce smooth muscle cell loss.

Abstract Background Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. Results We develop CellAge ( http://genomics.senescence.info/cells ), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes (C9orf40, CDC25A, CDCA4, CKAP2, GTF3C4, HAUS4, IMMT, MCM7, MTHFD2, MYBL2, NEK2, NIPA2, and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. Conclusions Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence.

“Performing” and “performance” are potentially contentious words within the context of contemporary Christian worship. However, performative elements are explicit in the lyrics of contemporary congregational songs (CCS), and in video recordings of CCS, through the actions of those on stage and in the congregation, as well as in the broader context of staging, lighting, projection, production, and video editing. However, to date, there is only a handful of scholarly works that explore performing in contemporary worship or contemporary worship as performance and most of them are ethnomusicological. This paper seeks to address notions of performing and performance through a broader lens of the most-sung CCS globally, examined through the disciplinary fields of performance studies, musicology, media studies and theology. It involves a two-fold complementary textual analysis of the most-sung CCS lyrics and the most-watched ‘live worship’ videos of those songs on YouTube. In so doing, this study identifies how the Christian music industry at large officially portrays and languages performance in worship songs and also identifies how performative elements are enacted in the live worship videos released. These analyses are finally synthesized to identify how performing and performance are understood and actively portrayed to and by the contemporary church.

We report the discovery and characterization of three giant exoplanets orbiting solar-analog stars, detected by the TESS space mission and confirmed through ground-based photometry and radial velocity measurements taken at La Silla observatory with FEROS. TOI-2373 b is a warm Jupiter orbiting its host star every ∼13.3 days, and is one of the most massive known exoplanet with a precisely determined mass and radius around a star similar to the Sun, with an estimated mass of m _p = ${9.3}_{-0.2}^{+0.2}\,{M}_{\mathrm{jup}}$ and a radius of r _p = ${0.93}_{-0.2}^{+0.2}\,{R}_{\mathrm{jup}}$ . With a mean density of $\rho ={14.4}_{-1.0}^{+0.9}\,{\rm{g}}\,{\mathrm{cm}}^{-3}$ , TOI-2373 b is among the densest planets discovered so far. TOI-2416 b orbits its host star on a moderately eccentric orbit with a period of ∼8.3 days and an eccentricity of e = ${0.32}_{-0.02}^{+0.02}$ . TOI-2416 b is more massive than Jupiter with m _p = ${3.0}_{-0.09}^{+0.10}\,{M}_{\mathrm{jup}}$ , however is significantly smaller with a radius of r _p = ${0.88}_{-0.02}^{+0.02},{R}_{\mathrm{jup}}$ , leading to a high mean density of $\rho ={5.4}_{-0.3}^{+0.3}\,{\rm{g}}\,{\mathrm{cm}}^{-3}$ . TOI-2524 b is a warm Jupiter near the hot Jupiter transition region, orbiting its star every ∼7.2 days on a circular orbit. It is less massive than Jupiter with a mass of m _p = ${0.64}_{-0.04}^{+0.04}\,{M}_{\mathrm{jup}}$ , and is consistent with an inflated radius of r _p = ${1.00}_{-0.03}^{+0.02}\,{R}_{\mathrm{jup}}$ , leading to a low mean density of $\rho ={0.79}_{-0.08}^{+0.08}\,{\rm{g}}\,{\mathrm{cm}}^{-3}$ . The newly discovered exoplanets TOI-2373 b, TOI-2416 b, and TOI-2524 b have estimated equilibrium temperatures of ${860}_{-10}^{+10}$ K, ${1080}_{-10}^{+10}$ K, and ${1100}_{-20}^{+20}$ K, respectively, placing them in the sparsely populated transition zone between hot and warm Jupiters.

Large-scale exoplanet surveys like the Transiting Exoplanet Survey Satellite (TESS) mission are powerful tools for discovering large numbers of exoplanet candidates. Single-transit events are commonplace within the resulting candidate list due to the unavoidable limitation of the observing baseline. These single-transit planets often remain unverified due to their unknown orbital periods and consequent difficulty in scheduling follow-up observations. In some cases, radial velocity (RV) follow up can constrain the period enough to enable a future targeted transit detection. We present the confirmation of one such planet: TOI-2010 b. Nearly three years of RV coverage determined the period to a level where a broad window search could be undertaken with the Near-Earth Object Surveillance Satellite, detecting an additional transit. An additional detection in a much later TESS sector solidified our final parameter estimation. We find TOI-2010 b to be a Jovian planet ( M _P = 1.29 M _Jup , R _P = 1.05 R _Jup ) on a mildly eccentric orbit ( e = 0.21) with a period of P = 141.83403 days. Assuming a simple model with no albedo and perfect heat redistribution, the equilibrium temperature ranges from about 360 to 450 K from apastron to periastron. Its wide orbit and bright host star ( V = 9.85) make TOI-2010 b a valuable test bed for future low-insolation atmospheric analysis.

Kepler-289 is a three-planet system containing two sub-Neptunes and one cool giant planet orbiting a young, Sun-like star. All three planets exhibit transit timing variations (TTVs), with both adjacent planet pairs having orbital periods close to the 2:1 orbital resonance. We observe two transits of Kepler-289c with the Wide-field InfraRed Camera on the 200″ Hale Telescope at Palomar Observatory, using diffuser-assisted photometry to achieve space-like photometric precision from the ground. These new transit observations extend the original four-year Kepler TTV baseline by an additional 7.5 yr. We rereduce the archival Kepler data with an improved stellar activity correction and carry out a joint fit with the Palomar data to constrain the transit shapes and derive updated transit times. We then model the TTVs to determine the masses of the three planets and constrain their densities and bulk compositions. Our new analysis improves on previous mass and density constraints by a factor of two or more for all three planets, with the innermost planet showing the largest improvement. Our updated atmospheric mass fractions for the inner two planets indicate that they have hydrogen-rich envelopes, consistent with their location on the upper side of the radius valley. We also constrain the heavy element composition of the outer Saturn-mass planet, Kepler-289c, for the first time, finding that it contains 30.5 ± 6.9 M _⊕ of metals. We use dust evolution models to show that Kepler-289c must have formed beyond 1 au, and likely beyond 3 au, and then migrated inward.

During RV MS Merian expedition MSM75, an international, multidisciplinary team explored the Reykjanes Ridge from June to August 2018. The first area of study, Steinahóll (150–350 m depth), was chosen based on previous seismic data indicating hydrothermal activity. The sampling strategy included ship- and AUV-mounted multibeam surveys, Remotely Operated Vehicle (ROV), Epibenthic Sledge (EBS), and van Veen grab (vV) deployments. Upon returning to Steinahóll during the final days of MSM75, hydrothermal vent sites were discovered using the ROV Phoca (Kiel, GEOMAR). Here we describe and name three new, distinct hydrothermal vent site vulnerable marine ecosystems (VMEs); Hafgufa, Stökkull, Lyngbakr. The hydrothermal vent sites consisted of multiple anhydrite chimneys with large quantities of bacterial mats visible. The largest of the three sites (Hafgufa) was mapped, and reconstructed in 3D. In total 23,310 individual biological specimens were sampled comprising 41 higher taxa. Unique fauna located in the hydrothermally venting areas included two putative new species of harpacticoid copepod (Tisbe sp. nov. and Amphiascus sp. nov.), as well as the sponge Lycopodina cupressiformis (Carter, 1874). Capitellidae Grube, 1862 and Dorvilleidae Chamberlin, 1919 families dominated hydrothermally influenced samples for polychaetes. Around the hydrothermally influenced sites we observed a notable lack of megafauna, with only a few species being present. While we observed hydrothermal associations, the overall species composition is very similar to that seen at other shallow water vent sites in the north of Iceland, such as the Mohns Ridge vent fields, particularly with peracarid crustaceans. We therefore conclude the community overall reflects the usual “background” fauna of Iceland rather than consisting of “vent endemic” communities as is observed in deeper vent systems, with a few opportunistic species capable of utilizing this specialist environment.

Translation as a form of music localization does not only occur in diverse cultural or lingual contexts, it also occurs within an ostensibly homogenous culture and language. The global genre of contemporary congregational songs (CCS) is written and performed through a variety of theological lenses. Sometimes a theological position conveyed in, or ascribed to, CCS can be problematic for certain local expressions of the Christian faith to replicate without needing to alter lyrics, and/or musical content, or at least reinterpret those lyrics in a way which aligns with their theological understanding. This article explores popular CCS, as measured by Christian Copyright Licensing International (CCLI) which have been either accepted, rejected, reinterpreted, or otherwise altered in order to play their part in defining local (English-speaking) church worship and identity. Translation studies and music semiology are applied to selected CCS to demonstrate this nuanced interpretation of “translation” in the localizing of religious musical practice

Species interactions like parasitism influence the outcome of climate-driven shifts in species ranges. For some host species, parasitism can only occur in that part of its range that overlaps with a second host species. Thus, predicting future parasitism may depend on how the ranges of the two hosts change in relation to each other. In this study, we tested whether the climate driven species range shift of Odocoileus virginianus (white-tailed deer) accounts for predicted changes in parasitism of two other species from the family Cervidae, Alces alces (moose) and Rangifer tarandus (caribou), in North America. We used MaxEnt models to predict the recent (2000) and future (2050) ranges (probabilities of occurrence) of the cervids and a parasite Parelaphostrongylus tenuis (brainworm) taking into account range shifts of the parasite’s intermediate gastropod hosts. Our models predicted that range overlap between A. alces/R. tarandus and P. tenuis will decrease between 2000 and 2050, an outcome that reflects decreased overlap between A. alces/R. tarandus and O. virginianus and not the parasites, themselves. Geographically, our models predicted increasing potential occurrence of P. tenuis where A. alces/R. tarandus are likely to decline, but minimal spatial overlap where A. alces/R. tarandus are likely to increase. Thus, parasitism may exacerbate climate-mediated southern contraction of A. alces and R. tarandus ranges but will have limited influence on northward range expansion. Our results suggest that the spatial dynamics of one host species may be the driving force behind future rates of parasitism for another host species.

Self-incompatibility (SI) is a mechanism that many flowering plants employ to prevent fertilisation by self- and self-like pollen ensuring heterozygosity and hybrid vigour. Although a number of single locus mechanisms have been characterised in detail, no multi-locus systems have been fully elucidated. Historically, examples of the genetic analysis of multi-locus SI, to make analysis tractable, are either made on the progeny of bi-parental crosses, where the number of alleles at each locus is restricted, or on crosses prepared in such a way that only one of the SI loci segregates. Perennial ryegrass (Lolium perenne L.) possesses a well-documented two locus (S and Z) gametophytic incompatibility system. A more universal, realistic proof of principle study was conducted in a perennial ryegrass population in which allelic and non-allelic diversity was not artificially restricted. A complex pattern of pollinations from a diallel cross was revealed which could not possibly be interpreted easily per se, even with an already established genetic model. Instead, pollination scores were distilled into principal component scores described as Compatibility Components (CC1-CC3). These were then subjected to a conventional genome-wide association analysis. CC1 associated with markers on linkage groups (LGs) 1, 2, 3, and 6, CC2 exclusively with markers in a genomic region on LG 2, and CC3 with markers on LG 1. BLAST alignment with the Brachypodium physical map revealed highly significantly associated markers with peak associations with genes adjacent and four genes away from the chromosomal locations of candidate SI genes, S- and Z-DUF247, respectively. Further significant associations were found in a Brachypodium distachyon chromosome 3 region, having shared synteny with Lolium LG 1, suggesting further SI loci linked to S or extensive micro-re-arrangement of the genome between B. distachyon and L. perenne. Significant associations with gene sequences aligning with marker sequences on Lolium LGs 3 and 6 were also identified. We therefore demonstrate the power of a novel association genetics approach to identify the genes controlling multi-locus gametophytic SI systems and to identify novel loci potentially involved in already established SI systems.

We report a range extension and new country record for Scarthyla vigilans in Trinidad, West Indies. The species was previously known only from populations on mainland South America. We include notes on behavior, habitat and tadpole development, and discuss the biogeographical significance of the species’ presence in Trinidad, particularly with respect to consequences for understanding colonization events on this Caribbean island.

Many instruments have been developed to measure the multidimensional construct of quality of life. One of them has been developed by the World Health Organization (WHOQOL-100) and adapted into different languages and cultures around the world. The authors of this study wanted to assess the measurement properties of the Turkish version of WHOQOL-100, to find out the latent factors underlying quality of life, and to determine the direction and magnitude of the interdependent effects among these factors by using structural equation modeling (SEM). The measurement properties of the Turkish version of WHOQOL-100 scale were assessed on 520 voluntary participants who were immigrants in Stockholm/Sweden. SEM gave us one second-order factor QOL and the five correlated first-order factors labelled: physical, social relations, psychological, environment and independence. In the model for total participants, all the factor loadings were high (ranging from 0.60 to 0.92 except for “sexuality” which was 0.47), indicating a strong association between each of the latent factors and their respective items. In the models which were separately constructed regarding birthplace, the authors found a strong association between each of the latent factors and their respective items. The most substantial possible effect on QOL was psychological domain (0.93), which was larger than physical health (0.84), social relations (0.82), level of independence (0.91) and environment (0.73). The effect of psychological domain on the overall quality of life is greater than those of other domains.

Harald Cramér is one of the great persons in the history of mathematical statistics and insurance mathematics in the twentieth century. He is perhaps the most well known Swedish statistician in modern time. The editor of “Lithuanian Journal of Statistics” has kindly asked me to write some notes on Harald Cramér, may be because my supervisor was one of Cramér’s pupils. I am not the best person to do so, but I will do my best. At the end I will also give some references for those who want to read more about Cramér.

Objective: To examine the effects and safety of using endoscopic spray cryotherapy (ESC) on bladder, ureteral, and renal pelvis urothelium in a live porcine model. Subjects and methods: ESC treatments were systematically applied to urothelial sites in the bladder, ureter, and renal pelvis of eight female Yorkshire swine in a prospective trial. Freeze–thaw cycles ranged from 5 to 60 s/cycle for one to six cycles using a 7 French cryotherapy catheter. Tissue was evaluated histologically for treatment-related effects. Acute physiologic effects were evaluated with pulse oximetry, Doppler sonography, and postmortem findings. Results: In bladder, treatment depth was inconsistent regardless of dose, demonstrating urothelial necrosis in one, muscularis propria depth necrosis in two, and full thickness necrosis in all remaining samples. In ureter, full thickness necrosis was seen in all samples, even with the shortest spray duration (5 s/cycle for six cycles or 30 s/cycle for one cycle). Treatment to the renal pelvis was complicated by adiabatic gas expansion of liquid nitrogen to its gaseous state, resulting in high intraluminal pressures requiring venting to avoid organ perforation, even at the lowest treatment settings. At a planned dose of 5 s/cycle for six cycles of the first renal pelvis animal, treatment was interrupted by sudden and unrecoverable cardiopulmonary failure after three cycles. Repeated studies replicated this event. Ultrasound and immediate necropsy confirmed the creation of a large gaseous embolism and reproducible cardiopulmonary effects. Conclusion: ESC in a porcine urothelial treatment model results in full-thickness tissue necrosis in bladder, ureter, and renal pelvis at a minimal treatment settings of 5 s/cycle for six cycles. Adiabatic gas expansion may result in fatal pyelovenous gas embolism and collateral organ injury, as seen in both animals receiving treatment to the renal pelvis in this study. These results raise safety concerns for use of ESC as a treatment modality in urothelial tissues with current device settings.

Comedy, as a discourse, is often the object of censorship and moral outrage, both of which are misguided. Here, it is argued both that censorship of any discourse is to be avoided, as it can serve no progressive purpose, and that moral outrage directed at comedy fundamentally misunderstands its nature, as it serves as a cathartic, vaccinating discourse that allows us greater understanding of ourselves and the world in which we live.

Obesity is a major cause of morbidity and mortality resulting in pathologic changes in virtually every organ system. Although the cardiovascular system has been a focus of intense study, the effects of obesity on the lymphatic system remain essentially unknown. The purpose of this study was to identify the pathologic consequences of diet induced obesity (DIO) on the lymphatic system.Adult male wild-type or RAG C57B6-6J mice were fed a high fat (60%) or normal chow diet for 8-10 weeks followed by analysis of lymphatic transport capacity. In addition, we assessed migration of dendritic cells (DCs) to local lymph nodes, lymph node architecture, and lymph node cellular make up.High fat diet resulted in obesity in both wild-type and RAG mice and significantly impaired lymphatic fluid transport and lymph node uptake; interestingly, obese wild-type but not obese RAG mice had significantly impaired migration of DCs to the peripheral lymph nodes. Obesity also resulted in significant changes in the macro and microscopic anatomy of lymph nodes as reflected by a marked decrease in size of inguinal lymph nodes (3.4-fold), decreased number of lymph node lymphatics (1.6-fold), loss of follicular pattern of B cells, and dysregulation of CCL21 expression gradients. Finally, obesity resulted in a significant decrease in the number of lymph node T cells and increased number of B cells and macrophages.Obesity has significant negative effects on lymphatic transport, DC cell migration, and lymph node architecture. Loss of T and B cell inflammatory reactions does not protect from impaired lymphatic fluid transport but preserves DC migration capacity. Future studies are needed to determine how the interplay between diet, obesity, and the lymphatic system modulate systemic complications of obesity.

Introduction: Paediatric consultations require safe and unambiguous communication. For children and adolescents of foreign ethnic and language backgrounds, professional interpretation may be crucial to avoid misunderstandings and malpractice. Knowledge about language barriers in paediatric consultations in the Danish healthcare is sparse., Methods: The study was based on questionnaires completed by medical professionals at two paediatric emergency units in Copenhagen from March through June 2018. Questionnaire A, completed by doctors, addressed all patients aged 0-18 years regardless of the parents' first language and, if foreign, the presence of language barriers, whether clinical management was affected and use of professional interpretation. All doctors and nurses were asked to complete questionnaire B addressing their knowledge, experiences and practices with language barriers in their clinical work., Results: Language barriers were present in 37% of 136 non-native-Danish consultations. In 44% of these, clinical management was affected. Professional interpretation was not used in any consultations. Almost half of the medical professionals reported insufficient communication opportunities with non-native-Danish-speaking patients (48%)., Conclusions: Language barriers frequently affected communication and clinical decision-making in the two Danish paediatric emergency units studied. Even so, professional interpretation was not used. Further studies are needed to explore whether language is a barrier to equal health., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)