In physically realistic, scalar-field-based dynamical dark energy models (including, e.g., quintessence), one naturally expects the scalar field to couple to the rest of the model’s degrees of ...freedom. In particular, a coupling to the electromagnetic sector leads to a time (redshift) dependence in the fine-structure constant and a violation of the weak equivalence principle. Here we extend the previous
Euclid
forecast constraints on dark energy models to this enlarged (but physically more realistic) parameter space, and forecast how well
Euclid
, together with high-resolution spectroscopic data and local experiments, can constrain these models. Our analysis combines simulated
Euclid
data products with astrophysical measurements of the fine-structure constant,
α
, and local experimental constraints, and it includes both parametric and non-parametric methods. For the astrophysical measurements of
α
, we consider both the currently available data and a simulated dataset representative of Extremely Large Telescope measurements that are expected to be available in the 2030s. Our parametric analysis shows that in the latter case, the inclusion of astrophysical and local data improves the
Euclid
dark energy figure of merit by between 8% and 26%, depending on the correct fiducial model, with the improvements being larger in the null case where the fiducial coupling to the electromagnetic sector is vanishing. These improvements would be smaller with the current astrophysical data. Moreover, we illustrate how a genetic algorithms based reconstruction provides a null test for the presence of the coupling. Our results highlight the importance of complementing surveys like
Euclid
with external data products, in order to accurately test the wider parameter spaces of physically motivated paradigms.
Purpose
In order to better define the breast cancer (BC) genetic risk factors in men, a germline investigation was carried out on 81 Male BC cases by screening the 24 genes involved in BC ...predisposition, genome stability maintenance and DNA repair mechanisms by next-generation sequencing.
Methods
Germline DNAs were tested in a custom multi-gene panel focused on all coding exons and exon–intron boundaries of 24 selected genes using two amplicon-based assays on PGM-Ion Torrent (ThermoFisher Scientific) and MiSeq (Illumina) platforms. All variants were recorded and classified by using a custom pipeline.
Results
Clinical pathological data and the family history of 81 Male BC cases were gathered and analysed, revealing the average age of onset to be 61.3 years old and that in 35 cases there was a family history of BC. Our genetic screening allowed us to identify a germline mutation in 22 patients (23%) in 4 genes:
BRCA2
,
BRIP1
,
MUTYH
and
PMS2
. Moreover, 12 variants of unknown clinical significance (VUS) in 9 genes (
BARD1
,
BRCA1
,
BRIP1
,
CHEK2
,
ERCC1
,
NBN
,
PALB2
,
PMS1
,
RAD50
) were predicted as potentially pathogenic by in silico analysis bringing the mutation detection rate up to 40%.
Conclusion
As expected, a positive family history is a strong predictor of germline
BRCA2
mutations in male BC. Understanding the potential pathogenicity of VUS represents an extremely urgent need for the management of BC risk in Male BC cases and their own families.
Oceanographic changes adjacent to Antarctica have global climatic and ecological impacts. However, this is the most challenging place in the world to obtain marine data due to its remoteness and ...inhospitable nature, especially in winter. Here, we present more than 2000 Conductivity-Temperature-Depth (CTD) profiles and associated water sample data collected with (almost uniquely) full year-round coverage from the British Antarctic Survey Rothera Research Station at the west Antarctic Peninsula. Sampling is conducted from a small boat or a sled, depending on the sea ice conditions. When conditions allow, sampling is twice weekly in summer and weekly in winter, with profiling to nominally 500 m and with discrete water samples taken at 15 m water depth. Daily observations are made of the sea ice conditions in the area. This paper presents the first 20 years of data collection, 1997-2017. This time series represents a unique and valuable resource for investigations of the high-latitude ocean's role in climate change, ocean/ice interactions, and marine biogeochemistry and carbon drawdown.
Summary
Patients with cystic fibrosis awaiting lung transplantation for end-stage respiratory failure have high prevalence of reduced bone mineral density and fragility fracture. Suboptimal ...25-hydroxyvitamin D levels could significantly contribute to the development of cystic fibrosis-related bone disease.
Introduction
The assessment of the prevalence of cystic fibrosis-related bone disease (CFBD) and its associated risk factors in young adults with cystic fibrosis (CF) awaiting lung transplantation for end-stage respiratory failure.
Methods
Clinical characteristics, bone mineral density (BMD), the parameters of calcium metabolism, including vitamin D (25OHVitD) levels, and the presence of fragility fractures were evaluated in 42 CF patients (24 females, age 34.0 ± 8.4 years) consecutively referred as lung transplant candidates.
Results
Mean 25OHVitD levels (54.9 ± 26.2 nmol/L) were below the reference range and hypovitaminosis D (25OHVitD < 75 nmol/L) was found in 34 patients (81%) and daily calcium intakes (median 550 mg/day) were lower than recommended. A BMD below the expected range for age (Z-score of − 2.0 or lower) and at least one prevalent fragility fracture were found in 22 patients (52.4%) and 18 patients (45.2%), respectively. The coexistence of low BMD and the presence of fracture was observed in 13 patients (31.0%). In these patients, the prevalence of nephrolithiasis was higher than in the remaining ones (
p
= 0.046). The presence of kidney stones was associated with a worse bone status and with severe vitamin D deficiency. In the whole sample, femoral BMD Z-scores were directly correlated with albumin-adjusted calcium (
p
< 0.05) and 25OHVitD levels (
p
< 0.01).
Conclusions
Despite the improvement of CF care, CFBD is still highly prevalent in young adults awaiting lung transplantation for end-stage CF. Suboptimal 25OHVitD levels could significantly contribute to the development of CFBD. The presence of nephrolithiasis could be an additional warning about the need for a careful evaluation of bone health in CF patients.
The Planck clusters in the LOFAR sky Botteon, A.; Shimwell, T. W.; Cassano, R. ...
Astronomy and astrophysics (Berlin),
04/2022, Letnik:
660
Journal Article
Recenzirano
Context.
Relativistic electrons and magnetic fields permeate the intra-cluster medium (ICM) and manifest themselves as diffuse sources of synchrotron emission observable at radio wavelengths, namely ...radio halos and radio relics. Although there is broad consensus that the formation of these sources is connected to turbulence and shocks in the ICM, the details of the required particle acceleration, the strength and morphology of the magnetic field in the cluster volume, and the influence of other sources of high-energy particles are poorly known.
Aims.
Sufficiently large samples of radio halos and relics, which would allow us to examine the variation among the source population and pinpoint their commonalities and differences, are still missing. At present, due to the physical properties of the sources and the capabilities of existing facilities, large numbers of these sources are easiest to detect at low radio frequencies, where they shine brightly.
Methods.
We examined the low-frequency radio emission from all 309 clusters in the second catalog of
Planck
Sunyaev Zel’dovich detected sources that lie within the 5634 deg
2
covered by the Second Data Release of the LOFAR Two-meter Sky Survey (LoTSS-DR2). We produced LOFAR images at different resolutions, with and without discrete sources subtracted, and created overlays with optical and X-ray images before classifying the diffuse sources in the ICM, guided by a decision tree.
Results.
Overall, we found 83 clusters that host a radio halo and 26 that host one or more radio relics (including candidates). About half of them are new discoveries. The detection rate of clusters that host a radio halo and one or more relics in our sample is 30 ± 11% and 10 ± 6%, respectively. Extrapolating these numbers, we anticipate that once LoTSS covers the entire northern sky it will provide the detection of 251 ± 92 clusters that host a halo and 83 ± 50 clusters that host at least one relic from
Planck
clusters alone. All images and results produced in this work are publicly available via the project website.
Cytomegalovirus (CMV) infection, either de novo or as reactivation after allotransplantation and chronic immunosuppression, is recognized to cause detrimental alloimmune effects, inclusive of higher ...susceptibility to graft rejection and substantive impact on chronic graft injury and reduced transplant survival. To obtain further insights into the evolution and pathogenesis of CMV infection in an immunocompromised host we evaluated changes in the circulating host proteome serially, before and after transplantation, and during and after CMV DNA replication (DNAemia), as measured by quantitative polymerase chain reaction (QPCR).
LC-MS-based proteomics was conducted on 168 serially banked plasma samples, from 62 propensity score-matched kidney transplant recipients. Patients were stratified by CMV replication status into 31 with CMV DNAemia and 31 without CMV DNAemia. Patients had blood samples drawn at protocol times of 3- and 12-months post-transplant. Additionally, blood samples were also drawn before and 1 week and 1 month after detection of CMV DNAemia. Plasma proteins were analyzed using an LCMS 8060 triple quadrupole mass spectrometer. Further, public transcriptomic data on time matched PBMCs samples from the same patients was utilized to evaluate integrative pathways. Data analysis was conducted using R and Limma.
Samples were segregated based on their proteomic profiles with respect to their CMV Dnaemia status. A subset of 17 plasma proteins was observed to predict the onset of CMV at 3 months post-transplant enriching platelet degranulation (FDR, 4.83E-06), acute inflammatory response (FDR, 0.0018), blood coagulation (FDR, 0.0018) pathways. An increase in many immune complex proteins were observed at CMV infection. Prior to DNAemia the plasma proteome showed changes in the anti-inflammatory adipokine vaspin (SERPINA12), copper binding protein ceruloplasmin (CP), complement activation (FDR = 0.03), and proteins enriched in the humoral (FDR = 0.01) and innate immune responses (FDR = 0.01).
Plasma proteomic and transcriptional perturbations impacting humoral and innate immune pathways are observed during CMV infection and provide biomarkers for CMV disease prediction and resolution. Further studies to understand the clinical impact of these pathways can help in the formulation of different types and duration of anti-viral therapies for the management of CMV infection in the immunocompromised host.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Individuals with autism spectrum disorder (ASD) exhibit an increased burden of de novo mutations (DNMs) in a broadening range of genes. While these studies have implicated hundreds of genes in ASD ...pathogenesis, which DNMs cause functional consequences in vivo remains unclear. We functionally test the effects of ASD missense DNMs using Drosophila through “humanization” rescue and overexpression-based strategies. We examine 79 ASD variants in 74 genes identified in the Simons Simplex Collection and find 38% of them to cause functional alterations. Moreover, we identify GLRA2 as the cause of a spectrum of neurodevelopmental phenotypes beyond ASD in 13 previously undiagnosed subjects. Functional characterization of variants in ASD candidate genes points to conserved neurobiological mechanisms and facilitates gene discovery for rare neurodevelopmental diseases.
Display omitted
•We generate and characterize >300 (TG4 and cDNA) Drosophila mutants and transgenics•Humanization and overexpression strategies to functionally assess ASD variants in vivo•ASD variant data in flies help identify GLRA2-related neurodevelopmental disorders•Basic and clinical collaboration facilitates variant testing and disease gene discovery
Marcogliese et al. generate >300 Drosophila mutants and use complementary rescue-based and overexpression approaches to study the function of de novo missense variants found in autism. They find that 38% of missense changes have functional consequences and identify variants in GLRA2 that cause a variable neurological disorder.
We investigate the statistical properties and the origin of the scatter within the spatially resolved surface brightness profiles of the CHEX–MATE sample, formed by 118 galaxy clusters selected via ...the SZ effect. These objects have been drawn from the
Planck
SZ catalogue and cover a wide range of masses,
M
500
= 2 − 15×10
14
M
⊙
, and redshift,
z
= 0.05, 0.6. We derived the surface brightness and emission measure profiles and determined the statistical properties of the full sample and sub-samples according to their morphology, mass, and redshift. We found that there is a critical scale,
R
∼ 0.4
R
500
, within which morphologically relaxed and disturbed object profiles diverge. The median of each sub-sample differs by a factor of ∼10 at 0.05
R
500
. There are no significant differences between mass- and redshift-selected sub-samples once proper scaling is applied. We compare CHEX–MATE with a sample of 115 clusters drawn from the T
HE
T
HREE
H
UNDRED
suite of cosmological simulations. We found that simulated emission measure profiles are systematically steeper than those of observations. For the first time, the simulations were used to break down the components causing the scatter between the profiles. We investigated the behaviour of the scatter due to object-by-object variation. We found that the high scatter, approximately 110%, at
R
< 0.4
R
500
Y
SZ
is due to a genuine difference between the distribution of the gas in the core of the clusters. The intermediate scale,
R
500
Y
SZ
= 0.4−0.8, is characterised by the minimum value of the scatter on the order of 0.56, indicating a region where cluster profiles are the closest to the self-similar regime. Larger scales are characterised by increasing scatter due to the complex spatial distribution of the gas. Also for the first time, we verify that the scatter due to projection effects is smaller than the scatter due to genuine object-by-object variation in all the considered scales.
To evaluate the ability of additional central testing locations to improve detection of macular visual field (VF) defects in glaucoma.
Prospective cross-sectional study.
Four hundred forty healthy ...people and 499 patients with glaucomatous optic neuropathy (GON) were tested with a fundus tracked perimeter (CMP; CenterVue) using a 24-2 grid with 12 additional macular locations (24-2+).
Glaucomatous optic neuropathy was identified based on expert evaluation of optic nerve head photographs and OCT scans, independently of the VF. We defined macular defects as locations with measurements outside the 5% and 2% normative limits on total deviation (TD) and pattern deviation (PD) maps within the VF central 10°. Classification was based on the total number of affected macular locations (overall detection) or the largest number of affected macular locations connected in a contiguous cluster (cluster detection). Criteria based on the number of locations and cluster size were used to obtain equivalent specificity between the 24-2 grid and the 24-2+ grids, calculated using false detections in the healthy cohort. Partial areas under the receiver operating characteristic curve (pAUCs) were also compared at specificities of 95% or more.
Matched specificity comparison of the ability to detect glaucomatous macular defects between the 24-2 and 24-2+ grids.
At matched specificity, cluster detection identified more macular defects with the 24-2+ grid compared with the 24-2 grid. For example, the mean increase in percentage of detection was 8% (95% confidence interval CI, 5%-11%) and 10% (95% CI, 7%-13%) for 5% TD and PD maps, respectively, and 5% (95% CI, 2%-7%) and 6% (95% CI, 4%-8%) for the 2% TD and PD maps, respectively. Good agreement was found between the 2 grids. The improvement measured by pAUCs was also significant but generally small. The percentage of eyes with macular defects ranged from about 30% to 50%. Test time for the 24-2+ grid was longer (21% increase) for both cohorts. Between 74% and 98% of defects missed by the 24-2 grid had at least 1 location with sensitivity of < 20 dB.
Visual field examinations with additional macular locations can improve the detection of macular defects in GON modestly without loss of specificity when appropriate criteria are selected.
PDF
