Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, ...and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454‐489.
BACKGROUND:Scoliosis affects 50% of children with Gross Motor Function Classification System (GMFCS) level IV or V cerebral palsy (CP). In children with complex neurodisability following ...intervention, the WHO considers quality of life (QoL) should be assessed to aid decision-making and assess the effects. This study assesses whether scoliosis surgery improves carer-assessed QoL for children with severe CP.
METHODS:Retrospective review of 33 children (16 male:17 female) with GMFCS level IV/V CP and significant scoliosis. Fifteen underwent observational treatment during childhood, and 18 underwent surgery. Questionnaire and radiographic data were recorded over a 2-year period. The carer-completed Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) questionnaire was used to assess QoL.
RESULTS:In the observational group, Cobb angle and pelvic obliquity increased from 46 (40 to 60) and 8 degrees (0 to 28) to 62 (42 to 94) and 12 degrees (1 to 35). Mean CPCHILD score decreased from 50 (30 to 69) to 48 (27 to 69) (P<0.05). In the operative group, Cobb angle and pelvic obliquity decreased from 78 (52 to 125) and 14 degrees (1 to 35) to 44 (16 to 76) and 9 degrees (1 to 24). Mean CPCHILD score increased from 45 (20 to 60) to 58 (37 to 76) (P<0.05). Change in pain, and not presence of associated impairments, was the most significant factor affecting QoL changes for children in both groups. There was no difference in mobility, GMFCS level, feeding, or communication in either group before and after treatment.
CONCLUSIONS:Nonoperative treatment for children with GMFCS level IV/V CP and a significant scoliosis was associated with a small decrease in carer-assessed QoL over 2 years. Spinal fusion was associated with an increase in QoL. Change in pain was the most significant factor affecting QoL changes, and is therefore an important factor to consider when deciding upon surgery.
LEVEL OF EVIDENCELevel III—therapeutic retrospective study.
Age is a fundamental life history attribute that is used to understand the dynamics of wild animal populations. Unfortunately, most animals do not have a practical or nonlethal method to determine ...age. This makes it difficult for wildlife managers to carry out population assessments, particularly for elusive and long‐lived fauna such as marine turtles. In this study, we present an epigenetic clock that predicts the age of marine turtles from skin biopsies. The model was developed and validated using DNA from known‐age green turtles (Chelonia mydas) from two captive populations, and mark‐recapture wild turtles with known time intervals between captures. Our method, based on DNA methylation levels at 18 CpG sites, was highly accurate with a median absolute error of 2.1 years (4.7% of maximum age in data set). This is the first epigenetic clock developed for a reptile and illustrates their broad applicability across a broad variety of vertebrate species. It has the potential to transform marine turtle management through a nonlethal and inexpensive method to provide key life history information.
The residence, home range, and habitat use of juvenile (42.0–63.5 cm midline curved carapace length, CCL), subadult (68.6–84.6 cm CCL), and adult (81.9–104.2 cm CCL) green turtles (Chelonia mydas) ...was investigated using passive acoustic telemetry in Ningaloo Marine Park, north‐western Australia. Eighty‐one turtles ranging in size from 42 to 104 cm CCL were captured on their foraging grounds and tagged with acoustic tags.
Individuals were monitored for up to 913 days (range 48–913 days, median 367 days). Turtles of all sizes demonstrated very high fidelity to their foraging area. Residence declined with turtle body size and home range increased with turtle body size, with an average 50% kernel utilization distribution (KUD) area of 0.29, 0.47, and 0.57 km2 for juveniles, subadults, and adults, respectively.
Juveniles occurred only in shallow inshore habitat dominated by seagrass and macroalgae‐covered pavement. Subadults and adults selected macroalgae‐covered pavement, sandy areas of the lagoon, and macroalgae‐dominated patch reefs within the lagoon.
At high tide, juveniles were approximately 200 m closer to the shore than at low tide, but there was no tidal pattern of space use in subadult and adult turtles.
Less than 5% of turtles departed the array within 6 months and there was no evidence of developmental migrations in subadults.
The results highlight the conservation potential for go‐slow areas to minimize boat strike in areas of high turtle density, given the small and stable home ranges. Furthermore, the spatial segregation of juveniles, subadults, and adults will result in variability in the susceptibility of individuals to boat strike.
The influencing factors that drive the developmental migrations of turtles to consecutive habitats as they grow, as well as movement away from foraging grounds in response to changes in habitat quality, are complex. The ability of acoustic telemetry to provide long‐term data on all size classes of turtles within foraging areas provides a tool to enable the long‐term monitoring of turtle populations, which is required for at‐risk populations and/or habitats.
Abstract
We present the first linear polarization measurements from the 2015 long-duration balloon flight of
Spider
, which is an experiment that is designed to map the polarization of the cosmic ...microwave background (CMB) on degree angular scales. The results from these measurements include maps and angular power spectra from observations of 4.8% of the sky at 95 and 150 GHz, along with the results of internal consistency tests on these data. While the polarized CMB anisotropy from primordial density perturbations is the dominant signal in this region of sky, Galactic dust emission is also detected with high significance. Galactic synchrotron emission is found to be negligible in the
Spider
bands. We employ two independent foreground-removal techniques to explore the sensitivity of the cosmological result to the assumptions made by each. The primary method uses a dust template derived from
Planck
data to subtract the Galactic dust signal. A second approach, which constitutes a joint analysis of
Spider
and
Planck
data in the harmonic domain, assumes a modified-blackbody model for the spectral energy distribution of the dust with no constraint on its spatial morphology. Using a likelihood that jointly samples the template amplitude and
r
parameter space, we derive 95% upper limits on the primordial tensor-to-scalar ratio from Feldman–Cousins and Bayesian constructions, finding
r
< 0.11 and
r
< 0.19, respectively. Roughly half the uncertainty in
r
derives from noise associated with the template subtraction. New data at 280 GHz from
Spider
’s second flight will complement the
Planck
polarization maps, providing powerful measurements of the polarized Galactic dust emission.
Rationale
Ecologists often need to make choices about what body parts (tissues or organs) of an animal to sample. The decision is typically guided by the need to treat animals as humanely as ...possible, as well as the information that different body parts can provide. When using stable isotopes, decisions are also influenced by whether specimens would require preservation, and whether they have properties (such as high lipid concentrations) that would influence measurements. Sometimes we cannot use a preferred tissue (for example, because of ethical or logistical constraints), and in such cases an ability to reliably predict stable isotope composition for one tissue from data yielded by another would be useful.
Methods
In this study we analysed multiple tissues (skin, whole blood, red blood cells, plasma and nail) from green turtles (Chelonia mydas) to evaluate variation in C:N ratios, and test hypotheses about the intercept and slope of regressions of stable carbon and nitrogen isotope compositions among tissues.
Results
Regression models revealed that linear relationships were present for most comparisons, except those involving the δ13C of skin, and the slopes (β1) of most regressions were different from unity. The C:N ratios of skin were significantly higher and more variable than those of other tissues. The δ13C and δ15N of nail were highly correlated with those of the whole blood, red blood cells and plasma. Nail and red blood cells showed low variation in C:N.
Conclusions
The patterns in slopes of regressions indicate that comparisons of measurements yielded by different tissues of wild animals are complicated by the fact that the tissues are unlikely to be in isotopic equilibrium with their diet. Of the tissues used in this study, nail is simple to collect, requires minimal disturbance to the animal and no special preservation; these traits should make it attractive to turtle ecologists, but more information is needed on aspects such as growth rates.
We present the temperature and polarization angular power spectra measuredby the Atacama Cosmology Telescope Polarimeter (ACTPol). We analyze night-time datacollected during 2013-14 using two ...detector arrays at 149 GHz, from 548 deg(exp. 2) of sky onthe celestial equator. We use these spectra, and the spectra measured with the MBAC camera on ACT from 2008-10, in combination with Planck and WMAP data to estimate cosmological parameters from the temperature, polarization, and temperature-polarization cross-correlations. We find the new ACTPol data to be consistent with the CDM model. The ACTPol temperature-polarization cross-spectrum now provides stronger constraints on multiple parameters than the ACTPol temperature spectrum, including the baryon density, the acoustic peak angular scale, and the derived Hubble constant. The new ACTPol dataprovide information on damping tail parameters. The joint uncertainty on the number of neutrino species and the primordial helium fraction is reduced by 20% when adding ACTPol to Planck temperature data alone.
Genetic changes underlying clear cell renal cell carcinoma(ccRCC) include alterations in genes controlling cellularoxygen sensing (for example, VHL) and the maintenance of chromatin states (for ...example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreasedAMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment. PUBLICATION ABSTRACT
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Acute cardiac injury is prevalent in critical COVID-19 and associated with increased mortality. Its etiology remains debated, as initially presumed causes - myocarditis and cardiac necrosis - have ...proved uncommon. To elucidate the pathophysiology of COVID-19-associated cardiac injury, we conducted a prospective study of the first 69 consecutive COVID-19 decedents at CUIMC in New York City. Of 6 acute cardiac histopathologic features, presence of microthrombi was the most commonly detected among our cohort. We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with in-hospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak erythrocyte sedimentation rate and C-reactive protein were independently associated with increased odds of microthrombi, supporting an immunothrombotic etiology. Using single-nuclei RNA-sequencing analysis on 3 patients with and 4 patients without cardiac microthrombi, we discovered an enrichment of prothrombotic/antifibrinolytic, extracellular matrix remodeling, and immune-potentiating signaling among cardiac fibroblasts in microthrombi-positive, relative to microthrombi-negative, COVID-19 hearts. Non-COVID-19, nonfailing hearts were used as reference controls. Our study identifies a specific transcriptomic signature in cardiac fibroblasts as a salient feature of microthrombi-positive COVID-19 hearts. Our findings warrant further mechanistic study as cardiac fibroblasts may represent a potential therapeutic target for COVID-19-associated cardiac microthrombi.
We report on measurements of the cosmic microwave background (CMB) and celestial polarization at 146 GHz made with the Atacama Cosmology Telescope Polarimeter (ACTPol) in its first three months of ...observing. Four regions of sky covering a total of 270 square degrees were mapped with an angular resolution of 1.3'. The map noise levels in the four regions are between 11 and 17 μK-arcmin. We present TT, TE, EE, TB, EB, and BB power spectra from three of these regions. The observed E-mode polarization power spectrum, displaying six acoustic peaks in the range 200 < ℓ < 3000, is an excellent fit to the prediction of the best-fit cosmological models from WMAP9+ACT and Planck data. The polarization power spectrum, which mainly reflects primordial plasma velocity perturbations, provides an independent determination of cosmological parameters consistent with those based on the temperature power spectrum, which results mostly from primordial density perturbations. We find that without masking any point sources in the EE data at ℓ < 9000, the Poisson tail of the EE power spectrum due to polarized point sources has an amplitude less than 2.4 μ {sup 2} at ℓ = 3000 at 95% confidence. Finally, we report that the Crab Nebula, an important polarization calibration source at microwave frequencies, has 8.7% polarization with an angle of 150.7{sup o} ± 0.6{sup o} when smoothed with a 5' Gaussian beam.
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