Pneumonitis as a side effect of breast cancer treatment: T-DXd and/or SBRT?

Breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2) is considered to be HER2-positive. The novel HER2- directed antibody drug conjugate, trastuzumab deruxtecan (T-DXd), is formed by covalently joining the monoclonal antibody trastuzumab with the topoisomerase I inhibitor deruxtecan. It exhibits significant anti-tumor activity in previously overtreated patients

Pan-Arctic surface ozone: modelling vs. measurements

Within the framework of the International Arctic Systems for Observing the Atmosphere (IASOA), we report a modelling-based study on surface ozone across the Arctic. We use surface ozone from six sites – Summit (Greenland), Pallas (Finland), Barrow (USA), Alert (Canada), Tiksi (Russia), and Villum Research Station (VRS) at Station Nord (North Greenland, Danish realm) – and ozone-sonde data from three Canadian sites: Resolute, Eureka, and Alert. Two global chemistry models – a global chemistry transport model (parallelised-Tropospheric Offline Model of Chemistry and Transport, p-TOMCAT) and a global chemistry climate model (United Kingdom Chemistry and Aerosol, UKCA) – are used for model data comparisons. Remotely sensed data of BrO from the GOME-2 satellite instrument and ground-based multi-axis differential optical absorption spectroscopy (MAX-DOAS) at Eureka, Canada, are used for model validation. The observed climatology data show that spring surface ozone at coastal sites is heavily depleted, making ozone seasonality at Arctic coastal sites distinctly different from that at inland sites. Model simulations show that surface ozone can be greatly reduced by bromine chemistry. In April, bromine chemistry can cause a net ozone loss (monthly mean) of 10–20 ppbv, with almost half attributable to open-ocean-sourced bromine and the rest to sea-ice-sourced bromine. However, the open-ocean-sourced bromine, via sea spray bromide depletion, cannot by itself produce ozone depletion events (ODEs; defined as ozone volume mixing ratios, VMRs, < 10 ppbv). In contrast, sea-ice-sourced bromine, via sea salt aerosol (SSA) production from blowing snow, can produce ODEs even without bromine from sea spray, highlighting the importance of sea ice surface in polar boundary layer chemistry. Modelled total inorganic bromine (BrY) over the Arctic sea ice is sensitive to model configuration; e.g. under the same bromine loading, BrY in the Arctic spring boundary layer in the p-TOMCAT control run (i.e. with all bromine emissions) can be 2 times that in the UKCA control run. Despite the model differences, both model control runs can successfully reproduce large bromine explosion events (BEEs) and ODEs in polar spring. Model-integrated tropospheric-column BrO generally matches GOME-2 tropospheric columns within ∼ 50 % in UKCA and a factor of 2 in p-TOMCAT. The success of the models in reproducing both ODEs and BEEs in the Arctic indicates that the relevant parameterizations implemented in the models work reasonably well, which supports the proposed mechanism of SSA production and bromide release on sea ice. Given that sea ice is a large source of SSA and halogens, changes in sea ice type and extent in a warming climate will influence Arctic boundary layer chemistry, including the oxidation of atmospheric elemental mercury. Note that this work dose not necessary rule out other possibilities that may act as a source of reactive bromine from the sea ice zone

Registered replication report: a large multilab cross-cultural conceptual replication of Turri, Buckwalter, & Blouw (2015)

According to the Justified True Belief account of knowledge (JTB), a person can only truly know something if they have a belief that is both justified and true (i.e., knowledge is justified true belief). This account was challenged by Gettier (1963), who argued that JTB does not explain knowledge attributions in certain situations, later called Gettier-type cases, wherein a protagonist is justified in believing something to be true, but their belief was only correct due to luck. Lay people may not attribute knowledge to protagonists with justified but only luckily true beliefs. While some research has found evidence for these so-called Gettier intuitions (e.g., Machery et al., 2017a), Turri et al. (2015) found no evidence that participants attributed knowledge in a counterfeit-object Gettier-type case differently than in a matched case of justified true belief. In a large-scale, cross-cultural conceptual replication of Turri and colleagues’ (2015) Experiment 1 (N = 4,724) using a within-participants design and three vignettes across 19 geopolitical regions, we did find evidence for Gettier intuitions; participants were 1.86 times more likely to attribute knowledge to protagonists in standard cases of justified true belief than to protagonists in Gettier-type cases. These results suggest that Gettier intuitions may be detectable across different scenarios and cultural contexts. However, the size of the Gettier intuition effect did vary by vignette, and the Turri et al. (2015) vignette produced the smallest effect, which was similar in size to that observed in the original study. Differences across vignettes suggest epistemic intuitions may also depend on contextual factors unrelated to the criteria of knowledge, such as the characteristics of the protagonist being evaluated

Detta är inte Afrika - Västafrikanska undervisningsmetoder i Sverige

Title: This is not Africa - West African teaching methods in Sweden. This is a work of "translation". The study started with a musical journey to Guinea, West Africa. It was a field study where I had the opportunity to open my senses towards another culture and another kind of music. I found another learning tradition and decided to try to bring it with me back to Sweden, into the Swedish school system. In Africa I learned about the importance of cooperation and listening. I did the actual "translation" in a music school in Skåne where I am working. I wrote a process folio after each lesson I had with the fourth grade class and with two piano students. I could soon tell that something was missing: the children did not know how to listen to each other. My methods for finding a good collaboration through the master apprenticemethodology (to see, to hear and to do) were an attempt to make the learning in the subject of music meaningful, sustainable and useful. The attempt to translate my experiences turned out to be quite difficult - although some aspects of the West African teaching methodologies were applicable

Thymic Atrophy and Apoptosis of CD4+CD8+ Thymocytes in the Cuprizone Model of Multiple Sclerosis.

Previous studies on the degenerative animal model of multiple sclerosis suggested that the copper-chelator cuprizone might directly suppress T-cell functions. Peripheral T-cell function in the cuprizone model has already been explored; therefore, in the present study, we investigated, for the first time, how cuprizone feeding affects the thymus, the organ of T-cell maturation and selection. We found that even one week of cuprizone treatment induced significant thymic atrophy, affecting the cortex over the medulla. Fluorescent microscopy and flow-cytometric analyses of thymi from cuprizone- and vehicle-treated mice indicated that eradication of the cluster of the differentiation-4 (CD4)-CD8 double-positive T-cell subset was behind the substantial cell loss. This result was confirmed with CD3-CD4-CD8 triple-staining experiments. Ultrastructurally, we observed degraded as well as enlarged mitochondria, myelin-bodies, large lipid droplets, and large lysosomes in the thymi of cuprizone-treated mice. Some of these features were similar to those in physiological and steroid-induced accelerated aging. According to our results, apoptosis was mainly of mitochondrial origin mediated by both caspase-3- and apoptosis inducing factor-mediated mechanisms. Additionally, mitogen activated protein kinase activation and increased pro-apoptotic B cell lymphoma-2 family protein expression were the major underlying processes. Our results do not indicate a functional relationship between cuprizone-induced thymus involution and the absence of inflammatory responses or the selective demyelination observed in the cuprizone model. On the other hand, due to the reversible nature of cuprizone's deleterious effects, the cuprizone model could be valuable in studying thymus regeneration as well as remyelination processes

Surface snow bromide and nitrate at Eureka, Canada in early spring and implications for polar boundary layer chemistry [preprint]

This study explores the role of snowpack in polar boundary layer chemistry, especially as a di-rect source of reactive bromine (BrOX=BrO+Br) and nitrogen (NOX=NO+NO2) in the Arctic springtime. Surface snow samples were collected daily from a Canadian high Arctic location at Eureka, Nunavut (80° N, 86° W) from the end of February to the end of March in 2018 and 2019. The snow was sampled at several sites representing distinct environments: sea ice, inland close to sea level, and a hilltop ~600 m above sea level (asl). At the inland sites, surface snow salinity has a double-peak distribution with the first and low-est peak at 0.001–0.002 practical salinity unit (psu), which corresponds to the precipitation ef-fect, and the second peak at 0.01–0.04 psu, likely due to the condensation effect. Snow salinity on sea ice has a triple-peak distribution; its first and second peaks overlap with the inland peaks, and the third peak at 0.2–0.4 psu can be clearly attributed to sea water contamination. At all sites, sodium and chloride concentrations in surface snow increase by almost 10-fold from the top 0.2 cm to ~1 cm in depth. Bromide in surface snow is significantly enriched, indi-cating that surface snow at Eureka is a net sink of atmospheric bromine. Moreover, daily data show that top surface snow bromide at all sampling sites has an increasing trend over the measurement time period (late February to late March), with mean slopes of 1.9 and 1.3 ppb d-1 in the 0–0.2 cm and the 0.2–0.5 cm layers, respectively. At the sea level sites, snow nitrate also shows a significant increasing trend, with mean slopes of 12.1, 12.4, and 4.3 ppb d-1 in the top 0.2 cm, 0.2–0.5 cm, and 0.5–1.5 cm layers, respectively. Using these trends, we derive a novel method to calculate deposition flux of bromide and nitrate to the snowpack. For bromide, the integrated deposition flux is 1.29×107 molecules cm-2 s-1 at sea level and 1.01×107 molecules cm-2 s-1 at ~600 m. For nitrate, the integrated deposition flux is 2.4×108 molecules cm-2 s-1 at sea level and -1.0×108 molecules cm-2 s-1 at ~600 m; the negative flux indicates that snow at the hilltop sites is losing nitrate. The smaller vertical gradient of bromide deposition flux strongly indicates that local snowpack emission on sea ice and inland is not likely to be a large source of reactive bromine. In contrast, nitrate deposition flux has a large vertical gradient, e.g., with a positive flux at sea level and a negative flux at ~600 m, indicating that snowpack at sea level is a large source of reactive nitrate. In addition, we found a significant correlation (with coefficient R values of 0.48-0.76) between surface snow nitrate and bromide at the inland sites. The [NO3-] / [Br-] ratio ranges from 4 to 7, highlighting the effect of reactive bromine in accelerating the atmospheric NOX-to-nitrate con-version. This is the first time we see such an effect over the course of one day

Effect of cuprizone on thymic epithelial cells.

<p>Four week-old male mice were treated with cuprizone for one week, then immune-staining (A) with FITC-labelled anti-EpCAM1 (green) and PE-labelled anti-Ly-51 (red) antibodies was performed on thymic sections of untreated (Control) and cuprizone-treated (CPZ) mice. Representative images (A) are presented of the green channel (top panels), the red channel (middle panels) and the merged channels (bottom panels) of three independent experiments, including at least three animals in each group for each experiment. Fluorescent photographs were taken using a 10x objective. The scale bar indicates 200 μm. In a parallel experiment, thymic MHC II and AIRE mRNA expression (B) was determined by using qPCR analysis in untreated (grey bars) and cuprizone-treated (black bars) mice. Results are presented as fold change, mean + SEM (n≥9). Significant difference from control; *p<0.05.</p

Macroscopic changes of the thymi upon cuprizone treatment.

<p>Four week-old male mice were treated with cuprizone for one week. Representative photographs (A) of the open chest of a control (Cont.) and a cuprizone-treated (CPZ) animal are demonstrated. Arrows point to the thymi of the mice. The scale bar indicates 5 mm. Thymus mass (B), body mass (C) and relative thymus mass (thymus tissue mass/ body mass) (E) of control (grey bars) and cuprizone-treated (black bars) animals are presented as bar diagrams, mean + SEM (n≥9). * denotes a significant difference from control p<0.05.</p

Effect of cuprizone treatment on subcellular morphology.

<p>Four week-old male mice were treated with cuprizone for one week. Subcellular morphology was assessed in ultrathin thymic sections of control (A) and cuprizone-treated (B-E) mice. Representative images are presented of three independent experiments including at least three animals in each group for each experiment. Arrows indicate normal (A) and enlarged (B) mitochondria, a large lipid droplet (D), and large lysosomes packed with darkly stained material (E). Horizontal thin and vertical thick arrows in (C) point to myelin body and a degraded mitochondrion, respectively. Scale bars indicate 200 nm.</p

Characterisation of cuprizone-induced cell death.

<p>Four week-old male mice were treated with cuprizone for one week. Type of cell death was determined using flow cytometry following double staining with FITC-labelled AnnexinV and propidium iodide thymus suspensions of untreated (Control, grey bars) and cuprizone-treated (CPZ, black bars) mice. Results are presented as representative dot-plots (A) and bar diagrams (B), mean + SEM (n≥9). Significant difference from control; **p<0.01, *** p<0.001. DN: live cells (lower left quadrant); AnnexinV: early apoptotic cells (lower right quadrant); PI: necrotic cells (upper left quadrant); DP: late apoptotic cells (upper right quadrant).</p