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1. Monitoring the response of wild mammal populations to threatening processes is fundamental to effective conservation management. This is especially true for infectious diseases, which may have dynamic and therefore unpredictable interactions with their host. 2. We investigate the long-term impact of a transmissible cancer, devil facial tumour disease (DFTD), on the endemic Tasmanian devil. We analyse trends in devil spotlight counts and density across the area impacted by the disease. We investigate the demographic parameters which might be driving these trends, and use spatial capture-recapture models to examine whether DFTD has affected home range size. 3. We found that devils have declined by an average of 77% in areas affected by DFTD, and that there is a congruent trend of ongoing small decline in spotlight counts and density estimates. Despite this, devils have persisted to date within each of nine monitoring sites. One site is showing as yet unexplained small increases in density 8-10 years after the emergence of DFTD. 4. We also found the prevalence of DFTD has not abated despite large declines in density and that diseased sites continue to be dominated by young devils. The long-term impact of the disease has been partially offset by increased fecundity in the form of precocial breeding in 1-year-old females, and more pouch young per female in diseased sites. The lower densities resulting from DFTD did not affect home range size. 5. Synthesis and applications. Transmission of devil facial tumour disease continues despite large declines in devil density over multiple generations. Plasticity in life history traits has ameliorated the impact of devil facial tumour disease, however broad-scale trends in density show ongoing decline. In light of this, devil facial tumour disease and the impact of stochastic events on the reduced densities wrought by the disease, continue to threaten devils. In the absence of methods to manage disease in wild populations, we advocate managing the low population densities resulting from disease rather than disease per se.

[...]does treatment with pirtobrutinib exert selective pressure on the population of CLL cells to allow re-sensitization to cBTKi or other targeted agents or combinations? [...]what are potential therapeutic intensification options for patients who progress on pirtobrutinib, including those who resolve C481S but develop new BTK-mutant clones, and those who have Bcl-2i-resistant disease? [...]the time-to-progression was shorter for patients with BTK mutation (Fig. 1D). Disease progression on pirtobrutinib is associated with enhanced sensitivity to ibrutinib We then tested peripheral blood cells ex vivo from patients during therapy or at the time of disease progression. [...]ex vivo response to pirtobrutinib mirrored clinical disease progression on pirtobrutinib (Fig. 2A).

Oncotype DX (ODX) recurrence score (RS) is a validated tool to guide the use of adjuvant chemotherapy (AC) in hormone receptor+/HER2- breast cancer. In this analysis, we examine (1) characteristics associated with ODX testing and (2) the association between ODX RS and receipt of AC across age and nodal status. Women with HR+/HER2–, early-stage (T1-2, N0-1) breast cancers from 2010–2017 in the National Cancer Database were included. 530,125 met inclusion and 255,971 received ODX testing. Older women were less likely to receive testing; however, nodal positivity increased use of testing. High ODX RS was associated with increased mortality, though the association was not consistent across age and was most strongly associated with mortality among younger, node-negative women. Older women with high ODX RS, regardless of nodal status, were less likely to receive AC. Clinicians may be employing ODX RS to support treatment decisions against the receipt of AC.

Very high‐resolution satellite (VHR) imagery is a promising tool for estimating the abundance of wildlife populations, especially in remote regions where traditional surveys are limited by logistical challenges. Emperor penguins Aptenodytes forsteri were the first species to have a circumpolar population estimate derived via VHR imagery. Here we address an untested assumption from Fretwell et al. (2012) that a single image of an emperor penguin colony is a reasonable representation of the colony for the year the image was taken. We evaluated satellite‐related and environmental variables that might influence the calculated area of penguin pixels to reduce uncertainties in satellite‐based estimates of emperor penguin populations in the future. We focused our analysis on multiple VHR images from three representative colonies: Atka Bay, Stancomb‐Wills (Weddell Sea sector) and Coulman Island (Ross Sea sector) between September and December during 2011. We replicated methods in Fretwell et al. (2012), which included using supervised classification tools in ArcGIS 10.7 software to calculate area occupied by penguins (hereafter referred to as ‘population indices’) in each image. We found that population indices varied from 2 to nearly 6‐fold, suggesting that penguin pixel areas calculated from a single image may not provide a complete understanding of colony size for that year. Thus, we further highlight the important roles of: (i) sun azimuth and elevation through image resolution and (ii) penguin patchiness (aggregated vs. distributed) on the calculated areas. We found an effect of wind and temperature on penguin patchiness. Despite intra‐seasonal variability in population indices, simulations indicate that reliable, robust population trends are possible by including satellite‐related and environmental covariates and aggregating indices across time and space. Our work provides additional parameters that should be included in future models of population size for emperor penguins. Most emperor penguin breeding colonies are projected to be quasi‐extinct by 2100 under ‘business as usual’ emissions scenarios and thus it is now critical to gain empirical evidence of population changes. Very high‐resolution satellite images (VHR) provide us unprecedented, remote access to monitor emperor penguin populations. Our study is the first to address the cause of uncertainties in emperor penguin population estimates derived via VHR, and to account for uncertainty to optimize population estimates. We found that (i) the assumption within Fretwell et al. (2012) that a single VHR image of an emperor penguin colony is a reasonable representation of the colony size for that year was violated, and that (ii) environmental and satellite‐related covariates helped determine population indices, in an effort toward realistic population estimates. This work has major implications for the future assessment of emperor penguin responses to climate change.

The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types.

Erdheim-Chester Disease (ECD) is a non-inherited multifocal lipid storing histiocytosis. It is a rare disease characterised by lipid-laden monocyte infiltration of long bones causing cortical sclerosis and characteristic X-ray appearances. It also involves extraskeletal tissue in up to 50% of cases including retroperitoneal and renal infiltration. We report a patient with long standing ECD with widespread extraskeletal involvement, including significant renal infiltration, presenting with left hydronephrosis secondery obstruction from a proximal ureteric calculas.

Your leader (December 19) rightly concludes that \"the overriding objective in Northern Ireland is to build the politics of the future\". It's not the only way of doing this but we could make a start by educating our children here together by seeking to make an integrated school choice for all...