Reproducibility of the peritoneal regression grading score for assessment of response to therapy in peritoneal metastasis.

The four-tiered peritoneal regression grading score (PRGS) assesses the response to chemotherapy in peritoneal metastasis (PM). The PRGS is used, for example, to assess the response to pressurised intraperitoneal aerosol chemotherapy (PIPAC). However, the reproducibility of the PRGS is currently unknown. We aimed to evaluate the inter- and intraobserver variability of the PRGS. Thirty-three patients who underwent at least three PIPAC treatments as part of the PIPAC-OPC1 or PIPAC-OPC2 clinical trials at Odense University Hospital, Denmark, were included. Prior to each therapy cycle, peritoneal quadrant biopsies were obtained and three haematoxylin and eosin (H&E)-stained step sections were scanned and uploaded to a pseudonymised web library. For determining interobserver variability, eight pathologists assessed the PRGS for each quadrant biopsy, and Krippendorff's alpha and intraclass correlation coefficients (ICCs) were calculated. For determining intraobserver variability, three pathologists repeated their own assessments and Cohen's kappa and ICCs were calculated. A total of 331 peritoneal biopsies were analysed. Interobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was moderate to good/substantial. The intraobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was good to excellent/almost perfect. Our data support the PRGS as a reproducible and useful tool to assess response to intraperitoneal chemotherapy in PM. Future studies should evaluate the prognostic and predictive role of the PRGS

Tin-Containing Silicates: Identification of a Glycolytic Pathway via 3-Deoxyglucosone

We identify a glycolytic pathway through 3-deoxyglucosone using Lewis acid catalysts resulting in the formation of bio-based monomers.</p

Role of immunohistochemistry for interobserver agreement of Peritoneal Regression Grading Score in peritoneal metastasis.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC)-directed therapy is a new treatment option for peritoneal metastasis (PM). The 4-tiered Peritoneal Regression Grading Score (PRGS) has been proposed for assessment of histological treatment response. We aimed to evaluate the effect of immunohistochemistry (IHC) on interobserver agreement of the PRGS. Hematoxylin and eosin (H&amp;E)-stained and IHC-stained slides (n = 662) from 331 peritoneal quadrant biopsies (QBs) taken prior to 99 PIPAC procedures performed on 33 patients were digitalized and uploaded to a web library. Eight raters (five consultants and three residents) assessed the PRGS, and Krippendorff's alpha coefficients (α) were calculated. Results (IHC-PRGS) were compared with data published in 2019, using H&amp;E-stained slides only (H&amp;E-PRGS). Overall, agreement for IHC-PRGS was substantial to almost perfect. Agreement (all raters) regarding single QBs after treatment was substantial for IHC-PRGS (α = 0.69, 95% confidence interval [CI] = 0.66-0.72) and moderate for H&amp;E-PRGS (α = 0.60, 95% CI = 0.56-0.64). Agreement (all raters) regarding the mean PRGS per QB set after treatment was higher for IHC-PRGS (α = 0.78, 95% CI = 0.73-0.83) than for H&amp;E-PRGS (α = 0.71, 95% CI = 0.64-0.78). Among residents, agreement was almost perfect for IHC-PRGS and substantial for H&amp;E-PRGS. Agreement (all raters) regarding maximum PRGS per QB set after treatment was substantial for IHC-PRGS (α = 0.61, 95% CI = 0.54-0.68) and moderate for H&amp;E-PRGS (α = 0.60, 95% CI = 0.53-0.66). Among residents, agreement was substantial for IHC-PRGS (α = 0.66, 95% CI = 0.57-0.75) and moderate for H&amp;E-PRGS (α = 0.55, 95% CI = 0.45-0.64). Additional IHC seems to improve the interobserver agreement of PRGS, particularly between less experienced raters

Anthropogenic noise events perturb acoustic communication networks

Anthropogenic noise sources impact ecological processes by altering wildlife behavior and interactions with cascading impacts on community structure. The distribution and magnitude of such noise has grown exponentially over the past century, and now inundates even remote areas. Here we investigate biological responses to prolific, anthropogenic noise sources associated with the physical presence of the source (vehicle noise and human voices) and disconnected from it (aircraft overflight). Bioacoustic responses to these noise sources were documented at 103 sites in 40 U. S. National Park units. The presence of bird sounds was noted in 10-s audio samples every 2 min, for 8 days at each site and related to the presence of human voices, vehicle noise, and aircraft noise in the same and preceding samples. Generalized additive models were used to fit smoothing splines to weight the influence of noise in past samples on the probability of detecting bird sounds in the present sample. We found that the probability of hearing birds increased immediately following noise events, and decreased about 2 h after the event. The negative effects were persistent more than 3 h after a noise event. The persistence of these responses – especially for noise from jets that were many kilometers distant – raises questions about the functional significance and ecological consequences of this altered activity, particularly in light of the widespread and diverse habitats in this study and ubiquity of the noise sources evaluated

Three-dimensional beam pattern of regular sperm whale clicks confirms bent-horn hypothesis

Author Posting. © Acoustical Society of America, 2005. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 117 (2005): 1473-1485, doi:10.1121/1.1828501.The three-dimensional beam pattern of a sperm whale (Physeter macrocephalus) tagged in the Ligurian Sea was derived using data on regular clicks from the tag and from hydrophones towed behind a ship circling the tagged whale. The tag defined the orientation of the whale, while sightings and beamformer data were used to locate the whale with respect to the ship. The existence of a narrow, forward-directed P1 beam with source levels exceeding 210 dBpeak re: 1 µPa at 1 m is confirmed. A modeled forward-beam pattern, that matches clicks >20° off-axis, predicts a directivity index of 26.7 dB and source levels of up to 229 dBpeak re: 1 µPa at 1 m. A broader backward-directed beam is produced by the P0 pulse with source levels near 200 dBpeak re: 1 µPa at 1 m and a directivity index of 7.4 dB. A low-frequency component with source levels near 190 dBpeak re: 1 µPa at 1 m is generated at the onset of the P0 pulse by air resonance. The results support the bent-horn model of sound production in sperm whales. While the sperm whale nose appears primarily adapted to produce an intense forward-directed sonar signal, less-directional click components convey information to conspecifics, and give rise to echoes from the seafloor and the surface, which may be useful for orientation during dives.This work was funded by grants from the Office of Naval Research Grants N00014-99-1-0819 and N00014-01-1-0705, and the Packard Foundation

High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

<p>Abstract</p> <p>Background</p> <p>Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression.</p> <p>Methods</p> <p>Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer.</p> <p>Results</p> <p>The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies.</p> <p>Conclusion</p> <p>The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer.</p

Imagining transitions in old age through the visual matrix method: thinking about what is hard to bear

Dominant discourses of ageing are often confined to what is less painful to think about and therefore idealise or denigrate ageing and later life. We present findings from an exploratory psychosocial study, in a Nordic context into three later-life transitions: from working life to retirement, from mental health to dementia, and from life to death. Because, for some, these topics are hard to bear, and therefore defended against and routinely excluded from everyday awareness, we used a method led by imagery and affect - the Visual Matrix - to elicit participants’ free associative personal and collective imagination. Through analysis of data extracts, on the three transitions, we illustrate oscillations between defending against the challenges of ageing and realism in facing the anxieties it can provoke. A recurring theme includes the finality of individual life and the inter-generational continuity, which together link life and death, hope and despair, separation and connectedness

The Behavioural Response of Australian Fur Seals to Motor Boat Noise

Australian fur seals breed on thirteen islands located in the Bass Strait, Australia. Land access to these islands is restricted, minimising human presence but boat access is still permissible with limitations on approach distances. Thirty-two controlled noise exposure experiments were conducted on breeding Australian fur seals to determine their behavioural response to controlled in-air motor boat noise on Kanowna Island (39°10′S, 146°18′E). Our results show there were significant differences in the seals' behaviour at low (64–70 dB) versus high (75–85 dB) sound levels, with seals orientating themselves towards or physically moving away from the louder boat noise at three different sound levels. Furthermore, seals responded more aggressively with one another and were more alert when they heard louder boat noise. Australian fur seals demonstrated plasticity in their vocal responses to boat noise with calls being significantly different between the various sound intensities and barks tending to get faster as the boat noise got louder. These results suggest that Australian fur seals on Kanowna Island show behavioural disturbance to high level boat noise. Consequently, it is recommended that an appropriate level of received boat sound emissions at breeding fur seal colonies be below 74 dB and that these findings be taken into account when evaluating appropriate approach distances and speed limits for boats