Donaldson (United States)

Abstract Background: The NeoSphere trial first established docetaxel-based dual HER2 blockade with pertuzumab and trastuzumab as an effective neoadjuvant regimen, yielding superior pathologic complete response (pCR) rates, though without conclusive long-term survival benefit. The subsequent PEONY trial confirmed the pCR advantage and demonstrated improved 5-year event-free survival with this regimen. Despite this, paclitaxel—administered weekly (P1) or every 3 weeks (P3)—is commonly used in clinical practice due to its more favorable tolerability profile. Whether the choice of taxane impacts efficacy or toxicity in the context of modern dual HER2-targeted therapy remains unclear, particularly in Canada, where pertuzumab reimbursement has been variable. Methods: We conducted a single-center retrospective cohort study at the Jewish General Hospital in Montreal, Quebec, Canada. Eligible patients were adults with HER2-positive stage II-III breast cancer who received at least one dose of pertuzumab and trastuzumab between December 2021 and December 2024, and underwent complete (R0) surgical resection. Patients were grouped by neoadjuvant taxane: docetaxel 75-100 mg/m2 every 3 weeks (D3), paclitaxel 175 mg/m2 every 3 weeks (P3), or paclitaxel 80 mg/m2 weekly (P1). The primary endpoint was pCR; the secondary endpoint was the highest CTCAE v5.0 grade of adverse events. Fisher’s exact test was used to calculate odds ratios for pCR, and the Mann-Whitney U test compared toxicity grade distributions. Prism 10.5 was used in the analysis. Results: Cohort: We identified 87 patients: 60 received paclitaxel (45 weekly, 15 every 3 weeks) and 27 received docetaxel. The median age was 55 years (range 25-83) and median clinical stage was IIB (range IIA-IIIC); these were balanced between taxane cohorts (P = 0.37 and P = 0.59, respectively). Estrogen receptor status was similarly distributed (P = 0.48). Efficacy: Paclitaxel either every 3 or 1 week showed similar efficacy to Docetaxel every 3 weeks (P = 0.35), with a slight trend in our data towards better response with Paclitaxel. Safety: Paclitaxel either every 3 or 1 week and docetaxel every 3 weeks yielded safety profiles as measured by adverse events (CTCAE v5), P = 0.68 for paclitaxel every 3 weeks versus docetaxel, and P = 0.60 when comparing docetaxel against paclitaxel every 3 weeks and every 1 week. Conclusion: In routine clinical practice, paclitaxel—whether weekly or q3-weekly—achieves comparable pCR rates and acute toxicity to docetaxel when combined with pertuzumab and trastuzumab. Given paclitaxel’s logistical and tolerability advantages, these data support its use as an alternative taxane backbone in HER2-positive neoadjuvant therapy. Prospective randomized studies with survival endpoints are warranted. Adjustment for confounders will be addressed in future analyses. Citation Format: R. Barros, B. Jiao, A. Lozano, A. Shah, E. Bushatsky Andrade de Alencar, M. Frija-Gruman, J. Cools-Lartigue, N. Gagnon-Choy, I. Prakash, K. Ma. Choice in HER2-positive locally Advanced breast cancer of Neoadjuvant Taxane: a retrospective review of practice [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-11-16.

Abstract The second Trump administration is widely seen as destructive of the liberal international order and, indeed, many of its actions are. On NATO, however, the United States may be poised to strengthen the alliance in unexpected ways. Two trends create an opportunity for NATO to be a stronger alliance of more equal powers. First, the United States needs to shift resources to East Asia, creating incentives to do less in Europe. Second, Russian revanchism is creating insecurity in European capitals without threatening core U.S. security interests. Combined, these two trends are creating political will to increase European defense spending and break NATO’s long-standing problem with buck-passing.

Researchers have seldom discussed the effect of supervision on non‐work related outcomes. Using displaced aggression theory, we developed a trickledown model of supervisor incivility at the hierarchical levels of manager, supervisor, and employee. We analyzed multilevel, multisource data from 424 Employees and supervisors in 78 work groups, revealing a negative relationship between manager incivility and employee life satisfaction, with supervisor incivility mediating this relationship. Further, attributions of a supervisor’s behavior to the motive of promoting employee performance alleviated the negative effect of supervisor incivility on employee life satisfaction, while this negative effect was enhanced among workers who attributed their supervisor’s behavior to the motive of inflicting harm on employees. Our findings provide practical insights into mitigating the trickle‐down effect of supervisor incivility and boosting employee life satisfaction.

Diabetes is a widespread chronic disease that impacts millions of individuals around the globe. Recent advances in artificial intelligence have highlighted the potential of machine learning (ML) and deep learning (DL) techniques for the early detection of diabetes, offering improvements in both diagnostic precision and efficiency. This research introduces an innovative stacked ensemble learning framework that integrates various ML and DL algorithms to boost predictive accuracy. The approach begins by utilizing individual models—such as one-dimensional convolutional neural networks (1D-CNN), long short-term memory (LSTM) networks, random forest (RF), logistic regression (LR), and support vector machines (SVM), each selected for its distinct strengths in prediction. These models are then strategically combined through a stacked ensemble method to capitalize on their complementary capabilities and enhance overall performance. The proposed ensemble model achieves a prediction precision of 0.95, a recall of 0.68, an F1-score of 0.79, and an ROC-AUC of 0.97, demonstrating its effectiveness in early diabetes detection. This integrated approach ensures not only high predictive accuracy but also robustness against variations in patient data, ultimately facilitating timely intervention and improved healthcare outcomes.

Itch expectancies play a key role in itch perception and may elicit avoidance behaviors to prevent itch, even when it is costly. Despite theoretical evidence that expectancies can influence avoidance behaviors, no studies have empirically investigated their association in the context of itch. The aim of this study was to investigate whether negative expectancy manipulation led to more costly itch-related avoidance behavior. This study was conducted using a within-subjects repeated measures experimental design. Thirty-four participants underwent an instructional learning and conditioning procedure in which a sham experimental solution paired with a "high" quantity of cowhage spicules was used to induce high itch-expectations. A control solution paired with a medium quantity of cowhage spicules was used to induce medium itch-expectations. Subsequently, participants learned that by effortfully gripping a dynamometer above a certain level, they could avoid strong itching. In anticipation of two other itch stimuli after reapplication of the experimental solution and the control solution, average grip strength (reflecting costly itch-avoidance behavior) was measured. Results indicated that negative itch expectations were successfully induced (p < 0.001, d = 1.16). However, while participants engaged in avoidance behavior in both experimental and control trials, negative expectancy learning did not lead to more costly avoidance behavior (p = 0.74, ηp2 = 0.003). Results suggested that acute itch induced avoidance behavior regardless of expectations toward itch. Extending the research on the role of avoidance and its impact on itch may shed light on new approaches for itch management.

This paper explores the ontology of photogrammetry beyond its role as an analytical process to accurately record places. It identifies photogrammetric scans as hybrid artefacts, which can capture a wide array of spatial and temporal information upon their surfaces. Such traces are explored through the work of Object Oriented Ontology philosopher Timothy Morton, with cues also taken from the work of John Ruskin who places emphasis on the stained surface as the site of a building’s value. Presented alongside these propositions are a series of photogrammetric studies where antagonistic and disruptive data is maintained in the outcome to allow the manifestation of these concealed relationships. The awareness of these syncopated chronologies questions the futurity of a recorded object, accommodating both its presence and absence. What is argued here can allow the scan to become a site for speculation and proposition beyond the deferral to a real-world object. Author Biography Cameron Stebbing, Architectural Designer, Donald Insall Associates York Cameron Setbbing is an architectural designer at Donald Insall Associates and a visiting lecturer at Leeds Beckett University. Completing his MArch at the University of Huddersfield in 2023, he received the RIBA Silver and Dissertation Medals nominations and RIBA for his thesis project, which explored themes of conservation and temporality structured around Ruskin’s ‘The Seven Lamps of Architecture’. Portions of this were subsequently published in AD magazine in 2024. He was named RIBA East Midlands Student of the Year in 2019 and received the RIBA Bronze Medal nomination for his undergraduate work at the University of Lincoln.

In pathologic health anxiety (pHA), a more liberal interoceptive response bias and health-threat related biases are observed. In predictive processing terms, this could be translated into a precise prior on high somatic symptom probability (symptom-prior) and an imprecise prior on one's current (and future) health state (hidden-state-prior). In an online experiment, we used an adapted version of the affect and symptom paradigm (ASP), previously shown to sufficiently elicit somatic symptoms. N = 261 participants (age: M = 27.79, SD = 9.61; sex: 77.8% females, 21.5% males, 0.8% divers) were randomly assigned to 4 conditions, manipulating priors on somatic symptom probability (symptom-prior: precise and high probability vs precise and low probability) and origins of somatic symptoms (hidden-state-prior: imprecise vs precise and nonillness). We did not observe any significant effects of symptom-prior manipulation on symptom report ( p = .27). Inducing an imprecise prior on the origin of somatic symptoms (imprecise hidden-state-prior), though, was significantly associated with higher health anxiety after negative (compared with neutral) pictures in people with higher preexisting health anxiety [ b =0.113, SE = 0.045, 95% BCa CI (0.025, 0.201)]. This effect was not attributable to a simultaneous change in valence or arousal ( pval = .73; paro = .56). The findings suggest a possible central role of imprecise priors, especially on one's health state, in pHA. Further evidence in clinical samples is needed.