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Background KRISTINE is an open-label, phase III study of trastuzumab emtansine + pertuzumab (T-DM1 + P) versus docetaxel + carboplatin + trastuzumab + pertuzumab (TCH + P) in patients with HER2-positive, stage II–III breast cancer. We investigated the association of biomarkers with clinical outcomes in KRISTINE. Methods Patients were randomized to receive neoadjuvant T-DM1 + P or TCH + P and assessed for pathologic complete response (pCR; ypT0/is, ypN0). HER2 status (per central assessment), hormone receptor status, PIK3CA mutation status, HER2/HER3 mRNA levels, tumor-infiltrating lymphocyte levels, PD-L1 status, and NanoString data were analyzed. pCR rates by treatment arm were compared across biomarker subgroups. Analyses were descriptive. Results Biomarker analyses included data from all 444 patients (T-DM1 + P, n  = 223; TCH + P, n  = 221) enrolled in KRISTINE. Biomarker distribution was balanced across treatment arms. All subgroups with higher HER2 amplification/expression and immune marker levels showed numerically higher pCR rates in both arms. Mutated versus non-mutated PIK3CA tumors were associated with numerically lower pCR rates in the T-DM1 + P arm but not in the TCH + P arm. In a multivariate analysis, Prediction Analysis of Microarray with the 50-gene classifier (PAM50) HER2-enriched subtype, HER2 gene ratio ≥ 4, and PD-L1-positive status positively influenced the pCR rate. Biomarkers associated with lower pCR rates (e.g., low HER2 levels, positive hormone receptor status, mutated PIK3CA ) were more likely to co-occur. Dynamic on-treatment biomarker changes were observed. Differences in the treatment effects for T-DM1 + P versus TCH + P were similar to those observed in the intent-to-treat population for the majority of the biomarker subgroups. Conclusions Although our biomarker analysis did not identify a subgroup of patients that benefited from neoadjuvant T-DM1 + P versus TCH + P, the data revealed that patients with higher HER2 amplification/expression and immune marker levels had improved response irrespective of treatment arm. These analyses confirm the role of HER2 tumor biology and the immune microenvironment in influencing pCR in the neoadjuvant setting and reaffirm the molecular diversity of HER2-positive breast cancer. Trial Registration : ClinicalTrials.gov NCT02131064. Registered 06 May 2014.

During the years of the Nazi regime, well over 1,000 European Jewish youths migrated to the United States in organized unaccompanied child migration schemes. These youths left an abundant, and largely untapped, trove of sources in which they constructed narratives of their lives and emotions to their parents in letters, to their social workers in their various interactions, and to themselves in their diaries. Though refugee youths undeniably felt a range of emotions, in this article I suggest that emotional expression tells us less about the emotional inner lives of youths than the attempt to exert and subvert control and power in a topsy-turvy world. By drawing attention to the language of emotions, their inherent power dynamics, and the potential gulf between emotions and experience, this article opens a conversation about our capacity to document children's agency and to study emotions to explain decision-making and experience.

In this profile, Kristine M. Alpi, AHIP, FMLA, Medical Library Association (MLA) president, 2021–2022, is described as committed to public health, professional development, and the growth and evolution of MLA. She teaches and speaks on the shared health impact from interactions among animals, humans, and the environment, and she mentors graduate students and fellows in librarianship and informatics. Alpi earned her PhD in educational research and policy analysis in 2018 and directs the Oregon Health & Science University Library. 

Kjersti Aagaard is a practicing maternal–fetal medicine obstetrician at Texas Children’s and Ben Taub Hospitals and a reproductive biologist at Baylor College of Medicine. She studies a myriad of aspects of the microbiome, including how it can influence pregnancy and the developing infant.

Crop species have been deeply affected by the domestication process, and there have been many efforts to identify selection signatures at the genome level. This knowledge will help geneticists to better understand the evolution of organisms, and at the same time, help breeders to implement successful breeding strategies. Here, we focused on domestication in the Mesoamerican gene pool of by sequencing 49 gene fragments from a sample of 45 wild and domesticated accessions, and as controls, two accessions each of the closely related species and . An excess of nonsynonymous mutations within the domesticated germplasm was found. Our data suggest that the cost of domestication alone cannot explain fully this finding. Indeed, the significantly higher frequency of polymorphisms in the coding regions observed only in the domesticated plants (compared to noncoding regions), the fact that these mutations were mostly nonsynonymous and appear to be recently derived mutations, and the investigations into the functions of their relative genes (responses to biotic and abiotic stresses), support a scenario that involves new functional mutations selected for adaptation during domestication. Moreover, consistent with this hypothesis, selection analysis and the possibility to compare data obtained for the same genes in different studies of varying sizes, data types, and methodologies allowed us to identify four genes that were strongly selected during domestication. Each selection candidate is involved in plant resistance/tolerance to abiotic stresses, such as heat, drought, and salinity. Overall, our study suggests that domestication acted to increase functional diversity at target loci, which probably controlled traits related to expansion and adaptation to new agro-ecological growing conditions.

This article assesses how Ismaili Muslim leaders in British colonial Tanganyika utilized Guiding and Victorian schooling philosophies in an attempt to negotiate for advancement within the colonial structure. Aga Khan III understood the role that followers were expected to play in the “Great Game” of imperialism and attempted to use cooperation to broker for increased opportunities within the system of subjugation. This article sets out to analyze then how the Aga Khan and his representative leaders in British colonial Tanganyika used youth programs to operate within these liminal spaces, in turn revealing the ongoing negotiations that took place between colonizer and the colonized.

Since 2017, the Canadian government has published excerpts from questionnaires that prospective judges completed as part of the judicial selection process, subjecting newly appointed superior and federal court judges to a degree of scrutiny that is unprecedented in Canadian history. Using this novel source material, this article explores what a sample of 16 judges' questionnaires do and do not say about the individuals behind the robes. This review suggests that those appointed to the bench in 2017 generally demonstrate insight into the judicial role in Canada. However, some provide only superficial responses, others parrot back normative values that the government has already prescribed, and many offer substantially similar answers. This suggests, first, that not all successful applications or, for that matter, applicants are created equal and, second, that applicants use the questionnaire less as an opportunity to demonstrate free thought and more as a test to prove their fealty to dominant assumptions about the court's role in society. The questionnaire therefore misses an opportunity to show that diversity on the bench is more than skin-deep. Meanwhile, recent trends show that the government has lagged behind on its commitment to make judges' applications public. The article concludes that if the government is serious about introducing greater transparency and accountability to the judicial selection process, then it should revise the questionnaire to elicit more meaningful responses from applicants and table legislation to codify the government's political promise to publish appointees' views on the role of the judiciary in Canadian society.

Leslie Holmes: Well, the problem is that everybody-especially the younger generation-is so visual, because they are watching so much on their phones, on TV, and at the movies, that it has to be somewhat visually believable at the opera house in order to get them in the second time. [...]if I choose a profession, which is being an artist and giving something to the audience, I don't have fun just to stay and sing for myself. The Russian language she just heard from me and from my mother. [...]a Russian nanny came, because Andris was more busy, and Adriana sort of switched off to Russian language.