Pathogenic and likely pathogenic variants in PALB2, CHEK2, and other known breast cancer susceptibility genes among 1054 BRCA-negative Hispanics with breast cancer.

BACKGROUND: Breast cancer (BC) is the most common cancer and related cause of mortality among Hispanics, yet susceptibility has been understudied. BRCA1 and BRCA2 (BRCA) mutations explain less than one-half of hereditary BC, and the proportion associated with other BC susceptibility genes is unknown. METHODS: Germline DNA from 1054 BRCA-mutation-negative Hispanic women with hereditary BC (BC diagnosed at age <51 years, bilateral BC, breast and ovarian cancer, or BC diagnosed at ages 51-70 years with ≥2 first-degree or second-degree relatives who had BC diagnosed at age <70 years), 312 local controls, and 887 multiethnic cohort controls was sequenced and analyzed for 12 known and suspected, high-penetrance and moderate-penetrance cancer susceptibility genes (ataxia telangiectasia mutated [ATM], breast cancer 1 interacting protein C-terminal helicase 1 [BRIP1], cadherin 1 [CDH1], checkpoint kinase 2 [CHEK2], nibrin [NBN], neurofibromatosis type 1 [NF1], partner and localizer of BRCA2 [PALB2], phosphatase and tensin homolog [PTEN], RAD51 paralog 3 [RAD51C], RAD51D, serine/threonine kinase 11 [STK11], and TP53). RESULTS: Forty-nine (4.6%) pathogenic or likely pathogenic variants (PVs) in 47 of 1054 participants (4.5%), including 21 truncating frameshift, 20 missense, 5 nonsense, and 4 splice variants, were identified in CHEK2 (n = 20), PALB2 (n = 18), ATM (n = 5), TP53 (n = 3), BRIP1 (n = 2), and CDH1 and NF1 (both n = 1) and none were identified in NBN, PTEN, STK11, RAD51C, or RAD51D. Nine participants carried the PALB2 c.2167_2168del PV (0.85%), and 14 carried the CHEK2 c.707T>C PV (1.32%). CONCLUSIONS: Of 1054 BRCA-negative, high-risk Hispanic women, 4.5% carried a PV in a cancer susceptibility gene, increasing understanding of hereditary BC in this population. Recurrent PVs in PALB2 and CHEK2 represented 47% (23 of 49) of the total, suggesting a founder effect. Accurate classification of variants was enabled by carefully controlling for ancestry and the increased identification of at-risk Hispanics for screening and prevention.

Gene Expression Differences in Prostate Cancers between Young and Old Men.

Prostate cancer incidence is increasing in younger men. We investigated whether men diagnosed with Gleason 7 (3+4) T2 prostate cancer at younger ages (≤ 45 years, young cohort) had different mRNA and miRNA expression profiles than men diagnosed at older ages (71-74 years, older cohort). We identified differentially expressed genes (DEGs) related to tumor-normal differences between the cohorts. Subsequent pathway analysis of DEGs revealed that the young cohort had significantly more pronounced inflammatory and immune responses to tumor development compared to the older cohort. Further supporting a role of inflammation-induced immune-suppression in the development of early-onset prostate cancer, we observed significant up-regulation of CTLA4 and IDO1/TDO2 pathways in tumors of the young cohort. Moreover, over-expression of CTLA4 and IDO1 was significantly associated with biochemical recurrence. Our results provide clues on the mechanisms of tumor development and point to potential biomarkers for early detection and treatment for prostate cancer in young men.

DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers.

INTRODUCTION: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. METHODS: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. RESULTS: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P <10(-6) in the analyses by PR status, HER2 status, TN phenotype, morphologic subtypes, histological grade and nodal involvement. CONCLUSIONS: Differences in associations of common BC susceptibility alleles between BRCA1 and BRCA2 carriers and the general population are explained to a large extent by differences in the prevalence of ER-positive and ER-negative tumors. Estimates of the risks associated with these variants based on population-based studies are likely to be applicable to mutation carriers after taking ER status into account, which has implications for risk prediction.

Is there a place for extended assessments in addressing child sexual abuse allegations? How sensitivity and specificity impact professional perspectives.

Using data from a survey of perceptions of 932 child welfare professionals about the utility of extended assessments, the researchers constructed a scale to measure respondents' views about sensitivity (ensuring sexually abused children are correctly identified) and specificity (ensuring nonabused children are correctly identified) in child sexual abuse evaluations. On average, respondents scored high (valuing sensitivity) on the sensitivity versus specificity scale. Next, the researchers undertook bivariate analyses to identify independent variables significantly associated with the sensitivity versus specificity scale. Then those variables were entered into a multiple regression. Four independent variables were significantly related to higher sensitivity scores: encountering cases requiring extended assessments, valuing extended assessments among scarce resources, less concern about proving cases in court, and viewing the goal of extended assessments as understanding needs of child and family (adjusted R2 = .34).

Reparations for people living with dementia: Recognition, accountability, change, now!

There is a significant and longstanding problem of harm to people living with dementia in long term care institutions ('LTC institutions', referred to by others as 'care homes', 'nursing homes', 'long term care', 'residential aged care facilities'), along with a failure to redress the harm or hold people accountable for this harm. This article reports on an Australian project that found reparations must be a response to harm to people living with dementia in residential aged care. Using a disability human rights methodology, focus groups were conducted with people living with dementia, care partners and family members, advocates and lawyers to explore perspectives on why and how to redress harm to people living with dementia in Australian LTC institutions. Researchers found four key themes provide the basis for the necessity and design of a reparative approach to redress - recognition, accountability, change, now. The article calls for further attention to reparations in dementia scholarship, with a particular focus on the role that can be played in the delivery of reparations by the LTC industry, dementia practitioners, and dementia scholars. Ultimately, this article provides a new understanding of responses to violence, abuse, neglect and other harms experienced by people living with dementia in LTC institutions, which centres justice, rights, and transformative change.

Policies, Guidelines, and Practices Supporting Women's Menstruation, Menstrual Disorders and Menopause at Work: A Critical Global Scoping Review.

(1) Objectives: This paper presents a scoping review of global evidence relating to interventions (i.e., policies, practices, guidelines, and legislation) aimed at supporting women to manage menstruation, menstrual disorders, and menopause at work. (2) Methods: Databases including Medline (Ebsco), CINAHL (Ebsco), Scopus, Web of Science, APA PsychInfo (Ebsco), Humanities International Complete (Ebsco), Academic Search Premier (Ebsco), HeinOnline and OSH Update, and Google Scholar were searched in May 2022. (3) Results: Of 1181 unique articles screened, 66 articles are included. Less half of the articles (42%, 28/66) presented/reviewed an intervention related to women's workplace health. A total of 55 out of the 66 articles are set across 13 countries with the remaining 12 articles described as multi-country studies or reviews. Half of the articles presenting/reviewing an intervention were grey literature, with several undertaken in UK and EU member countries. Interventions focusing on supporting women with menopause at work were the most common (43%, 12/28), followed by menstruation (25%, 7/28) and menstrual disorders (7%, 2/28). Across the reviewed articles, recommendations were categorised as adjustments to the physical work environment, information and training needs, and policy and processes. Few articles explicitly presented or affirmed a design-process and/or evaluation tied to their intervention. In lieu of design-process, this review categorises the rationales driving the development of an intervention as: pronatalist, economic rationalism, gendered occupational health concern, cultural shift towards gender equity objectives, and efforts to reduced shame and stigma. (4) Conclusions: There is a growing body of evidence aimed at understanding women's experiences of managing their menstrual and reproductive health in the workplace and how this impacts their work/career trajectories. However, little research is explicitly concerned with exploring or understanding interventions, including their design or evaluation. Most articles report menopause guidelines and are typically confined to the UK and EU-member countries. Despite the prevalence of menstrual disorders (e.g., endometriosis and polycystic ovarian syndrome (PCOS)) there is limited literature focused on how women might be supported to manage symptoms associated with these conditions at work. Accordingly, future policies should consider how women can be better supported to manage menstruation and menstrual disorders at work and recognise the importance of co-design during policy development and post-intervention evaluation. Further research needs to be undertaken on the impact of workplace policies on both employers and employees.

Whole exome sequencing and replication for breast cancer among Hispanic/Latino women identifies FANCM as a susceptibility gene for estrogen-receptor-negative breast cancer.

Introduction: Breast cancer (BC) is one of the most common cancers globally. Genetic testing can facilitate screening and risk-reducing recommendations, and inform use of targeted treatments. However, genes included in testing panels are from studies of European-ancestry participants. We sequenced Hispanic/Latina (H/L) women to identify BC susceptibility genes. Methods: We conducted a pooled BC case-control analysis in H/L women from the San Francisco Bay area, Los Angeles County, and Mexico (4,178 cases and 4,344 controls). Whole exome sequencing was conducted on 1,043 cases and 1,188 controls and a targeted 857-gene panel on the remaining samples. Using ancestry-adjusted SKAT-O analyses, we tested the association of loss of function (LoF) variants with overall, estrogen receptor (ER)-positive, and ER-negative BC risk. We calculated odds ratios (OR) for BC using ancestry-adjusted logistic regression models. We also tested the association of single variants with BC risk. Results: We saw a strong association of LoF variants in FANCM with ER-negative BC (p=4.1×10-7, OR [CI]: 6.7 [2.9-15.6]) and a nominal association with overall BC risk. Among known susceptibility genes, BRCA1 (p=2.3×10-10, OR [CI]: 24.9 [6.1-102.5]), BRCA2 (p=8.4×10-10, OR [CI]: 7.0 [3.5-14.0]), and PALB2 (p=1.8×10-8, OR [CI]: 6.5 [3.2-13.1]) were strongly associated with BC. There were nominally significant associations with CHEK2, RAD51D, and TP53. Conclusion: In H/L women, LoF variants in FANCM were strongly associated with ER-negative breast cancer risk. It previously was proposed as a possible susceptibility gene for ER-negative BC, but is not routinely tested in clinical practice. Our results demonstrate that FANCM should be added to BC gene panels.

Profiling the Somatic Mutational Landscape of Breast Tumors from Hispanic/Latina Women Reveals Conserved and Unique Characteristics.

Somatic mutational profiling is increasingly being used to identify potential targets for breast cancer. However, limited tumor-sequencing data from Hispanic/Latinas (H/L) are available to guide treatment. To address this gap, we performed whole-exome sequencing (WES) and RNA sequencing on 146 tumors and WES of matched germline DNA from 140 H/L women in California. Tumor intrinsic subtype, somatic mutations, copy-number alterations, and expression profiles of the tumors were characterized and compared with data from tumors of non-Hispanic White (White) women in The Cancer Genome Atlas (TCGA). Eight genes were significantly mutated in the H/L tumors including PIK3CA, TP53, GATA3, MAP3K1, CDH1, CBFB, PTEN, and RUNX1; the prevalence of mutations in these genes was similar to that observed in White women in TCGA. Four previously reported Catalogue of Somatic Mutations in Cancer (COSMIC) mutation signatures (1, 2, 3, 13) were found in the H/L dataset, along with signature 16 that has not been previously reported in other breast cancer datasets. Recurrent amplifications were observed in breast cancer drivers including MYC, FGFR1, CCND1, and ERBB2, as well as a recurrent amplification in 17q11.2 associated with high KIAA0100 gene expression that has been implicated in breast cancer aggressiveness. In conclusion, this study identified a higher prevalence of COSMIC signature 16 and a recurrent copy-number amplification affecting expression of KIAA0100 in breast tumors from H/L compared with White women. These results highlight the necessity of studying underrepresented populations. SIGNIFICANCE: Comprehensive characterization of genomic and transcriptomic alterations in breast tumors from Hispanic/Latina patients reveals distinct genetic alterations and signatures, demonstrating the importance of inclusive studies to ensure equitable care for patients. See related commentary by Schmit et al., p. 2443.

Reparations for Harms Experienced in Residential Aged Care.

This paper explores the possibility of reparations for harms suffered by people in residential aged care, focusing on experiences of people with dementia. We first explain how systemic and structural harms occur within residential aged care and outline how they constitute human rights violations. Using Australia as a case study, we then consider the limitations of court-based approaches to pursuit of redress and the current absence of redress from policy responses. We then propose an expansive and multifaceted notion of redress as reparations, where governments, residential aged care operators, medical and legal professionals, and civil society engage in ongoing recognition of harms and specific actions to prevent recurrence. By drawing on the United Nations Convention on the Rights of Persons with Disabilities and the Van Boven Principles, we consider the application to aged care of the framework of access to justice and reparations for human rights violations. This framework encompasses inclusive and accessible processes to access reparations for individuals in such forms as compensation and rehabilitation, and collective reparations, including apologies and public education. In order to ensure that reparations support the prevention of further harm in aged care, the design of redress could form part of broader government strategies directed toward increasing funding and access to community-based support, care, and accommodation, and enhancing the human rights of people with dementia.

Mutations in BRCA2 and PALB2 in male breast cancer cases from the United States.

Male breast cancer (MBC) is an uncommon disease with a frequency of approximately one in 1000. Due to the rarity of MBC, it is understudied and its etiology is poorly understood. Our objectives are to determine the frequency of pathogenic mutations in BRCA2 and PALB2 in MBC cases and to investigate the correlations between mutation status and cancer phenotypes. Single strand conformation polymorphism analysis, direct sequencing, and multiplex ligation-dependent probe amplification were employed to screen for mutations in the BRCA2 gene, followed by direct sequencing of the PALB2 gene in BRCA2-negative MBC cases. Pathogenic BRCA2 mutations were identified in 18 of the 115 MBC cases, including four of the ten cases (40%) from breast cancer families and 14 of the 105 cases (13%) unselected for family history of breast cancer. The difference in BRCA2-mutation frequencies between cases with and without family history of breast cancer was not statistically significant (P = 0.145), suggesting that family history is not a strong predictor of carrying a mutation in males. We observed a highly significant association of carrying a pathogenic BRCA2 mutation with high tumor grade (P < 0.001) and a weak association with positive lymph nodes (P < 0.02). Of the 97 BRCA2-negative MBC cases, we identified one PALB2 mutation with confirmed pathogenicity and one mutation predicted to be pathogenic, a prevalence of pathogenic PALB2-mutation of 1-2%. Based on our results and previous studies, genetic testing for BRCA2 should be recommended for any diagnosed MBC case, regardless of family history of breast cancer.

Germline mutations in PALB2 in African-American breast cancer cases.

Breast cancer incidence is lower in African Americans than in Caucasian Americans. However, African-American women have higher breast cancer mortality rates and tend to be diagnosed with earlier-onset disease. Identifying factors correlated to the racial/ethnic variation in the epidemiology of breast cancer may provide better understanding of the more aggressive disease at diagnosis. Truncating germline mutations in PALB2 have been identified in approximately 1% of early-onset and/or familial breast cancer cases. To date, PALB2 mutation testing has not been performed in African-American breast cancer cases. We screened for germline mutations in PALB2 in 139 African-American breast cases by denaturing high-performance liquid chromatography and direct sequencing. Twelve variants were identified in these cases and none caused truncation of the protein. Three missense variants, including two rare variants (P8L and T300I) and one common variant (P210L), were predicted to be pathogenic, and were located in a coiled-coil domain of PALB2 required for RAD51- and BRCA1-binding. We investigated and found no significant association between the P210L variant and breast cancer risk in a small case-control study of African-American women. This study adds to the literature that PALB2 mutations, although rare, appear to play a role in breast cancer in all populations investigated to date.

Prostate cancer in young men represents a distinct clinical phenotype: gene expression signature to predict early metastases.

AIM: Several genomic signatures are available to predict Prostate Cancer (CaP) outcomes based on gene expression in prostate tissue. However, no signature was tailored to predict aggressive CaP in younger men. We attempted to develop a gene signature to predict the development of metastatic CaP in young men. METHODS: We measured genome-wide gene expression for 119 tumor and matched benign tissues from prostatectomies of men diagnosed at ≤ 50 years and > 70 years and identified age-related differentially expressed genes (DEGs) for tissue type and Gleason score. Age-related DEGs were selected using the improved Prediction Analysis of Microarray method (iPAM) to construct and validate a classifier to predict metastasis using gene expression data from 1,232 prostatectomies. Accuracy in predicting early metastasis was quantified by the area under the curve (AUC) of receiver operating characteristic (ROC), and abundance of immune cells in the tissue microenvironment was estimated using gene expression data. RESULTS: Thirty-six age-related DEGs were selected for the iPAM classifier. The AUC of five-year survival ROC for the iPAM classifier was 0.87 (95%CI: 0.78-0.94) in young (≤ 55 years), 0.82 (95%CI: 0.76-0.88) in middle-aged (56-70 years), and 0.69 (95%CI: 0.55-0.69) in old (> 70 years) patients. Metastasis-associated immune responses in the tumor microenvironment were more pronounced in young and middle-aged patients than in old ones, potentially explaining the difference in accuracy of prediction among the groups. CONCLUSION: We developed a genomic classifier with high precision to predict early metastasis for younger CaP patients and identified age-related differences in immune response to metastasis development.

Creating a dementia enabling university using a Knowledge Translation approach: Innovative practice.

Universities can promote social impact by developing a dementia literate workforce. The Dementia Enabling University Strategy utilised a knowledge translation framework in an Australian university to inspire and support academics to engage students and consider how their skills and knowledge could contribute to the creation of more supportive environments for people with dementia. Dementia Enabling University Strategy ran across eight disciplines: law, media, social sciences, public health, engineering, business, marketing and psychology and was successful in engaging university academics and students. However, a longer term strategy is needed to embed 'dementia' as core business to the university impact agenda.

Methylation biomarkers of polybrominated diphenyl ethers (PBDEs) and association with breast cancer risk at the time of menopause.

BACKGROUND: Exposure to polybrominated diphenyl ethers (PBDEs) may influence risk of developing post-menopausal breast cancer. Although mechanisms are poorly understood, epigenetic regulation of gene expression may play a role. OBJECTIVES: To identify DNA methylation (DNAm) changes associated with PBDE serum levels and test the association of these biomarkers with breast cancer risk. METHODS: We studied 397 healthy women (controls) and 133 women diagnosed with breast cancer (cases) between ages 40 and 58 years who participated in the California Teachers Study. PBDE levels were measured in blood. Infinium Human Methylation EPIC Bead Chips were used to measure DNAm. Using multivariable linear regression models, differentially methylated CpG sites (DMSs) and regions (DMRs) associated with serum PBDE levels were identified using controls. For top-ranked DMSs and DMRs, targeted next-generation bisulfite sequencing was used to measure DNAm for 133 invasive breast cancer cases and 301 age-matched controls. Conditional logistic regression was used to evaluate associations between DMSs and DMRs and breast cancer risk. RESULTS: We identified 15 DMSs and 10 DMRs statistically significantly associated with PBDE levels (FDR < 0.05). Methylation changes in a DMS at BMP8B and DMRs at TP53 and A2M-AS1 were statistically significantly (FDR < 0.05) associated with breast cancer risk. CONCLUSION: We show for the first time that serum PBDE levels are associated with differential methylation and that PBDE-associated DNAm changes in blood are associated with breast cancer risk.

Common Susceptibility Loci for Male Breast Cancer.

BACKGROUND: The etiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study of MBC identified 2 predisposition loci for the disease, both of which were also associated with risk of FBC. METHODS: We performed genome-wide single nucleotide polymorphism genotyping of European ancestry MBC case subjects and controls in 3 stages. Associations between directly genotyped and imputed single nucleotide polymorphisms with MBC were assessed using fixed-effects meta-analysis of 1380 cases and 3620 controls. Replication genotyping of 810 cases and 1026 controls was used to validate variants with P values less than 1 × 10-06. Genetic correlation with FBC was evaluated using linkage disequilibrium score regression, by comprehensively examining the associations of published FBC risk loci with risk of MBC and by assessing associations between a FBC polygenic risk score and MBC. All statistical tests were 2-sided. RESULTS: The genome-wide association study identified 3 novel MBC susceptibility loci that attained genome-wide statistical significance (P < 5 × 10-08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen receptor-positive FBC. Men in the top quintile of genetic risk had a fourfold increased risk of breast cancer relative to those in the bottom quintile (odds ratio = 3.86, 95% confidence interval = 3.07 to 4.87, P = 2.08 × 10-30). CONCLUSIONS: These findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic etiology with FBC and identifying a fourfold high-risk group of susceptible men.

Allegations of sexual abuse of a child: what to do when a single forensic interview isn't enough.

This article describes the state of knowledge about extended assessments/forensic evaluations in situations of possible sexual abuse. It provides a critical review of the modest body of relevant research, describes two models for extended assessments, and presents descriptive survey findings of 62 professionals conducting extended assessments, most of whom conduct extended assessments intermittently as part of their other work on sexual abuse cases. Agencies should consider conducting extended assessments with young or traumatized children whose sexual abuse allegations are not resolved with a single interview as well as in complex child sexual abuse cases.

Learner-centered characteristics of nurse educators.

The purpose of this study was to describe the learner-centered teaching characteristics of nurse faculty who report using contemporary pedagogy. A secondary analysis of data collected by an international survey of nurse educators regarding pedagogical teaching approaches and strategies was used to answer the research questions. The study sought to: 1) describe characteristics emerging from faculty response, 2) make inferences from faculty responses regarding meaning, and 3) make inferences regarding the importance of the meaning to nursing. A qualitative research design was used to address the research question. Themes that emerged were placed under the concepts of power, role of teacher, responsibility of learner, and philosophy of evaluation guided by Weimer's (2002) conceptual framework of a learner-centered philosophy of teaching. Themes and meaning units derived from the study helped to generate textual and structure statements that represent the characterizations of learner-centered nurse educators.

Human Rights and the Confinement of People Living with Dementia in Care Homes.

This paper responds to growing concerns in human rights practice and scholarship about the confinement of people living with dementia in care homes. Moving beyond the existing focus in human rights scholarship on the role of restrictive practices in confinement, the paper broadens and nuances our understanding of confinement by exploring the daily facilitators of confinement in the lives of people with dementia. The paper draws on data from focus groups and interviews with people living with dementia, care partners, aged care workers, and lawyers and advocates about Australian care homes. It argues that microlevel interrelated and compounding factors contribute to human rights abuses of people living with dementia related to limits on freedom of movement and community access of people living with dementia, at times irrespective of the use of restrictive practices. These factors include immobilization and neglect of residents, limited and segregated recreational activities, concerns about duty of care and liability, apprehension of community exclusion, and pathologization and subversion of resistance. It is necessary to challenge the organizational, cultural, economic, and social dynamics that shape day-to-day, microlevel, routine, and compounding factors that remove the agency of people living with dementia and in turn facilitate entrenched and systematic human rights breaches in care homes.

Molecular subtypes of triple-negative breast cancer in women of different race and ethnicity.

Molecular subtypes of triple negative breast cancer (TNBC) are associated with variation in survival and may assist in treatment selection. However, the association of patient race or ethnicity with subtypes of TNBC and clinical outcome has not been addressed. Using nCounter Gene Expression Codesets, we classified TNBCs into subtypes: basal-like immune-activated (BLIA), basal-like immunosuppressed (BLIS), luminal androgen receptor (LAR), and mesenchymal (MES) in 48 Hispanic, 12 African-American, 21 Asian, and 34 White patients. Mean age at diagnosis was significantly associated with subtype, with the youngest mean age (50 years) in MES and the oldest mean age (64 years) in LAR (p < 0.0005). Subtype was significantly associated with tumor grade (p = 0.0012) and positive lymph nodes (p = 0.021), with a marginally significant association of tumor stage (p = 0.076). In multivariate Cox-proportional hazards modeling, BLIS was associated with worst survival and LAR with best survival. Hispanics had a significantly higher proportion of BLIS (53%, p = 0.03), whereas Asians had a lower proportion of BLIS (19%, p = 0.05) and a higher proportion of LAR (38%, p = 0.06) compared to the average proportion across all groups. These differences in proportions of subtype across racial and ethnic groups may explain differences in their outcomes. Determining subtypes of TNBC facilitates understanding of the heterogeneity of the TNBCs and provides a foundation for developing subtype-specific therapies and better predictors of TNBC prognosis for all races and ethnicities.