Managerialism: A workforce health hazard in human service settings.

Background: This study assesses the relationship between managerialism and health among human service workers.

Methods: A total of 2154 New York City human service workers participated in an electronic survey that included validated measures of a system of work organization (the Organizational Commitment to Managerialism scale [OCTM]) and a work stressor (the Effort Reward Imbalance scale [ERI]), and single items about physical, mental, and behavioral health. Controlling for demographic variables, logistic regression models were used to predict health outcomes assess the potential role of ERI as a mediator.

On the Front Lines: The Impact of Managerialism on the New York City Addiction Treatment Workforce.

Since the mid-1970s, neoliberal policies have relied on privatization and other tactics to down-size the state, transforming human service organizations in the process. The impact of this approach, also known as managerialism, has not been examined in addiction treatment, where the opioid epidemic has intensified the need for services. Using qualitative semi-structured interviews, we explore how managerialism has affected the workforce, service delivery, and the quality of care in New York City addiction treatment programs.

Explaining covid-19 performance: what factors might predict national responses?

fran.baum@flinders.edu.

Social determinants of health affect unplanned readmissions following acute myocardial infarction.

Low socioeconomic status predicts inferior clinical outcomes in many patient populations. The effects of patient insurance status and hospital safety-net status on readmission rates following acute myocardial infarction are unclear. A retrospective review of State Inpatient Databases for New York, California, Florida and Maryland, 2007-2014.

The Perils of Privatization: Bringing the Business Model into Human Services.

During the last three decades in both the United States and Europe, neoliberal policies, especially privatization, have restructured services in ways that dramatically affect the capacity of human services workers and agencies to serve all clients. Privatization means not only transforming public programs such as Social Security, but also managerialism-the incorporation of business principles, methods, and goals into public and nonprofit human services organizations. Few researchers have looked at the impact of market-based managerialism (focused on productivity, accountability, efficiency, and standardization) on social work's mission and the effectiveness of human services workers and organizations.

Dasatinib attenuates overexpression of Src signaling induced by the combination treatment of veliparib plus carboplatin in triple-negative breast cancer.

Purpose: Triple-negative breast cancer (TNBC) has a poor prognosis because of limited treatment options. The combination of a poly ADP ribose polymerase (PARP) inhibitor with a DNA-damaging agent has shown promise in treating TNBC; however, not all patients respond to this combination. The Src protein kinase modulates multiple cancer cell properties and plays a key role in tumorigenic processes.

Exploratory Analysis of Single-Gene Predictive Biomarkers in HERA DASL Cohort Reveals That C8A mRNA Expression Is Prognostic of Outcome and Predictive of Benefit of Trastuzumab.

Purpose: The Herceptin Adjuvant study is an international multicenter randomized trial that compared 1 or 2 years of trastuzumab given every 3 weeks with observation in women with human epidermal growth factor 2-positive (HER2+) breast cancer after chemotherapy. Identification of biomarkers predictive of a benefit from trastuzumab will minimize overtreatment and lower health care costs.

Methods: To identify possible single-gene biomarkers, an exploratory analysis of 3,669 gene probes not expected to be expressed in normal breast tissue was conducted.

High Expression of FGD3, a Putative Regulator of Cell Morphology and Motility, Is Prognostic of Favorable Outcome in Multiple Cancers.

Purpose: Identification of single-gene biomarkers that are prognostic of outcome can shed new insights on the molecular mechanisms that drive breast cancer and other cancers.

Methods: Exploratory analysis of 20,464 single-gene messenger RNAs (mRNAs) in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) discovery cohort indicates that low expression of mRNA is prognostic for poor outcome. Prognostic significance of faciogenital dysplasia 3 (FGD3), SUSD3, and other single-gene proliferation markers was evaluated in breast cancer and The Cancer Genome Atlas (TCGA) cohorts.

Identifying biomarkers to select patients with early breast cancer suitable for extended adjuvant endocrine therapy.

Purpose Of Review: In this review, we summarize recent and current biomarkers and assays that are being considered in the selection of suitable patients with estrogen receptor-positive early breast cancer for extended (years 5-10) adjuvant endocrine therapy (AET).

Recent Findings: Women with estrogen receptor-positive early-stage breast cancer (65% of cases) continue to have late risk for distant recurrence extending beyond 5 years from surgery. Recent large trials have consistently demonstrated improvement for prolonging endocrine therapy.

Dual Blockade of HER-2 Provides a Greater Magnitude of Benefit in Patients With Hormone-Negative Versus Hormone-Positive Breast Cancer.

The dual small molecule tyrosine kinase inhibitor lapatinib blocks both human epidermal growth factor receptor (HER-1) and human epidermal growth factor receptor 2 (HER-2) tyrosine kinase activity by binding reversibly to the ATP-binding site of the receptor's intracellular domain. Lapatinib, in combination with capecitabine, has been approved in 2007 for the treatment of patients with advanced HER-2 breast cancer upon progressive disease following standard chemotherapy. Approval was also extended to the treatment of postmenopausal women with advanced hormone receptor (HR)-positive and HER-2-positive breast cancer in 2010.

Single Gene Prognostic Biomarkers in Ovarian Cancer: A Meta-Analysis.

Purpose: To discover novel prognostic biomarkers in ovarian serous carcinomas.

Methods: A meta-analysis of all single genes probes in the TCGA and HAS ovarian cohorts was performed to identify possible biomarkers using Cox regression as a continuous variable for overall survival. Genes were ranked by p-value using Stouffer's method and selected for statistical significance with a false discovery rate (FDR) <.

A metastatic colon adenocarcinoma harboring BRAF V600E has a durable major response to dabrafenib/trametinib and chemotherapy.

The subset of metastatic colorectal adenocarcinomas that harbor BRAF V600E mutations are aggressive tumors with significantly shortened survival and limited treatment options. Here we present a colorectal cancer patient whose disease progressed through standard chemotherapy and who developed liver metastasis. Comprehensive genomic profiling (FoundationOne(®)) identified a BRAF V600E mutation in the liver lesion, as well as other genomic alterations consistent with colorectal cancers.

ESR1 and ESR2 polymorphisms in the BIG 1-98 trial comparing adjuvant letrozole versus tamoxifen or their sequence for early breast cancer.

Estrogen receptor 1 (ESR1) and ESR2 gene polymorphisms have been associated with endocrine-mediated physiological mechanisms, and inconsistently with breast cancer risk and outcomes, bone mineral density changes, and hot flushes/night sweats. DNA was isolated and genotyped for six ESR1 and two ESR2 single-nucleotide polymorphisms (SNPs) from tumor specimens from 3691 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1-98 trial to receive tamoxifen and/or letrozole for 5 years. Associations with recurrence and adverse events (AEs) were assessed using Cox proportional hazards models.

CYP19A1 polymorphisms and clinical outcomes in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial.

To determine whether CYP19A1 polymorphisms are associated with abnormal activity of aromatase and with musculoskeletal and bone side effects of aromatase inhibitors. DNA was isolated from tumor specimens of 4861 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1-98 trial to receive tamoxifen and/or letrozole for 5 years. Tumors were genotyped for six CYP19A1 polymorphisms using PCR-based methods.

Wnt signaling in triple negative breast cancer is associated with metastasis.

Background: Triple Negative subset of (TN) Breast Cancers (BC), a close associate of the basal-like subtype (with limited discordance) is an aggressive form of the disease which convey unpredictable, and poor prognosis due to limited treatment options and lack of proven effective targeted therapies.

Methods: We conducted an expression study of 240 formalin-fixed, paraffin-embedded (FFPE) primary biopsies from two cohorts, including 130 TN tumors, to identify molecular mechanisms of TN disease.

Results: The annotation of differentially expressed genes in TN tumors contained an overrepresentation of canonical Wnt signaling components in our cohort and others.

Differential activation of Wnt-β-catenin pathway in triple negative breast cancer increases MMP7 in a PTEN dependent manner.

Mutations of genes in tumor cells of Triple Negative subset of Breast Cancer (TNBC) deregulate pathways of signal transduction. The loss of tumor suppressor gene PTEN is the most common first event associated with basal-like subtype (Martins, De, Almendro, Gonen, and Park, 2012). Here we report for the first time that the functional upregulation of secreted-MMP7, a transcriptional target of Wnt-β-catenin signature pathway in TNBC is associated to the loss of PTEN.

Molecular characterisation of formalin-fixed paraffin-embedded (FFPE) breast tumour specimens using a custom 512-gene breast cancer bead array-based platform.

Background: Formalin-fixed, paraffin-embedded (FFPE) tumour tissue represents an immense but mainly untapped resource with respect to molecular profiling. The DASL (cDNA-mediated Annealing, Selection, extension, and Ligation) assay is a recently described, RT-PCR-based, highly multiplexed high-throughput gene expression platform developed by Illumina specifically for fragmented RNA typically obtained from FFPE specimens, which enables expression profiling. In order to extend the utility of the DASL assay for breast cancer, we have custom designed and validated a 512-gene human breast cancer panel.

Protein-coding and microRNA biomarkers of recurrence of prostate cancer following radical prostatectomy.

An important challenge in prostate cancer research is to develop effective predictors of tumor recurrence following surgery to determine whether immediate adjuvant therapy is warranted. To identify biomarkers predictive of biochemical recurrence, we isolated the RNA from 70 formalin-fixed, paraffin-embedded radical prostatectomy specimens with known long-term outcomes to perform DASL expression profiling with a custom panel that we designed of 522 prostate cancer-relevant genes. We identified a panel of 10 protein-coding genes and two miRNA genes (RAD23B, FBP1, TNFRSF1A, CCNG2, NOTCH3, ETV1, BID, SIM2, LETMD1, ANXA1, miR-519d, and miR-647) that could be used to separate patients with and without biochemical recurrence (P < 0.

The effect of a DNA repair gene on cellular invasiveness: XRCC3 over-expression in breast cancer cells.

Over-expression of DNA repair genes has been associated with resistance to radiation and DNA-damage induced by chemotherapeutic agents such as cisplatin. More recently, based on the analysis of genome expression profiling, it was proposed that over-expression of DNA repair genes enhances the invasive behaviour of tumour cells. In this study we present experimental evidence utilizing functional assays to test this hypothesis.

Differential signaling of cysteinyl leukotrienes and a novel cysteinyl leukotriene receptor 2 (CysLT₂) agonist, N-methyl-leukotriene C₄, in calcium reporter and β arrestin assays.

The cysteinyl leukotrienes (cysLTs) LTC₄, LTD₄, and LTE₄ are lipid mediators with physiological and pathophysiological functions. They exert their effects through G protein-coupled receptors (GPCRs), most notably via CysLT₁ and CysLT₂ receptor. The roles of the CysLT₂ receptor are beginning to emerge.

Double jeopardy: the impact of neoliberalism on care workers in the United States and South Africa.

Many researchers have explored how neoliberal restructuring of the workplace has reduced the standard of living and increased workplace stress among private sector employees. However, few have focused on how neoliberal restructuring of public policy has had similar effects on the public sector workforce. Using original case study research, the authors examine how two iconic pieces of neoliberal policy--the 1996 welfare reform bill in the United States and the GEAR macroeconomic policy in South Africa--affected public/nonprofit human service workers in New York City, United States, and public sector nurses in KwaZulu-Natal, South Africa.

Prostate cancer genes associated with TMPRSS2-ERG gene fusion and prognostic of biochemical recurrence in multiple cohorts.

Background: Recent studies have indicated that prostate cancer patients with the TMPRSS2-ERG gene fusion have a higher risk of recurrence. To identify markers associated with TMPRSS2-ERG fusion and prognostic of biochemical recurrence, we analysed a cohort of 139 men with prostate cancer for 502 molecular markers.

Methods: RNA from radical prostatectomy tumour specimens was analysed using cDNA-mediated, annealing, selection, extension and ligation (DASL) to determine mRNAs associated with TMPRSS2-ERG T1/E4 fusion and prognostic of biochemical recurrence.

Disease-free survival according to degree of HER2 amplification for patients treated with adjuvant chemotherapy with or without 1 year of trastuzumab: the HERA Trial.

Purpose: To determine whether (1) immunohistochemical (IHC) HER2 status (ie, 2+ or 3+), (2) degree of fluorescence in situ hybridization (FISH) amplification according to (2a) HER2/CEP17 ratio or (2b) HER2 gene copy number, or (3) polysomy significantly influenced clinical outcome for patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer enrolled in the Herceptin Adjuvant trial of trastuzumab versus no trastuzumab administered after completion of chemotherapy.

Patients And Methods: IHC and/or FISH analyses were performed locally and required central confirmation as indicating HER2 positivity for trial entry. FISH data from the central HER2 analysis on patients in the 1-year trastuzumab and no trastuzumab arms were assessed in relation to disease-free survival (DFS) after a median 2 years of follow-up.

Proteomics: new technologies and clinical applications.

During the past decade, various genomics-based techniques have been applied with increasing success to the molecular characterisation of breast tumours, which has resulted in a more detailed classification scheme and has produced clinical diagnostic tests, which have been applied to both the prognosis and the prediction of outcome to treatment. Application of proteomics-based techniques is also seen as crucial if we are to develop a systems biology approach to the discovery of biomarkers of early diagnosis, prognosis and prediction of outcome to breast cancer therapies. However, proteomics is met with greater challenges to overcome that include optimising specimen handling and preparation, as well as determining the most appropriate proteomic platforms to apply to the identification of differentially expressed biomarker candidates and their subsequent validation.