Principles to Guide the Office of Legal Counsel

Former members of Office of Legal Counsel ( OLC ) in the Department of Justice offer guidance for their successors. Among the document\u27s recommendations are suggestions that the OLC provide an accurate and honest appraisal of applicable law, even if that advice will constrain the administration’s pursuit of desired policies; and publicly disclose its written legal opinions in a timely manner, absent strong reasons for delay or nondisclosure

Working Group on Chapter 1 of the Proposed Restatement of Employment Law: Existence of Employment Relationship

This article presents a critique of chapter 1 of the Proposed Restatement of Employment Law. The critique is organized to follow the organization of the proposed Restatement, which begins with a provision of black letter law, a series of comments and illustrations explaining the meaning and application of the black letter law, and the reporters\u27 notes providing support for the black letter law and the commentary. This critique will follow that structure, with each part focusing on a section of the chapter: the introductory note; section 1.01; section 1.02; section 1.03; and section 1.04. The subdivisions of the parts will, likewise, generally follow the subdivisions of the sections in the chapter, although sometimes a critique of the reporters\u27 notes will be its own subpart, and sometimes it will be discussed in the subsections analyzing the comments

Working Group on Chapter 1 of the Proposed Restatement of Employment Law: Existence of Employment Relationship

This article presents a critique of chapter 1 of the Proposed Restatement of Employment Law. The critique is organized to follow the organization of the proposed Restatement, which begins with a provision of black letter law, a series of comments and illustrations explaining the meaning and application of the black letter law, and the reporters\u27 notes providing support for the black letter law and the commentary. This critique will follow that structure, with each part focusing on a section of the chapter: the introductory note; section 1.01; section 1.02; section 1.03; and section 1.04. The subdivisions of the parts will, likewise, generally follow the subdivisions of the sections in the chapter, although sometimes a critique of the reporters\u27 notes will be its own subpart, and sometimes it will be discussed in the subsections analyzing the comments

Raising a Small Flock of Sheep in Ohio

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'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

Elevated expression of STK3 mRNA and protein is associated with poor outcome in invasive breast cancer

Purpose of the study: The mammalian sterile 20-like kinase (MST2/STK3) and its close homologue MST1(STK4) are members of the germinal centre kinase group II (GCK II) family of mitogen-activated protein kinases (MAPK). High STK3 expression is known to be correlated with poor prognosis in various cancers playing a role in cell migration and invasion. This study aimed to determine correlations of STK3 expression with clinicopathological variables in BCs. Methods: STK3 mRNA expression was investigated in the METABRIC BC cohort (n=1980) and externally validated using online BC expression datasets [bc-GenExMiner v4.0]. STK3 protein expression was studied in a well characterised series of primary invasive BCs (n=1024) using immunohistochemistry including correlations with clinicopathological parameters, other biomarkers and patient outcome. Results: Copy number (CN) gain of STK3 was correlated with adverse prognostic features: higher grade and poor NPI (p<0.0001) High STK3 expression was also associated with poor prognostic factors, including high grade, younger age, larger tumour size, poorer NPI and negative ER/PR status (p<0.001). In PAM50 subtypes, high STK3 expression was associated with Luminal B/basal like tumours. Cytoplasmic STK3(c-STK3) protein expression was associated with increased mitotic index, poorer NPI (p<0.001) and basal-like markers CK5/6 and EGFR (p<0.05). In univariate analysis, high c-STK3 expression showed poorer outcome in the whole cohort and ER+ subgroups (p<0.05). Pooled STK3 gene expression data in the external validation cohort confirmed association with poor outcome (p<0.0001, HR = 1.60, 95% CI 1.28–2.01). Conclusions: Results suggest c-STK3 as a poor prognostic marker in invasive BC including ER+ subgroups warranting further functional studies

Cell division cycle 25C (CDC25C) expression confers poor prognosis in invasive breast cancer

Background: CDC25C, belonging to the Cdc25 phosphatase family, plays a major role in cell cycle control, impacting on DNA repair and apoptosis. It has been shown that poor prognosis/copy number high Luminal A breast cancers (BCs) are enriched for the Aurora kinase pathway including CDC25C leading to CDK1 activation (Ciriello et al, Breast Cancer Research Treatment, 2013:409). This study examined the associations of CDC25C with clinicopathological and molecular features in BCs including the low grade ER positive cohort. Methodology: CDC25C mRNA expression was studied in the METABRIC BC cohort (n=1980) and externally validated using online expression datasets [bc-GenExMiner v4.0]. CDC25C protein expression level was assessed immunohistochemically on a large annotated series of BC (n= 1330) and correlations made with clinicopathological parameters and patient outcome. Results: High CDC25C expression was significantly associated with poor prognostic factors including high grade, large tumour size, medullary like tumours, poorer NPI, ER-/PR- Her2+ status (p<0.001) and was differentially expressed in poor prognosis integrative clusters 5 and 10 (p<0.001). Cytoplasmic CDC25C (c-CDC25C) protein showed positive association with non-NST and non-medullary tumour subtypes while nuclear CDC25C (n-CDC25C) negatively associated with tumour stage (p<0.05). There was no association with ER, PR status, NPI and lymph nodes. However, high c-CDC25C resulted in poor survival at 20 years in the Grade 1 ER+ cohort (p=0.007), while high n-CDC25C showed better long term survival (p<0.001). Pooled CDC25C expression data in the external validation cohort showed an association with poor outcome (p<0.0001, HR = 1.45, 95 % CI 1.28—1.64). Conclusion: CDC25C appears to be associated with poor prognosis in BC including the Grade 1 ER+ cohort, indicating the importance of further functional analyses

Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer

Background. Immunotherapy has shown efficacy in small cell lung cancer (SCLC), but only a subset of patients benefits. Surrogate biomarkers are urgently needed. Our aim was to evaluate serum Th1, Th2, and proinflammatory cytokines in two cohorts of SCLC patients before and during treatment with chemotherapy with or without ipilimumab and to correlate them with survival. Patients and methods. Two cohorts of SCLC patients were studied: patients treated with chemotherapy (n = 47), and patients treated with chemotherapy plus ipilimumab (n = 37). Baseline, on-treatment and after-treatment serum samples were evaluated for the presence of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, GM-CSF, and Mip-1alpha using a Luminex assay. Differential changes in cytokines between cohorts were analyzed. Associations between cytokine levels and their changes with overall survival were evaluated. Results. Patients treated with ipilimumab showed a global increase of all cytokines after treatment initiation. A high level of IL-8 at baseline was associated with worse prognosis regardless of treatment. Baseline increased IL-2 levels predicted sensitivity to ipilimumab, while high IL-6 and TNF-alpha predicted resistance. An on-treatment increase in IL-4 levels in patients treated with immune-chemotherapy was associated with a better overall survival. Conclusions. The addition of ipilimumab to standard chemotherapy in SCLC modulates the serum levels of cytokines. Baseline levels and their change over time relate to overall survival. Blood-based biomarkers are convenient for patients, and our results support prospective validation of cytokines as predictive biomarkers for ipilimumab in SCLC

Physical Activity and Insulin Sensitivity: The RISC Study

OBJECTIVE— Physical activity is a modifiable risk factor for type 2 diabetes, partly through its action on insulin sensitivity. We report the relation between insulin sensitivity and physical activity measured by accelerometry

A lab-on-a-chip for the concurrent electrochemical detection of SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies in saliva and plasma

Rapid, accurate and frequent detection of the RNA of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and of serological host antibodies to the virus would facilitate the determination of the immune status of individuals who have Coronavirus disease 2019 (COVID-19), were previously infected by the virus, or were vaccinated against the disease. Here we describe the development and application of a 3D-printed lab-on-a-chip that concurrently detects, via multiplexed electrochemical outputs and within 2 h, SARS-CoV-2 RNA in saliva as well as anti-SARS-CoV-2 immunoglobulins in saliva spiked with blood plasma. The device automatedly extracts, concentrates and amplifies SARS-CoV-2 RNA from unprocessed saliva, and integrates the Cas12a-based enzymatic detection of SARS-CoV-2 RNA via isothermal nucleic acid amplification with a sandwich-based enzyme-linked immunosorbent assay on electrodes functionalized with the Spike S1, nucleocapsid and receptor-binding-domain antigens of SARS-CoV-2. Inexpensive microfluidic electrochemical sensors for performing multiplexed diagnostics at the point of care may facilitate the widespread monitoring of COVID-19 infection and immunity