Fleeing the Rat’s Nest: Title VII Jurisprudence After Ortiz v. Werner Enterprises, Inc.

In 2016, the Seventh Circuit issued an opinion that may be a harbinger for an important shift in the federal judiciary’s long-standing employment discrimination jurisprudence. In Ortiz v. Werner Enterprises, Judge Easterbrook reiterated the frustration with the existing “rat’s nest” of tests and standards used in Title VII discrimination and retaliation claims. The note contains two overarching arguments. First, the Supreme Court’s employment discrimination and “rat’s nest” of tests and standards has led to an untenable situation in which federal district courts apply different standards at different stages of litigations. This in turn has caused confusion amongst the various federal courts and has resulted in employee-plaintiffs to unfairly face different burdens across the country. Second, the Ortiz decision evinces that at least some judges and courts are tiring of this “rat’s nest” when it comes to evidentiary standards in employment discrimination cases. To solve this quandary, the federal judiciary should simplify the evidentiary standard at summary judgment so that an employee may present his or her evidence as a whole. With such a holistic standard, an employee need not be concerned with whether the evidence is direct, indirect, merely suggestive, or iron clad. Rather, a common sense evaluation of the evidence as a whole by the judge would suffice

Fleeing the Rat’s Nest: Title VII Jurisprudence After Ortiz v. Werner Enterprises, Inc.

In 2016, the Seventh Circuit issued an opinion that may be a harbinger for an important shift in the federal judiciary’s long-standing employment discrimination jurisprudence. In Ortiz v. Werner Enterprises, Judge Easterbrook reiterated the frustration with the existing “rat’s nest” of tests and standards used in Title VII discrimination and retaliation claims. The note contains two overarching arguments. First, the Supreme Court’s employment discrimination and “rat’s nest” of tests and standards has led to an untenable situation in which federal district courts apply different standards at different stages of litigations. This in turn has caused confusion amongst the various federal courts and has resulted in employee-plaintiffs to unfairly face different burdens across the country. Second, the Ortiz decision evinces that at least some judges and courts are tiring of this “rat’s nest” when it comes to evidentiary standards in employment discrimination cases. To solve this quandary, the federal judiciary should simplify the evidentiary standard at summary judgment so that an employee may present his or her evidence as a whole. With such a holistic standard, an employee need not be concerned with whether the evidence is direct, indirect, merely suggestive, or iron clad. Rather, a common sense evaluation of the evidence as a whole by the judge would suffice

Effect of Short-Term Antiretroviral Therapy Interruption on Levels of Integrated HIV DNA

Analytic treatment interruption (ATI) studies are required to evaluate strategies aimed at achieving ART-free HIV remission, but the impact of ATI on the viral reservoir remains unclear. We validated a DNA size selection-based assay for measuring levels of integrated HIV DNA and applied it to assess the effects of short-term ATI on the HIV reservoir. Samples from participants from four AIDS Clinical Trials Group ATI studies were assayed for integrated HIV DNA levels. Cryopreserved peripheral blood mononuclear cells (PBMCs) were obtained for 12 participants with available samples pre-ATI and approximately 6 months after ART resumption. Four participants also had samples available during the ATI. The median duration of ATI was 12 weeks. Validation of the HIV integrated DNA size-exclusion (HIDE) assay was performed using samples spiked with unintegrated HIV DNA, HIV-infected cell lines, and participant PBMCs. The HIDE assay eliminated 99% of unintegrated HIV DNA species and strongly correlated with the established Alu-gag assay. For the majority of individuals, integrated DNA levels increased during ATI and subsequently declined upon ART resumption. There was no significant difference in the levels of integrated HIV DNA between the pre- and post-ATI time points, with a median ratio of post- to pre-ATI HIV DNA levels of 0.95. Using a new integrated HIV DNA assay, we found minimal change in the levels of integrated HIV DNA in participants who underwent an ATI, followed by 6 months of ART. This suggests that short-term ATI can be conducted without a significant impact on the levels of integrated proviral DNA in the peripheral blood. IMPORTANCE Interventions aimed at achieving sustained antiretroviral therapy (ART)free HIV remission require treatment interruption trials to assess their efficacy. However, these trials are accompanied by safety concerns related to the expansion of the viral reservoir. We validated an assay that uses an automated DNA size-selection platform for quantifying levels of integrated HIV DNA and is less sample- and labor-intensive than current assays. Using stored samples from AIDS Clinical Trials Group studies, we found that short-term ART discontinuation had minimal impact on integrated HIV DNA levels after ART resumption, providing reassurance about the reservoir effects of short-term treatment interruption trials.National Institute of Allergy and Infectious Diseases of the National Institutes of Health [AI125109, AI068634, AI068636, UM1 AI106701, UM1 AI126617, AI120011]; Gilead Sciences; Merck6 month embargo; published online: 28 March 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The role of CD101-expressing CD4 T cells in HIV/SIV pathogenesis and persistence.

Despite the advent of effective antiretroviral therapy (ART), human immunodeficiency virus (HIV) continues to pose major challenges, with extensive pathogenesis during acute and chronic infection prior to ART initiation and continued persistence in a reservoir of infected CD4 T cells during long-term ART. CD101 has recently been characterized to play an important role in CD4 Treg potency. Using the simian immunodeficiency virus (SIV) model of HIV infection in rhesus macaques, we characterized the role and kinetics of CD101+ CD4 T cells in longitudinal SIV infection. Phenotypic analyses and single-cell RNAseq profiling revealed that CD101 marked CD4 Tregs with high immunosuppressive potential, distinct from CD101- Tregs, and these cells also were ideal target cells for HIV/SIV infection, with higher expression of CCR5 and α4β7 in the gut mucosa. Notably, during acute SIV infection, CD101+ CD4 T cells were preferentially depleted across all CD4 subsets when compared with their CD101- counterpart, with a pronounced reduction within the Treg compartment, as well as significant depletion in mucosal tissue. Depletion of CD101+ CD4 was associated with increased viral burden in plasma and gut and elevated levels of inflammatory cytokines. While restored during long-term ART, the reconstituted CD101+ CD4 T cells display a phenotypic profile with high expression of inhibitory receptors (including PD-1 and CTLA-4), immunsuppressive cytokine production, and high levels of Ki-67, consistent with potential for homeostatic proliferation. Both the depletion of CD101+ cells and phenotypic profile of these cells found in the SIV model were confirmed in people with HIV on ART. Overall, these data suggest an important role for CD101-expressing CD4 T cells at all stages of HIV/SIV infection and a potential rationale for targeting CD101 to limit HIV pathogenesis and persistence, particularly at mucosal sites

TREM2+ and interstitial-like macrophages orchestrate airway inflammation in SARS-CoV-2 infection in rhesus macaques

‘The induction and coordination of immune cells in response to SARS-CoV-2 infection are critical in the immunopathology of COVID-19. Here the authors use a rhesus macaque model of SARS-CoV-2 infection and show key populations of macrophage drive the inflammatory cytokine production in the alveolar space’