Meritor Savings Bank v. Vinson: Title VII Liability for Sexual Harassment

In Meritor Savings Bank v. Vinson,! the United States Supreme Court addressed the issue of sexual harassment for the first time. The Court held that when sexual harassment creates a hostile or offensive working environment, it is actionable under Title VII of the Civil Rights Act of 1964. The Court interpreted Title VII as demonstrating a congressional intent to preserve the economic, psychological and emotional benefits of employment. This interpretation has been advanced by the Equal Employment Opportunity Commission (EEOC) and in lower court opinions. The Supreme Court rejected the District of Columbia Circuit Court of Appeals ruling that an employer is strictly liable for hostile environment sex discrimination regardless of the circumstances of the case. Instead, the Court stated that courts must look to agency principles for guidance in determining employer liability, and must examine the totality of the circumstances. Notice or absence of notice to the employer of the harassment will not be dispositive of the liability issue

Meritor Savings Bank v. Vinson: Title VII Liability for Sexual Harassment

In Meritor Savings Bank v. Vinson,! the United States Supreme Court addressed the issue of sexual harassment for the first time. The Court held that when sexual harassment creates a hostile or offensive working environment, it is actionable under Title VII of the Civil Rights Act of 1964. The Court interpreted Title VII as demonstrating a congressional intent to preserve the economic, psychological and emotional benefits of employment. This interpretation has been advanced by the Equal Employment Opportunity Commission (EEOC) and in lower court opinions. The Supreme Court rejected the District of Columbia Circuit Court of Appeals ruling that an employer is strictly liable for hostile environment sex discrimination regardless of the circumstances of the case. Instead, the Court stated that courts must look to agency principles for guidance in determining employer liability, and must examine the totality of the circumstances. Notice or absence of notice to the employer of the harassment will not be dispositive of the liability issue

Aboriginal Community-led Preservice Teacher Education: Learning from Country in the City

In Australia it is well documented that teachers continue to struggle with implementing Aboriginal content, pedagogies and engaging with Aboriginal communities. This paper describes a research project analysing place-based learning for preservice teachers at an urban university led by Aboriginal community members. We argue that place-based learning is critical in developing preservice teacher’s knowledge and confidence in Aboriginal education. Surveys, individual and group yarns provided in-depth data from 64 participants completing elective courses including place-based ‘Learning from Country’ (LFC) experiences. Three key findings emerge from the data. Firstly, the utility of an experiential ‘learning by doing’ approach, secondly, the profound shifts in participant understandings of the diversity of Aboriginal cultures, histories and communities and thirdly, how these experiences highlighted the strength and presence of the local urban Aboriginal community. These findings suggest that LFC holds promise as a pedagogical strategy to improve teacher capacity in Aboriginal education

Evaluation of ‘The Exercise Effect’: A pilot project integrating an exercise practitioner into outpatient mental health services in Ireland

In April 2019, a submission for funding was made to the Sláintecare Integration Fund (2019) to establish the ‘Exercise Effect’ project, including an independent evaluation of the project. The Exercise Effect builds on a longstanding collaborative partnership between key stakeholders, Health Service Executive (HSE) South East Wexford Mental Health Services, Sports Active Wexford (SAW) (a Local Sports Partnership) and Waterford Institute of Technology (WIT). Exercise is well recognised as a therapeutic tool that can benefit a range of mental health symptoms and cognitive function among trans-diagnostic mental health populations. Exercise interventions are also a valuable resource for improving the disproportionately poor physical health states of people with mental disorders. This report presents a detailed account of the Exercise Effect project and the findings from the research evaluation undertaken

Research conference summary from the 2014 International Task Force on

OBJECTIVE: METHODS: In 2014, the Alternating Hemiplegia of Childhood Foundation hosted a multidisciplinary workshop intended to address fundamental challenges surrounding the diagnosis and management of individuals with RESULTS: Workshop attendees were charged with the following: (1) to achieve consensus on expanded diagnostic criteria to facilitate the identification of additional patients, intended to supplement existing syndrome-specific diagnostic paradigms; (2) to standardize definitions for the broad range of paroxysmal manifestations associated with AHC to disseminate to families; (3) to create clinical recommendations for common recurrent issues facing families and medical care providers; (4) to review data related to the death of individuals in the Alternating Hemiplegia of Childhood Foundation database to guide future efforts in identifying at-risk subjects and potential preventative measures; and (5) to identify critical gaps where we most need to focus national and international research efforts. CONCLUSIONS: This report summarizes recommendations of the workshop committee, highlighting the key phenotypic features to facilitate the diagnosis of possibl

Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus

Objectives: Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Here, we detail a systematic and structured evidence-based approach to inform consensus decision making to select the first two drugs for evaluation in Motor Neuron Disease-Systematic Multi-arm Adaptive Randomised Trial (MND-SMART: NCT04302870), an adaptive platform trial. We aim to identify and prioritise candidate drugs which have the best available evidence for efficacy, acceptable safety profiles and are feasible for evaluation within the trial protocol. Methods: We conducted a two-stage systematic review to identify potential neuroprotective interventions. First, we reviewed clinical studies in MND, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and multiple sclerosis, identifying drugs described in at least one MND publication or publications in two or more other diseases. We scored and ranked drugs using a metric evaluating safety, efficacy, study size and study quality. In stage two, we reviewed efficacy of drugs in MND animal models, multicellular eukaryotic models and human induced pluripotent stem cell (iPSC) studies. An expert panel reviewed candidate drugs over two shortlisting rounds and a final selection round, considering the systematic review findings, late breaking evidence, mechanistic plausibility, safety, tolerability and feasibility of evaluation in MND-SMART. Results: From the clinical review, we identified 595 interventions. 66 drugs met our drug/disease logic. Of these, 22 drugs with supportive clinical and preclinical evidence were shortlisted at round 1. Seven drugs proceeded to round 2. The panel reached a consensus to evaluate memantine and trazodone as the first two arms of MND-SMART. Discussion: For future drug selection, we will incorporate automation tools, text-mining and machine learning techniques to the systematic reviews and consider data generated from other domains, including high-throughput phenotypic screening of human iPSCs

Probenecid Inhibits the Human Bitter Taste Receptor TAS2R16 and Suppresses Bitter Perception of Salicin

Bitter taste stimuli are detected by a diverse family of G protein-coupled receptors (GPCRs) expressed in gustatory cells. Each bitter taste receptor (TAS2R) responds to an array of compounds, many of which are toxic and can be found in nature. For example, human TAS2R16 (hTAS2R16) responds to β-glucosides such as salicin, and hTAS2R38 responds to thiourea-containing molecules such as glucosinolates and phenylthiocarbamide (PTC). While many substances are known to activate TAS2Rs, only one inhibitor that specifically blocks bitter receptor activation has been described. Here, we describe a new inhibitor of bitter taste receptors, p-(dipropylsulfamoyl)benzoic acid (probenecid), that acts on a subset of TAS2Rs and inhibits through a novel, allosteric mechanism of action. Probenecid is an FDA-approved inhibitor of the Multidrug Resistance Protein 1 (MRP1) transporter and is clinically used to treat gout in humans. Probenecid is also commonly used to enhance cellular signals in GPCR calcium mobilization assays. We show that probenecid specifically inhibits the cellular response mediated by the bitter taste receptor hTAS2R16 and provide molecular and pharmacological evidence for direct interaction with this GPCR using a non-competitive (allosteric) mechanism. Through a comprehensive analysis of hTAS2R16 point mutants, we define amino acid residues involved in the probenecid interaction that result in decreased sensitivity to probenecid while maintaining normal responses to salicin. Probenecid inhibits hTAS2R16, hTAS2R38, and hTAS2R43, but does not inhibit the bitter receptor hTAS2R31 or non-TAS2R GPCRs. Additionally, structurally unrelated MRP1 inhibitors, such as indomethacin, fail to inhibit hTAS2R16 function. Finally, we demonstrate that the inhibitory activity of probenecid in cellular experiments translates to inhibition of bitter taste perception of salicin in humans. This work identifies probenecid as a pharmacological tool for understanding the cell biology of bitter taste and as a lead for the development of broad specificity bitter blockers to improve nutrition and medical compliance

Genomic profiling of pediatric hematologic malignancies and diagnosis of cancer predisposition syndromes: tumor-only <i>versus</i> paired tumor-normal sequencing

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