The Public Advocacy of the American Jewish Committee, 1906-1929

The American Jewish Committee (AJC) was founded in 1906 by a group of elite Jewish communal leaders. In the historiography on the organization, the Committee’s earliest activities are described as limited to “quiet diplomacy,” involving the discreet lobbying of public officials. This dissertation challenges this account of the AJC’s early activism, arguing that, from its founding, the Committee was involved in more overt forms of public advocacy and was building the infrastructure to carry out the public advocacy work of modern special interest groups. While the AJC’s leaders continued to practice quiet diplomacy, they also released public statements, sponsored research, subsidized the publication of books, became involved in public interest litigation, and widely distributed pamphlets in an effort to influence public opinion. Using documents from the AJC’s archives, this dissertation presents a series of case studies of the organization’s earliest public advocacy work and describes its leaders’ deliberations about how to expand the Committee’s research and advocacy infrastructure and avert an intensification of anti-Semitism in the United States. The advocacy tactics the AJC employed were adaptations of techniques used by older European Jewish leadership organizations. The Committee’s leaders tailored these approaches according to their understanding of the threats the American Jewish community faced during the early-twentieth century. The activities of the Committee’s founders and early leaders shaped the AJC’s later, more conspicuous public advocacy on behalf of American Jewry and other minority communities in the United States

Modulating Protein-Protein Interactions Through Peptidomimetics Utilizing Thioether Oxidation States, Noncovalent Interactions & Epigenetic Regulation

University of Minnesota Ph.D. dissertation. September 2017. Major: Chemistry. Advisor: William Pomerantz. 1 computer file (PDF); xxiv, 279 pages.Interactions among proteins play a fundamental role in regulating all biological processes. Such interactions that dictate disease progression are viable regions to target with chemical probes and inhibitors. With an array of interacting sites that vary in size, polarity, and structure, these intransigent chemical targets have been termed undruggable due to the difficulties to target; however, advancements in the area of chemical biology now allow for exploration and progress of this formidable territory. With an estimated 650,000 protein-protein interactions (PPIs) found in the human interactome, probes that can target such interactions are highly sought after due to their significance in disease suppression. In Chapter 2, we explore the importance of a new non-covalent interaction between aromatic π-systems and sulfoxide moieties that contribute to binding energy. With an enrichment of aromatic amino acids at protein interfaces, the utility of this interaction can be exploited at protein interaction sites. We further probe protein interfaces in Chapter 3 by incorporating oxidizable thioether-bridged -helical peptidomimetics. These probes modulate the polarity, structure, stability, affinity, and permeability, thereby allowing the mimetics to disrupt native PPIs. We utilized a specific Protein Observed 19F (PrOF) NMR technique to monitor crosslinked peptide affinity, as well as circular dichroism, tryptic digests, HPLC, fluorescence microscopy, fluorescence polarization, and computational calculations to evaluate biophysical characteristics. We further probe perfluorinated sulfone crosslinks in collaboration with Ratimir Derda in Chapter 3 for interactions with human serum albumin. By using two different methods to incorporate thioether crosslinks, either with an SN2 dibromoalkylation or a thiol-ene reaction as discussed in Chapter 4, we can alter the oxidation states of either one or two sulfur groups within the macrocycle. Chapter 5 is an assessment of a histone variant, H2A.Z for specific acetylation patterns to interact with certain bromodomains, BPTF and PfGCN5. Using PrOF NMR, a ligand observed NMR technique CPMG, and photo-crosslinking, we identify from of a series of various acetylation patterns, that H2A.Z Ack4,11 shows the highest affinity towards the bromodomain BPTF. We further investigate a different bromodomain, CBP in collaboration with Stuart Conway for interactions with five previously identified small molecules. Using PrOF NMR, and fluorescence polarization, we identify affinity towards three bromodomains: CBP, Brd4 and BrdT

Cancers of unknown primary origin (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin

BACKGROUND: Cancers of unknown primary (CUPs) constitute ~5% of all cancers. The tumors have an aggressive biological and clinical behavior. The aim of the present study has been to uncover whether CUPs exhibit distinct molecular features compared to metastases of known origin. METHODS: Employing genome wide transcriptome analysis, Linear Discriminant Analysis (LDA) and Quadratic Discriminant Analysis (QDA), we defined the putative origins of a large series of CUP and how closely related a particular CUP was to corresponding metastases of known origin. LDA predictions were subsequently used to define a universal CUP core set of differentially expressed genes, that by means of gene set enrichment analysis was exploited to depict molecular pathways characterizing CUP. RESULTS: The analyses show that CUPs are distinct from metastases of known origin. CUPs exhibit inconsistent expression of conventional cancer biomarkers and QDA derived outlier scores show that CUPs are more distantly related to their primary tumor class than corresponding metastases of known origin. Gene set enrichment analysis showed that CUPs display increased expression of genes involved in DNA damage repair and mRNA signatures of chromosome instability (CIN), indicating that CUPs are chromosome unstable compared to metastases of known origin. CONCLUSIONS: CIN may account for the uncommon clinical presentation, chemoresistance and poor outcome in patients with CUP and warrant selective diagnostic strategies and treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1128-x) contains supplementary material, which is available to authorized users

Variations in Implementation of Specifications Grading in STEM Courses

Specifications grading is an assessment strategy based on mastery learning, clear learning objectives, and frequent evaluations and feedback. Twelve instructors at a southeastern four-year public college implemented the specifications grading method across eight discrete courses in four STEM areas. In this modified assessment strategy, the students controlled their grades through multiple attempts, with limitations, on assessments of course objectives. The instructors designed and executed specifications grading in unique ways that aligned with their content areas, teaching beliefs, and individual teaching styles. Preliminary observations suggest that, regardless of subject area, specifications grading can be used as an alternative to traditional assessment methodologies in STEM courses, regardless of the content area. In general, three major variations of implementation arose from this initial trial. Major differences and commonalities among these types are discussed as they relate to the course subject area in which they are used. The results of this work add a unique set of assessment practices to the current body of knowledge in that other practitioners may gain insight on variations of the specifications grading method that may be practical and applicable in their own classrooms

Predicting the risk of falling – efficacy of a risk assessment tool compared to nurses' judgement: a cluster-randomised controlled trial [ISRCTN37794278]

BACKGROUND: Older people living in nursing homes are at high risk of falling because of their general frailty and multiple pathologies. Prediction of falls might lead to an efficient allocation of preventive measures. Although several tools to assess the risk of falling have been developed, their impact on clinically relevant endpoints has never been investigated. The present study will evaluate the clinical efficacy and consequences of different fall risk assessment strategies. STUDY DESIGN: Cluster-randomised controlled trial with nursing home clusters randomised either to the use of a standard fall risk assessment tool alongside nurses' clinical judgement or to nurses' clinical judgement alone. Standard care of all clusters will be optimised by structured education on best evidence strategies to prevent falls and fall related injuries. 54 nursing home clusters including 1,080 residents will be recruited. Residents must be ≥ 70 years, not bedridden, and living in the nursing home for more than three months. The primary endpoint is the number of participants with at least one fall at 12 months. Secondary outcome measures are the number of falls, clinical consequences including side effects of the two risk assessment strategies. Other measures are fall related injuries, hospital admissions and consultations with a physician, and costs

Fall prevention intervention technologies: A conceptual framework and survey of the state of the art

In recent years, an ever increasing range of technology-based applications have been developed with the goal of assisting in the delivery of more effective and efficient fall prevention interventions. Whilst there have been a number of studies that have surveyed technologies for a particular sub-domain of fall prevention, there is no existing research which surveys the full spectrum of falls prevention interventions and characterises the range of technologies that have augmented this landscape. This study presents a conceptual framework and survey of the state of the art of technology-based fall prevention systems which is derived from a systematic template analysis of studies presented in contemporary research literature. The framework proposes four broad categories of fall prevention intervention system: Pre-fall prevention; Post-fall prevention; Fall injury prevention; Cross-fall prevention. Other categories include, Application type, Technology deployment platform, Information sources, Deployment environment, User interface type, and Collaborative function. After presenting the conceptual framework, a detailed survey of the state of the art is presented as a function of the proposed framework. A number of research challenges emerge as a result of surveying the research literature, which include a need for: new systems that focus on overcoming extrinsic falls risk factors; systems that support the environmental risk assessment process; systems that enable patients and practitioners to develop more collaborative relationships and engage in shared decision making during falls risk assessment and prevention activities. In response to these challenges, recommendations and future research directions are proposed to overcome each respective challenge.The Royal Society, grant Ref: RG13082

Validity of the Falls Risk for Older People in the Community (FROP‑Com) tool to predict falls and fall injuries for older people presenting to the emergency department after falling

The aims of this study were to (1) externally validate the accuracy of the Falls Risk for Older People in the Community (FROP-Com) falls risk assessment tool in predicting falls and (2) undertake initial validation of the accuracy of the FROPCom to predict injurious falls (requiring medical attention) in people aged ≥ 60 years presenting to emergency departments (EDs) after falling. Two hundred and thirteen participants (mean age = 72.4 years; 59.2% women) were recruited (control group of a randomised controlled trial). A FROP-Com assessment was completed at a home visit within 2 weeks of ED discharge. Data on falls and injurious falls requiring medical attention were collected via monthly falls calendars for the next 12 months. Predictive accuracy was evaluated using sensitivity and specificity of a high-risk FROP-Com classification (score ≥ 19) in predicting a fall and injurious falls requiring medical attention. Fifty per cent of participants fell, with 60.4% of falls requiring medical attention. Thirty-two per cent were classified as high, 49% as moderate and 19% low falls risk. Low sensitivity was achieved for the FROP-Com high-risk classification for predicting falls (43.4%) and injurious falls (34.4%), although specificity was high (79.4% and 78.6%, respectively). Despite the FROP-Com’s low predictive accuracy, the high fall rate and high falls risk of the sample suggest that older people who fall, present to ED and are discharged home are at high risk of future falls. In high-falls-risk populations such as in this study, the FROP-Com is not a valid tool for classifying risk of falls or injurious falls. Its potential value may instead be in identifying risk factors for falling to direct tailoring of falls prevention interventions to reduce future falls