Impact of DNA-Encoded Chemical Library Technology on Drug Discovery

DNA-Encoded Chemical Libraries (DELs) have gained momentum over the recent years for the discovery of small-molecule ligands and the technology has been integrated in most of the larger pharmaceutical companies. With this perspective we would like to summarize the development of DEL technology and present some representative DEL-derived hits which may soon enter the pharmaceutical market

Being Different: A Study of Relational Demography and the Influence of Individual and Team Characteristics

This study examined the effects of gender and ethnic dissimilarity to team members on the individual level outcomes of team commitment, turnover intentions, and psychological empowerment. Results provided some support that dissimilarity to one's teammates has the most adverse effects for males and African Americans. In addition, there was some support that ethnic and gender identification and climate for ethnic diversity may be important moderators of this relationship. Specifically, individuals with low ethnic and gender identification felt more empowered when dissimilar to teammates, while individuals with high ethnic and gender identification had similar levels of empowerment regardless of their dissimilarity to teammates. Focusing on the team context, a positive climate for ethnic diversity reduced the negative consequences for individuals who often find themselves in the demographic minority, while, unexpectedly, a low climate for ethnic diversity seemed to heighten feelings of empowerment for individuals more dissimilar to their teammates

Power Conflict: Struggles for Intragroup Control and Dominance

There has been a considerable amount of research at the individual level of analysis examining strivings for power and influence within an organizational context. However, research has largely yet to examine how these individual motives and behaviors designed to garner power may translate to processes at the interpersonal and group level, and in particular, the extent to which they may result in conflicts or power struggles between individuals. Therefore, the goal of this dissertation was to delineate and explore a construct of power conflict using both qualitative and quantitative methods in two complementary studies. In the first study of this dissertation, I conducted an inductive, qualitative examination of power conflict designed to provide an in depth exploration of different types or manifestations of power conflict. Using data obtained from 58 semi-structured interviews with employees across 23 different bank branches, this study explored how conflicts over power are enacted within context, including key actions and motives. In addition, this study explored potential antecedents and consequences of power conflict in an effort to begin developing a nomological network. In Study 2, I then built upon these qualitative results by using survey data from 131 bank branches to empirically establish power conflict as an important fourth factor of intragroup conflict, along with the already established task, relationship, and process factors. In support of this, the confirmatory factor analysis results provide evidence that power conflict is a distinct factor of intragroup conflict and is distinct from the potentially related construct of dominating conflict management strategies. I also test a portion of the nomological network developed through the qualitative study by examining the relationship of power conflict to several group level antecedents and consequences. Regression results indicate that groups with higher mean levels of extraversion, lower mean levels of agreeableness, and that are predominantly female tend to have higher levels of power conflict. In contrast, groups that have high learning goal orientation climates tend to have lower levels of power conflict. In terms of consequences, power conflict was significantly related to branch stress and greater branch turnover above and beyond the other three conflict types

Design, Implementation, and Evaluation of a Pharmacist-Led Outpatient Benzodiazepine-Tapering Clinic

Background Benzodiazepines are commonly used among older adults, despite well-known risks. Clinical pharmacists can lead tapering efforts, leveraging their clinical expertise and relieving time-pressured primary care providers. Objectives The objective of this study is to describe the design, implementation, and evaluation of an outpatient pharmacist-led benzodiazepine-tapering clinic. Practice description The clinic is based within a community medical group associated with a large academic health system in Los Angeles, California. Practice innovation The clinic is staffed by clinical pharmacists and supervised by a psychiatrist. The initial visit consists of patient education, design of patient-driven tapering schedule, and medical history review. Follow-up phone/video visits are used to monitor withdrawal symptoms and provide support. Evaluation methods We used chart review to assess tapering status among those enrolled in the tapering clinic versus those who did not enroll. We compared outcomes across the 2 groups using bivariate statistics. Results From March 2017 to May 2019, 176 patients were referred to the clinic; 17 were deemed ineligible. Of the 159 patients contacted, 62 patients enrolled in the clinic; 97 patients did not enroll. Among patients in the clinic, 13 (27%) of patients were tapered down, 29 (60%) completely tapered off, 6 (13%) were unable to taper, and 14 (23%) were in the process of tapering. In contrast, among patients who did not enroll, 3 (4%) of patients were tapered down, 15 (20%) completely tapered off, 57 (76%) were unable to taper, and 22 (22%) were in the process of tapering. Ninety percent of patients had at least some benzodiazepine tapering when enrolled in the clinic compared to 41% among not enrolled in the clinic (P\u3c0.001). Conclusion A pharmacist-led benzodiazepine-tapering clinic can be an effective way to engage patients motivated to taper down. Lessons learned include the importance of ensuring referring providers adequately counsel patients prior to referral

An Integrated Oncology Data Warehouse for Clinical Decision Support and Complex Patient Cohort Identification in a Hybrid Cancer Center

BACKGROUND: A data warehouse is a repository that centralizes and integrates data from disparate systems to provide the ability to easily access historical, consistent data. Integration of disparate source systems into one centralized location can enable rapid identification of more robust research cohorts and enable data-driven decision making. The objective of the Miami Cancer Institute (MCI) Oncology Data Warehouse (ODW) is to collect and organize data from clinical records, research, and administrative systems to support information retrieval, business intelligence, and analytics for high-level decision making for oncology patients. The design, architecture, and implementation aligns with industry best practices which includes Data Governance, Enterprise Data Modeling, and Metadata Management. METHODS: We integrated structured and unstructured data from disparate sources into one centralized data model optimized for querying known as the ODW. The ODW is modeled as a star schema, with fact tables and conformed dimension tables, and expands to a galaxy schema with constellation facts and dimensions that can snowflake to other data models as needed. Each fact table represents a subject area (i.e. pathology), that is directly related to the conformed dimension tables using surrogate and foreign keys. Conformed dimensions represent the attributes associated to the subject area (i.e. date of encounter). The source data is extracted, transformed and loaded (ETL) automatically from different databases into a set of tables. The ETL code performs incremental loads at regular prescribed intervals into two parallel storage areas, a relational database management system (RDMS) as well as a Big Data file storage system. RESULTS: An interdisciplinary team of physicians, engineers, scientists, and subject matter experts at the Miami Cancer Institute of Baptist Health South Florida, has designed, developed, and implemented the ODW with information originating from different data sources which include: Electronic Medical Record (EMR) systems, Financial Systems, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Pathology synoptic reports and archives, and Next Generation Sequencing services. Structurally it is a subject-oriented, integrated collection of data leveraging conformed dimensions. The ODW is capable of connecting most business intelligence (i.e. Tableau) or statistical (i.e. SAS) tools for automated or static report development. CONCLUSION: The growing ODW enables physicians, clinical management teams, and medical analysts to systematically mine and review the molecular, genomic, and associated clinical or administrative information of patients, and identify patterns that may influence treatment decisions and potential outcomes. By implementing an innovative combination of technology tools and methods, we were able to organize enterprise information about oncology patients which can be utilized for clinical decision support and precision medicine use cases

Evolution Of A Higher Intracellular Oxidizing Environment In Caenorhabditis Elegans Under Relaxed Selection

We explored the relationship between relaxed selection, oxidative stress, and spontaneous mutation in a set of mutation-accumulation (MA) lines of the nematode Caenorhabditis elegans and in their common ancestor. We measured steady-state levels of free radicals and oxidatively damaged guanosine nucleosides in the somatic tissues of five MA lines for which nuclear genome base substitution and GC-TA transversion frequencies are known. The two markers of oxidative stress are highly correlated and are elevated in the MA lines relative to the ancestor; point estimates of the per-generation rate of mutational decay (DM) of these measures of oxidative stress are similar to those reported for fitness-related traits. Conversely, there is no significant relationship between either marker of oxidative stress and the per-generation frequencies of base substitution or GC-TA transversion. Although these results provide no direct evidence for a causative relationship between oxidative damage and base substitution mutations, to the extent that oxidative damage may be weakly mutagenic in the germline, the case for condition-dependent mutation is advanced

Shear wave elastography and parathyroid adenoma: A new tool for diagnosing parathyroid adenomas

AbstractObjectivesThis study prospectively determines the shear wave elastography characteristics of parathyroid adenomas using virtual touch imaging quantification, a non-invasive ultrasound based shear wave elastography method.MethodsThis prospective study examined 57 consecutive patients with biochemically proven primary hyperparathyroidism and solitary parathyroid adenoma identified by ultrasound and confirmed by at least one of the following: surgical resection, positive Technetium–99m Sestamibi Scintigraphy (MIBI) scan, or fine needle aspiration biopsy with positive PTH washout (performed only in MIBI negative patients). Vascularity and shear wave elastography were performed for all patients. Parathyroid adenoma stiffness was measured as shear wave velocity in meters per second.ResultsThe median (range) pre-surgical value for PTH and calcium were 58pg/mL (19, 427) and 10.8mg/dL (9.5, 12.1), respectively. 37 patients had positive MIBI scan. 20 patients had negative MIBI scan but diagnosis was confirmed with positive PTH washout. 42 patients underwent parathyroidectomy, and an adenoma was confirmed in all. The median (range) shear wave velocity for all parathyroid adenomas enrolled in this study was 2.02m/s (1.53, 2.50). The median (range) shear wave velocity for thyroid tissue was 2.77m/s (1.89, 3.70). The shear wave velocity of the adenomas was independent of adenoma size, serum parathyroid hormone concentration, or plasma parathyroid hormone concentration.ConclusionsTissue elasticity of parathyroid adenoma is significantly lower than thyroid tissue. B-mode features and distinct vascularity pattern are helpful tools in diagnosing parathyroid adenoma with ultrasound. Shear wave elastography may provide valuable information in diagnosing parathyroid adenoma

The Purr of the Lionfish: Sound and Behavioral Context of Wild Lionfish in the Greater Caribbean

Passive acoustic technology has become a useful and cost-effective method to collect data with very high temporal resolution that can be used to detect the presence, distribution, and remotely monitor soniferous marine biodiversity. In order to maximize the potential of bioacoustic and soundscape research in the oceans, understanding the association between the different realms of sound sources, species-specific calls and behavioral context of sound production are fundamental. A previously unknown vocalization was associated with a behavioral display of lionfish (Pterois spp.) by recordings with synchronous audio and video at deep coral reefs in both Puerto Rico and the Florida Keys. Calls of variable length in bouts of intermittent calls were heard along displays between pairs of lionfish. Calls had a mean frequency of 251 Hz and very low mean SPL (72-67 dB re 1μPa). This sound may be classified as courtship related as it was observed between two lionfish that appeared of dissimilar size (presumably male and female), engaged in following and circling displays. The sound occurred in the afternoons near sunset at both sites. This is the first reported sound produced by lionfish in association with a behavioral display in the wild. Low sound pressure levels suggest this is a quiet signal for communication between individuals in close proximity. With this description the presence of lionfish in areas deeper than normal diving limits or during inaccessible times, e.g., during the evening, could be pursued

Experiences managing behavioral symptoms among Latino caregivers of Latino older adults with dementia and memory problems: a qualitative study

BackgroundLatinos are more likely than non-Latino Whites to develop dementia and be prescribed antipsychotics for dementia-related behavioral symptoms. Antipsychotics have significant risks yet are often overprescribed. Our understanding of how Latino caregivers of Latino older adults living with dementia perceive and address behavioral issues is limited, impeding our ability to address the root causes of antipsychotic overprescribing.MethodsWe interviewed Latino older adults' caregivers and community-based organization workers serving older adults with cognitive impairment (key informants), focusing on the management of behavioral symptoms and experiences with health services.ResultsWe interviewed 8 caregivers and 2 key informants. Caregivers were the spouses, children, or grandchildren of the older adult living with cognitive impairment; their ages ranged from 30 to 95. We identified three categories of how caregivers learned about, managed, and coped with behavioral symptoms: caregivers often faced shortcomings with dementia care in the medical system, receiving limited guidance and support; caregivers found community organizations and senior day centers to be lifelines, as they received relevant, timely advice and support, caregivers often devised their own creative strategies to manage behavioral symptoms.ConclusionIn-depth interviews suggest that the healthcare system is failing to provide support for behavioral symptoms from dementia; caregivers of Latino older adults rely on community organizations instead

A Code of Conduct for Marine Carbon Dioxide Removal Research

Given the clear need to inform societal decision-making on the role marine Carbon Dioxide Removal (mCDR) can play in solving the climate crisis, it is imperative that researchers begin to answer questions about its effectiveness and impacts. Yet overly hasty deployment of new ocean-based climate interventions risks harm to communities and ecosystems and could jeopardize public perception of the field as a whole. In addition, the harms, risks and benefits of mCDR efforts are unlikely to be evenly distributed. Unabated, climate change could have a devastating impact on global ecosystems and human populations, and the impacts of mCDR should be contemplated in this context. This Code of Conduct exclusively applies to mCDR research and does not attempt to put any affiliated risk in the context of the risk of delaying climate action. Its purpose is to ensure that the impacts of mCDR research activities themselves are adequately understood and accounted for as they progress. It provides a roadmap of processes, procedures, and activities that project leads should follow to ensure that decisions regarding whether, when, where, and how to conduct mCDR research are informed by relevant ethical, scientific, economic, environmental, and regulatory considerations