Calling Foul: Deficiencies in Approaches to Environmental Whistleblowers and Suggested Reforms

Whistleblowers could facilitate the regulation of the environmental sector at little to no cost to the taxpayer. Often, potential whistleblowers have timely access to information that would enable them to avert or minimize environmental damage and to protect our communities. However, existing federal and state regulations fail to adequately protect environmental whistleblowers and to incentivize potential environmental whistleblowers. These failures unjustly penalize whistleblowers and discourage potential whistleblowers. This article uses research findings and a case study to illuminate these failings and to argue for reforms that would better protect and incentivize whistleblower

Atividades de pesquisa em produção e nutrição de peixes de corte e ornamental

TCC (graduação) - Universidade Federal de Santa Catarina. Centro de Ciências Agrárias. Curso de Agronomia.O estágio de conclusão de curso foi realizado no Setor de Piscicultura do Departamento de Biologia Animal (DBA), da Universidade Federal de Viçosa (UFV), em Viçosa-MG, com duração de 390 horas. No referido setor foram desenvolvidas atividades de ensino pesquisa e extensão, usufruindo de uma estrutura com três laboratórios de nutrição de peixes e também dos laboratórios: de digestibilidade e reprodução induzida de peixes, de biometria de peixes e análise de água, de fisiologia e nutrição de peixes e o laboratório de processamento e armazenamento de rações. Dentre as atividades realizadas, a montagem e adequação do Laboratório de Nutrição de Peixes 3 foi de grande valia, pois pude participar dos processos de tomada de decisão, desde a aquisição do material até a instalação dos aquários, sistemas de aeração, aquecimento e ajustes finais. Participar dos manejos de rotina como banho de sal nos peixes após a coleta nos tanques, arraçoamento diário, controle dos parâmetros de qualidade da água e do manejo reprodutivo das espécies cultivadas no setor de piscicultura, serviu para reforçar a importância de serem realizadas boas práticas de manejo produtivo. Dos experimentos acompanhados, no de determinação dos níveis de proteína bruta e energia bruta para juvenis de pacamã (Lophiosilurus alexandri), pude auxiliar na recepção dos animais, biometria e distribuição dos peixes nos aquários, dentro do delineamento experimental. No experimento de transporte de juvenis de carpa ornamental (KOI) Cyprinus carpio, sobre o efeito do óleo de hortelã e do tempo de jejum, pude auxiliar nas análises de estresse oxidativo. Durante o estágio foram também cursadas as disciplinas de Ictiologia, Limnologia e Piscicultura e de Manejo e Administração em Piscicultura. O objetivo deste relatório foi acompanhar e auxiliar as diferentes etapas de desenvolvimento de experimentos de produção e nutrição de peixes, assim como das atividades rotineiras do Setor de Piscicultura

The Experiences of Occupational Therapists in Natural Disasters: A Qualitative Study

OBJECTIVE. This study explored the experiences of occupational therapists who have lived through a natural disaster within the last five years. METHOD. Researchers conducted a literature review and developed a semi-structured interview using the Person Environment Occupation Performance (PEOP) model as a guide. Six occupational therapists (1 male and 5 females) were selected using convenience and purposive snowball sampling. Each participant was interviewed one time. Interviews were recorded, transcribed verbatim, and data was analyzed using an open coding system. FINDINGS. Following the data analysis process, four categories were identifies. These categories included personal experience, environmental influence, social experience, and professional experience. Two final assertions emerged from the data. The first assertion is that the floods affected the occupational aspects of the participants’ lives personally, environmentally, socially, and professionally. The second assertion is that the participants’ identities as occupational therapists influenced the way in which they responded to the disruptions in their lives. Natural disasters impact all aspects of individuals’ lives. Occupational therapists have the skills and knowledge base to assist individuals in recovering from natural disasters. Additional research is needed to further develop and support the role of occupational therapy in natural disaster relief

A Survey of Psychologists’ Attitudes Towards and Utilization of Exposure Therapy for PTSD

Although research supports the efficacy of exposure therapy for PTSD, some evidence suggests that exposure is under-utilized in general clinical practice. The purpose of this study was to assess licensed psychologists’ use of imaginal exposure for PTSD and to investigate perceived barriers to its implementation. A total of 852 psychologists from 3 states were randomly selected and surveyed. An additional 50 members of a trauma special interest group of a national behavior therapy organization were also surveyed. The main survey results indicate that a large majority of licensed doctoral level psychologists do not report use of exposure therapy to treat patients with PTSD. Although approximately half of the main study sample reported that they were at least somewhat familiar with exposure for PTSD, only a small minority used it to treat PTSD in their clinical practice. Even among psychologists with strong interest and training in behavioral treatment for PTSD, exposure therapy is not completely accepted or widely used. Clinicians also appear to perceive a significant number of barriers to implementing exposure

T cell homing in inflammatory bowel diseases and single cell exposure-efficacy characteristics of the anti-α4β7 antibody vedolizumab

Inflammatory bowel diseases (IBDs) describe multifactorial, chronically relapsing inflammatory disorders of the gastrointestinal tract, the two major entities being ulcerative colitis (UC) and Crohn’s disease (CD). Although the incidence and prevalence of these diseases are increasing worldwide, their aetiology is still poorly understood, and no medical cure is available. One key element of IBD pathogenesis is a profound dysregulation of the intestinal immune system, including unchecked infiltration of immune cells, especially T cells, into the intestine. Such infiltration requires T cell gut homing, a multistep process, which is controlled by a variety of molecules, including selectins, integrins and chemokines and offers a plethora of potential targets for therapeutic interventions. Therefore, several approved and candidate therapeutic agents have emerged over the last decade that interfere with this process and aim to reduce inflammation by blocking cell infiltration into the tissue. Yet, insights into the precise mechanisms of these agents are still sorely lacking. Therefore, three aims were formulated in this thesis, under the overall goal to better characterise the mode of action of anti-trafficking agents, with a particular emphasis on the anti-α4β7 integrin antibody vedolizumab: 1) to acquire a thourough overview of the efficacy and mode of action of current and potential future anti-trafficking therapies, 2) to develop a new technique to assess the effect of anti-adhesion molecules on the dynamic cell adhesion of different immune cell subsets under flow conditions and 3) to characterise the dose-dependent effect of vedolizumab on regulatory and effector T cells. In the first part of this thesis, we performed a thorough literature research on current and future anti-trafficking agents, thereby focusing on the different target molecules involved in T cell homing. By comparing the efficacy of these agents in pre-clinical animal trials with phase II and phase III clinical trials, we identified discrepancies between different experimental setups. Furthermore, we uncovered differences in effectiveness and safety dependent on administration route, gut selectivity or regarding specific subgroups of patients. This work provides and extensive overview of the mode of action of anti-trafficking agents and underlines some important aspects that need to be taken into consideration for future translational research. Although tremendous efforts have been made in the development of anti-trafficking agents, mechanistic insights are still sparse. Therefore, in the second part of this thesis, we developed a new technique to qualitatively and quantitatively analyse the effect of such agents on the dynamic adhesion of immune cells under flow conditions. By coating ultrathin capillaries with different cell adhesion molecules (CAMs) expressed on endothelial cells and perfusing cells using a peristaltic pump, we were able to mimic the situation in blood vessels in a controlled, easy-to-modify setting. The number of cells specifically adhering to different CAMs was visualised using fluorescent microscopy. Pre-treatment of the cells with anti-integrin antibodies or chemokines reduced and enhanced the cell adhesion, respectively. Our method provides a useful tool for the detailed analysis of molecules interfering with cell adhesion and can be applied to gain mechanistic insights into the mode of action of anti-trafficking agents. One of these agents is the anti-α4β7 integrin antibody vedolizumab. Since its approval in 2014, this drug is broadly used for the treatment of IBDs. However, for unknown reasons, less than half of the patients treated with vedolizumab respond to therapy. As two independent dose-ranging phase II trials demonstrated a non-linear exposure-efficacy correlation, we hypothesised that vedolizumab may have an optimal therapeutic range. Hence, in the third part of this thesis, we characterised the dose-dependent effect of vedolizumab. Using flow cytometry, we quantified the binding of vedolizumab to regulatory (TReg) and effector (TEff) CD4+ T cells at different concentrations and identified a preferential binding to TEff cells at medium concentrations. This preferential binding resulted in stronger impairment of dynamic adhesion and transmigration of TEff cells in vitro as well as in reduced homing of TEff cells in an in vivo homing mouse model compared to TReg cells. Further, a preferential binding to TEff compared to TReg cells at medium vedolizumab serum concentrations was validated in a real-world patient cohort. To better understand this differential binding, we performed a single cell RNA sequencing of cells binding or not binding vedolizumab. Thereby, we identified a TReg subset expressing high levels of integrin β1 and peptidase inhibitor 16 (PI16) resistant to vedolizumab and could confirm these findings by flow cytometry. We observed a highly regulatory potential of these cells, which was present both in the peripheral blood and intestinal tissue samples. Additionally, we could demonstrate the accumulation of CD4+Foxp3+ and Foxp3+β1+ cells in gut biopsies from patients under vedolizumab treatment. Lastly, we re-analysed data from two large phase III trials for the use of vedolizumab in CD. We were able to demonstrate that the serum levels associated with the highest remission rates were similar to the serum levels of patients with the highest TReg/TEff cell ratio identified in our own cohort. Taken together, this work summarises and interprets the current data on anti-trafficking agents, presents a useful tool for the qualitative and quantitative analysis of dynamic cell adhesion and the analysis of anti-adhesion molecules and is the first to provide an explanation for the non-linear exposure-efficacy correlation of vedolizumab, which has important translational implications for future clinical therapy.Chronisch entzündliche Darmerkrankungen (CED) bezeichnen eine Gruppe von multifaktoriellen, chronisch rezidivierenden entzündlichen Erkrankungen des Magen-Darm-Trakts. Die wichtigsten Entitäten sind hierbei Colitis ulcerosa (CU) und Morbus Crohn (MC) Obwohl die Inzidenz und Prävalenz dieser Krankheiten weltweit zunehmen, ist ihre Ätiologie noch immer schlecht verstanden, und es ist keine Heilung bekannt. Ein Hauptmerkmal der Pathogenese von CED ist die Dysregulation des intestinalen Immunsystems mit einer unkontrollierten Infiltration von Immunzellen, insbesondere T-Zellen, in den Darm. Dieser Infiltration liegt das Darm-Homing von T-Zellen zugrunde, einen mehrstufigen Prozess, der durch eine Vielzahl von Molekülen, darunter Selektine, Integrine und Chemokine, gesteuert wird. Dieser bietet eine Fülle von potenziellen Angriffspunkten für die Entwicklung neuer Therapeutika. Im letzten Jahrzehnt wurden mehrere Medikamente entwickelt, die in diesen Prozess eingreifen und durch die Blockade der Zellinfiltration in das Gewebe die Entzündung verringern. Allerdings fehlen mechanistische Erkenntnisse über diese Wirkstoffe. Daher wurden in dieser Arbeit drei Ziele formuliert, um die Wirkungsweise von Medikamenten besser zu charakterisieren, die die Zelleinwanderung in den Darm beeinflussen. Hierbei wurde ein besonderer Schwerpunkt auf den anti-α4β7-Integrin-Antikörper Vedolizumab gelegt: 1) Einen vollständigen Überblick über die Wirksamkeit und Wirkungsweise aktueller und zukünftiger Anti-Trafficking-Therapien zu gewinnen, 2) Eine neue Technik zu entwickeln, um die Wirkung von Anti-Adhäsionsmolekülen auf die dynamische Zelladhäsion unter Strömungsbedingungen zu beurteilen und 3) Die dosisabhängige Wirkung von Vedolizumab auf regulatorische und Effektor-T-Zellen zu charakterisieren. Im ersten Teil dieser Arbeit wurde eine gründliche Literaturrecherche zu aktuellen und zukünftigen Anti-Einwanderungs-Wirkstoffen durchgeführt, mit Fokus auf die verschiedenen Zielmoleküle, die am Homing von T-Zellen beteiligt sind. Durch den Vergleich der Wirksamkeit dieser Wirkstoffe in präklinischen Tierversuchen mit klinischen Studien der Phasen II und III konnten wir Diskrepanzen zwischen verschiedenen Versuchsanordnungen feststellen. Darüber hinaus entdeckten wir Unterschiede in der Wirksamkeit und Sicherheit in Abhängigkeit von der Art der Verabreichung und der Darmselektivität dieser Therapeutika oder abhängig von bestimmten Untergruppen von Patienten. Diese Arbeit bietet einen umfassenden Überblick über die Wirkungsweise von Agenzien, die das Einwandern von Zellen beeinflussen und unterstreicht einige wichtige Aspekte, die bei der künftigen translationalen Forschung berücksichtigt werden müssen. Obwohl enorme Anstrengungen bei der Entwicklung von Therapeutika gegen Zelleinwanderung unternommen wurden, sind die mechanistischen Erkenntnisse immer noch spärlich. Daher haben wir im zweiten Teil dieser Arbeit eine neue Technik entwickelt, mit der wir die Wirkung solcher Mittel auf die dynamische Adhäsion von Immunzellen unter Strömungsbedingungen qualitativ und quantitativ analysieren können. Durch die Beschichtung ultradünner Kapillaren mit verschiedenen Zelladhäsionsmolekülen (englisch: cell adhesion molecules (CAMs)), die auf Endothelzellen exprimiert werden, und durch die Perfusion von Zellen mit einer Peristaltikpumpe, konnten wir die Situation in Blutgefäßen in einer kontrollierten, leicht modifizierbaren Umgebung nachahmen. Die Anzahl der Zellen, die spezifisch an verschiedenen CAMs haften, wurde mit Hilfe von Fluoreszenzmikroskopie visualisiert. Die Behandlung der Zellen mit Anti-Integrin-Antikörpern oder Chemokinen verringerte bzw. verstärkte die Zelladhäsion. Unsere Methode stellt ein nützliches Instrument für die detaillierte Analyse von Molekülen dar, die die Zelladhäsion beeinträchtigen. Sie kann in Zukunft angewandt werden, um dringend benötigte mechanistische Einblicke in die Wirkungsweise von Therapeutika gegen Zelleinwanderung zu gewinnen. Einer dieser Wirkstoffe ist der anti-α4β7-Integrin-Antikörper Vedolizumab. Seit seiner Zulassung im Jahr 2014 wird dieses Medikament auf breiter Basis für die Behandlung von CED eingesetzt. Allerdings sprechen, aus bisher unbekannten Gründen, weniger als die Hälfte der mit Vedolizumab behandelten Patienten auf die Therapie an. Zwei unabhängige Phase-II-Studien demonstrierten eine nicht lineare Korrelation zwischen Exposition und Wirksamkeit, weswegen wir die Hypothese aufstellten, dass Vedolizumab möglicherweise eine optimale therapeutische Bandbreite aufweist. Daher wurde im dritten Teil dieser Arbeit die dosisabhängige Wirkung von Vedolizumab charakterisiert. Mit Hilfe von Durchflusszytometrie quantifizierten wir die Bindung von Vedolizumab an regulatorische (TReg) und Effektor (TEff) CD4+ T-Zellen bei unterschiedlichen Konzentrationen und stellten eine bevorzugte Bindung an TEff-Zellen bei mittleren Konzentrationen fest. Diese bevorzugte Bindung führte zu einer stärkeren Beeinträchtigung der dynamischen Adhäsion und Transmigration von TEff-Zellen in vitro, sowie zu einem verminderten Homing von TEff-Zellen in einem in vivo Mausmodell im Vergleich zu TReg-Zellen. Darüber hinaus wurde eine bevorzugte Bindung an TEff-Zellen im Vergleich zu TReg-Zellen bei mittleren Vedolizumab-Serumkonzentrationen in einer mit dem Medikament behandelten Patientenkohorte validiert. Um diese unterschiedliche Bindungspräferenz besser zu verstehen, führten wir eine Einzelzell-RNA-Sequenzierung von Zellen durch, die Vedolizumab binden oder nicht binden. Dabei konnten wir eine Untergruppe von TReg-Zellen identifizieren, die hohe Mengen an Integrin β1 und Peptidase-Inhibitor 16 (PI16) exprimiert und bei der verwendeten Konzentration resistent gegen Vedolizumab ist. Diese Befunde konnten wir durchflusszytometrisch bestätigen. Wir beobachteten eine höchst regulatorische Funktion dieser Zellen und fanden, dass sie sowohl im peripheren Blut als auch in Darmgewebeproben vorhanden waren. Des Weiteren konnten wir eine Akkumulation von CD4+Foxp3+ und Foxp3+β1+ Zellen in Darmbiopsien von Patienten nach der Behandlung mit Vedolizumab nachweisen. Schließlich analysierten wir die Daten aus zwei großen Phase-III-Studien zur Anwendung von Vedolizumab bei MC neu. Dabei konnten wir zeigen, dass die Serumspiegel, die mit den höchsten Remissionsraten assoziiert waren, den Serumspiegeln der Patienten mit dem höchsten TReg/TEff-Zell-Verhältnis in unserer eigenen Kohorte glichen. Insgesamt fasst diese Arbeit die aktuellen Daten zu Wirkstoffen gegen die Zelleinwanderung zusammen und interpretiert diese, präsentiert eine neue Technik zur qualitativen und quantitativen Analyse der dynamischen Zelladhäsion und zur Untersuchung von Anti-Adhäsionsmoleküle und liefert erstmals eine Erklärung für die nichtlineare Korrelation zwischen Exposition und Wirksamkeit von Vedolizumab, welche weitreichende Folgen für zukünftige translationale und klinische Therapien haben könnte

Mt. Carmel, PA Community Welcome Packet

The Mt. Carmel, PA Community Welcome Packet is an 18 page document prepared by four students for the Bucknell University undergraduate course Geography 218, taught by Vanessa Massaro. The document includes an index of local services, a section of four possible programs for the community to initiate, and a source section with references to successful programs

Bioactivities of Synthesized Curcumin, Curcuminoids, and Their Metal Complexes

Curcumin is a compound, derived from the Curcuma longa plant, which has shown anticancer activity and relatively low toxicity in humans. It has been a subject of significant interest in recent years as an adjuvant chemotherapy agent. Literature data for curcumin and related curcuminoids have shown discrepancies in the irreported bioactivities, and this has spurred disputes in the scientific community about their purported benefits. A possible explanation for these inconsistencies is variability between curcumin sources in purity and content. A systematic study has been conducted on the biological properties of curcumin from various sources, both naturally sourced and synthesized using neat and solvent-based methods. Bioactivities tested included antioxidative capacity and cell growth inhibition. This study has also been expanded to include curcuminoids containing varied electronic and structural features, and biological properties were also evaluated after coordination to a metal

Hotline Number to Reach and Offer Agricultural Information to Plain Anabaptists during the COVID-19 Workplace Closures

The Penn State Extension Animal Systems Team developed a toll-free hotline phone number to convey short educational messages to maintain contact and outreach to Pennsylvania’s animal producing Amish, Mennonite, and other plain Anabaptist populations. During the COVID-19 pandemic, Penn State Extension’s programming went largely online via webinars, online courses, and emails. This change in programming excluded a large sector of Pennsylvania farmers who do not use or have access to the internet and, as such, were liable to miss important best management practice reviews and timely updates in animal agriculture. The Animal Systems Hotline offered callers the choice to listen to pre-recorded messages from dairy, equine, livestock, and poultry Extensions. Across the Animal Systems Team, during a span of approximately 22 weeks, a total of 111 messages were uploaded to the Hotline, with a total of 2,201 people calling in to the Hotline. Topics varied across the Extensions from the basics of animal husbandry and health to pasture and nutrition management. Since the development of the Hotline, Extension educators have received calls from plain producers requesting more information about the topics covered on the Hotline messages. While there were challenges with the system used for the Hotline and data collection, the broad reach and numerous callers indicates that the Hotline was a successful method of connecting with plain audiences. [Abstract by authors.