Immunotherapy in hepatocellular carcinoma: the complex interface between inflammation, fibrosis, and the immune response.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and confers a poor prognosis. Beyond standard systemic therapy with multikinase inhibitors, recent studies demonstrate the potential for robust and durable responses from immune checkpoint inhibition in subsets of HCC patients across disease etiologies. The majority of HCC arises in the context of chronic inflammation and from within a fibrotic liver, with many cases associated with hepatitis virus infections, toxins, and fatty liver disease. Many patients also have concomitant cirrhosis which is associated with both local and systemic immune deficiency. Furthermore, the liver is an immunologic organ in itself, which may enhance or suppress the immune response to cancer arising within it. Here, we explore the immunobiology of the liver from its native state to chronic inflammation, fibrosis, cirrhosis and then to cancer, and summarize how this unique microenvironment may affect the response to immunotherapy

Erlotinib in the treatment of advanced pancreatic cancer

Single agent gemcitabine has been the mainstay of therapy for advanced pancreatic cancer over the past decade. Multiple trials of newer chemotherapeutic agents both alone and in combination have yielded disappointing results, spurring the ongoing search for new agents and combinations in this aggressive malignancy. Inhibitors of the epidermal growth factor receptor (EGFR) have shown promising activity in multiple solid tumors types, and preclinical data support a role for EGFR inhibition in pancreatic cancer. A recent phase III study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) demonstrated a significant survival benefit with the addition of the EGFR tyrosine kinase inhibitor, erlotinib, to gemcitabine chemotherapy for the first-line treatment of patients with advanced pancreatic cancer, becoming the first phase III study to demonstrate a survival benefit of combination therapy as well as targeted therapy in this disease. This article reviews the evidence supporting EGFR inhibition and the use of erlotinib in advanced pancreatic cancer as well as future implications of targeted therapy in this challenging malignancy

Integrating Students into Interdisciplinary Health and Health Disparities Research Teams

Major initiatives by the U.S. Department of Health and Human Services as well as the World Health Organization have produced a large and compelling body of evidence on how to reduce health disparities, which entails having a clear understanding of how social factors shape health and healthcare outcomes. Specifically, there is a need for healthcare professionals to understand social determinants of health (e.g., low socioeconomic status, lack of health insurance, and poor education) and how these lead to disparities in health for people of minority racial and ethnic groups. Little is known about how students are developed as health disparities researchers or how their research experiences impact their views about addressing social determinants of health as a career goal. The purpose of this paper is to describe how health and human sciences students were integrated into three minority HIV prevention and testing projects using the lifelong learning for health professionals (LLHP) principles and activities framework, which entails a focus on: (a) education, (b) community, and (c) organization in the planning, development, implementation, and evaluation of interdisciplinary research

Exploring Child Welfare Workers\u27 Attitudes and Practice With Fathers

This cross-sectional study explored child welfare agency workers\u27 attitudes and practice regarding working with fathers whose children are at-risk for abuse and neglect. Agency workers completed a questionnaire about their attitudes towards working with fathers, their knowledge of barriers to fathers\u27 engagement, and their experiences with their own fathers. They also completed open-ended items about services and supports they felt would be most helpful to fathers. A content analysis of the data revealed critical themes for four areas that workers felt could be enhanced to effectively engage fathers: (a) use diligent efforts that ensure fathers are present to contribute, (b) provide equitable services, supports, and policies for fathers, (c) address father-specific needs, and (d) promote a positive worker-father relationship. The findings provide insight into ways that social workers can maximize fathers\u27 strengths and reduce their challenges

Discrepant Alcohol Use, Intimate Partner Violence, and Relationship Adjustment Among Lesbian Women and Their Same-Sex Intimate Partners

This study examined the association between relationship adjustment and discrepant alcohol use among lesbian women and their same-sex intimate partners after controlling for verbal and physical aggression. Lesbian women (N = 819) who were members of online marketing research panels completed an online survey in which they reported both their own and same-sex intimate partner\u27s alcohol use, their relationship adjustment, and their own and their partner\u27s physical aggression and psychological aggression (i.e., verbal aggression and dominance/isolation). Partners\u27 alcohol use was moderately correlated. Discrepancy in alcohol use was associated with poorer relationship adjustment after controlling for psychological aggression and physical aggression. Results are discussed in terms of the similarity and differences with previous literature primarily focused on heterosexual couples

Nematode Spatial and Ecological Patterns from Tropical and Temperate Rainforests

Large scale diversity patterns are well established for terrestrial macrobiota (e.g. plants and vertebrates), but not for microscopic organisms (e.g. nematodes). Due to small size, high abundance, and extensive dispersal, microbiota are assumed to exhibit cosmopolitan distributions with no biogeographical patterns. This assumption has been extrapolated from local spatial scale studies of a few taxonomic groups utilizing morphological approaches. Recent molecularly-based studies, however, suggest something quite opposite. Nematodes are the most abundant metazoans on earth, but their diversity patterns are largely unknown. We conducted a survey of nematode diversity within three vertical strata (soil, litter, and canopy) of rainforests at two contrasting latitudes in the North American meridian (temperate: the Olympic National Forest, WA, U.S.A and tropical: La Selva Biological Station, Costa Rica) using standardized sampling designs and sample processing protocols. To describe nematode diversity, we applied an ecometagenetic approach using 454 pyrosequencing. We observed that: 1) nematode communities were unique without even a single common species between the two rainforests, 2) nematode communities were unique among habitats in both rainforests, 3) total species richness was 300% more in the tropical than in the temperate rainforest, 4) 80% of the species in the temperate rainforest resided in the soil, whereas only 20% in the tropics, 5) more than 90% of identified species were novel. Overall, our data provided no support for cosmopolitanism at both local (habitats) and large (rainforests) spatial scales. In addition, our data indicated that biogeographical patterns typical of macrobiota also exist for microbiota

Nematode Spatial and Ecological Patterns from Tropical and Temperate Rainforests

Large scale diversity patterns are well established for terrestrial macrobiota (e.g. plants and vertebrates), but not for microscopic organisms (e.g. nematodes). Due to small size, high abundance, and extensive dispersal, microbiota are assumed to exhibit cosmopolitan distributions with no biogeographical patterns. This assumption has been extrapolated from local spatial scale studies of a few taxonomic groups utilizing morphological approaches. Recent molecularly-based studies, however, suggest something quite opposite. Nematodes are the most abundant metazoans on earth, but their diversity patterns are largely unknown. We conducted a survey of nematode diversity within three vertical strata (soil, litter, and canopy) of rainforests at two contrasting latitudes in the North American meridian (temperate: the Olympic National Forest, WA, U.S.A and tropical: La Selva Biological Station, Costa Rica) using standardized sampling designs and sample processing protocols. To describe nematode diversity, we applied an ecometagenetic approach using 454 pyrosequencing. We observed that: 1) nematode communities were unique without even a single common species between the two rainforests, 2) nematode communities were unique among habitats in both rainforests, 3) total species richness was 300% more in the tropical than in the temperate rainforest, 4) 80% of the species in the temperate rainforest resided in the soil, whereas only 20% in the tropics, 5) more than 90% of identified species were novel. Overall, our data provided no support for cosmopolitanism at both local (habitats) and large (rainforests) spatial scales. In addition, our data indicated that biogeographical patterns typical of macrobiota also exist for microbiota

Inseguro: Policiamento sob o capitalismo racial

This paper outlines the nature of policing under racial capitalism in the USA and makes a case for the abolition of the police. It reviews the history of the police in the country, focusing particularly on racist ideas and practices against African Americans. It includes analysis of recent cases of police murders of black people and discusses the diverse movements for racial justice, including Black Lives Matter. It relies on an ample base of historical and contemporary evidence and widely utilizes both the academic literature in history, sociology and political science and journalistic sources. Tradução inédita em português do artigo originalmente publicado em Spectre: A Marxist Journal em 2020.Traduzido por Sean PurdyEste artigo descreve a natureza do policiamento sob o capitalismo racial nos EUA e defende a abolição da polícia. Ele faz um levantamento da história da polícia no país, concentrando-se principalmente nas ideias e práticas racistas contra os afro-americanos. Inclui a análise de casos recentes de assassinatos de negros pela polícia e discute os diversos movimentos por justiça racial, incluindo Black Lives Matter. A análise se baseia em uma ampla base de evidências históricas e contemporâneas e utiliza a literatura acadêmica em história, sociologia e ciência política, bem como fontes jornalísticas

Wiki Justice, Social Ergonomics, and Ethical Collaborations

In this essay we explore various theoretical, pedagogical, and historical aspects of wikis focusing on three questions as points of departure—"What is a wiki?"; "How do you teach with a wiki?" and finally "What is the point of a wiki?

Bigger Than You Think: The Economic Impact of Microbusinesses in the U.S.

AEO embarked on a two-year study to build the data and the evidence base that documents the economic impact of microbusiness in the U.S. The evidence gathered paints a compelling portrait of a remarkably vigorous microbusiness community that plays an essential role in American economic productivity