24 research outputs found

    States and the political economy of unfree labour

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    A growing body of academic and policy research seeks to understand and address the problem of contemporary unfree labour. In this article, we argue that this literature could be strengthened by a stronger conceptualization of, and more systematic attention towards, the role of national states. In particular, we argue that there is a need to move beyond simplistic conceptualisations of states as simple agents of regulation and criminal justice enforcement who respond to the problem of unfree labour, and to recognize the causal and multifaceted role that national states play in creating the conditions in which unfree labour can flourish. We propose a framework to understand and compare the ways in which national states shape the political economy of unfree labour. Focusing on the United States, we outline three arenas of governance in which national states have been particularly central to enabling the conditions for unfree labour: the regulation of labour mobility, labour market regulation, and business regulation. We conclude by reflecting on the comparative political economy research that will be required to understand the role of different states in shaping the conditions in which unfree labour thrives or is eliminated

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    Immunodeficiency-Related Lymphoid Proliferations: New Insights With Relevance to Practice

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    © 2020, Springer Science+Business Media, LLC, part of Springer Nature. Purpose of Review: Our understanding of risk factors and mechanisms underlying immunosuppression-related lymphoproliferative disorders continues to evolve. An increasing number of patients are living with altered immune status due to HIV, solid organ or hematopoietic stem cell transplant, treatment of autoimmune disease, or advanced age. This review covers advances in understanding, emerging trends, and revisions to diagnostic guidelines. Recent Findings: The tumor microenvironment, including interactions between the host immune system and tumor cells, is of increasing interest in the setting of immunosuppression. While some forms of lymphoproliferative disease are associated with unique risk factors, common mechanisms are also emerging. Indolent forms, such as Epstein-Barr virus positive mucocutaneous ulcer, are important to recognize. As methods to modulate the immune system evolve, more data are needed to understand and minimize lymphoproliferative disease risk. Summary: A better understanding of individual risk factors and common mechanisms underlying immunosuppression-related lymphoproliferations will ultimately enable improved prevention and treatment of these disorders

    Biallelic TET2 mutations and canonical ASXL1 mutations are frequent and cooccur in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): An institutional experience and review of literature

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    Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is recurrently mutated in epigenetic pathway genes. We studied the myeloid‐related genetic mutations in a cohort of five patients with BPDCN and one paired relapse case at our institution and identified a high frequency of biallelic TET2 and canonical ASXL1 (c.1934dupG) mutations. The number of cases is small, but the variant allele fraction (VAF) sums of the TET2 mutations, as well as the persistence of TET2 mutations in a case of relapsed BPDCN, suggest an ancestral/founder nature of TET2 clones in the cases. Further literature review shows a high frequency of biallelic TET2 mutations in reported cases of BPDCN

    Metastatic Extrapulmonary Small Cell Carcinoma to the Cerebellopontine Angle: A Case Report and Review of the Literature

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    Extrapulmonary small cell carcinomas (EPSCC) are rare malignancies with poor patient prognoses. We present the case of a 63-year-old male who underwent surgical resection of a poorly differentiated small cell carcinoma, likely from a small intestinal primary tumor that metastasized to the cerebellopontine angle (CPA). A 63-year-old male presented with mild left facial paralysis, hearing loss, and balance instability. MRI revealed a 15 mm mass in the left CPA involving the internal auditory canal consistent with a vestibular schwannoma. Preoperative MRI eight weeks later demonstrated marked enlargement to 35 mm. The patient underwent a suboccipital craniectomy and the mass was grossly different visually and in consistency from a standard vestibular schwannoma. The final pathology revealed a poorly differentiated small cell carcinoma. Postoperative PET scan identified avid uptake in the small intestine suggestive of either a small intestinal primary tumor or additional metastatic disease. The patient underwent whole brain radiation therapy and chemotherapy and at last follow-up demonstrated improvement in his symptoms. Surgical resection and radiotherapy are potential treatment options to improve survival in patients diagnosed with NET brain metastases. We present the first documented case of skull base metastasis of a poorly differentiated small cell carcinoma involving the CPA

    Impact of Low-Level Viremia on Clinical and Virological Outcomes in Treated HIV Infected Patients

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    Electronic coverage as of Dec. 30, 2003: Vol. 1, no. 1 (spring 2001)-; Description based on: Vol. 2, issue 1 (winter 2003); title from caption (viewed Dec. 30, 2003).; Harvested from the web on 10/25/0

    Higher rates of AIDS during the first year of antiretroviral therapy among migrants: the importance of tuberculosis

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    In lower-income countries rates of AIDS-defining events (ADEs) and death are high during the first year of combination antiretroviral therapy (ART). We investigated differences between foreign-born (migrant) and native-born (nonmigrant) patients initiating ART in Europe, the US and Canada, and examined rates of the most common ADEs and mortality during the first year of ART. Observational cohort study. We studied HIV-positive adults participating in one of 12 cohorts in the Antiretroviral Therapy Cohort Collaboration (ART-CC). Of 48 854 patients, 25.6% were migrants: 16.1% from sub-Saharan Africa, 5.6% Latin America, 2.3% North Africa/Middle East, and 1.6% Asia. Incidence of ADEs during the first year of ART was 60.8 per 1000 person-years: 69.9 for migrants and 57.7 for nonmigrants [crude hazard ratio (HR) 1.18; 95% confidence interval (CI) 1.08-1.29], adjusted HR (for sex, age, CD4, HIV-1 RNA, ART regimen, prior ADE, probable route of infection and year of initiation, and stratified by cohort) 1.21 (95% CI 1.09-1.34). Rates of tuberculosis were substantially higher in migrants than nonmigrants (14.3 vs. 6.3; adjusted HR 1.94; 95% CI 1.53-2.46). In contrast, mortality was higher among nonmigrants than migrants (crude HR 0.71; 95% CI 0.61-0.84), although excess mortality was partially explained by patient characteristics at start of ART (adjusted HR 0.91; 95% CI 0.76-1.09). During the first year of ART, HIV-positive migrants had higher rates of ADEs than nonmigrants. Tuberculosis was the most common ADE among migrants, highlighting the importance of screening for tuberculosis prior to ART initiation in this populatio

    Tumor-Infiltrating Macrophages in Post-Transplant, Relapsed Classical Hodgkin Lymphoma Are Donor-Derived

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    <div><p>Tumor-associated inflammatory cells in classical Hodgkin lymphoma (CHL) typically outnumber the neoplastic Hodgkin/Reed-Sternberg (H/RS) cells. The composition of the inflammatory infiltrate, particularly the fraction of macrophages, has been associated with clinical behavior. Emerging work from animal models demonstrates that most tissue macrophages are maintained by a process of self-renewal under physiologic circumstances and certain inflammatory states, but the contribution from circulating monocytes may be increased in some disease states. This raises the question of the source of macrophages involved in human disease, particularly that of CHL. Patients with relapsed CHL following allogeneic bone marrow transplant (BMT) provide a unique opportunity to begin to address this issue. We identified 4 such patients in our archives. Through molecular chimerism and/or XY FISH studies, we demonstrated the DNA content in the post-BMT recurrent CHL was predominantly donor-derived, while the H/RS cells were derived from the patient. Where possible to evaluate, the cellular composition of the inflammatory infiltrate, including the percentage of macrophages, was similar to that of the original tumor. Our findings suggest that the H/RS cells themselves define the inflammatory environment. In addition, our results demonstrate that tumor-associated macrophages in CHL are predominantly derived from circulating monocytes rather than resident tissue macrophages. Given the association between tumor microenvironment and disease progression, a better understanding of macrophage recruitment to CHL may open new strategies for therapeutic intervention.</p></div
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