The medical student

The Medical Student was published from 1888-1921 by the students of Boston University School of Medicine

Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study.

The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts

Synthesis

Human activity in the last century has led to a substantial increase in nitrogen (N) emissions and deposition. This N deposition has reached a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. One approach for quantifying the level of pollution that would be harmful to ecosystems is the critical loads approach. The critical load is dei ned as the level of a pollutant below which no detrimental ecological effect occurs over the long term according to present knowledge. The objective of this project was to synthesize current research relating atmospheric N deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The receptors that we evaluated included freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical, and (2) individual species, population, and community responses. This report synthesizes current research relating atmospheric nitrogen (N) deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The report evaluates the following receptors: freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical; and (2) individual species, population, and community responses. The range of critical loads for nutrient N reported for U.S. ecoregions, inland surface waters, and freshwater wetlands is 1 to 39 kg N ha-1 y-1. This range spans the range of N deposition observed over most of the country. The empirical critical loads for N tend to increase in the following sequence for different life forms: diatoms, lichens and bryophytes, mycorrhizal fungi, herbaceous plants and shrubs, trees

Germline IKAROS dimerization haploinsufficiency causes hematologic cytopenias and malignancies

IKAROS is a transcription factor forming homo- and heterodimers and regulating lymphocyte development and function. Germline mutations affecting the IKAROS N-terminal DNA binding domain, acting in a haploinsufficient or dominant-negative manner, cause immunodeficiency. Herein, we describe 4 germline heterozygous IKAROS variants affecting its C-terminal dimerization domain, via haploinsufficiency, in 4 unrelated families. Index patients presented with hematologic disease consisting of cytopenias (thrombocytopenia, anemia, neutropenia)/Evans syndrome and malignancies (T-cell acute lymphoblastic leukemia, Burkitt lymphoma). These dimerization defective mutants disrupt homo- and heterodimerization in a complete or partial manner, but they do not affect the wild-type allele function. Moreover, they alter key mechanisms of IKAROS gene regulation, including sumoylation, protein stability, and the recruitment of the nucleosome remodeling and deacetylase complex; none affected in N-terminal DNA binding defects. These C-terminal dimerization mutations are largely associated with hematologic disorders, display dimerization haploinsufficiency and incomplete clinical penetrance, and differ from previously reported allelic variants in their mechanism of action. Dimerization mutants contribute to the growing spectrum of IKAROS-associated diseases displaying a genotype-phenotype correlation

Synthesis

Human activity in the last century has led to a substantial increase in nitrogen (N) emissions and deposition. This N deposition has reached a level that has caused or is likely to cause alterations to the structure and function of many ecosystems across the United States. One approach for quantifying the level of pollution that would be harmful to ecosystems is the critical loads approach. The critical load is dei ned as the level of a pollutant below which no detrimental ecological effect occurs over the long term according to present knowledge. The objective of this project was to synthesize current research relating atmospheric N deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The receptors that we evaluated included freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical, and (2) individual species, population, and community responses. This report synthesizes current research relating atmospheric nitrogen (N) deposition to effects on terrestrial and aquatic ecosystems in the United States and to identify empirical critical loads for atmospheric N deposition. The report evaluates the following receptors: freshwater diatoms, mycorrhizal fungi and other soil microbes, lichens, herbaceous plants, shrubs, and trees. The main responses reported fell into two categories: (1) biogeochemical; and (2) individual species, population, and community responses. The range of critical loads for nutrient N reported for U.S. ecoregions, inland surface waters, and freshwater wetlands is 1 to 39 kg N ha-1 y-1. This range spans the range of N deposition observed over most of the country. The empirical critical loads for N tend to increase in the following sequence for different life forms: diatoms, lichens and bryophytes, mycorrhizal fungi, herbaceous plants and shrubs, trees

Defective Interfering Viral Particles in Acute Dengue Infections

While much of the genetic variation in RNA viruses arises because of the error-prone nature of their RNA-dependent RNA polymerases, much larger changes may occur as a result of recombination. An extreme example of genetic change is found in defective interfering (DI) viral particles, where large sections of the genome of a parental virus have been deleted and the residual sub-genome fragment is replicated by complementation by co-infecting functional viruses. While most reports of DI particles have referred to studies in vitro, there is some evidence for the presence of DI particles in chronic viral infections in vivo. In this study, short fragments of dengue virus (DENV) RNA containing only key regulatory elements at the 3′ and 5′ ends of the genome were recovered from the sera of patients infected with any of the four DENV serotypes. Identical RNA fragments were detected in the supernatant from cultures of Aedes mosquito cells that were infected by the addition of sera from dengue patients, suggesting that the sub-genomic RNA might be transmitted between human and mosquito hosts in defective interfering (DI) viral particles. In vitro transcribed sub-genomic RNA corresponding to that detected in vivo could be packaged in virus like particles in the presence of wild type virus and transmitted for at least three passages in cell culture. DENV preparations enriched for these putative DI particles reduced the yield of wild type dengue virus following co-infections of C6–36 cells. This is the first report of DI particles in an acute arboviral infection in nature. The internal genomic deletions described here are the most extensive defects observed in DENV and may be part of a much broader disease attenuating process that is mediated by defective viruses

Bridging reproductive and microbial ecology: a case study in arbuscular mycorrhizal fungi

Offspring size is a key trait for understanding the reproductive ecology of species, yet studies addressing the ecological meaning of offspring size have so far been limited to macro-organisms. We consider this a missed opportunity in microbial ecology and provide what we believe is the first formal study of offspring-size variation in microbes using reproductive models developed for macro-organisms. We mapped the entire distribution of fungal spore size in the arbuscular mycorrhizal (AM) fungi (subphylum Glomeromycotina) and tested allometric expectations of this trait to offspring (spore) output and body size. Our results reveal a potential paradox in the reproductive ecology of AM fungi: while large spore-size variation is maintained through evolutionary time (independent of body size), increases in spore size trade off with spore output. That is, parental mycelia of large-spored species produce fewer spores and thus may have a fitness disadvantage compared to small-spored species. The persistence of the large-spore strategy, despite this apparent fitness disadvantage, suggests the existence of advantages to large-spored species that could manifest later in fungal life history. Thus, we consider that solving this paradox opens the door to fruitful future research establishing the relationship between offspring size and other AM life history traits

Empirical Legal Studies Before 1940: A Bibliographic Essay

The modern empirical legal studies movement has well-known antecedents in the law and society and law and economics traditions of the latter half of the 20th century. Less well known is the body of empirical research on legal phenomena from the period prior to World War II. This paper is an extensive bibliographic essay that surveys the English language empirical legal research from approximately 1940 and earlier. The essay is arranged around the themes in the research: criminal justice, civil justice (general studies of civil litigation, auto accident litigation and compensation, divorce, small claims, jurisdiction and procedure, civil juries), debt and bankruptcy, banking, appellate courts, legal needs, legal profession (including legal education), and judicial staffing and selection. Accompanying the essay is an extensive bibliography of research articles, books, and reports