Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark

Background: Hypothesised associations between in utero exposure to selective serotonin reuptake inhibitors (SSRIs) and congenital anomalies, particularly congenital heart defects (CHD), remain controversial. We investigated the putative teratogenicity of SSRI prescription in the 91 days either side of first day of last menstrual period (LMP). Methods and Findings: Three population-based EUROCAT congenital anomaly registries- Norway (2004–2010), Wales (2000–2010) and Funen, Denmark (2000–2010)—were linked to the electronic healthcare databases holding prospectively collected prescription information for all pregnancies in the timeframes available. We included 519,117 deliveries, including foetuses terminated for congenital anomalies, with data covering pregnancy and the preceding quarter, including 462,641 with data covering pregnancy and one year either side. For SSRI exposures 91 days either side of LMP, separately and together, odds ratios with 95% confidence intervals (ORs, 95%CI) for all major anomalies were estimated. We also explored: pausing or discontinuing SSRIs preconception, confounding, high dose regimens, and, in Wales, diagnosis of depression. Results were combined in meta-analyses. SSRI prescription 91 days either side of LMP was associated with increased prevalence of severe congenital heart defects (CHD) (as defined by EUROCAT guide 1.3, 2005) (34/12,962 [0.26%] vs. 865/506,155 [0.17%] OR 1.50, 1.06–2.11), and the composite adverse outcome of 'anomaly or stillbirth' (473/12962, 3.65% vs. 15829/506,155, 3.13%, OR 1.13, 1.03–1.24). The increased prevalence of all major anomalies combined did not reach statistical significance (3.09% [400/12,962] vs. 2.67% [13,536/506,155] OR 1.09, 0.99–1.21). Adjusting for socio-economic status left ORs largely unchanged. The prevalence of anomalies and severe CHD was reduced when SSRI prescriptions were stopped or paused preconception, and increased when >1 prescription was recorded, but differences were not statistically significant. The dose-response relationship between severe CHD and SSRI dose (meta-regression OR 1.49, 1.12–1.97) was consistent with SSRI-exposure related risk. Analyses in Wales suggested no associations between anomalies and diagnosed depression. Conclusion: The additional absolute risk of teratogenesis associated with SSRIs, if causal, is small. However, the high prevalence of SSRI use augments its public health importance, justifying modifications to preconception care

Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity

The bacteriophage population is large, dynamic, ancient, and genetically diverse. Limited genomic information shows that phage genomes are mosaic, and the genetic architecture of phage populations remains ill-defined. To understand the population structure of phages infecting a single host strain, we isolated, sequenced, and compared 627 phages of Mycobacterium smegmatis. Their genetic diversity is considerable, and there are 28 distinct genomic types (clusters) with related nucleotide sequences. However, amino acid sequence comparisons show pervasive genomic mosaicism, and quantification of inter-cluster and intra-cluster relatedness reveals a continuum of genetic diversity, albeit with uneven representation of different phages. Furthermore, rarefaction analysis shows that the mycobacteriophage population is not closed, and there is a constant influx of genes from other sources. Phage isolation and analysis was performed by a large consortium of academic institutions, illustrating the substantial benefits of a disseminated, structured program involving large numbers of freshman undergraduates in scientific discovery

Book Review: \u3ci\u3eThe Allen Site: A Paleoindian Camp in Southwestern Nebraska\u3c/i\u3e Edited by Douglas B. Bamforth

Douglas Bamforth and his colleagues demonstrate in this edited volume the valuable role in modern archaeology for thoughtful reinvestigation of previously studied site locations and archaeological collections. Containing 14 chapters by 11 contributors, The Allen Site includes comprehensive paleoenvironmental research and detailed reanalysis of cultural materials recovered from renowned excavations conducted in the Medicine Creek Basin between 1947 and 1949, deposits that hold a series of human occupations ranging from 10,550 to 8,000 radiocarbon years in age. These new studies provide valuable improvements to our understanding of environmental change and early human adaptations during the Terminal Pleistocene and Early Holocene on the Central Great Plains. The book also offers essential perspectives on the original paleontological and archaeological research in this region with a primary focus on the Allen Site (although updated geomorphic and paleoenvironmental information is presented for the nearby sites of Red Smoke, Lime Creek, and Stafford)

Lithic Raw Material Variability in the Central Duck River Basin: Reflections of Middle and Late Archaic Organizational Strategies

The purpose of this study was to develop a model for understanding prehistoric chipped-stone debris distribution in the central Duck River Basin region located in Middle Tennessee. The model design consists of theoretical and empirical observations which are integrated to form an interpretive framework. Seven lithic assemblages ranging from Middle to Late Archaic periods (ca. 7000 to 3000 years B.P.) in age were analyzed to assess the model. The first stage of model-building was the development of a theoretical foundation for approaching the problem. A cultural adaptation paradigm is the foundation cornerstone. Understanding cultural process and organization are emphasized. Lithic technology is viewed as an integral part of prehistoric cultural adaptation and lithic remains are regarded as critical indicators of behavioral variability. Environmental variables are stressed in interpreting lithic debris patterning across the landscape. The second stage of model-building involved the construction of a set of observations on lithic resource types and their distributions in the study area. A regional lithic resource survey was implemented. Several chert types are defined and described. Emphasis is placed on macroscopic identification techniques. Quantification of lithic resource distribution patterns was achieved through a regional gravel study. Application of the model to archaeological data was the last stage of model-building. Seven Middle-Late Archaic assemblages are compared. A pilot study of two assemblages initiates the comparison. Results of the interassemblage analysis suggest that Late Archaic settlement systems were more logistically organized and technological systems were less expediently organized than those of Middle Archaic groups. Differences between Middle and Late Archaic adaptations are viewed as responses to regional environmental and demographic trends. Documentation of these trends and their implications for subsistence, settlement, and social organization is considered. Evaluation of the model suggests adequate explanatory ability. The consideration of more assemblages is recommended for improving model accuracy