Activatable T1 and T2 Magnetic Resonance Imaging Contrast Agents

Magnetic resonance imaging (MRI) has become one of the most important diagnosis tools available in medicine. Typically MRI is not capable of sensing biochemical activities. However, recently emerged activatable MRI contrast agents (CAs), whose relaxivity is variable in response to a specific parameter change in the surrounding physiological microenvironment, potentially allow for MRI to indicate biological processes. Among the various factors influencing the relaxivity of a CA, the number of inner-sphere water molecules (q) directly coordinated to the metal center, the residence time of the coordinated water molecule (τm), and the rotational correlation time representing the molecular tumbling time of a complex (τR) contribute strongly to the relaxivity of an activatable CA. Tuning the ligand structure and properties has been the subject of intensive research for activatable MR CA designs. This review summarizes a variety of activatable MRI CAs sensitive to common variables in microenvironment in vivo, i.e., pH, luminescence, metal ions, redox, and enzymes, etc., with emphasis on the influence of ligand design on parameters q, τm, and τR

HD-CNV: hotspot detector for copy number variants.

SUMMARY: Copy number variants (CNVs) are a major source of genetic variation. Comparing CNVs between samples is important in elucidating their potential effects in a wide variety of biological contexts. HD-CNV (hotspot detector for copy number variants) is a tool for downstream analysis of previously identified CNV regions from multiple samples, and it detects recurrent regions by finding cliques in an interval graph generated from the input. It creates a unique graphical representation of the data, as well as summary spreadsheets and UCSC (University of California, Santa Cruz) Genome Browser track files. The interval graph, when viewed with other software or by automated graph analysis, is useful in identifying genomic regions of interest for further study. AVAILABILITY AND IMPLEMENTATION: HD-CNV is an open source Java code and is freely available, with tutorials and sample data from http://daleylab.org. CONTACT: [email protected]

BB rat Gimap gene expression in sorted lymphoid T and B cells

Aims: The Gimap gene family has been shown to be integral to T cell survival and development. A frameshift mutation in Gimap5, one of seven members of the Gimap family, results in lymphopenia and is a prerequisite for spontaneous type 1 diabetes (T1D) in the BioBreeding (BB) rat. While not contributing to lymphopenia, the Gimap family members proximal to Gimap5, encompassed within the Iddm39 quantitative trait locus (QTL), have been implicated in T1D. We hypothesized that expression of the Gimap family members within the Iddm39 QTL, during thymocyte development as well as in peripheral T and B cells contribute to T1D. Main methods: Cell sorted subpopulations were analyzed by quantitative real time (qRT) PCR. Key findings: Gimap4 expression was reduced in DR.(lyp/lyp) rat double negative, double positive and CD8 single positive (SP) thymocytes while expression of Gimap8, Gimap6, and Gimap7 was reduced only in CD8 SP thymocytes. Interestingly, expression of the entire Gimap gene family was reduced in DR.(lyp/lyp) rat peripheral T cells compared to non-lymphopenic, non-diabetic DR.(+/+) rats. With the exception of Gimap6. the Gimap family genes were not expressed in B cells from spleen and mesenteric lymph node (MLN). Expression of Gimap9 was only detected in hematopoietic cells of non B cell lineage such as macrophage, dendritic or NK cells. Significance: These results suggest that lack of the Gimap5 protein in the DR.(lyp/lyp) congenic rat was associated with impaired expression of the entire family of Gimap genes and may regulate T cell homeostasis in the peripheral lymphoid organs. (C) 2011 Elsevier Inc. All rights reserved

Predicting the environmental suitability for onchocerciasis in Africa as an aid to elimination planning

Recent evidence suggests that, in some foci, elimination of onchocerciasis from Africa may be feasible with mass drug administration (MDA) of ivermectin. To achieve continental elimination of transmission, mapping surveys will need to be conducted across all implementation units (IUs) for which endemicity status is currently unknown. Using boosted regression tree models with optimised hyperparameter selection, we estimated environmental suitability for onchocerciasis at the 5 × 5-km resolution across Africa. In order to classify IUs that include locations that are environmentally suitable, we used receiver operating characteristic (ROC) analysis to identify an optimal threshold for suitability concordant with locations where onchocerciasis has been previously detected. This threshold value was then used to classify IUs (more suitable or less suitable) based on the location within the IU with the largest mean prediction. Mean estimates of environmental suitability suggest large areas across West and Central Africa, as well as focal areas of East Africa, are suitable for onchocerciasis transmission, consistent with the presence of current control and elimination of transmission efforts. The ROC analysis identified a mean environmental suitability index of 0·71 as a threshold to classify based on the location with the largest mean prediction within the IU. Of the IUs considered for mapping surveys, 50·2% exceed this threshold for suitability in at least one 5 × 5-km location. The formidable scale of data collection required to map onchocerciasis endemicity across the African continent presents an opportunity to use spatial data to identify areas likely to be suitable for onchocerciasis transmission. National onchocerciasis elimination programmes may wish to consider prioritising these IUs for mapping surveys as human resources, laboratory capacity, and programmatic schedules may constrain survey implementation, and possibly delaying MDA initiation in areas that would ultimately qualify

The transition to parenthood in obstetrics: Enhancing prenatal care for 2-generation impact

Obstetrics, the specialty overseeing infant and parent health before birth, could be expanded to address the interrelated areas of parents\u27 prenatal impact on children\u27s brain development and their own psychosocial needs during a time of immense change and neuroplasticity. Obstetrics is primed for the shift that is happening in pediatrics, which is moving from its traditional focus on physical health to a coordinated, whole-child, 2- or multigeneration approach. Pediatric care now includes developmental screening, parenting education, parent coaching, access to developmental specialists, brain-building caregiving skills, linkages to community resources, and tiered interventions with psychologists. Drawing on decades of developmental origins of health and disease research highlighting the prenatal beginnings of future health and new studies on the transition to parenthood describing adult development from pregnancy to early postpartum, we have proposed that, similar to pediatrics, the integration of education and intervention strategies into the prenatal care ecosystem should be tested for its potential to improve child cognitive and social-emotional development and parental mental health. Pediatric care programs can serve as models of change for the systematic development, testing and, incorporation of new content into prenatal care as universal, first-tier treatment and evidenced-based, triaged interventions according to the level of need. To promote optimal beginnings for the whole family, we have proposed an augmented prenatal care ecosystem that aligns with, and could build on, current major efforts to enhance perinatal care individualization through consideration of medical, social, and structural determinants of health

Veterans’ civilian employment experiences: Lessons learnt from focus groups

Emerging evidence highlights employment as a key factor influencing the success of transition from military to civilian life. Historically, employment programs have focused on improving skills such as resume writing and interview skills. However, it is likely that employment challenges are more than these practical barriers. Four focus groups with employed and unemployed Gulf War Era II veterans were conducted aimed at moving past a practical perspective by gaining experiential understandings of veterans’ employment. Thematic analysis indicated that the veterans’ employment experiences were best understood temporally in two master themes: pretransition and the divergent experiences of veterans who did and did not plan ahead and living the transition and the veterans’ experiences of employment barriers and facilitators. Further to the two master themes, an underlying thread of the need for self-determination was evident. Interpretation of the results led to the development of recommendations for policy, service provision, and future research

Fertility, Living Arrangements, Care and Mobility

There are four main interconnecting themes around which the contributions in this book are based. This introductory chapter aims to establish the broad context for the chapters that follow by discussing each of the themes. It does so by setting these themes within the overarching demographic challenge of the twenty-first century – demographic ageing. Each chapter is introduced in the context of the specific theme to which it primarily relates and there is a summary of the data sets used by the contributors to illustrate the wide range of cross-sectional and longitudinal data analysed

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes