The 2004-06 drought (2nd ed.)

This report reviews the 2004-06 drought within a hydrological and water resources framework. It was prepared as part of the National Hydrological Monitoring Programme (NHMP) – a collaborative enterprise between the Centre for Hydrology & Ecology and the British Geological Survey (both component bodies of the Natural Environment Research Council). The NHMP relies on the active cooperation of many organizations - the Environment Agency, Scottish Environment Protection Agency, Rivers Agency (Northern Ireland) and the Met Office in particular. The provision of the basic data which provides the foundation both of this report and the wider activities of the NHMP is gratefully acknowledged. A primary source of information for this review is the series of monthly UK Hydrological Summaries (for further details please visit: http://www.ceh.ac.uk/data/nrfa)

Beyond CD19: Opportunities for Future Development of Targeted Immunotherapy in Pediatric Relapsed-Refractory Acute Leukemia

Chimeric antigen receptor (CAR) T cell therapy has been used as a targeted approach in cancer therapy. Relapsed and refractory acute leukemia in pediatrics has been difficult to treat with conventional therapy due to dose limiting toxicities. With the recent success of CD 19 CAR in pediatric patients with B cell ALL, this mode of therapy has become a very attractive option for these patients with high risk disease. In this review, we will discuss current treatment paradigms of pediatric acute leukemia, and potential therapeutic targets for additional high risk populations, including T cell ALL, AML, and infant ALL

PII: S1471-4906(01)02028-2

Recent evidence has implicated interleukin-7 (IL-7) as a master regulator of T-cell homeostasis, based upon its essential role in the homeostatic expansion of naive T-cell populations in response to low-affinity antigens (Ags) and its capacity to enhance dramatically the expansion of peripheral T-cell populations in response to high-affinity Ags. Furthermore, T-cell-depleted humans have a unique inverse relationship between the peripheral CD4 + + T-cell count and the level of circulating IL-7. Together, these data suggest that increased amounts of IL-7 become available following T-cell depletion, thus, enhancing the high-and low-affinity Ag-driven expansion of the population of residual, mature T cells and boosting thymic regenerative capacity, as a means to restore T-cell homeostasis

Changing the Custody of Children Whose Parents Have Been Divorced: A General View of the Process

The purpose of this project was to obtain a preliminary description, through study of the legal files, of that group of persons who appear before the Court of Domestic Relations for a reconsideration of the custody decision made initially, at the time of divorce. A sample of 92 cases heard in Multnomah County in 1965 was obtained. A survey of the literature revealed that much of what has been written on the subject of divorce and custody is primarily from a statistical or legalistic standpoint and very little bears directly on the granting or obtaining of custody or the problems encountered by the custodial or non-custodial parents and the children. A reading schedule was developed for the purpose of recording the information in the legal files maintained by the court. The characteristics of the sample group were tallied in an effort to obtain a statistical profile of that group requiring additional court appearances to settle the matter of custody. A number of hypotheses were developed and tested by means of Chi Square. Though this study was limited by the fact that no control group was used and no personal interviews were obtained, it clearly indicates the need for additional research in the area of divorce and custody and suggestions are made for future projects

CEH-GEAR: 1 km resolution daily and monthly areal rainfall estimates for the UK for hydrological and other applications

The Centre for Ecology & Hydrology – Gridded Estimates of Areal Rainfall (CEH-GEAR) data set was developed to provide reliable 1 km gridded estimates of daily and monthly rainfall for Great Britain (GB) and Northern Ireland (NI) (together with approximately 3500 km2 of catchment in the Republic of Ireland) from 1890 onwards. The data set was primarily required to support hydrological modelling. The rainfall estimates are derived from the Met Office collated historical weather observations for the UK which include a national database of rain gauge observations. The natural neighbour interpolation methodology, including a normalisation step based on average annual rainfall (AAR), was used to generate the daily and monthly rainfall grids. To derive the monthly estimates, rainfall totals from monthly and daily (when complete month available) rain gauges were used in order to obtain maximum information from the rain gauge network. The daily grids were adjusted so that the monthly grids are fully consistent with the daily grids. The CEH-GEAR data set was developed according to the guidance provided by the British Standards Institution. The CEH-GEAR data set contains 1 km grids of daily and monthly rainfall estimates for GB and NI for the period 1890–2012. For each day and month, CEH-GEAR includes a secondary grid of distance to the nearest operational rain gauge. This may be used as an indicator of the quality of the estimates. When this distance is greater than 100 km, the estimates are not calculated due to high uncertainty

A Role for Thymic Stromal Lymphopoietin in CD4+ T Cell Development

Thymic stromal lymphopoietin (TSLP) signals via a receptor comprising the interleukin (IL)-7 receptor α chain and a distinctive subunit, TSLP receptor (TSLPR), which is most related to the common cytokine receptor γ chain, γc. We have generated TSLPR knockout (KO) mice and found that although these mice had normal lymphocyte numbers, γc/TSLPR double KO mice had a greater lymphoid defect than γc KO mice. This indicates that TSLP contributes to lymphoid development and accounts for some of the residual lymphoid development in γc KO mice and presumably in patients with X-linked severe combined immunodeficiency. Injection of TSLP into γc KO mice induced the expansion of T and B cells. Moreover, sublethally irradiated TSLPR KO mice showed weaker recovery of lymphocyte populations than wild-type (WT) littermates, even when neutralizing anti–IL-7 antibodies were injected. Interestingly, TSLP preferentially stimulated the proliferation and survival of CD4+ single positive thymocytes and peripheral T cells in vitro. Additionally, CD4+ T cells from TSLPR KO mice expanded less efficiently than WT CD4+ T cells in irradiated hosts, and TSLP preferentially expanded CD4+ T cells both in vitro and in vivo. Thus, as compared with other known cytokines, TSLP is distinctive in exhibiting a lineage preference for the expansion and survival of CD4+ T cells

Absence of Replication-Competent Lentivirus in the Clinic: Analysis of Infused T Cell Products

Exposure to replication-competent lentivirus (RCL) is a theoretical safety concern for individuals treated with lentiviral gene therapy. For certain ex vivo gene therapy applications, including cancer immunotherapy trials, RCL detection assays are used to screen the vector product as well as the vector-transduced cells. In this study, we reviewed T cell products screened for RCL using methodology developed in the National Gene Vector Biorepository. All trials utilized third-generation lentiviral vectors produced by transient transfection. Samples from 26 clinical trials totaling 460 transduced cell products from 375 subjects were evaluated. All cell products were negative for RCL. A total of 296 of the clinical trial participants were screened for RCL at least 1 month after infusion of the cell product. No research subject has shown evidence of RCL infection. These findings provide further evidence attesting to the safety of third-generation lentiviral vectors and that testing T cell products for RCL does not provide added value to screening the lentiviral vector product