Rangeland Fires and Cheatgrass: Values at Risk and Support for Preservation

The high desert sagebrush ecosystems of the Great Basin evolved with fire. However, the introduction of cheatgrass (t. bromus), a highly flammable invasive annual grass, has contributed to the increased intensity and frequency of wildfires we have seen in recent years. Cheatgrass-fueled fires often kill native perennials, which creates openings for further cheatgrass expansion. Winters with more moisture than usual result in more cheatgrass and increased fire risk. Over time the result is ever larger areas dominated by cheatgrass and other invasive weeds that burn with greater frequency, and increasingly severe fire seasons

CD80 Expressed by CD8+ T Cells Contributes to PD-L1-Induced Apoptosis of Activated CD8+ T Cells

Tumor cells are capable of limiting antitumor CD8+ T cell responses through their cell surface expression of PD-L1. In addition to PD-1 expressed by CD8+ T cells, PD-L1 also binds to CD80 expressed by CD8+ T cells. The influence of the PD-L1/CD80 interaction on CD8+ T cell function has not been fully characterized, so we sought to investigate the impact of the PD-L1/CD80 interaction on PD-L1-induced apoptosis of activated CD8+ T cells. We found that CD8+ T cells that lacked CD80 expression got activated to the same extent as wild-type CD8+ T cells, but when cultured with anti-CD3 and PD-L1/Fc protein, activated CD8+ T cells that lacked CD80 expression survived better than activated wild-type CD8+ T cells. These findings indicate that PD-L1 induces apoptosis in activated CD8+ T cells in part by signaling through CD80. Thus, in the design and implementation of checkpoint blockade therapies that target PD-L1, it is essential that both binding partners for PD-L1, PD-1, and CD80 are considered

Sensitivity of WTP Estimates to Definition of \u27Yes\u27: Reinterpreting Expressed Response Intensity

Willingness to pay (WTP) estimation typically involves some strategy for mapping nondichotomous contingent valuation (CV) responses onto a dichotomous yes/no dependent variable. We propose a new approach to selecting which responses qualify as ‘yes.’ We apply the proposed method to polychotomous CV data for preventative land management programs in the Great Basin. We also estimate WTP using other methods of response recoding found in the literature. By contrasting the results under different approaches, we demonstrate how and why WTP point estimates vary across recoding methods and discuss the comparative advantages of our more generalized recoding approach that is based on predicted probabilities of ‘yes’ responses

FR900482, a close cousin of mitomycin C that exploits mitosene-based DNA cross-linking

AbstractBackground: The class of antitumor antibiotics that includes FR900482 has a very close structural analogy to the mitomycins, one of which, mitomycin C, has been in widespread clinical use for more than 20 years. Like mitomycin C, these antitumor antibiotics are reductively activated in vivo and covalently cross-link DNA as a result of activity of the mitosene moiety generated on reduction. Owing to differences in structure and the attendant mechanistic differences in bioreductive activation between the mitomycins and FR900482, FR900482 does not produce an adventitious superoxide radical anion during reductive activation and thus does not exhibit oxidative strand scission of DNA. It is postulated that the low clinical toxicity of FR900482 relative to mitomycin C is a direct manifestation of the mechanistic differences of bioreductive activation leading to the highly reactive DNA cross-linking mitosenes.Results: Using Fe(II)-EDTA footprinting, we showed that the two natural products FR900482 (1) and dihydro, FR66979 (3), and the semi-synthetically derived triacetate FK973 (2), display remarkable selectivity for 5′ deoxy-CG sequences of DNA, and that this selectivity is abolished upon deletion of the exocyclic N2 amine of either participating guanosine residue. In addition, we investigated the mono alkylation abilities of FR66979 with respect to a number of inosine-substituted oligonuclectides and observed that the FR900482 class of compounds were able to give rise to easily separable orientation isomers of their respective cross-links.Conclusions: The FR900482 class of antitumor antibiotics cross-link DNA in a fashion analogous to the mitomycins. The cross-linking reaction yields two orientation, isomers which are of vastly different electrophoretic mobility and which also exhibit radically different DNA-protein recognition properties upon reaction with Alul restriction endonuclease. In addition, mono-alkylation of DNA by FR66979 shows little, if any, dependence upon pre-covalent interactions deemed necessary for the mitomycins. These insights support the proposal that the FR900482 class of compounds represents a compelling clinical replacement for mitomycin C, given its greatly reduced host toxicity and superior DNA interstrand cross-linking efficacy

The use of protocol in breaking bad news: evidence and ethos

This article discusses health professionals use of protocol in the breaking of bad news, focusing particularly on the well-known SPIKES framework. The evidence of impact on the patient experience is examined and recommendations are made for further outcome-based research. Existing evidence suggests that the model as commonly interpreted may not fully meet the needs of patients or reflect the clinical experience of breaking bad news for some professionals and further guidance may be needed to support them in their practice. The ethos of the step-wise protocol is debated, questioning whether it helps or hinders individualised care and the formation of a genuine relationship between patient and professional. Finally, recommendations for practice are offered

Liquefaction Hazard Mitigation by Prefabricated Vertical Drains

Liquefaction has typically been mitigated by in-situ densification; however vertical composite drains offer the possibility of preventing liquefaction and associated settlement while reducing the cost and time required for treatment. Three case histories are presented which describe the use of vertical drains to mitigate liquefaction hazard and techniques to control the flow of water exiting the drains. In addition, results from a test case are presented where controlled blasting techniques were used to evaluate drain performance in-situ. Blasting was successful in liquefying loose sand in an untreated test site. Similar blast charges were then detonated at adjacent sites treated with drains. Measurements demonstrated that the drains significantly increased the rate of pore pressure dissipation. In addition, the installation process typically densified the surrounding soil, thereby decreasing the liquefaction potential. Computer analyses successfully matched the measured response and suggest that the drains could be effective for earthquake events

Messages about dual contraception in areas of high HIV prevalence are not heeded

Background. Dual protection is recommended for prevention of unwanted pregnancies and protection against sexually transmitted infections, including HIV. It is critical for HIV-negative women to prevent seroconversion and HIV transmission to their infants during pregnancy and breastfeeding. Methods. Women were followed up after delivery, monthly for the first 9 months and then 3-monthly to 24 months, in a cohort study investigating postnatal HIV transmission. Study nurses discussed family planning, including condom use, at each visit. Contraceptive methods used since the last visit were recorded. All women knew their HIV status, and most women breastfed for a minimum of 6 months. Results. Among 1 137 HIV-positive and 1 220 HIV-negative women the most common contraceptive method was the hormonal injectable; few women used condoms alone or as dual contraception (0 - 3 months 6.8%; 7 - 12 months 16.3%; 19 - 24 months 14.4%). Compared with uninfected women, HIV-positive women were more likely to use condoms in years 1 and 2 after delivery (adjusted odds ratio (AOR) 1.72, 95% confidence interval (CI) 1.38 - 2.14,