Challenges in quantifying changes in the global water cycle

Human influences have likely already impacted the large-scale water cycle but natural variability and observational uncertainty are substantial. It is essential to maintain and improve observational capabilities to better characterize changes. Understanding observed changes to the global water cycle is key to predicting future climate changes and their impacts. While many datasets document crucial variables such as precipitation, ocean salinity, runoff, and humidity, most are uncertain for determining long-term changes. In situ networks provide long time-series over land but are sparse in many regions, particularly the tropics. Satellite and reanalysis datasets provide global coverage, but their long-term stability is lacking. However, comparisons of changes among related variables can give insights into the robustness of observed changes. For example, ocean salinity, interpreted with an understanding of ocean processes, can help cross-validate precipitation. Observational evidence for human influences on the water cycle is emerging, but uncertainties resulting from internal variability and observational errors are too large to determine whether the observed and simulated changes are consistent. Improvements to the in situ and satellite observing networks that monitor the changing water cycle are required, yet continued data coverage is threatened by funding reductions. Uncertainty both in the role of anthropogenic aerosols, and due to large climate variability presently limits confidence in attribution of observed changes

Heterodinuclear ruthenium(II)-cobalt(III) complexes as models for a new approach to selective cancer treatment

Heterodinuclear ruthenium(ii)-cobalt(iii) complexes have been prepared as part of investigations into a new approach to selective cancer treatment. A cobalt(iii) centre bearing amine ligands, which serve as models for cytotoxic nitrogen mustard ligands, is connected by a bridging ligand to a ruthenium(ii)-polypyridyl moiety. Upon excitation of the ruthenium centre by visible light, electron transfer to the cobalt(iii) centre results in reduction to cobalt(ii) and consequent release of its ligands. We have synthesised several such structures and demonstrated their ability to release ligands upon excitation of the ruthenium centre by visible light

The class IA phosphatidylinositol 3-kinase p110-β subunit is a positive regulator of autophagy

p110-β associates with the Vps34–Vps15–Beclin 1–Atg14L complex and facilitates generation of PtdIns(3)P to promote autophagy

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

PRODUCTION RELATIONSHIPS IN SOUTH CENTRAL AGRICULTURE

Output supplies and input demands were estimated for each of five South Central states. The model structure in each state was based on prior parametric tests of homothetic separability, and estimates were generally consistent with a competitive, profit-maximizing industry. Considerable diversity among states was evident in selected production relationships. These results further document the non-uniform ways in which producers respond to government farm programs and market information

The Use of Transperineal Sector Biopsy as A First-Line Biopsy Strategy:A Multi-Institutional Analysis of Clinical Outcomes and Complications

PURPOSE: Systematic transrectal ultrasound biopsies have been the first-line biopsy strategy in men with suspected prostate cancer for over 30 years. Transperineal biopsy is an alternative approach but has been predominately reserved as a repeat biopsy strategy and not widely used as a first-line approach. This study evaluates the diagnostic and clinical outcomes of transperineal sector biopsy (TPSB) as a first-line biopsy strategy in the diagnosis and management of prostate cancer. MATERIALS AND METHODS: A multi-institutional review of 402 consecutive patients who underwent primary transperineal sector biopsy. All patients had no prior history of prostate biopsy. TPSB was carried out as a day-case procedure under general or regional anaesthesia. The cancer detection rate, location and complications for all cases were evaluated. RESULTS: Prostate cancer was identified in 249 patients (61.9%) and was comparably sited across anterior, middle and posterior sectors. The disease was clinically significant (Gleason 3+4 or > 4mm maximum cancer length) in 187 patients (47%). Post biopsy urinary retention occurred in 6 patients (1.5%). Hematuria requiring overnight hospital admission occurred in 4 patients (1.0%). There were no cases of urosepsis. CONCLUSIONS: As a primary diagnostic strategy, TPSB is a safe and effective technique with high cancer detection rates. It also offers an attractive compromise to more extensive transperineal protocols, which can be more time-consuming and associated with higher morbidity.&nbsp