Technologies for Climate Change Mitigation - Agriculture Sector

This guidebook describes crop and livestock management technologies and practices that contribute to climate change mitigation while improving crop productivity, reducing reliance on synthetic fertilizers, and lowering water consumption. It is co-authored by internationally recognised experts in the areas of crops, livestock, emissions, and economics, and we are grateful for their efforts in producing this cross disciplinary work.This publication is part of a technical guidebook series produced by the UNEP Risø Centre on Energy, Climate and Sustainable Development (URC) as part of the Technology Needs Assessment (TNA) project(http://tech-action.org) that is assisting developing countries in identifying and analysing the priority technology needs for mitigating and adapting to climate change. The TNA process involves differentstakeholders in a consultative process, enabling all stakeholders to understand their technology needs in a cohesive manner, and prepare Technology Action Plans (TAPs) accordingly.The TNA project is funded by the Global Environment Facility (GEF) and is being implemented by UNEP and the URC in 36 developing countries

Atypical antipsychotic medications and hyponatremia in older adults: a population-based cohort study

Background: A number of case reports have suggested a possible association between atypical antipsychotic medications and hyponatremia. Currently, there are no reliable estimates of hyponatremia risk from atypical antipsychotic drugs. Objective: The objective of this study was to examine the 30-day risk of hospitalization with hyponatremia in older adults dispensed an atypical antipsychotic drug relative to no antipsychotic use. Design: The design of this study was a retrospective, population-based cohort study. Setting: The setting of this study was in Ontario, Canada, from 2003 to 2012. Patients: Adults 65 years or older with an identified psychiatric condition who were newly dispensed risperidone, olanzapine, or quetiapine in the community setting compared to adults with similar indicators of baseline health who were not dispensed such a prescription. Measurements: The primary outcome was the 30-day risk of hospitalization with hyponatremia. The tracer outcome (an outcome that is not expected to be influenced by the study drugs) was the 30-day risk of hospitalization with bowel obstruction. These outcomes were assessed using hospital diagnosis codes. Methods: Using health administrative data, we applied a propensity score technique to match antipsychotic users 1:1 to non-users of antipsychotic drugs (58,008 patients in each group). We used conditional logistic regression to compare outcomes among the matched users and non-users. Results: A total of 104 baseline characteristics were well-balanced between the two matched groups. Atypical antipsychotic use compared to non-use was associated with an increased risk of hospitalization with hyponatremia within 30 days (86/58,008 (0.15 %) versus 53/58,008 (0.09 %); relative risk 1.62 (95 % confidence interval (CI) 1.15 to 2.29); absolute risk increase 0.06 % (95 % CI 0.02 to 0.10)). The limited number of events precluded some additional analyses to confirm if the association was robust. Atypical antipsychotic use compared to non-use was not associated with hospitalization with bowel obstruction within 30 days (55/58,008 (0.09 %) versus 44/58,008 (0.08 %); relative risk 1.25 (95 % CI 0.84 to 1.86)). Limitations: We could only study older adults within our data sources. Conclusions: In this study, the use of an atypical antipsychotic was associated with a modest but statistically significant increase in the 30-day risk of a hospitalization with hyponatremia. The association was less pronounced than that described with other psychotropic drugs

Pharmacokinetic and exposure-response analysis of pertuzumab in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer

Purpose: To characterize the pharmacokinetics (PK) of pertuzumab and trastuzumab in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer in the randomized, double-blind, phase III JACOB study (NCT01774786), and to evaluate the appropriateness of the pertuzumab regimen in these patients. Methods: Patients received 840 mg intravenous pertuzumab or placebo plus trastuzumab q3w and chemotherapy. Pertuzumab and trastuzumab were administered until disease progression or unacceptable toxicity. Chemotherapy was administered for up to six cycles or disease progression or unacceptable toxicity. Serum concentrations of pertuzumab and trastuzumab were measured. Pertuzumab PK was characterized across treatment cycles. The impact of anti-drug antibodies (ADAs) on pertuzumab PK and the impact of pertuzumab on trastuzumab PK were assessed. An exploratory exposure-efficacy analysis was also conducted. Results: In total, 374 patients in the pertuzumab arm had evaluable PK data. The mean observed pertuzumab steady-state serum trough (minimum) concentration (C) ± standard deviation was 114 ± 51.8 μg/mL. The target pertuzumab C of ≥ 20 μg/mL was reached in 99.3% of patients at Cycle 5 (steady state) and beyond. Greater than 90% of patients were above the PK target right after the first pertuzumab dose. There was no apparent impact of ADAs on pertuzumab PK nor of pertuzumab on trastuzumab PK. There were no differences in overall survival across Cycle 1 pertuzumab (C) or Cycle 5 pertuzumab (C) exposure quartiles. Conclusions: Pertuzumab exposure in JACOB was consistent with prior studies in advanced gastric cancer and breast cancer. The 840 mg q3w dose allowed the majority of patients in JACOB to achieve target pertuzumab concentrations and appears to be an appropriate dose selectio

The Identification of Potential Therapeutic Targets for Cutaneous Squamous Cell Carcinoma

We performed a small interfering RNA screen to identify targets for cutaneous squamous cell carcinoma (cSCC) therapy in the ubiquitin/ubiquitin-like system. We provide evidence for selective anti-cSCC activity of knockdown of the E3 ubiquitin ligase MARCH4, the ATPase p97/VCP, the deubiquitinating enzyme USP8, the cullin-RING ligase (CRL) 4 substrate receptor CDT2/DTL, and components of the anaphase-promoting complex/cyclosome (APC/C). Specifically attenuating CRL4CDT2 by CDT2 knockdown can be more potent in killing cSCC cells than targeting CRLs or CRL4s in general by RBX1 or DDB1 depletion. Suppression of the APC/C or forced APC/C activation by targeting its repressor EMI1 are both potential therapeutic approaches. We observed that cSCC cells can be selectively killed by small-molecule inhibitors of USP8 (DUBs-IN-3/compound 22c) and the NEDD8 E1 activating enzyme/CRLs (MLN4924/pevonedistat). A substantial proportion of cSCC cell lines are very highly MLN4924-sensitive. Pathways that respond to defects in proteostasis are involved in the anti-cSCC activity of p97 suppression. Targeting USP8 can reduce the expression of growth factor receptors that participate in cSCC development. EMI1 and CDT2 depletion can selectively cause DNA re-replication and DNA damage in cSCC cells

Quantifiable Assurance: From IPs to Platforms

Hardware vulnerabilities are generally considered more difficult to fix than software ones because they are persistent after fabrication. Thus, it is crucial to assess the security and fix the vulnerabilities at earlier design phases, such as Register Transfer Level (RTL) and gate level. The focus of the existing security assessment techniques is mainly twofold. First, they check the security of Intellectual Property (IP) blocks separately. Second, they aim to assess the security against individual threats considering the threats are orthogonal. We argue that IP-level security assessment is not sufficient. Eventually, the IPs are placed in a platform, such as a system-on-chip (SoC), where each IP is surrounded by other IPs connected through glue logic and shared/private buses. Hence, we must develop a methodology to assess the platform-level security by considering both the IP-level security and the impact of the additional parameters introduced during platform integration. Another important factor to consider is that the threats are not always orthogonal. Improving security against one threat may affect the security against other threats. Hence, to build a secure platform, we must first answer the following questions: What additional parameters are introduced during the platform integration? How do we define and characterize the impact of these parameters on security? How do the mitigation techniques of one threat impact others? This paper aims to answer these important questions and proposes techniques for quantifiable assurance by quantitatively estimating and measuring the security of a platform at the pre-silicon stages. We also touch upon the term security optimization and present the challenges for future research directions

Erratum: Oral salt and water versus intravenous saline for the prevention of acute kidney injury following contrast-enhanced computed tomography: study protocol for a pilot randomized trial Salmonella blood stream infections in a tertiary care setting in Ghana.

[This corrects the article DOI: 10.1186/s40697-015-0048-7.]

Identification and Characterization of Trimethylamine-N-oxide Uptake and Efflux Transporters

Trimethylamine-N-oxide (TMAO) is a recently identified predictor of cardiovascular and chronic kidney disease. TMAO is primarily generated through gut-microbiome mediated conversion of dietary choline and carnitine to TMA, which is converted to TMAO by hepatic flavin monooxygenase 3 (FMO3) and subsequently undergoes renal elimination. We investigated the role of uptake and efflux drug transporters in TMAO disposition in vitro and in vivo. After screening a large array of uptake transporters, we show organic cation transporter 2 (OCT2) is the key transporter for TMAO cellular uptake. In Oct1/2 knockout mice, we observed increased plasma TMAO levels with reduced renal retention, suggesting the importance of Oct2 in facilitating the uptake of TMAO into renal tubular cells in vivo. Multiple transporters of the ATP-binding cassette (ABC) family, including ABCG2 (BCRP) and ABCB1 (MDR1), were capable of TMAO efflux. In human subjects, clinical, dietary, and pharmacogenetic covariates were evaluated for contribution to TMAO levels in a cohort of dyslipidemic patients (n = 405). Interestingly, genetic variation in ABCG2, but not other transporters, appeared to play a role in modulating TMAO exposure