Leverage demand-side policies for energy security.

Conventional supply-side approaches overlook potential benefits.

Economy-wide evaluation of CO2 and air quality impacts of electrification in the United States.

Adopting electric end-use technologies instead of fossil-fueled alternatives, known as electrification, is an important economy-wide decarbonization strategy that also reduces criteria pollutant emissions and improves air quality. In this study, we evaluate CO2 and air quality co-benefits of electrification scenarios by linking a detailed energy systems model and a full-form photochemical air quality model in the United States. We find that electrification can substantially lower CO2 and improve air quality and that decarbonization policy can amplify these trends, which yield immediate and localized benefits. In particular, transport electrification can improve ozone and fine particulate matter (PM2.5), though the magnitude of changes varies regionally. However, growing activity from non-energy-related PM2.5 sources-such as fugitive dust and agricultural emissions-can offset electrification benefits, suggesting that additional measures beyond CO2 policy and electrification are needed to meet air quality goals. We illustrate how commonly used marginal emissions approaches systematically underestimate reductions from electrification.

Mapping interactions between the sustainable development goals: lessons learned and ways forward.

Pursuing integrated research and decision-making to advance action on the sustainable development goals (SDGs) fundamentally depends on understanding interactions between the SDGs, both negative ones ("trade-offs") and positive ones ("co-benefits"). This quest, triggered by the 2030 Agenda, has however pointed to a gap in current research and policy analysis regarding how to think systematically about interactions across the SDGs. This paper synthesizes experiences and insights from the application of a new conceptual framework for mapping and assessing SDG interactions using a defined typology and characterization approach. Drawing on results from a major international research study applied to the SDGs on health, energy and the ocean, it analyses how interactions depend on key factors such as geographical context, resource endowments, time horizon and governance. The paper discusses the future potential, barriers and opportunities for applying the approach in scientific research, in policy making and in bridging the two through a global SDG Interactions Knowledge Platform as a key mechanism for assembling, systematizing and aggregating knowledge on interactions.

Using linked administrative and census data for migration research.

Migration is a core component of population change and is both a symptom and a cause of major economic and social phenomena. However, data limitations mean that gaps remain in our understanding of the patterns and processes of mobility. This is particularly the case for internal migration, which remains under-researched, despite being quantitatively much more significant than international migration. Using the Scottish Longitudinal Study, this paper evaluates the potential value of General Practitioner administrative health data from the National Health Service that can be linked into census-based longitudinal studies for advancing migration research. Issues relating to data quality are considered and, using the illustrative example of internal migration by country of birth, an argument is developed contending that such approaches can offer novel ways of comprehending internal migration, by shedding additional light on the nature of both movers and the moves that they make.

Limited emission reductions from fuel subsidy removal except in energy-exporting regions.

Hopes are high that removing fossil fuel subsidies could help to mitigate climate change by discouraging inefficient energy consumption and levelling the playing field for renewable energy. In September 2016, the G20 countries re-affirmed their 2009 commitment (at the G20 Leaders' Summit) to phase out fossil fuel subsidies and many national governments are using today's low oil prices as an opportunity to do so. In practical terms, this means abandoning policies that decrease the price of fossil fuels and electricity generated from fossil fuels to below normal market prices. However, whether the removal of subsidies, even if implemented worldwide, would have a large impact on climate change mitigation has not been systematically explored. Here we show that removing fossil fuel subsidies would have an unexpectedly small impact on global energy demand and carbon dioxide emissions and would not increase renewable energy use by 2030. Subsidy removal would reduce the carbon price necessary to stabilize greenhouse gas concentration at 550 parts per million by only 2-12 per cent under low oil prices. Removing subsidies in most regions would deliver smaller emission reductions than the Paris Agreement (2015) climate pledges and in some regions global subsidy removal may actually lead to an increase in emissions, owing to either coal replacing subsidized oil and natural gas or natural-gas use shifting from subsidizing, energy-exporting regions to non-subsidizing, importing regions. Our results show that subsidy removal would result in the largest CO2 emission reductions in high-income oil- and gas-exporting regions, where the reductions would exceed the climate pledges of these regions and where subsidy removal would affect fewer people living below the poverty line than in lower-income regions.

Long-term Follow-up of Kidney Transplant Recipients in the Spare-the-Nephron-Trial.

In the Spare-the-Nephron (STN) Study, kidney transplant recipients randomized about 115 days posttransplant to convert from CNI (calcineurin inhibitor)/MMF to sirolimus (SRL)/MMF had a significantly greater improvement in measured GFR (mGFR) at 12 months compared with those kept on CNI/MMF. The difference at 24 months was not statistically significant. From 14 top enrolling centers, 128 of 175 patients identified with a functioning graft at 2 years consented to enroll in an observational, noninterventional extension study to collect retrospectively and prospectively annual follow-up data for the interval since baseline (completion of the parent STN study at 24 months posttransplant). Overall, 11 patients died, including 5 (7.6%) in the SRL/MMF group and 6 (9.7%) in the CNI/MMF group. Twenty-two grafts have been lost including 10 (15.2%) in the SRL/MMF arm and 12 (19.4%) in the CNI/MMF arm. Death and chronic rejection were the most common causes of graft loss in both arms. There were modestly more cardiovascular events in the MMF/SRL group. Estimated creatinine clearance (Cockcroft-Gault) from baseline out to 6 additional years (8 years posttransplant, ITT analysis, SRL/MMF, n = 34; CNI/MMF, n = 26) was 63.2 ± 28.5 mL/min/1.73 m in the SRL/MMF group and 59.2 ± 27.2 mL/min/1.73 m in the CNI/MMF group and was not statistically significant, but there is a clinically meaningful trend for improved long-term renal function in the SRL/MMF group compared with the CNI/MMF group. The long-term decision for immunosuppression needs to be carefully individualized.

Probabilistic cost estimates for climate change mitigation.

For more than a decade, the target of keeping global warming below 2 °C has been a key focus of the international climate debate. In response, the scientific community has published a number of scenario studies that estimate the costs of achieving such a target. Producing these estimates remains a challenge, particularly because of relatively well known, but poorly quantified, uncertainties, and owing to limited integration of scientific knowledge across disciplines. The integrated assessment community, on the one hand, has extensively assessed the influence of technological and socio-economic uncertainties on low-carbon scenarios and associated costs. The climate modelling community, on the other hand, has spent years improving its understanding of the geophysical response of the Earth system to emissions of greenhouse gases. This geophysical response remains a key uncertainty in the cost of mitigation scenarios but has been integrated with assessments of other uncertainties in only a rudimentary manner, that is, for equilibrium conditions. Here we bridge this gap between the two research communities by generating distributions of the costs associated with limiting transient global temperature increase to below specific values, taking into account uncertainties in four factors: geophysical, technological, social and political. We find that political choices that delay mitigation have the largest effect on the cost-risk distribution, followed by geophysical uncertainties, social factors influencing future energy demand and, lastly, technological uncertainties surrounding the availability of greenhouse gas mitigation options. Our information on temperature risk and mitigation costs provides crucial information for policy-making, because it clarifies the relative importance of mitigation costs, energy demand and the timing of global action in reducing the risk of exceeding a global temperature increase of 2 °C, or other limits such as 3 °C or 1.5 °C, across a wide range of scenarios.

Detection, treatment, and prevention of Clostridium difficile infection.

Clostridium difficile is a gram-positive anaerobic bacillus responsible for approximately 1 of 5 cases of antibiotic-associated diarrhea. C difficile infection (CDI) is defined by at least 3 unformed stools in a 24-hour period and stool, endoscopic, or histopathologic test results that indicate the presence of this bacteria. The history of CDI research can be divided into early (before 2000) and modern eras (after 2000). C difficile was first described in 1935, and the characteristics and causes of CDI as well as therapies were identified during the early era of research. During the modern era, CDI has become a more common, aggressive nosocomial infection. Our understanding of the epidemiology, diagnosis, treatment, and prevention of CDI has increased at a rapid pace. We review features of CDI diagnosis, treatment, and prevention.

Trends in A8 migration to the UK during the recession.

A substantial proportion of contemporary migration flows to the UK are made by nationals from countries which have recently joined the EU. The nature of A8 migration during the recession is examined in this paper, mainly using data from the Worker Registration Scheme. The recession has seen a decline in new A8 migrants entering the UK labour market, but the decline has been sectorally uneven, with demand for migrant labour being most persistent in the agricultural sector, raising questions about why this part of the UK economy is so different.

Update of the past year: a review from IDSA 2011.

The Infectious Diseases Society of America Annual Meeting serves as a time of expert review of the year's most important innovations. Important new information on HIV infection incidence was discussed. The remarkable efficacy of "treatment as prevention" in the HIV Prevention Trials Network (HPTN) 052 study and the proper place of oral preexposure prophylaxis were among the important prevention topics. Key engagement-in-care research indicates that only 19% of HIV-infected persons in the United States have a plasma HIV RNA level below the limits of assay detection. Among antiretroviral topics, the role of the newly approved nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine was discussed. Primary care topics for the HIV-infected population included treatment of triglyceride level elevations and bone health. The newly published data on the proper timing of antiretroviral therapy initiation after starting tuberculosis treatment were highlighted. Finally, exciting advances in the treatment of hepatitis C virus (HCV) infection necessitate that practitioners understand the complexities of treating HIV/HCV coinfections.

Dosing considerations for capecitabine-irinotecan regimens in the treatment of metastatic and/or locally advanced colorectal cancer.

Capecitabine (Xeloda), Roche Laboratories Inc., Nutley, NJ) is an orally administered fluoropyrimidine carbamate that serves as a prodrug of 5-fluorouracil (5-FU), an integral component of chemotherapy (CT) regimens for metastatic colorectal cancer (mCRC). As the drug is orally administered, capecitabine permits greater convenience and flexibility in dosing by eliminating the need for continuous infusion and its potential complications. In phase 3 trials, capecitabine has been used as an alternative to 5-FU, both as a monotherapy and in combination with agents such as oxaliplatin (as XELOX), with good efficacy and tolerability. Combination therapy with capecitabine and irinotecan (XELIRI), however, has produced more variable results, with some dose combinations and schedules resulting in excessive and/or unexplained treatment-related toxicity. Recent initiatives using lower doses of capecitabine and irinotecan, as well as alternative dosing schedules, have resulted in more favorable outcomes (efficacy and tolerability), even in combination with targeted-agents such as bevacizumab. Dose reduction in elderly populations and in those with moderate renal impairment also appears to be important for minimizing toxicity with XELIRI regimens. Although additional phase 3 studies are needed, XELIRI may be an effective base CT regimen, allowing a greater number of treatment options for tumor control in patients with mCRC.

Patient charting. Turning a routine activity into an opportunity for injury prevention.

Injuries can be predicted and prevented. The first step in doing so is gathering data about who was injured and how. Because injury data is based on documentation in patients' medical charts, physicians play an important role in injury prevention. This article describes how to document all types of injuries, including those that are self-inflicted or caused by abuse.

A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer.

PURPOSE: Panitumumab, a fully human antibody targeting the epidermal growth factor receptor, is active in patients with metastatic colorectal cancer (mCRC). This trial evaluated panitumumab added to bevacizumab and chemotherapy (oxaliplatin- and irinotecan-based) as first-line treatment for mCRC. PATIENTS AND METHODS: Patients were randomly assigned within each chemotherapy cohort to bevacizumab and chemotherapy with or without panitumumab 6 mg/kg every 2 weeks. The primary end point was progression-free survival (PFS) within the oxaliplatin cohort. Tumor assessments were performed every 12 weeks and reviewed centrally. RESULTS: A total of 823 and 230 patients were randomly assigned to the oxaliplatin and irinotecan cohorts, respectively. Panitumumab was discontinued after a planned interim analysis of 812 oxaliplatin patients showed worse efficacy in the panitumumab arm. In the final analysis, median PFS was 10.0 and 11.4 months for the panitumumab and control arms, respectively (HR, 1.27; 95% CI, 1.06 to 1.52); median survival was 19.4 months and 24.5 months for the panitumumab and control arms, respectively. Grade 3/4 adverse events in the oxaliplatin cohort (panitumumab v control) included skin toxicity (36% v 1%), diarrhea (24% v 13%), infections (19% v 10%), and pulmonary embolism (6% v 4%). Increased toxicity without evidence of improved efficacy was observed in the panitumumab arm of the irinotecan cohort. KRAS analyses showed adverse outcomes for the panitumumab arm in both wild-type and mutant groups. CONCLUSION: The addition of panitumumab to bevacizumab and oxaliplatin- or irinotecan-based chemotherapy results in increased toxicity and decreased PFS. These combinations are not recommended for the treatment of mCRC in clinical practice.

First-line gefitinib in patients with advanced non-small-cell lung cancer harboring somatic EGFR mutations.

PURPOSE: Somatic mutations in the epidermal growth factor receptor (EGFR) correlate with increased response in patients with non-small-cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). The multicenter iTARGET trial prospectively examined first-line gefitinib in advanced NSCLC patients harboring EGFR mutations and explored the significance of EGFR mutation subtypes and TKI resistance mechanisms. PATIENTS AND METHODS: Chemotherapy-naïve patients with advanced NSCLC with >or= 1 clinical characteristic associated with EGFR mutations underwent direct DNA sequencing of tumor tissue EGFR exons 18 to 21. Patients found to harbor any EGFR mutation were treated with gefitinib 250 mg/d until progression or unacceptable toxicity. The primary outcome was response rate. RESULTS: Ninety-eight patients underwent EGFR screening and mutations were detected in 34 (35%). EGFR mutations were primarily exon 19 deletions (53%) and L858R (26%) though 21% of mutation-positive cases had less common subtypes including exon 20 insertions, T790M/L858R, G719A, and L861Q. Thirty-one patients received gefitinib. The response rate was 55% (95% CI, 33 to 70) and median progression-free survival was 9.2 months (95% CI, 6.2 to 11.8). Therapy was well tolerated; 13% of patients had grade 3 toxicities including one grade 3 pneumonitis. Two patients with classic activating mutations exhibited de novo gefitinib resistance and had concurrent genetic anomalies usually associated with acquired TKI resistance, specifically the T790M EGFR mutation and MET amplification. CONCLUSION: First-line therapy with gefitinib administered in a genotype-directed fashion to patients with advanced NSCLC harboring EGFR mutations results in very favorable clinical outcomes with good tolerance. This strategy should be compared with combination chemotherapy, the current standard of care.