Epi-illumination SPIM for volumetric imaging with high spatial-temporal resolution.

We designed an epi-illumination SPIM system that uses a single objective and has a sample interface identical to that of an inverted fluorescence microscope with no additional reflection elements. It achieves subcellular resolution and single-molecule sensitivity, and is compatible with common biological sample holders, including multi-well plates. We demonstrated multicolor fast volumetric imaging, single-molecule localization microscopy, parallel imaging of 16 cell lines and parallel recording of cellular responses to perturbations

Clinical and microbiological outcomes of ceftazidime-avibactam treatment in adults with Gram-negative bacteremia: A subset analysis from the phase 3 clinical trial program

INTRODUCTION: This exploratory analysis assessed efficacy and safety outcomes in patients with Gram-negative bacteremia treated with ceftazidime-avibactam or comparator across five phase 3, randomized, controlled, multi-center trials in adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI)/pyelonephritis, hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). METHODS: In each trial, RECLAIM and RECLAIM 3 (cIAI; NCT01499290/NCT01726023), REPRISE (cIAI/cUTI; NCT01644643), RECAPTURE (cUTI; NCT01595438/NCT01599806), and REPROVE (HAP/VAP; NCT01808092), patients were randomized 1:1 to intravenous ceftazidime-avibactam (plus metronidazole for those with cIAI) or comparators (carbapenems in \u3e 97% patients) for 5-21 days. Efficacy assessments included clinical and microbiological responses at the test-of-cure visit in the pooled Gram-negative extended microbiologically evaluable (GNeME) population (bacteremia subset). Safety outcomes were summarized for patients with positive bacterial blood culture(s) at baseline who received ≥ 1 dose of study treatment. RESULTS: The overall safety population included 4050 patients (ceftazidime-avibactam, n = 2024; comparator, n = 2026). The GNeME population (bacteremia subset) comprised 101 patients (ceftazidime-avibactam, n = 54; comparator, n = 47). Clinical cure rates (all indications combined) were 47/54 (87.0%) for ceftazidime-avibactam and 39/47 (83.0%) for comparators; favorable microbiological response rates were 43/54 (79.6%) and 32/47 (68.1%), respectively. Clinical and microbiological responses in the bacteremia subset were generally similar to those in the overall set. The pattern of adverse events in patients with bacteremia was similar between treatment groups and was consistent with the known safety profile of ceftazidime-avibactam. CONCLUSION: This analysis provides supportive evidence of the efficacy and safety of ceftazidime-avibactam in patients with Gram-negative bacteremia associated with cIAI, cUTI/pyelonephritis, or HAP/VAP

FAPRI 2000 U.S. Agricultural Outlook

Crop Production/Industries, Livestock Production/Industries,

FAPRI 2001 U.S. and World Agricultural Outlook

Crop Production/Industries, Livestock Production/Industries,

FAPRI 2000 World Agricultural Outlook

The Food and Agricultural Policy Research Institute (FAPRI) prepares a preliminary agricultural outlook on world agricultural production, consumption, and trade every fall. This is followed by an outside review, re-evaluation of projections, and completion of the final baseline in January. The FAPRI 2000 World Agricultural Outlook presents these final projections for world agricultural markets. A companion volume, the FAPRI 2000 U.S. Agricultural Outlook, presents the U.S. component of the baseline. FAPRI projections assume average weather patterns worldwide, existing policy, and policy commitments under current trade agreements. FAPRI projections do not include conjectures on potential policy changes, such as those resulting from the likely eastward enlargement of the European Union (EU). The baseline predicts recovery of world agricultural production, consumption, and trade, but with remaining price weakness for crops. Stock-to-use ratios in world crop markets remain high despite the strong recovery of Asian and Latin American economies. Above-average yields kept world production high relative to demand in 1999. In contrast, pork and beef prices are increasing significantly above their 1999 level. The physical volume of U.S. agricultural exports is projected to reverse the downward trend of fiscal year (FY) 1999, whereas the value of agricultural exports continue to decline for one more year before recovering because of low crop prices in 2000/01. World crop trade is projected to increase by 55 million metric tons (mmt) in the coming decade, with the United States capturing 49 percent of the expanded market, but still unable to increase its market share by a large percentage. Following this expansion of the market, grain prices increase by 35 percent in the projection period, but still stay well below the peak of 1995/96. The increase in world crop trade reflects the increasing specialization occurring in world agriculture. Increased market access and land scarcity in many Asian economies induce them to import grains and oilseeds to meet their feed demand. Developing Asia remains the fastest growing market for corn in the next decade. With implementation of Agenda 2000 reforms, the EU will reduce its wheat domestic price relative to the world price and will export wheat without subsidies after 2004, constraining gains in market shares for the United States. EU barley exports will expand significantly in the coming years but are likely to be constrained by General Agreement on Tariffs and Trade (GATT) commitments on export subsidies after 2004. World meat trade will increase by 31 percent over the next decade. The United States has become a competitive producer and exporter of meat products. In the coming decade, the United States will experience the largest meat export growth rates among major exporters of beef, pork, and broilers. U.S. exporters capture more than 70 percent of the growth in trade, increasing their share of the combined meat markets from 23 percent in 1999 to 37 percent in 2009. Meat imports are recovering and expanding rapidly in Japan, South Korea, and Taiwan. In Japan, the share of imports in consumption increases from 38 percent in the 1990s to 49 percent at the end of the next decade. Taiwan meat imports will triple from 1990-1999 levels to 2000-2009 levels, driven by imports of beef, non muscle pork products, and the opening of the poultry market. Recovery of Asian food demand will prompt dairy prices to grow by about 1 percent per year over the next decade. Total milk production is projected to increase, with particularly strong growth in the United States, Mexico, Argentina, and Brazil. Most of the growth occurs through yield increases. Per capita cheese consumption is expected to grow by 1 to 2 percent a year in most countries.Crop Production/Industries, Livestock Production/Industries,

A large proportion of asymptomatic Plasmodium infections with low and sub-microscopic parasite densities in the low transmission setting of Temotu Province, Solomon Islands: challenges for malaria diagnostics in an elimination setting

Background: Many countries are scaling up malaria interventions towards elimination. This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities. Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination. A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting

FAPRI 2002 World Agricultural Outlook

Crop Production/Industries, Livestock Production/Industries,

FAPRI 1999 U.S. Agricultural Outlook

Crop Production/Industries, Livestock Production/Industries,

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors