Ru-Catalyzed, cis-Selective Living Ring-Opening Metathesis Polymerization of Various Monomers, Including a Dendronized Macromonomer, and Implications to Enhanced Shear Stability

An unsaturated polymer’s cis/trans-olefin content has a significant influence on its properties. For polymers obtained by ring-opening metathesis polymerization (ROMP), the cis/trans-olefin content can be tuned by using specific catalysts. However, cis-selective ROMP has suffered from narrow monomer scope and lack of control over the polymerization (giving polymers with broad molecular weight distributions and prohibiting the synthesis of block copolymers). Herein, we report the versatile cis-selective controlled living ROMP of various endo-tricyclo[4.2.2.0^(2,5)]deca-3,9-diene and various norbornene derivatives using a fast-initiating dithiolate-chelated Ru catalyst. Polymers with cis-olefin content as high as 99% could be obtained with high molecular weight (up to M_n of 105.1 kDa) and narrow dispersity (<1.4). The living nature of the polymerization was also exploited to prepare block copolymers with high cis-olefin content for the first time. Furthermore, owing to the successful control over the stereochemistry and narrow dispersity, we could compare cis- and trans-rich polynorbornene and found the former to have enhanced resistance to shear degradation

A Case of Santorinicele without Pancreas Divisum: Diagnosis with Multi-detector Row Computed Tomography

A santorinicele is defined as a focal cystic dilatation of the terminal portion of the dorsal pancreatic duct at the minor papilla. Most cases reported previously were associated with pancreas divisum and a santorinicele without pancreas divisum is known to be rare. We recently experienced a typical case of a santorinicele without pancreas divisum in a 67-yr-old woman with abdominal pain and hematochezia, subsequently proven to be the result of an ischemic colitis. The santorinicele was diagnosed incidentally with multi-detector row computed tomography using a minimum intensity projection technique, which clearly showed a cystic dilatation of the terminal portion of the dorsal pancreatic duct and a communication between the ventral and dorsal pancreatic ducts. This finding was also confirmed by a magnetic resonance cholangiopancreatography

A Tale of Four “Carp”: Invasion Potential and Ecological Niche Modeling

. We assessed the geographic potential of four Eurasian cyprinid fishes (common carp, tench, grass carp, black carp) as invaders in North America via ecological niche modeling (ENM). These “carp” represent four stages of invasion of the continent (a long-established invader with a wide distribution, a long-established invader with a limited distribution, a spreading invader whose distribution is expanding, and a newly introduced potential invader that is not yet established), and as such illustrate the progressive reduction of distributional disequilibrium over the history of species' invasions.We used ENM to estimate the potential distributional area for each species in North America using models based on native range distribution data. Environmental data layers for native and introduced ranges were imported from state, national, and international climate and environmental databases. Models were evaluated using independent validation data on native and invaded areas. We calculated omission error for the independent validation data for each species: all native range tests were highly successful (all omission values <7%); invaded-range predictions were predictive for common and grass carp (omission values 8.8 and 19.8%, respectively). Model omission was high for introduced tench populations (54.7%), but the model correctly identified some areas where the species has been successful; distributional predictions for black carp show that large portions of eastern North America are at risk.ENMs predicted potential ranges of carp species accurately even in regions where the species have not been present until recently. ENM can forecast species' potential geographic ranges with reasonable precision and within the short screening time required by proposed U.S. invasive species legislation

Implementation and evaluation of a multisite drug usage evaluation program across Australian hospitals - a quality improvement initiative

Background: With the use of medicines being a broad and extensive part of health management, mechanisms to ensure quality use of medicines are essential. Drug usage evaluation (DUE) is an evidence-based quality improvement methodology, designed to improve the quality, safety and cost-effectiveness of drug use. The purpose of this paper is to describe a national DUE methodology used to improve health care delivery across the continuum through multi-faceted intervention involving audit and feedback, academic detailing and system change, and a qualitative assessment of the methodology, as illustrated by the Acute Postoperative Pain Management (APOP) project. Methods. An established methodology, consisting of a baseline audit of inpatient medical records, structured patient interviews and general practitioner surveys, followed by an educational intervention and follow-up audit, is used. Australian hospitals, including private, public, metropolitan and regional, are invited to participate on a voluntary basis. De-identified data collected by hospitals are collated and evaluated nationally to provide descriptive comparative analyses. Hospitals benchmark their practices against state and national results to facilitate change. The educational intervention consists of academic detailing, group education, audit and feedback, point-of-prescribing prompts and system changes. A repeat data collection is undertaken to assess changes in practice. An online qualitative survey was undertaken to evaluate the APOP program. Qualitative assessment of hospitals' perceptions of the effectiveness of the overall DUE methodology and changes in procedure/prescribing/policy/clinical practice which resulted from participation were elicited. Results: 62 hospitals participated in the APOP project. Among 23 respondents to the evaluation survey, 18 (78%) reported improvements in the documentation of pain scores at their hospital. 15 (65%) strongly agreed or agreed that participation in APOP directly resulted in increased prescribing of multimodal analgesia for pain relief in postoperative patients. Conclusions: This national DUE program has facilitated the engagement and participation of a number of acute health care facilities to address issues relating to quality use of medicine. This approach has been perceived to be effective in helping them achieve improvements in patient care

The Accumulation of Organic Carbon in Mineral Soils by Afforestation of Abandoned Farmland

The afforestation of abandoned farmland significantly influences soil organic carbon (OC). However, the dynamics between OC inputs after afforestation and the original OC are not well understood. To learn more about soil OC dynamics after afforestation of farmland, we measured the soil OC content in paired forest and farmland plots in Shaanxi Province, China. The forest plots had been established on farmland 18, 24, 48, 100, and 200 yr previously. The natural 13C abundance of soil organic matter was also analyzed to distinguish between crop- and forest-derived C in the afforested soils. We observed a nonlinear accumulation of total OC in the 0–80 cm depth of the mineral soil across time. Total soil OC accumulated more rapidly under forest stands aged 18 to 48 yr than under forest stands aged 100 or 200 yrs. The rate of OC accumulation was also greater in the 0–10 cm depth than in the 10–80 cm depth. Forest-derived OC in afforested soils also accumulated nonlinearly across time, with the greatest increase in the 0–20 cm depth. Forest-derived OC in afforest soils accounted for 52–86% of the total OC in the 0–10 cm depth, 36–61% of the total OC in the 10–20 cm depth, and 11–50% of the total OC in the 20–80 cm depth. Crop-derived OC concentrations in the 0–20 cm depth decreased slightly after afforestation, but there was no change in crop-derived OC concentrations in the 20–80 cm depth. The results of our study support the claim that afforestation of farmland can sequester atmospheric CO2 by increasing soil OC stocks. Changes in the OC stocks of mineral soils after afforestation appear to be influenced mainly by the input of forest-derived C rather than by the loss of original OC

In vivo bioimaging with tissue-specific transcription factor activated luciferase reporters.

The application of transcription factor activated luciferase reporter cassettes in vitro is widespread but potential for in vivo application has not yet been realized. Bioluminescence imaging enables non-invasive tracking of gene expression in transfected tissues of living rodents. However the mature immune response limits luciferase expression when delivered in adulthood. We present a novel approach of tissue-targeted delivery of transcription factor activated luciferase reporter lentiviruses to neonatal rodents as an alternative to the existing technology of generating germline transgenic light producing rodents. At this age, neonates acquire immune tolerance to the conditionally responsive luciferase reporter. This simple and transferrable procedure permits surrogate quantitation of transcription factor activity over the lifetime of the animal. We show principal efficacy by temporally quantifying NFκB activity in the brain, liver and lungs of somatotransgenic reporter mice subjected to lipopolysaccharide (LPS)-induced inflammation. This response is ablated in Tlr4(-/-) mice or when co-administered with the anti-inflammatory glucocorticoid analogue dexamethasone. Furthermore, we show the malleability of this technology by quantifying NFκB-mediated luciferase expression in outbred rats. Finally, we use somatotransgenic bioimaging to longitudinally quantify LPS- and ActivinA-induced upregulation of liver specific glucocorticoid receptor and Smad2/3 reporter constructs in somatotransgenic mice, respectively

Defining Plasmodium falciparum Treatment in South West Asia: A Randomized Trial Comparing Artesunate or Primaquine Combined with Chloroquine or SP

INTRODUCTION: Antimalarial resistance has led to a global policy of artemisinin-based combination therapy. Despite growing resistance chloroquine (CQ) remained until recently the official first-line treatment for falciparum malaria in Pakistan, with sulfadoxine-pyrimethamine (SP) second-line. Co-treatment with the gametocytocidal primaquine (PQ) is recommended for transmission control in South Asia. The relative effect of artesunate (AS) or primaquine, as partner drugs, on clinical outcomes and gametocyte carriage in this setting were unknown. METHODS: A single-blinded, randomized trial among Afghan refugees in Pakistan compared six treatment arms: CQ; CQ+(single-dose)PQ; CQ+(3 d)AS; SP; SP+(single-dose)PQ, and SP+(3 d)AS. The objectives were to compare treatment failure rates and effect on gametocyte carriage, of CQ or SP monotherapy against the respective combinations (PQ or AS). Outcomes included trophozoite and gametocyte clearance (read by light microscopy), and clinical and parasitological failure. FINDINGS: A total of 308 (87%) patients completed the trial. Failure rates by day 28 were: CQ 55/68 (81%); CQ+AS 19/67 (28%), SP 4/41 (9.8%), SP+AS 1/41 (2.4%). The addition of PQ to CQ or SP did not affect failure rates (CQ+PQ 49/67 (73%) failed; SP+PQ 5/33 (16%) failed). AS was superior to PQ at clearing gametocytes; gametocytes were seen on d7 in 85% of CQ, 40% of CQ+PQ, 21% of CQ+AS, 91% of SP, 76% of SP+PQ and 23% of SP+AS treated patients. PQ was more effective at clearing older gametocyte infections whereas AS was more effective at preventing emergence of mature gametocytes, except in cases that recrudesced. CONCLUSIONS: CQ is no longer appropriate by itself or in combination. These findings influenced the replacement of CQ with SP+AS for first-line treatment of uncomplicated falciparum malaria in the WHO Eastern Mediterranean Region. The threat of SP resistance remains as SP monotherapy is still common. Three day AS was superior to single-dose PQ for reducing gametocyte carriage. TRIAL REGISTRATION: ClinicalTrials.gov NCT00959517

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts