Performance of cages as large animal-exclusion devices in the deep sea

Sedimentary, deep-sea communities include megafaunal animals (e.g., sea cucumbers, brittle stars, crabs) and demersal fishes, collectively termed the large, motile epifauna (LME). Individuals of the LME are common, and their biomass approximates that of the macrofauna. Based on analogies with shallow-water animals, they are likely to be sources of mortality for the infauna and to create spatial and temporal heterogeneity in the community. Given present theories of deep-sea community organization, such effects could be important. Unfortunately, this hypothesis has not been tested because of the difficulty of conducting experiments in the deep sea and because tools for manipulating the LME have not been developed. We studied the suitability of exclusion cages for this purpose at 780 m depth in San Diego Trough. We placed 16 cages of two mesh sizes for 4.5 months over regions of the seafloor that appeared free of LME. Time-lapse photographs of a cage and a control plot coupled with observations of all cages at the end of the experiment indicated that small (1.27-cm × 1.27-cm square)-mesh cages were effective at excluding LME. Further, the cages were essentially free of cage artifacts that have been reported in shallow-water studies. Large, mobile and disruptive animals (e.g., fishes, crabs) did not establish long-term residence adjacent to or on the cages. Bio-fouling slightly reduced the open surface area of the cage mesh, potentially reducing flow through the cage, but the composition of surface sediments in terms of organic C and N, phytoplankton-derived pigments, and grain size was indistinguishable between cages and control areas. Activities of excess 234Th were significantly higher (average = 37%) inside of small-mesh cages, which might suggest enhanced particulate deposition inside cages. However, this measurement was an artifact of experimental manipulation. Particles that accumulated on the cage during the experiment were dislodged and settled to the seafloor when the cage was opened just prior to sampling. These particles would have been highly enriched in 234Th, and their inclusion in core samples artificially inflated the calculated sediment accumulation rates inside cages. Therefore, the cages performed well; they excluded the targeted LME without causing artifacts and thus should be useful for experimental study of a group of animals that may have substantial impact on the structure and organization of deep-sea communities

Activation of an Endogenous Retrovirus-Associated Long Non-Coding RNA in Human Adenocarcinoma

Background Long non-coding RNAs (lncRNAs) are emerging as molecules that significantly impact many cellular processes and have been associated with almost every human cancer. Compared to protein-coding genes, lncRNA genes are often associated with transposable elements, particularly with endogenous retroviral elements (ERVs). ERVs can have potentially deleterious effects on genome structure and function, so these elements are typically silenced in normal somatic tissues, albeit with varying efficiency. The aberrant regulation of ERVs associated with lncRNAs (ERV-lncRNAs), coupled with the diverse range of lncRNA functions, creates significant potential for ERV-lncRNAs to impact cancer biology. Methods We used RNA-seq analysis to identify and profile the expression of a novel lncRNA in six large cohorts, including over 7,500 samples from The Cancer Genome Atlas (TCGA). Results We identified the tumor-specific expression of a novel lncRNA that we have named Endogenous retroViral-associated ADenocarcinoma RNA or ‘EVADR’, by analyzing RNA-seq data derived from colorectal tumors and matched normal control tissues. Subsequent analysis of TCGA RNA-seq data revealed the striking association of EVADR with adenocarcinomas, which are tumors of glandular origin. Moderate to high levels of EVADR were detected in 25 to 53% of colon, rectal, lung, pancreas and stomach adenocarcinomas (mean = 30 to 144 FPKM), and EVADR expression correlated with decreased patient survival (Cox regression; hazard ratio = 1.47, 95% confidence interval = 1.06 to 2.04, P = 0.02). In tumor sites of non-glandular origin, EVADR expression was detectable at only very low levels and in less than 10% of patients. For EVADR, a MER48 ERV element provides an active promoter to drive its transcription. Genome-wide, MER48 insertions are associated with nine lncRNAs, but none of the MER48-associated lncRNAs other than EVADR were consistently expressed in adenocarcinomas, demonstrating the specific activation of EVADR. The sequence and structure of the EVADR locus is highly conserved among Old World monkeys and apes but not New World monkeys or prosimians, where the MER48 insertion is absent. Conservation of the EVADR locus suggests a functional role for this novel lncRNA in humans and our closest primate relatives. Conclusions Our results describe the specific activation of a highly conserved ERV-lncRNA in numerous cancers of glandular origin, a finding with diagnostic, prognostic and therapeutic implications

Incomplete Polyp Resection During Colonoscopy—Results of the Complete Adenoma Resection (CARE) Study

Although the adenoma detection rate is used as a measure of colonoscopy quality, there are limited data on the quality of endoscopic resection of detected adenomas. We determined the rate of incompletely resected neoplastic polyps in clinical practice.We performed a prospective study on 1427 patients who underwent colonoscopy at 2 medical centers and had at least 1 nonpedunculated polyp (5-20 mm). After polyp removal was considered complete macroscopically, biopsies were obtained from the resection margin. The main outcome was the percentage of incompletely resected neoplastic polyps (incomplete resection rate [IRR]) determined by the presence of neoplastic tissue in post-polypectomy biopsies. Associations between IRR and polyp size, morphology, histology, and endoscopist were assessed by regression analysis. Of 346 neoplastic polyps (269 patients; 84.0% men; mean age, 63.4 years) removed by 11 gastroenterologists, 10.1% were incompletely resected. IRR increased with polyp size and was significantly higher for large (10-20 mm) than small (5-9 mm) neoplastic polyps (17.3% vs 6.8%; relative risk = 2.1), and for sessile serrated adenomas/polyps than for conventional adenomas (31.0% vs 7.2%; relative risk = 3.7). The IRR for endoscopists with at least 20 polypectomies ranged from 6.5% to 22.7%; there was a 3.4-fold difference between the highest and lowest IRR after adjusting for size and sessile serrated histology. Neoplastic polyps are often incompletely resected, and the rate of incomplete resection varies broadly among endoscopists. Incomplete resection might contribute to the development of colon cancers after colonoscopy (interval cancers). Efforts are needed to ensure complete resection, especially of larger lesions

Secondary organic aerosol production from diesel vehicle exhaust: impact of aftertreatment, fuel chemistry and driving cycle

Environmental chamber ("smog chamber") experiments were conducted to investigate secondary organic aerosol (SOA) production from dilute emissions from two medium-duty diesel vehicles (MDDVs) and three heavy-duty diesel vehicles (HDDVs) under urban-like conditions. Some of the vehicles were equipped with emission control aftertreatment devices, including diesel particulate filters (DPFs), selective catalytic reduction (SCR) and diesel oxidation catalysts (DOCs). Experiments were also performed with different fuels (100% biodiesel and low-, medium- or high-aromatic ultralow sulfur diesel) and driving cycles (Unified Cycle,~Urban Dynamometer Driving Schedule, and creep + idle). During normal operation, vehicles with a catalyzed DPF emitted very little primary particulate matter (PM). Furthermore, photooxidation of dilute emissions from these vehicles produced essentially no SOA (below detection limit). However, significant primary PM emissions and SOA production were measured during active DPF regeneration experiments. Nevertheless, under reasonable assumptions about DPF regeneration frequency, the contribution of regeneration emissions to the total vehicle emissions is negligible, reducing PM trapping efficiency by less than 2%. Therefore, catalyzed DPFs appear to be very effective in reducing both primary PM emissions and SOA production from diesel vehicles. For both MDDVs and HDDVs without aftertreatment substantial SOA formed in the smog chamber – with the emissions from some vehicles generating twice as much SOA as primary organic aerosol after 3 h of oxidation at typical urban VOC / NO_x ratios (3 : 1). Comprehensive organic gas speciation was performed on these emissions, but less than half of the measured SOA could be explained by traditional (speciated) SOA precursors. The remainder presumably originates from the large fraction (~30%) of the nonmethane organic gas emissions that could not be speciated using traditional one-dimensional gas chromatography. The unspeciated organics – likely comprising less volatile species such as intermediate volatility organic compounds – appear to be important SOA precursors; we estimate that the effective SOA yield (defined as the ratio of SOA mass to reacted precursor mass) was 9 ± 6% if both speciated SOA precursors and unspeciated organics are included in the analysis. SOA production from creep + idle operation was 3–4 times larger than SOA production from the same vehicle operated over the Urban Dynamometer Driving Schedule (UDDS). Fuel properties had little or no effect on primary PM emissions or SOA formation

A regioselectively 1, 1',3 ,3'-tetrazincated ferrocene complex displaying core and peripheral reactivity

Regioselective 1,1′,3,3′-tetrazincation [C-H to C-Zn(tBu)] of ferrocene has been achieved by reaction of a fourfold excess of di-t-butylzinc (tBu2Zn) with sodium 2,2,6,6-tetramethylpiperidide (NaTMP) in hexane solution manifested in the trimetallic iron-sodium-zinc complex [Na4(TMP)4Zn4(tBu)4{(C5H3)2Fe}], 1. X-ray crystallographic studies supported by DFT modelling reveal the structure to be an open inverse crown in which two [Na(TMP)Zn(tBu)Na(TMP)Zn(tBu)]2+ cationic units surround a {(C5H3)2Fe}4- tetraanion. Detailed C6D6 NMR studies have assigned the plethora of 1H and 13C chemical shifts of this complex. It exists in a major form in which capping and bridging TMP groups interchange, as well as a minor form that appears to be an intermediate in this complicated exchange phenomenon. Investigation of 1 has uncovered two distinct reactivities. Two of its peripheral t-butyl carbanions formally deprotonate toluene at the lateral methyl group to generate benzyl ligands that replace these carbanions in [Na4(TMP)4Zn4(tBu)2(CH2Ph)2{(C5H3)2Fe}], 2, which retains its tetrazincated ferrocenyl core. Benzyl-Na π-arene interactions are a notable feature of 2. In contrast, reaction with pyridine affords the crystalline product {[Na·4py][Zn(py∗)2(tBu)·py]}∞, 3, where py is neutral pyridine (C5H5N) and py∗ is the anion (4-C5H4N), a rare example of pyridine deprotonated/metallated at the 4-position. This ferrocene-free complex appears to be a product of core reactivity in that the core-positioned ferrocenyl anions of 1, in company with TMP anions, have formally deprotonated the heterocycle

Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

<p>Background: Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.</p> <p>Methods: This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.</p> <p>Results: There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.</p> <p>Conclusions: Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.</p&gt

The ELT-2 GATA-factor and the global regulation of transcription in the C. elegans intestine

AbstractA SAGE library was prepared from hand-dissected intestines from adult Caenorhabditis elegans, allowing the identification of >4000 intestinally-expressed genes; this gene inventory provides fundamental information for understanding intestine function, structure and development. Intestinally-expressed genes fall into two broad classes: widely-expressed “housekeeping” genes and genes that are either intestine-specific or significantly intestine-enriched. Within this latter class of genes, we identified a subset of highly-expressed highly-validated genes that are expressed either exclusively or primarily in the intestine. Over half of the encoded proteins are candidates for secretion into the intestinal lumen to hydrolyze the bacterial food (e.g. lysozymes, amoebapores, lipases and especially proteases). The promoters of this subset of intestine-specific/intestine-enriched genes were analyzed computationally, using both a word-counting method (RSAT oligo-analysis) and a method based on Gibbs sampling (MotifSampler). Both methods returned the same over-represented site, namely an extended GATA-related sequence of the general form AHTGATAARR, which agrees with experimentally determined cis-acting control sequences found in intestine genes over the past 20 years. All promoters in the subset contain such a site, compared to <5% for control promoters; moreover, our analysis suggests that the majority (perhaps all) of genes expressed exclusively or primarily in the worm intestine are likely to contain such a site in their promoters. There are three zinc-finger GATA-type factors that are candidates to bind this extended GATA site in the differentiating C. elegans intestine: ELT-2, ELT-4 and ELT-7. All evidence points to ELT-2 being the most important of the three. We show that worms in which both the elt-4 and the elt-7 genes have been deleted from the genome are essentially wildtype, demonstrating that ELT-2 provides all essential GATA-factor functions in the intestine. The SAGE analysis also identifies more than a hundred other transcription factors in the adult intestine but few show an RNAi-induced loss-of-function phenotype and none (other than ELT-2) show a phenotype primarily in the intestine. We thus propose a simple model in which the ELT-2 GATA factor directly participates in the transcription of all intestine-specific/intestine-enriched genes, from the early embryo through to the dying adult. Other intestinal transcription factors would thus modulate the action of ELT-2, depending on the worm's nutritional and physiological needs

Early referral strategies for management of people with markers of renal disease: a systematic review of the evidence of clinical effectiveness, costeffectiveness and economic analysis

Background Chronic kidney disease (CKD) is a long-term condition and has been described as the gradual loss of kidney function over time. Early in the disease process, people with CKD often experience no symptoms. For a long time, CKD has been an underdiagnosed condition. Even in the absence of symptoms, CKD appears to add significantly to the burden of cardiovascular disease and death and, for an important minority, can progress to kidney failure. Objective To systematically review the evidence of the clinical effectiveness and cost-effectiveness of early referral strategies for management of people with markers of renal disease. Data sources Electronic searches of 12 major databases (such as MEDLINE, EMBASE, CINAHL, etc.) were conducted for the time period of 1990 to April 2008 to identify studies comparing early referral to other care options for people with CKD. Additional searching was performed in the NHS Economic Evaluation Database to support the cost-effectiveness literature review. Review methods Two authors reviewed all titles, abstracts and full papers to select relevant literature. A Markov model was constructed to represent the natural history of CKD. The model allowed cohorts to be tracked according to estimated glomerular filtration rate (eGFR) status and the presence of other complications known to influence CKD progression and the incidence of cardiovascular events. Results From 36 relevant natural history studies, CKD was found to be, despite marked heterogeneity between studies, a marker of increased risk of mortality, renal progression and end-stage renal disease. Mortality was generally high and increased with stage of CKD. After adjustment for comorbidities, the relative risk of mortality among those with CKD identified from the general population increased with stage. For clinical populations, the relative risk was higher. All three outcomes increased as eGFR fell. Only seven studies, and no randomised controlled trials, were identified as relevant to assessing the clinical effectiveness of early referral strategies for CKD. In the five retrospective studies constructed from cohorts starting on renal replacement therapy (RRT), mortality was reduced in the early referral group (more than 12 months prior to RRT) even as late as 5 years after initiation of RRT. Only two studies included predialysis participants. One study, in people screened for diabetic nephropathy, reported a reduction in the decline in renal function associated with early referral to nephrology specialists (eGFR decline 3.4 ml/min/1.73 m(2)) when compared with a similar group that had no access to nephrology services until dialysis was required (eGFR decline 12.0 ml/min/1.73 m(2)). The second study, among a group of veterans with two creatinine levels of at least 140 mg/dl, reported that a composite end point of death or progression was lower in the group receiving nephrology follow-up than in those receiving only primary care follow-up. The greatest effect was observed in those with stage 3 or worse disease after adjustment for comorbidities, age, race, smoking and proteinuria {stage 3: hazard ratio (HR) 0.8 [95% confidence interval (CI) 0.61 to 0.9)]; stage 4: HR 0.75 (95% CI 0.45 to 0.89)}. In the base-case analysis, all early referral strategies produced more quality-adjusted life-years (QALYs) than referral upon transit to stage 5 CKD (eGFR 15 ml/min/1.73 m(2)). Referral for everyone with an eGFR below 60 ml/min/1.73 m(2) (stage 3a CKD) generated the most QALYs and, compared with referral for stage 4 CKD (eGFR < 30 ml/min/1.73 m(2)), had an incremental cost-effectiveness ratio of approximately 3806 pounds per QALY. Limitations Because of a lack of data on the natural history of CKD in individuals without diabetes, and a lack of evidence on the costs and effects of early referral, the Markov model relied on many assumptions. The findings were particularly sensitive to changes in eGFR decline rates and the relative effect of early referral on CKD progression and cardiovascular events; the latter parameter being derived from a single non-randomised study. Conclusions Despite substantial focus on the early identification and proactive management of CKD in the last few years, we have identified significant evidence gaps about how best to manage people with CKD. There was some evidence to suggest that the care of people with CKD could be improved and, because these people are at risk from both renal and cardiovascular outcomes, strategies to improve the management of people with CKD have the potential to offer an efficient use of health service resources. Given the number of people now being recognised as having markers of kidney impairment, there is an urgent need for further research to support service change