Synthesis, characterization of a new carbonylated zirconium metallocene using a dichloro-zirconocene derived from partially alkylated s-indacene

Indexación: ScieloThis work describes the synthesis and characterization of new organometallic species, an unprecedented mononuclear zirconium complex bearing a tetraalkylated s-indacene ligand, and secondly, its respective dicarbonyl complex obtained by reduction with Mg/HgCl2. Theoretical calculations of these two compounds were carried out to gain further understanding of these novel molecular systems.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-97072009000300014&lng=es&nrm=is

Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance

AbstractMany different definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae (other than Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter spp., all bacteria often responsible for healthcare-associated infections and prone to multidrug resistance. Epidemiologically significant antimicrobial categories were constructed for each bacterium. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories, XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) and PDR was defined as non-susceptibility to all agents in all antimicrobial categories. To ensure correct application of these definitions, bacterial isolates should be tested against all or nearly all of the antimicrobial agents within the antimicrobial categories and selective reporting and suppression of results should be avoided

TBCRC 002: A phase II, randomized, open-label trial of preoperative letrozole with or without bevacizumab in postmenopausal women with newly diagnosed stage 2/3 hormone receptor-positive and HER2-negative breast cancer

Background: In preclinical studies, the expression of vascular endothelial growth factor (VEGF) in hormone receptor-positive breast cancer is associated with estrogen-independent tumor growth and resistance to endocrine therapies. This study investigated whether the addition of bevacizumab, a monoclonal antibody against VEGF, to letrozole enhanced the antitumor activity of the letrozole in the preoperative setting. Methods: Postmenopausal women with newly diagnosed stage 2 or 3 estrogen and/or progesterone receptor-positive, HER2-negative breast cancer were randomly assigned (2:1) between letrozole 2.5 mg PO daily plus bevacizumab 15 mg/kg IV every 3 weeks (Let/Bev) and letrozole 2.5 mg PO daily (Let) for 24 weeks prior to definitive surgery. Primary objective was within-arm pathologic complete remission (pCR) rate. Secondary objectives were safety, objective response, and downstaging rate. Results: Seventy-five patients were randomized (Let/Bev n = 50, Let n = 25). Of the 45 patients evaluable for pathological response in the Let/Bev arm, 5 (11%; 95% CI, 3.7-24.1%) achieved pCR and 4 (9%; 95% CI, 2.5-21.2%) had microscopic residual disease; no pCRs or microscopic residual disease was seen in the Let arm (0%; 95% CI, 0-14.2%). The rates of downstaging were 44.4% (95% CI, 29.6-60.0%) and 37.5% (95% CI, 18.8-59.4%) in the Let/Bev and Let arms, respectively. Adverse events typically associated with letrozole (hot flashes, arthralgias, fatigue, myalgias) occurred in similar frequencies in the two arms. Hypertension, headache, and proteinuria were seen exclusively in the Let/Bev arm. The rates of grade 3 and 4 adverse events and discontinuation due to adverse events were 18% vs 8% and 16% vs none in the Let/Bev and Let arms, respectively. A small RNA-based classifier predictive of response to preoperative Let/Bev was developed and confirmed on an independent cohort. Conclusion: In the preoperative setting, the addition of bevacizumab to letrozole was associated with a pCR rate of 11%; no pCR was seen with letrozole alone. There was additive toxicity with the incorporation of bevacizumab. Responses to Let/Bev can be predicted from the levels of 5 small RNAs in a pretreatment biopsy. Trial registration: This trial is registered with ClinicalTrials.gov (Identifier: NCT00161291), first posted on September 12, 2005, and is completed

Heritability of attention problems in children II: longitudinal results from a study of twins age 3 to 12.

this paper we present data of large samples of twin families, with an equal number of girls and boys. The well-known gender difference with boys displaying more OA and AP was observed at each age. Even at the age of 3, boys display more OA problems than girls. Clinical studies have indicated that severe problem behavior can be identified in very young children (see for review, Campbell, 1995; Keenan & Wakschlag, 2000; Shaw, Owens, Giovannelli, & Winslow, 2001) and that the onset of ADHD is during the pre-school period (Barkley, Fisher, Edelbrock, & Smallish, 1990; Table 6 Top part includes percentages of total variances (diagonal) and covariances (off-diagonal) explained by additive genetic, genetic dominance, and unique environmental components based on best fitting models. Percentages for boys and girls are reported below and above diagonal, respectively. Lower part includes correlations calculated for additive genetic, genetic dominance, and unique environmental sources of variance between different ages. Correlations for boys and girls are reported below and above diagonal, respectively Relative proportions of variance and covariance BoysnGirls A% D% E% OA 3 AP 7 AP 10 AP 12 OA 3 AP 7 AP 10 AP 12 OA 3 AP 7 AP 10 AP 12 OA 3 50n41 73 79 75 22n33 17 13 14 28n26 10 8 11 AP 7 59 33n57 50 53 31 39n16 31 28 10 28n27 19 19 AP 10 86 31 41n48 47 6 51 31n25 32 8 18 28n27 21 AP 12 71 24 31 40n54 16 55 45 30n18 13 21 24 30n28 Correlations between different ages BoysnGirls ADE OA 3 AP 7 AP 10 AP 12 OA 3 AP 7 AP 10 AP 12 OA 3 AP 7 AP 10 AP 12 OA 3 1.00 .60 .66 .57 1.00 .30 .16 .20 1.00 .15 .12 .14 AP 7 .57 1.00 .62 .57 .41 1.00 .99 1.00 .15 1.00 .46 .41 AP 10 .68 .56 1.00 .61 .08 .94 1.00 1.00 .11 .42 1.00 .50 AP 12 .49 .42 .53 1.00 .20 .98 .99 1.00 .14 .45 .58 1.00 ..

Materializing digital collecting: an extended view of digital materiality

If digital objects are abundant and ubiquitous, why should consumers pay for, much less collect them? The qualities of digital code present numerous challenges for collecting, yet digital collecting can and does occur. We explore the role of companies in constructing digital consumption objects that encourage and support collecting behaviours, identifying material configuration techniques that materialise these objects as elusive and authentic. Such techniques, we argue, may facilitate those pleasures of collecting otherwise absent in the digital realm. We extend theories of collecting by highlighting the role of objects and the companies that construct them in materialising digital collecting. More broadly, we extend theories of digital materiality by highlighting processes of digital material configuration that occur in the pre-objectification phase of materialisation, acknowledging the role of marketing and design in shaping the qualities exhibited by digital consumption objects and consequently related consumption behaviours and experiences

FOXA1 and adaptive response determinants to HER2 targeted therapy in TBCRC 036

Inhibition of the HER2/ERBB2 receptor is a keystone to treating HER2-positive malignancies, particularly breast cancer, but a significant fraction of HER2-positive (HER2+) breast cancers recur or fail to respond. Anti-HER2 monoclonal antibodies, like trastuzumab or pertuzumab, and ATP active site inhibitors like lapatinib, commonly lack durability because of adaptive changes in the tumor leading to resistance. HER2+ cell line responses to inhibition with lapatinib were analyzed by RNAseq and ChIPseq to characterize transcriptional and epigenetic changes. Motif analysis of lapatinib-responsive genomic regions implicated the pioneer transcription factor FOXA1 as a mediator of adaptive responses. Lapatinib in combination with FOXA1 depletion led to dysregulation of enhancers, impaired adaptive upregulation of HER3, and decreased proliferation. HER2-directed therapy using clinically relevant drugs (trastuzumab with or without lapatinib or pertuzumab) in a 7-day clinical trial designed to examine early pharmacodynamic response to antibody-based anti-HER2 therapy showed reduced FOXA1 expression was coincident with decreased HER2 and HER3 levels, decreased proliferation gene signatures, and increased immune gene signatures. This highlights the importance of the immune response to anti-HER2 antibodies and suggests that inhibiting FOXA1-mediated adaptive responses in combination with HER2 targeting is a potential therapeutic strategy

Effects of Intermittent IL-2 Alone or with Peri-Cycle Antiretroviral Therapy in Early HIV Infection: The STALWART Study

The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

Biomass offsets little or none of permafrost carbon release from soils, streams, and wildfire: an expert assessment

As the permafrost region warms, its large organic carbon pool will be increasingly vulnerable to decomposition, combustion, and hydrologic export. Models predict that some portion of this release will be offset by increased production of Arctic and boreal biomass; however, the lack of robust estimates of net carbon balance increases the risk of further overshooting international emissions targets. Precise empirical or model-based assessments of the critical factors driving carbon balance are unlikely in the near future, so to address this gap, we present estimates from 98 permafrost-region experts of the response of biomass, wildfire, and hydrologic carbon flux to climate change. Results suggest that contrary to model projections, total permafrost-region biomass could decrease due to water stress and disturbance, factors that are not adequately incorporated in current models. Assessments indicate that end-of-the-century organic carbon release from Arctic rivers and collapsing coastlines could increase by 75% while carbon loss via burning could increase four-fold. Experts identified water balance, shifts in vegetation community, and permafrost degradation as the key sources of uncertainty in predicting future system response. In combination with previous findings, results suggest the permafrost region will become a carbon source to the atmosphere by 2100 regardless of warming scenario but that 65%–85% of permafrost carbon release can still be avoided if human emissions are actively reduced

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two demonstrating sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of further common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signalling and cell cycle regulation, in diabetes pathogenesis