An intercomparison of procedures for the determination of total mercury in seawater and recommendations regarding mercury speciation during GEOTRACES cruises

Author Posting. © Association for the Sciences of Limnology and Oceanography, 2012. This article is posted here by permission of Association for the Sciences of Limnology and Oceanography for personal use, not for redistribution. The definitive version was published in Limnology and Oceanography: Methods 10 (2012): 90-100, doi:10.4319/lom.2012.10.90.We conducted a laboratory intercomparison of total mercury (Hg) determination in seawater collected during U.S. GEOTRACES Intercalibration cruises in 2008 and 2009 to the NW Atlantic and NE Pacific Oceans. Results indicated substantial disagreement between the participating laboratories, which appeared to be affected most strongly by bottle cleanliness and preservation procedures. In addition, we examined the effectiveness of various collection and sample preparation procedures that may be used on future GEOTRACES cruises. The type of sampling system and filtration medium appeared to make little difference to results. Finally, and in light of results from experiments that considered sample bottle material effect and the development of new methods for CH3Hg+ extraction from seawater, we propose a recommended procedure for determining all four of the major Hg species in seawater (elemental, dimethyl-, monomethyl-, and total Hg).This work was supported by the National Science Foundation program in Chemical Oceanography under grants OCE–0825157, –0825108, –0825583 and –0825068

The Acidic Tail of the Cdc34 Ubiquitin-conjugating Enzyme Functions in Both Binding to and Catalysis with Ubiquitin Ligase SCFC^(dc4*)

Ubiquitin ligases, together with their cognate ubiquitin-conjugating enzymes, are responsible for the ubiquitylation of proteins, a process that regulates a myriad of eukaryotic cellular functions. The first cullin-RING ligase discovered, yeast SCF^(Cdc4), functions with the conjugating enzyme Cdc34 to regulate the cell cycle. Cdc34 orthologs are notable for their highly acidic C-terminal extension. Here we confirm that the Cdc34 acidic C-terminal tail has a role in Cdc34 binding to SCF^(Cdc4) and makes a major contribution to the submicromolar K_m of Cdc34 for SCF^(Cdc4). Moreover, we demonstrate that a key functional property of the tail is its acidity. Our analysis also uncovers an unexpected new function for the acidic tail in promoting catalysis. We demonstrate that SCF is functional when Cdc34 is fused to the C terminus of Cul1 and that this fusion retains partial function even when the acidic tail has been deleted. The Cdc34-SCF fusion proteins that lack the acidic tail must interact in a fundamentally different manner than unfused SCF and wild type Cdc34, demonstrating that distinct mechanisms of E2 recruitment to E3, as is seen in nature, can sustain substrate ubiquitylation. Finally, a search of the yeast proteome uncovered scores of proteins containing highly acidic stretches of amino acids, hinting that electrostatic interactions may be a common mechanism for facilitating protein assembly

Vortex Loop Phase Transitions in Liquid Helium, Cosmic Strings, and High-T_c Superconductors

The distribution of thermally excited vortex loops near a superfluid phase transition is calculated from a renormalized theory. The number density of loops with a given perimeter is found to change from exponential decay with increasing perimeter to algebraic decay as T_c is approached, in agreement with recent simulations of both cosmic strings and high-T_c superconductors. Predictions of the value of the exponent of the algebraic decay at T_c and of critical behavior in the vortex density are confirmed by the simulations, giving strong support to the vortex-folding model proposed by Shenoy.Comment: Version to appear in Phys. Rev. Lett, with a number of corrections and addition

Neonatal resuscitation and immediate newborn assessment and stimulation for the prevention of neonatal deaths: a systematic review, meta-analysis and Delphi estimation of mortality effect

BACKGROUND: Of 136 million babies born annually, around 10 million require assistance to breathe. Each year 814,000 neonatal deaths result from intrapartum-related events in term babies (previously "birth asphyxia") and 1.03 million from complications of prematurity. No systematic assessment of mortality reduction from tactile stimulation or resuscitation has been published. OBJECTIVE: To estimate the mortality effect of immediate newborn assessment and stimulation, and basic resuscitation on neonatal deaths due to term intrapartum-related events or preterm birth, for facility and home births. METHODS: We conducted systematic reviews for studies reporting relevant mortality or morbidity outcomes. Evidence was assessed using GRADE criteria adapted to provide a systematic approach to mortality effect estimates for the Lives Saved Tool (LiST). Meta-analysis was performed if appropriate. For interventions with low quality evidence but strong recommendation for implementation, a Delphi panel was convened to estimate effect size. RESULTS: We identified 24 studies of neonatal resuscitation reporting mortality outcomes (20 observational, 2 quasi-experimental, 2 cluster randomized controlled trials), but none of immediate newborn assessment and stimulation alone. A meta-analysis of three facility-based studies examined the effect of resuscitation training on intrapartum-related neonatal deaths (RR= 0.70, 95%CI 0.59-0.84); this estimate was used for the effect of facility-based basic neonatal resuscitation (additional to stimulation). The evidence for preterm mortality effect was low quality and thus expert opinion was sought. In community-based studies, resuscitation training was part of packages with multiple concurrent interventions, and/or studies did not distinguish term intrapartum-related from preterm deaths, hence no meta-analysis was conducted. Our Delphi panel of 18 experts estimated that immediate newborn assessment and stimulation would reduce both intrapartum-related and preterm deaths by 10%, facility-based resuscitation would prevent a further 10% of preterm deaths, and community-based resuscitation would prevent further 20% of intrapartum-related and 5% of preterm deaths. CONCLUSION: Neonatal resuscitation training in facilities reduces term intrapartum-related deaths by 30%. Yet, coverage of this intervention remains low in countries where most neonatal deaths occur and is a missed opportunity to save lives. Expert opinion supports smaller effects of neonatal resuscitation on preterm mortality in facilities and of basic resuscitation and newborn assessment and stimulation at community level. Further evaluation is required for impact, cost and implementation strategies in various contexts. FUNDING: This work was supported by the Bill & Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to the Saving Newborn Lives program of Save the Children, through Save the Children US

Association between monosodium glutamate intake and sleep-disordered breathing among Chinese adults with normal body weight

ObjectiveTo assess whether monosodium glutamate (MSG) intake is associated with sleep-disordered breathing (SDB).MethodsData from 1227 Chinese subjects who participated in the Jiangsu Nutrition Study were analyzed. All the participants were examined at two time points (baseline in 2002 and follow-up in 2007). The MSG intake was assessed quantitatively in 2002 and a sleep questionnaire was used to assess snoring and to construct an SDB probability score in 2007. Those within the fifth quintile of the score (highest) were defined as having a high probability of SDB.ResultsThe MSG intake was positively associated with snoring and a high probability of SDB in participants who had a normal body weight but in those who were overweight. A comparison of the extreme quartiles of MSG intake in subjects with a body mass index lower than 23 kg/m² showed an odds ratio of 2.02 (95% confidence interval 1.02-4.00) for snoring and an odds ratio of 3.11 (95% confidence interval 1.10-8.84) for a high probability of SDB. There was a joint effect between MSG and overweight in relation to SDB.ConclusionThe intake of MSG may increase the risk of SDB in Chinese adults with a normal body weight.Zumin Shi, Gary A. Wittert, Baojun Yuan, Yue Dai, Tiffany K. Gill, Gang Hu, Robert Adams, Hui Zuo, Anne W. Taylo

Sydney principles for reducing the commercial promotion of foods and beverages to children

A set of seven principles (the &lsquo;Sydney Principles&rsquo;) was developed by an International Obesity Taskforce (IOTF) Working Group to guide action on changing food and beverage marketing practices that target children. The aim of the present communication is to present the Sydney Principles and report on feedback received from a global consultation (November 2006 to April 2007) on the Principles.The Principles state that actions to reduce marketing to children should: (i) support the rights of children; (ii) afford substantial protection to children; (iii) be statutory in nature; (iv) take a wide definition of commercial promotions; (v) guarantee commercial-free childhood settings; (vi) include cross-border media; and (vii) be evaluated, monitored and enforced.The draft principles were widely disseminated and 220 responses were received from professional and scientific associations, consumer bodies, industry bodies, health professionals and others. There was virtually universal agreement on the need to have a set of principles to guide action in this contentious area of marketing to children. Apart from industry opposition to the third principle calling for a statutory approach and several comments about the implementation challenges, there was strong support for each of the Sydney Principles. Feedback on two specific issues of contention related to the age range to which restrictions should apply (most nominating age 16 or 18 years) and the types of products to be included (31 % nominating all products, 24 % all food and beverages, and 45 % energy-dense, nutrient-poor foods and beverages).The Sydney Principles, which took a children&rsquo;s rights-based approach, should be used to benchmark action to reduce marketing to children. The age definition for a child and the types of products which should have marketing restrictions may better suit a risk-based approach at this stage. The Sydney Principles should guide the formation of an International Code on Food and Beverage Marketing to Children.<br /

Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study.

BackgroundInternal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia.MethodsIn this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment. Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). Cohort expansion was based on safety and tolerability, FLT3 inhibition in correlative assays, and antileukaemic activity. Although the presence of an FLT3 mutation was not an inclusion criterion, we required ten or more patients with locally confirmed FLT3 mutations (FLT3mut+) to be enrolled in expansion cohorts at each dose level. On the basis of emerging findings, we further expanded the 120 mg and 200 mg dose cohorts to include FLT3mut+ patients only. The primary endpoints were the safety, tolerability, and pharmacokinetics of gilteritinib. Safety and tolerability were assessed in the safety analysis set (all patients who received at least one dose of gilteritinib). Responses were assessed in the full analysis set (all patients who received at least one dose of study drug and who had at least one datapoint post-treatment). Pharmacokinetics were assessed in a subset of the safety analysis set for which sufficient data for concentrations of gilteritinib in plasma were available to enable derivation of one or more pharmacokinetic variables. This study is registered with ClinicalTrials.gov, number NCT02014558, and is ongoing.FindingsBetween Oct 15, 2013, and Aug 27, 2015, 252 adults with relapsed or refractory acute myeloid leukaemia received oral gilteritinib once daily in one of seven dose-escalation (n=23) or dose-expansion (n=229) cohorts. Gilteritinib was well tolerated; the maximum tolerated dose was established as 300 mg/day when two of three patients enrolled in the 450 mg dose-escalation cohort had two dose-limiting toxicities (grade 3 diarrhoea and grade 3 elevated aspartate aminotransferase). The most common grade 3-4 adverse events irrespective of relation to treatment were febrile neutropenia (97 [39%] of 252), anaemia (61 [24%]), thrombocytopenia (33 [13%]), sepsis (28 [11%]), and pneumonia (27 [11%]). Commonly reported treatment-related adverse events were diarrhoea (92 [37%] of 252]), anaemia (86 [34%]), fatigue (83 [33%]), elevated aspartate aminotransferase (65 [26%]), and increased alanine aminotransferase (47 [19%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (98 [39%] of 252; five related to treatment), progressive disease (43 [17%]), sepsis (36 [14%]; two related to treatment), pneumonia (27 [11%]), acute renal failure (25 [10%]; five related to treatment), pyrexia (21 [8%]; three related to treatment), bacteraemia (14 [6%]; one related to treatment), and respiratory failure (14 [6%]). 95 people died in the safety analysis set, of which seven deaths were judged possibly or probably related to treatment (pulmonary embolism [200 mg/day], respiratory failure [120 mg/day], haemoptysis [80 mg/day], intracranial haemorrhage [20 mg/day], ventricular fibrillation [120 mg/day], septic shock [80 mg/day], and neutropenia [120 mg/day]). An exposure-related increase in inhibition of FLT3 phosphorylation was noted with increasing concentrations in plasma of gilteritinib. In-vivo inhibition of FLT3 phosphorylation occurred at all dose levels. At least 90% of FLT3 phosphorylation inhibition was seen by day 8 in most patients receiving a daily dose of 80 mg or higher. 100 (40%) of 249 patients in the full analysis set achieved a response, with 19 (8%) achieving complete remission, ten (4%) complete remission with incomplete platelet recovery, 46 (18%) complete remission with incomplete haematological recovery, and 25 (10%) partial remission INTERPRETATION: Gilteritinib had a favourable safety profile and showed consistent FLT3 inhibition in patients with relapsed or refractory acute myeloid leukaemia. These findings confirm that FLT3 is a high-value target for treatment of relapsed or refractory acute myeloid leukaemia; based on activity data, gilteritinib at 120 mg/day is being tested in phase 3 trials.FundingAstellas Pharma, National Cancer Institute (Leukemia Specialized Program of Research Excellence grant), Associazione Italiana Ricerca sul Cancro

Screening Analysis for the Environmental Risk Evaluation System Task 2.1.1.2: Evaluating Effects of Stressors Fiscal Year 2011 Progress Report - Environmental Effects of Marine and Hydrokinetic Energy

Potential environmental effects of marine and hydrokinetic (MHK) energy development are not well understood, and yet regulatory agencies are required to make decisions in spite of substantial uncertainty about environmental impacts and their long-term consequences. An understanding of risks associated with interactions between MHK installations and aquatic receptors, including animals, habitats, and ecosystems, can help define key uncertainties and focus regulatory actions and scientific studies on interactions of most concern. As a first step in developing the Pacific Northwest National Laboratory (PNNL) Environmental Risk Evaluation System (ERES), PNNL scientists conducted a preliminary risk screening analysis on three initial MHK cases. During FY 2011, two additional cases were added: a tidal project in the Gulf of Maine using Ocean Renewable Power Company TidGenTM turbines and a wave project planned for the coast of Oregon using Aquamarine Oyster surge devices. Through an iterative process, the screening analysis revealed that top-tier stressors in the two FY 2011 cases were the dynamic effects of the device (e.g., strike), accidents/disasters, and effects of the static physical presence of the device (e.g., habitat alteration). Receptor interactions with these stressors at the highest tiers of risk were dominated by threatened and endangered animals. Risk to the physical environment from changes in flow regime also ranked high. Peer review of this process and results will be conducted in early FY 2012. The ERES screening analysis provides an analysis of vulnerability of environmental receptors to stressors associated with MHK installations, probability analysis is needed to determine specific risk levels to receptors. “Risk” has two components: (1) The likelihood, or “probability”, of the occurrence of a given interaction or event, and (2) the potential “consequence” if that interaction or event were to occur. During FY 2011, the ERES screening analysis focused primarily on the second component of risk, “consequence”, with focused probability analysis for interactions where data was sufficient for probability modeling. Consequence analysis provides an assessment of vulnerability of environmental receptors to stressors associated with MHK installations. Probability analysis is needed to determine specific risk levels to receptors and requires significant data inputs to drive risk models. During FY 2011, two stressor-receptor interactions were examined for the probability of occurrence. The two interactions (spill probability due to an encounter between a surface vessel and an MHK device; and toxicity from anti-biofouling paints on MHK devices) were seen to present relatively low risks to marine and freshwater receptors of greatest concern in siting and permitting MHK devices. A third probability analysis was scoped and initial steps taken to understand the risk of encounter between marine animals and rotating turbine blades. This analysis will be completed in FY 2012

The velocity modulation of galaxy properties in and near clusters: quantifying the decrease in star formation in backsplash galaxies

The efficiency of recent star formation (SF) in galaxies increases with increasing projected distance from the centre of a cluster out to several times its virial radius (R_v). Using a complete sample of galaxies in 268 clusters from the SDSS DR4, we investigate how, at a given projected radius from the cluster centre, M* and SF properties of a galaxy depend on its absolute line-of-sight velocity in the cluster rest frame, |v_LOS|. We find that for R<0.5 R_v, the fraction of high mass non-BCG galaxies increases towards the centre for low |v_LOS|. At a given projected radius, the fraction of Galaxies with Ongoing or Recent (<1-3 Gyr) Efficient Star Formation (GORES, with EW(H_delta)>2 ang & D_4000>1.5) is slightly but significantly lower for low |v_LOS| galaxies than for their high velocity counterparts. We study these observational trends with the help of a dark matter (DM) cosmological simulation. We find that the backsplash particles account for at least one-third (half) of all particles at projected radii slightly greater than the virial radius and |v_LOS|<sigma_v. The deprojection of the GORES fraction leads to a saturated linear increase with radius. We fit simple models of the fraction of GORES as a function of class only or class and distance to the cluster centre (as in our deprojected fraction). In our best-fitting model GORES account for 13% of galaxies within the virial sphere, 11% of the virial population, 34% of the distant (for projected radii R<2 R_v) infall population and 19% of the backsplash galaxies. Given the 1-3 Gyr lookback time of our GORES indicators, these results suggest that SF in a galaxy is almost completely quenched in a single passage through the cluster.Comment: 22 pages, 17 figures, MNRAS, 416, 2882, Labels for Figure 14 revise

Non-Equilibrium Large N Yukawa Dynamics: marching through the Landau pole

The non-equilibrium dynamics of a Yukawa theory with N fermions coupled to a scalar field is studied in the large N limit with the goal of comparing the dynamics predicted from the renormalization group improved effective potential to that obtained including the fermionic backreaction. The effective potential is of the Coleman-Weinberg type. Its renormalization group improvement is unbounded from below and features a Landau pole. When viewed self-consistently, the initial time singularity does not arise. The different regimes of the dynamics of the fully renormalized theory are studied both analytically and numerically. Despite the existence of a Landau pole in the model, the dynamics of the mean field is smooth as it passes the location of the pole. This is a consequence of a remarkable cancellation between the effective potential and the dynamical chiral condensate. The asymptotic evolution is effectively described by a quartic upright effective potential. In all regimes, profuse particle production results in the formation of a dense fermionic plasma with occupation numbers nearly saturated up to a scale of the order of the mean field. This can be interpreted as a chemical potential. We discuss the implications of these results for cosmological preheating.Comment: 36 pages, 14 figures, LaTeX, submitted to Physical Review