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The reactions between alcohols and the tetranuclear ethyl-Zn complexes of an ortho-phenylene-bridged polypyrrole macrocycle, Zn4Et4(L1) 1 and the related anthracenyl-bridged macrocyclic complex, Zn4Et4(THF)4(L2) 2 have been studied. With long-chain alcohols such as n-hexanol, the clean formation of the tetranuclear hexoxide complex Zn4(OC6H13)4(L1) 3 occurs. In contrast, the use of shorter-chain alcohols such as i-propanol results in the trinuclear complex Zn3(μ2-OiPr)2(μ3-OiPr)(HL1) 4 that arises from demetalation; this complex was characterised by X-ray crystallography. The clean formation of these polynuclear zinc clusters allowed a study of their use as catalysts in the ring-opening copolymerisation (ROCOP) reaction between cyclohexene oxide and CO2. In situ reactions involving the pre-catalyst 1 and n-hexanol formed the desired polymer with the best selectivity for polycarbonate (90%) at 30 atm CO2, whilst the activity and performance of pre-catalyst 2 was poor in comparison.

Controlled, photocatalytic C-H bond activations are key reactions in the toolkits of the modern synthetic chemist. While it is known that the uranyl (VI) ion (UVIO22+), the environmentally dominant form of uranium, is photoactive, most literature examines its luminescent properties, neglecting its potential synthetic utility for photocatalytic C-H bond cleavage. Here, we synthesise and fully characterise an air-stable and organicsoluble uranyl phenanthroline complex, [UO2(NO3)2(Ph2phen)], UPh2phen, and demonstrate that it can catalytically abstract hydrogen atoms from a variety of organic substrates under visible light irradiation. We show that the commercially available parent complex, uranyl nitrate, UNO3 is also competent, but using electronic spectroscopy we attribute the higher rates and selectivity of UPh2phen to ligand-mediated electronic effects. Ketones are selectively formed over other oxygenated products (alcohols, etc.), and the catalytic oxidation of substrates containing a benzylic C-H position is particularly improved for UPh2phen. We also show uranyl-mediated photocatalytic C-C bond cleavage in a model lignin compound for the first time.

The recycling of metals such as gold and copper from discarded end-of-life electronic waste (e-waste or WEEE) is an important aspect to the development of environmentally benign manufacturing processes that exhibit circularity in materials flow. Global e-waste production is increasing at a 3–5% rate, so it is concerning that only 30% is recycled using regulated processes. We present here a new hydrometallurgical route for the technically feasible recycling of copper and gold from waste printed circuit boards (WPCBs) of mobile phones. This process comprises the liberation of the metallic fractions from downsized WPCBs, a two-stage acid leaching process to provide a bulk separation of copper and gold from the other metals present, and subsequent purification of the copper and gold-containing solutions by solvent extraction using highly selective phenolic oxime and amide extractants, respectively. Complete dissolution of the base metals was seen using 3 M nitric acid at 30 °C and the selective separation of copper from this leach liquor was achieved by solvent extraction using ACORGA M5640 dissolved in kerosene. The residues from base-metal leaching were treated with a mixture of 3 M sulfuric acid and 3 M sodium bromide at 70 °C, resulting in greater than 95% gold dissolution. The selective separation of gold from this precious metal leachate was achieved by solvent extraction using 0.1 M tertiary amide extractant dissolved in toluene. This process delivers complete copper and gold recycling from WPCBs under relatively benign laboratory conditions and represents a proof of concept for liberating valuable and critical metals back into active service from end-of-life electronic devices.

The possibility of recovering rare earth elements from solutions containing their chloridometalate anions [LnClx](x−3)− via the process: LnClx(x−3)− + (x − 3)Lorg + (x–3)H+ ⇌ [(LH)x−3LnClx]org has been tested using 2-(1,3-bis(hexylamino)-1,3-dioxopropan-2-yl)-4,6-di-tert-butylpyridine (PMA), tri-n-butylphosphate (TBP), and tri-n-octylamine (TOA), which are known to be strong extractants for transition metal chloridometalates. While DFT calculations indicate that the formation of the neutral assembly [(PMAH)3LaCl6] in the gas phase is favorable, no uptake of La(III) from 6 M HCl by toluene solutions of PMA (or of TBP or TOA) was observed in solvent extraction experiments. Successful uptake of the [PtCl6]2− dianion by PMA and the failure to extract the [IrCl6]3− trianion under the same conditions indicate that the higher hydration energy of the latter makes transfer to the toluene solution less favorable and that this militates against extraction of La(III) chlorido complexes carrying charges of −3 or larger in which all the inner-sphere water molecules have been replaced. Computational results confirm literature observations that, in contrast to transition metal trications, formation of REE metalate anions such as [LnClx](x−3)− is not very favorable, particularly so for chloride, compared with nitrato or sulfato systems. Also, they indicate that the formation of outer-sphere assemblies such as {[La(H2O)9]·xCl} in which water ligands are retained in the inner sphere, H-bonded to anions, is more stable than inner-sphere complexes containing an equivalent number of anions. The high level of hydration of such species disfavors their transfer into nonpolar water-immiscible solvents. It is unlikely that recovery of [LnClx](x−3)− from acidic solutions can be achieved efficiently using currently available anion exchange extractants operating in a “pH-swing” process. Receptors giving very high binding energies to chloridolanthanates will be needed to offset the high dehydration energies required.

Extraction and binding studies of [PtCl6](2-) are reported for 24 mono-, bi-, and tripodal extractants containing tris(2-aminoethyl)amine (TREN) or tris(3-aminopropyl)arnine (TRPN) scaffolds. These reagents are designed to recognize the outer coordination sphere of [PtCl6](2-) and to show selectivity over chloride anion under acidic conditions. Extraction from 0.6 M HCl involves protonation of the N-center in tertiary amines containing one, two, or three urea, amide, or sulfonamide hydrogen-bond donors to set up the following equilibrium: 2L((org)) + 2H(+) + [PtCl6](2-) (sic) [(LH)(2)PtCl6] (org). All reagents show higher Pt loading than trioctylamine, which was used as a positive control to represent commercial trialkylamine reagents. The loading of [PtCl6](2-) depends on the number of pendant amides in the extractant and follows the order tripodal > bipodal > monopodal, with urea containing extractants outperforming amide and sulfonamide analogues. A different series of reagents in which one, two, or three of the alkyl groups in tris-2-ethylhexylamine are replaced by 3-Ni-hexylpropanamide groups all show a comparably high affinity for [PtCl6](2-) and high selectivity over chloride anion in extractions from aqueous acidic solutions. H-1 NMR titration of three extractants [LH center dot Cl] with [(Oct(4)N)(2)PtCl6] in CDCl3 provides evidence for high selectivity for [PtCl6](2-) over chloride for tri- and bipodal extractants, which show higher binding constants than a monopodal analogue.

Studies of transuranic organometallic complexes provide a particularly valuable insight into covalent contributions to the metal–ligand bonding, in which the subtle differences between the transuranium actinide ions and their lighter lanthanide counterparts are of fundamental importance for the effective remediation of nuclear waste. Unlike the organometallic chemistry of uranium, which has focused strongly on UIII and has seen some spectacular advances, that of the transuranics is significantly technically more challenging and has remained dormant. In the case of neptunium, it is limited mainly to NpIV. Here we report the synthesis of three new NpIII organometallic compounds and the characterization of their molecular and electronic structures. These studies suggest that NpIII complexes could act as single-molecule magnets, and that the lower oxidation state of NpII is chemically accessible. In comparison with lanthanide analogues, significant d- and f-electron contributions to key NpIII orbitals are observed, which shows that fundamental neptunium organometallic chemistry can provide new insights into the behaviour of f-elements. Probing the chemistry of transuranic elements is notoriously challenging. Now, three neptunium(III) organometallic sandwich complexes have been prepared using a flexible macrocycle as ligand, and their molecular and electronic structures characterized, adding to our understanding of the behaviour of f-elements and suggesting that the lower oxidation state Np(II) may be chemically accessible.

The effect of pressure on the intranuclear M···M separation and intermolecular secondary interactions in the dinuclear chromium Pacman complex [Cr2(L)](C6H6) was evaluated because this compound contains both a short Cr···Cr separation and an exogenously bound molecule of benzene in the solid state. The electronic structure of [Cr2(L)] was determined by electron paramagnetic resonance spectroscopy, SQUID magnetometry, and density functional theory calculations and shows a diamagnetic ground state through antiferromagnetic exchange, with no evidence for a Cr-Cr bond. Analysis of the solid-state structures of [Cr2(L)](C6H6) at pressures varying from ambient to 3.0 GPa shows little deformation in the Cr···Cr separation, i.e., no Cr-Cr bond formation, but instead a significantly increased interaction between the exogenous arene and the chromium iminopyrrolide environment. It is therefore apparent from this analysis that [Cr2(L)] would be best exploited as a rigid chemical synthon, with pressure regulation being used to mediate the approach and secondary interactions of possible substrates.

The relations between psychopathy, romantic relationships, and well-being were investigated in 431 undergraduates. For both males and females, various components of romantic relationship quality were positively correlated with subjective well-being (SWB) and negatively correlated with ill-being. However, only for females was overall romantic relationship quality positively correlated with life satisfaction, happiness and positive affect, and negatively correlated with negative affect and depression. High levels of psychopathy were found in 23.1 % of males and 7.4 % of females. Psychopathy accounted for significant variance in overall relationship quality (7.0 %), commitment (14.1 %), satisfaction (9.3 %), romance (10.7 %) and trust (6.4 %) in romantic relationships for males and in overall relationship quality (3.2 %), commitment (5.3 %), and trust (5.9 %) for females. Romantic relationship quality was able to mediate the relations between psychopathy and SWB and this mediation was moderated by gender.

Background: Small for gestational age (SGA) babies are at high risk of perinatal mortality. We aimed to determine the potential to reduce perinatal mortality by improving antenatal detection of SGA babies in Scotland. Methods: We conducted a retrospective population study of all singleton SGA babies born in the 15 Consultant-led maternity units in Scotland in a 3-month period (1st Dec 2014 to 28th Feb 2015 inclusive). Demographic and pregnancy outcome data were extracted from Scottish birth records for all pregnancies; case note review was performed for all SGA cases [defined as birthweight less than the 10th centile for their gestational age at delivery as defined by the appropriate sex-specific UK-WHO Child Growth Standards]. Results: The SGA rate in Scotland was 5.5% (673/12218; 95% confidence interval [CI] 5.1, 5.9) and 27.6% (186/673; 95% CI 24.3, 31.2) of SGA cases were identified prior to delivery. SGA was associated with 18.2% (12/66; 95% CI [10.1%, 30.0%) of all perinatal deaths. The majority (10/12, 83.3%) of SGA babies who died had been identified as SGA in the antenatal period. There was no difference in perinatal mortality whether SGA was detected or not (5.4% [10/186; 95% CI 2.8, 10.0] in the SGA detected group vs 0.4% [2/487 [95% CI 0.3, 2.2] in the non-detected group after adjusting for risk factors for SGA, gestation at delivery and birthweight centile (Adjusted odds ratio [AOR] 0.85 [95% CI 0.5, 1.5], p=0.556). Conclusions: Despite only around a quarter of SGA babies being identified antenatally, the potential to reduce perinatal mortality in the Scottish population by improving SGA detection is limited. Only a minority of perinatal deaths occurred in SGA babies; and in the majority of these SGA was detected antenatally.

We measured direct photons for pT

We present measurements of two-particle angular correlations between high-transverse-momentum (2

Professor Geoff Cloke FRS celebrates his 65th birthday in 2018. In a career spanning four decades, his research endeavours have accounted for some of the most innovative synthetic chemistry of the modern era, with his many publications describing truly exceptional compounds and experimental methods that portray a unique chemical imagination. In addition to his scientific accomplishments, Cloke can be particularly proud of his successful mentoring, a level of dedication that propelled many students and post-docs on to become research leaders in their own right. In compiling this collection of some of his research articles, a small cross-section of his friends, colleagues and collaborators, wish to pay tribute to his modesty, compassion and generous personality.

Furan and thiophene diarylmethenes are potential redox-active ligands for metal centers that could be exploited in the development of nontraditional, stoichiometric, and catalytic redox reactions. As such, we describe here the selective meso-deprotonations of dithiophene, difuran, and diimine-difuran diarylmethanes to form the π-conjugated anions, for which only the diimino-difuryl anion is truly isolable and studied by X-ray crystallography. In all cases, facile one-electron oxidation of these anions occurs, which allows the isolation of the neutral dithienyl and diimino-difuryl radicals. UV-Visible and time-dependent density functional theory studies reveal that the oxidation of the dithienyl anion to its radical is associated with an increase in the highest (singly) occupied molecular orbital-lowest unoccupied molecular orbital gap, evident through a hypsochromic shift of the main absorption band in the electronic spectrum, whereas oxidation of the diimino-difuryl anion causes only minor spectroscopic changes. Electrochemical studies support the stability of the radicals with respect to the anion, showing strongly negative oxidation potentials. The control of the redox activity of these diarylmethene carbanions through variation of the nature of the substituents, donor-atom, and the conjugated π-system and their potential as ligands for redox-inert metal centers makes them intriguing candidates as noninnocent partners for redox reactions.

We present a detailed measurement of charged two- pion correlation functions in 0–30% centrality sNN=200 GeV Au+Au collisions by the PHENIX experiment at the Relativistic Heavy Ion Collider. The data are well described by Bose- Einstein correlation functions stemming from Levy-stable source distributions. Using a fine transverse momentum binning, we extract the correlation strength parameter λ, the Levy index of stability α, and the Levy length scale parameter R as a function of average transverse mass of the pair mT. We find that the positively and the negatively charged pion pairs yield consistent results, and their correlation functions are represented, within uncertainties, by the same Levy-stable source functions. The λ(mT) measurements indicate a decrease of the strength of the correlations at low mT. The Levy length scale parameter R(mT) decreases with increasing mT, following a hydrodynamically predicted type of scaling behavior. The values of the Levy index of stability α are found to be significantly lower than the Gaussian case of α=2, but also significantly larger than the conjectured value that may characterize the critical point of a second-order quark-hadron phase transition.

The oxygenation of aliphatic and aromatic hydrocarbons using earth-abundant Fe and Cu catalysts and "green" oxidants such as hydrogen peroxide is becoming increasingly important to atom-economical chemical processing. In light of this, we describe that dinuclear CuII complexes of pyrrolic Schiff-base macrocycles, in combination with ferric chloride (FeCl3), catalyze the oxygenation of π-activated benzylic substrates with hydroperoxide oxidants at room temperature and low loadings, representing a novel design in oxidation catalysis. Mass spectrometry and extended X-ray absorption fine structure analysis indicate that a cooperative action between CuII and FeIII occurs, most likely because of the interaction of FeCl3 or FeCl4 - with the dinuclear CuII macrocycle. Voltammetric measurements highlight a modulation of both CuII and FeIII redox potentials in this adduct, but electron paramagnetic resonance spectroscopy indicates that any Cu-Fe intermetallic interaction is weak. High ketone/alcohol product ratios, a small reaction constant (Hammett analysis), and small kinetic isotope effect for H-atom abstraction point toward a free-radical reaction. However, the lack of reactivity with cyclohexane, oxidation of 9,10-dihydroanthracene, oxygenation by the hydroperoxide MPPH (radical mechanistic probe), and oxygenation in dinitrogen-purge experiments indicate a metal-based reaction. Through detailed reaction monitoring and associated kinetic modeling, a network of oxidation pathways is proposed that includes "well-disguised" radical chemistry via the formation of metal-associated radical intermediates.

The controlled manipulation of the axial oxo and equatorial halide ligands in the uranyl dipyrrin complex, UO2Cl(L) allows the uranyl reduction potential to be shifted by 1.53 V into the range accessible to naturally occurring reductants that are present during uranium remediation and storage processes. Abstraction of the equatorial halide ligand to form the uranyl cation causes a 780 mV positive shift in the UV/UIV reduction potential. Borane-functionalization of the axial oxo groups causes the spontaneous homolysis of the equatorial U-Cl bond and a further 750 mV shift of this po-tential. The combined effect of chloride loss and borane co-ordination to the oxo groups allows reduction of UVI to UIV by H2 or other very mild reductants such as Cp*2Fe. The reduction with H2 is accompanied by a B-C bond cleavage process in the oxo-coordinated borane.

This chapter describes the testing of the computer-human interface of Virtual Internship Authorware (VIA), an authoring tool for creating web-based virtual internships. The authors describe several benchmark tasks that would be performed by authors who create lessons on the subject matter of land science. Performance on each task was measured by task completion times and the likelihood of completing the task. Data were collected from ten novices and three experts familiar with the broader learning environment called Intershipinator. Task completion times and the number of steps to complete the tasks were also modeled by GOMS (Goals, Operators, Methods, and Selection), a theoretical model that predicts these measures of user interaction based on a computational psychological model of computer-human interaction. The output from the GOMS simulations of task completion times and number of steps robustly predicted the performance of both novices and experts. Large deviations between model predictions and human performance are expected to guide modifications of the authoring tool.

BACKGROUND: The objective of this study was to review the international experience in lung transplantation using lung donation after circulatory death (DCD).METHODS: In this retrospective study, data from the International Society for Heart and Lung Transplantation (ISHLT) DCD Registry were analyzed. The study cohort included DCD lung transplants performed between January 2003 and June 2013, and reported to the ISHLT DCD Registry as of April 2014. The participating institutions included 10 centers in North America, Europe and Australia. The control group was a cohort of lung recipients transplanted using brain-dead donors (DBDs) during the same study period. The primary end-point was survival after lung transplantation.RESULTS: There were 306 transplants performed using DCD donors and 3,992 transplants using DBD donors during the study period. Of the DCD transplants, 94.8% were Maastricht Category whereas 4% were Category IV and 1.2% Category V (euthanasia). Heparin was given in 54% of the cases, donor extubation occurred in 90% of the cases, and normothermic ex vivo lung perfusion (EVLP) was used in 12%. The median time from withdrawal of life support therapy (WLST) to cardiac arrest was 15 minutes (5th to 95th percentiles of 5 to 55 minutes), and from WLST to cold flush was 33 minutes (5th to 95th percentiles of 19.5 to 79.5 minutes). Recipient age and medical diagnosis were similar in DCD and DBD groups (p = not significant ENS]). Median hospital length of stay was 18 days in DCD lung transplants and 16 days in DBD transplants (p = 0.016). Thirty-day survival was 96% in the DCD group and 97% in the DBD group. One-year survival was 89% in the DCD group and 88% in the DBD group (p = NS). Five-year survival was 61% in both groups (p = NS). The mechanism of donor death within the DCD group seemed to influence recipient early survival. The survival rates through 30 days were significantly different by donor mechanism of death (p = 0.0152). There was no significant correlation between the interval of WLST to pulmonary flush with survival (p = 0.11).CONCLUSION: This large study of international, multi-center experience demonstrates excellent survival after lung transplantation using DCD donors. It should be further evaluated whether the mechanism of donor death influences survival after DCD transplant. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.

High anion selectivity for PtCl6(2-) over Cl(-) is shown by a series of amidoamines, R(1)R(2)NCOCH2CH2NR(3)R(4) (L1 with R(1) = R(4) = benzyl and R(2) = R(3) = phenyl and L3 with R(1) = H, R(2) = 2-ethylhexyl, R(3) = phenyl and R(4) = methyl), and amidoethers, R(1)R(2)NCOCH2CH2OR(3) (L5 with R(1) = H, R(2) = 2-ethylhexyl and R(3) = phenyl), which provide receptor sites which extract PtCl6(2-) preferentially over Cl(-) in extractions from 6 M HCl solutions. The amidoether receptor L5 was found to be a much weaker extractant for PtCl6(2-) than its amidoamine analogues. Density functional theory calculations indicate that this is due to the difficulty in protonating the amidoether to generate a cationic receptor, LH(+), rather than the latter showing weaker binding to PtCl6(2-). The most stable forms of the receptors, LH(+), contain a tautomer in which the added proton forms an intramolecular hydrogen bond to the amide oxygen atom to give a six-membered proton chelate. Dispersion-corrected DFT calculations appear to suggest a switch in ligand conformation for the amidoamine ligands to an open tautomer state in the complex, such that the cationic N-H or O-H groups are also readily available to form hydrogen bonds to the PtCl6(2-) ion, in addition to the array of polarized C-H bonds. The predicted difference in energies between the proton chelate and nonchelated tautomer states for L1 is small, however, and the former is found in the X-ray crystal structure of the assembly [(L1H)2PtCl6]. The DFT calculations and the X-ray structure indicate that all LH(+) receptors present an array of polarized C-H groups to the large, charge diffuse PtCl6(2-) anion resulting in high selectivity of extraction of PtCl6(2-) over the large excess of chloride.

In this review, we discuss the current state of donation after circulatory death (DCD). We define the DCD donor and describe the current protocols in management of the DCD patient. We then discuss current techniques in organ procurement of the lung and abdominal organs.Although donation after brain death is preferable to DCD, recent data have demonstrated acceptable early outcomes in both thoracic and abdominal organ transplant. In spite of advancements in surgical techniques and organ preservation, much has yet to be learned to minimize warm ischemia time and reperfusion injury in the DCD population.In light of the continually growing disparity between organ supply and demand, DCD has regained traction as a means to increase the donor pool.

The design of ligands that can act as platforms for the controlled, “bottom-up” synthesis of transition-metal clusters is a promising approach to accessing enzymatic mimics and new small-molecule reaction chemistry. This approach is exemplified here through the coordination chemistry of two compartmental Schiff-base calixpyrroles (H4L) that usually act as dinucleating ligands for transition metals. While reactions between H4L and Zn{N(SiMe3)2}2 form the expected dinuclear Zn “Pacman” complexes Zn2(L), reactions with ZnEt2 result in the tetranuclear Zn alkyl complexes Zn4Et4(THF)4(L), in which open, “bowl-shaped” structures are adopted due to the flexibility of the macrocyclic platform. The outcome of hydrolysis reactions of these tetranuclear complexes is found to depend on the macrocyclic cavity size, with the smaller macrocycle favoring oxo formation in Zn4(μ4-O)Et2(L) and the larger macrocycle favoring complete hydrolysis to form the hydroxide-bridged cluster Zn4(μ2-OH)4(L). This latter complex reacts ...

U(III) complexes of the conformationally flexible, small-cavity macrocycle trans-calix[2]benzene[2]pyrrolide (L)2–, [U(L)X] (X = O-2,6-tBu2C6H3, N(SiMe3)2), have been synthesized from [U(L)BH4] and structurally characterized. These complexes show binding of the U(III) center in the bis(arene) pocket of the macrocycle, which flexes to accommodate the increase in the steric bulk of X, resulting in long U–X bonds to the ancillary ligands. Oxidation to the cationic U(IV) complex [U(L)X][B(C6F5)4] (X = BH4) results in ligand rearrangement to bind the smaller, harder cation in the bis(pyrrolide) pocket, in a conformation that has not been previously observed for (L)2–, with X located between the two ligand arene rings.

Organic-phase supramolecular ion pair (SIP) host-guest assemblies of perrhenate anions (ReO4(-)) with ammonium amide receptor cations are reported. These compounds act as catalysts for the epoxidation of alkenes by aqueous hydrogen peroxide under biphasic conditions and can be recycled several times with no loss in activity.

Oxidation of acyclic Schiff-base dipyrromethanes cleanly results in dipyrrins, whereas the macrocyclic 'Pacman' analogues either decompose or form new dinuclear copper(ii) complexes that are inert to ligand oxidation; the unhindered hydrogen substituent at the meso-carbon allows new structural motifs to form.

Simple ammonium and pyridinium perrhenate salts were evaluated as catalysts for the deoxydehydration (DODH) of diols into alkenes. Pyridinium perrhenates were found to be effective catalysts at much lower temperatures than those in previous reports, outperforming primary, secondary, and tertiary ammonium salts, while quaternary ammonium salts are effectively inactive. The mechanism of reaction was studied computationally using DFT calculations which indicate that proton shuttling between the ion pair is intrinsic to the mechanism and that the reduction of rhenium by the phosphine occurs before the diol condensation.

Introduction The continual reassessment method (CRM) is a model-based design for phase I trials, which aims to find the maximum tolerated dose (MTD) of a new therapy. The CRM has been shown to be more accurate in targeting the MTD than traditional rule-based approaches such as the 3 + 3 design, which is used in most phase I trials. Furthermore, the CRM has been shown to assign more trial participants at or close to the MTD than the 3 + 3 design. However, the CRM’s uptake in clinical research has been incredibly slow, putting trial participants, drug development and patients at risk. Barriers to increasing the use of the CRM have been identified, most notably a lack of knowledge amongst clinicians and statisticians on how to apply new designs in practice. No recent tutorial, guidelines, or recommendations for clinicians on conducting dose-finding studies using the CRM are available. Furthermore, practical resources to support clinicians considering the CRM for their trials are scarce. Methods To help overcome these barriers, we present a structured framework for designing a dose-finding study using the CRM. We give recommendations for key design parameters and advise on conducting pre-trial simulation work to tailor the design to a specific trial. We provide practical tools to support clinicians and statisticians, including software recommendations, and template text and tables that can be edited and inserted into a trial protocol. We also give guidance on how to conduct and report dose-finding studies using the CRM. Results An initial set of design recommendations are provided to kick-start the design process. To complement these and the additional resources, we describe two published dose-finding trials that used the CRM. We discuss their designs, how they were conducted and analysed, and compare them to what would have happened under a 3 + 3 design. Conclusions The framework and resources we provide are aimed at clinicians and statisticians new to the CRM design. Provision of key resources in this contemporary guidance paper will hopefully improve the uptake of the CRM in phase I dose-finding trials. Electronic supplementary material The online version of this article (10.1186/s12874-018-0638-z) contains supplementary material, which is available to authorized users.

We report the coordination chemistry of the tripodal tris[2-amido(2-pyridyl)ethyl]amine ligand, L, with thorium(iv) and uranium(iv). Using a salt-metathesis strategy from the potassium salt of this ligand, K3L, new actinide complexes were isolated, namely the dimeric thorium complex [ThCl(L)]2 (1) and the monomeric uranium complex UI(THF)(L) (2); under different crystallisation conditions, the dimeric uranium complex is also isolated, [UI(L)]2 (2-dimer). With the aim of studying electronic phenomena such as magnetic exchange between two actinide ions, we have synthesised the first examples of dinuclear, quinoid-bridged actinide complexes from dianionic 2,5-bis[2,6-(diisopropyl)anilide]-1,4-benzoquinone (QDipp) and 2,5-bis[2-(methoxy)anilide]-1,4-benzoquinone (QOMe) ligands. The resulting complexes are [Th(L)]2QDipp (3), [Th(THF)(L)]2QOMe (5) and [U(L)]2QOMe (6). The targeted [U(L)]2QDipp complex (4) could not be isolated. All isolated complexes have been characterised by spectroscopic methods and X-ray crystallography. The uranium(iv) complexes 2-dimer and 6 have been studied by SQUID magnetometry but indicate that there is negligible magnetic exchange between the two uranium(iv) ions. The reduced form of 6, [K(18-c-6)][6-] is unstable and highly sensitive, but X-ray crystallography indicates that it is a novel UIVUIV complex bridged by a quinoid-radical.

We report a measurement of e+e− pairs from semileptonic heavy-flavor decays in p+p collisions at sNN=200 GeV. The e+e− pair yield from bb¯ and cc¯ is separated by exploiting a double differential fit done simultaneously in dielectron invariant mass and pT. We used three different event generators, pythia, mc@nlo, and powheg, to simulate the e+e− spectra from cc¯ and bb¯ production. The data can be well described by all three generators within the detector acceptance. However, when using the generators to extrapolate to 4π, significant differences are observed for the total cross section. These difference are less pronounced for bb¯ than for cc¯. The same model dependence was observed in already published d+A data. The p+p data are also directly compared with d+A data in mass and pT, and within the statistical accuracy no nuclear modification is seen.

The simple perrhenate salt [N(hexyl)4][(ReO4)] acts as a catalyst for the reduction of organic carbonyls and carbon dioxide by primary and secondary hydrosilanes. In the case of CO2, this results in the formation of methanol equivalents via silylformate and silylacetal intermediates. Furthermore, the addition of alkylamines to the reaction mixture favours catalytic amine N-methylation over methanol production under certain conditions. DFT analysis of the mechanism of CO2 reduction shows that the perrhenate anion activates the silylhydride forming a hypervalent silicate transition state such that the CO2 can directly cleave a Si–H bond.

The reduction of UVI uranyl halides or amides with simple LnII or UIII salts forms highly symmetric, linear, oxo-bridged trinuclear UV /LnIII /UV , LnIII /UIV /LnIII , and UIV /UIV /UIV complexes or linear LnIII /UV polymers depending on the stoichiometry and solvent. The reactions can be tuned to give the products of one- or two-electron uranyl reduction. The reactivity and magnetism of these compounds are discussed in the context of using a series of strongly oxo-coupled homo- and heterometallic poly(f-block) chains to better understand fundamental electronic structure in the f-block.

The first use of a dinuclear UIII/UIII complex in the activation of small molecules is reported., The first use of a dinuclear UIII/UIII complex in the activation of small molecules is reported. The octadentate Schiff-base pyrrole, anthracene-hinged ‘Pacman’ ligand LA combines two strongly reducing UIII centres and three borohydride ligands in [M(THF)4][{U(BH4)}2(μ-BH4)(LA)(THF)2] 1-M, (M = Li, Na, K). The two borohydride ligands bound to uranium outside the macrocyclic cleft are readily substituted by aryloxide ligands, resulting in a single, weakly-bound, encapsulated endo group 1 metal borohydride bridging the two UIII centres in [{U(OAr)}2(μ-MBH4)(LA)(THF)2] 2-M (OAr = OC6H2tBu3-2,4,6, M = Na, K). X-ray crystallographic analysis shows that, for 2-K, in addition to the endo-BH4 ligand the potassium counter-cation is also incorporated into the cleft through η5-interactions with the pyrrolides instead of extraneous donor solvent. As such, 2-K has a significantly higher solubility in non-polar solvents and a wider U–U separation compared to the ‘ate’ complex 1. The cooperative reducing capability of the two UIII centres now enforced by the large and relatively flexible macrocycle is compared for the two complexes, recognising that the borohydrides can provide additional reducing capability, and that the aryloxide-capped 2-K is constrained to reactions within the cleft. The reaction between 1-Na and S8 affords an insoluble, presumably polymeric paramagnetic complex with bridging uranium sulfides, while that with CS2 results in oxidation of each UIII to the notably high UV oxidation state, forming the unusual trithiocarbonate (CS3)2– as a ligand in [{U(CS3)}2(μ-κ2:κ2-CS3)(LA)] (4). The reaction between 2-K and S8 results in quantitative substitution of the endo-KBH4 by a bridging persulfido (S2)2– group and oxidation of each UIII to UIV, yielding [{U(OAr)}2(μ-κ2:κ2-S2)(LA)] (5). The reaction of 2-K with CS2 affords a thermally unstable adduct which is tentatively assigned as containing a carbon disulfido (CS2)2– ligand bridging the two U centres (6a), but only the mono-bridged sulfido (S)2– complex [{U(OAr)}2(μ-S)(LA)] (6) is isolated. The persulfido complex (5) can also be synthesised from the mono-bridged sulfido complex (6) by the addition of another equivalent of sulfur.

The heterotetra- and bimetallic uranium(IV)–rhodium(I) complexes [UIVI2(μ-OArP-1κ1O,2κ1P)2RhI(μ-I)]2 (2) (ArPO− = 2-(diphenylphosphino)-6-tert-butyl-4-methylphenoxide) and UIVI(μ-I)(μ-OArP-1κ1O,2κ1P)3RhI (3) were prepared by treatment of UIVI(OArP-κ2O,P)3 (1) with rhodium(I) iodide olefin complexes. The reaction of 1 with the monodentate cyclooctene (coe) rhodium(I) precursor [(coe)2RhII]2 gives only the bimetallic complex [UIVRhI] 3, and with the diene [(cod)RhII]2 (5) (cod = 1,5-cyclooctadiene), mixtures of [UIVRhI]2 complex 2 and [UIVRhI] 3 along with (cod)RhIOArP-κ2O,P (4), a RhI side-product from the formation of 2. The complexes were characterised by single crystal X-ray diffraction, NMR and UV-vis-NIR spectroscopy, and electrochemistry. The UIV–RhI intermetallic distances in 2 (2.7601(5) A) and 3 (2.7630(5) A) are among the shortest between f-elements and transition metals reported to date. Despite almost identical U–Rh bond lengths in the solid state, in solution only weak, and very different interactions between the metal centres are found.

Background: Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM). Methods: We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation. Results: We describe the benefits of model-based designs (flexibility, superior operating characteristics, extended scope), their current uptake, and existing resources. The most prominent barriers to implementation of a model-based design were lack of suitable training, chief investigators’ preference for algorithm-based designs (e.g., 3+3), and limited resources for study design before funding. We use a real-world example to illustrate how these barriers can be overcome. Conclusions: There is overwhelming evidence for the benefits of CRM. Many leading pharmaceutical companies routinely implement model-based designs. Our analysis identified barriers for academic statisticians and clinical academics in mirroring the progress industry has made in trial design. Unified support from funders, regulators, and journal editors could result in more accurate doses for later-phase testing, and increase the efficiency and success of clinical drug development. We give recommendations for increasing the uptake of model-based designs for dose-finding trials in academia.

The first thorium(IV) and uranium(IV) hydrocarbyl complexes of a trans-calix[2]benzene[2]pyrrolide macrocycle can use ligand non-innocence to enable multiple C-H bond activation reactions at the metal. Both alkyl and alkynylcomplexes supported by the (L) dianion and (L-2H) tetraanion are reported. The ThIV and UIV mono-alkyl –ate complexes [M(L-2H)An(R)] (M = K for R = CH2Ph, M = Li for R = Me, CH2SiMe3), in which the ligand aryl groups are metallated, add the C-H bonds of terminal alkynes across the metal and ligand, forming the AnIV-alkynyl complexes [(L)An(C≡CR’)2] (R’ =SiMe3, SiiPr3). This ligand reprotonation from (L-2H)4- to (L)2- is accompanied by a change in coordination mode of the ligand from η5:η5 to η5:η1:η5:η1. Alternatively, the original alkyl group can be retained if the ligand is reprotonated using[Et3NH][BPh4], affording the ThIV cations [(L)Th(R)][BPh4] (R = CH2Ph, N(SiMe3)2). Again, ligand rearrangement to the κ1:η6:κ1:η6 coordination mode occurs. These complexes provide rare examples of bis(arene) actinide sandwich geometry. The two η1-alkynides in [(L)Th(C≡CSiMe3)2] rearrange upon coordination of [Ni0], forming [(L)Th(C≡CSiMe3)2·Ni(PR''3)] (R'' =phenyl, cyclohexyl) – featuring the shortest yet reported distance between Th and Ni, and giving unprecedented insight into the changes in macrocyclic ligand coordination between κ1:η6:κ1:η6 and η5:η5 coordination modes. A computational study of this conformational change demonstrates the η5:η5 coordination mode to be the more stable in the Th/Ni bimetallics (and hypothetical Pt analogues), an observation rationalised by detailed analysis of the Kohn-Sham orbital structure of the κ1:η6:κ1:η6 and η5:η5 conformers. Although remarkably inert to even high-pressures of CO2 at room temperature, the bis(alkynyl) complexes [(L)An(C≡CSiMe3)2] completely cleave one CO bond of CO2 when heated under a 1 bar pressure, resulting in the formation, and elimination from the metal, of a new, CO-inserted, bicyclic, carbonylated macrocycle with complete control over the C-C and C-N bond forming reactions.

bibtex: ISI:000391454500009 bibtex\location:'THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND',publisher:'ROYAL SOC CHEMISTRY',type:'Article',affiliation:'Arnold, PL; Love, JB (Reprint Author), Univ Edinburgh, EaStCHEM Sch Chem, Joseph Black Bldg,David Brewster Rd, Edinburgh EH9 3FJ, Midlothian, Scotland. Pankhurst, James R.; Bell, Nicola L.; Zegke, Markus; Platts, Lucy N.; Arnold, Polly L.; Love, Jason B., Univ Edinburgh, EaStCHEM Sch Chem, Joseph Black Bldg,David Brewster Rd, Edinburgh EH9 3FJ, Midlothian, Scotland. Lamfsus, Carlos Alvarez; Maron, Laurent, Univ Toulouse, INSA, LPCNO, 135 Ave Rangueil, F-31077 Toulouse 4, France. Natrajan, Louise S., Univ Manchester, Sch Chem, Ctr Radiochem Res, Oxford Rd, Manchester M13 9PL, Lancs, England. Sproules, Stephen, Univ Glasgow, WestCHEM Sch Chem, Glasgow G12 8QQ, Lanark, Scotland.','author-email':'polly.arnold@ed.ac.uk jason.love@ed.ac.uk',da:'2018-12-05','doc-delivery-number':'EH0LC',eissn:'2041-6539','funding-acknowledgement':'University of Edinburgh; EPSRC; Royal Society of Chemistry; Leverhulme Trust [RL-2012-072]; Engineering and Physical Sciences Research Council [EP/M010554/1]','funding-text':'We thank the University of Edinburgh and the EPSRC for financial support. We also thank Dr J. A. Hlina for preparing [TiCp\textlessINF\textgreater2\textless/INF\textgreaterCl]\textlessINF\textgreater2\textless/INF\textgreater and [\textlessSUP\textgreatern\textless/SUP\textgreaterBu\textlessINF\textgreater4\textless/INF\textgreaterN][BPh\textlessINF\textgreater4\textless/INF\textgreater], Dr J. Bella for NMR support, and Dr G. S. Nichol for guidance with X-ray crystallography. S. S. gratefully acknowledges the Royal Society of Chemistry for a J. W. T. Jones Travelling Fellowship Grant. L. S. N. thanks the Leverhulme Trust for a Research Leadership Award (RL-2012-072).','journal-iso':'Chem. Sci.','keywords-plus':'PENTAVALENT-URANYL; URANIUM COMPLEXES; LIGANDS; OXO; COORDINATION; SILYLATION; ION; FUNCTIONALIZATION; CRYSTAL; OXIDE','number-of-cited-references':'61',oa:'DOAJ Gold, Green Published','orcid-numbers':'Pankhurst, James/0000-0003-1410-1980 Arnold, Polly/0000-0001-6410-5838 Alvarez Lamsfus, Carlos/0000-0002-4442-7052 Bell, Nicola L./0000-0002-7497-9667','research-areas':'Chemistry','researcherid-numbers':'Pankhurst, James/P-6404-2018','times-cited':'19','unique-id':'ISI:000391454500009','usage-count-last-180-days':'4','usage-count-since-2013':'64','web-of-science-categories':'Chemistry, Multidisciplinary'\; International audience; The uranyl(VI) complex UO2Cl(L) of the redox-active, acyclic diimino-dipyrrin anion, L- is reported and its reaction with inner-and outer-sphere reductants studied. Voltammetric, EPR-spectroscopic and X-ray crystallographic studies show that chemical reduction by the outer-sphere reagent CoCp2 initially reduces the ligand to a dipyrrin radical, and imply that a second equivalent of CoCp2 reduces the U(VI) centre to form U(V). Cyclic voltammetry indicates that further outer-sphere reduction to form the putative U(IV) trianion only occurs at strongly cathodic potentials. The initial reduction of the dipyrrin ligand is supported by emission spectra, X-ray crystallography, and DFT; the latter also shows that these outer-sphere reactions are exergonic and proceed through sequential, one-electron steps. Reduction by the inner-sphere reductant [TiCp2Cl](2) is also likely to result in ligand reduction in the first instance but, in contrast to the outer-sphere case, reduction of the uranium centre becomes much more favoured, allowing the formation of a crystallographically characterised, doubly-titanated U(IV) complex. In the case of inner-sphere reduction only, ligand-to-metal electron-transfer is thermodynamically driven by coordination of Lewis-acidic Ti(IV) to the uranyl oxo, and is energetically preferable over the disproportionation of U(V). Overall, the involvement of the redox-active dipyrrin ligand in the reduction chemistry of UO2Cl(L) is inherent to both inner-and outer-sphere reduction mechanisms, providing a new route to accessing a variety of U(VI), U(V), and U(IV) complexes.

The US National Library of Medicine (NLM) offers Internet-based, no-cost resources useful for responding to the 2014 West Africa Ebola outbreak. Resources for health professionals, planners, responders, and researchers include PubMed, Disaster Lit, the Web page “Ebola Outbreak 2014: Information Resources,” and the Virus Variation database of sequences for Ebolavirus. In cooperation with participating publishers, NLM offers free access to full-text articles from over 650 biomedical journals and 4000 online reference books through the Emergency Access Initiative. At the start of a prolonged disaster event or disease outbreak, the documents and information of most immediate use may not be in the peer-reviewed biomedical journal literature. To maintain current awareness may require using any of the following: news outlets; social media; preliminary online data, maps, and situation reports; and documents published by nongovernmental organizations, international associations, and government agencies. Similar to the pattern of interest shown in the news and social media, use of NLM Ebola-related resources is also increasing since the start of the outbreak was first reported in March 2014 (Disaster Med Public Health Preparedness. 2014;0:1-4)

From 2010 to 2013, the National Library of Medicine (NLM) Disaster Information Management Research Center (DIMRC) continued to build its programs and services on the foundation laid in its starting years, 2008–2010. Prior to 2008, NLM had a long history of providing health information, training, and tools in response to disasters. Aware of this legacy, the NLM long range plan (Charting a Course for the 21st Century: NLM’s Long Range Plan 2006–2016) called for creation of a center to show “a strong commitment to disaster remediation and to provide a platform for demonstrating how libraries and librarians can be part of the solution to this national problem”. NLM is continuing efforts to ensure that medical libraries have plans for the continuity of their operations, librarians are trained to understand their roles in preparedness and response, online disaster health information resources are available for many audiences and in multiple formats, and research is conducted on tools to enhance the exchange of critical information during and following disasters. This paper describes the 2010–2013 goals and activities of DIMRC and its future plans.

Psychopathy is a personality construct characterized by shallow affect, lack of empathy, and impulsiveness. We investigated the relations between psychopathy, subjective well-being and personality in 427 undergraduates. Prevalence rates for psychopathy, based on participants who endorsed eight or more primary psychopathy items, were 22.6% of males and 7.5% of females. Psychopathy was associated with high levels of depression and negative affect, and low levels of life satisfaction, happiness and positive affect. Psychopathy accounted for significant portions of the variance in depression (16.6%), negative affect (16.9%), life satisfaction (13.7%), happiness (14.4–18.3%) and positive affect (9.8%). However, psychopathy failed to account for variance in either ill-being or well-being above and beyond the variance accounted for by personality. These results support the position that psychopathy can be thought of as a constellation of extreme levels of normative personality traits.

Alexithymia is a personality construct characterized by a cognitive and an affective deficit in recognizing and communicating emotional states. The present research investigated the relations between alexithymia, well-being, and romantic relationships in 437 undergraduates. High levels of alexithymia were found in 18.5 % of the sample and were associated with high levels of depression and negative affect, and low levels of life satisfaction, happiness and positive affect. Alexithymia was also negatively correlated with the quality of romantic relationships and with commitment, romance, trust, satisfaction and love in romantic relationships. The relation between alexithymia and subjective well-being was mediated in part by the poor quality of their romantic relationships. Alexithymia accounted for significant portions of the variance in depression (19.0 %), negative affect (17.4 %), life satisfaction (14.4 %), happiness (20.4–29.8 %) and positive affect (20.1 %). However, alexithymia failed to account for variance in either negative or positive well-being above and beyond the variance accounted for by the Big Five personality traits. These results are consistent with the position that alexithymia can be thought of as a constellation of extreme levels of normative personality traits.

The PHENIX experiment at the BNL Relativistic Heavy Ion Collider has measured second- and third-order Fourier coefficients of the azimuthal distributions of direct photons emitted at midrapidity in Au+Au collisions at sNN=200 GeV for various collision centralities. Combining two different analysis techniques, results were obtained in the transverse momentum range of 0.4

Aspiration of gastroesophageal refluxate has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and the progression of bronchiolitis obliterans syndrome after lung transplantation. The goals of the present study were to identify lung transplant patients at the greatest risk of aspiration and to investigate the causative factors.From September 2009 to November 2011, 252 bronchoalveolar lavage fluid (BALF) samples were collected from 100 lung transplant patients. The BALF pepsin concentrations and the results of transbronchial biopsy, esophageal function testing, barium swallow, and gastric emptying scan were compared among those with the most common end-stage lung diseases requiring lung transplantation: IPF, chronic obstructive pulmonary disease, cystic fibrosis, and α1-antitrypsin deficiency.Patients with IPF had higher BALF pepsin concentrations and a greater frequency of acute rejection than those with α1-antitrypsin deficiency, cystic fibrosis, or chronic obstructive pulmonary disease (P = 0.037). Moreover, the BALF pepsin concentrations correlated negatively with a lower esophageal sphincter pressure and distal esophageal amplitude; negatively with distal esophageal amplitude and positively with total esophageal acid time, longest reflux episode, and DeMeester score in those with chronic obstructive pulmonary disease; and negatively with the upright acid clearance time in those with IPF.Our results suggest that patients with IPF after lung transplantation are at increased risk of aspiration and a greater frequency of acute rejection episodes, and that the risk factors for aspiration might be different among those with the most common end-stage lung diseases who have undergone lung transplantation. These results support the role of evaluating the BALF for markers of aspiration in assessing lung transplant patients as candidates for antireflux surgery.

In 2008, the National Library of Medicine NLM established the Disaster Information Management Research Center DIMRC. Prior to 2008, NLM had a long history of involvement in providing health information for disaster management. Aware of this legacy and moved by the catastrophic aftermath of Hurricane Katrina, the NLM long range plan Charting a Course for the 21st Century: NLM's Long Range Plan 2006--2016 called for creation of a center to show “a strong commitment to disaster remediation and to provide a platform for demonstrating how libraries and librarians can be part of the solution to this national problem”. NLM was urged to “ensure continuous access to health information and effective use of libraries and librarians when disasters occur”. In response to this charge, NLM has undertaken substantial efforts to ensure that medical libraries have plans for the continuity of their operations, librarians are trained to understand their roles in preparedness and response, online disaster health information resources are available for many audiences and in multiple formats, and research is conducted on tools to enhance the exchange of critical information during and following disasters. This paper documents the history, goals, initiatives, accomplishments and future plans of the Center.

OBJECTIVE To estimate the rates of early neonatal and maternal complications in a consecutive series of successful Kielland's rotational forceps deliveries. METHODS This was a retrospective cohort study of consecutive cases of successful rotational forceps deliveries performed in singleton pregnancies at 36 weeks of gestation or more in a tertiary referral center in Scotland, UK, from 2001 to 2008 (n=873). We also compared outcomes associated with successful rotational forceps deliveries in 2008 (n=150) with those of nonrotational forceps delivery (n=873), ventouse delivery (n=159), spontaneous vertex delivery (n=3,494), and emergency cesarean delivery (n=947). RESULTS There was one stillbirth associated with a rotational forceps delivery. This was diagnosed before application of forceps. After rotational forceps deliveries, 58 of 872 (6.7%) of live-born neonates were admitted to the neonatal unit. Twenty-seven of 872 (3.1%) neonates had one or more complications that could be attributable to traumatic delivery and seven neonates (0.8%) had a diagnosis of neonatal encephalopathy. When compared with alternative methods of delivery over a single year, neonatal admission rates after delivery by rotational forceps deliveries (5 of 150 [3.3%]) were not significantly different from spontaneous vertex delivery (128 of 3,494 [3.7%; P=1.00]) or ventouse delivery (6 of 159 [3.8%; P=1.00]) and lower than emergency cesarean delivery (106 of 947 [11.2%; P=.002). Postpartum hemorrhage rates after rotational forceps deliveries (8 of 150 [5.3%; P=.008]) were lower than those associated with emergency cesarean delivery (142 of 947 [15.0%; P=.008]). CONCLUSION Rates of short-term neonatal and maternal complications after successful rotational forceps deliveries are low. LEVEL OF EVIDENCE II.

IL-2 is a growth factor for activated T cells and is required for maintenance of naturally arising regulatory T cells (nTregs). Mice defective in IL-2/IL-2 receptor signaling pathways have impaired nTregs and suffer from lymphoproliferative disorders, suggesting that IL-2 is present and functional in healthy animals. However, the cellular source of IL-2 is currently unknown. To determine which cells produce IL-2 in healthy animals, we established mice carrying cre gene knock in at the il-2 locus (termed IL-2(cre)). When IL-2(cre) mice were crossed with EGFP reporter mice, EGFP was exclusively expressed by a fraction of CD4 T cells present in both lymphoid and non-lymphoid tissues. Live imaging of IL-2(cre) mice that carry the luciferase reporter showed concentrated localization of luciferase(+) cells in Peyer's patches. These cells were not observed in new born mice but appeared within 3days after birth. Reduction of antigen receptor repertoire by transgene expression reduced their number, indicating that recognition of environmental antigens is necessary for generation of these IL-2 producers in healthy animals. A substantial fraction of EGFP(+) cells also produce IL-10 and IFN-γ, a characteristic profile of type 1 regulatory T cells (Tr1). The data suggest that a group of Tr1 cells have addition roles in immune homeostasis by producing IL-2 along with other cytokines and help maintaining Tregs.

Background: There is a paucity of information regarding the management of blunt thoracic aortic injury in the pediatric population compared to adults. This article adds three cases of blunt thoracic aortic injuries in pediatric patients to the literature and analyzes these in conjunction with several of the previous case series which have been published. Methods: Three cases were reviewed along with 38 previously reported cases in an attempt to identify trends in demographics and management. The three new cases presented over a four year period. All are male. A six year old and a 17-year-old were involved in motor vehicle crashes and a 10-year-old was struck by a vehicle while skateboarding. Results: The 6-year-old and the 17-year-old were treated non-interventionally due to severe closed head injuries. One received beta blockade. Both survived. The third, without head injury, underwent interposition graft and also survived. Conclusions: These findings are not greatly dissimilar from the adult experience. In reviewing all 41 pediatric cases, findings reveal a high mortality, predominantly due to head injury as well as the aortic injury. Open repair and interposition grafting continue to be the mainstay of management, with endovascular procedures and non-operative management becoming more prevalent recently. The role of beta-blockade is unclear in children with this injury. Further multicenter prospective studies of this rare pediatric injury may be useful.

Background Metformin is widely used to treat gestational diabetes (GDM), but many women remain hyperglycaemic and require additional therapy. We aimed to determine recruitment rate and participant throughput in a randomised trial of glibenclamide compared with standard therapy insulin (added to maximum tolerated metformin) for treatment of GDM. Methods We conducted an open label feasibility study in 5 UK antenatal clinics among pregnant women 16 to 36 weeks’ gestation with metformin-treated GDM. Women failing to achieve adequate glycaemic control on metformin monotherapy were randomised to additional glibenclamide or insulin. The primary outcome was recruitment rate. We explored feasibility with uptake, retention, adherence, safety, glycaemic control, participant satisfaction and clinical outcomes. Results Records of 197 women were screened and 23 women randomised to metformin and glibenclamide (n = 13) or metformin and insulin (n = 10). Mean (SD) recruitment rate was 0.39 (0.62) women/centre/month. 9/13 (69.2%, 95%CI 38.6–90.9%) women adhered to glibenclamide and all provided outcome data (100% retention). There were no episodes of severe hypoglycaemia, but metformin and insulin gave superior glycaemic control to metformin and glibenclamide, with fewer blood glucose readings