To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
We summarize recent results from our study of the massive young super star clusters (SSCs) in the dwarf galaxy NGC 1569, and present new high-resolution NIRSPEC spectra that permit the measurement of a cluster's intrinsic stellar velocity dispersion. Thus we derive kinematic masses for the two brightest SSCs: 2.3 × 105 Msun for SSC B, and 3.9 × 105 and 4.4 × 105 Msun for the two components of SSC A.
The chromosphere is a complex region that acts as an intermediary between the magnetic flux emergence in the photosphere and the magnetic features seen in the corona. Large eruptions in the chromosphere of flares and filaments are often accompanied by ejections of coronal mass off the sun. Several studies have observed fast-moving progressive trains of compact bright points (called Sequential Chromospheric Brightenings or SCBs) streaming away from chromospheric flares that also produce a coronal mass ejection (CME). In this work, we review studies of SCBs and search for commonalties between them. We place these findings into a larger context with contemporary chromospheric and coronal observations. SCBs are fleeting indicators of the solar atmospheric environment as it existed before their associated eruption. Since they appear at the very outset of a flare eruption, SCBs are good early indication of a CME measured in the chromosphere.
The youngest super star clusters (SSCs) in the Antennae Galaxies (NGC 4038/39) drive supersonic mass-loaded outflows. High-resolution Keck/NIRSPEC spectroscopy reveals broad, spatially extended Brγ emission lines that are well-fit by simple wind models. Cluster mass-loss rates are up to 1.5 M⊙ yr−1 and terminal velocities are up to 205 km s−1. These emission-line clusters (ELCs) constitute at least 15% of the star formation rate in the Antennae, and their high star formation efficiencies imply that they will probably evolve into bound SSCs. The youngest ELC outflows are driven primarily by stellar winds, and they efficiently entrain ambient matter. They transfer or dissipate most of their energy and momentum in a hot or cool medium that does not emit Brγ. ELCs are the individual engines that power galactic-scale superwinds, viewed in their earliest evolutionary stage.
The youngest super star clusters (SSCs) in the merging Antennae Galaxies (NGC 4038/39) drive supersonic mass-loaded outflows from the HII regions in which they are embedded. High-resolution K-band Keck/NIRSPEC spectroscopy reveals broad, spatially extended Brγ emission in 16 targets. Simple wind models for the line profiles provide good fits and imply cluster mass-loss rates of up to 1.5 M⊙/year and terminal velocities of up to 205 km s−1. The emission-line clusters (ELCs) that drive these outflows constitute at least 15% of the star formation rate in the Antennae, and their high star formation efficiencies imply that they will probably evolve into bound SSCs. The youngest ELC outflows, which are driven primarily by stellar winds, very efficiently entrain ambient matter. The cluster winds transfer or dissipate a large fraction of their energy and momentum in a hot or cool medium that does not emit Brγ. ELCs are the individual engines that power galactic-scale superwinds, viewed in their earliest evolutionary stage.
The epidemiology of laboratory-confirmed respiratory syncytial virus (RSV) infections in young children has not recently been described in England, and is an essential step in identifying optimal target groups for future licensed RSV vaccines. We used two laboratory surveillance systems to examine the total number and number of positive RSV tests in children aged <5 years in England from 2010 to 2014. We derived odds ratios (ORs) with 95% confidence intervals (CIs) comparing children by birth month, using multivariable logistic regression models adjusted for age, season and sex. Forty-seven percent of RSV tests (29 851/63 827) and 57% (7405/13 034) of positive results in children aged <5 years were in infants aged <6 months. Moreover, 38% (4982/13 034) of positive results were in infants aged <3 months. Infants born in September, October and November had the highest odds of a positive RSV test during their first year of life compared to infants born in January (OR 2·1, 95% CI 1·7–2·7; OR 2·4, 95% CI 2·1–2·8; and OR 2·4, 95% CI 2·1–2·7, respectively). Our results highlight the importance of young age and birth month near the beginning of the RSV season to the risk of laboratory-confirmed RSV infection. Future control measures should consider protection for these groups.
Cambrian biostratigraphy of the Indian subcontinent is best documented from the Parahio Formation of the Tethyan Himalaya. Recently established trilobite biostratigraphy shows that the formation encompasses the latest part of unnamed Stage 4 and much of unnamed Stage 5. A variety of small shelly fossils have been recovered via acid digestion of carbonate beds and include tetract and pentact hexactinellid sponge spicules, chancelloriid spicules belonging to Chancelloria sp. and a new species, Archiasterella dhiraji, shells of an helcionelloid comparable to Igorella maidipingensis, a meraspid ptychopariid trilobite, the tubular Cupitheca sp., a poorly preserved hyolith, and an assortment of spinose microfossils of uncertain affinity. These newly recovered microfossils are consistent with the trilobite-based lower and middle Cambrian age determination and do not support a late Cambrian age for the top of the Parahio Formation advocated in some recent literature. The microfossils reported herein significantly expand the known diversity of such fossils from Cambrian strata in the Himalayan region, and allow for comparison of this fauna with others from Gondwanaland and elsewhere. Integration with trilobite data indicate that the stratigraphic ranges of many small shelly fossils described in this study are greater than previously recognized.
Apatites are often seen as good potential candidates for the immobilization of halide-rich wastes. In particular, phosphate apatites have received much attention in recent years, however, their synthesis often produces complicated multi-phase systems, with a number of secondary phases forming [1.2]. Calcium vanadinite (Ca5(VO4)3Cl) demonstrates a much simpler phase system, with only a single Ca2V2O7 secondary phase which can easily be retarded by the addition of excess CaCl2. However, when doping with SmCl3 (as an inactive analogue for AnCl3) the Sm forms a wakefieldite (SmVO4) phase rather than being immobilized within the vanadinite, a result of having to form an energetically unfavourable Ca vacancy in order for the lattice to remain neutral overall. It has been postulated that charge-balancing the lattice via co-substitution of a monovalent cation will be less disfavoured and therefore help stabilise formation of a (Ca5-2xSmxAx)(VO4)3Cl solid solution (A = monovalent cation). This has been investigated using a combined modelling and experimental approach. Static lattice calculations performed using Li+, Na+ and K+ as charge-balancing species have shown the energy cost to be less than half that of charge-balancing via formation of a Ca vacancy. As a result, solid state synthesis of (Ca5-2xSmxLix)(VO4)3Cl, (Ca5−2xSmxNax)(VO4)3Cl and (Ca5-2xSmxKx)(VO4)3Cl solid solutions have been trialled, and analysis of the resulting products has shown a significant reduction in both the SmVO4 and Ca2V2O7 secondary phases across all dopant levels.
Sodalite (Na8[AlSiO4]6Cl2), a naturally occurring Cl-containing mineral, has long been regarded as a potential immobilization matrix for the chloride salt wastes arising from pyrochemical reprocessing operations, as it allows for the conditioning of the waste salt as a whole without the need for any pre-treatment. Here the consolidation and densification of Sm-doped sodalite (as an analogue for AnCl3) has been investigated with the aim of producing fully dense (i.e. > 95 % t.d.) ceramic monoliths via conventional cold-press-and-sinter techniques at temperatures of < 1000 °C. Microstructural analysis of pressed and sintered sodalite powders under these conditions is shown to produce poorly sintered, porous, inhomogeneous pellets. However, by the addition of a sodium aluminophosphate glass sintering aid, fully dense Sm-sodalite ceramic monoliths can successfully be produced by sintering at temperatures as low as 800 °C.
Calcium chlorosilicate (Ca3(SiO4)Cl2) is seen as a potential host phase for the immobilization of Cl-rich wastes arising from pyrochemical reprocessing, a waste stream often containing a mix of both di- and trivalent cations. Substitution of trivalent cations into the lattice requires some form of charge compensation to ensure the lattice remains charge neutral overall. Whilst previous work has only examined this through the formation of Ca vacancies, this study investigates the feasibility of charge-balancing via the substitution of a monovalent cation onto the Ca sites of the lattice. To that end, a series of static lattice calculations were performed to determine the site selectivity of monovalent cations of differing size when substituted onto the Ca sites of the calcium chlorosilicate lattice and the solution energies for the overall substitution processes compared with those for charge compensation via vacancy formation. In all cases the monovalent charge-balancing species shows a clear preference for substitution onto the Ca1 site in the calcium chlorosilicate lattice. The solution energy of the substitution process increases with the increasing ionic radii of both the mono- and trivalent species as the steric stresses associated with substitution of larger cations than the Ca2+ host increase. As such, only charge-balancing using Li+, Na+ or K+ is more favourable than via formation of a Ca vacancy.
The Ebola Virus Disease (EVD) outbreak in West Africa has been declared a public health emergency of international concern by the World Health Organization. The Ebola outbreak has led to the disruption of already fragile but essential health services and drug distribution systems; HIV clinical services in Liberia, Sierra Leone, and Guinea were particularly affected. Targeted approaches are necessary to protect the continuity of HIV treatment for people living with HIV and should be integrated within the broader Ebola response; this will save lives, prevent drug resistance, and decrease the likelihood of HIV transmission. (Disaster Med Public Health Preparedness. 2015;9:522–526)
Paediatricians recognize that using the time-dependent community-acquired vs. hospital-acquired bloodstream infection (BSI) dichotomy to guide empirical treatment no longer distinguishes between causative pathogens due to the emergence of healthcare-associated BSIs. However, paediatric epidemiological evidence of the aetiology of BSIs in relation to hospital admission in England is lacking. For 12 common BSI-causing pathogens in England, timing of laboratory reports of positive paediatric (3 months to 5 years) bacterial blood isolates were linked to in-patient hospital data and plotted in relation to hospital admission. The majority (88·6%) of linked pathogens were isolated <2 days after hospital admission, including pathogens widely regarded as hospital acquired: Enterococcus spp. (67·2%) and Klebsiella spp. (88·9%). Neisseria meningitidis, Streptococcus pneumoniae, group A streptococcus and Salmonella spp. were unlikely to cause hospital-acquired BSI. Pathogens commonly associated with hospital-acquired BSI are being isolated <2 days after hospital admission alongside pathogens commonly associated with community-acquired BSI. We confirm that timing of blood samples alone does not differentiate between bacterial pathogens. Additional factors including clinical patient characteristics and healthcare contact should be considered to help predict the causative pathogen and guide empirical antibiotic therapy.
The quiet Sun observed in polarized light exhibits a rich and complex magnetic structuring which is still not fully resolved nor understood. The present work is intended to contribute to the debate about the origin of the quiet sun magnetic fields, in relation or not to the global solar dynamo. We present analysis of center-to-limb polarization measurements obtained with the SOT/SP spectropolarimeter onboard the Hinode satellite outside active regions, in 2007 and 2013, i.e. at a minimum and a maximum of the solar cycle, respectively. We compare the spatial fluctuation Fourier spectra of unsigned circular and linear polarization images after corrections for polarization bias and focus variations between the two data sets. The decay of active regions is clearly a source of magnetic fields in the quiet Sun. It leads to a global increase of the polarization fluctuation power spectrum in 2013 in the network. In the internetwork, we observe no variation of the polarization fluctuation power at mesogranular and granular scales, whereas it increases at sub-granular scales. We interpret these results in the following way. At the mesogranular and granular scales very efficient mechanisms of magnetic field removal are operating in the internetwork, that leads to a dissipation or a concentration of magnetic fields on smaller scales. So the cycle-invariant magnetic signal that we detect at mesogranular and granular scales must be continuously created by a dynamo mechanism which is independent of the solar cycle.
Antarctic and Southern Ocean science is vital to understanding natural variability, the processes that govern global change and the role of humans in the Earth and climate system. The potential for new knowledge to be gained from future Antarctic science is substantial. Therefore, the international Antarctic community came together to ‘scan the horizon’ to identify the highest priority scientific questions that researchers should aspire to answer in the next two decades and beyond. Wide consultation was a fundamental principle for the development of a collective, international view of the most important future directions in Antarctic science. From the many possibilities, the horizon scan identified 80 key scientific questions through structured debate, discussion, revision and voting. Questions were clustered into seven topics: i) Antarctic atmosphere and global connections, ii) Southern Ocean and sea ice in a warming world, iii) ice sheet and sea level, iv) the dynamic Earth, v) life on the precipice, vi) near-Earth space and beyond, and vii) human presence in Antarctica. Answering the questions identified by the horizon scan will require innovative experimental designs, novel applications of technology, invention of next-generation field and laboratory approaches, and expanded observing systems and networks. Unbiased, non-contaminating procedures will be required to retrieve the requisite air, biota, sediment, rock, ice and water samples. Sustained year-round access to Antarctica and the Southern Ocean will be essential to increase winter-time measurements. Improved models are needed that represent Antarctica and the Southern Ocean in the Earth System, and provide predictions at spatial and temporal resolutions useful for decision making. A co-ordinated portfolio of cross-disciplinary science, based on new models of international collaboration, will be essential as no scientist, programme or nation can realize these aspirations alone.
Apatites are often seen as good potential candidates for the immobilization of halide-rich wastes and, in particular, chlorapatite (Ca5(PO4)3Cl) has received much attention in recent years. However, synthesis of chlorapatite waste-forms can produce a complicated multi-phase system, with a number of secondary phases forming, including β-TCP (Ca3(PO4)2), spodiosite (Ca2(PO4)Cl) and pyrophosphate (Ca2P2O7), many of which require elevated temperatures and extended calcinations times to reduce. Calcium vanadinite (Ca5(VO4)3Cl) demonstrates a much simpler phase system, with calcination at 750 °C yielding Ca5(VO4)3Cl together a small quantity of a Ca2V2O7 secondary phase, the formation of which can be retarded by the addition of excess CaCl2. Characterization of compositions doped with SmCl3 as an inactive analogue for AnCl3 show the Cl to be immobilized in the vanadinite whilst the Sm forms a wakefieldite (SmVO4) phase.
Zirconolite (CaZrTi2O7), a durable and compositionally flexible titanate ceramic for the immobilization of separated actinides, is currently the UK’s preferred candidate phase for the immobilization of plutonium dioxide arising from aqueous reprocessing. Here, its suitability as a waste-form for actinide chlorides arising from pyrochemical reprocessing is investigated through synthesis via a molten salt mediated reaction using a number of different salt eutectics (MgCl2:NaCl, CaCl2:NaCl and KCl:NaCl). It is found that the effectiveness of the molten salt synthesis of zirconolite is governed by the solubility of ZrO2 in the salt medium used; the synthesis proceeding via the formation of a perovskite (CaTiO3) intermediate which then reacts with ZrO2 to form zirconolite via a solution-diffusion mechanism. Most notably, in the KCl:NaCl eutectic different zirconolite polytypes are formed at different synthesis temperatures, with zirconolite-3T forming at 900 °C, giving way to zirconolite-2M at 1200 °C.
Insight into dynamic electrochemical processes can be obtained with in situ electrochemical-scanning/transmission electron microscopy (ec-S/TEM), a technique that utilizes microfluidic electrochemical cells to characterize electrochemical processes with S/TEM imaging, diffraction, or spectroscopy. The microfluidic electrochemical cell is composed of microfabricated devices with glassy carbon and platinum microband electrodes in a three-electrode cell configuration. To establish the validity of this method for quantitative in situ electrochemistry research, cyclic voltammetry (CV), choronoamperometry (CA), and electrochemical impedance spectroscopy (EIS) were performed using a standard one electron transfer redox couple [Fe(CN)6]3−/4−-based electrolyte. Established relationships of the electrode geometry and microfluidic conditions were fitted with CV and chronoamperometic measurements of analyte diffusion coefficients and were found to agree with well-accepted values that are on the order of 10−5 cm2/s. Influence of the electron beam on electrochemical measurements was found to be negligible during CV scans where the current profile varied only within a few nA with the electron beam on and off, which is well within the hysteresis between multiple CV scans. The combination of experimental results provides a validation that quantitative electrochemistry experiments can be performed with these small-scale microfluidic electrochemical cells provided that accurate geometrical electrode configurations, diffusion boundary layers, and microfluidic conditions are accounted for.