Evolving Landscape of Carbapenem-Resistant

OBJECTIVES: The increased identification of carbapenem-resistant METHODS: A total of 169 CR-PA isolated from clinical specimens at a single centre in Houston, TX, USA were studied. Among them, 61 isolates collected between 1999 and 2005 were defined as historical strains, and 108 collected between 2017 and 2018 were defined as contemporary strains. Antimicrobial susceptibilities against selected β-lactams was determined. WGS data were used for the identification of antimicrobial resistance determinants and phylogenetic analysis. RESULTS: Non-susceptibility to ceftolozane/tazobactam and ceftazidime/avibactam increased from 2% (1/59) to 17% (18/108) and from 7% (4/59) to 17% (18/108) from the historical to the contemporary collection, respectively. Carbapenemase genes, which were not identified in the historical collection, were harboured by 4.6% (5/108) of the contemporary strains, and the prevalence of ESBL genes also increased from 3.3% (2/61) to 16% (17/108). Genes encoding acquired β-lactamases were largely confined to the high-risk clones. Among ceftolozane/tazobactam-resistant isolates, non-susceptibility to ceftazidime/avibactam, imipenem/relebactam and cefiderocol was observed in 94% (15/16), 56% (9/16) and 12.5% (2/16), respectively. Resistance to ceftolozane/tazobactam and imipenem/relebactam was primarily associated with the presence of exogenous β-lactamases. CONCLUSIONS: Acquisition of exogenous carbapenemases and ESBLs may be a worrisome trend i

Astrometry with the Hubble Space Telescope: Trigonometric Parallaxes of Selected Hyads

We present absolute parallaxes and proper motions for seven members of the Hyades open cluster, pre-selected to lie in the core of the cluster. Our data come from archival astrometric data from FGS 3, and newer data for 3 Hyads from FGS 1R, both white-light interferometers on the Hubble Space Telescope (HST). We obtain member parallaxes from six individual Fine Guidance Sensor (FGS) fields and use the field containing van Altena 622 and van Altena 627 (= HIP 21138) as an example. Proper motions, spectral classifications and VJHK photometry of the stars comprising the astrometric refer- ence frames provide spectrophotometric estimates of reference star absolute parallaxes. Introducing these into our model as observations with error, we determine absolute parallaxes for each Hyad. The parallax of vA 627 is significantly improved by including a perturbation orbit for this previously known spectroscopic binary, now an astrometric binary. Compared to our original (1997) determina- tions, a combination of new data, updated calibration, and improved analysis lowered the individual parallax errors by an average factor of 4.5. Comparing parallaxes of the four stars contained in the Hipparcos catalog, we obtain an average factor of 11 times improvement with the HST . With these new results, we also have better agreement with Hipparcos for the four stars in common. These new parallaxes provide an average distance for these seven members, = 47.5 pc, for the core a \pm 1 - {\sigma} dispersion depth of 3.6 pc, and a minimum depth from individual components of 16.0 \pm 0.9 pc. Absolute magnitudes for each member are compared to established main sequences, with excellent agreement. We obtain a weighted average distance modulus for the core of the Hyades of m-M=3.376 \pm 0.01, a value close to the previous Hipparcos values, m-M=3.33\pm 0.02.Comment: 21 pages, 7 figures, Astronomical Journal, accepted 2011-3-

Choices: Future Trade-Offs and Plausible Pathways

Policy development and management of deltas in the Anthropocene involves the consideration of trade-offs and the balancing of positive and negative consequences for delta functions and the societies that rely on them. This assessment outlines policy-driven and spatial trade-offs that dominate the landscape of choice. It highlights examples of such trade-offs using plausible delta futures and the governance choices associated with them. The analysis is based on modelling broad-scale processes and individual adaptive actions. It highlights how policy choices to maximise economic growth can, for example, have unforeseen consequences such as diminished well-being for some populations. Hence the chapter concludes that trade-offs are a crucial governance challenge for future sustainability of deltas

Manipulating a qubit through the backaction of sequential partial measurements and real-time feedback

Quantum measurements not only extract information from a system but also alter its state. Although the outcome of the measurement is probabilistic, the backaction imparted on the measured system is accurately described by quantum theory. Therefore, quantum measurements can be exploited for manipulating quantum systems without the need for control fields. We demonstrate measurement-only state manipulation on a nuclear spin qubit in diamond by adaptive partial measurements. We implement the partial measurement via tunable correlation with an electron ancilla qubit and subsequent ancilla readout. We vary the measurement strength to observe controlled wavefunction collapse and find post-selected quantum weak values. By combining a novel quantum non-demolition readout on the ancilla with real-time adaption of the measurement strength we realize steering of the nuclear spin to a target state by measurements alone. Besides being of fundamental interest, adaptive measurements can improve metrology applications and are key to measurement-based quantum computing.Comment: 6 pages, 4 figure

Insight Into the Formation of the Milky Way Through Cold Halo Substructure. II. The Elemental Abundances of ECHOS

We determine the average metallicities of the elements of cold halo substructure (ECHOS) that we previously identified in the inner halo of the Milky Way within 17.5 kpc of the Sun. As a population, we find that stars kinematically associated with ECHOS are chemically distinct from the background kinematically smooth inner halo stellar population along the same Sloan Extension for Galactic Understanding and Exploration (SEGUE) line of sight. ECHOS are systematically more iron-rich, but less alpha-enhanced than the kinematically-smooth component of the inner halo. ECHOS are also chemically distinct from other Milky Way components: more iron-poor than typical thick-disk stars and both more iron-poor and alpha-enhanced than typical thin-disk stars. In addition, the radial velocity dispersion distribution of ECHOS extends beyond sigma ~ 20 km s^-1. Globular clusters are unlikely ECHOS progenitors, as ECHOS have large velocity dispersions and are found in a region of the Galaxy in which iron-rich globular clusters are very rare. Likewise, the chemical composition of stars in ECHOS do not match predictions for stars formed in the Milky Way and subsequently scattered into the inner halo. Dwarf spheroidal (dSph) galaxies are possible ECHOS progenitors, and if ECHOS are formed through the tidal disruption of one or more dSph galaxies, the typical ECHOS [Fe/H] ~ -1.0 and radial velocity dispersion sigma ~ 20 km s^-1 implies a dSph with M_tot >~ 10^9 M_Sun. Our observations confirm the predictions of theoretical models of Milky Way halo formation that suggest that prominent substructures are likely to be metal-rich, and our result implies that the most likely metallicity for a recently accreted star currently in the inner halo is [Fe/H] ~ -1.0.Comment: 31 pages and 16 figures, and 3 tables in emulateapj format; accepted for publication in ApJ. Full tables can be extracted from TeX sourc

IUPAC specification for the FAIR management of spectroscopic data in chemistry (IUPAC FAIRSpec) - guiding principles

set of guiding principles for the development of a standard for FAIR management of spectroscopic data are outlined and discussed. The principles form the basis for future recommendations of IUPAC Project 2019-031-1-024 specifying a detailed data model and metadata schema for describing the contents of an “IUPAC FAIRData Collection” and the organization of digital objects within that collection. Foremost among the recommendations will be a specification for an “IUPAC FAIRData Finding Aid” that describes the collection in such a way as to optimize the findability, accessibility, interoperability, and reusability of its contents. Results of an analysis of data provided by an American Chemical Society Publications pilot study are discussed in relation to potential workflows that might be used in implementing the “IUPAC FAIRSpec” standard based on these principles

Future developments in brain-machine interface research

Neuroprosthetic devices based on brain-machine interface technology hold promise for the restoration of body mobility in patients suffering from devastating motor deficits caused by brain injury, neurologic diseases and limb loss. During the last decade, considerable progress has been achieved in this multidisciplinary research, mainly in the brain-machine interface that enacts upper-limb functionality. However, a considerable number of problems need to be resolved before fully functional limb neuroprostheses can be built. To move towards developing neuroprosthetic devices for humans, brain-machine interface research has to address a number of issues related to improving the quality of neuronal recordings, achieving stable, long-term performance, and extending the brain-machine interface approach to a broad range of motor and sensory functions. Here, we review the future steps that are part of the strategic plan of the Duke University Center for Neuroengineering, and its partners, the Brazilian National Institute of Brain-Machine Interfaces and the École Polytechnique Fédérale de Lausanne (EPFL) Center for Neuroprosthetics, to bring this new technology to clinical fruition

Measuring the Initial Mass Function of Low Mass Stars and Brown Dwarfs

I review efforts to determine the form and any lower limit to the initial mass function in the Galactic disk, using observations of low-mass stars and brown dwarfs in the field, young clusters and star forming regions. I focus on the methodologies that have been used and the uncertainties that exist due to observational limitations and to systematic uncertainties in calibrations and theoretical models. I conclude that whilst it is possible that the low-mass IMFs deduced from the field and most young clusters are similar, there are too many problems to be sure; there are examples of low-mass cluster IMFs that appear to be very discrepant and the IMFs for brown dwarfs in the field and young clusters have yet to be reconciled convincingly.Comment: From a series of lectures presented at the Evry-Schatzman school on Low-mass stars and the transition from stars to brown dwarfs, edited by C. Charbonnel, C. Reyle, M. Schultheis. To appear in the EAS Conference Series. 47p

Características clínicas, microbiología y resultados de una cohorte de pacientes tratados con ceftolozane/tazobactam en centros de hospitalización de cuidados agudos, Houston, Texas, EE.UU

Antecedentes Ceftolozane/tazobactam es una combinación de β-lactámico/β-inhibidor de lactamasa con actividad contra una variedad de bacterias Gram-negativas, incluyendo Pseudomonas aeruginosa MDR. Este agente está aprobado para la neumonía bacteriana adquirida en el hospital y asociada a la ventilación mecánica. Sin embargo, la mayoría de los datos de resultados en el mundo real proceden de pequeñas cohortes observacionales. Por lo tanto, se trató de evaluar la utilización de ceftolozane/tazobactam en múltiples hospitales terciarios en Houston, TX, EE.UU.. Métodos Realizamos un estudio retrospectivo multicéntrico de pacientes que recibieron al menos 48 h de terapia con ceftolozano/tazobactam desde enero de 2016 hasta septiembre de 2019 en dos sistemas hospitalarios en Houston. Se recopilaron datos demográficos, clínicos y microbiológicos, incluido el aislado bacteriano infectante, cuando estaba disponible. El resultado primario fue el éxito clínico compuesto al alta hospitalaria. Los resultados secundarios incluyeron la mortalidad intrahospitalaria y la disposición clínica a los 14 y 30 días después del inicio de ceftolozane/tazobactam. Se utilizó un análisis de regresión logística multivariable para identificar los factores predictivos del resultado primario y la mortalidad. Los aislados recuperados se sometieron a pruebas de sensibilidad a ceftolozano/tazobactam y a WGS. Resultados Se incluyó a un total de 263 pacientes, y se alcanzó el éxito clínico compuesto en 185 pacientes (70,3%). La gravedad de la enfermedad fue el factor predictivo más consistente del éxito clínico. El tratamiento combinado con ceftolozane/tazobactam y otro agente Gram negativo activo se asoció a una reducción de las probabilidades de éxito clínico (OR 0,32; IC del 95%: 0,16-0,63). Se observó resistencia a ceftolozano/tazobactam en el 15,4% de los aislados disponibles para WGS; las mutaciones en ampC y ftsI fueron frecuentes pero no se agruparon con una ST concreta. Conclusiones La tasa de éxito clínico entre esta cohorte de pacientes tratados con ceftolozane/tazobactam fue similar en comparación con experiencias anteriores. Ceftolozane/tazobactam sigue siendo un agente alternativo para el tratamiento de aislados susceptibles de P. aeruginosaBackground Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA. Methods We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS. Results A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16–0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST. Conclusions Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa

UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes: RAD51C, RAD51D, BRIP1 and PALB2.

Germline pathogenic variants (GPVs) in the cancer predisposition genes BRCA1, BRCA2, MLH1, MSH2, MSH6, BRIP1, PALB2, RAD51D and RAD51C are identified in approximately 15% of patients with ovarian cancer (OC). While there are clear guidelines around clinical management of cancer risk in patients with GPV in BRCA1, BRCA2, MLH1, MSH2 and MSH6, there are few guidelines on how to manage the more moderate OC risk in patients with GPV in BRIP1, PALB2, RAD51D and RAD51C, with clinical questions about appropriateness and timing of risk-reducing gynaecological surgery. Furthermore, while recognition of RAD51C and RAD51D as OC predisposition genes has been established for several years, an association with breast cancer (BC) has only more recently been described and clinical management of this risk has been unclear. With expansion of genetic testing of these genes to all patients with non-mucinous OC, new data on BC risk and improved estimates of OC risk, the UK Cancer Genetics Group and CanGene-CanVar project convened a 2-day meeting to reach a national consensus on clinical management of BRIP1, PALB2, RAD51D and RAD51C carriers in clinical practice. In this paper, we present a summary of the processes used to reach and agree on a consensus, as well as the key recommendations from the meeting