Systematic review of antimicrobial drug prescribing in hospitals.

Prudent antibiotic prescribing to hospital inpatients has the potential to reduce the incidences of antimicrobial resistance and healthcare-associated infection. We reviewed the literature from January 1980 to November 2003 to identify rigorous evaluations of interventions to improve hospital antibiotic prescribing. We identified 66 studies with interpretable data of which 16 reported 20 microbiological outcomes: Gram negative resistant bacteria (GNRB), 10 studies; Clostridium difficile associated diarrhoea (CDAD), 5 studies; vancomycin resistant enterococci (VRE), 3 studies and methicillin resistant Staphylococcus aureus (MRSA), 2 studies. Four studies provide good evidence that the intervention changed microbial outcomes with low risk of alternative explanations, eight studies provide less convincing evidence and four studies were negative. The strongest and most consistent evidence was for CDAD but we were able to analyse only the immediate impact of interventions because of nonstandardised durations of follow up. The ability to compare results of studies could be substantially improved by standardising methodology and reporting

The Triple Pulsar System PSR B1620-26 in M4

The millisecond pulsar PSR B1620-26, in the globular cluster M4, has a white dwarf companion in a half-year orbit. Anomalously large variations in the pulsar's apparent spin-down rate have suggested the presence of a second companion in a much wider orbit. Using timing observations made on more than seven hundred days spanning eleven years, we confirm this anomalous timing behavior. We explicitly demonstrate, for the first time, that a timing model consisting of the sum of two non-interacting Keplerian orbits can account for the observed signal. Both circular and elliptical orbits are allowed, although highly eccentric orbits require improbable orbital geometries. The motion of the pulsar in the inner orbit is very nearly a Keplerian ellipse, but the tidal effects of the outer companion cause variations in the orbital elements. We have measured the change in the projected semi-major axis of the orbit, which is dominated by precession-driven changes in the orbital inclination. This measurement, along with limits on the rate of change of other orbital elements, can be used to significantly restrict the properties of the outer orbit. We find that the second companion most likely has a mass m~0.01 Msun --- it is almost certainly below the hydrogen burning limit (m<0.036 Msun, 95% confidence) --- and has a current distance from the binary of ~35 AU and orbital period of order one hundred years. Circular (and near-circular) orbits are allowed only if the pulsar magnetic field is ~3x10^9 G, an order of magnitude higher than a typical millisecond pulsar field strength. In this case, the companion has mass m~1.2x10^-3 Msun and orbital period ~62 years.Comment: 12 pages, 6 figures, 3 tables. Very minor clarifications and rewording. Accepted for publication in the Astrophys.

Functional implications of the dynamic regulation of EpCAM during epithelial-to-mesenchymal transition

Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein expressed in epithelial tissues. EpCAM forms intercellular, homophilic adhesions, modulates epithelial junctional protein complex formation, and promotes epithelial tissue homeostasis. EpCAM is a target of molecular therapies and plays a prominent role in tumor biology. In this review, we focus on the dynamic regulation of EpCAM expression during epithelial-to-mesenchymal transition (EMT) and the functional implications of EpCAM expression on the regulation of EMT. EpCAM is frequently and highly expressed in epithelial cancers, while silenced in mesenchymal cancers. During EMT, EpCAM expression is downregulated by extracellular signal-regulated kinases (ERK) and EMT transcription factors, as well as by regulated intramembrane proteolysis (RIP). The functional impact of EpCAM expression on tumor biology is frequently dependent on the cancer type and predominant oncogenic signaling pathways, suggesting that the role of EpCAM in tumor biology and EMT is multifunctional. Membrane EpCAM is cleaved in cancers and its intracellular domain (EpICD) is transported into the nucleus and binds β-catenin, FHL2, and LEF1. This stimulates gene transcription that promotes growth, cancer stem cell properties, and EMT. EpCAM is also regulated by epidermal growth factor receptor (EGFR) signaling and the EpCAM ectoderm (EpEX) is an EGFR ligand that affects EMT. EpCAM is expressed on circulating tumor and cancer stem cells undergoing EMT and modulates metastases and cancer treatment responses. Future research exploring EpCAM\u27s role in EMT may reveal additional therapeutic opportunities

Joint evolution of multiple social traits: a kin selection analysis

General models of the evolution of cooperation, altruism and other social behaviours have focused almost entirely on single traits, whereas it is clear that social traits commonly interact. We develop a general kin-selection framework for the evolution of social behaviours in multiple dimensions. We show that whenever there are interactions among social traits new behaviours can emerge that are not predicted by one-dimensional analyses. For example, a prohibitively costly cooperative trait can ultimately be favoured owing to initial evolution in other (cheaper) social traits that in turn change the cost-benefit ratio of the original trait. To understand these behaviours, we use a two-dimensional stability criterion that can be viewed as an extension of Hamilton's rule. Our principal example is the social dilemma posed by, first, the construction and, second, the exploitation of a shared public good. We find that, contrary to the separate one-dimensional analyses, evolutionary feedback between the two traits can cause an increase in the equilibrium level of selfish exploitation with increasing relatedness, while both social (production plus exploitation) and asocial (neither) strategies can be locally stable. Our results demonstrate the importance of emergent stability properties of multidimensional social dilemmas, as one-dimensional stability in all component dimensions can conceal multidimensional instability

Collecting biomedical and social data in a longitudinal survey: A comparison of two approaches

The inclusion of the collection of biomeasures within social surveys, and longitudinal surveys in particular, is becoming ever more common. Combining objective measurements of health with detailed information about lifestyles and behaviour collected over long periods of time offers enormous research potential. Studies that combine an interview with the collection of biomeasures can be conducted in various ways. One model is that field interviewers make initial contact with participants, conduct the interviews and arrange follow-up visits for a nurse to collect the biomeasures. Alternatively, field interviewers can be trained to collect biomeasures, but there remain questions about whether the quality of data collected is comparable to that collected by a nurse. Other studies invite participants to visit clinics, but this can be very costly in a large-scale national study. There is no consensus on the optimal strategy for combining a social survey with the collection of biomeasures. The 1970 British Cohort Study (BCS70) is a longitudinal birth cohort study which began in 1970. The 11th sweep of the study began in 2016, when study members were aged 46, and included an interview component alongside the collection of a range of biomeasures. The first phase of fieldwork was conducted using a new approach where nurses conducted all of the data collection. Midway through fieldwork BCS70 switched to a two-stage approach where interviews were conducted by interviewers followed by a separate nurse visit. This presented a unique opportunity to evaluate the success of the two approaches

Inferring neural dynamics during burst suppression using a neurophysiology-inspired switching state-space model

Burst suppression is an electroencephalography (EEG) pattern associated with profoundly inactivated brain states characterized by cerebral metabolic depression. Its distinctive feature is alternation between short temporal segments of near-isoelectric inactivity (suppressions) and relatively high-voltage activity (bursts). Prior modeling studies suggest that burst-suppression EEG is a manifestation of two alternating brain states associated with consumption (during a burst) and production (during a suppression) of adenosine triphosphate (ATP). This finding motivates us to infer latent states characterizing alternating brain states and underlying ATP kinetics from instantaneous power of multichannel EEG using a switching state-space model. Our model assumes Gaussian distributed data as a broadcast network manifestation of one of two global brain states. The two brain states are allowed to stochastically alternate with transition probabilities that depend on the instantaneous ATP level, which evolves according to first-order kinetics. The rate constants governing the ATP kinetics are allowed to vary as first-order autoregressive processes. Our latent state estimates are determined from data using a sequential Monte Carlo algorithm. Our neurophysiology-informed model not only provides unsupervised segmentation of multi-channel burst-suppression EEG but can also generate additional insights on the level of brain inactivation during anesthesia.Comment: To appear in the proceedings of the 2020 IEEE Asilomar Conference on Signals, Systems, and Computer

Evolution of the Dark Matter Distribution with 3-D Weak Lensing

We present a direct detection of the growth of large-scale structure, using weak gravitational lensing and photometric redshift data from the COMBO-17 survey. We use deep R-band imaging of two 0.25 square degree fields, affording shear estimates for over 52000 galaxies; we combine these with photometric redshift estimates from our 17 band survey, in order to obtain a 3-D shear field. We find theoretical models for evolving matter power spectra and correlation functions, and fit the corresponding shear correlation functions to the data as a function of redshift. We detect the evolution of the power at the 7.7 sigma level given minimal priors, and measure the rate of evolution for 0<z<1. We also fit correlation functions to our 3-D data as a function of cosmological parameters sigma_8 and Omega_Lambda. We find joint constraints on Omega_Lambda and sigma_8, demonstrating an improvement in accuracy by a factor of 2 over that available from 2D weak lensing for the same area.Comment: 11 pages, 4 figures; submitted to MNRA