Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials

Objective To evaluate the effectiveness of comprehensive geriatric assessment in hospital for older adults admitted as an emergency

Deepwater overflow through Luzon Strait

Author Posting. © American Geophysical Union, 2006. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 111 (2006): C01002, doi:10.1029/2005JC003139.This study examines water property distributions in the deep South China Sea and adjoining Pacific Ocean using all available hydrographic data. Our analysis reveals that below about 1500 m there is a persistent baroclinic pressure gradient driving flow from the Pacific into the South China Sea through Luzon Strait. Applying hydraulic theory with assumptions of zero potential vorticity and flat bottom to the Luzon Strait yields a transport estimate of 2.5 Sv (1 Sv=106 m3 s-1). Some implications of this result include: (i) a residence time of less than 30 years in the deep South China Sea, (ii) a mean diapycnal diffusivity as large as 10-3 m2 s-1, and (iii) an abyssal upwelling rate of about 3×10-6 m s-1. These quantities are consistent with residence times based on oxygen consumption rates. The fact that all of the inflowing water must warm up before leaving the basin implies that this marginal sea contributes to the water mass transformations that drive the meridional overturning circulation in the North Pacific. Density distributions within the South China Sea basin suggest a cyclonic deep boundary current system, as might be expected for an overflow-driven abyssal circulation.This study was supported by National Science Foundation (NSF) through Grant OCE00-95906 and by Japan Marine Science and Technology Center through its sponsorship of the International Pacific Research center (IPRRC). Support is also from NSF grant OCE-0325102

Screening for coping style increases the power of gene expression studies

Background: Individuals of many vertebrate species show different stress coping styles and these have a striking influence on how gene expression shifts in response to a variety of challenges. Principal Findings: This is clearly illustrated by a study in which common carp displaying behavioural predictors of different coping styles (characterised by a proactive, adrenaline-based or a reactive, cortisol-based response) were subjected to inflammatory challenge and specific gene transcripts measured in individual brains. Proactive and reactive fish differed in baseline gene expression and also showed diametrically opposite responses to the challenge for 80% of the genes investigated. Significance: Incorporating coping style as an explanatory variable can account for some the unexplained variation that is common in gene expression studies, can uncover important effects that would otherwise have passed unnoticed and greatly enhances the interpretive value of gene expression data

Photodynamic antimicrobial chemotherapy coupled with the use of the photosensitizers methylene blue and temoporfin as a potential novel treatment for Staphylococcus aureus in burn infections

Photodynamic antimicrobial chemotherapy (PACT) is a novel alternative antimicrobial therapy that elicits a broad mechanism of action and therefore has a low probability of generating resistance. Such properties make PACT ideally suited for utilization in localized applications such as burn wounds. The aim of this study was to determine the antimicrobial activity of MB and temoporfin against both a S. aureus isolate and a P. aeruginosa isolate in light (640 nm) and dark conditions at a range of time points (0–20 min). A Staphylococcus aureus isolate and a Pseudomonas aeruginosa isolate were treated in vitro with methylene blue (MB) and temoporfin under different conditions following exposure to light at 640 nm and in no-light (dark) conditions. Bacterial cell viability [colony-forming units (c.f.u.) ml−1] was then calculated. Against P. aeruginosa , when MB was used as the photosensitizer, no phototoxic effect was observed in either light or dark conditions. After treatment with temoporfin, a reduction of less than one log (7.00×107 c.f.u. ml−1) was observed in the light after 20 min of exposure. However, temoporfin completely eradicated S. aureus in both light and dark conditions after 1 min (where a seven log reduction in c.f.u. ml−1 was observed). Methylene blue resulted in a loss of S. aureus viability, with a two log reduction in bacterial viability (c.f.u. ml−1) reported in both light and dark conditions after 20 min exposure time. Temoporfin demonstrated greater antimicrobial efficacy than MB against both the S. aureus and P. aeruginosa isolates tested. At 12.5 µM temoporfin resulted in complete eradication of S. aureus . In light of this study, further research into the validity of PACT, coupled with the photosensitizers (such as temoporfin), should be conducted in order to potentially develop alternative antimicrobial treatment regimes for burn wounds.</jats:p

Integrated whole transcriptome and DNA methylation analysis identifies gene networks specific to late-onset Alzheimer’s disease

Previous transcriptome studies observed disrupted cellular processes in late-onset Alzheimer\u27s disease (LOAD), yet it is unclear whether these changes are specific to LOAD, or are common to general neurodegeneration. In this study, we address this question by examining transcription in LOAD and comparing it to cognitively normal controls and a cohort of disease controls. Differential transcription was examined using RNA-seq, which allows for the examination of protein coding genes, non-coding RNAs, and splicing. Significant transcription differences specific to LOAD were observed in five genes: C10orf105, DIO2, a lincRNA, RARRES3, and WIF1. These findings were replicated in two independent publicly available microarray data sets. Network analyses, performed on 2,504 genes with moderate transcription differences in LOAD, reveal that these genes aggregate into seven networks. Two networks involved in myelination and innate immune response specifically correlated to LOAD. FRMD4B and ST18, hub genes within the myelination network, were previously implicated in LOAD. Of the five significant genes, WIF1 and RARRES3 are directly implicated in the myelination process; the other three genes are located within the network. LOAD specific changes in DNA methylation were located throughout the genome and substantial changes in methylation were identified within the myelination network. Splicing differences specific to LOAD were observed across the genome and were decreased in all seven networks. DNA methylation had reduced influence on transcription within LOAD in the myelination network when compared to both controls. These results hint at the molecular underpinnings of LOAD and indicate several key processes, genes, and networks specific to the disease

A new foundational crisis in mathematics, is it really happening?

The article reconsiders the position of the foundations of mathematics after the discovery of HoTT. Discussion that this discovery has generated in the community of mathematicians, philosophers and computer scientists might indicate a new crisis in the foundation of mathematics. By examining the mathematical facts behind HoTT and their relation with the existing foundations, we conclude that the present crisis is not one. We reiterate a pluralist vision of the foundations of mathematics. The article contains a short survey of the mathematical and historical background needed to understand the main tenets of the foundational issues.Comment: Final versio

Summary of the 2012 Inductive Pulsed Plasma Thruster Development and Testing Program

Inductive pulsed plasma thrusters are spacecraft propulsion devices in which energy is capacitively stored and then discharged through an inductive coil. While these devices have shown promise for operation at high efficiency on a range of propellants, many technical issues remain before they can be used in flight applications. A conical theta-pinch thruster geometry was fabricated and tested to investigate potential improvements in propellant utilization relative to more common, flat-plate planar coil designs. A capacitor charging system is used to permit repetitive discharging of thrusters at multiple cycles per second, with successful testing accomplished at a repetition-rate of 5 Hz at power levels of 0.9, 1.6, and 2.5 kW. The conical theta-pinch thruster geometry was tested at cone angles of 20deg, 38deg, and 60deg, with single-pulse operation at 500 J/pulse and repetitionrate operation with the 38deg model quantified through direct thrust measurement using a hanging pendulum thrust stand. A long-lifetime valve was designed and fabricated, and initial testing was performed to measure the valve response and quantify the leak rate at beginning-of-life. Subscale design and testing of a capacitor charging system required for operation on a spacecraft is reported, providing insights into the types of components needed in the circuit topology employed. On a spacecraft, this system would accept as input a lower voltage from the spacecraft DC bus and boost the output to the high voltage required to charge the capacitors of the thruster

Several types of types in programming languages

Types are an important part of any modern programming language, but we often forget that the concept of type we understand nowadays is not the same it was perceived in the sixties. Moreover, we conflate the concept of "type" in programming languages with the concept of the same name in mathematical logic, an identification that is only the result of the convergence of two different paths, which started apart with different aims. The paper will present several remarks (some historical, some of more conceptual character) on the subject, as a basis for a further investigation. The thesis we will argue is that there are three different characters at play in programming languages, all of them now called types: the technical concept used in language design to guide implementation; the general abstraction mechanism used as a modelling tool; the classifying tool inherited from mathematical logic. We will suggest three possible dates ad quem for their presence in the programming language literature, suggesting that the emergence of the concept of type in computer science is relatively independent from the logical tradition, until the Curry-Howard isomorphism will make an explicit bridge between them.Comment: History and Philosophy of Computing, HAPOC 2015. To appear in LNC

Doing gender locally: The importance of ‘place’ in understanding marginalised masculinities and young men’s transitions to ‘safe’ and successful futures

Observable anxieties have been developing about the position of boys and young men in contemporary society in recent years. This is expressed as a crisis of masculinity, in which place is often implicitly implicated, but is rarely considered for its role in the shaping of young men’s practices, trajectories and aspirations. Drawing on research conducted with young people who accessed a range of social care support services, this article argues that transition means different things for young men in different locales and that local definitions of masculinity are required to better understand young men’s lives and the opportunities available to them. The authors argue that home life, street life, individual neighbourhoods, regions and nations all shaped the young men’s identities and the practices they (and the staff working with them) drew on in order to create successful futures and ‘safe’ forms of masculinity. It is suggested that this place-based approach has the potential to re-shape the ‘crisis’ discourse surrounding masculinity and the anxieties associated with young men

Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation

While the catalog of mammalian transcripts and their expression levels in different cell types and disease states is rapidly expanding, our understanding of transcript function lags behind. We present a robust technology enabling systematic investigation of the cellular consequences of repressing or inducing individual transcripts. We identify rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90%–99% knockdown with minimal off-target effects, and activators (CRISPRa) to endogenous genes via endonuclease-deficient Cas9. Together they enable modulation of gene expression over a ∼1,000-fold range. Using these rules, we construct genome-scale CRISPRi and CRISPRa libraries, each of which we validate with two pooled screens. Growth-based screens identify essential genes, tumor suppressors, and regulators of differentiation. Screens for sensitivity to a cholera-diphtheria toxin provide broad insights into the mechanisms of pathogen entry, retrotranslocation and toxicity. Our results establish CRISPRi and CRISPRa as powerful tools that provide rich and complementary information for mapping complex pathways