Heart failure syndrome and predicting response to cardiac resynchronisation therapy.

Heart failure results from the heart pumping insufficient quantities of blood to meet the body’s metabolic requirements. This condition affects around 600,000 people in the United Kingdom and carries with it a significant morbidity and mortality. Patients typically complain of reduced exercise capacity and a poor quality of life. Whilst there are various pharmaceutical options available to clinicians, none directly augment cardiac function. Cardiac resynchronisation therapy (CRT) is proven to reverse the progression of left ventricular systolic dysfunction, the most common cause of heart failure. The device resynchronises inefficient cardiac function, reducing symptoms and improving stroke volume and life expectancy. However, only two thirds of patients typically derive benefit from this pacemaker, it being unclear why. Finding a sensitive and specific predictor of response would be invaluable, preventing potential harm to patients, reducing waste and targeting the patient groups who will derive benefit. In this body of work, the heart failure syndrome is delineated; the evidence underpinning CRT discussed and the difficulties in defining response outlined. There are 2 main research themes in this body of work, measuring and predicting response to CRT. In the former, the role of patient specific three-­‐dimensional computational models and biophysical properties are investigated, and, in the latter, the influence of CRT on the heart failure syndrome using biomarkers. It is concluded that CRT response can be predicted using patient specific computational models of the left ventricle, but they are too complex for routine clinical use. Biophysical markers have more merit in the immediate future, being simper and quicker, with measures of endothelial and skeletal muscle function, demonstrating promise in a small cohort of patients. Finally, there exists a significant level of undiagnosed pathology in this patient group, such as hyperuricaemia and hyperparathyroidism, but it remains unclear what impact CRT has on this comorbidity

A phase of liposomes with entangled tubular vesicles

An equilibrium phase belonging to the family of bilayer liposomes in ternary mixtures of dimyristoylphosphatidylcholine (DMPC), water, and geraniol (a biological alcohol derived from oil-soluble vitamins that acts as a cosurfactant) has been identified. Electron and optical microscopy reveal the phase, labeled Ltv, to be composed of highly entangled tubular vesicles. In situ x-ray diffraction confirms that the tubule walls are multilamellar with the lipids in the chain-melted state. Macroscopic observations show that the Ltv phase coexists with the well-known L4 phase of spherical vesicles and a bulk L alpha phase. However, the defining characteristic of the Ltv phase is the Weissenberg rod climbing effect under shear, which results from its polymer-like entangled microstructure

Exposure to exogenous egg cortisol does not rescue juvenile Chinook salmon body size, condition, or survival from the effects of elevated water temperatures

Climate change is leading to altered temperature regimes which are impacting aquatic life, particularly for ectothermic fish. The impacts of environmental stress can be translated across generations through maternally derived glucocorticoids, leading to altered offspring phenotypes. Although these maternal stress effects are often considered negative, recent studies suggest this maternal stress signal may prepare offspring for a similarly stressful environment (environmental match). We applied the environmental match hypothesis to examine whether a prenatal stress signal can dampen the effects of elevated water temperatures on body size, condition, and survival during early development in Chinook salmon Oncorhynchus tshawytscha from Lake Ontario, Canada. We exposed fertilized eggs to prenatal exogenous egg cortisol (1,000 ng/ml cortisol or 0 ng/ml control) and then reared these dosed groups at temperatures indicative of current (+0°C) and future (+3°C) temperature conditions. Offspring reared in elevated temperatures were smaller and had a lower survival at the hatchling developmental stage. Overall, we found that our exogenous cortisol dose did not dampen effects of elevated rearing temperatures (environmental match) on body size or early survival. Instead, our eyed stage survival indicates that our prenatal cortisol dose may be detrimental, as cortisol-dosed offspring raised in elevated temperatures had lower survival than cortisol-dosed and control reared in current temperatures. Our results suggest that a maternal stress signal may not be able to ameliorate the effects of thermal stress during early development. However, we highlight the importance of interpreting the fitness impacts of maternal stress within an environmentally relevant context

Towards designer organelles by subverting the peroxisomal import pathway

The development of ‘designer’ organelles could be a key strategy to enable foreign pathways to be efficiently controlled within eukaryotic biotechnology. A fundamental component of any such system will be the implementation of a bespoke protein import pathway that can selectively deliver constituent proteins to the new compartment in the presence of existing endogenous trafficking systems. Here we show that the protein–protein interactions that control the peroxisomal protein import pathway can be manipulated to create a pair of interacting partners that still support protein import in moss cells, but are orthogonal to the naturally occurring pathways. In addition to providing a valuable experimental tool to give new insights into peroxisomal protein import, the variant receptor-signal sequence pair forms the basis of a system in which normal peroxisomal function is downregulated and replaced with an alternative pathway, an essential first step in the creation of a designer organelle

Mimicking Transgenerational Signals of Future Stress: Thermal Tolerance of Juvenile Chinook Salmon Is More Sensitive to Elevated Rearing Temperature Than Exogenously Increased Egg Cortisol

Elevated temperatures resulting from climate change are expected to disproportionately affect ectotherms given their biological function has a direct link to environmental temperature. Thus, as climate change leads to rapid increases in water temperatures in rivers, aquatic ectotherms, such as fish may be highly impacted. Organisms can respond to these stressors through flexible and rapid phenotypic change induced via developmental and/or transgenerational plasticity. In oviparous species, gravid females may translate environmental stress across generations via increased exposure of eggs to maternally derived glucocorticoids (i.e., maternal stress), which has been shown to result in diverse phenotypic effects in offspring. Recent studies suggest these phenotypic changes from maternal glucocorticoids may elicit predictive adaptive responses, where offspring exposed to maternal stress may be better prepared for the stressful environment they will encounter (i.e., environmental match hypothesis). We applied the environmental match hypothesis to examine whether a prenatal exogenous increase in egg cortisol may prepare Chinook salmon offspring (Oncorhynchus tshawytscha) to cope with thermal challenges after being reared in chronically elevated temperatures. Specifically, we exposed eggs to aqueous bath of cortisol-dosed (1,000 ng/mL) or control (0 ng/ml) solutions, and then raised both treatments at current (+0°C—contemporary ambient river temperature) or elevated (+3°C—projected future river temperature) thermal regimes. We quantified thermal performance in fish 7–9 month post fertilization using two methods: via critical thermal maximum (CTMax), and energetic responses (in plasma cortisol, glucose, and lactate) to environmentally relevant, but challenging thermal spikes over 3 days. Overall, we found that exposure to elevated rearing temperatures had a large impact on thermal tolerance, where elevated-temperature reared offspring had significantly higher CTMax. In comparison, egg cortisol treatment had little to no clear effects on CTMax and blood energetic response. Our study demonstrates the importance of elevated water temperatures as an inducer of offspring phenotypes (via early developmental cues), and highlights the significance of examining offspring performance in environments with ecologically relevant stressors

A laboratory characterisation of inorganic iodine emissions from the sea surface: dependence on oceanic variables and parameterisation for global modelling

Reactive iodine compounds play a significant role in the atmospheric chemistry of the oceanic boundary layer by influencing the oxidising capacity through catalytically removing O3 and altering the HOx and NOx balance. The sea-to-air flux of iodine over the open ocean is therefore an important quantity in assessing these impacts on a global scale. This paper examines the effect of a number of relevant environmental parameters, including water temperature, salinity and organic compounds, on the magnitude of the HOI and I2 fluxes produced from the uptake of O3 and its reaction with iodide ions in aqueous solution. The results of these laboratory experiments and those reported previously (Carpenter et al., 2013), along with sea surface iodide concentrations measured or inferred from measurements of dissolved total iodine and iodate reported in the literature, were then used to produce parameterised expressions for the HOI and I2 fluxes as a function of wind speed, sea-surface temperature and O3. These expressions were used in the Tropospheric HAlogen chemistry MOdel (THAMO) to compare with MAX-DOAS measurements of iodine monoxide (IO) performed during the HaloCAST-P cruise in the eastern Pacific ocean (Mahajan et al., 2012). The modelled IO agrees reasonably with the field observations, although significant discrepancies are found during a period of low wind speeds (< 3 m s&minus;1), when the model overpredicts IO by up to a factor of 3. The inorganic iodine flux contributions to IO are found to be comparable to, or even greater than, the contribution of organo-iodine compounds and therefore its inclusion in atmospheric models is important to improve predictions of the influence of halogen chemistry in the marine boundary layer

SentiBench - a benchmark comparison of state-of-the-practice sentiment analysis methods

In the last few years thousands of scientific papers have investigated sentiment analysis, several startups that measure opinions on real data have emerged and a number of innovative products related to this theme have been developed. There are multiple methods for measuring sentiments, including lexical-based and supervised machine learning methods. Despite the vast interest on the theme and wide popularity of some methods, it is unclear which one is better for identifying the polarity (i.e., positive or negative) of a message. Accordingly, there is a strong need to conduct a thorough apple-to-apple comparison of sentiment analysis methods, \textit{as they are used in practice}, across multiple datasets originated from different data sources. Such a comparison is key for understanding the potential limitations, advantages, and disadvantages of popular methods. This article aims at filling this gap by presenting a benchmark comparison of twenty-four popular sentiment analysis methods (which we call the state-of-the-practice methods). Our evaluation is based on a benchmark of eighteen labeled datasets, covering messages posted on social networks, movie and product reviews, as well as opinions and comments in news articles. Our results highlight the extent to which the prediction performance of these methods varies considerably across datasets. Aiming at boosting the development of this research area, we open the methods' codes and datasets used in this article, deploying them in a benchmark system, which provides an open API for accessing and comparing sentence-level sentiment analysis methods

Change management: The case of the elite sport performance team

The effective and efficient implementation of change is often required for both successful performance and management survival across a host of contemporary domains. However, although of major theoretical and practical significance, research to date has overlooked the application of change management (hereafter CM) knowledge to the elite sport performance team environment. Considering that the success of ‘off-field’ sports businesses are largely dependent on the performances of their ‘on-field’ team, this article explores the application of current CM theorizing to this specific setting and the challenges facing its utility. Accordingly, we identify the need and importance of developing theory specific to this area, with practical application in both sport and business, through examination of current knowledge and identification of the domain's unique, dynamic and contested properties. Markers of successful change are then suggested to guide initial enquiry before the article concludes with proposed lines of research which may act to provide a valid and comprehensive theoretical account of CM to optimize the research and practice of those working in the field