Sex-linked markers facilitate genetic parentage analyses in knobbed whelk broods.

To explore the potential of sex-linked polymorphisms for genetic parentage analyses in natural populations, we have employed a recently discovered "X-linked" microsatellite marker (in conjunction with polymorphic autosomal loci) to deduce biological paternity and maternity for large numbers of encapsulated embryos within individual broods of the knobbed whelk (Busycon carica). Empirical findings illustrate how such sex-linked genetic tags can in special instances find at least three novel utilities in genetic dissections of large-clutch species: clarification of paternity assignments that had remained ambiguous from di-locus autosomal data alone; elucidation of linkage relationships among pairs of autosomal loci; and illumination of maternity (and thereby paternity also) in broods for which neither biological parent was known from independent evidence

Modelling & characterization of a compliant tethered microgripper for microsurgical applications

The development of microscale surgical tools could pave the way for truly minimally invasive microsurgical procedures. This work demonstrates the application of direct laser writing (DLW) using two-photon polymerization (TPP), a rapid prototyping microfabrication technique, to create a tethered, passively actuated three-dimensional gripper with potential applications in microbiopsy. A microgripper design was devised, modelled and optimized. The gripper was then fabricated and characterized for validation of the theoretical model. The results demonstrate that modelling the behavior of compliant microtools provides a useful approximation for the observed trends and, thus, can be utilized in the design of TPP tools. Future work on the incorporation of viscoelastic material into the model will further improve agreement between the predicted and experimental performance

Multiple paternity and female sperm usage along egg-case strings of the knobbed whelk, Busycon carica (Mollusca; Melongenidae)

We used genotypic data from three highly polymorphic microsatellite loci (two autosomal and one sex-linked) to examine micro-spatial and temporal arrangements of genetic paternity for more than 1,500 embryos housed along 12 egg-case strings of the knobbed whelk, Busycon carica. Multiple paternity proved to be the norm in these single-dam families, with genetic contributions of several sires (at least 3.5 on average) being represented among embryos within individual egg capsules as well as along the string. Two strings were studied in much greater detail; five and seven fathers were identified, none of which was among the several males found in consort with the female at her time of egg-laying. Each deduced sire had fathered roughly constant proportions of embryos along most of the string, but those proportions differed consistently among fathers. A few significant paternity shifts at specifiable positions along an egg-case string were also observed. Although the precise physical mechanisms inside a female whelk's reproductive tract remain unknown, our genetic findings indicate that successive fertilization events (and/or depositions of zygotes into egg capsules) normally occur as near-random draws from a well-but-not-perfectly blended pool of gametes (or zygotes) stemming from stored ejaculates, perhaps in different titers, of a dam's several mates. © 2006 Springer-Verlag

Using historical data to detect temporal changes in the abundances of intertidal species on Irish shores

An historical data set, collected in 1958 by Southward and Crisp, was used as a baseline for detecting change in the abundances of species in the rocky intertidal of Ireland. In 2003, the abundances of each of 27 species was assessed using the same methodologies (ACFOR [which stands for the categories: abundant, common, frequent, occasional and rare] abundance scales) at 63 shores examined in the historical study. Comparison of the ACFOR data over a 45-year period, between the historical survey and re-survey, showed statistically significant changes in the abundances of 12 of the 27 species examined. Two species (one classed as northern and one introduced) increased significantly in abundance while ten species (five classed as northern, one classed as southern and four broadly distributed) decreased in abundance. The possible reasons for the changes in species abundances were assessed not only in the context of anthropogenic effects, such as climate change and commercial exploitation, but also of operator error. The error or differences recorded among operators (i.e. research scientists) when assessing species abundance using ACFOR categories was quantified on four shores. Significant change detected in three of the 12 species fell within the margin of operator error. This effect of operator may have also contributed to the results of no change in the other 15 species between the two census periods. It was not possible to determine the effect of operator on our results, which can increase the occurrence of a false positive (Type 1) or of a false negative (Type 2) outcom

Self-Optimising Reactive Extractions: Towards the Efficient Development of Multi-Step Continuous Flow Processes

Downstream purification of products and intermediates is essential for the development of continuous flow processes. Described herein, is a study on the use of a modular and reconfigurable continuous flow platform for the self-optimisation of reactive extractions and multi-step reaction-extraction processes. The selective extraction of one amine from a mixture of two similar amines was achieved with an optimum separation of 90%, and in this case, the black-box optimisation approach was superior to global polynomial modelling. Furthermore, this methodology was utilised to simultaneously optimise the continuous flow synthesis and work-up of N-benzyl-α-methylbenzylamine with respect to four variables, resulting in a significantly improved purity

Can mid-regional pro-adrenomedullin (MR-proADM) increase the prognostic accuracy of NEWS in predicting deterioration in patients admitted to hospital with mild to moderately severe illness? A prospective single-centre observational study

Objective: To assess the value added to the National Early Warning Score (NEWS) by mid-regional pro-adrenomedullin (MR-proADM) blood level in predicting deterioration in mild to moderately ill people. Design: Prospective observational study. Setting: The Medical Admissions Suite of the Royal Victoria Infirmary, Newcastle. Participants: 300 adults with NEWS between 2 and 5 on admission. Exclusion criteria included receiving palliative care, or admitted for social reasons or self-harming. Patients were enrolled between September and December 2015, and followed up for 30 days after discharge. Outcome measure: The primary outcome measure was the proportion of patients who, within 72 hours, had an acuity increase, defined as any combination of an increase of at least 2 in the NEWS; transfer to a higher-dependency bed or monitored area; death; or for those discharged from hospital, readmission for medical reasons. Results: NEWS and MR-proADM together predicted acuity increase more accurately than NEWS alone, increasing the area under the curve (AUC) to 0.61 (95% CI 0.54 to 0.69) from 0.55 (95% CI 0.48 to 0.62). When the confounding effects of presence of chronic obstructive pulmonary disease or heart failure and interaction with MR-proADM were included, the prognostic accuracy further increased the AUC to 0.69 (95% CI 0.63 to 0.76). Conclusions: MR-proADM is potentially a clinically useful biomarker for deterioration in patients admitted to hospital with a mild to moderately severe acute illness, that is, with NEWS between 2 and 5. As a growing number of National Health Service hospitals are routinely recording the NEWS on their clinical information systems, further research should assess the practicality and use of developing a decision aid based on admission NEWS, MR-proADM level, and possibly other clinical data and other biomarkers that could further improve prognostic accuracy

Intergenerational change and familial aggregation of body mass index

The relationship between parental BMI and that of their adult offspring, when increased adiposity can become a clinical issue, is unknown. We investigated the intergenerational change in body mass index (BMI) distribution, and examined the sex-specific relationship between parental and adult offspring BMI. Intergenerational change in the distribution of adjusted BMI in 1,443 complete families (both parents and at least one offspring) with 2,286 offspring (1,263 daughters and 1,023 sons) from the west of Scotland, UK, was investigated using quantile regression. Familial correlations were estimated from linear mixed effects regression models. The distribution of BMI showed little intergenerational change in the normal range (\25 kg/m2), decreasing overweightness (25– \30 kg/m2) and increasing obesity (C30 kg/m2). Median BMI was static across generations in males and decreased in females by 0.4 (95% CI: 0.0, 0.7) kg/m2; the 95th percentileincreased by 2.2 (1.1, 3.2) kg/m2 in males and 2.7 (1.4, 3.9) kg/m2 in females. Mothers’ BMI was more strongly associated with daughters’ BMI than was fathers’ (correlation coefficient (95% CI): mothers 0.31 (0.27, 0.36), fathers 0.19 (0.14, 0.25); P = 0.001). Mothers’ and fathers’ BMI were equally correlated with sons’ BMI (correlation coefficient: mothers 0.28 (0.22, 0.33), fathers 0.27 (0.22, 0.33). The increase in BMI between generations was concentrated at the upper end of the distribution. This, alongside the strong parent-offspring correlation, suggests that the increase in BMI is disproportionally greater among offspring of heavier parents. Familial influences on BMI among middle-aged women appear significantly stronger from mothers than father

Mitochondrial function remains impaired in the hypertrophied right ventricle of pulmonary hypertensive rats following short duration metoprolol treatment

Pulmonary hypertension (PH) increases the work of the right ventricle (RV) and causes right-sided heart failure. This study examined RV mitochondrial function and ADP transfer in PH animals advancing to right heart failure, and investigated a potential therapy with the specific β1-adrenergic-blocker metoprolol. Adult Wistar rats (317 ± 4 g) were injected either with monocrotaline (MCT, 60 mg kg-1) to induce PH, or with an equivalent volume of saline for controls (CON). At three weeks post-injection the MCT rats began oral metoprolol (10 mg kg-1 day-1-) or placebo treatment until heart failure was observed in the MCT group. Mitochondrial function was then measured using high-resolution respirometry from permeabilised RV fibres. Relative to controls, MCT animals had impaired mitochondrial function but maintained coupling between myofibrillar ATPases and mitochondria, despite an increase in ADP diffusion distances. Cardiomyocytes from the RV of MCT rats were enlarged, primarily due to an increase in myofibrillar protein. The ratio of mitochondria per myofilament area was decreased in both MCT groups (p ≤ 0.05) in comparison to control (CON: 1.03 ± 0.04; MCT: 0.74 ± 0.04; MCT + BB: 0.74 ± 0.03). This not only implicates impaired energy production in PH, but also increases the diffusion distance for metabolites within the MCT cardiomyocytes, adding an additional hindrance to energy supply. Together, these changes may limit energy supply in MCT rat hearts, particularly at high cardiac workloads. Metoprolol treatment did not delay the onset of heart failure symptoms, improve mitochondrial function, or regress RV hypertrophy

Integrated Visualization of Human Brain Connectome Data

Visualization plays a vital role in the analysis of multi-modal neuroimaging data. A major challenge in neuroimaging visualization is how to integrate structural, functional and connectivity data to form a comprehensive visual context for data exploration, quality control, and hypothesis discovery. We develop a new integrated visualization solution for brain imaging data by combining scientific and information visualization techniques within the context of the same anatomic structure. New surface texture techniques are developed to map non-spatial attributes onto the brain surfaces from MRI scans. Two types of non-spatial information are represented: (1) time-series data from resting-state functional MRI measuring brain activation; (2) network properties derived from structural connectivity data for different groups of subjects, which may help guide the detection of differentiation features. Through visual exploration, this integrated solution can help identify brain regions with highly correlated functional activations as well as their activation patterns. Visual detection of differentiation features can also potentially discover image based phenotypic biomarkers for brain diseases

Combining computational effects: commutativity and sum

We begin to develop a unified account of modularity for computational effects. We use the notion of enriched Lawvere theory, together with its relationship with strong monads, to reformulate Moggi’s paradigm for modelling computational effects; we emphasise the importance here of the operations that induce computational effects. Effects qua theories are then combined by appropriate bifunctors (on the category of theories). We give a theory of the commutative combination of effects, which in particular yields Moggi’s side-effects monad transformer (an application is the combination of side-effects with nondeterminism). And we give a theory for the sum of computational effects, which in particular yields Moggi’s exceptions monad transformer (an application is the combination of exceptions with other effects)