Understanding the transition to seizure by modeling the epileptiform activity of general anesthetic agents

A central difficulty in modeling epileptogenesis using biologically plausible computational and mathematical models is not the production of activity characteristic of a seizure, but rather producing it in response to specific and quantifiable physiologic change or pathologic abnormality. This is particularly problematic when it is considered that the pathophysiological genesis of most epilepsies is largely unknown. However, several volatile general anesthetic agents, whose principle targets of action are quantifiably well characterized, are also known to be proconvulsant. The authors describe recent approaches to theoretically describing the electroencephalographic effects of volatile general anesthetic agents that may be able to provide important insights into the physiologic mechanisms that underpin seizure initiation.

The sources of phosphorus in the waters of Great Britain

Total phosphorus (TP) and soluble reactive phosphorus (SRP) loads to watercourses of the River Basin Districts (RBDs) of Great Britain (GB) were estimated using inventories of industrial P loads and estimates of P loads from sewage treatment works and diffuse P loads calculated using region-specific export coefficients for particular land cover classes combined with census data for agricultural stocking densities and human populations. The TP load to GB waters was estimated to be 60 kt yr(-1), of which households contributed 73, agriculture contributed 20, industry contributed 3, and 4 came from background sources. The SRP load to GB waters was estimated to be 47 kt yr(-1), of which households contributed 78, agriculture contributed 13, industry contributed 4, and 6 came from background Sources. The 'average' area-normalized TP and SRP loads to GB waters approximated 2.4 kg ha(-1) yr(-1) and 1.8 kg ha(-1) yr(-1), respectively. A consideration of uncertainties in the data contributing to these estimates suggested that the TP load to GB waters might lie between 33 and 68 kt yr(-1), with agriculture contributing between 10 and 28 of the TP load. These estimates are consistent with recent appraisals of annual TP and SRP loads to GB coastal waters and area-normalized TP loads from their catchments. Estimates of the contributions of RBDs to these P loads were consistent with the geographical distribution of P concentrations in GB rivers and recent assessments of surface waters at risk from P Pollution.

A longitudinal investigation of maternal influences on the development of child hostile attributions and aggression

Aggression in children is associated with an enhanced tendency to attribute hostile intentions to others. However, limited information is available regarding the factors that contribute to the development of such hostile attribution tendencies. We examined factors that contribute to individual differences in child hostile attributions and aggression, focusing on potential pathways from maternal hostile attributions via negative parenting behavior. We conducted a longitudinal study of 98 mothers and children (47 male, 51 female), recruited from groups experiencing high and low levels of psychosocial adversity. Maternal hostile attributions, observed parenting, and child behaviour were assessed at 18 months and 5 years child age, and child hostile attributions were also examined at 5 years. Independent assessments of maternal and child processes were utilized where possible. Analyses provided support for a direct influence of maternal hostile attributions on the development of child hostile attributions and aggressive behaviour. Maternal hostile attributions were also associated with negative parenting behaviour, which in turn influenced child adjustment. Even taking account of possible parenting influences and preexisting child difficulties, hostile attributions in the mother showed a direct link with child aggression at 5 years. Maternal hostile attributions were themselves related to psychosocial adversity. We conclude that maternal hostile attributions are prevalent in high-risk samples and are related to less optimal parenting behaviour, child hostile attributions, and child aggression. Targeting hostile maternal cognitions may be a useful adjunct to parenting programs

A comparison of GOCE and drifter-based estimates of the North Atlantic steady-state surface circulation

Over the last decade, due to the Gravity Recovery And Climate Experiment (GRACE) mission and, more recently, the Gravity and steady state Ocean Circulation Explorer (GOCE) mission, our ability to measure the ocean’s mean dynamic topography (MDT) from space has improved dramatically. Here we use GOCE to measure surface current speeds in the North Atlantic and compare our results with a range of independent estimates that use drifter data to improve small scales. We find that, with filtering, GOCE can recover 70% of the Gulf Steam strength relative to the best drifter-based estimates. In the subpolar gyre the boundary currents obtained from GOCE are close to the drifter-based estimates. Crucial to this result is careful filtering which is required to remove small-scale errors, or noise, in the computed surface. We show that our heuristic noise metric, used to determine the degree of filtering, compares well with the quadratic sum of mean sea surface and formal geoid errors obtained from the error variance–covariance matrix associated with the GOCE gravity model. At a resolution of 100 km the North Atlantic mean GOCE MDT error before filtering is 5 cm with almost all of this coming from the GOCE gravity model.

Paralog re-emergence: a novel, historically contingent mechanism in the evolution of antimicrobial resistance

Evolution of resistance to drugs and pesticides poses a serious threat to human health and agricultural production. CYP51 encodes the target site of azole fungicides, widely used clinically and in agriculture. Azole resistance can evolve due to point mutations or overexpression of CYP51, and previous studies have shown that fungicide-resistant alleles have arisen by de novo mutation. Paralogs CYP51A and CYP51B are found in filamentous ascomycetes, but CYP51A has been lost from multiple lineages. Here, we show that in the barley pathogen Rhynchosporium commune, re-emergence of CYP51A constitutes a novel mechanism for the evolution of resistance to azoles. Pyrosequencing analysis of historical barley leaf samples from a unique long-term experiment from 1892 to 2008 indicates that the majority of the R. commune population lacked CYP51A until 1985, after which the frequency of CYP51A rapidly increased. Functional analysis demonstrates that CYP51A retains the same substrate as CYP51B, but with different transcriptional regulation. Phylogenetic analyses show that the origin of CYP51A far predates azole use, and newly sequenced Rhynchosporium genomes show CYP51A persisting in the R. commune lineage rather than being regained by horizontal gene transfer; therefore, CYP51A re-emergence provides an example of adaptation to novel compounds by selection from standing genetic variation.

Those Essex girls: the lives and letters of Lettice Knollys, Penelope Rich, Dorothy Perrott Percy, and Frances Walsingham

This essay examines the lives and letters of four of the most influential women at the court of Queen Elizabeth I: Lettice Knollys her daughters Penelope Rich and Dorothy Perrott Percy and her daughter-in-law Frances Walsingham, all of whom lived scandalous but powerful lives.

A comparison of duality and energy a posteriori estimates for $\mathrm {L}_{\infty }(0,T;\mathrm {L}_2(\varOmega ))$ in parabolic problems

We use the elliptic reconstruction technique in combination with a duality approach to prove a posteriori error estimates for fully discrete backward Euler scheme for linear parabolic equations. As an application, we combine our result with the residual based estimators from the a posteriori estimation for elliptic problems to derive space-error indicators and thus a fully practical version of the estimators bounding the error in the $ \mathrm {L}_{\infty }(0,T;\mathrm {L}_2(\varOmega ))$ norm. These estimators, which are of optimal order, extend those introduced by Eriksson and Johnson in 1991 by taking into account the error induced by the mesh changes and allowing for a more flexible use of the elliptic estimators. For comparison with previous results we derive also an energy-based a posteriori estimate for the $ \mathrm {L}_{\infty }(0,T;\mathrm {L}_2(\varOmega ))$-error which simplifies a previous one given by Lakkis and Makridakis in 2006. We then compare both estimators (duality vs. energy) in practical situations and draw conclusions.

Regulating working families in the European Union: a history of disjointed strategies

Families in market economies worldwide have long been confronted with the demands of participating in paid work and providing care for their dependent members. The social, economic and political contexts within which families do so differ from country to country but an increasing number of governments are being asked to engage, or better engage, with this important area of public policy. What seems like a relatively simple goal – to enable families to better balance care-giving and paid employment – has raised several difficulties and dilemmas for policy makers which have been approached in different ways. This paper aims to identify and critique the nature and development of the means by which legal engagement with work-family reconciliation has, historically, been framed in the European Union. In doing so, and with reference to specific cohorts of workers, we demonstrate how disjointed the strategies are in relation to working carers and argue that the EU is unlikely to provide the legal framework necessary to bring about effective change in this fundamentally important area of social policy.

Monitoring scan asymmetry of microwave humidity sounding channels using simultaneous all angle collocations (SAACs)

Simultaneous all angle collocations (SAACs) of microwave humidity sounders (AMSU-B and MHS) on-board polar orbiting satellites are used to estimate scan-dependent biases. This method has distinct advantages over previous methods, such as that the estimated scan-dependent biases are not influenced by diurnal differences between the edges of the scan and the biases can be estimated for both sides of the scan. We find the results are robust in the sense that biases estimated for one satellite pair can be reproduced by double differencing biases of these satellites with a third satellite. Channel 1 of these instruments shows the least bias for all satellites. Channel 2 has biases greater than 5 K, thus needs to be corrected. Channel 3 has biases of about 2 K and more and they are time varying for some of the satellites. Channel 4 has the largest bias which is about 15 K when the data are averaged for 5 years, but biases of individual months can be as large as 30 K. Channel 5 also has large and time varying biases for two of the AMSU-Bs. NOAA-15 (N15) channels are found to be affected the most, mainly due to radio frequency interference (RFI) from onboard data transmitters. Channel 4 of N15 shows the largest and time varying biases, so data of this channel should only be used with caution for climate applications. The two MHS instruments show the best agreement for all channels. Our estimates may be used to correct for scan-dependent biases of these instruments, or at least used as a guideline for excluding channels with large scan asymmetries from scientific analyses.

Family-friendly employment laws (re)assessed: the potential of care ethics

In light of various reforms in recent years, this article provides a (re)assessment of the broad package of family-friendly employment rights and relevant dispute resolution procedure now available to pregnant workers and working carers. It exposes how the realities of working life for many pregnant workers and carers and the long standing desire to promote gender equality in informal care-work remain at odds with the legal framework. An argument is presented in favour of an approach that, based upon the concept of care ethics, better engages with the impact of the provisions upon crucial interdependent care relationships.