From a microscopic solution to a continuum description of active particles with a recoil interaction in one dimension.

We consider a model system of persistent random walkers that can jam, pass through each other, or jump apart (recoil) on contact. In a continuum limit, where particle motion between stochastic changes in direction becomes deterministic, we find that the stationary interparticle distribution functions are governed by an inhomogeneous fourth-order differential equation. Our main focus is on determining the boundary conditions that these distribution functions should satisfy. We find that these do not arise naturally from physical considerations, but they need to be carefully matched to functional forms that arise from the analysis of an underlying discrete process. The interparticle distribution functions, or their first derivatives, are generically found to be discontinuous at the boundaries.

Statistical mechanics of a single active slider on a fluctuating interface.

We study the statistical mechanics of a single active slider on a fluctuating interface, by means of numerical simulations and theoretical arguments. The slider, which moves by definition towards the interface minima, is active as it also stimulates growth of the interface. Even though such a particle has no counterpart in thermodynamic systems, active sliders may provide a simple model for ATP-dependent membrane proteins that activate cytoskeletal growth. We find a wide range of dynamical regimes according to the ratio between the timescales associated with the slider motion and the interface relaxation. If the interface dynamics is slow, the slider behaves like a random walker in a random environment, which, furthermore, is able to escape environmental troughs by making them grow. This results in different dynamic exponents to the interface and the particle: the former behaves as an Edward-Wilkinson surface with dynamic exponent 2, whereas the latter has dynamic exponent 3/2. When the interface is fast, we get sustained ballistic motion with the particle surfing a membrane wave created by itself. However, if the interface relaxes immediately (i.e., it is infinitely fast), particle motion becomes symmetric and goes back to diffusive. Due to such a rich phenomenology, we propose the active slider as a toy model of fundamental interest in the field of active membranes and, generally, whenever the system constituent can alter the environment by spending energy.

Width Scaling of an Interface Constrained by a Membrane.

We investigate the shape of a growing interface in the presence of an impenetrable moving membrane. The two distinct geometrical arrangements of the interface and membrane, obtained by placing the membrane behind or ahead of the interface, are not symmetrically related. On the basis of numerical results and an exact calculation, we argue that these two arrangements represent two distinct universality classes for interfacial growth: while the well-established Kardar-Parisi-Zhang (KPZ) growth is obtained in the "ahead" arrangement, we find an arrested KPZ growth with a smaller roughness exponent in the "behind" arrangement. This suggests that the surface properties of growing cell membranes and expanding bacterial colonies, for example, are fundamentally distinct.

Active Growth and Pattern Formation in Membrane-Protein Systems.

Inspired by recent experimental observations of patterning at the membrane of a living cell, we propose a generic model for the dynamics of a fluctuating interface driven by particlelike inclusions which stimulate its growth. We find that the coupling between interfacial and inclusions dynamics yields microphase separation and the self-organization of traveling waves. These patterns are strikingly similar to those detected in experiments on biological membranes. Our results further show that the active growth kinetics do not fall into the Kardar-Parisi-Zhang universality class for growing interfaces, displaying instead a novel superposition of scaling and sustained oscillations.

Jamming and Attraction of Interacting Run-and-Tumble Random Walkers.

We study a model of bacterial dynamics where two interacting random walkers perform run-and-tumble motion on a one-dimensional lattice under mutual exclusion and find an exact expression for the probability distribution in the steady state. This stationary distribution has a rich structure comprising three components: a jammed component, where the particles are adjacent and block each other; an attractive component, where the probability distribution for the distance between particles decays exponentially; and an extended component in which the distance between particles is uniformly distributed. The attraction between the particles is sufficiently strong that even in the limit where continuous space is recovered for a finite system, the two walkers spend a finite fraction of time in a jammed configuration. Our results potentially provide a route to understanding the motility-induced phase separation characteristic of active matter from a microscopic perspective.

Transthyretin V122I amyloidosis with clinical and histological evidence of amyloid neuropathy and myopathy.

Hereditary transthyretin amyloidosis (ATTR) is a genetically and clinically heterogeneous disease manifesting with predominant peripheral and autonomic neuropathy; cardiomyopathy, or both. ATTR V122I is the most common variant associated with non-neuropathic familial amyloid cardiomyopathy. We present an unusual case of V122I amyloidosis with features of amyloid neuropathy and myopathy, supported by histological confirmation in both sites and diffuse tracer uptake on (99m)Tc-3,3-Diphosphono-1,2-Propanodicarboxylic acid (DPD) scintigraphy throughout skeletal and cardiac muscle. A 64 year old Jamaican man presented with cardiac failure. Cardiac MR revealed infiltrative cardiomyopathy; abdominal fat aspirate confirmed the presence of amyloid, and he was homozygous for the V122I variant of transthyretin. He also described general weakness and EMG demonstrated myopathic features. Sural nerve and vastus lateralis biopsy showed TTR amyloid. The patient is being treated with diflunisal, an oral TTR stabilising agent. Symptomatic myopathy and neuropathy with confirmation of tissue amyloid deposition has not previously been described. Extracardiac amyloidosis has implications for diagnosis and treatment.

The impact of the media on the decision of parents in South Wales to accept measles-mumps-rubella (MMR) immunization.

A large measles outbreak occurred in South Wales in 2012/2013. The outbreak has been attributed to low take-up of measles-mumps-rubella (MMR) immunization in the early 2000s. To understand better the factors that led to this outbreak we present the findings of a case-control study carried out in the outbreak area in 2001 to investigate parents' decision on whether to accept MMR. Parents who decided not to take-up MMR at the time were more likely to be older and better educated, more likely to report being influenced by newspapers [adjusted odds ratio (aOR) 3·07, 95% confidence interval (CI) 1·62-5·80], television (aOR 3·30, 95% CI 1·70-6·43), the internet (aOR 7·23, 3·26-16·06) and vaccine pressure groups (aOR 5·20, 95% CI 2·22-12·16), and less likely to be influenced by a health visitor (aOR 0·30, 95% CI 0·16-0·57). In this area of Wales, daily English-language regional newspapers, UK news programmes and the internet appeared to have a powerful negative influence. We consider the relevance of these findings to the epidemiology of the outbreak and the subsequent public health response.

Modelling the effect of myosin X motors on filopodia growth.

We present a numerical simulation study of the dynamics of filopodial growth in the presence of active transport by myosin X motors. We employ both a microscopic agent-based model, which captures the stochasticity of the growth process, and a continuum mean-field theory which neglects fluctuations. We show that in the absence of motors, filopodia growth is overestimated by the continuum mean-field theory. Thus fluctuations slow down the growth, especially when the protrusions are driven by a small number (10 or less) of F-actin fibres, and when the force opposing growth (coming from membrane elasticity) is large enough. We also show that, with typical parameter values for eukaryotic cells, motors are unlikely to provide an actin transport mechanism which enhances filopodial size significantly, unless the G-actin concentration within the filopodium greatly exceeds that of the cytosol bulk. We explain these observations in terms of order-of-magnitude estimates of diffusion-induced and advection-induced growth of a bundle of Brownian ratchets.

Laboratory-based surveillance of Campylobacter and Salmonella infection and the importance of denominator data.

Laboratory data are the cornerstone in surveillance of infectious disease. We investigated whether changes in reported incidence of Campylobacter and Salmonella infection might be explained by changes in stool sampling rates. Data were extracted from a national database on 585 843 patient stool samples tested by microbiology laboratories in Wales between 1998 and 2008. Salmonella incidence fell from 43 to 19 episodes/100 000 population but Campylobacter incidence after declining from 111/100 000 in 1998 to 84/100 000 in 2003 rose to 119/100 000 in 2008. The proportion of the population sampled rose from 2·0% in 1998 to 2·8% in 2008, mostly due to increases in samples from hospital patients and older adults. The proportion of positive samples declined for both Salmonella and Campylobacter from 3·1% to 1·1% and from 8·9% to 7·5%, respectively. The decline in Salmonella incidence is so substantial that it is not masked even by increased stool sampling, but the recent rise in Campylobacter incidence may be a surveillance artefact largely due to the increase in stool sampling in older people.

The public health response to the re-emergence of syphilis in Wales, UK.

During the 1990s, cases of infectious syphilis were uncommon in Wales. In 2002, an outbreak occurred in a sexual network of men who have sex with men (MSM) attending a sauna. A multidisciplinary outbreak control team was convened to raise awareness of the outbreak among MSM and health professionals, assess the extent of outbreak, and initiate surveillance measures. It is likely that early intensive control efforts dampened the epidemic curve. However, since 2006 the number of cases has increased steadily to a peak of four cases per 100,000 population in 2008. The majority of cases continue to occur in MSM (81% in 2009) and in those attending genitourinary (GU) medicine clinics in south east Wales (76%). Traditional sexual networks such as saunas, bars/clubs and cruising grounds remain frequently reported, but Internet-based networks are assuming increasing importance. Public health interventions have been sustained, using traditional partner notification, health promotion initiatives, and more innovative Internet network tracing methods.

Two waves of pandemic influenza A(H1N1) 2009 in Wales--the possible impact of media coverage on consultation rates, April-December 2009.

In the United Kingdom, the influenza A(H1N1) 2009 pandemic had a distinct two-wave pattern of general practice consultations for influenza-like illness (ILI). We describe the epidemiology of the influenza pandemic in Wales between April and December 2009 using integrated data from a number of independent sources: GP surveillance, community virology surveillance, hospital admissions and deaths, and media enquiries monitoring. The first wave peaked in late July at 100 consultations per 100,000 general practice population and attracted intensive media coverage. The positivity rate for the A(H1N1)2009 influenza did not exceed 25% and only 44 hospitalisations and one death were recorded. By contrast, the second wave peaked in late October and although characterised by lower ILI consultation rates (65 consultations per 100,000 general practice population) and low profile media activity, was associated with much higher positivity rates for pandemic influenza A(H1N1)2009 (60%) and substantially more hospital admissions (n=379) and deaths (n=26). The large number of ILI-related consultations during the first wave in Wales probably reflected the intensive media activity rather than influenza virus circulating in the community. Data from community surveillance schemes may therefore have considerably overestimated the true incidence of influenza. This has implications for the future interpretation of ILI surveillance data and their use in policy making, and underlines the importance of using integrated epidemiological, virological and hospital surveillance data to monitor influenza activity.

Testosterone manipulation postcastration does not alter cloacal gland growth differences in male quail selected for divergent plasma corticosterone stress response.

Japanese quail selected for reduced (low-stress, LS) rather than exaggerated (high-stress, HS) plasma corticosterone response to brief restraint have consistently shown greater cloacal gland (CG) development, an androgen-dependent trait. In this study, the effects of testosterone implants on levels of plasma testosterone and CG development in castrated LS and HS quail were determined. Stress-line males were castrated and randomly allocated to 1 of 3 testosterone treatments: the empty testosterone (ET), low testosterone (LT), or high testosterone (HT) implant group. Cloacal gland volume was determined at 4 weekly intervals that represented ranges of 1 to 9 d, 8 to 17 d, 15 to 24 d, and 22 to 31 d after castration and testosterone implantation. Levels of plasma testosterone were also assessed at the end of the study. Development of the CG was affected by quail line (LS > HS), testosterone treatment (HT > LT > ET), and time of measurement (1 to 9 d < 8 to 17 d < 15 to 24 d = 22 to 31 d after castration and testosterone implantation). A significant interaction between testosterone treatment and time of measurement on CG volume was also detected (with CG volume generally increasing with time in LT- and HT-treated quail, but not in ET-treated quail). However, even though HT implant treatments induced higher CG development than did LT treatments beyond the first interval of CG volume measurement, and despite the finding of greater CG volumes in LS than HS quail during the last 2 measurement intervals within each of the LT and HT groups, no interaction was observed between testosterone implant dosages and quail stress line on CG volume. Thus, by the end of the study, regardless of testosterone dose, CG volume was consistently greater in LS quail than in their HS counterparts. In addition, although, as expected, the testosterone implant treatment significantly altered levels of plasma testosterone (HT > LT > ET), neither quail line nor its interaction with testosterone treatment affected plasma testosterone. The present findings suggest that the often-observed depressed CG development in the HS line may be independent of testosterone effects.

A community outbreak of Legionnaires' disease in South Wales, August-September 2010.

During August and September 2010, an outbreak comprising 22 cases of Legionnaires' disease was identified by the public health service in Wales. The cases are distributed over a wide geographical area in South East Wales. There are two space-time clusters centred on the upper Rhymney Valley and the lower Cynon Valley respectively. Epidemiological investigations are compatible with cooling towers in each location as the potential source, but environmental inspections were satisfactory and microbiological investigations are inconclusive.

Female Cape sugarbirds (Promerops cafer) modify egg investment both for extra-pair mates and for male tail length.

The differential allocation hypothesis predicts that females should invest more in reproduction when paired with attractive males. We measured egg volume in Cape sugarbirds (Promerops cafer), a sexually dimorphic passerine, in relation to paternity of the offspring and in response to an experimental tail length treatment. We manipulated tail length, after pair formation, but before egg laying: males had their tails either shortened or left unmanipulated. Our manipulation was designed to affect female allocation in a particular breeding attempt rather than long-term mate choice: males with shortened tails would appear to be signalling at a lower level than they should given their quality. We found that egg volume was smaller in the nests of males with experimentally shortened tails but larger when the offspring were the result of extra-pair matings. Both these findings are consistent with the differential allocation hypothesis. We suggest that tail length may be used by females as a cue for mate quality, eliciting reduced female investment when breeding with social mates; and with males with shortened tails.

Condensation transition in polydisperse hard rods.

We study a mass transport model, where spherical particles diffusing on a ring can stochastically exchange volume v, with the constraint of a fixed total volume V= sum(i=1) (N)v(i), N being the total number of particles. The particles, referred to as p-spheres, have a linear size that behaves as v(i) (1/p) and our model thus represents a gas of polydisperse hard rods with variable diameters v(i) (1/p). We show that our model admits a factorized steady state distribution which provides the size distribution that minimizes the free energy of a polydisperse hard-rod system, under the constraints of fixed N and V. Complementary approaches (explicit construction of the steady state distribution on the one hand; density functional theory on the other hand) completely and consistently specify the behavior of the system. A real space condensation transition is shown to take place for p>1; beyond a critical density a macroscopic aggregate is formed and coexists with a critical fluid phase. Our work establishes the bridge between stochastic mass transport approaches and the optimal polydispersity of hard sphere fluids studied in previous articles.

Sexual selection and condition-dependence.

The handicap theory of sexual selection suggests that females prefer mates who display extravagant ornaments that advertise their quality or condition. It is often assumed that as such ornamental traits undergo sexually-selected exaggeration, they must inevitably become more sensitive to condition, and thus more informative. Here, we show that this is not necessarily the case. Depending on the precise form of the relationship between trait size and cost, expression may become more or less condition-dependent as the trait undergoes exaggeration, or may remain unchanged. This leads us to question how much of the information content of sexual signals can be attributed to sexual selection, and how much to pre-existing, naturally-selected condition-dependence.

Nonequilibrium phase transitions in the extraction of membrane tubes by molecular motors.

The extraction of membrane tubes by molecular motors is known to play an important role for the transport properties of eukaryotic cells. By studying a generic class of models for the tube extraction, we discover a rich phase diagram. In particular we show that the density of motors along the tube can exhibit shocks, inverse shocks, and plateaux, depending on parameters which could in principle be probed experimentally. In addition the phase diagram exhibits interesting reentrant behavior.

An evaluation of the completeness of reporting of childhood tuberculosis.

The sensitivity of the Enhanced Tuberculosis Surveillance (ETS) scheme for monitoring tuberculosis in children is unknown. We used the British Paediatric Surveillance Unit (BPSU) reporting scheme to conduct a prospective observational study of tuberculosis in children aged <16 yrs in the UK. Reported cases were then matched with records from the ETS database. A total of 320 cases were reported to the BPSU between January and December 2004. We estimated that there were 557 paediatric cases in England, Wales and Northern Ireland in 2004: 222 (40%) cases reported to both BPSU and ETS, 98 (18%) reported to BPSU but not ETS and 237 (42%) reported to ETS but not BPSU. Children aged <5 yrs were significantly less likely to be reported to ETS compared with older children (p<0.01). There is substantial under-reporting of childhood tuberculosis, especially of children aged <5 yrs. ETS provides a representative picture of the demographics but may miss approximately 20% of cases. This should be taken into account when planning training and resource requirements for tuberculosis. Increased efforts are needed to ensure that all paediatric cases are reported to ETS.

Tuberculosis in the United Kingdom and Republic of Ireland.

AIMS: To describe the clinical features, diagnosis and management of children with tuberculosis in the United Kingdom and Republic of Ireland. METHODS: Cases of culture-confirmed and clinically diagnosed tuberculosis were reported to the British Paediatric Surveillance Unit from December 2003 to January 2005. RESULTS: 385 eligible cases were reported. Pulmonary disease was present in 154 (40%) children. Just over half (197, 51%) of children presented clinically and most of the remainder (166, 43%) at contact tracing. A probable source case was identified for 73/197 (36%) of the children presenting clinically. The majority (253, 66%) of children had a microbiological and/or histological investigation, and culture results were available for 240 (62%), of whom 102 (26%) were culture positive. Drug resistance was reported in 15 (0.4%) cases. 44% (128/292) of non-white children did not receive the recommended quadruple drug therapy. Seven children died. Only 57% (217) of children were managed by a paediatric subspecialist in respiratory or infectious diseases or a general paediatrician with a special interest in one of these areas. Fewer than five cases were reported from 119/143 (83%) respondents and 72 of 96 (75%) centres. CONCLUSIONS: Many paediatricians and centres see few children with tuberculosis. This may affect adherence to national guidelines. Managed clinical networks for children with tuberculosis may improve management and should be the standard of care.

A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26.

Bipolar affective disorder is a heritable, relatively common, severe mood disorder with lifetime prevalence up to 4%. We report the results of a genome-wide linkage analysis conducted on a cohort of 35 Australian bipolar disorder families which identified evidence of significant linkage on chromosome 15q25-26 and suggestive evidence of linkage on chromosomes 4q, 6q and 13q. Subsequent fine-mapping of the chromosome 15q markers, using allele frequencies calculated from our cohort, gave significant results with a maximum two-point LOD score of 3.38 and multipoint LOD score of 4.58 for marker D15S130. Haplotype analysis based on pedigree-specific, identical-by-descent allele sharing, supported the location of a bipolar susceptibility gene within the Z(max-1) linkage confidence interval of 17 cM, or 6.2 Mb, between markers D15S979 and D15S816. Non-parametric and affecteds-only linkage analysis further verified the linkage signal in this region. A maximum NPL score of 3.38 (P=0.0008) obtained at 107.16 cM (near D15S130), and a maximum two-point LOD score of 2.97 obtained at marker D15S1004 (affecteds only), support the original genome-wide findings on chromosome 15q. These results are consistent with four independent positive linkage studies of mood and psychotic disorders, and raise the possibility that a common gene for susceptibility to bipolar disorder, and other psychiatric disorders may lie in this chromosome 15q25-26 region.