Sports participation, physical activity, and friendship quality are theorized to have protective effects on the developmental emergence of substance use and self-harm behavior in adolescence, but existing research has been mixed. This ambiguity could reflect, in part, the potential for confounding of observed associations by genetic and environmental factors, which previous research has been unable to rigorously rule out. We used data from the prospective, population-based Child and Adolescent Twin Study in Sweden (n = 18,234 born 1994–2001) and applied a co-twin control design to account for potential genetic and environmental confounding of sports participation, physical activity, and friendship quality (assessed at age 15) as presumed protective factors for adolescent substance use and self-harm behavior (assessed at age 18). While confidence intervals widened to include the null in numerous co-twin control analyses adjusting for childhood psychopathology, parent-reported sports participation and twin-reported positive friendship quality were associated with increased odds of alcohol problems and nicotine use. However, parent-reported sports participation, twin-reported physical activity, and twin-reported friendship quality were associated with decreased odds of self-harm behavior. The findings provide a more nuanced understanding of the risks and benefits of putative protective factors for risky behaviors that emerge during adolescence.

Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.

Surveillance for acute flaccid paralysis (AFP) cases are essential for polio eradication. However, as most poliovirus infections are asymptomatic and some regions of the world are inaccessible, additional surveillance tools require development. Within England and Wales, we demonstrate how inclusion of environmental sampling (ENV) improves the sensitivity of detecting both wild and vaccine-derived polioviruses (VDPVs) when compared to current surveillance. Statistical modelling was used to estimate the spatial risk of wild and VDPV importation and circulation in England and Wales. We estimate the sensitivity of each surveillance mode to detect poliovirus and the probability of being free from poliovirus, defined as being below a pre-specified prevalence of infection. Poliovirus risk was higher within local authorities in Manchester, Birmingham, Bradford and London. The sensitivity of detecting wild poliovirus within a given month using AFP and enterovirus surveillance was estimated to be 0.096 (95% CI 0.055–0.134). Inclusion of ENV in the three highest risk local authorities and a site in London increased surveillance sensitivity to 0.192 (95% CI 0.191–0.193). The sensitivity of ENV strategies can be compared using the framework by varying sites and the frequency of sampling. The probability of being free from poliovirus slowly increased from the date of the last case in 1993. ENV within areas thought to have the highest risk improves detection of poliovirus, and has the potential to improve confidence in the polio-free status of England and Wales and detect VDPVs.

The Iron Age of Mainland Southeast Asia began in the fifth century bc and lasted for about a millennium. In coastal regions, the development of trade along the Maritime Silk Road led to the growth of port cities. In the interior, a fall in monsoon rains particularly affected the Mun River valley. This coincided with the construction of moats/reservoirs round Iron Age settlements from which water was channelled into wet rice fields, the production of iron ploughshares and sickles, population growth, burgeoning exchange and increased conflict. We explore the social impact of this agricultural revolution through applying statistical analyses to mortuary samples dating before and after the development of wet rice farming. These suggest that there was a swift formation of social elites represented by the wealth of mortuary offerings, followed by a decline. Two associated changes are identified. The first involved burying the dead in residential houses; the second considers the impact of an increasingly aquatic environment on health by examining demographic trends involving a doubling of infant mortality that concentrated on neonates. A comparison between this sequence and that seen in coastal ports suggests two interconnected instances of rapid pathways to social change responding to different social and environmental stressors.

Given the challenges in accurately identifying unexposed controls in case–control studies of diarrhoea, we examined diarrhoea incidence, subclinical enteric infections and growth stunting within a reference population in the Global Enteric Multicenter Study, Kenya site. Within ‘control’ children (0–59 months old without diarrhoea in the 7 days before enrolment, n = 2384), we examined surveys at enrolment and 60-day follow-up, stool at enrolment and a 14-day post-enrolment memory aid for diarrhoea incidence. At enrolment, 19% of controls had ⩾1 enteric pathogen associated with moderate-to-severe diarrhoea (‘MSD pathogens’) in stool; following enrolment, many reported diarrhoea (27% in 7 days, 39% in 14 days). Controls with and without reported diarrhoea had similar carriage of MSD pathogens at enrolment; however, controls reporting diarrhoea were more likely to report visiting a health facility for diarrhoea (27% vs. 7%) or fever (23% vs. 16%) at follow-up than controls without diarrhoea. Odds of stunting differed by both MSD and ‘any’ (including non-MSD pathogens) enteric pathogen carriage, but not diarrhoea, suggesting control classification may warrant modification when assessing long-term outcomes. High diarrhoea incidence following enrolment and prevalent carriage of enteric pathogens have implications for sequelae associated with subclinical enteric infections and for design and interpretation of case–control studies examining diarrhoea.

Measles vaccination is estimated to have averted 13·8 million deaths between 2000 and 2012. Persisting heterogeneity in coverage is a major contributor to continued measles mortality, and a barrier to measles elimination and introduction of rubella-containing vaccine. Our objective is to identify determinants of inequities in coverage, and how vaccine delivery must change to achieve elimination goals, which is a focus of the WHO Decade of Vaccines. We combined estimates of travel time to the nearest urban centre (⩾50 000 people) with vaccination data from Demographic Health Surveys to assess how remoteness affects coverage in 26 African countries. Building on a statistical mapping of coverage against age and geographical isolation, we quantified how modifying the rate and age range of vaccine delivery affects national coverage. Our scenario analysis considers increasing the rate of delivery of routine vaccination, increasing the target age range of routine vaccination, and enhanced delivery to remote areas. Geographical isolation plays a key role in defining vaccine inequity, with greater inequity in countries with lower measles vaccine coverage. Eliminating geographical inequities alone will not achieve thresholds for herd immunity, indicating that changes in delivery rate or age range of routine vaccination will be required. Measles vaccine coverage remains far below targets for herd immunity in many countries on the African continent and is likely to be inadequate for achieving rubella elimination. The impact of strategies such as increasing the upper age range eligible for routine vaccination should be considered.

Polymeric nanostructures can be synthesized where the catalytic motif is covalently attached within the core domain and protected from the environment by a polymeric shell. Such nanoreactors can be easily recycled, and have shown unique properties when catalyzing reactions under pseudohomogeneous conditions. Many examples of how these catalytic nanostructures can act as nanosized reaction vessels have been reported in the literature. This prospective will focus on the exclusive features observed for these catalytic systems and highlight their potential as enzyme mimics, as well as the importance of further studies to unveil their full potential.

We present the first radiocarbon dates from previously unrecorded, secondary burials in the Cardamom Mountains, Cambodia. The mortuary ritual incorporates nautical tradeware ceramic jars and log coffins fashioned from locally harvested trees as burial containers, which were set out on exposed rock ledges at 10 sites in the eastern Cardamom Massif. The suite of 28 14C ages from 4 of these sites (Khnorng Sroal, Phnom Pel, Damnak Samdech, and Khnang Tathan) provides the first estimation of the overall time depth of the practice. The most reliable calendar date ranges from the 4 sites reveals a highland burial ritual unrelated to lowland Khmer culture that was practiced from cal AD 1395 to 1650. The time period is concurrent with the 15th century decline of Angkor as the capital of the Khmer kingdom and its demise about AD 1432, and the subsequent shift of power to new Mekong trade ports such as Phnom Penh, Udong, and Lovek. We discuss the Cardamom ritual relative to known funerary rituals of the pre- to post-Angkorian periods, and to similar exposed jar and coffin burial rituals in Mainland and Island Southeast Asia.

1. The susceptibility of sheep to infection with Langat virus has been studied. No viraemia or symptoms were detected in sheep inoculated either subcutaneously or intracerebrally.

2. Only those sheep inoculated intracerebrally with 106·0–108·0 mouse IC LD 50 of virus developed significant quantities of neutralizing antibody.

3. Two-thirds of sheep vaccinated with varying doses of Langat virus withstood subcutaneous challenge of louping-ill virus followed by intracerebral starch. All the intracerebrally vaccinated sheep survived this form of challenge but no sheep, whether vaccinated subcutaneously or intracerebrally, withstood intracerebral challenge of louping ill.

4. In a field trial, three of ten hoggs vaccinated with Langat virus and exposed to natural louping ill infection at Camlarg and Dalcairnie died of the disease compared with all eight of the non-vaccinated hoggs. At Knockgray, there was no louping ill infection, but 93% of the hoggs from this hirsel developed louping ill antibody after transfer to Camlarg.

5. Monkeys infected intracerebrally, subcutaneously or orally with Langat virus showed a low titre viraemia without clinical symptoms or histological changes in the brain and developed high titres of antibody. Vaccinated monkeys challenged with either Central European tick-borne encephalitis or Kyasanur Forest disease viruses remained healthy compared with control monkeys which showed evidence of disease.

Primary kitten kidney cultures are frequently contaminated with wild feline infectious enteritis (FIE) virus and this led the authors to develop feline embryo diploid cell lines. Monolayer cultures were prepared from the lungs or from eviscerated and decapitated carcases of embryos obtained by Caesarian section from healthy pregnant queens. At about the 30th passage, these cells lost their fibroblastic morphology to become polygonal. After a further thirty passages the monolayers exhibited foci of low cell density circumscribed by bands of cells stacked in disorganized arrangement. All the developed cell lines were susceptible to infection with FIE virus and produced intranuclear changes resembling those described by Johnson (1965) in primary kitten kidney monolayers.

On four occasions the cell lines became contaminated with Mycoplasma and although there was evidence that the virus could infect the cells, there was no production of infective virus.

A simple karyotype was devised in which the 38 chromosomes were arranged in three groups according to the arm-length ratio and the percentage mean index length. After the 50th passage many of the nuclei of lung-derived cultures exhibited abnormal chromosomes resulting from ring formation or translocation, whilst those of embryo culture demonstrated a new modal chromosome number of 37.

We are grateful to Mrs L. Hitchcock and Mrs P. Waller, A.I.S.T., for technical assistance, to Mr E. A. Jones, A.I.I.P., for the photomicrographs and to Dr R. H. Johnson, University of Bristol, for supplying the leopard and mink enteritis viruses.

The propensity of an attenuated strain of feline infectious enteritis (panleucopaenia) virus to spread from vaccinated cats affected with intercurrent feline respiratory disease to unvaccinated in-contact cats was eradicated by further passaging of the vaccine virus in tissue culture. No virus was recovered from, and no antibody was found in the sentinel cats in contact with seven vaccinated animals. Thus, a further 27 passages of the vaccine virus in tissue culture has eliminated the spread factor.

When ten cats were infected orally with undiluted or a 10−1 dilution of virulent feline infectious enteritis (panleucopaenia) virus, all developed severe leucopaenia followed by the development of demonstrable antibody, but none died. Eighteen of 29 cats given a 10−2 dilution of virus died of the disease. Three of the survivors had white blood cell counts of less than 4000 and three had counts between 4000 and 6000 cells. Although the remaining five animals never had individual counts of less than 6000 cells, the geometric means of these counts showed that a marked depression in the leucocyte counts had occurred. All surviving cats developed antibody.

Among the ten cats dosed with either 10−3 or 10−4 dilution of virus, four died of feline infectious enteritis and three developed antibody after falls in the leucocyte counts. It is suspected that low dilutions of feline infectious enteritis virulent virus in cats produce a phenomenon similar to that reported by von Magnus (1954) with influenza virus in eggs.

Leucopaenia is commonly defined as less than 4000 white blood cells/mm.3 of blood. Counts lower than this are usual in cats which either die of the disease or have received large doses of virus; they are less common in cats surviving after administration of diluted virus. Challenge of cats with pre-existing antibody did not provoke a depression in the leucocyte counts.

1. Following an epizootic of louping ill on certain farms in south-west Ayrshire in 1960, a long-term study of several farms was initiated.

2. The flocks on two hirsels of one farm were studied during spring and early summer of 1961. Although only one lamb death was confirmed as due to louping ill, the infection rates in sentinel hoggs on the two hirsels were 50–60. and 11% respectively. The difference between the hirsels is probably attributable to the difference in the amount of tick habitat on them.

3. The ewes were bled in March and June and their lambs in June. Haemagglutinin inhibition (HI) and neutralization tests revealed that the HI antibody is much shorter lasting than neutralizing antibody. Many ewes, therefore, had neutralizing but not HI antibody. Otherwise agreement between the tests was good. In March almost all the ewes aged 3 years or more had antibody. Of the gimmers (2-year-olds) about two-thirds on one hirsel and one-third on the other had antibody in March: by June almost all the former and about half of the latter had antibody.

4. About two-thirds of the lambs had the same antibody status as their mothers in June and almost all the rest had less antibody than their mothers. Serological evidence suggestive of louping ill without recognizable clinical disease was found in six lambs and a further lamb recovered from clinical disease.

5. Revaccination of two-thirds of the flock failed to cause any detectable change in antibody status.

6. The epidemiology and pathogenesis are discussed in relation to immunity and infection rates, and to the design of control measures.

We are greatly indebted to the late Mr James Murdoch at Dalmellington, Mr John Murdoch at Dalcairnie Farm, and Mr David Murdoch at Knockgray Farm for permission to work on their farms and for all the help they gave us during the study.

In the course of developing a living attenuated feline infectious enteritis (panleucopaenia) vaccine, it was found that respiratory disease-infected cats newly inoculated with this vaccine spread vaccine virus to respiratory disease-infected in-contact controls. These in-contact controls were able to infect other cats with which they were placed in contact so that after five natural transmissions in this way and two oral administrations and subsequent re-isolations, reversion to virulence became evident. It is clear that before general release of a new living feline infectious enteritis vaccine, there must be satisfactory evidence that con-current infection will not affect the safety of the modified antigen.

In cats infected with feline infectious enteritis there appears to be a short period, coinciding with the onset of leucopaenia, during which they are highly infectious. It seems possible that some infected animals may become immune carriers because virus has been recovered from the small intestine of two of four cats with significant antibody titres 22–24 days after exposure to infection.

Sheep, after infection with louping ill virus and after re-infection with the same strain of virus 19–21 months later, were bled at intervals and their sera examined for neutralizing and haemagglutinin-inhibiting antibodies. Each antibody type was measured by the constant serum/variable virus and constant virus/variable serum methods. The persistence of each type of antibody and its significance in epidemiological studies is discussed. The relationship of antibody levels in ewes and their lambs was also examined.