Extending backcalculation to analyse BSE data.

We review the origins of backcalculation (or back projection) methods developed for the analysis of AIDS (acquired immunodeficiency syndrome) incidence data. These techniques have been used extensively for >15 years to deconvolute clinical case incidence, given knowledge of the incubation period distribution, to obtain estimates of past HIV (human immunodeficiency virus) infection incidence and short-term predictions of future AIDS incidence. Adaptations required for the analysis of bovine spongiform encephalopathy (BSE) incidence included: stratification of BSE incidence by age as well as birth cohort; allowance for incomplete survival between infection and the onset of clinical signs of disease; and decomposition of the age- and time-related infection incidence into a time-dependent feed risk component and an age-dependent exposure/susceptibility function. The most recent methodological developments focus on the incorporation of data from clinically unaffected cattle screened using recently developed tests for preclinical BSE infection. Backcalculation-based predictions of future BSE incidence obtained since 1996 are examined. Finally, future directions of epidemiological analysis of BSE epidemics are discussed taking into account ongoing developments in the science of BSE and possible changes in BSE-related policies

Choice between alternative routes to go public: backdoor listing versus IPO

Going public is the dream of many private companies. It represents a major milestone in the development of a firm. The listing status brings a lot of advantages to a firm. Some of these advantages include (1) access to capital markets and lower cost of capital; (2) enhanced company reputation and profile; (3) providing liquidity for owners to cash out; and (4) use of stock to pay for acquisitions, among others. However, going public is also a costly process. The out-of-pocket costs for an IPO typically involve fees paid for investment banks, accountants, auditors, lawyers, other experts, underwriters and brokers. The IPO firm will also have to pay for the printing of a prospectus and listing fees and other compliance costs. Other hidden costs entail underpricing, more stringent disclosure and regulatory requirements and the time spent by senior management in preparing the company for public listing

Different epigenetic states define syncytiotrophoblast and cytotrophoblast nuclei in the trophoblast of the human placenta.

INTRODUCTION: The syncytiotrophoblast (STB) epithelial covering of the villous tree in the human placenta is a multi-nucleated syncytium that is sustained by continuous incorporation of differentiating cytotrophoblast (CTB) cells. STB nuclei display a variety of morphologies, but are generally more condensed in comparison to CTB nuclei. Here, we consider whether this condensation is a feature of epigenetic regulation of chromatin structure. METHODS: Semi-quantitative immunohistochemical investigations of a panel of histone modifications were performed to determine the relative proportions in CTB and STB nuclear populations. We also investigated the patterns of DNA methylation and distribution of DNA methyltransferases enzymes in these populations. RESULTS: Unexpectedly DNA methylation, and H3K9me3 and H3K27me3, which are modifications associated with heterochromatin, are present at lower levels in STB nuclei compared to CTB, despite the intensive condensation in the former nuclear population and the progenitor state of the latter. By contrast, STB nuclei are enriched for H4K20me3, which is also associated with repressive states. 5'hydroxymethylcytosine immunoreactivity is higher in STB, with intense staining observed in the highly condensed nuclei within syncytial knots. DISCUSSION: Cell-type specific epigenetic states exist within the trophoblast populations potentially regulating their different functions and developmental properties and suggesting non-canonical epigenetic states associated with the properties of these cells.This work was funded by a studentship from the Anatomical Society of Great Britain and Ireland. The study was also supported by the Centre for Trophoblast Research.This is the accepted manuscript. The final version is available at http://www.sciencedirect.com/science/article/pii/S0143400415009248

Managing and reducing uncertainty in an emerging influenza pandemic

published_or_final_versio

Perturbations to the IGF1 growth pathway and adult energy homeostasis following disruption of mouse chromosome 12 imprinting

AIM: Disruption to insulin-like growth factor (IGF) signalling pathways during early life causes growth retardation and defects of developing metabolic organs that can alter set points of energy homeostasis for a lifetime. Inheritance of two maternal copies of human chromosome 14q32.2 (Temple syndrome) causes severe foetal growth retardation and post-natal failure to thrive. Disruption of imprinted gene dosage in the orthologous region on mouse chromosome 12 also affects growth. Here, we investigated whether altering chromosome 12-imprinted gene dosage can affect IGF signalling. METHODS: We investigated mice with a transgene insertion at the imprinted domain of chromosome 12. This lesion causes misexpression of neighbouring genes such that the expression of non-coding RNAs is elevated, and levels of delta-like homologue 1 (Dlk1), retrotransposon-like 1 (Rtl1) and deiodinase 3 (Dio3) transcripts are reduced. RESULTS: We observed three key phenotypes in these mice: (i) embryonic growth retardation associated with altered expression of IGF1 binding proteins, (ii) peri-natal failure to thrive accompanied by hypothyroidism and low serum IGF1. Unexpectedly this phenotype was growth hormone independent. (iii) Adult animals had reduced glucose tolerance as a result of endocrine pancreatic insufficiency. CONCLUSIONS: We propose that all of these phenotypes are attributable to impaired IGF action and show for the first time that the chromosome 12 cluster in the mouse is an imprinted locus that modulates the IGF signalling pathway. We propose that growth retardation observed in human Temple syndrome might have a similar cause

Cavity-mediated coherent coupling of magnetic moments

We demonstrate the long range strong coupling of magnetostatic modes in spatially separated ferromagnets mediated by a microwave frequency cavity. Two spheres of yttrium iron garnet are embedded in the cavity and their magnetostatic modes probed using a dispersive measurement technique. We find they are strongly coupled to each other even when detuned from the cavity modes, and investigate the dependence of the magnet-magnet coupling on the cavity detuning. Dark states of the coupled magnetostatic modes of the system are observed, and ascribed to mismatches between the symmetries of the modes and the drive field.We would like to acknowledge support from Hitachi Cambridge Laboratory, EPSRC Grant No. EP/K027018/1 and ERC Grant No. 648613. A.J.F. is supported by a Hitachi Research Fellowship. A.C.D. is supported by the ARC via the Centre of Excellence in Engineered Quantum Systems (EQuS), Project No. CE110001013.This is the author accepted manuscript. The final version is available from the American Physical Society via http://dx.doi.org/10.1103/PhysRevA.93.02180

Key traveller groups of relevance to spatial malaria transmission: a survey of movement patterns in four sub-Saharan African countries

Background: As malaria prevalence declines in many parts of the world due to widescale control efforts and as drug-resistant parasites begin to emerge, a quantitative understanding of human movement is becoming increasingly relevant to malaria control. However, despite its importance, significant knowledge gaps remain regarding human movement, particularly in sub-Saharan Africa. Methods: A quantitative survey of human movement patterns was conducted in four countries in sub-Saharan Africa: Mali, Burkina Faso, Zambia, and Tanzania, with three to five survey locations chosen in each country. Questions were included on demographic and trip details, malaria risk behaviour, children accompanying travellers, and mobile phone usage to enable phone signal data to be better correlated with movement. A total of 4352 individuals were interviewed and 6411 trips recorded. Results: A cluster analysis of trips highlighted two distinct traveller groups of relevance to malaria transmission: women travelling with children (in all four countries) and youth workers (in Mali). Women travelling with children were more likely to travel to areas of relatively high malaria prevalence in Mali (OR = 4.46, 95 % CI = 3.42–5.83), Burkina Faso (OR = 1.58, 95 % CI = 1.23–1.58), Zambia (OR = 1.50, 95 % CI = 1.20–1.89), and Tanzania (OR = 2.28, 95 % CI = 1.71–3.05) compared to other travellers. They were also more likely to own bed nets in Burkina Faso (OR = 1.77, 95 % CI = 1.25–2.53) and Zambia (OR = 1.74, 95 % CI = 1.34 2.27), and less likely to own a mobile phone in Mali (OR = 0.50, 95 % CI = 0.39–0.65), Burkina Faso (OR = 0.39, 95 % CI = 0.30–0.52), and Zambia (OR = 0.60, 95 % CI = 0.47–0.76). Malian youth workers were more likely to travel to areas of relatively high malaria prevalence (OR = 23, 95 % CI = 17–31) and for longer durations (mean of 70 days cf 21 days, p < 0.001) compared to other travellers. Conclusions: Women travelling with children were a remarkably consistent traveller group across all four countries surveyed. They are expected to contribute greatly towards spatial malaria transmission because the children they travel with tend to have high parasite prevalence. Youth workers were a significant traveller group in Mali and are expected to contribute greatly to spatial malaria transmission because their movements correlate with seasonal rains and hence peak mosquito densities. Interventions aimed at interrupting spatial transmission of parasites should consider these traveller groups

The Open Access Advantage Revisited

This paper is a revision of one that appeared in 2008, incorporating the many developments and changes that have happened since then.published_or_final_versio