The chiral Gaussian two-matrix ensemble of real asymmetric matrices

We solve a family of Gaussian two-matrix models with rectangular Nx(N+nu) matrices,having real asymmetric matrix elements and depending on a non-Hermiticity parameter mu. Our model can be thought of asxthe chiral extension of the real Ginibre ensemble, relevant for Dirac operators in the same symmetry class. It has the property that its eigenvalues are either real, purely imaginary, or come in complex conjugate eigenvalue pairs. The eigenvalue joint probability distribution for our model is explicitly computed, leading to a non-Gaussian distribution including K-Bessel functions. All n-point density correlation functions are expressed for finite N in terms of a Pfaffian form. This contains a kernel involving Laguerre polynomials in the complex plane as a building block which was previously computed by the authors. This kernel can be expressed in terms of the kernel for complex non-Hermitian matrices, generalising the known relation among ensembles of Hermitian random matrices. Compact expressions are given for the density at finite N as an example, as well as its microscopic large-N limits at the origin for fixed nu at strong and weak non-Hermiticity

Vangl2-Regulated Polarisation of Second Heart Field-Derived Cells Is Required for Outflow Tract Lengthening during Cardiac Development.

Planar cell polarity (PCP) is the mechanism by which cells orient themselves in the plane of an epithelium or during directed cell migration, and is regulated by a highly conserved signalling pathway. Mutations in the PCP gene Vangl2, as well as in other key components of the pathway, cause a spectrum of cardiac outflow tract defects. However, it is unclear why cells within the mesodermal heart tissue require PCP signalling. Using a new conditionally floxed allele we show that Vangl2 is required solely within the second heart field (SHF) to direct normal outflow tract lengthening, a process that is required for septation and normal alignment of the aorta and pulmonary trunk with the ventricular chambers. Analysis of a range of markers of polarised epithelial tissues showed that in the normal heart, undifferentiated SHF cells move from the dorsal pericardial wall into the distal outflow tract where they acquire an epithelial phenotype, before moving proximally where they differentiate into cardiomyocytes. Thus there is a transition zone in the distal outflow tract where SHF cells become more polarised, turn off progenitor markers and start to differentiate to cardiomyocytes. Membrane-bound Vangl2 marks the proximal extent of this transition zone and in the absence of Vangl2, the SHF-derived cells are abnormally polarised and disorganised. The consequent thickening, rather than lengthening, of the outflow wall leads to a shortened outflow tract. Premature down regulation of the SHF-progenitor marker Isl1 in the mutants, and accompanied premature differentiation to cardiomyocytes, suggests that the organisation of the cells within the transition zone is important for maintaining the undifferentiated phenotype. Thus, Vangl2-regulated polarisation and subsequent acquisition of an epithelial phenotype is essential to lengthen the tubular outflow vessel, a process that is essential for on-going cardiac morphogenesis

Testing stock market convergence: a non-linear factor approach

This paper applies the Phillips and Sul (Econometrica 75(6):1771–1855, 2007) method to test for convergence in stock returns to an extensive dataset including monthly stock price indices for five EU countries (Germany, France, the Netherlands, Ireland and the UK) as well as the US between 1973 and 2008. We carry out the analysis on both sectors and individual industries within sectors. As a first step, we use the Stock and Watson (J Am Stat Assoc 93(441):349–358, 1998) procedure to filter the data in order to extract the long-run component of the series; then, following Phillips and Sul (Econometrica 75(6):1771–1855, 2007), we estimate the relative transition parameters. In the case of sectoral indices we find convergence in the middle of the sample period, followed by divergence, and detect four (two large and two small) clusters. The analysis at a disaggregate, industry level again points to convergence in the middle of the sample, and subsequent divergence, but a much larger number of clusters is now found. Splitting the cross-section into two subgroups including euro area countries, the UK and the US respectively, provides evidence of a global convergence/divergence process not obviously influenced by EU policies

Experimental demonstration of quantum memory for light

The information carrier of today's communications, a weak pulse of light, is an intrinsically quantum object. As a consequence, complete information about the pulse cannot, even in principle, be perfectly recorded in a classical memory. In the field of quantum information this has led to a long standing challenge: how to achieve a high-fidelity transfer of an independently prepared quantum state of light onto the atomic quantum state? Here we propose and experimentally demonstrate a protocol for such quantum memory based on atomic ensembles. We demonstrate for the first time a recording of an externally provided quantum state of light onto the atomic quantum memory with a fidelity up to 70%, significantly higher than that for the classical recording. Quantum storage of light is achieved in three steps: an interaction of light with atoms, the subsequent measurement on the transmitted light, and the feedback onto the atoms conditioned on the measurement result. Density of recorded states 33% higher than that for the best classical recording of light on atoms is achieved. A quantum memory lifetime of up to 4 msec is demonstrated.Comment: 22 pages (double line spacing) incl. supplementary information, 4 figures, accepted for publication in Natur

Using data from 'visible' populations to estimate the size and importance of 'hidden' populations in an epidemic: A modelling technique.

We used reported behavioural data from cisgender men who have sex with men and transgender women (MSM/TGW) in Bangalore, mainly collected from 'hot-spot' locations that attract MSM/TGW, to illustrate a technique to deal with potential issues with the representativeness of this sample. A deterministic dynamic model of HIV transmission was developed, incorporating three subgroups of MSM/TGW, grouped according to their reported predominant sexual role (insertive, receptive or versatile). Using mathematical modelling and data triangulation for 'balancing' numbers of partners and role preferences, we compared three different approaches to determine if our technique could be useful for inferring characteristics of a more 'hidden' insertive MSM subpopulation, and explored their potential importance for the HIV epidemic. Projections for 2009 across all three approaches suggest that HIV prevalence among insertive MSM was likely to be less than half that recorded in the surveys (4.5-6.5% versus 13.1%), but that the relative size of this subgroup was over four times larger (61-69% of all MSM/TGW versus 15%). We infer that the insertive MSM accounted for 10-20% of all prevalent HIV infections among urban males aged 15-49. Mathematical modelling can be used with data on 'visible' MSM/TGW to provide insights into the characteristics of 'hidden' MSM. A greater understanding of the sexual behaviour of all MSM/TGW is important for effective HIV programming. More broadly, a hidden subgroup with a lower infectious disease prevalence than more visible subgroups, has the potential to contain more infections, if the hidden subgroup is considerably larger in size

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Declining incidence of malaria imported into the UK from West Africa

BACKGROUND: Two thirds of all falciparum malaria cases reported in the United Kingdom (UK) are acquired in West Africa (WA). To ensure recommendations and guidelines for malaria prophylaxis in travellers to West Africa correlate to the risk of infection, a study was undertaken to examine recent trends and predict future patterns of imported malaria acquired by UK residents visiting West Africa and West African visitors to the UK between 1993 and 2006. METHODS AND RESULTS: Using passenger numbers and malaria surveillance reports, the data revealed a 2.3-fold increase in travel to West Africa with a five-fold increase in travelers visiting friends and relatives (VFR). Malaria incidence fell through the study period, the greatest decline noted in VFR with a fall from 196 cases/1,000 person-years to 52 cases/1,000 person-years, 9.8% per year p < 0.0001. The risk for travellers from the UK visiting for other reasons declined 2.7 fold, at an annual decrease of 7.0%, with the incidence in West African visitors to the UK falling by 2.3 fold, a rate of 7.9% annually. DISCUSSION: The reduction in incidence among all three groups of travellers may be explained by several factors; changing chemoprophylaxis usage and/or increased travel in urban areas where malaria risk has declined over the past decade, or widespread reduction in malaria transmission in West Africa. CONCLUSION: With the reduction in malaria incidence seen in both visitors to and from West Africa, the most rational explanation for these findings is a fall in malaria transmission in West Africa, which may require a change in chemoprophylaxis policy for UK travelers over the next 5-10 years

A novel isolator-based system promotes viability of human embryos during laboratory processing

In vitro fertilisation (IVF) and related technologies are arguably the most challenging of all cell culture applications. The starting material is a single cell from which one aims to produce an embryo capable of establishing a pregnancy eventually leading to a live birth. Laboratory processing during IVF treatment requires open manipulations of gametes and embryos, which typically involves exposure to ambient conditions. To reduce the risk of cellular stress, we have developed a totally enclosed system of interlinked isolator-based workstations designed to maintain oocytes and embryos in a physiological environment throughout the IVF process. Comparison of clinical and laboratory data before and after the introduction of the new system revealed that significantly more embryos developed to the blastocyst stage in the enclosed isolator-based system compared with conventional open-fronted laminar flow hoods. Moreover, blastocysts produced in the isolator-based system contained significantly more cells and their development was accelerated. Consistent with this, the introduction of the enclosed system was accompanied by a significant increase in the clinical pregnancy rate and in the proportion of embryos implanting following transfer to the uterus. The data indicate that protection from ambient conditions promotes improved development of human embryos. Importantly, we found that it was entirely feasible to conduct all IVF-related procedures in the isolator-based workstations

Support and Assessment for Fall Emergency Referrals (SAFER 1) trial protocol. Computerised on-scene decision support for emergency ambulance staff to assess and plan care for older people who have fallen: evaluation of costs and benefits using a pragmatic cluster randomised trial

Background: Many emergency ambulance calls are for older people who have fallen. As half of them are left at home, a community-based response may often be more appropriate than hospital attendance. The SAFER 1 trial will assess the costs and benefits of a new healthcare technology - hand-held computers with computerised clinical decision support (CCDS) software - to help paramedics decide who needs hospital attendance, and who can be safely left at home with referral to community falls services. Methods/Design: Pragmatic cluster randomised trial with a qualitative component. We shall allocate 72 paramedics ('clusters') at random between receiving the intervention and a control group delivering care as usual, of whom we expect 60 to complete the trial. Patients are eligible if they are aged 65 or older, live in the study area but not in residential care, and are attended by a study paramedic following an emergency call for a fall. Seven to 10 days after the index fall we shall offer patients the opportunity to opt out of further follow up. Continuing participants will receive questionnaires after one and 6 months, and we shall monitor their routine clinical data for 6 months. We shall interview 20 of these patients in depth. We shall conduct focus groups or semi-structured interviews with paramedics and other stakeholders. The primary outcome is the interval to the first subsequent reported fall (or death). We shall analyse this and other measures of outcome, process and cost by 'intention to treat'. We shall analyse qualitative data thematically. Discussion: Since the SAFER 1 trial received funding in August 2006, implementation has come to terms with ambulance service reorganisation and a new national electronic patient record in England. In response to these hurdles the research team has adapted the research design, including aspects of the intervention, to meet the needs of the ambulance services. In conclusion this complex emergency care trial will provide rigorous evidence on the clinical and cost effectiveness of CCDS for paramedics in the care of older people who have fallen