Sequence variation in the haemagglutinin-neuraminidase gene of human parainfluenza virus type 3 isolates in the UK

The sequence variation in a 934 base-pair region of the gene encoding the haemagglutinin-neuraminidase of five human parainfluenza virus type 3 (HPIV3) isolates was determined together with that of a prototype UK strain. All of the clinical isolates were from the Manchester area of the UK and were obtained in 1990. 1991 and 1993. The gene segment was amplified by the polymerase chain reaction using HPIVB-specific oligonucleotide primers. The nucleotide homology of the strains was high, around 99% and specific differences in the UK sequences when compared with that of the US prototype strain were identified. In addition, a number of isolate-specific differences were seen. No correlation was detected between the observed nucleotide mutations and the year of isolation, which supports the hypothesis that HPIV3 shows cocirculation of a heterogeneous population of viruses rather than varying with time in a linear fashion. However, the data suggested that geographically-defined genetic lineages of HPIV3 may exist

Forbush decreases and turbulence levels at CME fronts

We seek to estimate the average level of MHD turbulence near coronal mass ejection (CME) fronts as they propagate from the Sun to the Earth. We examine the cosmic ray data from the GRAPES-3 tracking muon telescope at Ooty, together with the data from other sources for three well observed Forbush decrease events. Each of these events are associated with frontside halo Coronal Mass Ejections (CMEs) and near-Earth magnetic clouds. In each case, we estimate the magnitude of the Forbush decrease using a simple model for the diffusion of high energy protons through the largely closed field lines enclosing the CME as it expands and propagates from the Sun to the Earth. We use estimates of the cross-field diffusion coefficient $D_{\perp}$ derived from published results of extensive Monte Carlo simulations of cosmic rays propagating through turbulent magnetic fields. Our method helps constrain the ratio of energy density in the turbulent magnetic fields to that in the mean magnetic fields near the CME fronts. This ratio is found to be $\sim$ 2% for the 11 April 2001 Forbush decrease event, $\sim$ 6% for the 20 November 2003 Forbush decrease event and $\sim$ 249% for the much more energetic event of 29 October 2003.Comment: Accepted for publication in Astronomy and Astrophysics. (Abstract abridged) Typos correcte

Molecular epidemiology of human rhinovirus infections in Kilifi, coastal Kenya

This study reports pediatric surveillance over 3 years for human rhinovirus (HRV) at the District Hospital of Kilifi, coastal Kenya. Nasopharyngeal samples were collected from children presenting at outpatient clinic with no signs of acute respiratory infection, or with signs of upper respiratory tract infection, and from children admitted to the hospital with lower respiratory tract infection. Samples were screened by real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) and classified further to species by nucleotide sequencing of the VP4/VP2 junction. Of 441 HRV positives by real-time RT-PCR, 332 were classified to species, with 47% (155) being HRV-A, 5% (18) HRV-B, and 48% (159) HRV-C. There was no clear seasonal pattern of occurrence for any species. The species were present in similar proportions in the inpatient and outpatient sample sets, and no significant association between species distribution and the severity of lower respiratory tract infection in the inpatients could be determined. HRV sequence analysis revealed multiple but separate clusters in circulation particularly for HRV-A and HRV-C. Most HRV-C clusters were distinct from reference sequences downloaded from GenBank. In contrast, most HRV-A and HRV-B sequences clustered with either known serotypes or strains from elsewhere within Africa and other regions of the world. This first molecular epidemiological study of HRV in the region defines species distribution in accord with reports from elsewhere in the world, shows considerable strain diversity and does not identify an association between any species and disease severity

PD-L1 testing for lung cancer in the UK: recognizing the challenges for implementation.

A new approach to the management of non-small-cell lung cancer (NSCLC) has recently emerged that works by manipulating the immune checkpoint controlled by programmed death receptor 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1). Several drugs targeting PD-1 (pembrolizumab and nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved or are in the late stages of development. Inevitably, the introduction of these drugs will put pressure on healthcare systems, and there is a need to stratify patients to identify those who are most likely to benefit from such treatment. There is evidence that responsiveness to PD-1 inhibitors may be predicted by expression of PD-L1 on neoplastic cells. Hence, there is considerable interest in using PD-L1 immunohistochemical staining to guide the use of PD-1-targeted treatments in patients with NSCLC. This article reviews the current knowledge about PD-L1 testing, and identifies current research requirements. Key factors to consider include the source and timing of sample collection, pre-analytical steps (sample tracking, fixation, tissue processing, sectioning, and tissue prioritization), analytical decisions (choice of biomarker assay/kit and automated staining platform, with verification of standardized assays or validation of laboratory-devised techniques, internal and external quality assurance, and audit), and reporting and interpretation of the results. This review addresses the need for integration of PD-L1 immunohistochemistry with other tests as part of locally agreed pathways and protocols. There remain areas of uncertainty, and guidance should be updated regularly as new information becomes available

Are we overestimating the permanence of cellulose triacetate cinematographic films? A mathematical model for the vinegar syndrome

Among the earliest signs of degradation in cellulose triacetate cinematographic films is the generation of acetic acid due to hydrolytic deacetylation of the polymer, marked by an increase in the acidity of the films and emissions of acetic acid leading to a characteristic vinegar odour. We propose a mathematical model for predicting the onset of the vinegar syndrome which accounts for the autocatalytic effect of acetic acid on the deacetylation reaction. Model parameters are estimated from previously published experimental data from other research groups. These show free acidity changes in cellulose triacetate films subjected to accelerated ageing at temperatures of 70–100 °C. The model is validated against a different set of previously published experimental data of cellulose triacetate films aged at 21 °C and 35 °C, at 20, 35 and 50% relative humidity. The model demonstrates good quantitative agreement with the published experimental data. Predictions of film permanence at lower temperatures, similar to those present in the archives in which the films are typically stored, are made and compared with the predictions of film conservation guidelines. The results indicate that film permanence may be overestimated by existing guidelines, which do not account for autocatalysis in their modelling of the deacetylation rate. Our results suggest that cold storage, a common film conservation strategy, may be less effective at inhibiting degradation than previously thought. As cold storage typically requires film to be kept in confined spaces with limited air movement, conditions which promote autocatalysis, the inclusion of autocatalysis in our model is highly applicable to simulating this environment

Relativistic Proton Production During the 14 July 2000 Solar Event: The Case for Multiple Source Mechanisms

Protons accelerated to relativistic energies by transient solar and interplanetary phenomena caused a ground-level cosmic ray enhancement on 14 July 2000, Bastille Day. Near-Earth spacecraft measured the proton flux directly and ground-based observatories measured the secondary responses to higher energy protons. We have modelled the arrival of these relativistic protons at Earth using a technique which deduces the spectrum, arrival direction and anisotropy of the high-energy protons that produce increased responses in neutron monitors. To investigate the acceleration processes involved we have employed theoretical shock and stochastic acceleration spectral forms in our fits to spacecraft and neutron monitor data. During the rising phase of the event (10:45 UT and 10:50 UT) we find that the spectrum between 140 MeV and 4 GeV is best fitted by a shock acceleration spectrum. In contrast, the spectrum at the peak (10:55 UT and 11:00 UT) and in the declining phase (11:40 UT) is best fitted with a stochastic acceleration spectrum. We propose that at least two acceleration processes were responsible for the production of relativistic protons during the Bastille Day solar event: (1) protons were accelerated to relativistic energies by a shock, presumably a coronal mass ejection (CME). (2) protons were also accelerated to relativistic energies by stochastic processes initiated by magnetohydrodynamic (MHD) turbulence.Comment: 38 pages, 9 figures, accepted for publication in the Astrophysical Journal, January, 200

On the Brightness and Waiting-time Distributions of a Type III Radio Storm observed by STEREO/WAVES

Type III solar radio storms, observed at frequencies below approximately 16 MHz by space borne radio experiments, correspond to the quasi-continuous, bursty emission of electron beams onto open field lines above active regions. The mechanisms by which a storm can persist in some cases for more than a solar rotation whilst exhibiting considerable radio activity are poorly understood. To address this issue, the statistical properties of a type III storm observed by the STEREO/WAVES radio experiment are presented, examining both the brightness distribution and (for the first time) the waiting-time distribution. Single power law behavior is observed in the number distribution as a function of brightness; the power law index is approximately 2.1 and is largely independent of frequency. The waiting-time distribution is found to be consistent with a piecewise-constant Poisson process. This indicates that during the storm individual type III bursts occur independently and suggests that the storm dynamics are consistent with avalanche type behavior in the underlying active region.Comment: 14 pages, 4 figures, 1 table. Accepted for publication in Astrophysical Journal Letter

Unveiling the importance of diffusion on the deterioration of cellulose acetate artefacts: The profile of plasticiser loss as assessed by infrared microscopy

Cellulose acetate (CA) artefacts are one of the most valued plastic items in museum collections and are known to present stability issues, with the loss of plasticiser being among the main degradation processes. This study investigates the concentration distribution of diethyl phthalate (DEP) plasticiser throughout the dimensions of CA using infrared microscopy for the first time. Artificial ageing experiments using reference and historic CA plasticised with DEP were performed to assess the change in the concentration profiles as a function of ageing time. Our analysis indicates that the plasticiser loss from CA artefacts is likely controlled by its diffusion, resulting in a concentration gradient in which lower plasticiser contents are observed at the external layers of the material

The effects on grain quality traits of a grain serpin protein and the VPM 1 segment in southern Australian wheat breeding

Trabalho final do 6º ano médico com vista à atribuição do Grau de Mestre no âmbito do ciclo de estudos de mestrado integrado em medicina da Faculdade de Medicina de Coimbra.Introdução: Estudos prévios estabeleceram que até 12% dos doentes com enfarte agudo do miocárdio não demonstravam lesão coronária aparente ao exame angiográfico. Contudo, existe muito pouca informação disponível acerca deste fenómeno em enfartes agudos do miocárdio sem elevação do segmento ST. O objectivo deste estudo foi avaliar uma população de doentes com esse diagnóstico sujeitos a angiografia coronária, analisando e comparando as características clínicas e os prognósticos entre os que não revelaram lesão coronária aparente e os que apresentavam doença coronária epicárdica. Métodos: O nosso estudo avaliou 270 doentes com enfarte agudo do miocárdio sem elevação do segmento ST que foram sujeitos a angiografia coronária nas primeiras 72 horas de enfarte. Foram valorizadas as características demográficas, clínicas, parâmetros analíticos, achados electrocardiográficos, fracção de ejecção ventricular esquerda, duração do internamento e prognóstico.Previous studies established that up to 12% of patients with acute myocardial infarction did not present coronary atherosclerotic disease demonstrable with angiographic exam. However, little information is available about this phenomenon in acute non-STelevation myocardial infarction. We examined a population of patients with this diagnosis who had undergone coronary angiography, assessing and comparing the clinical characteristics and prognosis between the subset of patients with angiographically normal coronary arteries and the subset of patients with coronary disease