Evaluating a novel patient pathway to manage symptomatic breast referrals (the blue flag clinic): a longitudinal observational study.

INTRODUCTION: A novel referral pathway for exhibited breast symptom (EBS) referrals to manage increasing referrals of urgent suspected cancer (USC) was implemented in our trust. We report on the safety and effect on compliance with the 2-week-wait rule (2WW). METHODS: A single-centre longitudinal observational study included all patients referred to a UK breast unit during 13 May 2019 to 27 March 2020 (period 1) and 8 February 2021 to 31 January 2022 (period 2). USC referrals were assessed in a one-stop clinic (red flag clinic [RFC]); EBS referrals were assessed in a new clinic in which clinical evaluation was performed and imaging occurred subsequently (blue flag clinic [BFC]). Patients were followed up to determine the symptomatic interval cancer rate. RESULTS: There were 9,695 referrals; 1,655 referrals (17%) were assessed in the BFC after 63 exclusions. Some 95.9% of patients had a benign clinical examination (P1/P2), 80.1% had imaging (mammogram or ultrasound) and 4% had a tissue biopsy. In total, 16/1,655 (0.97%) BFC patients and 510/7,977 (8.2%) RFC patients were diagnosed with breast cancer (breast cancer detection rate). Some 1,631 patients (with 1,639 referrals) were discharged and followed up for a median of 17 months (interquartile range 12-32) with one subsequent cancer diagnosis (symptomatic interval cancer rate, 0.06%). Implementation of the BFC pathway increased 3-month average trust performance of USC referrals with 2WW standard from 8.5% to 98.7% (period 1) and from 30% to 66% (period 2). CONCLUSIONS: The BFC pathway for EBS patients is safe and implementation led to improvement against the 2WW target for USC referrals, ensuring resources are prioritised to patients with the highest likelihood of breast cancer.

H9N2 avian influenza virus dispersal along Bangladeshi poultry trading networks.

Avian influenza virus subtype H9N2 is endemic in Bangladesh's poultry population. The subtype affects poultry production and poses a potential zoonotic risk. Insufficient understanding of how the poultry trading network shapes the dissemination of avian influenza viruses has hindered the design of targeted interventions to reduce their spread. Here, we use phylodynamic analyses of haemagglutinin sequences to investigate the spatial spread and dispersal patterns of H9N2 viruses in Bangladesh's poultry population, focusing on its two largest cities (Dhaka and Chattogram) and their poultry production and distribution networks. Our analyses suggest that H9N2 subtype avian influenza virus lineage movement occurs relatively less frequently between Bangladesh's two largest cities than within each city. H9N2 viruses detected in single markets are often more closely related to viruses from other markets in the same city than to each other, consistent with close epidemiological connectivity between markets. Our analyses also suggest that H9N2 viruses may spread more frequently between chickens of the three most commonly sold types (sunali-a cross-bred of Fayoumi hen and Rhode Island Red cock, deshi-local indigenous, and exotic broiler) in Dhaka than in Chattogram. Overall, this study improves our understanding of how Bangladesh's poultry trading system impacts avian influenza virus spread and should contribute to the design of tailored surveillance that accommodates local heterogeneity in virus dispersal patterns.

Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021.

Highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage (GsGd), which threaten the health of poultry, wildlife and humans, are spreading across Asia, Europe, Africa and North America but are currently absent from South America and Oceania. In December 2021, H5N1 HPAI viruses were detected in poultry and a free-living gull in St. John's, Newfoundland and Labrador, Canada. Our phylogenetic analysis showed that these viruses were most closely related to HPAI GsGd viruses circulating in northwestern Europe in spring 2021. Our analysis of wild bird migration suggested that these viruses may have been carried across the Atlantic via Iceland, Greenland/Arctic or pelagic routes. The here documented incursion of HPAI GsGd viruses into North America raises concern for further virus spread across the Americas by wild bird migration.

The role of national and international veterinary laboratories.

In the field of diagnostic test validation, World Organisation for Animal Health (OIE) Reference Laboratories (RLs) have a pivotal role and provide the international community with impartial advice and support in the selection, development and validation of diagnostic tests, which can be applied to the specialist diseases for which they are designated. National RLs provide an invaluable function in supporting the introduction, ongoing validation and application of validated diagnostic tests in line with international standards. Experienced staff with extensive knowledge of such systems and access to specialist facilities for conducting work are available to monitor changes or advancements in technology. They consider their relevance and value to evolving diagnostic test requirements. Reference Laboratories often have a broad mandate of activity linking research or development programmes and surveillance activities to benefit the continual assessment and, if necessary, improvement of diagnostic tools. Reference Laboratories maintain or have access to unique biological archives (known positive and negative sample populations) and produce international reference standards, both of which are vital in establishing the necessary and detailed validation of any diagnostic test. Reference Laboratories act either singularly or in collaborative partnerships with other RLs or science institutes, but also, when required, and with impartiality, with the commercial sector, to ensure new tests are validated according to OIE standards. They promote and apply formal programmes of quality assurance (including proficiency testing programmes) for newly validated tests, ensuring ongoing monitoring and compliance with standards, or as required set out any limitations or uncertainties. Reference Laboratories publish information on test validation in the scientific literature and on relevant websites, as well as disseminating information at workshops and international conferences. Furthermore, they can offer training in the processes and systems underpinning test validation.

Dans le domaine de la validation des tests de diagnostic, les Laboratoires de référence de l'Organisation mondiale de la santé animale (OIE) jouent un rôle central et fournissent à la communauté internationale des conseils impartiaux ainsi qu'un soutien pour la sélection, la mise au point et la validation des tests de diagnostic utilisés pour la détection des maladies correspondant à leur domaine de spécialisation. Les Laboratoires de référence nationaux remplissent une fonction inestimable en facilitant l'introduction, la validation continue et l'application de tests de diagnostic validés conformément aux normes internationales. Ces laboratoires sont dotés de personnels expérimentés possédant une connaissance approfondie de ces systèmes et qui ont accès à des installations spécialisées pour mener à bien leurs opérations et suivre de près les changements ou les avancées technologiques. Ils peuvent ainsi examiner leur pertinence et intérêt au regard de l'évolution des exigences relatives aux tests de diagnostic. Le mandat des Laboratoires de référence recouvre souvent un large éventail d'activités reliant les programmes de recherche ou développement et les activités de surveillance, ce qui permet de réaliser une évaluation continue des outils diagnostiques et, si besoin, de procéder à leur amélioration. Les Laboratoires de référence entretiennent ou ont accès à des banques de matériels biologiques uniques (panels d'échantillons positifs et négatifs connus) et produisent des réactifs de référence internationale, deux catégories de matériels essentielles pour procéder à la validation point par point d'un test diagnostique suivant les critères requis. Les Laboratoires de référence interviennent individuellement ou en partenariat avec d'autres Laboratoires de référence ou instituts scientifiques, mais aussi, lorsque c'est nécessaire et dans le respect des règles d'impartialité, avec le secteur privé, afin de s'assurer que les nouveaux tests sont validés conformément aux normes de l'OIE. Ils soutiennent et appliquent des programmes officiels d'assurance de la qualité (y compris en participant à des programmes d'essais d'aptitude inter-laboratoires) pour les tests nouvellement validés et garantissent leur suivi continu ainsi que leur conformité avec les normes, ou, suivant les cas, définissent les limites ou le niveau d'incertitude à prendre en considération. Les Laboratoires de référence publient les données relatives à la validation des tests dans des journaux scientifique et sur les sites Web pertinents et diffusent également des informations sur le sujet lors d'ateliers et de conférences internationales. En outre, ils peuvent proposer des formations sur les procédures et les systèmes qui sous-tendent la validation des tests.

En el terreno de la validación de pruebas de diagnóstico, los Laboratorios de Referencia de la Organización Mundial de Sanidad Animal (OIE) cumplen una función central y proporcionan a la comunidad internacional servicios de apoyo y asesoramiento imparcial para la selección, el desarrollo y la validación de pruebas de diagnóstico, que pueden aplicarse a la enfermedad para la que cada laboratorio esté designado. Los laboratorios de referencia nacionales cumplen una inestimable función de apoyo a la implantación, la continua validación y la utilización de pruebas de diagnóstico validadas con arreglo a las normas internacionales. Disponen de personal experimentado y muy buen conocedor de estos sistemas y de acceso a instalaciones especializadas de trabajo, lo que les permite seguir de cerca los cambios o adelantos tecnológicos y estudiar su utilidad o interés en relación con la evolución de los requisitos de las pruebas de diagnóstico. Los Laboratorios de Referencia suelen tener un mandato amplio, que a los programas de investigación y desarrollo aúna actividades de vigilancia, en aras de la continua evaluación y, en caso necesario, mejora de las herramientas de diagnóstico. Estos laboratorios poseen (o tienen acceso a) archivos biológicos únicos (conjuntos de muestras probadamente positivas y negativas) y elaboran patrones de referencia internacional, elementos ambos indispensables para llevar a buen fin la necesaria validación detallada de toda prueba de diagnóstico. Los Laboratorios de Referencia pueden trabajar en solitario o en colaboración con otros Laboratorios de Referencia, con institutos científicos e incluso, cuando hace falta, y procediendo con imparcialidad, con entidades del sector privado, a fin de garantizar que toda nueva prueba sea validada con arreglo a las normas de la OIE. También promueven y llevan adelante programas oficiales de garantía de la calidad de pruebas recién validadas (incluidos programas de pruebas de competencia), lo que asegura un seguimiento continuo y el cumplimiento de la normativa en todo momento, o fijan, cuando es necesario, limitaciones o niveles de incertidumbre. Asimismo, estos laboratorios publican datos sobre la validación de pruebas en revistas científicas y sitios web conexos y difunden información al respecto en talleres y conferencias internacionales. Además, pueden impartir formación sobre los procesos y sistemas que fundamentan la validación de pruebas de diagnóstico.

Highly pathogenic avian influenza virus H5N6 (clade 2.3.4.4b) has a preferable host tropism for waterfowl reflected in its inefficient transmission to terrestrial poultry.

Highly-pathogenic avian influenza virus (HPAIV) H5N6 (clade 2.3.4.4b) incurred into Europe in late 2017 and was predominantly detected in wild birds, with very few terrestrial poultry cases. Pekin ducks directly-infected with a UK virus (H5N6-2017) were donors of infection to investigate contact transmission to three recipient species: Ducks, chickens and turkeys. H5N6-2017 transmission to ducks was 100% efficient, but transmission to in-contact galliforme species was infrequent and unpredictable, thereby reflecting the European 2017-2018 H5N6 epidemiology. Although only two of 28 (7%) infected ducks died, the six turkeys and one chicken which became infected all died and displayed systemic H5N6-2017 dissemination, while pathogenesis in ducks was generally milder. Analysis of H5N6-2017 progeny in the contacts revealed no emergent polymorphisms in an infected duck, but the galliforme species included changes in the polymerase (PB2 A199T, PA D347A), matrix (M1 T218A) and neuraminidase genes (T88I). H5N6-2017 environmental contamination was associated with duck shedding.

International validation of a risk prediction algorithm for patients with malignant colorectal polyps.

AIM: The optimal management strategy for patients with endoscopically resected malignant colorectal polyps (MCP) has yet to be defined. The aim of this study was to validate a published decision-making tool, termed the Scottish Polyp Cancer Study (SPOCS) algorithm, on a large international population. METHODS: The SPOCS algorithm allocates patients to risk groups based on just two variables: the polyp resection margin and the presence of lymphovascular invasion (LVI). The risk groups are termed low (clear margin, LVI absent), medium (clear margin, LVI present) or high (involved/non-assessable margin). The International Polyp Cancer Collaborative was formed to validate the algorithm on data from Australia, Denmark, UK and New Zealand. RESULTS: In total, 1423 patients were included in the final dataset. 680/1423 (47.8%) underwent surgical resection and 108/680 (15.9%) had residual disease (luminal disease 8.8%, lymph node metastases 8.8%). The SPOCS algorithm classified 602 patients as low risk (in which 1.5% had residual disease), 198 patients as medium risk (in which 7.1% had residual disease) and 484 as high risk (in which 14.5% had residual disease) (P < 0.001, χ2 test). Receiver operating characteristic curve analysis demonstrated good accuracy of the algorithm in predicting residual disease (area under the curve 0.732, 95% CI 0.687-0.778, P < 0.001). When patients were designated as low risk, the negative predictive value was 98.5%. CONCLUSION: The SPOCS algorithm can be used to predict the risk of residual disease in patients with endoscopically resected MCPs. Surgery can be safely avoided in patients who have a clear margin of excision and no evidence of LVI.

Risk assessment for recrudescence of avian influenza in caged layer houses following depopulation: the effect of cleansing, disinfection and dismantling of equipment.

Following an outbreak of highly pathogenic avian influenza virus (HPAIV) in a poultry house, control measures are put in place to prevent further spread. An essential part of the control measures based on the European Commission Avian Influenza Directive 2005/94/EC is the cleansing and disinfection (C&D) of infected premises. Cleansing and disinfection includes both preliminary and secondary C&D, and the dismantling of complex equipment during secondary C&D is also required, which is costly to the owner and also delays the secondary cleansing process, hence increasing the risk for onward spread. In this study, a quantitative risk assessment is presented to assess the risk of re-infection (recrudescence) occurring in an enriched colony-caged layer poultry house on restocking with chickens after different C&D scenarios. The risk is expressed as the number of restocked poultry houses expected before recrudescence occurs. Three C&D scenarios were considered, namely (i) preliminary C&D alone, (ii) preliminary C&D plus secondary C&D without dismantling and (iii) preliminary C&D plus secondary C&D with dismantling. The source-pathway-receptor framework was used to construct the model, and parameterisation was based on the three C&D scenarios. Two key operational variables in the model are (i) the time between depopulation of infected birds and restocking with new birds (TbDR) and (ii) the proportion of infected material that bypasses C&D, enabling virus to survive the process. Probability distributions were used to describe these two parameters for which there was recognised variability between premises in TbDR or uncertainty due to lack of information in the fraction of bypass. The risk assessment estimates that the median (95% credible intervals) number of repopulated poultry houses before recrudescence are 1.2 × 104 (50 to 2.8 × 106), 1.9 × 105 (780 to 5.7 × 107) and 1.1 × 106 (4.2 × 103 to 2.9 × 108) under C&D scenarios (i), (ii) and (iii), respectively. Thus for HPAIV in caged layers, undertaking secondary C&D without dismantling reduces the risk by 16-fold compared to preliminary C&D alone. Dismantling has an additional, although smaller, impact, reducing the risk by a further 6-fold and thus around 90-fold compared to preliminary C&D alone. On the basis of the 95% credible intervals, the model demonstrates the importance of secondary C&D (with or without dismantling) over preliminary C&D alone. However, the extra protection afforded by dismantling may not be cost beneficial in the context of reduced risk of onward spread.

Lessons learned from the development of a hidradenitis suppurativa xenograft mouse model.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease originating from the pilosebaceous unit, in which patients develop painful abscesses, sinus tracts, nodules and scarring, typically in intertriginous areas. Major gaps in our understanding of HS exist, and these may be partially due to the lack of an animal model for experimental studies. We developed an HS xenograft mouse model using human HS lesions grafted onto immunocompromised mice. Although the model had its limitations, several informative lessons were learned, which may contribute to future attempts at an HS animal model.

A qualitative risk assessment of cleansing and disinfection requirements after an avian influenza outbreak in commercial poultry.

1. During an avian influenza (AI) outbreak in the United Kingdom, the joint aim of the poultry industry and the Government is to eliminate and prevent the spread of infection, through control measures based on the current European Union (EU) Council Directive (2005/94/EC). An essential part of these measures is the cleansing and disinfection (C&D) of infected premises.2. This risk assessment assessed the differences in re-infection in a repopulated flock if the EU Directive is interpreted to permit secondary C&D to be undertaken either with or without dismantling complex equipment. The assessment estimated the probability of virus survival on different types of equipment in a depopulated contaminated poultry house before and after preliminary and secondary C&D procedures. A risk matrix spreadsheet tool was used to carry out the assessment and concluded that, provided secondary C&D is carried out with due diligence (i.e. carried out to a defined code of practice as agreed by both industry and policymakers), the risk of re-infection from equipment is negligible, both with and without dismantling complex equipment in all farm types considered.3. By considering the equipment types individually, the assessment identified those areas of the house which may still contain viable virus post-preliminary C&D and on which attention should be focussed during secondary C&D. The generic risk pathway and matrix spreadsheet tool have the potential to be used for other pathogens and species, given appropriate data.

Atypical Chemokine Receptor 1 (DARC/ACKR1) in Breast Tumors Is Associated with Survival, Circulating Chemokines, Tumor-Infiltrating Immune Cells, and African Ancestry.

BACKGROUND: Tumor-specific immune response is an important aspect of disease prognosis and ultimately impacts treatment decisions for innovative immunotherapies. The atypical chemokine receptor 1 (ACKR1 or DARC) gene plays a pivotal role in immune regulation and harbors several single-nucleotide variants (SNV) that are specific to sub-Saharan African ancestry. METHODS: Using computational The Cancer Genome Atlas (TCGA) analysis, case-control clinical cohort Luminex assays, and CIBERSORT deconvolution, we identified distinct immune cell profile-associated DARC/ACKR1 tumor expression and race with increased macrophage subtypes and regulatory T cells in DARC/ACKR1-high tumors. RESULTS: In this study, we report the clinical relevance of DARC/ACKR1 tumor expression in breast cancer, in the context of a tumor immune response that may be associated with sub-Saharan African ancestry. Briefly, we found that for infiltrating carcinomas, African Americans have a higher proportion of DARC/ACKR1-negative tumors compared with white Americans, and DARC/ACKR1 tumor expression is correlated with proinflammatory chemokines, CCL2/MCP-1 (P <0.0001) and anticorrelated with CXCL8/IL8 (P <0.0001). Sub-Saharan African-specific DARC/ACKR1 alleles likely drive these correlations. Relapse-free survival (RFS) and overall survival (OS) were significantly longer in individuals with DARC/ACKR1-high tumors (P <1.0 × 10-16 and P <2.2 × 10-6, respectively) across all molecular tumor subtypes. CONCLUSIONS: DARC/AKCR1 regulates immune responses in tumors, and its expression is associated with sub-Saharan African-specific alleles. DARC/ACKR1-positive tumors will have a distinct immune response compared with DARC/AKCR1-negative tumors. IMPACT: This study has high relevance in cancer management, as we introduce a functional regulator of inflammatory chemokines that can determine an infiltrating tumor immune cell landscape that is distinct among patients of African ancestry.

Drought-induced Amazonian wildfires instigate a decadal-scale disruption of forest carbon dynamics.

Drought-induced wildfires have increased in frequency and extent over the tropics. Yet, the long-term (greater than 10 years) responses of Amazonian lowland forests to fire disturbance are poorly known. To understand post-fire forest biomass dynamics, and to assess the time required for fire-affected forests to recover to pre-disturbance levels, we combined 16 single with 182 multiple forest census into a unique large-scale and long-term dataset across the Brazilian Amazonia. We quantified biomass, mortality and wood productivity of burned plots along a chronosequence of up to 31 years post-fire and compared to surrounding unburned plots measured simultaneously. Stem mortality and growth were assessed among functional groups. At the plot level, we found that fire-affected forests have biomass levels 24.8 ± 6.9% below the biomass value of unburned control plots after 31 years. This lower biomass state results from the elevated levels of biomass loss through mortality, which is not sufficiently compensated for by wood productivity (incremental growth + recruitment). At the stem level, we found major changes in mortality and growth rates up to 11 years post-fire. The post-fire stem mortality rates exceeded unburned control plots by 680% (i.e. greater than 40 cm diameter at breast height (DBH); 5-8 years since last fire) and 315% (i.e. greater than 0.7 g cm-3 wood density; 0.75-4 years since last fire). Our findings indicate that wildfires in humid tropical forests can significantly reduce forest biomass for decades by enhancing mortality rates of all trees, including large and high wood density trees, which store the largest amount of biomass in old-growth forests. This assessment of stem dynamics, therefore, demonstrates that wildfires slow down or stall the post-fire recovery of Amazonian forests.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.

Direct evidence of H7N7 avian influenza virus mutation from low to high virulence on a single poultry premises during an outbreak in free range chickens in the UK, 2008.

H5 and H7 subtypes of low pathogenicity avian influenza viruses (LPAIVs) have the potential to evolve into highly pathogenic avian influenza viruses (HPAIVs), causing high mortality in galliforme poultry with substantial economic losses for the poultry industry. This study provides direct evidence of H7N7 LPAIV mutation to HPAIV on a single poultry premises during an outbreak that occurred in June 2008 in free range laying hens in Oxfordshire, UK. We report the first detection of a rare di-basic cleavage site (CS) motif (PEIPKKRGLF), unique to galliformes, that has previously been associated with a LPAIV phenotype. Three distinct HPAIV CS sequences (PEIPKRKKRGLF, PEIPKKKKRGLF and PEIPKKKKKKRGLF) were identified in the infected sheds suggesting molecular evolution at the outbreak premises. Further evidence for H7N7 LPAIV preceding mutation to HPAIV was derived by examining clinical signs, epidemiological descriptions and analysing laboratory results on the timing and proportions of seroconversion and virus shedding at each infected shed on the premises. In addition to describing how the outbreak was diagnosed and managed via statutory laboratory testing, phylogenetic analysis revealed reassortant events during 2006-2008 that suggested likely incursion of a wild bird origin LPAIV precursor to the H7N7 HPAIV outbreak. Identifying a precursor LPAIV is important for understanding the molecular changes and mechanisms involved in the emergence of HPAIV. This information can lead to understanding how and why only some H7 LPAIVs appear to readily mutate to HPAIV.

Evaluation of ELISA and haemagglutination inhibition as screening tests in serosurveillance for H5/H7 avian influenza in commercial chicken flocks.

Avian influenza virus (AIV) subtypes H5 and H7 can infect poultry causing low pathogenicity (LP) AI, but these LPAIVs may mutate to highly pathogenic AIV in chickens or turkeys causing high mortality, hence H5/H7 subtypes demand statutory intervention. Serological surveillance in the European Union provides evidence of H5/H7 AIV exposure in apparently healthy poultry. To identify the most sensitive screening method as the first step in an algorithm to provide evidence of H5/H7 AIV infection, the standard approach of H5/H7 antibody testing by haemagglutination inhibition (HI) was compared with an ELISA, which detects antibodies to all subtypes. Sera (n = 1055) from 74 commercial chicken flocks were tested by both methods. A Bayesian approach served to estimate diagnostic test sensitivities and specificities, without assuming any 'gold standard'. Sensitivity and specificity of the ELISA was 97% and 99.8%, and for H5/H7 HI 43% and 99.8%, respectively, although H5/H7 HI sensitivity varied considerably between infected flocks. ELISA therefore provides superior sensitivity for the screening of chicken flocks as part of an algorithm, which subsequently utilises H5/H7 HI to identify infection by these two subtypes. With the calculated sensitivity and specificity, testing nine sera per flock is sufficient to detect a flock seroprevalence of 30% with 95% probability.

What is the best way to determine bond-valence parameters?

Two recent systematic determinations of bond-valence parameters addressed the problem of the correlation between R0 and b in different ways raising the question of which is to be preferred.

Time to go wireless? A 15-year single institution experience of radioisotope occult lesion localisation (ROLL) for impalpable breast lesions.

INTRODUCTION: Wire guided localisation (WGL) is the standard localisation technique for impalpable breast lesions. Radio-guided occult lesion localisation (ROLL) has been proposed as an alternative. We have been performing ROLL for therapeutic wide local excisions (WLE) and diagnostic excision biopsies (DEB) for the last 15 years. We present the largest reported consecutive series of ROLL excisions to date. PATIENTS AND METHODS: One thousand thirty nine consecutive patients who underwent ROLL for impalpable breast lesions were identified from a prospectively collected database. 673 patients underwent WLE and 366 patients underwent DEB. Data were analysed from proformas completed at the time of the procedure by the radiologist and operating surgeon. These data were supplemented with an analysis of patient electronic records including specimen radiograph and histopathology reports. RESULTS: 99.1% of ROLL WLE revealed histological diagnoses of invasive cancer or DCIS. 98.7% of radiological abnormalities were identified on WLE post-excision radiographs (97.5% following DEB). Complete excision was recorded in 79.0% of the WLE patients following histological evaluation. 31.7% of DEB cases were pathologically upgraded to a malignant diagnosis. The presence of microcalcification, preoperative underestimation of the lesion size and symptomatic referral predisposed to incomplete excision status. DISCUSSION: ROLL is a safe and effective technique to localise impalpable breast lesions. In addition ROLL has potential technical and logistic advantages over WGL.

An Epizootiological Report of the Re-emergence and Spread of a Lineage of Virulent Newcastle Disease Virus into Eastern Europe.

A number of contemporary outbreaks of Newcastle disease (ND) in Israel, Turkey, Georgia and Bulgaria have all been caused by a very similar viruses related to lineage 5a (genotype VIIa). Comparison with published ND virus (NDV) sequences suggests that this virus strain originated in South-East Asia and on introduction has circulated widely in backyard poultry in the Middle East and into Eastern Europe. An intracerebral pathogenicity index of 1.9 was obtained for a representative isolate from Bulgaria. In addition, the International Reference Laboratory for ND has characterized a molecular epidemiologically linked virus that has been reported to have caused disease in well-vaccinated broiler chickens in Pakistan. In the 1990s, another strain from the 5a lineage NDV was introduced into Europe and spread across the continent causing numerous outbreaks up to 1999. Despite improved controls, including good diagnostic tests and widespread vaccination, in commercial poultry, the novel circulating NDV strains described here have been established widely in the region and represent an increased risk for similar disease outbreak events to reoccur within the EU.

Companion Animals as a Source of Viruses for Human Beings and Food Production Animals.

Companion animals comprise a wide variety of species, including dogs, cats, horses, ferrets, guinea pigs, reptiles, birds and ornamental fish, as well as food production animal species, such as domestic pigs, kept as companion animals. Despite their prominent place in human society, little is known about the role of companion animals as sources of viruses for people and food production animals. Therefore, we reviewed the literature for accounts of infections of companion animals by zoonotic viruses and viruses of food production animals, and prioritized these viruses in terms of human health and economic importance. In total, 138 virus species reportedly capable of infecting companion animals were of concern for human and food production animal health: 59 of these viruses were infectious for human beings, 135 were infectious for food production mammals and birds, and 22 were infectious for food production fishes. Viruses of highest concern for human health included hantaviruses, Tahyna virus, rabies virus, West Nile virus, tick-borne encephalitis virus, Crimean-Congo haemorrhagic fever virus, Aichi virus, European bat lyssavirus, hepatitis E virus, cowpox virus, G5 rotavirus, influenza A virus and lymphocytic choriomeningitis virus. Viruses of highest concern for food production mammals and birds included bluetongue virus, African swine fever virus, foot-and-mouth disease virus, lumpy skin disease virus, Rift Valley fever virus, porcine circovirus, classical swine fever virus, equine herpesvirus 9, peste des petits ruminants virus and equine infectious anaemia virus. Viruses of highest concern for food production fishes included cyprinid herpesvirus 3 (koi herpesvirus), viral haemorrhagic septicaemia virus and infectious pancreatic necrosis virus. Of particular concern as sources of zoonotic or food production animal viruses were domestic carnivores, rodents and food production animals kept as companion animals. The current list of viruses provides an objective basis for more in-depth analysis of the risk of companion animals as sources of viruses for human and food production animal health.

Cell growth on 3D microstructured surfaces.

Chinese Hamster Ovary (CHO) cell cultures were grown on surfaces lithographed with periodic 3D hexagonal microcavity array morphology. The range of microcavity size (inscribed circle diameter) was from 12 µm to 560 µm. CHO cells were grown also on flat surfaces. The characterization was performed with respect to cell growth density (number of nuclei per unit area) by fluorescence optical microscopy and evaluated by correlation function analysis. We found that optimum microcavity radius was 80 µm, concerning to the maximum cell growth density, being even greater than the growth density on a flat (unstructured) substrate of the same material. This finding can be important for optimization of biotechnological processes and devices.

Highly Pathogenic Avian Influenza H5N8 Clade 2.3.4.4 Virus: Equivocal Pathogenicity and Implications for Surveillance Following Natural Infection in Breeder Ducks in the United Kingdom.

Since early 2014, several outbreaks involving novel reassortant highly pathogenic avian influenza (HPAI) A(H5N8) viruses have been detected in poultry and wild bird species in Asia, Europe and North America. These viruses have been detected in apparently healthy and dead wild migratory birds, as well as in domestic chickens, turkeys, geese and ducks. In this study, we describe the pathology of an outbreak of H5N8 HPAIV in breeder ducks in the UK. A holding with approximately 6000 breeder ducks, aged approximately 60 weeks, showed a gradual reduction in egg production and increased mortality over a 7-day period. Post-mortem examination revealed frequent fibrinous peritonitis, with severely haemorrhagic ovarian follicles and occasional splenic and pancreatic necrosis and high incidence of mycotic granulomas in the air sacs and lung. Low-to-moderate levels of HPAI H5N8 virus were detected mainly in respiratory and digestive tract, with minor involvement of other organs. Although histopathological examination confirmed the gross pathology findings, intralesional viral antigen detection by immunohistochemistry was not observed. Immunolabelled cells were rarely only present in inflamed air sacs and serosa, usually superficial to granulomatous inflammation. Abundant bacterial microcolonies were observed in haemorrhagic ovaries and oviduct. The limited viral tissue distribution and presence of inter-current fungal and bacterial infections suggest a minor role for HPAIV H5N8 in clinical disease in layer ducks.

Serological Evidence of Pandemic H1N1 Influenza Virus Infections in Greek Swine.

The introduction of the 2009 pandemic H1N1 (pH1N1) influenza virus in pigs changed the epidemiology of influenza A viruses (IAVs) in swine in Europe and the rest of the world. Previously, three IAV subtypes were found in the European pig population: an avian-like H1N1 and two reassortant H1N2 and H3N2 viruses with human-origin haemagglutinin (HA) and neuraminidase proteins and internal genes of avian decent. These viruses pose antigenically distinct HAs, which allow the retrospective diagnosis of infection in serological investigations. However, cross-reactions between the HA of pH1N1 and the HAs of the other circulating H1 IAVs complicate serological diagnosis. The prevalence of IAVs in Greek swine has been poorly investigated. In this study, we examined and compared haemagglutination inhibition (HI) antibody titres against previously established IAVs and pH1N1 in 908 swine sera from 88 herds, collected before and after the 2009 pandemic. While we confirmed the historic presence of the three IAVs established in European swine, we also found that 4% of the pig sera examined after 2009 had HI antibodies only against the pH1N1 virus. Our results indicate that pH1N1 is circulating in Greek pigs and stress out the importance of a vigorous virological surveillance programme.