Rapid implementation of triaging system for assessment of breast referrals from primary care centres during the COVID-19 pandemic.

OBJECTIVE: The aim of this study was to establish a triaging system for assessment of breast referrals from primary care to ensure safe and effective breast services without compromising breast cancer management. BACKGROUND: COVID-19 was officially declared a global pandemic on 11 March 2020, and with no effective treatment available, preventing spread has been paramount. Previously, all referrals from primary care were seen in the rapid-access breast clinic (RABC). Clinic appointments exposed patients and healthcare professionals to risk. METHOD: Initial triage during the lockdown was in line with national governing body guidance, rejected low risk referrals and streamed remaining patients through a telephone consultation to RABC or discharge. A modified triage pathway streamed all patients through virtual triage to RABC, telephone clinic or discharge with advice and guidance categories. Demographics, reasons for referral and outcomes data were collected and presented as median with range and frequency with percentages. RESULTS: Initial triage (23 March-23 April 2020) found fewer referrals with a higher percentage of breast cancer diagnoses. Modified triage (22 June-17 July 2020) resulted in a 35.1% (99/282) reduction in RABC attendance. Overall cancer detection rate remained similar at 4.2% of all referrals pre-COVID (18/429) and 4.3% (12/282) during modified triage. After six months follow-up of patients not seen in RABC during the modified triage pathway, 18 patients were re-referred to RABC and none were diagnosed with cancer. CONCLUSION: A modified triage pathway has the potential to improve triage efficiency and prevent unnecessary visits during the COVID-19 pandemic. Further refinement of pathway is feasible in collaboration with primary care.

The challenge of invasive mosquito vectors in the U.K. during 2016-2018: a summary of the surveillance and control of Aedes albopictus.

Mosquito-borne diseases resulting from the expansion of two key vectors, Aedes aegypti and Aedes albopictus (Diptera: Culicidae), continue to challenge whole regions and continents around the globe. In recent years there have been human cases of disease associated with Chikungunya, dengue and Zika viruses. In Europe, the expansion of Ae. albopictus has resulted in local transmission of Chikungunya and dengue viruses. This paper considers the risk that Ae. aegypti and Ae. albopictus represent for the U.K. and details the results of mosquito surveillance activities. Surveillance was conducted at 34 points of entry, 12 sites serving vehicular traffic and two sites of used tyre importers. The most common native mosquito recorded was Culex pipiens s.l. (Diptera: Culicidae). The invasive mosquito Ae. albopictus was detected on three occasions in southern England (September 2016, July 2017 and July 2018) and subsequent control strategies were conducted. These latest surveillance results demonstrate ongoing incursions of Ae. albopictus into the U.K. via ground vehicular traffic, which can be expected to continue and increase as populations in nearby countries expand, particularly in France, which is the main source of ex-continental traffic.

Surveillance of biting midges (Culicoides spp.) in Northern Ireland: influence of seasonality, surrounding habitat and livestock housing.

Biting midges, Culicoides spp. (Diptera: Ceratopogonidae), are important vectors of viral pathogens. Following the outbreak of bluetongue serotype 8 in Europe between 2006 and 2009, many Culicoides surveillance programmes were initiated to identify vector-active periods, in accordance with European Commission regulation 2007/1266/EC. This study utilized surveillance data from 4 years of continuous light-trapping at 14 sites in Northern Ireland. The number of captured Culicoides varied from none during the vector-free period (December-April) to more than 36 000 per night during peak activity in the summer. The Obsoletus group represented 75% of Culicoides collected and the Pulicaris group represented 21%. A total of 91% of Culicoides were female, of which 42% were parous. Abundance data, sex ratios and parous rates suggested that both the Obsoletus and Pulicaris groups underwent three generations/year. The Obsoletus group was associated with cattle-rearing habitats and woodland, the Impunctatus group was found in habitats related to sheep rearing and the Pulicaris group were associated with both cattle and sheep. Housing did not reduce incursion of female Obsoletus group Culicoides but it did for males and for the Pulicaris group Culicoides. The influence of housing was strongly affected by time of year, probably reflecting the presence of livestock indoors/outdoors.

DEET (N,N-diethyl-meta-toluamide)/PMD (para-menthane-3,8-diol) repellent-treated mesh increases Culicoides catches in light traps.

Biting midges (Culicoides spp.) are vectors of bluetongue and Schmallenberg viruses. Treatment of mesh barriers is a common method for preventing insect-vectored diseases and has been proposed as a means of limiting Culicoides ingression into buildings or livestock transporters. Assessments using animals are costly, logistically difficult and subject to ethical approval. Therefore, initial screening of test repellents/insecticides was made by applying treatments to mesh (2 mm) cages surrounding Onderstepoort light traps. Five commercial treatments were applied to cages as per manufacturers' application rates: control (water), bendiocarb, DEET/p-menthane-3,8-diol (PMD) repellent, Flygo (a terpenoid based repellent) and lambda-cyhalothrin. The experimental design was a 5 × 5 Latin square, replicated in time and repeated twice. Incongruously, the traps surrounded by DEET/PMD repellent-treated mesh caught three to four times more Obsoletus group Culicoides (the commonest midge group) than the other treatments. A proposed hypothesis is that Obsoletus group Culicoides are showing a dose response to DEET/PMD, being attracted at low concentrations and repelled at higher concentrations but that the strong light attraction from the Onderstepoort trap was sufficient to overcome close-range repellence. This study does not imply that DEET/PMD is an ineffective repellent for Culicoides midges in the presence of an animal but rather that caution should be applied to the interpretation of light trap bioassays.

Blood pressure and TNF-α act synergistically to increase leucocyte CD11b adhesion molecule expression in the BELFAST study: implications for better blood pressure control in ageing.

Hypertension, a key risk factor for stroke, cardiovascular disease and dementia, is associated with chronic vascular inflammation, and although poorly understood, putative mechanisms include pro-inflammatory responses induced by mechanical stretching, with cytokine release and associated up-regulated expression of adhesion molecules. Because blood pressure increases with age, we measured baseline and tumour necrosis alpha (TNF-α)-stimulated CD11b/CD18 adhesion molecule expression on leucocytes to assess any association between the two. In 38 subjects (mean age 85 years), consecutively enrolled from Belfast Elderly Longitudinal Free-Living Aging Study (BELFAST), baseline and TNF-α-stimulated CD11b/CD18 expression on separated monocytes and neutrophils increased with systolic blood pressure >120 mmHg (p = 0.05) and for lymphocytes, with diastolic blood pressure >80 mmHg (p < 0.05).These findings show increased potential stickiness of intravascular cells with increasing blood pressure which is accentuated by TNF-α, and suggest mechanistic reasons why better hypertension control is important.

Design, recruitment, logistics, and data management of the GEHA (Genetics of Healthy Ageing) project.

In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90 years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50-75 years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7 years the number of families with all participating siblings aged 95 years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity.

Multi-wavelength study of light transmitted through a single marine centric diatom.

The characterization of partially coherent light transmission by micrometer sized valves of marine diatoms is an interesting optical challenge and, from the biological point of view, is of outmost relevance in order to understand evolution mechanisms of such organisms. In the present work, we have studied the transmission of light coming from a monochromator through single valves of Coscinodiscus wailesii diatoms. Incoming light is confined by the regular pore pattern of the diatom surface into a spot of few microns, its dimensions depending on wavelength. The effect is ascribed to the superposition of wavefronts diffracted by the pores' edges. Numerical simulations help to demonstrate how this effect is not present in the ultraviolet region of the light spectrum, showing one of the possible evolutionary advantages represented by the regular pores patterns of the valves.

BELFAST nonagenarians: nature or nurture? Immunological, cardiovascular and genetic factors.

Nonagenarians are the fastest growing sector of populations across Western European and the developed world. They are some of the oldest members of our societies and survivors of their generation and may help us understand how to age not only longer, but better.The Belfast Longevity Group enlisted the help of 500 community-living, mobile, mentally competent, 'elite' nonagenarians, as part of an ongoing study of ageing. We assessed some immunological, cardiovascular, nutritional and genetic factors and some aspects of their interaction in this group of 'oldest old'.Here we present some of the evidence related to genetic and nutritional factors which seem to be important for good quality ageing in nonagenarians from the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST).

BELFAST centenarians: a case of optimised cardiovascular risk?

INTRODUCTION: Centenarians are reservoirs of genetic and environmental information to successful ageing and local centenarian groups may help us to understand some of these secrets. The current centenarian cohort in Belfast survived the 1970s epidemic of death from coronary heart disease in Northern Ireland, where cardiovascular mortality was almost highest in the world. These centenarians provided an opportunity to assess biological and genetic factors important in cardiovascular risk and ageing. METHODS: Thirty-five (27 female, 8 male) centenarians, participants of the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST), were community-living and of good cognition at enrollment. RESULTS: Centenarians showed median Body Mass Index (BMI) at 25.7, systolic blood pressure 140 mmHg and diastolic blood pressure 90 mmHg respectively, and fasting glucose of 5.54 mmol/l with no sex-related difference. Lipoproteins showed median cholesterol 5.3, High Density Lipoprotein (HDL) 1.10 and Low Density Lipoprotein (LDL) 3.47 micromol/l respectively. Centenarian smokers showed no different blood pressure or lipid measurements compared with non-smokers. Malondialdehyde, a measure of lipid peroxidation, was low at 1.19, and measures of antioxidant status showed variable results. Male centenarians did not carry any of the vascular risk genotypes studied-Apolipoprotein E (ApoE), Angiotensin-Converting Enzyme (ACE) and Methylenetetrafolatedehydrogenase reductase (MTFHR), though this was not true for female centenarians. CONCLUSIONS: This small local study shows, apart from age, that Belfast centenarians carry a reasonably optimized risk profile with respect to cardiovascular disease. There is also some evidence suggesting that vascular risk factors and genotypes may be tolerated differently between the male and female centenarians. Maintaining an optimized cardiovascular risk profile seems likely to improve the chance of becoming a centenarian, especially for males.

Bioactive modification of silicon surface using self-assembled hydrophobins from Pleurotus ostreatus.

A crystalline silicon surface can be made biocompatible and chemically stable by a self-assembled biofilm of proteins, the hydrophobins (HFBs) purified from the fungus Pleurotus ostreatus. The protein-modified silicon surface shows an improvement in wettability and is suitable for immobilization of other proteins. Two different proteins were successfully immobilized on the HFBs-coated chips: the bovine serum albumin and an enzyme, a laccase, which retains its catalytic activity even when bound on the chip. Variable-angle spectroscopic ellipsometry (VASE), water contact angle (WCA), and fluorescence measurements demonstrated that the proposed approach in silicon surface bioactivation is a feasible strategy for the fabrication of a new class of hybrid devices.

Nature or nurture; BMI and blood pressure at 90. Findings from the Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST).

Hypertension is a key risk factor for stroke, cardiovascular disease and dementia. Although the link between weight, sodium and hypertension is established in younger people, little is known about their inter-relationship in people beyond 80 years of age. Associations between blood pressure, anthropometric indices and sodium were investigated in 495 apparently healthy, community-living participants (age 90, SD 4.8; range 80­106), from the cross-sectional Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST) study. In age-sex-adjusted logistic regression models, blood pressure ≥140/90 mmHg significantly associated with body mass index (BMI) [odds ratio (OR) = 1.28/ kg/m2], with weight (OR = 1.22/kg) approaching significance (P = 0.07). In further age-sex-adjusted models, blood pressure above the 120/80 mmHg normotensive reference value significantly associated with BMI (OR = 1.44/kg/m2), weight (OR = 1.36/kg), skin-fold-thickness (OR = 1.33/mm) and serum sodium (OR = 1.37 mmol/l). In BELFAST participants over 80 years old, blood pressure ≥140/90 mmHg is associated with BMI, in apparently similar ways to younger groups.

ABCB1 (MDR1) rs1045642 is associated with increased overall survival in plasma cell myeloma.

Multi-drug resistance (MDR) may compromise the successful management of haematological malignancies, impairing the effectiveness of chemotherapy. The P-glycoprotein (P-gp) drug efflux pump, encoded by the gene ABCB1 (MDR1), is the most widely studied component in MDR. A single nucleotide polymorphism (SNP) has been identified within ABCB1, rs1045642 (C3435T), which may alter P-gp substrate specificity and have an impact on the effectiveness of treatment, and hence overall survival (OS). We estimated the frequency of this SNP in the Northern Irish population and investigated its impact on the OS of patients with plasma cell myeloma (PCM). There was no significant difference in the frequency of rs1045642 between the PCM cohort and an age- and gender-matched control population. Findings within the PCM cohort suggest that rs1045642 genotype influences OS (p = 2 x 10(-2)). If confirmed in larger studies, these results suggest that genotyping rs1045642 may be a useful predictor of outcome in PCM and could indicate modified treatment modalities in certain individuals.

Langmuir-Blodgett film of hydrophobin protein from Pleurotus ostreatus at the air-water interface.

We present results concerning the formation of Langmuir-Blodgett (LB) films of a class I hydrophobin from Pleurotus ostreatus at the air-water interface, and their structure as Langmuir-Blodgett (LB) films when deposited on silicon substrates. LB films of the hydrophobin were investigated by atomic force microscopy (AFM). We observed that the compressed film at the air-water interface exhibits a molecular depletion even at low surface pressure. In order to estimate the surface molecular concentration, we fit the experimental isotherm with Volmer's equation describing the equation of state for molecular monolayers. We found that about (1)/ 10 of the molecules contribute to the surface film formation. When transferred on silicon substrates, compact and uniform monomolecular layers about 2.5 nm thick, comparable to a typical molecular size, were observed. The monolayers coexist with protein aggregates, under the typical rodlet form with a uniform thickness of about 5.0 nm. The observed rodlets appear to be a hydrophilic bilayer and can then be responsible for the surface molecular depletion.

Treatment of Bolivian mucosal leishmaniasis with miltefosine.

BACKGROUND: Although mucosal leishmaniasis is a prominent disease, it has been studied only to a limited extent. It is classically treated with parenteral antimony or, as a last resort, amphotericin B. METHODS: We treated Bolivian mucosal leishmaniasis due to Leishmania braziliensis with the oral agent miltefosine, 2.5 mg/kg/day for 28 days, and followed-up for 12 months. RESULTS: Seventy-two patients were evaluable. The cure rate for the 36 patients who had "mild" disease (i.e., affecting nasal skin and nasal mucosa) was 83%. The cure rate for the 36 patients who had more extensive disease (involving the palate, pharynx, and larynx) was 58%. Patients refused to be randomized to parenteral agents, but the cure rate for an almost contemporary group who was receiving amphotericin B (45 mg/kg over 90 days) was 7 (50%) of 14. CONCLUSIONS: In this unrandomized trial, oral miltefosine was at least as effective as heroic doses of parenteral amphotericin B. The cure rate for miltefosine was approximately equivalent to historical cure rates using parenteral pentavalent antimony for mild and extensive disease in neighboring Peru. Although gastrointestinal side reactions do occur with miltefosine, its toxicity profile is superior to that of antimony and far superior to that of amphotericin B--in part because of the inherent attractiveness of oral versus parenteral agents. Our results suggest that miltefosine should be the treatment of choice for mucosal disease in North and South America.

Investigation of KIR diversity in immunosenescence and longevity within the Irish population.

Natural killer (NK) cells play a pivotal role in the innate immune response. During the ageing process, variations occur in NK cell number and function. The cytolytic activity of NK cells is controlled by an array of activating and inhibitory cell surface receptors, including the killer cell immunoglobulin-like receptors (KIRs). In the present study, genetic diversity of the KIR loci was analysed with respect to successful ageing in the Irish population. A PCR-SSOP KIR gene identification system was employed to determine the frequency of the named KIR genes/pseudogenes and KIR genotypes within a healthy aged cohort and young control group. Although, two KIR genes (2DS3, 2DL5) displayed an initial increased frequency in the aged group, the significance of this association was lost when repeated in a second cohort. In view of the lack of studies to date, investigating the role of the KIR gene system in healthy ageing, further analysis of KIR diversity is required to fully elucidate it's role in respect to age-related disease and longevity.

Malondialdehyde and measures of antioxidant activity in subjects from the Belfast Elderly Longitudinal Free-living Aging Study.

Glutathione and glutathione peroxidase activity are important components in the complex body defense against oxidative damage. In this study, we have measured malondialdehyde (MDA) as a marker of oxidative stress, the antioxidant glutathione (GSH), and activity of the antioxidant enzyme (GSHPx), in a cohort of free-living elderly subjects from the Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST), hypothesizing that free-living Senieur-approximated nonagenarians might demonstrate enhanced antioxidant defense mechanisms. The main finding in the BELFAST octo/nonagenarians was that plasma antioxidant glutathione increased in nonagenarian compared with septo/octogenarian subjects (P =.015), whereas conversely antioxidant glutathione peroxidase activity fell in the nonagenarian group (P <.0001). In the same subject group, malondialdehyde, a measure of lipid peroxidation, showed no change across the age groups (P =.73). These results might overall represent a situation in which elderly survivors in the BELFAST study have evolved a sort of free radical/antioxidant equilibrium as a mechanism of successful aging.

Hypothetical soluble KIR2DS4 natural killer cell receptor molecule does not associate with successful ageing in the Irish.

The identification of immunogenetic longevity markers is a major area of molecular gerontological research. A number of genetic loci have been examined, e.g. the HLA and cytokine networks. This study investigated a genetic marker within the highly polymorphic KIR gene system with successful ageing in the Irish population. A 22 bp deletion was identified in the KIR2DS4 gene that predicts a truncated soluble KIR molecule with one intact Ig-like domain. The frequency of this variant was determined using a specific-primer PCR methodology. There was no observed association between this common polymorphic variation within this activatory KIR gene and the aged Irish population. This is the first study of KIR polymorphism in ageing and although no association was identified, the importance of the KIR network in the immune response and its polymorphic nature warrants more detailed analysis to ascertain its role in immunosenescence.

Functional promoter region polymorphism of the proinflammatory chemokine IL-8 gene associates with Parkinson's disease in the Irish.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders and is characterized by the progressive loss of dopamine neurons in the substantia nigra. There is increasing evidence to suggest the inflammatory response of the brain contributes to the pathogenesis of PD. This study investigated the frequency of polymorphism located in the critical promoter region of the proinflammatory cytokine genes: interleukin (IL)-2, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) within a cohort of patients with PD in comparison to a group of healthy elderly individuals. No association was observed for single nucleotide polymorphism in the promoter regions of the IL-2, IL-6, and TNF-alpha genes. The single nucleotide polymorphism in the chemokine IL-8 gene was observed to associate with PD and appeared to be independent of age at onset. This association further supports the theory that the proinflammatory response in the brains of patients with PD plays a role in the pathogenesis of the disease and warrants further investigation into the role of chemokines in the brain, and a more detailed analysis of the genetics involved in the immune response of the brain.