Copepods as biocontrols of an invasive mosquito in the UK

Aedes albopictus mosquitoes are highly invasive and are capable of transmitting debilitating diseases such as dengue, yellow fever, Zika, and chikungunya to humans. Cyclopoid copepods have previously been suggested as biocontrol agents against aedine mosquitoes, but they are rarely incorporated by most vector control programs due to heavy reliance on pyrethroid insecticides. In this thesis, I conducted a series of analyses to inform future Ae. albopictus biocontrol strategies in the UK. First, I used a meta-analysis approach to investigate the existing evidence for both consumptive and non-consumptive effects of predation on mosquito populations. I found that predation generally results in smaller mosquito body size, and this non-consumptive effect can lead to lower rates of disease transmission. Since Ae. albopictus are predicted to establish throughout most of England and Wales within the next fifty years, I examined the efficacy of UK copepod species against invasive larvae at temperatures that they are likely to experience in South East England. I found that cyclopoid copepods are effective predators against newly-hatched Ae. albopictus larvae across temperatures from 15 to 25°C, and that these predators exhibit type II functional response curves, indicating their suitability as biocontrols. The invasive mosquito larvae prey were preferred by copepod predators when both invasive Ae. albopictus prey and resident Culex pipiens prey were made available. I did not find any significant change in development time or size of Ae. albopictus mosquitoes that were exposed to copepod predation during the later stages of larval development. The absence of non-consumptive effects on Ae. albopictus may be due to their lack of a shared evolutionary history with UK copepod predators. In summary, my findings support the integration of local cyclopoid copepods as biocontrols into future vector control programs that target Ae. albopictus in the UK.Open Acces

Interstitial lung disease:A review of classification, aetiology, epidemiology, clinical diagnosis, pharmacological and non-pharmacological treatment

Interstitial lung diseases (ILDs) refer to a heterogeneous and complex group of conditions characterized by inflammation, fibrosis, or both, in the interstitium of the lungs. This results in impaired gas exchange, leading to a worsening of respiratory symptoms and a decline in lung function. While the etiology of some ILDs is unclear, most cases can be traced back to factors such as genetic predispositions, environmental exposures (including allergens, toxins, and air pollution), underlying autoimmune diseases, or the use of certain medications. There has been an increase in research and evidence aimed at identifying etiology, understanding epidemiology, improving clinical diagnosis, and developing both pharmacological and non-pharmacological treatments. This review provides a comprehensive overview of the current state of knowledge in the field of interstitial lung diseases

S06-1 Putting young people at the heart of physical activity research design: The Walking In ScHools (WISH) Study

BACKGROUND: Young people have the right to be informed and consulted about decisions affecting their lives. Youth Patient and Public Involvement (PPI) should be encouraged to ensure research is carried out ‘with' or ‘by' young people rather than ‘to', ‘about' or ‘for' them. PPI can ensure research is relevant, results are accessible and recruitment rates are improved. Young people have had limited involvement in the design, implementation and dissemination of public health research and there have been calls for a greater focus on youth PPI in research. METHODS: Following the WISH feasibility study that consulted young people pre and post-intervention, a Youth Advisory Group (YAG) was set up within the main trial. The WISH study is a clustered randomised controlled trial in which a peer-led, school-based, brisk walking intervention is compared to usual physical activity in adolescent females. The YAG was introduced to inform intervention delivery and provide researchers with an understanding of what would encourage/discourage participation. Schools were asked to invite pupils aged 12-14 years (participants) and 15-18 years (walk leaders). Participative methods were used to develop and review study documentation. The YAG completed a short questionnaire and recruitment rates were monitored. RESULTS: Fourteen pupils from 3 schools attended the 2019 YAG meeting. The YAG agreed the meeting was a good way of getting young people involved in research (93%) and attendees enjoyed the meeting (100%). As a result, changes were made to study documentation, incentives were purchased and recruitment materials developed. Participant recruitment was higher in schools who participated in the YAG (54%) compared to those who did not (47%). In 2021 the second YAG occurred and 1 teacher, 12 participants and 10 walk leaders from 2 schools provided feedback on the trials COVID-19 contingency plan. The girls felt their feedback was valued (100%) and it was important young people had the chance to contribute to research studies (100%). CONCLUSIONS: The views of young people have been central to the development of the WISH Study and although youth PPI is not without challenges, there are many benefits for researchers, the study and the young people involved

Home monitoring of physiology and symptoms to detect interstitial lung disease exacerbations and progression:a systematic review

Background: Acute exacerbations (AEs) and disease progression in interstitial lung disease (ILD) pose important challenges to clinicians and patients. AEs of ILD are variable in presentation but may result in rapid progression of ILD, respiratory failure and death. However, in many cases AEs of ILD may go unrecognised so that their true impact and response to therapy is unknown. The potential for home monitoring to facilitate early, and accurate, identification of AE and/or ILD progression has gained interest. With increasing evidence available, there is a need for a systematic review on home monitoring of patients with ILD to summarise the existing data. The aim of this review was to systematically evaluate the evidence for use of home monitoring for early detection of exacerbations and/or progression of ILD. Method: We searched Ovid-EMBASE, MEDLINE and CINAHL using Medical Subject Headings (MeSH) terms in accordance with the PRISMA guidelines (PROSPERO registration number CRD42020215166). Results: 13 studies involving 968 patients have demonstrated that home monitoring is feasible and of potential benefit in patients with ILD. Nine studies reported that mean adherence to home monitoring was &gt;75%, and where spirometry was performed there was a significant correlation (r=0.72–0.98, p&lt;0.001) between home and hospital-based readings. Two studies suggested that home monitoring of forced vital capacity might facilitate detection of progression in idiopathic pulmonary fibrosis. Conclusion: Despite the fact that individual studies in this systematic review provide supportive evidence suggesting the feasibility and utility of home monitoring in ILD, further studies are necessary to quantify the potential of home monitoring to detect disease progression and/or AEs.</p

The Effect of Atorvastatin on Breast Cancer Biomarkers in High-Risk Women

Statins have the potential to reduce breast cancer incidence and recurrence as shown in both epidemiologic and laboratory studies. The purpose of this study was to evaluate the effect of a lipophilic statin, atorvastatin, on breast cancer biomarkers of risk [mammographic density (MD) and insulin growth factor 1 (IGF-1)] in high-risk premenopausal women

Characterisation and classification of oligometastatic disease : a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation

Oligometastatic disease has been proposed as an intermediate state between localised and systemically metastasised disease. In the absence of randomised phase 3 trials, early clinical studies show improved survival when radical local therapy is added to standard systemic therapy for oligometastatic disease. However, since no biomarker for the identification of patients with true oligometastatic disease is clinically available, the diagnosis of oligometastatic disease is based solely on imaging findings. A small number of metastases on imaging could represent different clinical scenarios, which are associated with different prognoses and might require different treatment strategies. 20 international experts including 19 members of the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer OligoCare project developed a comprehensive system for characterisation and classification of oligometastatic disease. We first did a systematic review of the literature to identify inclusion and exclusion criteria of prospective interventional oligometastatic disease clinical trials. Next, we used a Delphi consensus process to select a total of 17 oligometastatic disease characterisation factors that should be assessed in all patients treated with radical local therapy for oligometastatic disease, both within and outside of clinical trials. Using a second round of the Delphi method, we established a decision tree for oligometastatic disease classification together with a nomenclature. We agreed oligometastatic disease as the overall umbrella term. A history of polymetastatic disease before diagnosis of oligometastatic disease was used as the criterion to differentiate between induced oligometastatic disease (previous history of polymetastatic disease) and genuine oligometastatic disease (no history of polymetastatic disease). We further subclassified genuine oligometastatic disease into repeat oligometastatic disease (previous history of oligometastatic disease) and de-novo oligometastatic disease (first time diagnosis of oligometastatic disease). In de-novo oligometastatic disease, we differentiated between synchronous and metachronous oligometastatic disease. We did a final subclassification into oligorecurrence, oligoprogression, and oligopersistence, considering whether oligometastatic disease is diagnosed during a treatment-free interval or during active systemic therapy and whether or not an oligometastatic lesion is progressing on current imaging. This oligometastatic disease classification and nomenclature needs to be prospectively evaluated by the OligoCare study

<i>C9orf72 </i>Repeat Expansion Discordance in 6 Multigenerational Kindreds

Background and Objectives:A hexanucleotide repeat expansion in the noncoding region of the C9orf72 gene is the most common genetically identifiable cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in populations of European ancestry. Pedigrees associated with this expansion exhibit phenotypic heterogeneity and incomplete disease penetrance, the basis of which is poorly understood. Relatives of those carrying the C9orf72 repeat expansion exhibit a characteristic cognitive endophenotype independent of carrier status. To examine whether additional shared genetic or environmental risks within kindreds could compel this observation, we have conducted a detailed cross-sectional study of the inheritance within multigenerational Irish kindreds carrying the C9orf72 repeat expansion.Methods:One hundred thirty-one familial ALS pedigrees, 59 of which carried the C9orf72 repeat expansion (45.0% [95% CI 36.7–53.5]), were identified through the Irish population-based ALS register. C9orf72 genotyping was performed using repeat-primed PCR with amplicon fragment length analysis. Pedigrees were further investigated using SNP, targeted sequencing data, whole-exome sequencing, and whole-genome sequencing.Results:We identified 21 kindreds where at least 1 family member with ALS carried the C9orf72 repeat expansion and from whom DNA was available from multiple affected family members. Of these, 6 kindreds (28.6% [95% CI 11.8–48.3]) exhibited discordant segregation. The C9orf72 haplotype was studied in 2 families and was found to segregate with the C9orf72-positive affected relative but not the C9orf72-negative affected relative. No other ALS pathogenic variants were identified within these discordant kindreds.Discussion:Family members of kindreds associated with the C9orf72 repeat expansion may carry an increased risk of developing ALS independent of their observed carrier status. This has implications for assessment and counseling of asymptomatic individuals regarding their genetic risk