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Drug delivery for fighting infectious diseases: a global perspective
No full textEpidemiologists have predicted that viral infections might spread fast in our highly globalized world. For example, a report on “Preparedness for a high-impact respiratory pathogen pandemic” was published in September 2019 by Johns Hopkins Centre for Health Security [1]. This report ranked aerosol transmitted viral diseases as the highest risk for a wide-spreading pandemic and named, as an example beyond infuenza, also severe acute respiratory syndrome (SARS) as a zoonotic coronavirus. In approximately 1 year, SARSCoV-2 (coronavirus type 2) has developed into a true pandemic and reminds
is that problems must be taken seriously in a timely manner. In the case of the current coronavirus disease 2019 (COVID-19), we profited from the protocols established during earlier pandemics. Following the infuenza (H1N1) pandemic in 2009, a pandemic preparedness plan was developed by the World Health Organization (WHO). SARS-CoV infections in 2003 and MERS (Middle East Respiratory Syndrome) in 2012 lead to research in this type of Coronaviridae and strategies to combat them. The Ebola epidemic in West Africa 2014–2016 activated a push for programs in preventive and therapeutic strategies driven by governmental and non-governmental institution
Enabling machine learning on the edge using SRAM conserving efficient neural networks execution approach
No full textEdge analytics refers to the application of data analytics and
Machine Learning (ML) algorithms on IoT devices. The concept of edge
analytics is gaining popularity due to its ability to perform AI-based analytics at the device level, enabling autonomous decision-making, without
depending on the cloud. However, the majority of Internet of Things
(IoT) devices are embedded systems with a low-cost microcontroller unit
(MCU) or a small CPU as its brain, which often are incapable of handling
complex ML algorithms.
In this paper, we propose an approach for the efficient execution of already
deeply compressed, large neural networks (NNs) on tiny IoT devices. After
optimizing NNs using state-of-the-art deep model compression methods,
when the resultant models are executed by MCUs or small CPUs using
the model execution sequence produced by our approach, higher levels
of conserved SRAM can be achieved. During the evaluation for nine
popular models, when comparing the default NN execution sequence with
the sequence produced by our approach, we found that 1.61-38.06% less
SRAM was used to produce inference results, the inference time was
reduced by 0.28-4.9 ms, and energy consumption was reduced by 4-84
mJ. Despite achieving such high conserved levels of SRAM, our methThis publication has emanated from research supported in part by a research grant
from Science Foundation Ireland (SFI) under Grant Number SFI/16/RC/3918
(Confirm) and also by a research grant from Science Foundation Ireland (SFI)
under Grant Number SFI/12/RC/2289 P2 (Insight), with both grants co-funded
by the European Regional Development Fund
Epidemiology of age-dependent prevalence of Bovine Herpes Virus Type 1 (BoHV-1) in dairy herds with and without vaccination
No full textMany studies report age as a risk factor for BoHV-1 infection or seropositivity. However, it is unclear whether this pattern reflects true epidemiological causation or is a consequence of study design and other issues. Here, we seek to understand the age-related dynamics of BoHV-1 seroprevalence in seasonal calving Irish dairy herds and provide decision support for the design and implementation of effective BoHV-1 testing strategies. We analysed seroprevalence data from dairy herds taken during two Irish seroprevalence surveys conducted between 2010 and 2017. Age-dependent seroprevalence profiles were constructed for herds that were seropositive and unvaccinated. Some of these profiles revealed a sudden increase in seroprevalence between adjacent age-cohorts, from absent or low to close to 100% of seropositive animals. By coupling the outcome of our data analysis with simulation output of an individual-based model at the herd scale, we have shown that these sudden increases are related to extensive virus circulation within a herd for a limited time, which may then subsequently remain latent over the following years. BoHV-1 outbreaks in dairy cattle herds affect animals independent of age and lead to almost 100% seroconversion in all age groups, or at least in all animals within a single epidemiological unit. In the absence of circulating infection, there is a year-on-year increase in the age-cohort at which seroprevalence changes from low to high. The findings of this study inform recommendations regarding testing regimes in the context of contingency planning or an eradication programme in seasonal calving dairy herds.Department of Agriculture, Food and the Marin
Quantification of risk factors for bovine viral diarrhea virus in cattle herds: A systematic search and meta-analysis of observational studies
No full textBovine viral diarrhea virus (BVDV) is endemic in many parts of the world, and multiple countries have implemented surveillance activities for disease control or eradication. In such control programs, the disease-free status can be compromised by factors that pose risks for introduction or persistence of the virus. The aim of the present study was to gain a comprehensive overview of possible risk factors for BVDV infection in cattle herds in Europe and to assess their importance. Papers that considered risk factors for BVDV infection in cattle were identified through a systematic search. Further selection of papers eligible for quantitative analysis was performed using a predefined checklist, including (1) appropriate region (i.e., studies performed in Europe), (2) representativeness of the study population, (3) quality of statistical analysis, and (4) availability of sufficient quantitative data. In total, 18 observational studies were selected. Data were analyzed by a random-effects meta-analysis to obtain pooled estimates of the odds of BVDV infection. Meta-analyses were performed on 6 risk factors: herd type, herd size, participation in shows or markets, introduction of cattle, grazing, and contact with other cattle herds on pasture. Significant higher odds were found for dairy herds (odds ratio, OR = 1.63, 95% confidence interval, CI: 1.06–2.50) compared with beef herds, for larger herds (OR = 1.04 for every 10 extra animals in the herd, 95% CI: 1.02–1.06), for herds that participate in shows or markets (OR = 1.45, 95% CI: 1.10–1.91), for herds that introduced cattle into the herd (OR = 1.41, 95% CI: 1.18–1.69), and for herds that share pasture or have direct contact with cattle of other herds at pasture (OR = 1.32, 95% CI: 1.07–1.63). These pooled values must be interpreted with care, as there was a high level of heterogeneity between studies. However, they do give an indication of the importance of the most frequently studied risk factors and can therefore assist in the development, evaluation, and optimization of BVDV control programs.Dutch Ministry of Agriculture, Nature and Food QualityEuropean Food Safety Authorit
Combining expert knowledge and machine-learning to classify herd types in livestock systems
No full textA detailed understanding of herd types is needed for animal disease control and surveillance activities, to inform epidemiological study design and interpretation, and to guide effective policy decision-making. In this paper, we present a new approach to classify herd types in livestock systems by combining expert knowledge and a machine-learning algorithm called self-organising-maps (SOMs). This approach is applied to the cattle sector in Ireland, where a detailed understanding of herd types can assist with on-going discussions on control and surveillance for endemic cattle diseases. To our knowledge, this is the first time that the SOM algorithm has been used to differentiate livestock systems. In compliance with European Union (EU) requirements, relevant data in the Irish livestock register includes the birth, movements and disposal of each individual bovine, and also the sex and breed of each bovine and its dam. In total, 17 herd types were identified in Ireland using 9 variables. We provide a data-driven classification tree using decisions derived from the Irish livestock registration data. Because of the visual capabilities of the SOM algorithm, the interpretation of results is relatively straightforward and we believe our approach, with adaptation, can be used to classify herd type in any other livestock system.Department of Agriculture, Food and the MarineProjekt DEA
Induction of the PPARγ (Peroxisome Proliferator-Activated Receptor γ)-GCM1 (Glial Cell Missing 1) syncytialization axis reduces sFLT1 (Soluble fms-Like Tyrosine Kinase 1) in the preeclamptic placenta
No full textPreeclampsia is a hypertensive disorder of pregnancy that is a major cause of maternal-fetal morbidity and mortality worldwide. Severe preeclampsia (sPE) is mediated by pathology of the placental villi resulting in repressed PIGF (placental growth factor) production and hyper-secretion of sFLT1 (soluble fms-like tyrosine kinase 1), the net effect being wide-spread maternal endothelial dysfunction. Villous trophoblast differentiation is under control of the PPARγ (peroxisome proliferator-activated receptor γ) and GCM1 (glial cell missing 1) axis which is dysregulated in sPE. We hypothesized that disruption of trophoblast differentiation via the PPARγ-GCM1 axis is a major contribution to excess production of sFLT1 and pharmacological activation of PPARγ in the sPE placenta could reduce sFLT1 to normal levels. sPE, age-matched control placentas and first-trimester villous explants, were used to investigate the molecular relationships between PPARγ-GCM1 and sFLT1. We modulated this pathway by pharmacological activation/inhibition of PPARγ using Rosiglitazone and T0070907, respectively, and through siRNA repression of GCM1. PPARγ and GCM1 protein expressions are reduced in the sPE placenta while FLT1 protein and sFLT1 secretion are increased. GCM1 reduction in the first trimester explants significantly increased sFLT1 secretion, suggesting GCM1 as a key player in this pathway. Activation of PPARγ restored GCM1 and significantly reduced sFLT1 expression and release in first trimester and sPE placental villi. Functional integrity of the PPARγ-GCM1 axis in the villous trophoblast is critical for normal pregnancy development and is disrupted in the sPE placenta to favor excessive production of sFLT1. Pharmacological manipulation of PPARγ activity has the potential to rescue the antiangiogenic state of sPE and thereby prolong pregnancy and deliver improved clinical outcomes
International student adjustment in Irish universities: Language-related challenges and the role of EAP
No full textThe present study explores the role of language in non-native English speaking (NNES) international students adaptation in Irish universities, as well as the role of EAP in-sessional programmes in adaptation. This is achieved by a thorough examination of the language-related challenges faced by NNES international students across the three adjustment domains academic, sociocultural and psychological together with the views of EAP students on an EAP in-sessional programme. The research is divided into two phases, both consisting of a convergent parallel design (i.e., QUAN + QUAL). These are connected through an exploratory sequential design, in which the qualitative component of Phase I leads to Phase II. Phase I aimed to identify the language-related challenges faced by NNES international students in Irish universities, and includes a large-scale questionnaire directed towards NNES international students in the nine public universities on the island of Ireland (n=330) as well as a first set of interviews directed towards NNES international students taking part in an EAP in-sessional programme at an Irish university (n=24). Results from Phase I identified language-related challenges across the three adjustment domains. These include challenges relating to academic reading, writing, speaking and listening skills pertinent to the academic domain; challenges relating to basic needs, social skills, adaptation to college, and cultural empathy and relatedness regarding the sociocultural domain; and lastly, challenges relating to stress, anxiety, and sadness and depression included in the psychological domain. Phase II aimed at identifying the role of EAP in-sessional programmes in student adaptation based on students views, and involved a needs analysis questionnaire directed towards EAP in-sessional students at an Irish university (n=34), and a second set of interviews (i.e., follow-up interview). Results from this phase indicated that EAP programmes may contribute to students adaptation by following a practical approach, the use of authentic materials that allowed them to put academic skills into practice and receiving individual feedback from EAP tutors
Statement on the derivation of Health-Based Guidance Values (HBGVs) for regulated products that are also nutrients
No full textThis Statement presents a proposal for harmonising the establishment of Health-Based Guidance Values (HBGVs) for regulated products that are also nutrients. This is a recurrent issue for food additives and pesticides, and may occasionally occur for other regulated products. The Statement describes the specific considerations that should be followed for establishing the HBGVs during the assessment of a regulated product that is also a nutrient. It also addresses the elements to be considered in the intake assessment; and proposes a decision tree for ensuring a harmonised process for the risk characterisation of regulated products that are also nutrients. The Scientific Committee recommends the involvement of the relevant EFSA Panels and units, in order to ensure an integrated and harmonised approach for the hazard and risk characterisation of regulated products that are also nutrients, considering the intake from all relevant sources
A systems‐based approach to the environmental risk assessment of multiple stressors in honey bees
No full textThe European Parliament requested EFSA to develop a holistic risk assessment of multiple stressors in honey bees. To this end, a systems-based approach that is composed of two core components: a monitoring system and a modelling system are put forward with honey bees taken as a showcase. Key developments in the current scientific opinion (including systematic data collection from sentinel beehives and an agent-based simulation) have the potential to substantially contribute to future development of environmental risk assessments of multiple stressors at larger spatial and temporal scales. For the monitoring, sentinel hives would be placed across representative climatic zones and landscapes in the EU and connected to a platform for data storage and analysis. Data on bee health status, chemical residues and the immediate or broader landscape around the hives would be collected in a harmonised and standardised manner, and would be used to inform stakeholders, and the modelling system, ApisRAM, which simulates as accurately as possible a honey bee colony. ApisRAM would be calibrated and continuously updated with incoming monitoring data and emerging scientific knowledge from research. It will be a supportive tool for beekeeping, farming, research, risk assessment and risk management, and it will benefit the wider society. A societal outlook on the proposed approach is included and this was conducted with targeted social science research with 64 beekeepers from eight EU Member States and with members of the EU Bee Partnership. Gaps and opportunities are identified to further implement the approach. Conclusions and recommendations are made on a way forward, both for the application of the approach and its use in a broader context
A cohort study to investigate sex‑specific differences in ANCA‑associated glomerulonephritis outcomes
No full textData surrounding sex-specific differences in ANCA-associated vasculitis glomerulonephritis (ANCA-GN) outcomes is sparse. We hypothesised that the previously observed increased risk of end-stage kidney disease (ESKD) in males is driven by sex-specific variation in immunosuppression dosing. Patients were recruited to the Irish Rare Kidney Disease Registry or followed by the Royal Free Hospital vasculitis team (2012–2020). Inclusion criteria: prior diagnosis of ANCA-GN (biopsy proven pauci-immune glomerulonephritis) and positive serology for anti-MPO or -PR3 antibodies. Renal and
patient survival, stratified by sex and Berden histological class, was analysed. The cumulative- and starting dose/kilogram of induction agents and prednisolone, respectively, was compared between sexes. 332 patients were included. Median follow-up was time 40.2 months (IQR 17.3–69.2). 73 (22%) reached ESKD and 47 (14.2%) died. Overall 1- and 5-year renal survival was 82.2% and 76.7% in males and 87.1% and 82.0% in females, respectively (p 0.13). The hazard ratio for ESKD in males versus
females, after adjustment for age, ANCA serology, baseline creatinine and histological class was 1.07 (95% CI 0.59–1.93). There was no difference between sexes in the dose/kilogram of any induction agent. We did not observe a strong impact of sex on renal outcome in ANCA-GN. Treatment intensity does not vary by sex