Representing mutations for predicting cancer drug response.

MOTIVATION: Predicting cancer drug response requires a comprehensive assessment of many mutations present across a tumor genome. While current drug response models generally use a binary mutated/unmutated indicator for each gene, not all mutations in a gene are equivalent. RESULTS: Here, we construct and evaluate a series of predictive models based on leading methods for quantitative mutation scoring. Such methods include VEST4 and CADD, which score the impact of a mutation on gene function, and CHASMplus, which scores the likelihood a mutation drives cancer. The resulting predictive models capture cellular responses to dabrafenib, which targets BRAF-V600 mutations, whereas models based on binary mutation status do not. Performance improvements generalize to other drugs, extending genetic indications for PIK3CA, ERBB2, EGFR, PARP1, and ABL1 inhibitors. Introducing quantitative mutation features in drug response models increases performance and mechanistic understanding. AVAILABILITY AND IMPLEMENTATION: Code and example datasets are available at https://github.com/pgwall/qms.

Prediction of Listeria monocytogenes Clonal Complexes from Multilocus Variable Number Tandem Repeat Analysis Patterns Using a Machine Learning Approach.

Multilocus variable number tandem repeat analysis (MLVA) is a molecular subtyping technique that remains useful for those without the resources to access whole genome sequencing for the tracking and tracing of bacterial contaminants. Unlike techniques such as multilocus sequence typing (MLST) and pulsed-field gel electrophoresis, MLVA did not emerge as a standardized subtyping method for Listeria monocytogenes, and as a result, there is no reference database of virulent or food-associated MLVA subtypes as there is for MLST-based clonal complexes (CCs). Having previously shown the close congruence of a 5-loci MLVA scheme with MLST, a predictive model was created using the XGBoost machine learning (ML) technique, which enabled the prediction of CCs from MLVA patterns with ∼85% (±4%) accuracy. As well as validating the model on existing data, a straightforward update protocol was simulated for if and when previously unseen subtypes might arise. This article illustrates how ML techniques can be applied with elementary coding skills to add value to previous-generation molecular subtyping data in-built food processing environments.

Exploring the psychological impact of contact tracing work on staff during the COVID-19 pandemic.

BACKGROUND: Contact tracing is a key control measure in the response to the COVID-19 pandemic. While quantitative research has been conducted on the psychological impact of the pandemic on other frontline healthcare workers, none has explored the impact on contact tracing staff. METHODS: A longitudinal study was conducted using two repeated measures with contact tracing staff employed in Ireland during the COVID-19 pandemic using two-tailed independent samples t tests and exploratory linear mixed models. RESULTS: The study sample included 137 contact tracers in March 2021 (T1) and 218 in September 2021 (T3). There was an increase from T1 to T3 in burnout related exhaustion (p < 0·001), post-traumatic stress disorder (PTSD) symptom scores (p < 0·001), mental distress (p < 0·01), perceived stress (p < 0·001) and tension and pressure (p < 0·001). In those aged 18-30, there was an increase in exhaustion related burnout (p < 0·01), PTSD symptoms (p < 0·05), and tension and pressure scores (p < 0·05). Additionally, participants with a background in healthcare showed an increase in PTSD symptom scores by T3 (p < 0·001), reaching mean scores equivalent to those of participants who did not have a background in healthcare. CONCLUSIONS: Contact tracing staff working during the COVID-19 pandemic experienced an increase in adverse psychological outcomes. These findings highlight a need for further research on psychological supports required by contact tracing staff with differing demographic profiles.

Core competencies in applied infectious disease epidemiology: a framework for countries in Europe.

In 2009, the European Centre for Disease Prevention and Control (ECDC) developed a competency framework to support European Union countries and the European Commission in ensuring a competent public health workforce for Europe. The coronavirus disease (COVID-19) pandemic emphasised the importance of harmonised public health strategies and competencies across international boundaries, specifically for infectious diseases. This perspective presents the process to update the competency framework for applied infectious disease epidemiology, highlighting ECDC's efforts to support countries with using the framework. ECDC commissioned the Association of Schools of Public Health in the European Region (ASPHER) to update the framework through publication and dissemination of a technical report and a self-assessment tool linked to training resources. A mixed methods approach to gather input from experts in relevant specialities included qualitative interviews with 42 experts, workshops with ECDC Technical Advisory Group and an online survey of 212 public health professionals across Europe and beyond. Modifications resulted in 157 core competencies in 23 domains, each mapping to one of six subject areas of importance in applied infectious disease epidemiology. The framework serves as a basis to update the curriculum of the ECDC Fellowship programme with two alternative paths: intervention epidemiology or public health microbiology.

COM902, a novel therapeutic antibody targeting TIGIT augments anti-tumor T cell function in combination with PVRIG or PD-1 pathway blockade.

Immune checkpoint inhibitors (ICIs) have emerged as promising therapies for the treatment of cancer. However, existing ICIs, namely PD-(L)1 and CTLA-4 inhibitors, generate durable responses only in a subset of patients. TIGIT is a co-inhibitory receptor and member of the DNAM-1 family of immune modulating proteins. We evaluated the prevalence of TIGIT and its cognate ligand, PVR (CD155), in human cancers by assessing their expression in a large set of solid tumors. TIGIT is expressed on CD4+ and CD8+ TILs and is upregulated in tumors compared to normal tissues. PVR is expressed on tumor cells and tumor-associated macrophages from multiple solid tumors. We explored the therapeutic potential of targeting TIGIT by generating COM902, a fully human anti-TIGIT hinge-stabilized IgG4 monoclonal antibody that binds specifically to human, cynomolgus monkey, and mouse TIGIT, and disrupts the binding of TIGIT with PVR. COM902, either alone or in combination with a PVRIG (COM701) or PD-1 inhibitor, enhances antigen-specific human T cell responses in-vitro. In-vivo, a mouse chimeric version of COM902 in combination with an anti-PVRIG or anti-PD-L1 antibody inhibited tumor growth and increased survival in two syngeneic mouse tumor models. In summary, COM902 enhances anti-tumor immune responses and is a promising candidate for the treatment of advanced malignancies.

Numbers of close contacts of individuals infected with SARS-CoV-2 and their association with government intervention strategies.

BACKGROUND: Contact tracing is conducted with the primary purpose of interrupting transmission from individuals who are likely to be infectious to others. Secondary analyses of data on the numbers of close contacts of confirmed cases could also: provide an early signal of increases in contact patterns that might precede larger than expected case numbers; evaluate the impact of government interventions on the number of contacts of confirmed cases; or provide data information on contact rates between age cohorts for the purpose of epidemiological modelling. We analysed data from 140,204 close contacts of 39,861 cases in Ireland from 1st May to 1st December 2020. RESULTS: Negative binomial regression models highlighted greater numbers of contacts within specific population demographics, after correcting for temporal associations. Separate segmented regression models of the number of cases over time and the average number of contacts per case indicated that a breakpoint indicating a rapid decrease in the number of contacts per case in October 2020 preceded a breakpoint indicating a reduction in the number of cases by 11 days. CONCLUSIONS: We found that the number of contacts per infected case was overdispersed, the mean varied considerable over time and was temporally associated with government interventions. Analysis of the reported number of contacts per individual in contact tracing data may be a useful early indicator of changes in behaviour in response to, or indeed despite, government restrictions. This study provides useful information for triangulating assumptions regarding the contact mixing rates between different age cohorts for epidemiological modelling.

Estimation of the serial interval and proportion of pre-symptomatic transmission events of COVID- 19 in Ireland using contact tracing data.

BACKGROUND: The serial interval is the period of time between the onset of symptoms in an infector and an infectee and is an important parameter which can impact on the estimation of the reproduction number. Whilst several parameters influencing infection transmission are expected to be consistent across populations, the serial interval can vary across and within populations over time. Therefore, local estimates are preferable for use in epidemiological models developed at a regional level. We used data collected as part of the national contact tracing process in Ireland to estimate the serial interval of SARS-CoV-2 infection in the Irish population, and to estimate the proportion of transmission events that occurred prior to the onset of symptoms. RESULTS: After data cleaning, the final dataset consisted of 471 infected close contacts from 471 primary cases. The median serial interval was 4 days, mean serial interval was 4.0 (95% confidence intervals 3.7, 4.3) days, whilst the 25th and 75th percentiles were 2 and 6 days respectively. We found that intervals were lower when the primary or secondary case were in the older age cohort (greater than 64 years). Simulating from an incubation period distribution from international literature, we estimated that 67% of transmission events had greater than 50% probability of occurring prior to the onset of symptoms in the infector. CONCLUSIONS: Whilst our analysis was based on a large sample size, data were collected for the primary purpose of interrupting transmission chains. Similar to other studies estimating the serial interval, our analysis is restricted to transmission pairs where the infector is known with some degree of certainty. Such pairs may represent more intense contacts with infected individuals than might occur in the overall population. It is therefore possible that our analysis is biased towards shorter serial intervals than the overall population.

Consumer perceptions on the origin of infant formula: a survey with urban Chinese mothers.

The consumer survey reported in this research paper aims to understand how Chinese mothers learn about and confirm the origin of powdered infant formulas (henceforward formulas), their knowledge level and preferences between formulas from different origins. With globalization, dairy companies can source ingredients for domestic production and manufacture finished products across the world. Chinese consumers are now facing a variety of formulas with different brand origin, main ingredient origin ('nai yuan'), manufacturing origin, and country-of-purchase. Drawing on a large representative sample of Chinese mothers who have purchased formulas, we found that most of them had intensively engaged in learning about and confirming formulas' origin through different strategies. However, they may not interpret related cues correctly: a majority of Chinese mothers incorrectly considered the 'main ingredient origin' as the 'manufacturing place' and could not necessarily recognize between 'foreign' and 'domestic' brands. Among formulas from different origins, authentic foreign branded, produced and packaged formulas showed a high popularity in Tier 1 & 2 cities and among more knowledgeable consumers. In low-tier cities, these products were equally popular as domestically branded and produced formulas using imported milk powders and other ingredients. Formulas directly acquired from overseas markets through unofficial channels were least favoured by consumers. The study shows that Chinese consumers' previous one-sided endorsement towards foreign formulas appears to have weakened. Decisions made by formula companies on the origin of the main ingredient and the place of manufacture would influence product attractiveness, and the segments of Chinese consumers to target.

A survey of Chinese consumers' knowledge, beliefs and behavioural intentions regarding salt intake and salt reduction.

OBJECTIVE: Globally, China is among the 'saltiest' nations. In order to support current nationwide salt reduction initiatives, we investigated Chinese consumers' knowledge, beliefs and behaviours related to salt intake and salt reduction. DESIGN: A cross-sectional face-to-face survey was carried out, focusing on salt knowledge, beliefs and behaviours related to salt intake and salt reduction, perceptions of salt reduction responsibility and support for different national strategies. SETTING: The survey was carried out in China mainland. PARTICIPANTS: Consumers (n 2444) from six of seven major geographical regions in China participated in the survey. After data cleaning, a sample of 2430 was included in the final analysis. RESULTS: A majority of Chinese consumers believed that salt added during home cooking was the biggest contributor to their salt intake. Knowledge gaps existed in the awareness of salt hidden in certain foods and flavouring products. Chinese consumers in general were interested in lowering their salt intake. They were aware of salt reduction tools, but the adoption level was low. Consumers expressed strong support for promotion of salt-restriction spoons and public education, but not fiscal policies (e.g. salt-related tax or subsidies). In terms of individual differences, education status demonstrated a substantial impact on salt reduction knowledge and behaviour. CONCLUSIONS: There is still big room to 'shake' Chinese consumers' salt habit. The present study provides important evidence and consumer insights to support China's efforts to meet its salt reduction targets.

Is it still a real treat? Adults' treat provision to children.

Consumption of high-energy foods in the absence of hunger has been identified as a key target to address in the area of obesity. For children, such foods are often provided by adults as treats. There is limited understating of adults' treat giving. The present study aimed to understand adults' provision of treats to children on the Island of Ireland. A total of 1039 participants, including parents, grandparents, child minders and education practitioners completed a face-to-face survey in their home. Participants defined their treats for children primarily as 'something nice', 'deserved/earned' and 'something special'. The top three motivations for treat foods provision were 'to reward for good behaviour' (42.3%), 'because the child(ren) ask' (42.2%) and 'to make the child(ren) feel better' (29.4%). Almost all participants would provide treat foods at celebrations and 52.5% always did so. In addition, 68% participants had structured weekly and/or daily treat for children. Treats provided to children were dominated by energy-dense foods. The top three were sweets, chocolates and ice-creams, being used by 45.2%, 45.1% and 38.8% participants. Variations were observed across different adult groups, in terms of their treat giving behaviour. The main observation was that adults' treat foods provision has become habitual. The findings can help develop targeted strategies to encourage the reduction or replacement of food treats for children.

The Bacterial Community Structure and Dynamics of Carbon and Nitrogen when Maize (Zea mays L.) and Its Neutral Detergent Fibre Were Added to Soil from Zimbabwe with Contrasting Management Practices.

Water infiltration, soil carbon content, aggregate stability and yields increased in conservation agriculture practices compared to conventionally ploughed control treatments at the Henderson research station near Mazowe (Zimbabwe). How these changes in soil characteristics affect the bacterial community structure and the bacteria involved in the degradation of applied organic material remains unanswered. Soil was sampled from three agricultural systems at Henderson, i.e. (1) conventional mouldboard ploughing with continuous maize (conventional tillage), (2) direct seeding with a Fitarelli jab planter and continuous maize (direct seeding with continuous maize) and (3) direct seeding with a Fitarelli jab planter with rotation of maize sunn hemp (direct seeding with crop rotation). Soil was amended with young maize plants or their neutral detergent fibre (NDF) and incubated aerobically for 56 days, while C and N mineralization and the bacterial community structure were monitored. Bacillus (Bacillales), Micrococcaceae (Actinomycetales) and phylotypes belonging to the Pseudomonadales were first degraders of the applied maize plants. At day 3, Streptomyces (Actinomycetales), Chitinophagaceae ([Saprospirales]) and Dyella (Xanthomonadales) participated in the degradation of the applied maize and at day 7 Oxalobacteraceae (Burkholderiales). Phylotypes belonging to Halomonas (Oceanospirillales) were the first degraders of NDF and were replaced by Phenylobacterium (Caulobacterales) and phylotypes belonging to Pseudomonadales at day 3. Afterwards, similar bacterial groups were favoured by application of NDF as they were by the application of maize plants, but there were also clear differences. Phylotypes belonging to the Micrococcaceae and Bacillus did not participate in the degradation of NDF or its metabolic products, while phylotypes belonging to the Acidobacteriaceae participated in the degradation of NDF but not in that of maize plants. It was found that agricultural practices had a limited effect on the bacterial community structure, but application of organic material altered it substantially.

Antimicrobial resistance and its association with tolerance to heavy metals in agriculture production.

Antimicrobial resistance is a recognized public health challenge that since its emergence limits the therapeutic options available to veterinarians and clinicians alike, when treatment is warranted. This development is further compounded by the paucity of new antibiotics. The agri-food industry benefits from the availability of antimicrobial compounds for food-animal production and crop protection. Nonetheless, their improper use can result in the selection for bacteria that are phenotypically resistant to these compounds. Another class of agents used in agriculture includes various cationic metals that can be included in animal diets as nutritional supplements or spread on pastures to support crop growth and protection. Heavy metals, in particular, are giving rise to concerns among public health professionals, as they can persist in the environment remaining stable for prolonged periods. Moreover, bacteria can also exhibit resistance to these chemical elements and the genes encoding this phenotype can be physically localized to plasmids that may also contain one or more antimicrobial resistance-encoding gene(s). This paper reviews our current understanding of the role that bacteria play in expressing resistance to heavy metals. It will describe how heavy metals are used in agri-food production, and explore evidence available to link resistance to heavy metals and antimicrobial compounds. In addition, possible solutions to reduce the impact of heavy metal resistance are also discussed, including using organic minerals and reducing the level of trace minerals in animal feed rations.

Multidrug-Resistant Escherichia coli in Bovine Animals, Europe.

Of 150 Escherichia coli strains we cultured from specimens taken from cattle in Europe, 3 had elevated MICs against colistin. We assessed all 3 strains for the presence of the plasmid-mediated mcr-1 gene and identified 1 isolate as mcr-1-positive and co-resistant to ß-lactam, florfenicol, and fluoroquinolone antimicrobial compounds.

Perspectives of the public on reducing population salt intake in Ireland.

OBJECTIVE: As countries struggle to meet the set targets for population salt intake, there have been calls for more regulated approaches to reducing dietary salt intake. However, little is known about how the public perceives various salt reduction policies; an important line of investigation given that the implementation and success of these policies often depend on public sentiment. We investigated the attitudes and beliefs of consumers towards salt reduction and their support for thirteen different government-led salt reduction policies. DESIGN: A cross-sectional online survey measured participants' knowledge, beliefs and attitudes in relation to salt reduction. SETTING: The survey was carried out with participants from the Republic of Ireland. SUBJECTS: Five hundred and one participants recruited via a market research agency completed the survey. RESULTS: We found that the vast majority of participants supported eleven of the government-led salt reduction policies, which included measures such as education, labelling and salt restriction in foods (both voluntary and regulated, across a range of settings). The two proposed fiscal policies (subsidising low-salt foods and taxing high-salt foods) received less support in comparison, with the majority of participants opposed to a tax on high-salt foods. A series of multiple regressions revealed that individual attitudes and beliefs related to health and salt were stronger predictors of support than sociodemographic factors, lifestyle or knowledge. CONCLUSIONS: The study provides an important evidence base from which policy makers may draw when making decisions on future policy steps to help achieve national salt targets.

Effects of dietary restraint and weight gain attitudes on gestational weight gain.

The aim of this study was to examine the impact of dietary restraint and attitudes to weight gain on gestational weight gain. This is a prospective cohort study of 799 women recruited at their first antenatal care visit. They provided information on pre-pregnancy dietary restraint behaviours (weight cycling, dieting and restrained eating) and attitudes to weight gain during pregnancy at a mean of 15 weeks' gestation. We examined the relationship of these variables with absolute gestational weight gain and both insufficient and excessive gestational weight gain, as defined by the Institute of Medicine recommendations. Multivariable analysis revealed that restrained eating, weight cycling and dieting were associated with higher absolute weight gain, whilst weight cycling only was associated with excessive weight gain. There was no evidence that the relationships between the dietary restraint measures and the weight gain outcomes were mediated by pregnancy-associated change in food intake. Increased concern about weight gain during pregnancy was independently associated with higher absolute weight gain and excessive weight gain. These relationships were attenuated following adjustments for pregnancy-associated change in food intake. These findings suggest that in early pregnancy, both a history of fluctuations in body weight and worry about gestational weight gain, are indicators of high pregnancy weight gain. Concern about weight gain during pregnancy seems to partly arise from an awareness of increased food intake since becoming pregnant. Prenatal dietary counselling should include consideration of past dieting practices and attitudes to pregnancy weight gain.

Exploring Coverage of the 2008 Irish Dioxin Crisis in the Irish and UK Newsprint Media.

The 2008 dioxin crisis occurred as a result of contamination of Irish pork. The event had significant implications for Ireland's economy and the reputation of its agricultural industry, as well as raising concerns for human health. This study describes the results of a content analysis of Irish and UK newspaper coverage of the 2008 Irish dioxin crisis, as this is likely to provide insight into how public perceptions of this issue were shaped. Articles from 16 print publications were systematically sampled for the period December 2008 to February 2009. The resulting data set of 141 articles was examined using a coding protocol developed based on previous research and refined during piloting. Results indicated that the dioxin crisis was primarily portrayed by the media as an industry/economic crisis, dominant in 26.9% of articles in the sample. Within this dominant portrayal, the agricultural industry was frequently cited as being in crisis (42.6%); however, the implications of the crisis on the wider economic environment also received attention (17.7%). Differences between Irish and UK-based media were also examined, revealing that while the Irish media most frequently described the crisis in terms of its impact on the industry and economy, the UK media were more likely to portray the crisis as a risk to health. These dominant media messages and message framings have implications for the public understanding of the issue in each country and potential consequences regarding perception of the adequacy of existing food policy and regulatory oversight.

Prediction of gestational weight gain - a biopsychosocial model.

OBJECTIVE: To examine the influence of health behaviours and psychological well-being on gestational weight gain using a biopsychosocial model. DESIGN: A prospective cohort study of pregnant women consecutively recruited at their first antenatal care visit. A self-administered questionnaire was used to collect data on health behaviours and psychological well-being in early pregnancy. Linear regression and logistic regression were used to identify predictors of total weight gain in kilograms and weight gain outside the current Institute of Medicine recommendations, respectively. SETTING: A maternity hospital in the Republic of Ireland. SUBJECTS: Data on 799 women were analysed. RESULTS: Pre-pregnant BMI ≥30·0 kg/m2, short stature, parity >0, decreased food intake and absence of health insurance predicted lower absolute gestational weight gain, while foreign nationality, consumption of takeaway meals more than once weekly and increased food intake predicted higher absolute gestational weight gain. Overweight and obesity, foreign nationality, increased food intake and height >170 cm were risk factors for excessive weight gain, while antenatal depression was protective against excessive weight gain. Notably, physical activity measures were not related to the gestational weight gain outcomes. Pre-pregnancy overweight and increased food intake were the strongest predictors of excessive gestational weight gain. CONCLUSIONS: None of the psychological well-being measures examined, with the exception of antenatal depression, was associated with any of the weight gain outcomes. The behavioural predictors of gestational weight gain were increased food intake and takeaway consumption. Public health promotions should target pre-pregnancy BMI and pregnancy-associated change in food intake.

Control of Listeria species food safety at a poultry food production facility.

Surveillance and control of food-borne human pathogens, such as Listeria monocytogenes, is a critical aspect of modern food safety programs at food production facilities. This study evaluated contamination patterns of Listeria species at a poultry food production facility, and evaluated the efficacy of procedures to control the contamination and transfer of the bacteria throughout the plant. The presence of Listeria species was studied along the production chain, including raw ingredients, food-contact, non-food-contact surfaces, and finished product. All isolates were sub-typed by pulsed-field gel electrophoresis (PFGE) to identify possible entry points for Listeria species into the production chain, as well as identifying possible transfer routes through the facility. The efficacy of selected in-house sanitizers against a sub-set of the isolates was evaluated. Of the 77 different PFGE-types identified, 10 were found among two or more of the five categories/areas (ingredients, food preparation, cooking and packing, bulk packing, and product), indicating potential transfer routes at the facility. One of the six sanitizers used was identified as unsuitable for control of Listeria species. Combining PFGE data, together with information on isolate location and timeframe, facilitated identification of a persistent Listeria species contamination that had colonized the facility, along with others that were transient.

Multiple measures on the Environmental Public Health Tracking Network.

SETTING: The Centers for Disease Control and Prevention's National Environmental Public Health Tracking Program is leading an initiative to build a National Environmental Public Health Tracking Network (Tracking Network) that integrates data into a network of standardized electronic data to provide valid scientific information on environmental exposures and adverse health conditions, as well as spatial and temporal relations between them. The Web-based Tracking Network is designed for different audiences including government, the academic community, and the public. A primary goal of the Tracking Network is to allow the exploration of data on health effects, environments, and demographics. The wide variety of data types along with stratifications present a complex problem when developing system functionality to query and display disparate data simultaneously in a comparable way using charts, tables, and maps. OBJECTIVE: While the ability to query and display data that span across geographies and multiple time periods for a single type of data has been the main feature set of the Tracking Network, allowing the same for multiple data types is needed to enable users to explore trends and possible associations among health and environmental data. METHODS: As a first step, a multidisciplinary team was formed to address complex issues related to developing the ability to view multiple measures on the Tracking Network. The team then iterated through steps involving requirements gathering, the segmentation of the requirements into functional areas, submission of proposals to address those functional areas, and finally evaluation of the proposals to address functional areas. CONCLUSIONS: Adding the ability to view multiple measures is an important step to improve Tracking Network users' exploration of the environmental health status of their communities. With this capability, public health practitioners and other users can formulate hypotheses, analyze trends, and explore possible relationships across a wide variety of environmental and health information.