Between 2005 and 2007, a warming anomaly of the Atlantic water inflow into the Arctic Ocean took ... more Between 2005 and 2007, a warming anomaly of the Atlantic water inflow into the Arctic Ocean took place in the Eastern Fram Strait. Together with a decrease in sea-ice coverage, this anomaly resulted in a decreased phytodetritus export to the deep sea. Only little is known about ecological consequences on Arctic warming on the entire ecosystem from surface to the seafloor. By annual sampling between 2003 to 2009 at the Long-Term Ecological Research (LTER) site HAUSGARTEN (79°N, 4°E; Eastern Fram Strait), we investigated how the warming and consequent variation in food supply affected benthic bacterial and eukaryotic communities, which were determined by 454 massively parallel tag sequencing. Bacterial richness decreased during the time of limited food supply, yet both abundant and rare bacterial types showed different responses in their relative abundances, resulting in a strong shift of the bacterial community structure. Also, eukaryotic richness of all size classes decreased at tim...
Bacterial biofilms provide cues for the settlement of marine invertebrates such as coral larvae, ... more Bacterial biofilms provide cues for the settlement of marine invertebrates such as coral larvae, and are therefore important for the resilience and recovery of coral reefs. This study aimed to better understand how ocean acidification may affect the community composition and diversity of bacterial biofilms on surfaces under naturally reduced pH conditions. Settlement tiles were deployed at coral reefs in Papua New Guinea along pH gradients created by two CO2 seeps, and upper and lower tiles surfaces were sampled 5 and 13 months after deployment. Automated Ribosomal Intergenic Spacer Analysis were used to characterize more than 200 separate bacterial communities, complemented by amplicon sequencing of the bacterial 16S rRNA gene of 16 samples. The bacterial biofilm consisted predominantly of Alpha-, Gamma- and Deltaproteobacteria, as well as Cyanobacteria, Flavobacteriia and Cytophaga, whereas putative settlement-inducing taxa only accounted for a small fraction of the community. Bacterial biofilm composition was heterogeneous with approximately 25% shared operational taxonomic units between samples. Among the observed environmental parameters, pH only had a weak effect on community composition (R² ~ 1%) and did not affect community richness and evenness. In contrast, there were strong differences between upper and lower surfaces (contrasting in light exposure and grazing intensity). There also appeared to be a strong interaction between bacterial biofilm composition and the macroscopic components of the tile community. Our results suggest that on mature settlement surfaces in situ, pH does not have a strong impact on the composition of bacterial biofilms. Other abiotic and biotic factors such as light exposure and interactions with other organisms may be more important in shaping bacterial biofilms than changes in seawater pH.
Introduction In contrast to countries where carbapenemase-producing Enterobacterales (CPE) are en... more Introduction In contrast to countries where carbapenemase-producing Enterobacterales (CPE) are endemic, only sporadic cases were reported in Switzerland until 2013. An aggravation of the epidemiological situation in neighbouring European countries indicated the need for a surveillance study in Switzerland. Aim We aimed to describe CPE distributions in Switzerland and identify epidemiological factors associated with changes in incidence. Methods Data on all human CPE isolates from 2013 to 2018 were collected by the Swiss Centre for Antibiotic Resistance (ANRESIS) and analysed for temporal and regional trends by Generalised Poisson regression. Isolates associated with infection or colonisation were included in a primary analysis; a secondary analysis included invasive isolates only. Statistical detection of regional clusters was performed with WHONET/SaTScan. Results We analysed 731 CPE isolates, of which 325 (44.5%) were associated with screenings and 173 (23.7%) with infections. Yea...
Chronic hepatitis B virus (HBV) infection affects >10% of the general population and is the le... more Chronic hepatitis B virus (HBV) infection affects >10% of the general population and is the leading cause of liver cirrhosis and cancer in West Africa. Despite current recommendations, HBV is often not tested for in clinical routine in the region. We included all people living with HIV (PLWH) in care between March and July 2019 at Fann University Hospital in Dakar (Senegal) and proposed hepatitis B surface antigen (HBsAg) test to those never tested. All HBsAg-positive underwent HIV and HBV viral load (VL) and liver stiffness measurement. We evaluated, using logistic regression, potential associations between patient characteristics and (a) HBV testing uptake; (b) HIV/HBV co-infection among individual HBsAg tested. We determined the proportion of co-infected who had HBV DNA >20 IU/ml on ART and sequenced HBV polymerase in those with HBV replication.of 1076 PLWH in care, 689 (64.0%) had never had an HBsAg test prior to our HBV testing intervention. Women and individuals >40 years old were less likely to have been previously tested. After HBV testing intervention,107/884 (12.1%) PLWH were HBsAg-positive. Seven of 58 (12.1%) individuals newly diagnosed with HIV/HBV co-infection had a detectable HBV VL, of whom five were HIV-suppressed. Two patients on ART including 3TC and AZT as backbone showed the presence of the triple resistance mutation 180M/204I/80V. In this Senegalese urban HIV clinic, the majority of patients on ART had never been tested for HBV infection. One in ten co-infected individuals had a detectable HBV VL despite HIV suppression, and 8% were not receiving a TDF-containing regimen.
Streptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determin... more Streptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determines the serotype and influences disease severity but the mechanism is largely unknown. Due to evidence of elevated cytokines levels in the meningeal inflammatory response, we measured 41 cytokines/chemokines and growth factors in cerebrospinal fluid (CSF) samples from 57 South African meningitis patients (collected in the period 2018–2019), with confirmed S. pneumoniae serotypes, using a multiplexed bead-based immunoassay. Based on multivariable Bayesian regression, using serotype 10A as a reference and after adjusting for HIV and age, we found IL-6 concentrations significantly lower in patients infected with serotypes 6D (undetectable) and 23A (1601 pg/ml), IL-8 concentrations significantly higher in those infected with 22A (40,459 pg/ml), 7F (32,400 pg/ml) and 15B/C (6845 pg/ml), and TNFα concentration significantly higher in those infected with serotype 18A (33,097 pg/ml). Although a r...
This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
The increase of the human population is accompanied by growing numbers of livestock to feed this ... more The increase of the human population is accompanied by growing numbers of livestock to feed this population, as well as by an increase of human invasion into natural habitats of wild animals. As a result, both animals and humans are becoming progressively vulnerable to infections with known (zoonotic) pathogens, but are also increasingly exposed to novel viruses. Global trade as well as climate changes can contribute to pathogen transmission, e.g. through import of infected vectors or expansion of habitats for arthropod vectors such as mosquitoes and midges. Infectious disease outbreaks, especially those by novel viruses, are generally unexpected, and therefore we should be prepared with tools and abilities for immediate action, including the identification of the causative agent, the evaluation of its pathogenic potential for animals and humans, and the fast development of diagnostic assays to allow contact tracing and quarantine measures. HONOURs is a Marie Skłodowska-Curie Actions Innovative Training Network (MSCA-ITN), teaching 15 talented young researchers to become "preparedness-experts". HONOURs, initiated in April 2017, involves 11 laboratories from 6 different European countries, all at the forefront of novel virus investigations and characterizations. The network includes surveillance experts in both the veterinary and the human health sector, who have developed and utilize highly sensitive virus discovery techniques, e.g. next generation sequencing based genomics and universal primers based PCR, to allow identification and characterization of novel viruses. Production of pure viral proteins, providing high-resolution structures, aids in the design of novel, fast and easyto-use diagnostics. Organotypic in vitro cell cultures systems (e.g. pseudostratified human airway epithelia) provide tools for virus replication, if needed via a reverse genetics platform, and the production of virus stocks permits inoculation in animal models to examine disease, evaluate candidate vaccines, and fulfilment of the Koch's postulates. Scientists of the various institutes will provide training in the HONOURs network through
The increase of the human population is accompanied by growing numbers of livestock to feed this ... more The increase of the human population is accompanied by growing numbers of livestock to feed this population, as well as by an increase of human invasion into natural habitats of wild animals. As a result, both animals and humans are becoming progressively vulnerable to infections with known (zoonotic) pathogens, but are also increasingly exposed to novel viruses. Global trade as well as climate changes can contribute to pathogen transmission, e.g. through import of infected vectors or expansion of habitats for arthropod vectors such as mosquitoes and midges. Infectious disease outbreaks, especially those by novel viruses, are generally unexpected, and therefore we should be prepared with tools and abilities for immediate action, including the identification of the causative agent, the evaluation of its pathogenic potential for animals and humans, and the fast development of diagnostic assays to allow contact tracing and quarantine measures. HONOURs is a Marie Skłodowska-Curie Actions Innovative Training Network (MSCA-ITN), teaching 15 talented young researchers to become "preparedness-experts". HONOURs, initiated in April 2017, involves 11 laboratories from 6 different European countries, all at the forefront of novel virus investigations and characterizations. The network includes surveillance experts in both the veterinary and the human health sector, who have developed and utilize highly sensitive virus discovery techniques, e.g. next generation sequencing based genomics and universal primers based PCR, to allow identification and characterization of novel viruses. Production of pure viral proteins, providing high-resolution structures, aids in the design of novel, fast and easyto-use diagnostics. Organotypic in vitro cell cultures systems (e.g. pseudostratified human airway epithelia) provide tools for virus replication, if needed via a reverse genetics platform, and the production of virus stocks permits inoculation in animal models to examine disease, evaluate candidate vaccines, and fulfilment of the Koch's postulates. Scientists of the various institutes will provide training in the HONOURs network through
One of the options to mitigate atmospheric CO 2 increase is CO 2 Capture and Storage in sub-seabe... more One of the options to mitigate atmospheric CO 2 increase is CO 2 Capture and Storage in sub-seabed geological formations. Since predicting long-term storage security is difficult, different CO 2 leakage scenarios and impacts on marine ecosystems require evaluation. Submarine CO 2 vents may serve as natural analogues and allow studying the effects of CO 2 leakage in a holistic approach. At the study site east of Basiluzzo Islet off Panarea Island (Italy), gas emissions (90-99% CO 2) occur at moderate flows (80-120 L m −2 h −1). We investigated the effects of acidified porewater conditions (pH T range: 5.5-7.7) on the diversity of benthic bacteria and invertebrates by sampling natural sediments in three subsequent years and by performing a transplantation experiment with a duration of one year, respectively. Both multiple years and one year of exposure to acidified porewater conditions reduced the number of benthic bacterial operational taxonomic units and invertebrate species diversity by 30-80%. Reduced biodiversity at the vent sites increased the temporal variability in bacterial and nematode community biomass, abundance and composition. While the release from CO 2 exposure resulted in a full recovery of nematode species diversity within one year, bacterial diversity remained affected. Overall our findings showed that seawater acidification, induced by seafloor CO 2 emissions, was responsible for loss of diversity across different size-classes of benthic organisms, which reduced community stability with potential relapses on ecosystem resilience.
The Journal of Allergy and Clinical Immunology: In Practice
Background External validation of prediction models is important to assess generalisability to ot... more Background External validation of prediction models is important to assess generalisability to other populations than the one used for model development. The Predicting Asthma Risk in Children (PARC) tool, developed in the Leicestershire Respiratory Cohort (LRC), uses information on preschool respiratory symptoms to predict asthma at school age. Objective We performed an external validation of PARC using the Avon Longitudinal Study of Parents and Children (ALSPAC). Methods We defined inclusion criteria, prediction score items at baseline and asthma at follow-up in ALSPAC to match those used in LRC using information from parentreported questionnaires. We assessed performance of PARC by calculating sensitivity, specificity, predictive values, likelihood ratios, area under the curve (AUC), Brier score and Nagelkerke's R-squared. Sensitivity analyses varied inclusion criteria, scoring items and outcomes. Results The validation population included 2690 children with preschool respiratory symptoms of which 373 (14%) had asthma at school age. Discriminative performance of PARC was similar in ALSPAC (AUC=0.77, Brier score 0.13) as in LRC (0.78, 0.22). The score cutoff of 4 showed the highest sum of sensitivity (69%) and specificity (76%) and positive and negative likelihood ratios of 2.87 and 0.41, respectively. 3. How does this study impact current management guidelines? PARC is a simple non-invasive tool for predicting school-age asthma in symptomatic preschool children. It can be used to recruit high-risk children for clinical trials and its use in clinical practice is ready to be tested.
We characterized the genetic environment of mcr-1 in colistin-resistant Escherichia coli strains ... more We characterized the genetic environment of mcr-1 in colistin-resistant Escherichia coli strains isolated in Switzerland during 2014-2016 from humans (n=3) and chicken meat (n=6). Whole genome and plasmid sequencing identified mcr-1 integrated in IncX4 (of which, one carrying the mcr-1.2 variant), IncI2, IncHI2 and novel IncK2 plasmids (overall, n=7), as well as in the bacterial chromosome (n=2) in single or duplicate copies. Our study supports the easy mobilization of mcr-1 across diverse genetic locations.
Cough in children is a common reason for medical consultations and affects quality of life. There... more Cough in children is a common reason for medical consultations and affects quality of life. There are little population-based data on the epidemiology of recurrent cough in children and how this varies by age and sex, or between children with and without wheeze. We determined the prevalence of cough throughout childhood, comparing several standardised cough questions. We did this for the entire population and separately for girls and boys, and for children with and without wheeze. In a population-based prospective cohort from Leicestershire, UK, we assessed prevalence of cough with repeated questionnaires from early childhood to adolescence. We asked whether the child usually coughed more than other children, with or without colds, had night-time cough or cough triggered by various factors (triggers, related to increased breathing effort, allergic or food triggers). We calculated prevalence from age 1 to 18 years using generalised estimating equations for all children, and for child...
Between 2005 and 2007, a warming anomaly of the Atlantic water inflow into the Arctic Ocean took ... more Between 2005 and 2007, a warming anomaly of the Atlantic water inflow into the Arctic Ocean took place in the Eastern Fram Strait. Together with a decrease in sea-ice coverage, this anomaly resulted in a decreased phytodetritus export to the deep sea. Only little is known about ecological consequences on Arctic warming on the entire ecosystem from surface to the seafloor. By annual sampling between 2003 to 2009 at the Long-Term Ecological Research (LTER) site HAUSGARTEN (79°N, 4°E; Eastern Fram Strait), we investigated how the warming and consequent variation in food supply affected benthic bacterial and eukaryotic communities, which were determined by 454 massively parallel tag sequencing. Bacterial richness decreased during the time of limited food supply, yet both abundant and rare bacterial types showed different responses in their relative abundances, resulting in a strong shift of the bacterial community structure. Also, eukaryotic richness of all size classes decreased at tim...
Bacterial biofilms provide cues for the settlement of marine invertebrates such as coral larvae, ... more Bacterial biofilms provide cues for the settlement of marine invertebrates such as coral larvae, and are therefore important for the resilience and recovery of coral reefs. This study aimed to better understand how ocean acidification may affect the community composition and diversity of bacterial biofilms on surfaces under naturally reduced pH conditions. Settlement tiles were deployed at coral reefs in Papua New Guinea along pH gradients created by two CO2 seeps, and upper and lower tiles surfaces were sampled 5 and 13 months after deployment. Automated Ribosomal Intergenic Spacer Analysis were used to characterize more than 200 separate bacterial communities, complemented by amplicon sequencing of the bacterial 16S rRNA gene of 16 samples. The bacterial biofilm consisted predominantly of Alpha-, Gamma- and Deltaproteobacteria, as well as Cyanobacteria, Flavobacteriia and Cytophaga, whereas putative settlement-inducing taxa only accounted for a small fraction of the community. Bacterial biofilm composition was heterogeneous with approximately 25% shared operational taxonomic units between samples. Among the observed environmental parameters, pH only had a weak effect on community composition (R² ~ 1%) and did not affect community richness and evenness. In contrast, there were strong differences between upper and lower surfaces (contrasting in light exposure and grazing intensity). There also appeared to be a strong interaction between bacterial biofilm composition and the macroscopic components of the tile community. Our results suggest that on mature settlement surfaces in situ, pH does not have a strong impact on the composition of bacterial biofilms. Other abiotic and biotic factors such as light exposure and interactions with other organisms may be more important in shaping bacterial biofilms than changes in seawater pH.
Introduction In contrast to countries where carbapenemase-producing Enterobacterales (CPE) are en... more Introduction In contrast to countries where carbapenemase-producing Enterobacterales (CPE) are endemic, only sporadic cases were reported in Switzerland until 2013. An aggravation of the epidemiological situation in neighbouring European countries indicated the need for a surveillance study in Switzerland. Aim We aimed to describe CPE distributions in Switzerland and identify epidemiological factors associated with changes in incidence. Methods Data on all human CPE isolates from 2013 to 2018 were collected by the Swiss Centre for Antibiotic Resistance (ANRESIS) and analysed for temporal and regional trends by Generalised Poisson regression. Isolates associated with infection or colonisation were included in a primary analysis; a secondary analysis included invasive isolates only. Statistical detection of regional clusters was performed with WHONET/SaTScan. Results We analysed 731 CPE isolates, of which 325 (44.5%) were associated with screenings and 173 (23.7%) with infections. Yea...
Chronic hepatitis B virus (HBV) infection affects >10% of the general population and is the le... more Chronic hepatitis B virus (HBV) infection affects >10% of the general population and is the leading cause of liver cirrhosis and cancer in West Africa. Despite current recommendations, HBV is often not tested for in clinical routine in the region. We included all people living with HIV (PLWH) in care between March and July 2019 at Fann University Hospital in Dakar (Senegal) and proposed hepatitis B surface antigen (HBsAg) test to those never tested. All HBsAg-positive underwent HIV and HBV viral load (VL) and liver stiffness measurement. We evaluated, using logistic regression, potential associations between patient characteristics and (a) HBV testing uptake; (b) HIV/HBV co-infection among individual HBsAg tested. We determined the proportion of co-infected who had HBV DNA >20 IU/ml on ART and sequenced HBV polymerase in those with HBV replication.of 1076 PLWH in care, 689 (64.0%) had never had an HBsAg test prior to our HBV testing intervention. Women and individuals >40 years old were less likely to have been previously tested. After HBV testing intervention,107/884 (12.1%) PLWH were HBsAg-positive. Seven of 58 (12.1%) individuals newly diagnosed with HIV/HBV co-infection had a detectable HBV VL, of whom five were HIV-suppressed. Two patients on ART including 3TC and AZT as backbone showed the presence of the triple resistance mutation 180M/204I/80V. In this Senegalese urban HIV clinic, the majority of patients on ART had never been tested for HBV infection. One in ten co-infected individuals had a detectable HBV VL despite HIV suppression, and 8% were not receiving a TDF-containing regimen.
Streptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determin... more Streptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determines the serotype and influences disease severity but the mechanism is largely unknown. Due to evidence of elevated cytokines levels in the meningeal inflammatory response, we measured 41 cytokines/chemokines and growth factors in cerebrospinal fluid (CSF) samples from 57 South African meningitis patients (collected in the period 2018–2019), with confirmed S. pneumoniae serotypes, using a multiplexed bead-based immunoassay. Based on multivariable Bayesian regression, using serotype 10A as a reference and after adjusting for HIV and age, we found IL-6 concentrations significantly lower in patients infected with serotypes 6D (undetectable) and 23A (1601 pg/ml), IL-8 concentrations significantly higher in those infected with 22A (40,459 pg/ml), 7F (32,400 pg/ml) and 15B/C (6845 pg/ml), and TNFα concentration significantly higher in those infected with serotype 18A (33,097 pg/ml). Although a r...
This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
The increase of the human population is accompanied by growing numbers of livestock to feed this ... more The increase of the human population is accompanied by growing numbers of livestock to feed this population, as well as by an increase of human invasion into natural habitats of wild animals. As a result, both animals and humans are becoming progressively vulnerable to infections with known (zoonotic) pathogens, but are also increasingly exposed to novel viruses. Global trade as well as climate changes can contribute to pathogen transmission, e.g. through import of infected vectors or expansion of habitats for arthropod vectors such as mosquitoes and midges. Infectious disease outbreaks, especially those by novel viruses, are generally unexpected, and therefore we should be prepared with tools and abilities for immediate action, including the identification of the causative agent, the evaluation of its pathogenic potential for animals and humans, and the fast development of diagnostic assays to allow contact tracing and quarantine measures. HONOURs is a Marie Skłodowska-Curie Actions Innovative Training Network (MSCA-ITN), teaching 15 talented young researchers to become "preparedness-experts". HONOURs, initiated in April 2017, involves 11 laboratories from 6 different European countries, all at the forefront of novel virus investigations and characterizations. The network includes surveillance experts in both the veterinary and the human health sector, who have developed and utilize highly sensitive virus discovery techniques, e.g. next generation sequencing based genomics and universal primers based PCR, to allow identification and characterization of novel viruses. Production of pure viral proteins, providing high-resolution structures, aids in the design of novel, fast and easyto-use diagnostics. Organotypic in vitro cell cultures systems (e.g. pseudostratified human airway epithelia) provide tools for virus replication, if needed via a reverse genetics platform, and the production of virus stocks permits inoculation in animal models to examine disease, evaluate candidate vaccines, and fulfilment of the Koch's postulates. Scientists of the various institutes will provide training in the HONOURs network through
The increase of the human population is accompanied by growing numbers of livestock to feed this ... more The increase of the human population is accompanied by growing numbers of livestock to feed this population, as well as by an increase of human invasion into natural habitats of wild animals. As a result, both animals and humans are becoming progressively vulnerable to infections with known (zoonotic) pathogens, but are also increasingly exposed to novel viruses. Global trade as well as climate changes can contribute to pathogen transmission, e.g. through import of infected vectors or expansion of habitats for arthropod vectors such as mosquitoes and midges. Infectious disease outbreaks, especially those by novel viruses, are generally unexpected, and therefore we should be prepared with tools and abilities for immediate action, including the identification of the causative agent, the evaluation of its pathogenic potential for animals and humans, and the fast development of diagnostic assays to allow contact tracing and quarantine measures. HONOURs is a Marie Skłodowska-Curie Actions Innovative Training Network (MSCA-ITN), teaching 15 talented young researchers to become "preparedness-experts". HONOURs, initiated in April 2017, involves 11 laboratories from 6 different European countries, all at the forefront of novel virus investigations and characterizations. The network includes surveillance experts in both the veterinary and the human health sector, who have developed and utilize highly sensitive virus discovery techniques, e.g. next generation sequencing based genomics and universal primers based PCR, to allow identification and characterization of novel viruses. Production of pure viral proteins, providing high-resolution structures, aids in the design of novel, fast and easyto-use diagnostics. Organotypic in vitro cell cultures systems (e.g. pseudostratified human airway epithelia) provide tools for virus replication, if needed via a reverse genetics platform, and the production of virus stocks permits inoculation in animal models to examine disease, evaluate candidate vaccines, and fulfilment of the Koch's postulates. Scientists of the various institutes will provide training in the HONOURs network through
One of the options to mitigate atmospheric CO 2 increase is CO 2 Capture and Storage in sub-seabe... more One of the options to mitigate atmospheric CO 2 increase is CO 2 Capture and Storage in sub-seabed geological formations. Since predicting long-term storage security is difficult, different CO 2 leakage scenarios and impacts on marine ecosystems require evaluation. Submarine CO 2 vents may serve as natural analogues and allow studying the effects of CO 2 leakage in a holistic approach. At the study site east of Basiluzzo Islet off Panarea Island (Italy), gas emissions (90-99% CO 2) occur at moderate flows (80-120 L m −2 h −1). We investigated the effects of acidified porewater conditions (pH T range: 5.5-7.7) on the diversity of benthic bacteria and invertebrates by sampling natural sediments in three subsequent years and by performing a transplantation experiment with a duration of one year, respectively. Both multiple years and one year of exposure to acidified porewater conditions reduced the number of benthic bacterial operational taxonomic units and invertebrate species diversity by 30-80%. Reduced biodiversity at the vent sites increased the temporal variability in bacterial and nematode community biomass, abundance and composition. While the release from CO 2 exposure resulted in a full recovery of nematode species diversity within one year, bacterial diversity remained affected. Overall our findings showed that seawater acidification, induced by seafloor CO 2 emissions, was responsible for loss of diversity across different size-classes of benthic organisms, which reduced community stability with potential relapses on ecosystem resilience.
The Journal of Allergy and Clinical Immunology: In Practice
Background External validation of prediction models is important to assess generalisability to ot... more Background External validation of prediction models is important to assess generalisability to other populations than the one used for model development. The Predicting Asthma Risk in Children (PARC) tool, developed in the Leicestershire Respiratory Cohort (LRC), uses information on preschool respiratory symptoms to predict asthma at school age. Objective We performed an external validation of PARC using the Avon Longitudinal Study of Parents and Children (ALSPAC). Methods We defined inclusion criteria, prediction score items at baseline and asthma at follow-up in ALSPAC to match those used in LRC using information from parentreported questionnaires. We assessed performance of PARC by calculating sensitivity, specificity, predictive values, likelihood ratios, area under the curve (AUC), Brier score and Nagelkerke's R-squared. Sensitivity analyses varied inclusion criteria, scoring items and outcomes. Results The validation population included 2690 children with preschool respiratory symptoms of which 373 (14%) had asthma at school age. Discriminative performance of PARC was similar in ALSPAC (AUC=0.77, Brier score 0.13) as in LRC (0.78, 0.22). The score cutoff of 4 showed the highest sum of sensitivity (69%) and specificity (76%) and positive and negative likelihood ratios of 2.87 and 0.41, respectively. 3. How does this study impact current management guidelines? PARC is a simple non-invasive tool for predicting school-age asthma in symptomatic preschool children. It can be used to recruit high-risk children for clinical trials and its use in clinical practice is ready to be tested.
We characterized the genetic environment of mcr-1 in colistin-resistant Escherichia coli strains ... more We characterized the genetic environment of mcr-1 in colistin-resistant Escherichia coli strains isolated in Switzerland during 2014-2016 from humans (n=3) and chicken meat (n=6). Whole genome and plasmid sequencing identified mcr-1 integrated in IncX4 (of which, one carrying the mcr-1.2 variant), IncI2, IncHI2 and novel IncK2 plasmids (overall, n=7), as well as in the bacterial chromosome (n=2) in single or duplicate copies. Our study supports the easy mobilization of mcr-1 across diverse genetic locations.
Cough in children is a common reason for medical consultations and affects quality of life. There... more Cough in children is a common reason for medical consultations and affects quality of life. There are little population-based data on the epidemiology of recurrent cough in children and how this varies by age and sex, or between children with and without wheeze. We determined the prevalence of cough throughout childhood, comparing several standardised cough questions. We did this for the entire population and separately for girls and boys, and for children with and without wheeze. In a population-based prospective cohort from Leicestershire, UK, we assessed prevalence of cough with repeated questionnaires from early childhood to adolescence. We asked whether the child usually coughed more than other children, with or without colds, had night-time cough or cough triggered by various factors (triggers, related to increased breathing effort, allergic or food triggers). We calculated prevalence from age 1 to 18 years using generalised estimating equations for all children, and for child...
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