Various models and datasets related to aflatoxins in the maize and dairy production chain have been developed and used but they have not yet been linked with each other. This study aimed to ...investigate the impacts of climate change on aflatoxin B1 production in maize and its consequences on aflatoxin M1 contamination in dairy cow's milk, using a full chain modelling approach. To this end, available models and input data were chained together in a modelling framework. As a case study, we focused on maize grown in Eastern Europe and imported to the Netherlands to be fed-as part of dairy cows' compound feed-to dairy cows in the Netherlands. Three different climate models, one aflatoxin B1 prediction model and five different carryover models were used. For this particular case study of East European maize, most of the calculations suggest an increase (up to 50%) of maximum mean aflatoxin M1 in milk by 2030, except for one climate (DMI) model suggesting a decrease. Results from all combinations of carryover and climate models suggest a similar or slight increase (up to 0.6%) of the chance of finding aflatoxin M1 in milk above the EC limit of 0.05 μg/kg by 2030. Results varied mainly with the climate model data and carryover model considered. The model framework infrastructure is flexible so that forecasting models for other mycotoxins or other food safety hazards as well as other production chains, together with necessary input databases, can easily be included as well. This modelling framework for the first time links datasets and models related to aflatoxin B1 in maize and related aflatoxin M1 the dairy production chain to obtain a unique predictive methodology based on Monte Carlo simulation. Such an integrated approach with scenario analysis provides possibilities for policy makers and risk managers to study the effects of changes in the beginning of the chain on the end product.
This paper develops a discrete‐time epidemiological model to characterize the spread of economic deterioration across sectors in the United States for the period 1952–2015. It is the first model to ...apply an epidemiological approach to consider such spread using macroeconomic Flow of Funds data. By extending the usual one‐period Markov model to a two‐period setting, we incorporate the possibility that an initial slow growth period may either continue further or improve such that further economic deterioration is averted. The estimated model can be used to classify more versus less contagious sectors and identify their channels of transmission.
Disability in Activities of Daily Living (ADL) is an adverse outcome of frailty that places a burden on frail elderly people, care providers and the care system. Knowing which physical frailty ...indicators predict ADL disability is useful in identifying elderly people who might benefit from an intervention that prevents disability or increases functioning in daily life. The objective of this study was to systematically review the literature on the predictive value of physical frailty indicators on ADL disability in community-dwelling elderly people.
A systematic search was performed in 3 databases (PubMed, CINAHL, EMBASE) from January 1975 until April 2010. Prospective, longitudinal studies that assessed the predictive value of individual physical frailty indicators on ADL disability in community-dwelling elderly people aged 65 years and older were eligible for inclusion. Articles were reviewed by two independent reviewers who also assessed the quality of the included studies.
After initial screening of 3081 titles, 360 abstracts were scrutinized, leaving 64 full text articles for final review. Eventually, 28 studies were included in the review. The methodological quality of these studies was rated by both reviewers on a scale from 0 to 27. All included studies were of high quality with a mean quality score of 22.5 (SD 1.6). Findings indicated that individual physical frailty indicators, such as weight loss, gait speed, grip strength, physical activity, balance, and lower extremity function are predictors of future ADL disability in community-dwelling elderly people.
This review shows that physical frailty indicators can predict ADL disability in community-dwelling elderly people. Slow gait speed and low physical activity/exercise seem to be the most powerful predictors followed by weight loss, lower extremity function, balance, muscle strength, and other indicators. These findings should be interpreted with caution because the data of the different studies could not be pooled due to large variations in operationalization of the indicators and ADL disability across the included studies. Nevertheless, our study suggests that monitoring physical frailty indicators in community-dwelling elderly people might be useful to identify elderly people who could benefit from disability prevention programs.
Summary Introduction Home mechanical ventilation (HMV) in the Netherlands is normally initiated in hospital, but this is expensive and often a burden for the patient. In this randomised controlled ...study we investigated whether initiation of HMV at home in patients with chronic respiratory failure is non-inferior to an in hospital based setting. Methods Seventy-seven patients were included, of which 38 patients started HMV at home. All patients were diagnosed with chronic respiratory failure due to a neuromuscular or thoracic cage disease. Primary outcome was the arterial carbon dioxide ( P aCO2 ) while quality of life and costs were secondary outcomes. Telemonitoring was used in the home group to provide therapeutic information, for example; transcutaneous carbon dioxide, oxygen saturation and ventilator information, to the caregivers. Follow-up was six months. Results P aCO2 , improved by 0.72 (SE ± 0.16) kPa in the hospital group and by 0.91 (±0.20) in the home group, both improvements being significant and the latter clearly not inferior. There were also significant improvements in quality of life in both groups, again not being inferior with home treatment. Conclusion This study is the first to show that initiation of HMV at home in a selective group of patients with chronic respiratory failure is as effective for gas exchange and quality of life as hospital initiation. In addition we found that it is safe, technically feasible and that more than € 3000 per patient can be saved compared to our standard care.
Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, and nearly 90% of patients have at least one copy of the Phe508del
...mutation. In a phase 2 trial involving patients who were heterozygous for the Phe508del
mutation and a minimal-function mutation (Phe508del-minimal function genotype), the next-generation CFTR corrector elexacaftor, in combination with tezacaftor and ivacaftor, improved Phe508del CFTR function and clinical outcomes.
We conducted a phase 3, randomized, double-blind, placebo-controlled trial to confirm the efficacy and safety of elexacaftor-tezacaftor-ivacaftor in patients 12 years of age or older with cystic fibrosis with Phe508del-minimal function genotypes. Patients were randomly assigned to receive elexacaftor-tezacaftor-ivacaftor or placebo for 24 weeks. The primary end point was absolute change from baseline in percentage of predicted forced expiratory volume in 1 second (FEV
) at week 4.
A total of 403 patients underwent randomization and received at least one dose of active treatment or placebo. Elexacaftor-tezacaftor-ivacaftor, relative to placebo, resulted in a percentage of predicted FEV
that was 13.8 points higher at 4 weeks and 14.3 points higher through 24 weeks, a rate of pulmonary exacerbations that was 63% lower, a respiratory domain score on the Cystic Fibrosis Questionnaire-Revised (range, 0 to 100, with higher scores indicating a higher patient-reported quality of life with regard to respiratory symptoms; minimum clinically important difference, 4 points) that was 20.2 points higher, and a sweat chloride concentration that was 41.8 mmol per liter lower (P<0.001 for all comparisons). Elexacaftor-tezacaftor-ivacaftor was generally safe and had an acceptable side-effect profile. Most patients had adverse events that were mild or moderate. Adverse events leading to discontinuation of the trial regimen occurred in 1% of the patients in the elexacaftor-tezacaftor-ivacaftor group.
Elexacaftor-tezacaftor-ivacaftor was efficacious in patients with cystic fibrosis with Phe508del-minimal function genotypes, in whom previous CFTR modulator regimens were ineffective. (Funded by Vertex Pharmaceuticals; VX17-445-102 ClinicalTrials.gov number, NCT03525444.).
This study describes cerebral ultrasound abnormalities caused by late-onset sepsis (LOS) in very preterm infants with a gestational age of < 32 weeks and/or birthweight < 1500 grams.
The prospective ...study ("INFANT study") included 117 preterm infants with suspected LOS. Proven LOS was defined as a positive blood culture after 72 hours of life. In case of coagulase-negative staphylococci an elevated C-reactive protein was additionally required to establish proven LOS. Patients were identified as proven LOS and patients with only clinical symptoms of LOS. Cerebral ultrasound images were obtained in the first week after birth, during/after LOS and before discharge. Cerebral findings were divided in no/minor and major abnormalities.
Eighty-six preterm infants had proven LOS and 31 preterm infants had only clinical signs of LOS. Four infants were excluded because pre-existing major brain abnormalities. No significant differences (p = 0.624) for incidence of major brain abnormalities on cerebral ultrasound were found.
No differences were revealed in prevalence of major brain abnormalities between the groups with proven LOS and with clinical signs of LOS. Both infants with a gram negative sepsis developed major brain abnormalities, whereas only two of 66 preterm infants coagulase-negative staphylococci sepsis developed major brain abnormalities.
Purpose
Medulloblastomas (MB) are highly malignant brain tumors that predominantly occur in young infants. Immunotherapy to boost the immune system is emerging as a novel promising approach, but is ...often hampered by inhibitory immune checkpoints. In the present study, we have studied immune checkpoint B7-H3 expression in a tissue cohort of human pediatric MB.
Methods
Expression of B7-H3 was detected by immunohistochemistry and classified via B7-H3 staining intensity and percentage of B7-H3 positive tumor cells. Subsequently, B7-H3 protein expression was distinguished in MB molecular subtypes and correlated to immune cell infiltrates, patient characteristics, and survival.
Results
B7-H3 protein expression was found in 23 out of 24 (96%) human pediatric MB cases and in 17 out of 24 (71%) MB cases > 25% of tumor cells had any level of B7-H3 expression. B7-H3 protein expression was more frequent on Group-4 MB as compared with other molecular subtypes (
p
= 0.02). Tumors with high B7-H3 expression showed less influx of γδT cells (
p
= 0.002) and CD3+ T cells (
p
= 0.041).
Conclusion
Immune checkpoint B7-H3 is differentially expressed by the large majority of pediatric MB. This further warrants the development of novel B7-H3-directed (immuno)therapeutic methods for children with incurable, metastatic, or chemo-resistant MB.
Consumers need information to compare alternatives for markets to function efficiently. Recognizing this, public policies often pair competition with easy access to comparative information. The ...implicit assumption is that comparison friction—the wedge between the availability of comparative information and consumers' use of it—is inconsequential because when information is readily available, consumers will access this information and make effective choices. We examine the extent of comparison friction in the market for Medicare Part D prescription drug plans in the United States. In a randomized field experiment, an intervention group received a letter with personalized cost information. That information was readily available for free and widely advertised. However, this additional step—providing the information rather than having consumers actively access it—had an impact. Plan switching was 28% in the intervention group, versus 17% in the comparison group, and the intervention caused an average decline in predicted consumer cost of about $100 a year among letter recipients—roughly 5% of the cost in the comparison group. Our results suggest that comparison friction can be large even when the cost of acquiring information is small and may be relevant for a wide range of public policies that incorporate consumer choice.
Legionnaires Disease incidence has risen in the Netherlands in recent years. For the majority of the cases, the source of infection is never identified. Two Dutch wastewater treatment plants (WWTPs) ...have previously been identified as source of outbreaks of Legionnaires Disease (LD) among local residents. The objective of this study is to examine if LD patients in the Netherlands are more exposed to aerosols originating from WWTPs than controls.
An atmospheric dispersion model was used to generate nationwide exposure maps of aerosols from 776 WWTPs in the Netherlands. Municipal sewage treatment plants and industrial WWTPs were both included. Exposure of LD cases and controls at the residential address was compared, in a matched case-control design using a conditional logistic regression. Cases were notified LD cases with onset of disease in the period 2013–2018 in the Netherlands (n = 1604).
Aerosols dispersed over a large part of the Netherlands, but modelled concentrations are estimated to be elevated in close proximity to WWTPs. A statistically significant association was found between LD and the calculated annual average aerosol concentrations originating from WWTPs (odds-ratio: 1.32 (1.06–1.63)). This association remained significant when the two outbreak-related WWTPs were removed from the analysis (odds-ratio: 1.28 (1.03–1.58)).
LD cases were more exposed to aerosols from WWTPs than controls. This indicates that exposure to aerosols dispersed from WWTPs caused Legionnaires Disease in residents living near WWTPs in the period 2013–2018. In order to investigate which characteristics of WWTPs are associated with an increased LD risk, the WWTP database should be updated and more data is needed on the presence and survival of aerosolized Legionella bacteria to improve the Legionella dispersion modelling. Furthermore, it is recommended to further investigate how aerosol dispersion of WWTPs can effectively be reduced in order to reduce the potential health risk.
•Exposure to aerosols from WWTPs likely caused LD in people near WWTPs in 2013–2018.•Atmospheric dispersion from wastewater treatment plants (WWTPs) was modelled.•Nationwide exposure maps were made for aerosols from 776 WWTPs in the Netherlands.•Spatial distribution of Legionnaires' disease (LD) was compared to exposure maps.•LD cases were estimated to be more exposed to aerosols from WWTPs than controls.
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