An Adverse Outcome Pathway for Sensitization of the Respiratory Tract by Low-Molecular-Weight Chemicals: Building Evidence to Support the Utility of In Vitro and In Silico Methods in a Regulatory Context

Sensitization of the respiratory tract is an important occupational health challenge, and understanding the mechanistic basis of this effect is necessary to support the development of toxicological tools to detect chemicals that may cause it. Here we use the adverse outcome pathway (AOP) framework to organize information that may better inform our understanding of sensitization of the respiratory tract, building on a previously published skin sensitization AOP, relying on literature evidence linked to low-molecular-weight organic chemicals and excluding other known respiratory sensitizers acting via different molecular initiating events. The established key events (KEs) are as follows: (1) covalent binding of chemicals to proteins, (2) activation of cellular danger signals (inflammatory cytokines and chemokines and cytoprotective gene pathways), (3) dendritic cell activation and migration, (4) activation, proliferation, and polarization of T cells, and (5) sensitization of the respiratory tract. These events mirror the skin sensitization AOP but with specific differences. For example, there is some evidence that respiratory sensitizers bind preferentially to lysine moieties, whereas skin sensitizers bind to both cysteine and lysine. Furthermore, exposure to respiratory sensitizers seems to result in cell behavior for KEs 2 and 3, as well as the effector T cell response, in general skewing toward cytokine secretions predominantly associated with T helper 2 (Th2) response. Knowledge gaps include the lack of understanding of which KE(s) drive the Th2 polarization. The construction of this AOP may provide insight into predictive tests that would in combination support the discrimination of respiratory-sensitizing from non- and skin-sensitizing chemicals, a clear regulatory need

A hand hygiene intervention to decrease infections among children attending day care centers: Design of a cluster randomized controlled trial

Background: Day care center attendance has been recognized as a risk factor for acquiring gastrointestinal and respiratory infections, which can be prevented with adequate hand hygiene (HH). Based on previous studies on environmental and sociocognitive determinants of caregivers' compliance with HH guidelines in day care centers (DCCs), an intervention has been developed aiming to improve caregivers' and children's HH compliance and decrease infections among children attending DCCs. The aim of this paper is to describe the design of a cluster randomized controlled trial to evaluate the effectiveness of this intervention.Methods/design: The intervention will be evaluated in a two-arm cluster randomized controlled trial among 71 DCCs in the Netherlands. In total, 36 DCCs will receive the intervention consisting of four components: 1) HH products (dispensers and refills for paper towels, soap, alcohol-based hand sanitizer, and hand cream); 2) training to educate about the Dutch national HH guidelines; 3) two team training sessions aimed at goal setting and formulating specific HH improvement activities; and 4) reminders and cues to action (posters/stickers). Intervention DCCs will be compared to 35 control DCCs continuing usual practice. The primary outcome measure will be observed HH compliance of caregivers and children, measured at baseline and one, three, and six months after start of the intervention. The secondary outcome measure will be the incidence of gastrointestinal and respiratory infections in 600 children attending DCCs, monitored over six months by parents using a calendar to mark th

Nature Balance 2002

To reach a National Ecological Network (NEN), further efforts in spatial planning of the green space are necessary. This is the main outcome of Nature Balance 2002. Nature has high social and economical values. According to the inhabitants of The Netherlands, nature areas and variation in landscape contribute significantly to their well-being. Nature and landscape also have ion and increases prices of housings in green areas. Evidence grows that green surroundings benefit people?s health. The European Union has composed a list of international protected plants and animal species. The Netherlands has accepted these duties as established in the Birds and Habitats Directives. More insight in the occurrence of these species in specific habitats is needed. This may increase public acceptance and implementation of species protection policies. In order to meet nature targets, spatial planning of the green environment is a necessity. Only in this way the coherent National Ecological Network can be realized. Offers of land to be incorporated in the NEN have increased during the last three years. The Dutch Government plans to halve the budget for acquiring land and instead have private land owners participate in nature management. Signing long-term contracts with these private owners can contribute to the nature goals, but is hardly less expensive than buying the land. Also more spatial protection of the NEN will be needed when less land for nature development is purchased.Om de Ecologische Hoofdstructuur te realiseren is verdere ordening van de groene ruimte noodzakelijk. Dat is de hoofdconclusie uit de Natuurbalans 2002. Natuur heeft grote sociale en economische betekenis. De inwoners van Nederland vinden dat natuurgebieden en gevarieerde landschappen een wezenlijke bijdrage leveren aan hun welzijn. Daarnaast hebben natuur en landschap een substantikle economische waarde, onder andere vanwege de inkomsten uit recreatie in natuurgebieden en de bereidheid van kopers om meer te betalen voor een huis in een groen gebied. Er zijn bovendien steeds meer gegevens die er op wijzen dat de gezondheid van mensen baat heeft bij een groene omgeving. Op Europees niveau is een lijst van internationaal te beschermen planten- en diersoorten samengesteld. Nederland is hiervoor verplichtingen aangegaan die zijn vastgelegd in de Vogelrichtlijn en Habitatrichtlijn van de Europese Unie. Om het maatschappelijke draagvlak voor dit soortenbeleid te vergroten en het beleid hanteerbaar te maken moet meer zicht komen op het verband tussen het voorkomen van individuen en populaties van soorten en de ligging van hun leefgebieden. Voor het bereiken van de natuurdoelen is ordening van de groene ruimte nodig om het beoogde samenhangende netwerk van natuurgebieden, de Ecologische Hoofdstructuur (EHS) te realiseren. Het aanbod van aan te kopen grond voor de realisatie van de EHS neemt de laatste drie jaar toe. De nieuwe regering heeft het voornemen het jaarlijkse budget voor de aankoop van grond te halveren en meer particuliere eigenaren in te zetten bij het ontwikkelen en beheren van natuur. Langjarige contracten met deze particulieren kunnen een bijdrage aan de natuurdoelen leveren, maar blijken nauwelijks goedkoper dan aankoop. Ook vergt een samenhangende EHS, indien minder grond voor natuurontwikkeling wordt opgekocht, een goede ruimtelijke bescherming

Costs and effects of screening and treating low risk women with a singleton pregnancy for asymptomatic bacteriuria, the ASB study

<p>Abstract</p> <p>Background</p> <p>The prevalence of asymptomatic bacteriuria (ASB) in pregnancy is 2-10% and is associated with both maternal and neonatal adverse outcomes as pyelonephritis and preterm delivery. Antibiotic treatment is reported to decrease these adverse outcomes although the existing evidence is of poor quality.</p> <p>Methods/Design</p> <p>We plan a combined screen and treat study in women with a singleton pregnancy. We will screen women between 16 and 22 weeks of gestation for ASB using the urine dipslide technique. The dipslide is considered positive when colony concentration ≥10⁵ colony forming units (CFU)/mL of a single microorganism or two different colonies but one ≥10⁵ CFU/mL is found, or when Group B Streptococcus bacteriuria is found in any colony concentration. Women with a positive dipslide will be randomly allocated to receive nitrofurantoin or placebo 100 mg twice a day for 5 consecutive days (double blind). Primary outcomes of this trial are maternal pyelonephritis and/or preterm delivery before 34 weeks. Secondary outcomes are neonatal and maternal morbidity, neonatal weight, time to delivery, preterm delivery rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal admission days and costs.</p> <p>Discussion</p> <p>This trial will provide evidence for the benefit and cost-effectiveness of dipslide screening for ASB among low risk women at 16–22 weeks of pregnancy and subsequent nitrofurantoin treatment.</p> <p>Trial registration</p> <p>Dutch trial registry: NTR-3068</p

Adapting to climate change in The Netherlands: an inventory of climate adaptation options and ranking of alternatives

In many countries around the world impacts of climate change are assessed and adaptation options identified. We describe an approach for a qualitative and quantitative assessment of adaptation options to respond to climate change in the Netherlands. The study introduces an inventory and ranking of adaptation options based on stakeholder analysis and expert judgement, and presents some estimates of incremental costs and benefits. The qualitative assessment focuses on ranking and prioritisation of adaptation options. Options are selected and identified and discussed by stakeholders on the basis of a sectoral approach, and assessed with respect to their importance, urgency and other characteristics by experts. The preliminary quantitative assessment identifies incremental costs and benefits of adaptation options. Priority ranking based on a weighted sum of criteria reveals that in the Netherlands integrated nature and water management and risk based policies rank high, followed by policies aiming at 'climate proof' housing and infrastructure

Climate policy and ancillary benefits : a survey and integration into the modelling of international negotiations on climate change

Currently informal and formal international negotiations on climate change take place in an intensive way since the Kyoto Protocol expires already in 2012. A post-Kyoto regulation to combat global warming is not yet stipulated. Due to rapidly increasing greenhouse gas emission levels, industrialized countries urge major polluters from the developing world like China and India to participate in a future agreement. Whether these developing countries will do so, depends on the prevailing incentives to participate in international climate protection efforts. This paper identifies ancillary benefits of climate policy to provide important incentives to attend a new international protocol and to positively affect the likelihood of accomplishing a post-Kyoto agreement which includes commitments of developing countries

The estimated disease burden of acute COVID-19 in the Netherlands in 2020, in disability-adjusted life-years

The impact of COVID-19 on population health is recognised as being substantial, yet few studies have attempted to quantify to what extent infection causes mild or moderate symptoms only, requires hospital and/or ICU admission, results in prolonged and chronic illness, or leads to premature death. We aimed to quantify the total disease burden of acute COVID-19 in the Netherlands in 2020 using the disability-adjusted life-years (DALY) measure, and to investigate how burden varies between age-groups and occupations. Using standard methods and diverse data sources (mandatory notifications, population-level seroprevalence, hospital and ICU admissions, registered COVID-19 deaths, and the literature), we estimated years of life lost (YLL), years lived with disability, DALY and DALY per 100,000 population due to COVID-19, excluding post-acute sequelae, stratified by 5-year age-group and occupation category. The total disease burden due to acute COVID-19 was 286,100 (95% CI: 281,700-290,500) DALY, and the per-capita burden was 1640 (95% CI: 1620-1670) DALY/100,000, of which 99.4% consisted of YLL. The per-capita burden increased steeply with age, starting from 60 to 64 years, with relatively little burden estimated for persons under 50 years old. SARS-CoV-2 infection and associated premature mortality was responsible for a considerable direct health burden in the Netherlands, despite extensive public health measures. DALY were much higher than for other high-burden infectious diseases, but lower than estimated for coronary heart disease. These findings are valuable for informing public health decision-makers regarding the expected COVID-19 health burden among population subgroups, and the possible gains from targeted preventative interventions

Age-specific severity of severe acute respiratory syndrome coronavirus 2 in February 2020 to June 2021 in the Netherlands

BACKGROUND: The severity of Severe Acute Respiratory Syndrome Coronavirus 2 infection varies with age and time. Here, we quantify how age-specific risks of hospitalization, intensive care unit (ICU) admission, and death upon infection changed from February 2020 to June 2021 in the Netherlands. METHODS: A series of large representative serology surveys allowed us to estimate age-specific numbers of infections in three epidemic periods (late-February 2020 to mid-June 2020, mid-June 2020 to mid-February 2021, and mid-February 2021 to late-June 2021). We accounted for reinfections and breakthrough infections. Severity measures were obtained by combining infection numbers with age-specific numbers of hospitalization, ICU admission, and excess all-cause deaths. RESULTS: There was an accelerating, almost exponential, increase in severity with age in each period. The rate of increase with age was the highest for death and the lowest for hospitalization. In late-February 2020 to mid-June 2020, the overall risk of hospitalization upon infection was 1.5% (95% confidence interval [CI] 1.3-1.8%), the risk of ICU admission was 0.36% (95% CI: 0.31-0.42%), and the risk of death was 1.2% (95% CI: 1.0-1.4%). The risk of hospitalization was significantly increased in mid-June 2020 to mid-February 2021, while the risk of ICU admission remained stable over time. The risk of death decreased over time, with a significant drop among ≥70-years-olds in mid-February 2021 to late-June 2021; COVID-19 vaccination started early January 2021. CONCLUSION: Whereas the increase in severity of Severe Acute Respiratory Syndrome Coronavirus 2 with age remained stable, the risk of death upon infection decreased over time. A significant drop in risk of death among elderly coincided with the introduction of COVID-19 vaccination

Gevoeligheidsanalyse berekening ammoniakemissie; Effect van variatie in penegratiegraden en emissiefactoren op de ammoniakemissie

Voor het monitoren van het ammoniakbeleid gericht op de landbouw is het van belang inzicht te hebben in de factoren die de hoogte van de ammoniakemissie beïnvloeden. Emissiefactoren en penetratie van emissiebeperkende technieken zijn voorbeelden van deze factoren. De vraag is wat het effect is van variatie rondom emissiefactoren en penetratiegraden op de hoogte van de ammoniakemissie. In het algemeen blijkt dat variatie rondom de emissiefactoren van meer invloed is op de hoogte van de ammoniakemissie dan de penetratiegraden van staltypen en mestaanwendingstechnieken. Deze conclusie geldt voor de monitoring van de ammoniakemissie op nationaal en provinciaal niveau. Op kleinere schaal kan de structuur van de landbouw sterk afwijken van het nationale c.q. provinciale beeld. Dit kan van invloed zijn op de prioriteitsstelling bij de verbetering van de monitoring van de ammoniakemissie