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HO2 uptake kinetics onto ambient aerosols play pivotal roles in tropospheric chemistry but are not fully understood. Field measurements of aerosol chemical and physical properties should be linked to molecular-level kinetics; however, given that the HO2 reactivity of ambient aerosols is low, traditional analytical techniques are unable to achieve this goal. We developed an online approach to precisely investigate the lower-limit values of (i) the HO2 reactivities of ambient gases and aerosols and (ii) HO2 uptake coefficients onto ambient aerosols (γ) during the 2019 Air QUAlity Study (AQUAS) in Yokohama, Japan. We identified the effects of individual chemical components of ambient aerosols on γ. The results were verified in laboratory studies on individual chemical components: transition metals play a key role in HO2 uptake processes, and chemical components indirectly influence such processes (i.e., by altering aerosol surface properties or providing active sites), with smaller particles tending to yield higher γ values than larger particles owing to the limitation of gas-phase diffusion being smaller with micrometer particles and the distribution of depleting species such as transition metal ions being mostly distributed in accumulation mode of aerosol. The modeling of γ utilized transition metal chemistry derived by previous studies, further confirming our conclusion. However, owing to the high NO concentrations in Yokohama, peroxy radical loss onto submicron aerosols has a negligible impact on O3 production rate and sensitivity regime.

Rare mutations in IRF6 and GRHL3 cause Van der Woude syndrome, an autosomal dominant orofacial clefting disorder. Common variants in IRF6 and GRHL3 also contribute risk for isolated orofacial clefting. Similarly, variants within genes that encode receptor tyrosine kinase (RTK) signaling components, including members of the FGF pathway, EPHA3 and SPRY2, also contribute risk for isolated orofacial clefting. In the mouse, loss of Irf6 or perturbation of Fgf signaling leads to abnormal oral epithelial adhesions and cleft palate. Oral adhesions can result from a disruption of periderm formation. Here, we find that IRF6 and SPRY4 signaling interact in periderm function. We crossed Irf6 heterozygous ( Irf6+/-) mice with transgenic mice that express Spry4 in the basal epithelial layer ( TgKRT14::Spry4). While embryos with either of these mutations can have abnormal oral adhesions, using a new quantitative assay, we observed a nonadditive effect of abnormal oral epithelial adhesions in the most severely affected double mutant embryos ( Irf6+/-;TgKRT14::Spry4). At the molecular level, the sites of abnormal oral adhesions maintained periderm-like cells that express keratin 6, but we observed abnormal expression of GRHL3. Together, these data suggest that Irf6 and RTK signaling interact in regulating periderm differentiation and function, as well as provide a rationale to screen for epistatic interactions between variants in IRF6 and RTK signaling pathway genes in human orofacial clefting populations.

Atmospheric aerosols play an important role in air pollution. Aerosol particle chemical composition is highly variable depending on the season, hour of the day, day of the week, meteorology, and location of the measurement site. Long measurement periods and highly time-resolved data are required in order to achieve a statistically relevant amount of data for assessing those variations and evaluating pollution episodes. In this study, we present continuous atmospheric PM1 (particulate matter < 1 µm) concentration and composition measurements at an urban street canyon site located in Helsinki, Finland. The study was performed for 4.5 years (2015–2019) and involved highly time-resolved measurements by taking advantage of a suite of online state-of-the-art instruments such as an aerosol chemical speciation monitor (ACSM), a multi-angle absorption photometer (MAAP), a differential mobility particle sizer (DMPS), and an Aethalometer (AE). PM1 consisted mostly of organics, with mean mass concentrations of 2.89 µg m−3 (53 % of PM1) followed by inorganic species (1.56 µg m−3, 29 %) and equivalent black carbon (eBC, 0.97 µg m−3, 18 %). A trend analysis revealed a decrease in BC from fossil fuel (BCFF), organics, and nitrate over the studied years. Clear seasonal and/or diurnal variations were found for the measured atmospheric PM1 constituents. Particle number and mass size distributions over different seasons revealed the possible influence of secondary organic aerosols (SOAs) during summer and the dominance of ultrafine traffic aerosols during winter. The seasonality of measured constituents also impacted the particle's coating and absorptive properties. The investigation of pollution episodes observed at the site showed that a large fraction of aerosol particle mass was comprised of inorganic species during long-range transport, while during local episodes eBC and organics prevailed together with elevated particle number concentration. Overall, the results increased knowledge of the variability of PM1 concentration and composition in a Nordic traffic site and its implications on urban air quality. Considering the effects of PM mitigation policies in northern Europe in the last decades, the results obtained in this study may be considered illustrative of probable future air quality challenges in countries currently adopting similar environmental regulations.

The aim of this study is to provide an understanding of context-based inquiry teaching within a humanistic perspective on science education by studying pre-service teachers' beliefs about inquiry and their implementations of inquiry in their context-based teaching sequences. Therefore, five pre-service teachers enrolled in a university undergraduate course called 'Inquiry-based chemistry education II' (5 ECTS) were involved in an empirical case study. The pre-service teachers' implementations of inquiry were studied from their reports on self-designed context-based inquiry teaching sequences for students age 13-15, and their beliefs by interviewing them after the course. The results indicate that the most frequent aspects of inquiry, which were implemented, were that inquiry (i) includes a context, (ii) is a way to act, (iii) is a way to think, and (iv) includes source/information evaluation and argumentation. The pre-service teachers' beliefs about inquiry were shown to reflect manifold aspects of inquiry, such as the difficulty in explaining it. However, this difficulty in encapsulating inquiry into a clear-cut definition is not necessarily an impediment to inquiry-based teaching. Furthermore, inquiry is inherently context-bound, and context-based teaching requires extra-situational knowledge from the context and not only declarative knowledge from science. This should be considered to support effective professional development.

Left atrial appendage closure (LAAC) has evolved as a safe alternative to oral anticoagulation therapy for stroke prophylaxis. However, the presence of a patent foramen ovale (PFO) occluder device is considered a relative contraindication. Here we report a successful case of LAAC in the presence of a PFO occluder device. (Level of Difficulty: Beginner.)

In this study, we present results from 12 years of black carbon (BC) measurements at 14 sites around the Helsinki metropolitan area (HMA) and at one background site outside the HMA. The main local sources of BC in the HMA are traffic and residential wood combustion in fireplaces and sauna stoves. All BC measurements were conducted optically, and therefore we refer to the measured BC as equivalent BC (eBC). Measurement stations were located in different environments that represented traffic environment, detached housing area, urban background, and regional background. The measurements of eBC were conducted from 2007 through 2018; however, the times and the lengths of the time series varied at each site. The largest annual mean eBC concentrations were measured at the traffic sites (from 0.67 to 2.64 µg m−3) and the lowest at the regional background sites (from 0.16 to 0.48 µg m−3). The annual mean eBC concentrations at the detached housing and urban background sites varied from 0.64 to 0.80 µg m−3 and from 0.42 to 0.68 µg m−3, respectively. The clearest seasonal variation was observed at the detached housing sites where residential wood combustion increased the eBC concentrations during the cold season. Diurnal variation in eBC concentration in different urban environments depended clearly on the local sources that were traffic and residential wood combustion. The dependency was not as clear for the typically measured air quality parameters, which were here NOx concentration and mass concentration of particles smaller that 2.5 µm in diameter (PM2.5). At four sites which had at least a 4-year-long time series available, the eBC concentrations had statistically significant decreasing trends that varied from −10.4 % yr−1 to −5.9 % yr−1. Compared to trends determined at urban and regional background sites, the absolute trends decreased fastest at traffic sites, especially during the morning rush hour. Relative long-term trends in eBC and NOx were similar, and their concentrations decreased more rapidly than that of PM2.5. The results indicated that especially emissions from traffic have decreased in the HMA during the last decade. This shows that air pollution control, new emission standards, and a newer fleet of vehicles had an effect on air quality.

Residential wood combustion (RWC) is an important contributor to air quality in numerous regions worldwide. This study is the first extensive evaluation of the influence of RWC on ambient air quality in several Nordic cities. We have analysed the emissions and concentrations of PM2.5 in cities within four Nordic countries: in the metropolitan areas of Copenhagen, Oslo, and Helsinki and in the city of Umeå. We have evaluated the emissions for the relevant urban source categories and modelled atmospheric dispersion on regional and urban scales. The emission inventories for RWC were based on local surveys, the amount of wood combusted, combustion technologies and other relevant factors. The accuracy of the predicted concentrations was evaluated based on urban concentration measurements. The predicted annual average concentrations ranged spatially from 4 to 7 µg m−3 (2011), from 6 to 10 µg m−3 (2013), from 4 to more than 13 µg m−3 (2013) and from 9 to more than 13 µg m−3 (2014), in Umeå, Helsinki, Oslo and Copenhagen, respectively. The higher concentrations in Copenhagen were mainly caused by the relatively high regionally and continentally transported background contributions. The annual average fractions of PM2.5 concentrations attributed to RWC within the considered urban regions ranged spatially from 0 % to 15 %, from 0 % to 20 %, from 8 % to 22 % and from 0 % to 60 % in Helsinki, Copenhagen, Umeå and Oslo, respectively. In particular, the contributions of RWC in central Oslo were larger than 40 % as annual averages. In Oslo, wood combustion was used mainly for the heating of larger blocks of flats. In contrast, in Helsinki, RWC was solely used in smaller detached houses. In Copenhagen and Helsinki, the highest fractions occurred outside the city centre in the suburban areas. In Umeå, the highest fractions occurred both in the city centre and its surroundings.

Objective To examine the effect of age on procedural and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) lesions. Methods Literature search was conducted across PubMed, Google Scholar and Web of science, databases till March 2019. Results Seven studies including 7671 patients with an overall follow-up period of 1.5 to 5 years were included in our review. A total of 6299/1372 patients were included in non-elderly and elderly groups, respectively, with mean age and 67%/61% male patients. CTO-PCI was similarly successful in younger and older patients (82.8%, n = 5070 vs. 78.1%, n = 1010). The incidence of short-term outcomes was low across the studies and comparable between the two groups (all-cause mortality: 0.4% younger vs. 0.85% elderly, cerebrovascular accidents: 0.3% vs. 0.4%, major adverse cardiovascular events (MACE): 1.53% vs. 3.72% and major bleeding: 0.57% vs. 2.18%). Long-term outcomes including all-cause mortality (8.89% vs. 29.5%), cardiac mortality (3.72% vs. 15%) and MACE (24.9% vs. 40%) occurred with a higher incidence in elderly patients. When results were segregated according to the success of CTO-PCI, reduced clinical events were noted with successful revascularization in either age group. Conclusion Compared with the younger age group, CTO-PCI in elderly patients is safe and feasible with a comparable incidence of short-term outcomes. In either population, the incidence of long-term outcomes including survival remains a concern but when successful, CTO-PCI may be associated with improvement in terms of multiple patient-important clinical end-points.

Sarcoidosis is a systemic disease with heterogeneous clinical manifestations that is characterized histologically by the presence of noncaseating granulomas in the affected organs. It can be a diagnostic challenge, especially when mimicking malignancy or fungal infections. Previous case reports of sarcoidosis presenting with multiple masses are highly suggestive of infectious or malignant etiology. In this case, our patient presented with enlarged lymph node and was found to have innumerable nodules in the mediastinum, lungs, and liver. Azygos vein enlargement was also seen on radiological imaging, and malignancy was highly suspected; hence, an extensive workup was conducted, including laboratory, radiology and biopsy evaluation, which were diagnostic of sarcoidosis. Our case showed the importance of correlation of the history, physical examination, radiological and histopathologic studies in confirming the diagnosis and the need to rule out other serious infections and malignancies, especially with azygous vein enlargement, which can sometimes be missed in chest radiograph.

This global study, which has been coordinated by the World Meteorological Organization Global Atmospheric Watch (WMO/GAW) programme, aims to understand the behaviour of key air pollutant species during the COVID-19 pandemic period of exceptionally low emissions across the globe. We investigated the effects of the differences in both emissions and regional and local meteorology in 2020 compared with the period 2015–2019. By adopting a globally consistent approach, this comprehensive observational analysis focuses on changes in air quality in and around cities across the globe for the following air pollutants PM2.5, PM10, PMC (coarse fraction of PM), NO2, SO2, NOx, CO, O3 and the total gaseous oxidant (OX = NO2 + O3) during the pre-lockdown, partial lockdown, full lockdown and two relaxation periods spanning from January to September 2020. The analysis is based on in situ ground-based air quality observations at over 540 traffic, background and rural stations, from 63 cities and covering 25 countries over seven geographical regions of the world. Anomalies in the air pollutant concentrations (increases or decreases during 2020 periods compared to equivalent 2015–2019 periods) were calculated and the possible effects of meteorological conditions were analysed by computing anomalies from ERA5 reanalyses and local observations for these periods. We observed a positive correlation between the reductions in NO2 and NOx concentrations and peoples’ mobility for most cities. A correlation between PMC and mobility changes was also seen for some Asian and South American cities. A clear signal was not observed for other pollutants, suggesting that sources besides vehicular emissions also substantially contributed to the change in air quality.As a global and regional overview of the changes in ambient concentrations of key air quality species, we observed decreases of up to about 70% in mean NO2 and between 30% and 40% in mean PM2.5 concentrations over 2020 full lockdown compared to the same period in 2015–2019. However, PM2.5 exhibited complex signals, even within the same region, with increases in some Spanish cities, attributed mainly to the long-range transport of African dust and/or biomass burning (corroborated with the analysis of NO2/CO ratio). Some Chinese cities showed similar increases in PM2.5 during the lockdown periods, but in this case, it was likely due to secondary PM formation. Changes in O3 concentrations were highly heterogeneous, with no overall change or small increases (as in the case of Europe), and positive anomalies of 25% and 30% in East Asia and South America, respectively, with Colombia showing the largest positive anomaly of ~70%. The SO2 anomalies were negative for 2020 compared to 2015–2019 (between ~25 to 60%) for all regions. For CO, negative anomalies were observed for all regions with the largest decrease for South America of up to ~40%. The NO2/CO ratio indicated that specific sites (such as those in Spanish cities) were affected by biomass burning plumes, which outweighed the NO2 decrease due to the general reduction in mobility (ratio of ~60%). Analysis of the total oxidant (OX = NO2 + O3) showed that primary NO2 emissions at urban locations were greater than the O3 production, whereas at background sites, OX was mostly driven by the regional contributions rather than local NO2 and O3 concentrations. The present study clearly highlights the importance of meteorology and episodic contributions (e.g., from dust, domestic, agricultural biomass burning and crop fertilizing) when analysing air quality in and around cities even during large emissions reductions. There is still the need to better understand how the chemical responses of secondary pollutants to emission change under complex meteorological conditions, along with climate change and socio-economic drivers may affect future air quality. The implications for regional and global policies are also significant, as our study clearly indicates that PM2.5 concentrations would not likely meet the World Health Organization guidelines in many parts of the world, despite the drastic reductions in mobility. Consequently, revisions of air quality regulation (e.g., the Gothenburg Protocol) with more ambitious targets that are specific to the different regions of the world may well be required.

The aims of this study were to determine low-achieving students' attitudes towards chemistry and how the attitudes differ within a low achieving group. The most preferred teaching methods were also defined. Empirical data (n = 2949) were collected by stratified sampling from fifteen-year-old Finnish lower-secondary school students as part of a Finnish National Board of Education assessment. The students were divided into five groups according to their achievement in the chemistry-exam. 159 of the students who had deficient exam results were defined as low-achieving (LA) students, and within that group non-native speakers, students with special needs and gender were selected as the background variables. Boys, non-native speakers and those who had special support had more positive attitudes towards chemistry within the LA group. The most preferred teaching methods in the low-achieving group were (i) visiting companies, institutes, museums and exhibitions; (ii) using the internet, videos, magazines and books for studying and (iii) small group working. According to the LA students their teachers should take more into account their wishes for teaching methods. This study suggests that more positive attitudes could lead to a better achievement when the teaching methods are preferred by most of the students. This paper proposes some ideas for both teachers and teacher training.

DNA variation in Interferon Regulatory Factor 6 (IRF6) causes Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate (CLP). However, an etiologic variant in IRF6 has been found in only 70% of VWS families. To test whether DNA variants in regulatory elements cause VWS, we sequenced three conserved elements near IRF6 in 70 VWS families that lack an etiologic mutation within IRF6 exons. A rare mutation (350dupA) was found in a conserved IRF6 enhancer element (MCS9.7) in a Brazilian family. The 350dupA mutation abrogated the binding of p63 and E47 transcription factors to cis-overlapping motifs, and significantly disrupted enhancer activity in human cell cultures. Moreover, using a transgenic assay in mice, the 350dupA mutation disrupted the activation of MCS9.7 enhancer element and led to failure of lacZ expression in all head and neck pharyngeal arches. Interestingly, disruption of the p63 Motif1 and/or E47 binding sites by nucleotide substitution did not fully recapitulate the effect of the 350dupA mutation. Rather, we recognized that the 350dupA created a CAAAGT motif, a binding site for Lef1 protein. We showed that Lef1 binds to the mutated site and that overexpression of Lef1/β-Catenin chimeric protein repressed MCS9.7-350dupA enhancer activity. In conclusion, our data strongly suggest that 350dupA variant is an etiologic mutation in VWS patients and disrupts enhancer activity by a loss- and gain-of-function mechanism, and thus support the rationale for additional screening for regulatory mutations in patients with CLP.

Mutations in interferon regulatory factor 6 (IRF6) account for ∼70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate. In 8 of 45 VWS-affected families lacking a mutation in IRF6, we found coding mutations in grainyhead-like 3 (GRHL3). According to a zebrafish-based assay, the disease-associated GRHL3 mutations abrogated periderm development and were consistent with a dominant-negative effect, in contrast to haploinsufficiency seen in most VWS cases caused by IRF6 mutations. In mouse, all embryos lacking Grhl3 exhibited abnormal oral periderm and 17% developed a cleft palate. Analysis of the oral phenotype of double heterozygote (Irf6(+/-);Grhl3(+/-)) murine embryos failed to detect epistasis between the two genes, suggesting that they function in separate but convergent pathways during palatogenesis. Taken together, our data demonstrated that mutations in two genes, IRF6 and GRHL3, can lead to nearly identical phenotypes of orofacial cleft. They supported the hypotheses that both genes are essential for the presence of a functional oral periderm and that failure of this process contributes to VWS.

We have numerically evaluated how effective selected potential measures would be for reducing the impact of road dust on ambient air particulate matter (PM10). The selected measures included a reduction of the use of studded tyres on light-duty vehicles and a reduction of the use of salt or sand for traction control. We have evaluated these measures for a street canyon located in central Helsinki for four years (2007–2009 and 2014). Air quality measurements were conducted in the street canyon for two years, 2009 and 2014. Two road dust emission models, NORTRIP (NOn-exhaust Road TRaffic Induced Particle emissions) and FORE (Forecasting Of Road dust Emissions), were applied in combination with the Operational Street Pollution Model (OSPM), a street canyon dispersion model, to compute the street increments of PM10 (i.e. the fraction of PM10 concentration originating from traffic emissions at the street level) within the street canyon. The predicted concentrations were compared with the air quality measurements. Both road dust emission models reproduced the seasonal variability of the PM10 concentrations fairly well but under-predicted the annual mean values. It was found that the largest reductions of concentrations could potentially be achieved by reducing the fraction of vehicles that use studded tyres. For instance, a 30 % decrease in the number of vehicles using studded tyres would result in an average decrease in the non-exhaust street increment of PM10 from 10 % to 22 %, depending on the model used and the year considered. Modelled contributions of traction sand and salt to the annual mean non-exhaust street increment of PM10 ranged from 4 % to 20 % for the traction sand and from 0.1 % to 4 % for the traction salt. The results presented here can be used to support the development of optimal strategies for reducing high springtime particulate matter concentrations originating from road dust.

Alkenes and aromatics significantly contribute to the photochemical reactions in the Kanto Region, where the level of ozone frequently exceeds the level for photochemical smog warnings in summer. The major aromatic sources have been cataloged in the Pollutant Release and Transfer Register (PRTR) database in Japan; however, the major alkene sources are not included. We investigated the hourly variations in the volatile organic compound (VOC) concentrations at four sampling sites in the Tokyo Bay coastal area, which has a variety of VOC sources, including the petrochemical industry, chemical facilities, iron–steel plants, and refineries. The 116-component VOC data were used to conduct a positive matrix factorization (PMF) analysis to apportion the VOC sources; then, the source regions were estimated by combining the concentration ratios of the factors with the wind direction data. We used the hourly VOC data for the PMF analysis because alkenes are short-lived. Six factors were estimated using the PMF method and identified as liquefied petroleum gas + industry, aged air mass, fuel evaporation, petrochemical industry, aromatics, and solvent usage. The mean contribution ratios of these six factors were 8.9%, 19.9%, 9.3%, 10.4%, 9.9%, and 14.0%, respectively, whereas the mean contribution ratio of the residual was 27.7%. By combining the alkene concentration and factor contribution ratios with the wind direction, the petrochemical industry in the Kawasaki coastal area was demonstrated to be the main alkene source. In addition, the petrochemical industry makes the largest contribution to ozone production according to the OH radical loss rates of the six factors.

Critically ill patients are known to have a variety of electrolyte abnormalities. Lactic acidosis can frequently be seen secondary to shock states and is usually treated with aggressive volume resuscitation. Interestingly, hypophosphatemia is a potential cause of resistant lactic acidosis, which may not be as commonly identified or considered. We present a case of a 42-year-old man admitted twice over a span of 6 months with an elevated lactate level that did not resolve with volume resuscitation. It was ultimately determined that his lactic acidosis was due to hypophosphatemia after ruling out other potential causes. Phosphate replacement therapy resulted in the normalization of his lactate. In the literature, multiple theories have indicated the association of hypophosphatemia with lactic acidosis though no prior cases exist supporting a direct relationship. In this case, we set forth to evaluate the complicated relationship between all of these factors and to highlight the importance of early detection and treatment of hypophosphatemia, which may be beneficial in treating lactic acidosis.

Reliable and self-consistent data on air quality are needed for an extensive period of time for conducting long-term, or even lifetime health impact assessments. We have modelled the urban-scale concentrations of fine particulate matter (PM2.5) in the Helsinki Metropolitan Area for a period of 35 years, from 1980 to 2014. The regional background concentrations were evaluated based on reanalyses of the atmospheric composition on global and European scales, using the SILAM model. The high-resolution urban computations included both the emissions originated from vehicular traffic (separately exhaust and suspension emissions) and those from small-scale combustion, and were conducted using the road network dispersion model CAR-FMI and the multiple-source Gaussian dispersion model UDM-FMI. The modelled concentrations of PM2.5 agreed fairly well with the measured data at a regional background station and at four urban measurement stations, during 1999–2014. The modelled concentration trends were also evaluated for earlier years, until 1988, using proxy analyses. There was no systematic deterioration of the agreement of predictions and data for earlier years (the 1980s and 1990s), compared with the results for more recent years (2000s and early 2010s). The local vehicular emissions were about 5 times higher in the 1980s, compared with the emissions during the latest considered years. The local small-scale combustion emissions increased slightly over time. The highest urban concentrations of PM2.5 occurred in the 1980s; these have since decreased to about to a half of the highest values. In general, regional background was the largest contribution in this area. Vehicular exhaust has been the most important local source, but the relative shares of both small-scale combustion and vehicular non-exhaust emissions have increased in time. The study has provided long-term, high-resolution concentration databases on regional and urban scales that can be used for the assessment of health effects associated with air pollution.

Abstract Background Electroencephalography at hospital presentation may offer important insights regarding prognosis that can inform understanding of cerebral malaria (CM) pathophysiology and potentially guide patient selection and risk stratification for future clinical trials. Electroencephalogram (EEG) findings in children with CM in Uganda and Malawi were compared and associations between admission EEG findings and outcome across this diverse population were assessed. Demographic, clinical and admission EEG data from Ugandan and Malawian children admitted from 2009 to 2012 with CM were gathered, and survivors assessed for neurological abnormalities at discharge. Results 281 children were enrolled (Uganda n = 122, Malawi n = 159). The Malawian population was comprised only of retinopathy positive children (versus 72.5% retinopathy positive in Uganda) and were older (4.2 versus 3.7 years; p = 0.046), had a higher HIV prevalence (9.0 versus 2.8%; p = 0.042), and worse hyperlactataemia (7.4 versus 5.2 mmol/L; p