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We analysed the effect of the 2018 European drought on greenhouse gas (GHG) exchange of five North European mire ecosystems. The low precipitation and high summer temperatures in Fennoscandia led to a lowered water table in the majority of these mires. This lowered both carbon dioxide (CO 2 ) uptake and methane (CH 4 ) emission during 2018, turning three out of the five mires from CO 2 sinks to sources. The calculated radiative forcing showed that the drought-induced changes in GHG fluxes first resulted in a cooling effect lasting 15–50 years, due to the lowered CH 4 emission, which was followed by warming due to the lower CO 2 uptake. This article is part of the theme issue ‘Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale’.

To determine the etiology of community-acquired pneumonia in the adult population of a defined area, specific antibody responses in paired serum samples, levels of circulating pneumococcal immune complexes in serum samples, and pneumococcal antigen in urine were measured. Samples (304 paired serum samples and 300 acute urine samples) were obtained from 345 patients ⩾15 years old with community-acquired, radiologically confirmed pneumonia, which comprised all cases in the population of 4 municipalities in eastern Finland during 1 year. Specific infecting organisms were identified in 183 patients (including 49 with mixed infection), as follows: Streptococcus pneumoniae, 125 patients; Haemophilus influenzae, 12; Moraxella catarrhalis, 8; chlamydiae, 37 (of which, Chlamydia pneumoniae, 30); Mycoplasma pneumoniae, 30; and virus species, 27. The proportion of patients with pneumococcal infections increased and of those with Mycoplasma infections decreased with age, but for each age group, the etiologic profile was similar among inpatients and among outpatients. S. pneumoniae was the most important etiologic agent. The annual incidence of pneumococcal pneumonia per 1000 inhabitants aged ⩾60 years was 8.0.

The patterned microtopography of subarctic mires generates a variety of environmental conditions, and carbon dioxide (CO2) and methane (CH4) dynamics vary spatially among different plant community types (PCTs). We studied the CO2 and CH4 exchange between a subarctic fen and the atmosphere at Kaamanen in northern Finland based on flux chamber and eddy covariance measurements in 2017–2018. We observed strong spatial variation in carbon dynamics between the four main PCTs studied, which were largely controlled by water table level and differences in vegetation composition. The ecosystem respiration (ER) and gross primary productivity (GPP) increased gradually from the wettest PCT to the drier ones, and both ER and GPP were larger for all PCTs during the warmer and drier growing season 2018. We estimated that in 2017 the growing season CO2 balances of the PCTs ranged from −20 g C m−2 (Trichophorum tussock PCT) to 64 g C m−2 (string margin PCT), while in 2018 all PCTs were small CO2 sources (10–22 g C m−2). We observed small growing season CH4 emissions (< 1 g C m−2) from the driest PCT, while the other three PCTs had significantly larger emissions (mean 7.9, range 5.6–10.1 g C m−2) during the two growing seasons. Compared to the annual CO2 balance (−8.5 ± 4.0 g C m−2) of the fen in 2017, in 2018 the annual balance (−5.6 ± 3.7 g C m−2) was affected by an earlier onset of photosynthesis in spring, which increased the CO2 sink, and a drought event during summer, which decreased the sink. The CH4 emissions were also affected by the drought. The annual CH4 balance of the fen was 7.3 ± 0.2 g C m−2 in 2017 and 6.2 ± 0.1 g C m−2 in 2018. Thus, the carbon balance of the fen was close to zero in both years. The PCTs that were adapted to drier conditions provided ecosystem-level resilience to carbon loss due to water level drawdown.

The subarctic landscape consists of a mosaic of forest, peatland, and aquatic ecosystems and their ecotones. The carbon (C) exchange between ecosystems and the atmosphere through carbon dioxide (CO2) and methane (CH4) fluxes varies spatially and temporally among these ecosystems. Our study area in Kaamanen in northern Finland covered 7 km2 of boreal subarctic landscape with upland forest, open peatland, pine bogs, and lakes. We measured the CO2 and CH4 fluxes with eddy covariance and chambers between June 2017 and June 2019 and studied the C flux responses to varying meteorological conditions. The landscape area was an annual CO2 sink of −45 ± 22 and −33 ± 23 g C m−2 and a CH4 source of 3.0 ± 0.2 and 2.7 ± 0.2 g C m−2 during the first and second study years, respectively. The pine forest had the largest contribution to the landscape-level CO2 sink, −126 ± 21 and −101 ± 19 g C m−2, and the fen to the CH4 emissions, 7.8 ± 0.2 and 6.3 ± 0.3 g C m−2, during the first and second study years, respectively. The lakes within the area acted as CO2 and CH4 sources to the atmosphere throughout the measurement period, and a lake located downstream from the fen with organic sediment showed 4-fold fluxes compared to a mineral sediment lake. The annual C balances were affected most by the rainy peak growing season in 2017, the warm summer in 2018, and a heatwave and drought event in July 2018. The rainy period increased ecosystem respiration (ER) in the pine forest due to continuously high soil moisture content, and ER was on a level similar to the following, notably warmer, summer. A corresponding ER response to abundant precipitation was not observed for the fen ecosystem, which is adapted to high water table levels, and thus a higher ER sum was observed during the warm summer 2018. During the heatwave and drought period, similar responses were observed for all terrestrial ecosystems, with decreased gross primary productivity and net CO2 uptake, caused by the unfavourable growing conditions and plant stress due to the soil moisture and vapour pressure deficits. Additionally, the CH4 emissions from the fen decreased during and after the drought. However, the timing and duration of drought effects varied between the fen and forest ecosystems, as C fluxes were affected sooner and had a shorter post-drought recovery time in the fen than forest. The differing CO2 flux response to weather variations showed that terrestrial ecosystems can have a contrasting impact on the landscape-level C balance in a changing climate, even if they function similarly most of the time.

Respiratory exposure to organic dust induces chronic pulmonary diseases both in farmers and horses. The aim of this study was to examine the variation of dustiness and hygiene quality of peat moss bedding. Materials studied were weakly decomposed sphagnum peat (A), weakly decomposed sphagnum peat warmed up in storage (> 30 degrees C) (B) and two more decomposed few-flowered sedge peats (C and D). The geometric mean of mesophilic fungi, thermotolerant fungi and thermophilic actinomycetes were determined from the material. Samples of inhalable dust and endotoxins were collected with IOM samplers and respirable dust with 10M foam samplers when the peat was rotated in a cylinder. The number of particles was detected with an optical particle counter. An LAL assay was used for analysing endotoxins from the filter samples. There were differences in the hygiene quality and dustiness between peat materials (p < 0.01). The geometric mean of fungi was smallest in material A. Warming-up increased the number of fungi in sphagnum peat, but on the other hand, it decreased the content of endotoxin (p < 0.01). Few-flowered peat materials contained thermophilic actinomycetes and material D also contained Aspergillus fumigatus. The concentrations of inhalable dust, respirable dust and the number of particles were smaller in the few-flowered peats (C-D) than in the sphagnum peats (A-B). It is concluded that there are differences in the dustiness and hygiene quality of peat bedding.

Andrew Hattersley, Noel Morgan, Juha Kere and colleagues identify de novo activating germline STAT3 mutations in five unrelated individuals with early-onset multi-organ autoimmune disease. Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in hyper IgE syndrome.

ObjectiveTo estimate scent dogs’ diagnostic accuracy in identification of people infected with SARS-CoV-2 in comparison with reverse transcriptase polymerase chain reaction (RT-PCR). We conducted a randomised triple-blinded validation trial, and a real-life study at the Helsinki-Vantaa International Airport, Finland.MethodsFour dogs were trained to detect COVID-19 using skin swabs from individuals tested for SARS-CoV-2 by RT-PCR. Our controlled triple-blinded validation study comprised four identical sets of 420 parallel samples (from 114 individuals tested positive and 306 negative by RT-PCR), randomly presented to each dog over seven trial sessions. In a real-life setting the dogs screened skin swabs from 303 incoming passengers all concomitantly examined by nasal swab SARS-CoV-2 RT-PCR. Our main outcomes were variables of diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value) for scent dog identification in comparison with RT-PCR.ResultsOur validation experiments had an overall accuracy of 92% (95% CI 90% to 93%), a sensitivity of 92% (95% CI 89% to 94%) and a specificity of 91% (95% CI 89% to 93%) compared with RT-PCR. For our dogs, trained using the wild-type virus, performance was less accurate for the alpha variant (89% for confirmed wild-type vs 36% for alpha variant, OR 14.0, 95% CI 4.5 to 43.4). In the real-life setting, scent detection and RT-PCR matched 98.7% of the negative swabs. Scant airport prevalence (0.47%) did not allow sensitivity testing; our only SARS-CoV-2 positive swab was not identified (alpha variant). However, ad hoc analysis including predefined positive spike samples showed a total accuracy of 98% (95% CI 97% to 99%).ConclusionsThis large randomised controlled triple-blinded validation study with a precalculated sample size conducted at an international airport showed that trained scent dogs screen airport passenger samples with high accuracy. One of our findings highlights the importance of continuous retraining as new variants emerge. Using scent dogs may present a valuable approach for high-throughput, rapid screening of large numbers of people.

Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny.

Background We conducted a phase I study with a granulocyte macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, ONCOS-102, in patients with solid tumors refractory to available treatments. The objectives of the study were to determine the optimal dose for further use and to assess the safety, tolerability and adverse event (AE) profile of ONCOS-102. Further, the response rate and overall survival were evaluated as well as preliminary evidence of disease control. As an exploratory endpoint, the effect of ONCOS 102 on biological correlates was examined. Methods The study was conducted using a classic 3 + 3 dose escalation study design involving 12 patients. Patients were repeatedly treated intratumorally with ONCOS-102 plus daily low-dose oral cyclophosphamide (CPO). Tumor response was evaluated with diagnostic positron emission tomography (PET) and computed tomography (CT). Tumor biopsies were collected at baseline and after treatment initiation for analysis of immunological correlates. Peripheral blood mononuclear cells (PBMCs) were collected at baseline and during the study to assess antigen specificity of CD8+ T cells by interferon gamma (IFNγ) enzyme linked immunospot assay (ELISPOT). Results No dose limiting toxicity (DLT) or maximum tolerated dose (MTD) was identified for ONCOS-102. Four out of ten (40 %) evaluable patients had disease control based on PET/CT scan at 3 months and median overall survival was 9.3 months. A short-term increase in systemic pro-inflammatory cytokines and a prominent infiltration of TILs to tumors was seen post-treatment in 11 out of 12 patients. Two patients showed marked infiltration of CD8+ T cells to tumors and concomitant systemic induction of tumor-specific CD8+ T cells. Interestingly, high expression levels of genes associated with activated T H 1 cells and T H 1 type immune profile were observed in the post-treatment biopsies of these two patients. Conclusions ONCOS-102 is safe and well tolerated at the tested doses. All three examined doses may be used in further development. There was evidence of antitumor immunity and signals of clinical efficacy. Importantly, treatment resulted in infiltration of CD8+ T cells to tumors and up-regulation of PD-L1, highlighting the potential of ONCOS-102 as an immunosensitizing agent for combinatory therapies with checkpoint inhibitors. Trial registration NCT01598129 . Registered 19/04/2012