Broader functions of TIR domains in Arabidopsis immunity.

TIR domains are NAD-degrading enzymes that function during immune signaling in prokaryotes, plants, and animals. In plants, most TIR domains are incorporated into intracellular immune receptors termed TNLs. In Arabidopsis, TIR-derived small molecules bind and activate EDS1 heterodimers, which in turn activate RNLs, a class of cation channel-forming immune receptors. RNL activation drives cytoplasmic Ca2+ influx, transcriptional reprogramming, pathogen resistance, and host cell death. We screened for mutants that suppress an RNL activation mimic allele and identified a TNL, SADR1. Despite being required for the function of an autoactivated RNL, SADR1 is not required for defense signaling triggered by other tested TNLs. SADR1 is required for defense signaling initiated by some transmembrane pattern recognition receptors and contributes to the unbridled spread of cell death in lesion simulating disease 1. Together with RNLs, SADR1 regulates defense gene expression at infection site borders, likely in a non-cell autonomous manner. RNL mutants that cannot sustain this pattern of gene expression are unable to prevent disease spread beyond localized infection sites, suggesting that this pattern corresponds to a pathogen containment mechanism. SADR1 potentiates RNL-driven immune signaling not only through the activation of EDS1 but also partially independently of EDS1. We studied EDS1-independent TIR function using nicotinamide, an NADase inhibitor. Nicotinamide decreased defense induction from transmembrane pattern recognition receptors and decreased calcium influx, pathogen growth restriction, and host cell death following intracellular immune receptor activation. We demonstrate that TIR domains can potentiate calcium influx and defense and are thus broadly required for Arabidopsis immunity.

The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe.

BACKGROUND: We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe. METHODS: We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use. RESULTS: The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53). CONCLUSIONS: The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Rubisco proton production can drive the elevation of CO2 within condensates and carboxysomes.

Membraneless organelles containing the enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) are a common feature of organisms utilizing CO2 concentrating mechanisms to enhance photosynthetic carbon acquisition. In cyanobacteria and proteobacteria, the Rubisco condensate is encapsulated in a proteinaceous shell, collectively termed a carboxysome, while some algae and hornworts have evolved Rubisco condensates known as pyrenoids. In both cases, CO2 fixation is enhanced compared with the free enzyme. Previous mathematical models have attributed the improved function of carboxysomes to the generation of elevated CO2 within the organelle via a colocalized carbonic anhydrase (CA) and inwardly diffusing HCO3-, which have accumulated in the cytoplasm via dedicated transporters. Here, we present a concept in which we consider the net of two protons produced in every Rubisco carboxylase reaction. We evaluate this in a reaction-diffusion compartment model to investigate functional advantages these protons may provide Rubisco condensates and carboxysomes, prior to the evolution of HCO3- accumulation. Our model highlights that diffusional resistance to reaction species within a condensate allows Rubisco-derived protons to drive the conversion of HCO3- to CO2 via colocalized CA, enhancing both condensate [CO2] and Rubisco rate. Protonation of Rubisco substrate (RuBP) and product (phosphoglycerate) plays an important role in modulating internal pH and CO2 generation. Application of the model to putative evolutionary ancestors, prior to contemporary cellular HCO3- accumulation, revealed photosynthetic enhancements along a logical sequence of advancements, via Rubisco condensation, to fully formed carboxysomes. Our model suggests that evolution of Rubisco condensation could be favored under low CO2 and low light environments.

Rubisco, the imperfect winner: it's all about the base.

Rubisco catalysis is complex and includes an activation step through the formation of a carbamate at the conserved active site lysine residue and the formation of a highly reactive enediol that is the key to its catalytic reaction. The formation of this enediol is both the basis of its success and its Achilles' heel, creating imperfections to its catalytic efficiency. While Rubisco originally evolved in an atmosphere of high CO2, the earth's multiple oxidation events provided challenges to Rubisco through the fixation of O2 that competes with CO2 at the active site. Numerous catalytic screens across the Rubisco superfamily have identified significant variation in catalytic properties that have been linked to large and small subunit sequences. Despite this, we still have a rudimentary understanding of Rubisco's catalytic mechanism and how the evolution of kinetic properties has occurred. This review identifies the lysine base that functions both as an activator and a proton abstractor to create the enediol as a key to understanding how Rubisco may optimize its kinetic properties. The ways in which Rubisco and its partners have overcome catalytic and activation imperfections and thrived in a world of high O2, low CO2, and variable climatic regimes is remarkable.

The Chlamydomonas reinhardtii chloroplast envelope protein LCIA transports bicarbonate in planta.

LCIA (low CO2-inducible protein A) is a chloroplast envelope protein associated with the CO2-concentrating mechanism of the green alga Chlamydomonas reinhardtii. LCIA is postulated to be a HCO3- channel, but previous studies were unable to show that LCIA was actively transporting bicarbonate in planta. Therefore, LCIA activity was investigated more directly in two heterologous systems: an Escherichia coli mutant (DCAKO) lacking both native carbonic anhydrases and an Arabidopsis mutant (ßca5) missing the plastid carbonic anhydrase ßCA5. Neither DCAKO nor ßca5 can grow in ambient CO2 conditions, as they lack carbonic anhydrase-catalyzed production of the necessary HCO3- concentration for lipid and nucleic acid biosynthesis. Expression of LCIA restored growth in both systems in ambient CO2 conditions, which strongly suggests that LCIA is facilitating HCO3- uptake in each system. To our knowledge, this is the first direct evidence that LCIA moves HCO3- across membranes in bacteria and plants. Furthermore, the ßca5 plant bioassay used in this study is the first system for testing HCO3- transport activity in planta, an experimental breakthrough that will be valuable for future studies aimed at improving the photosynthetic efficiency of crop plants using components from algal CO2-concentrating mechanisms.

Tobacco use in first-episode psychosis, a multinational EU-GEI study.

BACKGROUND: Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis. METHODS: The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use. RESULTS: After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1-3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2-2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (ß = -2.3; p ⩽ 0.001; 95% CI [-3.7 to -0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0-1.8]); however, these results were no longer significant after controlling for cannabis use. CONCLUSIONS: Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.

Mineral micronutrient status and spatial distribution among the Ethiopian population.

Multiple micronutrient deficiencies are widespread in Ethiopia. However, the distribution of Se and Zn deficiency risks has previously shown evidence of spatially dependent variability, warranting the need to explore this aspect for wider micronutrients. Here, blood serum concentrations for Ca, Mg, Co, Cu and Mo were measured (n 3102) on samples from the Ethiopian National Micronutrient Survey. Geostatistical modelling was used to test spatial variation of these micronutrients for women of reproductive age, who represent the largest demographic group surveyed (n 1290). Median serum concentrations were 8·6 mg dl-1 for Ca, 1·9 mg dl-1 for Mg, 0·4 µg l-1 for Co, 98·8 µg dl-1 for Cu and 0·2 µg dl-1 for Mo. The prevalence of Ca, Mg and Co deficiency was 41·6 %, 29·2 % and 15·9 %, respectively; Cu and Mo deficiency prevalence was 7·6 % and 0·3 %, respectively. A higher prevalence of Ca, Cu and Mo deficiency was observed in north western, Co deficiency in central and Mg deficiency in north eastern parts of Ethiopia. Serum Ca, Mg and Mo concentrations show spatial dependencies up to 140-500 km; however, there was no evidence of spatial correlations for serum Co and Cu concentrations. These new data indicate the scale of multiple mineral micronutrient deficiency in Ethiopia and the geographical differences in the prevalence of deficiencies suggesting the need to consider targeted responses during the planning of nutrition intervention programmes.

Mehler reaction plays a role in C3 and C4 photosynthesis under shade and low CO2.

Alternative electron fluxes such as the cyclic electron flux (CEF) around photosystem I (PSI) and Mehler reaction (Me) are essential for efficient photosynthesis because they generate additional ATP and protect both photosystems against photoinhibition. The capacity for Me can be estimated by measuring O2 exchange rate under varying irradiance and CO2 concentration. In this study, mass spectrometric measurements of O2 exchange were made using leaves of representative species of C3 and C4 grasses grown under natural light (control; PAR ~ 800 µmol quanta m-2 s-1) and shade (~ 300 µmol quanta m-2 s-1), and in representative species of gymnosperm, liverwort and fern grown under natural light. For all control grown plants measured at high CO2, O2 uptake rates were similar between the light and dark, and the ratio of Rubisco oxygenation to carboxylation (Vo/Vc) was low, which suggests little potential for Me, and that O2 uptake was mainly due to photorespiration or mitochondrial respiration under these conditions. Low CO2 stimulated O2 uptake in the light, Vo/Vc and Me in all species. The C3 species had similar Vo/Vc, but Me was highest in the grass and lowest in the fern. Among the C4 grasses, shade increased O2 uptake in the light, Vo/Vc and the assimilation quotient (AQ), particularly at low CO2, whilst Me was only substantial at low CO2 where it may contribute 20-50% of maximum electron flow under high light.

Seeded optical parametric generation in CdSiP2 pumped by a Raman fiber amplifier at 1.24 µm.

We report a seeded optical parametric generator (OPG) producing tunable radiation from 4.2-4.6 µm. The seeded OPG employs a 13 mm long CdSiP2 (CSP) crystal cut for non-critical phase-matching, pumped by a nanosecond-pulsed, MHz repetition rate Raman fiber amplifier system at 1.24 µm. A filtered, continuous-wave fiber supercontinuum source at 1.72 µm is used as the seed. The source generates up to 0.25 W of mid-infrared (MIR) idler power with a total pump conversion of 42% (combined signal and idler).

Predictors of treatment resistant schizophrenia: a systematic review of prospective observational studies.

Treatment-resistant schizophrenia, affecting approximately 20-30% of patients with schizophrenia, has a high burden both for patients and healthcare services. There is a need to identify treatment resistance earlier in the course of the illness, in order that effective treatment, such as clozapine, can be offered promptly. We conducted a systemic literature review of prospective longitudinal studies with the aim of identifying predictors of treatment-resistant schizophrenia from the first episode. From the 545 results screened, we identified 12 published studies where data at the first episode was used to predict treatment resistance. Younger age of onset was the most consistent predictor of treatment resistance. We discuss the gaps in the literature and how future prediction models can identify predictors of treatment response more robustly.

Post-operative volumes following endoscopic surgery for non-functioning pituitary macroadenomas are predictive of further intervention, but not endocrine outcomes.

BACKGROUND: Transsphenoidal surgery (TSS) remains the treatment of choice for non-functioning pituitary macroadenomas (NFPMA). The value of measuring tumour volumes before and after surgery, and its influence on endocrine outcomes and further treatment of the residual or recurrent tumour are unknown. METHODS: Data from patients who underwent endoscopic TSS for a NFPMA (2009-2018) in a UK tertiary centre were analysed for pre- and post-operative endocrine and surgical outcomes. RESULTS: Of 173 patients with NFPMA, 159 (61% male) were treatment naïve. At presentation, 76.2% (77/101) had ≥1 pituitary axis deficit. Older age (p = 0.002) was an independent predictor for multiple hormonal deficiencies. Preoperative tumour volume did not correlate with degree of hypopituitarism. Postoperative tumour volume and extent of tumour resection were not predictive of new onset hypopituitarism. Hormonal recovery was observed in 16 patients (20.8%) with impaired pituitary function, with the greatest recovery in the hypothalamic-pituitary-adrenal axis (21.2%, 7/33). A larger residual tumour volume was predictive of adjuvant radiotherapy (3.40 vs. 1.24 cm3, p = 0.005) and likelihood for repeat surgery (5.40 vs. 1.67cm3, p = 0.004). CONCLUSION: Pre- and post-operative NFPMA volumes fail to predict the number of pituitary hormone deficits, however, greater post-operative residual volumes increase the likelihood of further intervention to control tumour growth.

Review: mine tailings in an African tropical environment-mechanisms for the bioavailability of heavy metals in soils.

Heavy metals are of environmental significance due to their effect on human health and the ecosystem. One of the major exposure pathways of Heavy metals for humans is through food crops. It is postulated in the literature that when crops are grown in soils which have excessive concentrations of heavy metals, they may absorb elevated levels of these elements thereby endangering consumers. However, due to land scarcity, especially in urban areas of Africa, potentially contaminated land around industrial dumps such as tailings is cultivated with food crops. The lack of regulation for land-usage on or near to mine tailings has not helped this situation. Moreover, most countries in tropical Africa have not defined guideline values for heavy metals in soils for various land uses, and even where such limits exist, they are based on total soil concentrations. However, the risk of uptake of heavy metals by crops or any soil organisms is determined by the bioavailable portion and not the total soil concentration. Therefore, defining bioavailable levels of heavy metals becomes very important in HM risk assessment, but methods used must be specific for particular soil types depending on the dominant sorption phases. Geochemical speciation modelling has proved to be a valuable tool in risk assessment of heavy metal-contaminated soils. Among the notable ones is WHAM (Windermere Humic Aqueous Model). But just like most other geochemical models, it was developed and adapted on temperate soils, and because major controlling variables in soils such as SOM, temperature, redox potential and mineralogy differ between temperate and tropical soils, its predictions on tropical soils may be poor. Validation and adaptation of such models for tropical soils are thus imperative before such they can be used. The latest versions (VI and VII) of WHAM are among the few that consider binding to all major binding phases. WHAM VI and VII are assemblages of three sub-models which describe binding to organic matter, (hydr)oxides of Fe, Al and Mn and clays. They predict free ion concentration, total dissolved ion concentration and organic and inorganic metal ion complexes, in soils, which are all important components for bioavailability and leaching to groundwater ways. Both WHAM VI and VII have been applied in a good number of soils studies with reported promising results. However, all these studies have been on temperate soils and have not been tried on any typical tropical soils. Nonetheless, since WHAM VII considers binding to all major binding phases, including those which are dominant in tropical soils, it would be a valuable tool in risk assessment of heavy metals in tropical soils. A discussion of the contamination of soils with heavy metals, their subsequent bioavailability to crops that are grown in these soils and the methods used to determine various bioavailable phases of heavy metals are presented in this review, with an emphasis on prospective modelling techniques for tropical soils.

Partially Dissecting Electron Fluxes in Both Photosystems in Spinach Leaf Disks during Photosynthetic Induction.

Photosynthetic induction, a gradual increase in photosynthetic rate on a transition from darkness or low light to high light, has ecological significance, impact on biomass accumulation in fluctuating light and relevance to photoprotection in strong light. However, the experimental quantification of the component electron fluxes in and around both photosystems during induction has been rare. Combining optimized chlorophyll fluorescence, the redox kinetics of P700 [primary electron donor in Photosystem I (PSI)] and membrane inlet mass spectrometry in the absence/presence of inhibitors/mediator, we partially estimated the components of electron fluxes in spinach leaf disks on transition from darkness to 1,000 �mol photons�m-2�s-1 for up to 10 min, obtaining the following findings: (i) the partitioning of energy between both photosystems did not change noticeably; (ii) in Photosystem II (PSII), the combined cyclic electron flow (CEF2) and charge recombination (CR2) to the ground state decreased gradually toward 0 in steady state; (iii) oxygen reduction by electrons from PSII, partly bypassing PSI, was small but measurable; (iv) cyclic electron flow around PSI (CEF1) peaked before becoming somewhat steady; (v) peak magnitudes of some of the electron fluxes, all probably photoprotective, were in the descending order: CEF1 > CEF2 + CR2 > chloroplast O2 uptake; and (vi) the chloroplast NADH dehydrogenase-like complex appeared to aid the antimycin A-sensitive CEF1. The results are important for fine-tuning in silico simulation of in vivo photosynthetic electron transport processes; such simulation is, in turn, necessary to probe partial processes in a complex network of interactions in response to environmental changes.

Cyclic electron flow and light partitioning between the two photosystems in leaves of plants with different functional types.

Cyclic electron flow (CEF) around photosystem I (PSI) is essential for generating additional ATP and enhancing efficient photosynthesis. Accurate estimation of CEF requires knowledge of the fractions of absorbed light by PSI (fI) and PSII (fII), which are only known for a few model species such as spinach. No measures of fI are available for C4 grasses under different irradiances. We developed a new method to estimate (1) fII in vivo by concurrently measuring linear electron flux through both photosystems [Formula: see text] in leaf using membrane inlet mass spectrometry (MIMS) and total electron flux through PSII (ETR2) using chlorophyll fluorescence by a Dual-PAM at low light and (2) CEF as ETR1-[Formula: see text]. For a C3 grass, fI was 0.5 and 0.4 under control (high light) and shade conditions, respectively. C4 species belonging to NADP-ME and NAD-ME subtypes had fI of 0.6 and PCK subtype had 0.5 under control. All shade-grown C4 species had fI of 0.6 except for NADP-ME grass which had 0.7. It was also observed that fI ranged between 0.3 and 0.5 for gymnosperm, liverwort and fern species. CEF increased with irradiance and was induced at lower irradiances in C4 grasses and fern relative to other species. CEF was greater in shade-grown plants relative to control plants except for C4 NADP-ME species. Our study reveals a range of CEF and fI values in different plant functional groups. This variation must be taken into account for improved photosynthetic calculations and modelling.

Nanosecond pulsed 620 nm source by frequency-doubling a phosphosilicate Raman fiber amplifier.

We demonstrate a nanosecond pulsed source at 620 nm with watt-level average power by frequency-doubling a 1240 nm phosphosilicate Raman fiber amplifier. A gain-switched laser diode operating at 1064 nm is amplified in an ytterbium fiber master oscillator power amplifier system and then converted to 1240 nm using a phosphosilicate Raman fiber amplifier with a conversion efficiency of up to 66%. The Raman fiber amplifier is seeded with a continuous-wave 1240 nm laser diode to obtain narrow-linewidth radiation, which is subsequently frequency-doubled in a periodically poled lithium tantalate crystal. A maximum average power of 1.5 W is generated at 620 nm, corresponding to a pulse energy of 300 nJ at a repetition rate of 5 MHz. The source has excellent beam quality (M2≤1.16) and an optical efficiency (1064 nm to 620 nm) of 20%, demonstrating an effective architecture for generating red pulsed light for biomedical imaging applications.

Low-mobility sperm phenotype in the domestic turkey: Impact on sperm morphometry and early embryonic death.

The sperm mobility assay measures the ability of sperm to swim through a dense layer of Accudenz® , and the sperm mobility phenotype has been shown to predict fertility and other sperm performance traits in roosters and turkeys. In this study, we examined turkey sperm morphometry and rates of early embryonic death associated with high- and low-mobility semen. We also assessed whether the hypo-osmotic stress test, which evaluates the structural integrity of the sperm plasma membrane, may be used as a faster and simpler assay for sperm mobility and viability. We confirmed previous work that found that high-mobility sperm are faster and swim more linearly than low-mobility sperm, and that mobility traits were repeatable within males. In contrast to previous studies, we did not find higher rates of fertility, but low-mobility sperm was associated with higher rates of early embryonic death, though this trend was not significant. High-mobility sperm had longer sperm heads, explained by longer nuclei, despite shorter acrosomes. Although these sperm were faster, midpiece length and flagellum length did not differ between high- and low-mobility sperm. Finally, mobility was not found to be associated with sperm performance in the hypo-osmotic stress test.

Highly efficient nanosecond 560 nm source by SHG of a combined Yb-Raman fiber amplifier.

We demonstrate a nanosecond 560 nm pulse source based on frequency-doubling the output of a combined Yb-Raman fiber amplifier, achieving a pulse energy of 2.0 µJ with a conversion efficiency of 32% from the 976 nm pump light. By introducing a continuous-wave 1120 nm signal before the cladding pumped amplifier of a pulsed Yb:fiber master oscillator power amplifier system operating at 1064 nm, efficient conversion to 1120 nm occurs within the fiber amplifier due to stimulated Raman scattering. The output of the combined Yb-Raman amplifier is frequency-doubled to 560 nm using a periodically poled lithium tantalate crystal with a conversion efficiency of 47%, resulting in an average power of 3.0 W at a repetition rate of 1.5 MHz. The 560 nm pulse duration of 1.7 ns and the near diffraction-limited beam quality (M2≤1.18) make this source ideally suited to biomedical imaging applications such as optical-resolution photoacoustic microscopy and stimulated emission depletion microscopy.

Treatment of allergic rhinitis using mobile technology with real-world data: The MASK observational pilot study.

BACKGROUND: Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect "real-world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real-life treatment of allergic rhinitis (AR) using mobile technology. METHODS: A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries. RESULTS: A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control). CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.

Daily allergic multimorbidity in rhinitis using mobile technology: A novel concept of the MASK study.

BACKGROUND: Multimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary. METHODS: We undertook a 1-year prospective observational study in which 4 210 users and 32 585 days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels <20/100 were categorized as "Low" burden and VAS levels ≥50/100 as "High" burden. RESULTS: Visual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis-driven patterns were defined based on "Low" and "High" VAS levels. There were <0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis High-Asthma Low pattern. There were 1.7% days with a Rhinitis High-Asthma High-Conjunctivitis Low pattern. A novel Rhinitis High-Asthma High-Conjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels. CONCLUSIONS: In a novel approach examining daily symptoms with mobile technology, we found considerable intra-individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.

Tobacco smoking is associated with psychotic experiences in the general population of South London.

BACKGROUND: The association between cigarette smoking and psychosis remains unexplained, but could relate to causal effects in both directions, confounding by socioeconomic factors, such as ethnicity, or use of other substances, including cannabis. Few studies have evaluated the association between cigarettes and psychotic experiences (PEs) in diverse, inner-city populations, or relationships with number of cigarettes consumed. METHODS: We assessed associations and dose-response relationships between cigarette smoking and PEs in a cross-sectional survey of household residents (n = 1680) in South East London, using logistic regression to adjust for cannabis use, other illicit substances, and socioeconomic factors, including ethnicity. RESULTS: We found association between any PEs and daily cigarette smoking, which remained following adjustment for age, gender, ethnicity, cannabis and use of illicit stimulant drugs (fully adjusted odds ratio 1.47, 95% confidence interval 1.01-2.15). Fully adjusted estimates for the association, and with number of PEs, increased with number of cigarettes smoked daily, implying a dose-response effect (p = 0.001 and <0.001, respectively). Odds of reporting any PEs in ex-smokers were similar to never-smokers. CONCLUSIONS: In this diverse epidemiological sample, association between smoking and PEs was not explained by confounders such as cannabis or illicit drugs. Daily cigarette consumption showed a dose-response relationship with the odds of reporting PEs, and of reporting a greater number of PEs. There was no difference in odds of reporting PEs between ex-smokers and never-smokers, raising the possibility that the increase in PEs associated with smoking may be reversible.