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The importance of patient-reported outcome measurement in chronic kidney disease (CKD) populations has been established. However, there remains a lack of research that has synthesised data around CKD-specific symptom and health-related quality of life (HRQOL) burden globally, to inform focused measurement of the most relevant patient-important information in a way that minimises patient burden. The aim of this review was to synthesise symptom prevalence/severity and HRQOL data across the following CKD clinical groups globally: (1) stage 1-5 and not on renal replacement therapy (RRT), (2) receiving dialysis, or (3) in receipt of a kidney transplant. MEDLINE, PsycINFO, and CINAHL were searched for English-language cross-sectional/longitudinal studies reporting prevalence and/or severity of symptoms and/or HRQOL in CKD, published between January 2000 and September 2021, including adult patients with CKD, and measuring symptom prevalence/severity and/or HRQOL using a patient-reported outcome measure (PROM). Random effects meta-analyses were used to pool data, stratified by CKD group: not on RRT, receiving dialysis, or in receipt of a kidney transplant. Methodological quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data, and an exploration of publication bias performed. The search identified 1,529 studies, of which 449, with 199,147 participants from 62 countries, were included in the analysis. Studies used 67 different symptom and HRQOL outcome measures, which provided data on 68 reported symptoms. Random effects meta-analyses highlighted the considerable symptom and HRQOL burden associated with CKD, with fatigue particularly prevalent, both in patients not on RRT (14 studies, 4,139 participants: 70%, 95% CI 60%-79%) and those receiving dialysis (21 studies, 2,943 participants: 70%, 95% CI 64%-76%). A number of symptoms were significantly (p < 0.05 after adjustment for multiple testing) less prevalent and/or less severe within the post-transplantation population, which may suggest attribution to CKD (fatigue, depression, itching, poor mobility, poor sleep, and dry mouth). Quality of life was commonly lower in patients on dialysis (36-Item Short Form Health Survey [SF-36] Mental Component Summary [MCS] 45.7 [95% CI 45.5-45.8]; SF-36 Physical Component Summary [PCS] 35.5 [95% CI 35.3-35.6]; 91 studies, 32,105 participants for MCS and PCS) than in other CKD populations (patients not on RRT: SF-36 MCS 66.6 [95% CI 66.5-66.6], p = 0.002; PCS 66.3 [95% CI 66.2-66.4], p = 0.002; 39 studies, 24,600 participants; transplant: MCS 50.0 [95% CI 49.9-50.1], p = 0.002; PCS 48.0 [95% CI 47.9-48.1], p = 0.002; 39 studies, 9,664 participants). Limitations of the analysis are the relatively few studies contributing to symptom severity estimates and inconsistent use of PROMs (different measures and time points) across the included literature, which hindered interpretation. The main findings highlight the considerable symptom and HRQOL burden associated with CKD. The synthesis provides a detailed overview of the symptom/HRQOL profile across clinical groups, which may support healthcare professionals when discussing, measuring, and managing the potential treatment burden associated with CKD. PROSPERO CRD42020164737.

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Fully describes optimization methods that are currently most valuable in solving real-life problems.Since optimization has applications in almost every branch of science and technology, the text emphasizes their practical aspects in conjunction with the heuristics useful in making them perform more reliably and efficiently.

Stomata, the microvalves on leaf surfaces, exert major influences across scales, from plant growth and productivity to global carbon and water cycling. Stomatal opening enables leaf photosynthesis, and plant growth and water use, whereas plant survival of drought depends on stomatal closure. Here we report that stomatal function is constrained by a safety-efficiency trade-off, such that species with greater stomatal conductance under high water availability ( g max ) show greater sensitivity to closure during leaf dehydration, i.e., a higher leaf water potential at which stomatal conductance is reduced by 50% (Ψ gs50 ). The g max - Ψ gs50 trade-off and its mechanistic basis is supported by experiments on leaves of California woody species, and in analyses of previous studies of the responses of diverse flowering plant species around the world. Linking the two fundamental key roles of stomata—the enabling of gas exchange, and the first defense against drought—this trade-off constrains the rates of water use and the drought sensitivity of leaves, with potential impacts on ecosystems. Stomata enable gas exchange for photosynthesis but close to promote survival during drought. Here, Henry et al. provide evidence for a safety-efficiency trade-off whereby plants with greater stomatal conductance under well-watered conditions are more sensitive to stomatal closure during dehydration.

This comprehensive survey of the work of the Swiss-born modern master Alberto Giacometti offers a fresh and incisive account of his creative output. Published on the occasion of Giacometti?s first major museum presentation in the US in over a decade, the volume brings together nearly 200 sculptures, paintings and drawings to trace the artist?s wide-ranging and innovative engagement with the human form across various mediums. While Giacometti may be best known for his distinct figurative sculptures that emerged after World War II, including a series of elongated standing women, striding men and expressive busts, this volume devotes equal attention to the artist?s early and midcareer development. It explores his lesser-known engagement with Cubism and Surrealism as well as African, Oceanic and Cycladic art, while also highlighting his remarkable talents as a draftsman and painter alongside his sculptural oeuvre. Of particular focus is Giacometti?s studio practice, in addition to historical photographs documenting his relationship with the Guggenheim Museum - which hosted the artist?s first US museum exhibition, in 1955 - and with New York City.00Exhibition: Guggenheim Museum, New York, USA (8.6. - 12.9.2018).

Clostridioides difficile is a bacterial pathogen that causes a range of clinical disease from mild to moderate diarrhea, pseudomembranous colitis, and toxic megacolon. Typically, C. difficile infections (CDIs) occur after antibiotic treatment, which alters the gut microbiota, decreasing colonization resistance against C. difficile . Disease is mediated by two large toxins and the expression of their genes is induced upon nutrient depletion via the alternative sigma factor TcdR. Here, we use tcdR mutants in two strains of C. difficile and omics to investigate how toxin-induced inflammation alters C. difficile metabolism, tissue gene expression and the gut microbiota, and to determine how inflammation by the host may be beneficial to C. difficile . We show that C. difficile metabolism is significantly different in the face of inflammation, with changes in many carbohydrate and amino acid uptake and utilization pathways. Host gene expression signatures suggest that degradation of collagen and other components of the extracellular matrix by matrix metalloproteinases is a major source of peptides and amino acids that supports C. difficile growth in vivo. Lastly, the inflammation induced by C. difficile toxin activity alters the gut microbiota, excluding members from the genus Bacteroides that are able to utilize the same essential nutrients released from collagen degradation. The effects of antibiotics on the gut microbiota can lead to enhanced colonization of Clostridioides difficile ( C. difficile ) and toxin-mediated pathogenesis. Here, using defined toxin-mutant strains and a murine model, the authors provide insights into how toxin-induced inflammation alters C. difficile metabolism, host tissue gene expression and gut microbiota, together influencing a beneficial niche for infection.

BACKGROUND Self-monitoring of blood pressure (SMBP) can contribute to reduced blood pressure in people with hypertension. Potential mediators include increased medication, improved adherence, and changes in lifestyle factors including dietary change and increased physical activity. The objective of this review was to determine the effect of SMBP on medication adherence, medication persistence, and lifestyle factors in people with hypertension. METHODS Electronic bibliographic databases were searched through February 2014 to identify randomized controlled trials that compared SMBP to control/usual care in ambulatory hypertensive patients and reported medication or nonpharmacologic treatment adherence measures. RESULTS Twenty-eight trials with 7,021 participants fulfilled the inclusion criteria. Medication adherence was assessed in 25 trials (89%), dietary outcomes in 8 (29%), physical activity in 6 (21%), and medication persistence in 1 (4%). Blood pressure was assessed in 26 studies (93%). Follow-up ranged from 2 weeks to 12 months. Pooled results of 13 studies demonstrated a small but significant overall effect on medication adherence in favor of SMBP interventions (standardized mean difference 0.21, 95% CI 0.08, 0.34), with moderate heterogeneity (I 2 = 43%). Standardized mean difference was used to express the size of intervention effect in each study relative to the variability observed, and was used to combine the results of studies where different measures of medication adherence were used. Where SMBP interventions had a significant effect on lifestyle factor change, the effect was unlikely to be clinically significant. Pooled results of 11 studies demonstrate a significant overall effect on diastolic blood pressure in favor of SMBP (weighted mean difference −2.02, 95% CI −2.93, −1.11), with low heterogeneity (I 2 = 0%). A test for subgroup differences showed no difference when studies were grouped according to whether medication adherence was significantly improved or not. CONCLUSIONS SMBP may contribute to improvements in medication adherence in hypertensives. However, evidence for the effect of SMBP on lifestyle change and medication persistence is scarce, of poor quality, and suggests little clinically relevant benefit.

The advent of photosynthesis: postponing the event The oldest widely accepted evidence for oxygenic photosynthesis on Earth comes from hydro-carbon biomarkers extracted from 2.7-billion-year-old shales in the Pilbara Craton of Australia, thought to be evidence of eukaryotes and photosynthetic cyanobacteria. This early date has caused controversy because of the long delay between this earliest appearance of oxygen-producing cyanobacteria and the 'great oxidation event' that caused the rise of atmospheric oxygen some 300 million years later. New work by Rasmussen et al . shows that the organic biomarkers are not of Archaean age and must have entered the rocks later, some time after about 2.2 billion years ago. The earliest unambiguous fossil evidence for eukaryotes and cyanobacteria thus reverts to 1.78–1.68 and 2.15 billion years, respectively. The oldest widely accepted evidence for oxygenic photosynthesis comes from hydrocarbon biomarkers extracted from 2.7-billion-year-old shales in the Pilbara Craton, Australia, thought to be evidence of eukaryotes and photosynthetic cyanobacteria. But evidence now shows that the organic biomarkers were not indigenous to the rocks containing them, and must have entered the rocks after ∼2.2 Gyr ago. The earliest unambiguous fossil evidence for eukaryotes and cyanobacteria thus reverts to 1.78–1.68 and 2.15 Gyr, respectively. The evolution of oxygenic photosynthesis had a profound impact on the Earth’s surface chemistry, leading to a sharp rise in atmospheric oxygen between 2.45 and 2.32 billion years (Gyr) ago 1 , 2 and the onset of extreme ice ages 3 . The oldest widely accepted evidence for oxygenic photosynthesis has come from hydrocarbons extracted from ∼2.7-Gyr-old shales in the Pilbara Craton, Australia, which contain traces of biomarkers (molecular fossils) indicative of eukaryotes and suggestive of oxygen-producing cyanobacteria 4 , 5 , 6 , 7 . The soluble hydrocarbons were interpreted to be indigenous and syngenetic despite metamorphic alteration and extreme enrichment (10–20‰) of 13 C relative to bulk sedimentary organic matter 5 , 8 . Here we present micrometre-scale, in situ 13 C/ 12 C measurements of pyrobitumen (thermally altered petroleum) and kerogen from these metamorphosed shales, including samples that originally yielded biomarkers. Our results show that both kerogen and pyrobitumen are strongly depleted in 13 C, indicating that indigenous petroleum is 10–20‰ lighter than the extracted hydrocarbons 5 . These results are inconsistent with an indigenous origin for the biomarkers. Whatever their origin, the biomarkers must have entered the rock after peak metamorphism ∼2.2 Gyr ago 9 and thus do not provide evidence for the existence of eukaryotes and cyanobacteria in the Archaean eon. The oldest fossil evidence for eukaryotes and cyanobacteria therefore reverts to 1.78–1.68 Gyr ago and ∼2.15 Gyr ago 10 , 11 , respectively. Our results eliminate the evidence for oxygenic photosynthesis ∼2.7 Gyr ago and exclude previous biomarker evidence for a long delay (∼300 million years) between the appearance of oxygen-producing cyanobacteria and the rise in atmospheric oxygen 2.45–2.32 Gyr ago 1 .