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Background and study aims There is limited consensus on the optimal method for measuring disease severity in familial adenomatous polyposis (FAP). We aimed to systematically review the operating properties of existing endoscopic severity indices for FAP. Methods We searched MEDLINE, EMBASE, and the Cochrane Library from inception to February 2023 to identify randomized controlled trials (RCTs) that utilized endoscopic outcomes or studies that evaluated the operating properties of endoscopic disease severity indices in FAP. Results A total of 134 studies were included. We evaluated scoring indices and component items of scoring indices, such as polyp count, polyp size, and histology. Partial validation was observed for polyp count and size. The most commonly reported scoring index was the Spigelman classification system, which was used for assessing the severity of duodenal involvement. A single study reported almost perfect interobserver and intra-observer agreement for this system. The InSIGHT polyposis staging system, which was used for assessing colorectal polyp burden, has been partially validated. It showed substantial interobserver reliability; however, the intra-observer reliability was not assessed. Novel criteria for high-risk gastric polyps have been developed and assessed for interobserver reliability. However, these criteria showed a poor level of agreement. Other scoring indices assessing the anal transition zone, duodenal, and colorectal polyps have not undergone validation. Conclusions There are no fully validated endoscopic disease severity indices for FAP. Development and validation of a reliable and responsive endoscopic disease severity instrument will be informative for clinical care and RCTs of pharmacological therapies for FAP., Competing Interests: Conflict of Interest Disclosures: ALS: Nothing to disclose. HB: Nothing to disclose. AA: Nothing to disclose. JKM: Employee of Alimentiv Inc. AZ: Employee of Alimentiv Inc. JL: Employee of Alimentiv Inc. BGF: Received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor Inc., Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix, and Wyeth Pharmaceuticals Inc.; consulting fees from Millennium Pharmaceuticals, Merck, Centocor Inc., Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie, Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging Inc., Salix Pharmaceuticals, Novonordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc., and Sigmoid Pharma; and speaker’s fees from UCB, AbbVie, and J&J/Janssen. VJ: Received consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Avoro Capital, Bristol Myers Squibb, Celltrion, Eli Lilly, Endpoint Health, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, Gilde Healthcare, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus Biosciences, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso pharmaceuticals, Takeda, Teva, Topivert, Ventyx, and Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi. CM: Received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences Inc., Roche, Sanofi, Takeda, and Tillotts Pharma; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, and Takeda; royalties from Springer Publishing; research support from Ferring and Pfizer. ED: Endoscopic equipment on loan from FujiFilm; research grant: FujiFilm; honoraria for consultancy from Olympus, Fujifilm, Ambu, and InterVenn; and speaker’s fees from Olympus, GI Supply, Norgine, IPSEN, PAION, and FujiFilm. JS: Consultant for Jansen Research and Development, Recursion Pharmaceuticals, Tempest Pharmaceuticals, and Alimentiv Inc., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

O-GlcNAcase (OGA) is the only human enzyme that catalyzes the hydrolysis (deglycosylation) of O-linked beta- N -acetylglucosaminylation (O-GlcNAcylation) from numerous protein substrates. OGA has broad implications in many challenging diseases including cancer. However, its role in cell malignancy remains mostly unclear. Here, we report that a cancer-derived point mutation on the OGA's noncatalytic stalk domain aberrantly modulates OGA interactome and substrate deglycosylation toward a specific set of proteins. Interestingly, our quantitative proteomic studies uncovered that the OGA stalk domain mutant preferentially deglycosylated protein substrates with +2 proline in the sequence relative to the O-GlcNAcylation site. One of the most dysregulated substrates is PDZ and LIM domain protein 7 (PDLIM7), which is associated with the tumor suppressor p53. We found that the aberrantly deglycosylated PDLIM7 suppressed p53 gene expression and accelerated p53 protein degradation by promoting the complex formation with E3 ubiquitin ligase MDM2. Moreover, deglycosylated PDLIM7 significantly up-regulated the actin-rich membrane protrusions on the cell surface, augmenting the cancer cell motility and aggressiveness. These findings revealed an important but previously unappreciated role of OGA's stalk domain in protein substrate recognition and functional modulation during malignant cell progression., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background and Aims: In this systematic review we summarise existing scoring indices for assessing disease activity and quality of life in perianal fistulising Crohn's disease [PFCD], and highlight gaps in the literature., Methods: MEDLINE, EMBASE, and CENTRAL were searched from August 24, 2022, to identify studies evaluating clinical, radiological, or patient-reported outcome measures [PROMS] in PFCD. The primary objective was to identify all available scoring indices and describe the operating properties of these indices., Results: A total of 53 studies reported on the use of one clinical index [Perianal Disease Activity Index: PDAI], three PROMs, and 10 radiological indices; 25 studies evaluated the operating properties of these indices. The PDAI demonstrated content validity, construct validity, and responsiveness but criterion validity or reliability were not assessed. The Van Assche Index [VAI], modified VAI, and the Magnetic Resonance Index for Assessing Fistulas in Patients with CD [MAGNIFI-CD] were the most studied radiological indices. These indices demonstrated responsiveness and reliability. The VAI and MAGNIFI-CD demonstrated construct validity; criterion and content validity and feasibility have not been assessed. Among the three PROMs, the Crohn's Anal Fistula Quality of Life index demonstrated content and construct validity, inter-observer reliability, and responsiveness; criterion validity, intra-observer reliability, and feasibility have not been assessed for this index., Conclusions: There are no fully valid, reliable, and responsive clinical disease or radiological indices for PFCD. Although the radiological indices demonstrated responsiveness and reliability, well-defined cut-offs for response and remission are lacking. Future research should focus on establishing standardised definitions and thresholds for outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Iron and steel slags have a long history of both disposal and beneficial use in the coastal zone. Despite the large volumes of slag deposited, comprehensive assessments of potential risks associated with metal(loid) leaching from iron and steel by-products are rare for coastal systems. This study provides a national-scale overview of the 14 known slag deposits in the coastal environment of Great Britain (those within 100 m of the mean high-water mark), comprising geochemical characterisation and leaching test data (using both low and high ionic strength waters) to assess potential leaching risks. The seaward facing length of slag deposits totalled at least 76 km, and are predominantly composed of blast furnace (iron-making) slags from the early to mid-20th Century. Some of these form tidal barriers and formal coastal defence structures, but larger deposits are associated with historical coastal disposal in many former areas of iron and steel production, notably the Cumbrian coast of England. Slag deposits are dominated by melilite phases (e.g. gehlenite), with evidence of secondary mineral formation (e.g. gypsum, calcite) indicative of weathering. Leaching tests typically show lower element (e.g. Ba, V, Cr, Fe) release under seawater leaching scenarios compared to deionised water, largely ascribable to the pH buffering provided by the former. Only Mn and Mo showed elevated leaching concentrations in seawater treatments, though at modest levels (<3 mg/L and 0.01 mg/L, respectively). No significant leaching of potentially ecotoxic elements such as Cr and V (mean leachate concentrations <0.006 mg/L for both) were apparent in seawater, which micro-X-Ray Absorption Near Edge Structure (μXANES) analysis show are both present in slags in low valence (and low toxicity) forms. Although there may be physical hazards posed by extensive erosion of deposits in high-energy coastlines, the data suggest seawater leaching of coastal iron and steel slags in the UK is likely to pose minimal environmental risk., (© 2024. The Author(s).)

Background: Fistulas are a debilitating complication of Crohn's disease [CD]. We conducted a systematic review to assess the efficacy of medical therapies for fistulizing CD., Methods: MEDLINE, Embase, and CENTRAL were searched on May 26, 2022, for randomized controlled trials [RCTs] of pharmacological therapy in adults with fistulizing CD. The primary outcome was induction and maintenance of fistula response. Pooled risk ratios [RRs] and 95% confidence intervals [CIs] were calculated. GRADE was used to assess the certainty of evidence., Results: Thirty-eight RCTs were included. Nineteen trials [50%] exclusively involved perianal fistula. The remaining studies included some participants with non-perianal fistula. Pooled RRs for anti-tumour necrosis factor [TNF] agents were not statistically significant for induction [RR 1.36, 95% CI 0.97-1.91] or maintenance of fistula response [RR 1.48, 95% CI 0.97-2.27]. However, in a sensitivity analysis of studies with fistula response as the primary outcome, anti-TNFs were superior to placebo for induction [RR 1.94, 95% CI 1.10-3.41] and maintenance [RR 1.88, 95% CI 1.23-2.88] of fistula response. Oral small molecules [RR 2.56, 95% CI 1.18-5.53] and mesenchymal stem cell [MSC] therapy [RR 1.26, 95% CI 1.01-1.57] were effective for induction of fistula response. Ustekinumab was associated with maintenance of fistula response [RR 1.80, 95% CI 1.04-3.11]. Vedolizumab was not superior to placebo. The certainty of evidence ranged from very low to moderate., Conclusion: Very low- to moderate-certainty evidence suggests that anti-TNF therapy, oral small molecules, ustekinumab, and MSCs are effective for perianal fistulizing CD. Dedicated fistula studies evaluating biologics and small molecules are needed., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Accurate, reliable, and responsive disease activity indices are important to streamline drug approval and treatment modalities for pediatric inflammatory bowel disease (pIBD). We aimed to identify all scoring indices used in pIBD randomized controlled trials (RCTs) and to evaluate their operating properties., Methods: MEDLINE, EMBASE, and CENTRAL were searched on December 6, 2022, to identify studies evaluating clinical, endoscopic, imaging, or patient-reported outcome measures (PROMs) in pIBD including Crohn's disease (CD) and ulcerative colitis (UC). Validity, reliability, responsiveness, and feasibility were summarized., Results: Seventy RCTs evaluating pIBD indices were identified. Forty-one studies reported on the operating properties of 14 eligible indices (n = 9 CD, n = 5 UC). The Pediatric Crohn's Disease Activity Index (PCDAI) varied widely in terms of validity and reliability and was less feasible overall. In contrast, the Mucosal Inflammation Noninvasive Index, which includes fecal calprotectin, had better operating properties than the PCDAI. The Simplified Endoscopic Mucosal Assessment of Crohn's Disease appears more feasible and had similar operating properties than the longer Simple Endoscopic Score for Crohn's Disease. The Pediatric Ulcerative Colitis Activity Index was feasible, valid, and reliable, but responsiveness needs to be evaluated further. The Endoscopic Mayo score and the Ulcerative Colitis Endoscopic Index of Severity were reliable, but validity and responsiveness need to be evaluated further. Imaging and PROMs/quality of life indices need further evaluation., Conclusions: The operating properties of pIBD clinical trial end points varied widely. These results highlight the need for further validation and development of novel indices., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Problem Research Strategy and Findings: The negative impact of vacant and abandoned housing in city neighborhoods is extreme, affecting health and quality of life, promoting violence, and leading to further abandonment. One approach to addressing abandoned housing is to intervene with low-cost interventions that provide a visual sense of ownership. We tested whether a low-cost remediation of abandoned and vacant houses or a trash cleanup intervention would make a noticeable difference in the levels of nearby disrepair, disorder, and public safety. The abandoned housing remediation and trash cleanup interventions were a test of compliance with municipal ordinances. We used an experimental design to test the causal effects of the ordinances, and because the scale of abandonment was too large to provide treatment to all abandoned houses in the city. We used systematic social observation methods to rate changes in disrepair, disorder, and litter at housing sites and on the city blocks they were located, and police reported data on gun violence and illegal substance uses. Our experimental design allowed us to see if observed disrepair, disorder, and public safety improved after working windows and doors were installed on abandoned houses compared with a trash cleanup around properties or a no-intervention control condition. Our results showed significant changes in observed disrepair, disorder, and gun violence and illustrate the benefits of experimental evaluations of place-based changes to the built environment., Takeaway for Practice: Improving compliance with ordinances to remediate abandoned housing can make a noticeable difference in disrepair in neighborhoods and contribute improved public safety. We illustrate how planners can use field experiments in partnership with city agencies, nonprofit community groups, and local universities to discover novel approaches to advance place-based changes to the built environment that can help economically disadvantaged communities abate problems of physical disorder.

Water pollution arising from abandoned coal mines, is second only to sewage as a source of freshwater pollution and in coalfield catchments mine water can be the dominant pollutant, with oxidised iron smothering the bed of receiving rivers. This study measured greenhouse gases in mine water outflows from sixteen sites across the Midland Valley in Scotland. Radiogenic and stable carbon isotopes measurements (Δ 14 C and δ 13 C) were used to determine the sources of both methane (CH 4 ) and carbon dioxide (CO 2 ) produced within the flooded mine environment. Concentrations of CH 4 -C ranged from 20 to 215 μg l -1 and CO 2 -C from 30 to 120 mg l -1 , with CO 2 accounting for 97 % of the mine water global warming potential. Methane origins included 51 % modern biogenic, 41 % thermogenic and 8 % from hydrogenotrophic methanogenesis of coal. The most significant inverse impact on biogenic CH 4 concentrations was sulphate, most likely due to sulphate reducing bacteria outcompeting methanogens. Carbon dioxide origins included 64 % from the dissolution of limestone, 21 % from terrestrial organic carbon and 15 % from coal. The limestone derived CO 2 was positively correlated with high sulphate concentrations, which resulted in sulphuric acid and caused the dissolution of carbonate from limestone. The mine waters experienced significant carbonate buffering becoming only slightly acidic (pH 6-7), but with significant loss of inorganic carbon. The mine waters had low dissolved oxygen (6-25 %) and high dissolved iron (2 to 65 mg l -1 ) and manganese (0.5 to 5 mg l -1 ) concentrations. Dissolved greenhouse gases from abandoned mines were estimated as 0.27 +0.31-0.18% of Scotland's global warming potential. This novel work has contributed information about the sources and controls of greenhouse gas fluxes in mine waters and identified the need to quantify and report this emissions term., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: External control arms (ECAs) provide useful comparisons in clinical trials when randomised control arms are limited or not feasible. We conducted a systematic review to summarise applications of ECAs in trials of immune-mediated inflammatory diseases (IMIDs)., Design: Systematic review with an appraisal of ECA source quality rated across five domains (data collection, study populations, outcome definitions, reliability and comprehensiveness of the dataset, and other potential limitations) as high, low or unclear quality., Data Sources: Embase, Medline and Cochrane Central Register of Controlled Trial were searched through to 12 September 2023., Eligibility Criteria: Eligible studies were single-arm or randomised controlled trials (RCTs) of inflammatory bowel disease, pouchitis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and atopic dermatitis in which an ECA was used as the comparator., Data Extraction and Synthesis: Two authors independently screened the search results in duplicate. The characteristics of included studies, external data source(s), outcomes and statistical methods were recorded, and the quality of the ECA data source was assessed by two independent authors., Results: Forty-three studies met the inclusion criteria (inflammatory bowel disease: 16, pouchitis: 1, rheumatoid arthritis: 12, juvenile idiopathic arthritis: 1, ankylosing spondylitis: 5, psoriasis: 3, multiple indications: 4). The majority of these trials were single-arm (33/43) and enrolled adult patients (34/43). All included studies used a historical control rather than a contemporaneous ECA. In RCTs, ECAs were most often derived from the placebo arm of another RCT (6/10). In single-arm trials, historical case series were the most common ECA source (19/33). Most studies (31/43) did not employ a statistical approach to generate the ECA from historical data., Conclusions: Standardised ECA methodology and reporting conventions are lacking for IMIDs trials. The establishment of ECA reporting guidelines may enhance the rigour and transparency of future research., Competing Interests: Competing interests: AZ is an employee of Alimentiv. RE has received consulting fees from Alimentiv, CADTH, SpringWorks Therapeutics, and Turnstone Biologics. CEP is an employee of Alimentiv. JKM is an employee of Alimentiv. JC is a former employee of Alimentiv. BN is an employee of Alimentiv. GZ is an employee of Alimentiv. SS has received personal fees from Pfizer for ad hoc grant review, and his institute has received research grants from AbbVie and Janssen. BFG has received grant/research support from AbbVie, Amgen, AstraZeneca/MedImmune, Atlantic Pharmaceuticals, Boehringer-Ingelheim, Celgene Corporation, Celltech, Genentech Inc./Hoffmann-La Roche, Gilead Sciences, GSK, Janssen Research & Development, Pfizer, Receptos/Celgene International, Sanofi, Santarus, Takeda Development Center Americas, Tillotts, and UCB; consulting fees from AbbVie, Akebia Therapeutics, Allergan, Amgen, AMT, Aptevo Therapeutics, Astra Zeneca, Atlantic Pharma, Avir Pharma, Biogen Idec, BioMx Israel, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Gossamer Pharma, GSK, Inception IBD, Johnson & Johnson/Janssen, Kyowa Kakko Kirin Co, Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nestle, Nextbiotix, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Salix Pharma, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma, Takeda, Teva Pharma, TiGenix, Tillotts, UCB, Vertex Pharma, Vivelix Pharma, VHsquared, and Zyngenia; speaker’s bureau fees from Abbott/AbbVie, JnJ/Janssen, Lilly, Takeda, Tillotts, and UCB Pharma; is a scientific advisory board member for Abbott/AbbVie, Allergan, Amgen, Astra Zeneca, Atlantic Pharma, Avaxia Biologics, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Elan/Biogen, Galapagos, Genentech/Roche, JnJ/Janssen, Merck, Nestle, Novartis, Novo Nordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts, and UCB; and is the Senior Scientific Officer of Alimentiv. CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Prometheus Biosciences, Roche, Sanofi; speaker's fees from AbbVie, Amgen, AVIR Pharma, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, Takeda; royalties from Springer Publishing; research support from Ferring, Pfizer. VJ has received has received consulting/advisory board fees from AbbVie, Alimentiv, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso pharmaceuticals, Takeda, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Oral small-molecule drugs [SMDs] are expanding the therapeutic landscape for inflammatory bowel disease [IBD]. This systematic review and meta-analysis summarizes the efficacy and safety of JAK inhibitor [JAKi] and sphingosine-1-phosphate [S1P] receptor modulator treatments for ulcerative colitis [UC] and Crohn's disease [CD]., Methods: MEDLINE, Embase, and CENTRAL were searched from inception to May 30, 2022. Randomized controlled trials [RCTs] of JAKi and S1P receptor modulators in adults with UC or CD were eligible. Clinical, endoscopic, histological, and safety data were pooled and analysed using a random-effects model., Results: Thirty-five RCTs [26 UC, nine CD] were included. In UC, JAKi therapy was associated with induction of clinical (risk ratio [RR] 3.16, 95% confidence interval [CI] 2.03-4.92; I2 = 65%) and endoscopic [RR 3.99, 95% CI 2.36-6.75; I2 = 36%] remission compared to placebo. Upadacitinib was associated with histological response [RR 2.63, 95% CI 1.97-3.53]. S1P modulator therapy was associated with induction of clinical [RR 2.52, 95% CI 1.88-3.39; I2 = 1%] and endoscopic [RR 2.39, 95% CI 1.07-5.33; I2 = 0%] remission relative to placebo. Ozanimod was superior to placebo for inducing histological remission in UC [RR 2.20, 95% CI 1.43-3.37; I2 = 0%], while etrasimod was not [RR 2.36, 95% CI 0.71-7.88; I2 = 0%]. In CD, JAKi therapy was superior to placebo for induction of clinical remission [RR 1.53, 95% CI 1.19-1.98; I2 = 31%], and endoscopic remission [RR 4.78, 95% CI 1.63-14.06; I2 = 43%] compared to placebo. The risk of serious infections was similar for oral SMDs and placebo., Conclusion: JAKi and S1P receptor modulator therapies are effective in IBD for inducing clinical and endoscopic remission and, in some circumstances, histological response., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

CO 2 mineralization in slag has gained significant attention since it occurs with minimal human intervention and energy input. While the amount of theoretical CO 2 that can be captured within slag has been quantified based on slag composition in several studies, the microstructural and mineralogical effects of slag on its ability to capture CO 2 have not been fully addressed. In this work, the CO 2 uptake within legacy slag samples is analyzed through microstructural characterization. Slag samples were collected from the former Ravenscraig steelmaking site in Lanarkshire, Scotland. The collected samples were studied using X-ray Computed Tomography (XCT) to understand the distribution and geometry of pore space, as well as with scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy (EDS) to visualize the distribution of elements within the studied samples. Electron backscatter diffraction (EBSD) was used to study the minerals distribution. The samples were also characterized through X-ray diffraction (XRD) and X-ray fluorescence (XRF), and the amount of captured CO 2 was quantified using thermogravimetric analysis (TGA). Our results demonstrate that CO 2 uptake occurs to the extent of ∼9-30 g CO 2 / kg slag. The studied samples are porous in nature, with pore space occupying up to ∼30% of their volumes, and they are dominated by åkermanite-gehlenite minerals which interact with the atmospheric CO 2 slowly at ambient conditions. EDS and EBSD results illustrate that the precipitated carbonate in slag is calcite, and that the precipitation of calcite is accompanied by the formation of a Si-O-rich layer. The provided analysis concludes that the porous microstructure as well as the minerals distribution in slag should be considered in forecasting and designing large-scale solutions for passive CO 2 mineralization in slag., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Ulcerative proctitis (UP) is a common highly symptomatic form of ulcerative colitis that can be difficult to treat., Aim: To assess the efficacy of medical treatments for UP., Methods: We searched MEDLINE, EMBASE, and CENTRAL on 23 November 2022 for randomised controlled trials (RCTs) of medical therapy for adults with UP. Primary outcomes included induction and maintenance of clinical remission. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome., Results: We included 53 RCTs (n = 4096) including 46 induction studies (n = 3731) and seven maintenance studies (n = 365). First-line therapies included topical 5-aminosalicylic acid (5-ASA), conventional corticosteroids, budesonide, and oral 5-ASA. Therapy for refractory UP included topical tacrolimus and small molecules. Topical 5-ASA was superior to placebo for induction (RR 2.72, 95% CI 1.94-3.82) and maintenance of remission (RR 2.09, 95% CI 1.26-3.46). Topical corticosteroids were superior to placebo for induction of remission (RR 2.83, 95% CI 1.62-4.92). Topical budesonide was superior to placebo for induction of remission (RR 2.34, 95% CI 1.44-3.81). Combination therapy with topical 5-ASA and topical corticosteroids was superior to topical monotherapy with either agent. Topical tacrolimus was superior to placebo. Etrasimod was superior to placebo for induction (RR 4.71, 95% CI 1.2-18.49) and maintenance of remission (RR 2.08, 95% CI 1.31-3.32)., Conclusions: Topical 5-ASA and corticosteroids are effective for active UP. Topical 5-ASA may be effective for maintenance of remission. Tacrolimus may be effective for induction of remission. Etrasimod may be effective for induction and for maintenance of remission. Trials should include UP to expand the evidence base for this under-represented population., (© 2023 John Wiley & Sons Ltd.)

Background: Targeting interleukin-23 (IL-23) is an important therapeutic strategy for Crohn's disease (CD)., Aims: This systematic review and meta-analysis assessed the efficacy and safety of selective IL-23p19 and IL-12/23p40 inhibitors in patients with moderate-to-severe CD., Methods: MEDLINE, Embase, and the Cochrane library (CENTRAL) were searched from inception to May 24, 2023, for randomized, placebo- or active comparator-controlled induction and/or maintenance trials of selective IL-23p19 and IL-12/23p40 inhibitors in pediatric and adult patients with CD. The primary outcome was the proportion of patients in clinical remission. Secondary outcomes were clinical response, endoscopic remission, endoscopic response, and safety. Data were pooled using a random-effects model. Risk of bias and certainty of evidence were assessed using the Cochrane risk of bias tool and the GRADE criteria, respectively., Results: Eighteen trials (n = 5561) were included. Most studies were rated as low risk of bias. Targeting IL-23 was significantly superior to placebo for inducing clinical (risk ratio [RR] = 1.87, 95% confidence interval [CI] 1.58-2.21) and endoscopic (RR = 3.20, 95%CI 2.17-4.70) remission and maintaining clinical remission (RR = 1.39, 95%CI 1.10-1.77) (GRADE high certainty evidence for all outcomes). Subgroup analysis showed that targeting IL-23 was superior to placebo for inducing clinical remission in biologic-naïve (RR = 2.20, 95%CI 1.46-3.32, I 2  = 0%, p = 0.39) and biologic-experienced patients (RR = 1.82, 95%CI 1.27-2.60, I 2  = 56.5%, p = 0.01). Targeting IL-23 was associated with a decreased risk of serious adverse events in induction (RR = 0.55, 95%CI 0.44-0.73) and maintenance (RR = 0.72, 95%CI 0.53-0.98) trials compared to placebo (high certainty evidence)., Conclusion: Targeting IL-23 is effective and safe for inducing and maintaining clinical and endoscopic remission in patients with moderate-to-severe CD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recent events have made it apparent that the creatinine based estimating equations for glomerular filtration have their flaws. Some flaws have been known for some time; others have prompted radical modification of the equations themselves. These issues persist in part owing to the behaviour of the creatinine molecule itself, particularly in acute and critical illness. There are significant implications for patient treatment decisions, including drug and fluid therapies and choice of imaging modality (contrast vs. non-contrast CT scan for example). An alternative biomarker, Cystatin C, has been used with some success both alone and in combination with creatinine to help improve the accuracy of particular estimating equations. Problems remain in certain circumstances and costs may limit the more widespread use of the alternative assay. This review will explore both the historical and more recent evidence for glomerular filtration estimation, including options to directly measure glomerular filtration (rather than estimate), perhaps the holy grail for both Biochemistry and Nephrology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: We conducted a systematic review to assess medical therapy for the treatment and prevention of pouchitis., Methods: Randomised controlled trials (RCTs) of medical therapy in adults with or without pouchitis were searched to March 2022. Primary outcomes included clinical remission/response, maintenance of remission and prevention of pouchitis., Results: Twenty RCTs (N = 830) were included. Acute pouchitis: One study compared ciprofloxacin with metronidazole. At 2 weeks, 100% (7/7) of ciprofloxacin participants achieved remission, compared with 67% (6/9) of metronidazole participants (RR: 1.44, 95% CI: 0.88-2.35, very low certainty evidence). One study compared budesonide enemas with oral metronidazole. Fifty percent (6/12) of budesonide participants achieved remission compared with 43% (6/14) of metronidazole participants (RR: 1.17, 95% CI: 0.51-2.67, low certainty evidence). Chronic pouchitis: Two studies (n = 76) assessed De Simone Formulation. Eighty-five percent (34/40) of De Simone Formulation participants maintained remission at 9-12 months compared with 3% (1/36) placebo participants (RR: 18.50, 95% CI: 3.86-88.56, moderate certainty evidence). One study assessed vedolizumab. Thirty-one percent (16/51) of vedolizumab participants achieved clinical remission at 14 weeks compared with 10% (5/51) of placebo participants (RR: 3.20, 95% CI: 1.27-8.08, moderate certainty evidence)., Prophylaxis: Two studies assessed De Simone Formulation. Ninety percent (18/20) of De Simone Formulation participants did not develop pouchitis compared with 60% (12/20) of placebo participants (RR: 1.50, 95% CI: 1.02-2.21, moderate certainty evidence)., Conclusions: Apart from vedolizumab and the De Simone formulation, the effects of other medical interventions for pouchitis are uncertain., (© 2023 John Wiley & Sons Ltd.)

There is growing global concern that greenhouse gas (GHG) emissions from water bodies are increasing because of interactions between nutrient levels and climate warming. This paper investigates key land-cover, seasonal and hydrological controls of GHGs by comparison of the semi-natural, agricultural and urban environments in a detailed source-to-sea study of the River Clyde, Scotland. Riverine GHG concentrations were consistently oversaturated with respect to the atmosphere. High riverine concentrations of methane (CH 4 ) were primarily associated with point source inflows from urban wastewater treatment, abandoned coal mines and lakes, with CH 4 -C concentrations between 0.1 - 44 µg l -1 . Concentrations of carbon dioxide (CO 2 ) and nitrous oxide (N 2 O) were mainly driven by nitrogen concentrations, dominated by diffuse agricultural inputs in the upper catchment and supplemented by point source inputs from urban wastewater in the lower urban catchment, with CO 2 -C concentrations between 0.1 - 2.6 mg l -1 and N 2 O-N concentrations between 0.3 - 3.4 µg l -1 . A significant and disproportionate increase in all GHGs occurred in the lower urban riverine environment in the summer, compared to the semi-natural environment, where GHG concentrations were higher in winter. This increase and change in GHG seasonal patterns points to anthropogenic impacts on microbial communities. The loss of total dissolved carbon, to the estuary is approximately 48.4 ± 3.6 Gg C yr -1 , with the annual inorganic carbon export approximately double that of organic carbon and four times that of CO 2, with CH 4 accounting for 0.03%, with the anthropogenic impact of disused coal mines accelerating DIC loss. The annual loss of total dissolved nitrogen to the estuary is approximately 4.03 ± 0.38 Gg N yr -1 of which N 2 O represents 0.06%. This study improves our understanding of riverine GHG generation and dynamics which can contribute to our knowledge of their release to the atmosphere. It identifies where action could support reductions in aquatic GHG generation and emission., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background and Aims: Perianal fistulizing disease is a common complication of Crohn's disease [CD], for which new therapies are urgently needed. To assist the design of clinical trials for novel therapeutics, we conducted a systematic review and meta-analysis of randomised controlled trials [RCTs] to quantify placebo rates and identify factors influencing them in perianal CD [pCD]., Methods: We searched MEDLINE, Embase and CENTRAL from inception to June 2021. Eligible studies were placebo-controlled trials of pharmacological interventions for pCD. Placebo fistula response and remission rates for induction and maintenance trials were extracted and pooled using a random-effects model. Mixed-effects meta-regression was used to evaluate the impact of patient and study-level characteristics on point estimates., Results: In 17 RCTs [13 induction, five maintenance] the pooled placebo fistula response and remission rate for induction trials was 25% (95% confidence interval [CI] 17-36%) and 17% [95% CI 11-25%], respectively. For maintenance trials, the pooled placebo fistula response and remission rate was 23% [95% CI 17-32%] and 19% [95% CI 14-25%], respectively. Trials enrolling patients with less disease activity and a higher proportion with ileal predominant disease were associated with significantly higher placebo response rates. Trials originating in Europe [compared to North America], therapies requiring perianal injection and a longer timepoint to measure remission were associated with higher placebo remission rates., Conclusions: Placebo response and remission rates in pCD trials are influenced by patient and disease-related factors, as well as the type of intervention being studied. These contemporary rates will inform trial design for novel therapeutics., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Effective medical therapies for patients with microscopic colitis (MC) who fail budesonide are lacking. However, conducting randomised controlled trials (RCTs) in MC has been challenging due to small sample sizes. Understanding placebo responses can help inform more efficient future trials., Aims: The aim of this study is to estimate clinical and histologic placebo response rates and to determine factors associated with placebo response in MC., Methods: EMBASE, MEDLINE, and CENTRAL were searched until 7 January 2022, to identify placebo-controlled RCTs in adult patients with MC. Clinical and histologic response in the placebo arms were pooled using random-effects models. Stratified analyses based on disease- and trial-level characteristics, leave-one-out meta-analysis, and cumulative meta-analysis were performed., Results: Twelve RCTs enrolling a total of 391 patients (placebo n = 163) with MC were included. Pooled clinical and histologic placebo response rates were 24.4% (95% CI: 12.4%-38.4%), I 2  = 60.8%, p < 0.01, and 19.9% (95% CI: 5.3%-39.0%), I 2  = 66.4%, p = 0.01 (tests for heterogeneity), respectively. Clinical response to placebo was numerically higher in patients with lymphocytic compared to collagenous colitis (39.9% vs. 19.8%, p = 0.08). Heterogeneity in clinical response to placebo was significantly reduced when the Miehlke 2014 RCT was excluded in the leave-one-out meta-analysis or when a more stringent secondary definition of response based on the Hjortswang criteria was applied., Conclusions: Approximately one-quarter of patients in MC trials respond to placebo, although with substantial heterogeneity, reflecting the need for standardised outcome definitions and study designs for MC. This analysis also serves to inform future MC trials that may consider incorporating an external, historical placebo control arm, rather than directly randomising patients to placebo., (© 2023 John Wiley & Sons Ltd.)

Wildlife trafficking, whether local or transnational in scope, undermines sustainable development efforts, degrades cultural resources, endangers species, erodes the local and global economy, and facilitates the spread of zoonotic diseases. Wildlife trafficking networks (WTNs) occupy a unique gray space in supply chains-straddling licit and illicit networks, supporting legitimate and criminal workforces, and often demonstrating high resilience in their sourcing flexibility and adaptability. Authorities in different sectors desire, but frequently lack knowledge about how to allocate resources to disrupt illicit wildlife supply networks and prevent negative collateral impacts. Novel conceptualizations and a deeper scientific understanding of WTN structures are needed to help unravel the dynamics of interaction between disruption and resilience while accommodating socioenvironmental context. We use the case of ploughshare tortoise trafficking to help illustrate the potential of key advancements in interdisciplinary thinking. Insights herein suggest a significant need and opportunity for scientists to generate new science-based recommendations for WTN-related data collection and analysis for supply chain visibility, shifts in illicit supply chain dominance, network resilience, or limits of the supplier base.

Background and Aims: Treatment options for proctitis are limited. To assist trial design for novel therapeutics, we conducted a systematic review and meta-analysis of proctitis randomized controlled trials [RCTs] to quantify placebo rates and identify factors influencing them., Methods: We searched MEDLINE, EMBASE and CENTRAL from inception to June 2021. Placebo-controlled trials of pharmacological interventions for proctitis were eligible. Placebo clinical response and remission rates for induction and maintenance trials were extracted and pooled using a random-effects model. Mixed-effects meta-regression was used to evaluate the impact of patient and study-level characteristics., Results: Twenty RCTs [17 induction and four maintenance phases] were included. The most common intervention was aminosalicylates and most studies investigated topical medications. The pooled placebo clinical response and remission rates for induction trials were 28% (95% confidence interval [CI] 22-35%; n = 17) and 20% [95% CI 12-32%; n = 9], respectively. Pooled placebo endoscopic response and remission rates were 32% [95% CI 26-39%, n = 12] and 18% [95% CI 9-33%, n = 6], respectively. For maintenance trials, the pooled placebo clinical remission rate was 29% [95% CI 16-46%, n = 17]. Trials published after 2005 and trials with a longer duration of follow-up were associated with significantly lower placebo response rates. Nineteen of 20 studies were assessed as having an unclear risk of bias, reflecting the historical nature of trials., Conclusions: Placebo response and remission rates in proctitis trials are influenced by trial phase and the endpoint being assessed. These contemporary rates will inform trial design for novel therapeutics for treatment of proctitis, which is a large unmet need., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Structural racism has resulted in long-standing disinvestment and dilapidated environmental conditions in Black neighborhoods. Abandoned houses signal neglect and foster stress and fear for residents, weakening social ties and potentially contributing to poor health and safety., Objective: To determine whether abandoned house remediation reduces gun violence and substance-related outcomes and increases perceptions of safety and use of outdoor space., Design, Setting, and Participants: This cluster randomized trial was conducted from January 2017 to August 2020, with interventions occurring between August 2018 and March 2019. The study included abandoned houses across Philadelphia, Pennsylvania, and surveys completed by participants living nearby preintervention and postintervention. Data analysis was performed from March 2021 to September 2022., Interventions: The study consisted of 3 arms: (1) full remediation (installing working windows and doors, cleaning trash, weeding); (2) trash cleanup and weeding only; and (3) a no-intervention control., Main Outcomes and Measures: Difference-in-differences mixed-effects regression models were used to estimate the effect of the interventions on multiple primary outcomes: gun violence (weapons violations, gun assaults, and shootings), illegal substance trafficking and use, public drunkenness, and perceptions of safety and time outside for nearby residents., Results: A master list of 3265 abandoned houses was randomly sorted. From the top of this randomly sorted list, a total of 63 clusters containing 258 abandoned houses were formed and then randomly allocated to 3 study arms. Of the 301 participants interviewed during the preintervention period, 172 (57.1%) were interviewed during the postintervention period and were included in this analysis; participants were predominantly Black, and most were employed. Study neighborhoods were predominantly Black with high percentages of low-income households. Gun violence outcomes increased in all study arms, but increased the least in the full remediation arm. The full housing remediation arm, compared with the control condition, showed reduced weapons violations by -8.43% (95% CI, -14.68% to -1.19%), reduced gun assaults by -13.12% (95% CI, -21.32% to -3.01%), and reduced shootings by a nonsignificant -6.96% (95% CI, -15.32% to 3.03%). The trash cleanup arm was not associated with a significant differential change in any gun violence outcome. Instances of illegal substance trafficking and use and public drunkenness outcomes were not significantly affected by the housing remediation or trash cleanup treatment. Perceptions of neighborhood safety and time spent outside were unaffected by the intervention. The study arms did differ in a baseline characteristic and some preintervention trends, which raises questions regarding other potential nonmeasured differences between study arms that could have influenced estimates. No evidence of displacement of gun violence outcomes was found., Conclusions and Relevance: In this cluster randomized controlled trial among low-income, predominantly Black neighborhoods, inexpensive, straightforward abandoned housing remediation was directly linked to significant relative reductions in weapons violations and gun assaults, and suggestive reductions in shootings., Trial Registration: isrctn.org Identifier: ISRCTN14973997.

Gun violence rates increased in U.S. cities in 2020 and into 2021. Gun violence rates in U.S. cities is typically concentrated in racially segregated neighborhoods with higher poverty levels. However, poverty levels and demographics alone do not explain the high concentration of violence or its relative change over time. In this paper, we examine the extent to which the increase in shooting victimization in Philadelphia, New York, and Los Angeles during the 2020-2021 pandemic was concentrated in gun violence hot spots, and how the increase impacted race and ethnic disparities in shooting victimization rates. We find that 36% (Philadelphia), 47% (New York), and 55% (Los Angeles) of the increase in shootings observed during the period 2020-2021 occurred in the top decile of census block groups, by aggregate number of shootings, and that the race/ethnicity of victims in these gun violence hot spots were disproportionately Black and Hispanic. We discuss the implications of these findings as they relate to racial disparities in victimization and place-based efforts to reduce gun violence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background & Aims: Proactive therapeutic drug monitoring (TDM) has been proposed to improve outcomes in patients with inflammatory bowel disease (IBD) treated with tumor necrosis factor (TNF)α antagonists. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing proactive TDM with conventional management in patients with IBD., Methods: We identified RCTs in patients with IBD treated with TNFα antagonists comparing proactive TDM (routine assessments of trough concentration with dose adjustments to maintain predetermined trough concentration, regardless of disease activity) with conventional management (clinically driven dose adjustments). The primary outcome was failure to maintain clinical remission. Certainty of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluations., Results: On meta-analysis of 9 RCTs (8 RCTs in adults, and focusing on maintenance phase), there was no significant difference in the risk of failing to maintain clinical remission in patients who underwent proactive TDM (267/709; 38%) vs conventional management (292/696; 42%) (relative risk [RR], 0.96; 95% confidence interval [CI], 0.81-1.13) with moderate heterogeneity (inconsistency index = 36%) (Grading of Recommendations, Assessment, Development and Evaluations; low certainty evidence), with no differences in patients with Crohn's disease (RR, 0.87 ; 95% CI, 0.66-1.15) and ulcerative colitis (RR, 0.88; 95% CI, 0.72-1.07). Disease duration, concomitant immunomodulators, disease activity at baseline, and optimization of therapy before randomization did not modify this association. No differences were observed in risk of developing antidrug antibodies or serious adverse events. Patients in the proactive TDM arm were more likely to undergo dose escalation (RR, 1.56; 95% CI, 1.25-1.94)., Conclusions: Routine proactive TDM to target biologic concentration to specific thresholds, regardless of disease activity, did not offer clinical benefit in patients with IBD treated with TNFα antagonists in RCTs conducted to date. We cannot exclude the possibility of benefit in disease subtypes and phases of therapy (induction) not represented in these RCT populations., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The murder of George Floyd triggered a broad social response and noticeable shift in public opinion of policing. Since policing is dependent upon public cooperation, a question is whether the shift in opinion had an effect on police calls-for-service. Data from Los Angeles and New York City are evaluated using a regression discontinuity design. Violent crime, property crime, and quality-of-life disorder calls are analyzed to address differences in reporting norms. The role of racial-ethnic composition of local areas is assessed by examining census tracts where the majority of the residential population is Asian, Black, Hispanic, or White. Following the murder of George Floyd, in New York City violent crime, property crime, and quality-of-life calls all increased significantly. In Los Angeles, quality-of-life calls for service decreased significantly. The increase in violent crime calls observed in New York was greatest in areas where the majority of residents are Black, whereas the increase in property crime calls was the greatest in areas where a majority of residents are White. The decrease in quality-of-life calls observed in Los Angeles was in areas where the majority of residents are White. In both cases, the effect was relatively short-lived., (© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences.)

Objective: Place-based blight remediation programs have gained popularity in recent years as a crime reduction approach. This study estimated the impact of a citywide vacant lot greening program in Philadelphia on changes in crime over multiple years, and whether the effects were moderated by nearby land uses., Methods: The vacant lot greening program was assessed using quasi-experimental and experimental designs. Entropy distance weighting was used in the quasi-experimental analysis to match control lots to be comparable to greened lots on pre-existing crime trends. Fixed-effects difference-in-differences models were used to estimate the impact of the vacant lot greening program in quasi-experimental and experimental analyses., Results: Vacant lot greening was estimated to reduce total crime and multiple subcategories in both the quasi-experimental and experimental evaluations. Remediating vacant lots had a smaller effect on reducing crime when they were located nearby train stations and alcohol outlets. The crime reductions from vacant lot remediations were larger when they were located near areas of active businesses. There is some suggestive evidence that the effects of vacant lot greening are larger when located in neighborhoods with higher pre-intervention levels of social cohesion., Conclusions: The findings suggest that vacant lot greening provides a sustainable approache to reducing crime in disadvantaged neighborhoods, and the effects may vary by different surrounding land uses. To better understand the mechanisms through which place-based blight remediation interventions reduce crime, future research should measure human activities and neighborly socialization in and around places before and after remediation efforts are implemented.

Weathering of silicate-rich industrial wastes such as slag can reduce emissions from the steelmaking industry. During slag weathering, different minerals spontaneously react with atmospheric CO 2 to produce calcite. Here, we evaluate the CO 2 uptake during slag weathering using image-based analysis. The analysis was applied to an X-ray computed tomography (XCT) dataset of a slag sample associated with the former Ravenscraig steelworks in Lanarkshire, Scotland. The element distribution of the sample was studied using scanning electron microscopy (SEM), coupled with energy-dispersive spectroscopy (EDS). Two advanced image segmentation methods, namely trainable WEKA segmentation in the Fiji distribution of ImageJ and watershed segmentation in Avizo ® 9.3.0, were used to segment the XCT images into matrix, pore space, calcite, and other precipitates. Both methods yielded similar volume fractions of the segmented classes. However, WEKA segmentation performed better in segmenting smaller pores, while watershed segmentation was superior in overcoming the partial volume effect presented in the XCT data. We estimate that CO 2 has been captured in the studied sample with an uptake between 20 and 17 kg CO 2 /1,000 kg slag for TWS and WS, respectively, through calcite precipitation.

Background: Precision in estimating placebo rates is important for clinical trial design., Aim: To quantify placebo rates across relevant endpoints in Crohn's disease [CD] trials and identify the factors influencing these rates in a contemporary meta-analysis., Methods: We searched MEDLINE, EMBASE, and CENTRAL from inception to March 2021. Eligible studies were placebo-controlled trials of pharmacological interventions for CD. Placebo response and remission rates for induction and maintenance trials were extracted and pooled by random-effects to quantify placebo rates across studies. Mixed-effects meta-regression was used to evaluate the effects of study-level characteristics on placebo rates., Results: In 125 studies [91 induction, 46 maintenance], placebo clinical remission and response rates for induction studies were 18% (95% confidence interval [CI] 16, 21%], and 32% [95% CI 29, 35%], respectively, and for maintenance studies were 28% [95% CI 23, 34%] and 30% [95% CI 24, 37%], respectively. Endoscopic remission and response rates in induction studies were 8% [95% CI 4, 18%] and 16% [95% CI 11, 23%], respectively. Trials enrolling patients with prior biologic exposure, longer disease duration, and higher CD activity index scores were associated with lower placebo clinical remission rates. Increased duration of follow-up, more follow-up visits, and a greater proportion of patients with colonic disease distribution were associated with higher clinical placebo rates., Conclusions: Placebo remission and response rates in CD trials vary according to the phase of the trial, endpoint assessed, and induction or maintenance design. These contemporary estimates will help to inform future CD trial design., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Alkaline wastes have been the focus of many studies as they act as CO 2 sinks and have the potential to offset emissions from mining and steelmaking industries. Passive carbonation of alkaline wastes mimics natural silicate weathering and provides a promising alternative pathway for CO 2 capture and storage as carbonates, requiring marginal human intervention when compared to ex-situ carbonation. This review summarizes the extant research that has investigated the passive carbonation of alkaline wastes, namely ironmaking and steelmaking slag, mine tailings and demolition wastes, over the past two decades. Here we report different factors that affect passive carbonation to address challenges that this process faces and to identify possible solutions. We identify avenues for future research such as investigating how passive carbonation affects the surrounding environment through interaction with the biosphere and the hydrosphere. Future research should also consider economic analyses to provide investors with an in-depth understanding of passive carbonation techniques. Based on the reviewed materials, we conclude that passive carbonation can be an important contributor to climate change mitigation strategies, and its potential can be intensified by applying simple waste management practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Community-based research inclusive of self-assessment and objective environmental metrics can be enhanced by the collection of biomarker data in unity toward assessing the health impacts of the totality of environmental stress driven by structural racism. Cortisol dynamic range (CDR), a measure of chronic stress burden, may underpin place-based connections to health, but a gap remains in elucidating community-based CDR methodology., Purpose: To 1) assess the feasibility of cortisol collection and CDR measurement in a community-based study with home-based, participant-directed specimen collection, and 2) explore the association between CDR and other individual and environmental measures in a sample of predominantly Black participants. Methods : In this cross-sectional, observational study in predominantly Black urban neighborhoods, participants (n = 73) completed health assessments and in-home, self-collected salivary cortisol. For feasibility, CDR (peak-nadir) was compared to cortisol awakening response (CAR) slope over time. Comparisons of CDR quartile by person and place variables were explored (ANOVA)., Results: The cohort (77% Black, 39.7% <$15 k/year income, high perceived stress) completed 98.6% of cortisol collection timepoints. CDR was calculated in all participants without interruptions to sleep-wake cycle as seen with CAR collection. Participants in the lowest quartile of CDR were the oldest (p = 0.03) with lowest reported mental health (p = 0.048) with no associations seen for CAR., Conclusion: Participant-collected CDR is more feasible than cortisol measures dependent on slopes over time in a community-based, predominately Black cohort with exploratory findings supporting relevance to outcomes of interest to future work. Future community-based studies should integrate CDR with environment and psychosocial measures., Competing Interests: The authors received support in training and completion of the study from the University of Pennsylvania Perelman School of Medicine. The study was funded in part by grant 5R01AA024941 from the National Institutes of Health., (© 2022 The Authors. Published by Elsevier Ltd.)

Background: Patients treated with immune checkpoint inhibitors (ICIs) may develop ICI-associated enterocolitis, for which there is no approved treatment., Aims: We aimed to systematically review the efficacy and safety of medical interventions for the prevention and treatment of ICI-associated enterocolitis., Methods: MEDLINE, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials (RCTs), cohort and case-control studies, and case series/reports, evaluating interventions (including corticosteroids, biologics, aminosalicylates, immunosuppressants, and fecal transplantation) for ICI-associated enterocolitis. Clinical, endoscopic, and histologic efficacy endpoints were evaluated. The Grading of Recommendations, Assessment, Development, and Evaluation criteria were used to assess overall quality of evidence., Results: A total of 160 studies (n = 1514) were included (one RCT, 3 retrospective cohort studies, 156 case reports/case series). Very low quality evidence from one RCT suggests budesonide is not effective for prevention of ICI-associated enterocolitis in ipilimumab-treated patients (relative risk 0.93 [95% confidence interval 0.56, 1.56]). Very low quality evidence suggests that corticosteroids, infliximab, and vedolizumab may be effective for treatment of ICI-associated enterocolitis by inducing clinical response and remission. No validated indices for measuring disease activity were used. Biologic treatment was used in 42% (641/1528) of patients, as reported in 97 studies. ICIs were discontinued in 65% (457/702) of patients, as reported in 63 studies., Conclusions: Current treatment recommendations for ICI-associated enterocolitis are based on very low quality evidence, primarily from case reports and case series. Large-scale prospective cohort studies and RCTs are needed to develop prophylactic and therapeutic treatments to minimize interruption or discontinuation of oncological therapies., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: We aimed to quantify the magnitude of the association between endoscopic recurrence and clinical recurrence [symptom relapse] in patients with postoperative Crohn's disease., Methods: Databases were searched to October 2, 2020, for randomised controlled trials [RCTs] and cohort studies of adult patients with Crohn's disease with ileocolonic resection and anastomosis. Summary effect estimates for the association between clinical recurrence and endoscopic recurrence were quantified by risk ratios [RR] and 95% confidence intervals [95% CI]. Mixed-effects meta-regression evaluated the role of confounders. Spearman correlation coefficients were calculated to assess the relationship between these outcomes as endpoints in RCTs. An exploratory mixed-effects meta-regression model with the logit of the rate of clinical recurrence as the outcome and the rate of endoscopic recurrence as a predictor was also evaluated., Results: In all, 37 studies [N = 4053] were included. For eight RCTs with available data, the RR for clinical recurrence for patients who experienced endoscopic recurrence was 10.77 [95% CI 4.08 to 28.40; GRADE moderate certainty evidence]; the corresponding estimate from 11 cohort studies was 21.33 [95% CI 9.55 to 47.66; GRADE low certainty evidence]. A single cohort study showed a linear relationship between Rutgeerts score and clinical recurrence risk. There was a strong correlation between endoscopic recurrence and clinical recurrence treatment effect estimates as trial outcomes [weighted Spearman correlation coefficient 0.51]., Conclusions: The associations between endoscopic recurrence and subsequent clinical recurrence lend support to the choice of endoscopic recurrence to monitor postoperative disease activity and as a primary endpoint in clinical trials of postoperative Crohn's disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

CTEA (N,N-bis[2-(carboxylmethyl)thioethyl]amine) is a mixed donor ligand that has been incorporated into multiple fluorescent sensors such as NiSensor-1 that was reported to be selective for Ni 2+ . Other metal ions such as Zn 2+ do not produce an emission response in aqueous solution. To investigate the coordination chemistry and selectivity of this receptor, we prepared NiCast, a photocage containing the CTEA receptor. Cast photocages undergo a photoreaction that decreases electron density on a metal-bound aniline nitrogen atom, which shifts the binding equilibrium toward unbound metal ion. The unique selectivity of CTEA was examined by measuring the binding affinity of NiCast and the CTEA receptor for Ni 2+ , Zn 2+ , Cd 2+ and Cu 2+ under different conditions. In aqueous solution, Ni 2+ binds more strongly to the aniline nitrogen atom than Cd 2+ ; however, in CH 3 CN, the change in affinity virtually disappears. The crystal structure of [Cu(CTEA)], which exhibits a Jahn-Teller-distorted square pyramidal structure, was also analyzed to gain more insight into the underlying coordination chemistry. These studies suggest that the fluorescence selectivity of NiSensor-1 in aqueous solution is due to a stronger interaction between the aniline nitrogen atom and Ni 2+ compared to other divalent metal ions except Cu 2+ ., (© 2021 American Society for Photobiology.)

Immune checkpoint inhibitor-associated colitis (ICIC) affects approximately 15% of cancer patients treated with immunotherapy. Although histological evaluation is potentially valuable for both the diagnosis of ICIC and evaluation of disease activity, use in clinical practice is heterogeneous. We aimed to develop expert recommendations to standardize histological assessment of disease activity in patients with ICIC. Using the modified Research and Development/University of California Los Angeles (RAND/UCLA) appropriateness methodology, an international panel of 11 pathologists rated the appropriateness of 99 statements on a 9-point Likert scale during two rounds of anonymous voting. Results were discussed between rounds using moderated videoconferences. There are currently no disease-specific instruments for assessing histological features of ICIC. The panel considered that colonoscopy with at least three biopsies per segment from a total of at least five segments, including both endoscopically normal and inflamed areas, was appropriate for tissue acquisition. They agreed that biopsies should be oriented such that the long axis of the colonic crypts is visualized and should be stained with hematoxylin and eosin. Histological items that the panel voted were appropriate to evaluate in ICIC included the degree of structural/architectural change, chronic inflammatory infiltrate, lamina propria and intraepithelial neutrophils, crypt abscesses and destruction, erosions/ulcerations, apoptosis, surface intraepithelial lymphocytosis, and subepithelial collagen thickness. The appropriateness of routine immunohistochemistry was uncertain. These expert recommendations will help standardize assessment of histological activity in patients with ICIC. The panel also identified the development and validation of an ICIC-specific histological index as a research priority., Competing Interests: Competing interests: CM has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pfizer, Roche; speaker's fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Ferring, Janssen, Takeda, and Pfizer; research support from Pfizer. RiKP has received consulting fees from AbbVie, Eli Lilly, Allergan, Genentech, and Alimentiv. DFS has received consulting fees from Merck, Diaceutics, Pfizer, Allakos, and Alimentiv; stock ownership in Satisfai Health. JK has received advisory fees from Clovis Oncology, AstraZeneca, and Tesaro. LG is an employee of Alimentiv. SCM is an employee of Alimentiv. JKM is an employee of Alimentiv. RMF receives consulting fees from Alimentiv and has received fees from Bristol Myers Squibb, Janssen, and Takeda. RK has received consulting fees from Alimentiv. GYL has received consulting fees from Alimentiv. ReKP has received consulting fees from Alimentiv. CR has received consulting fees from Alimentiv. BGF is a scientific advisory board member for AbbVie, Allergan, Amgen, AstraZeneca, Avaxia Biologics Inc., Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Elan, Biogen, Ferring, Genentech–Roche, Janssen–Johnson & Johnson, Merck, Millennium, Nestlé, Novo Nordisk, Novartis, Pfizer, Prometheus, Protagonist, Receptos, Salix, Sigmoid Pharma, Takeda, Teva, TiGenix, Tillotts Pharma, and UCB Pharma; consulting fees from AbbVie, Actogenix, Akros, Albireo Pharma, Allergan, Amgen, AstraZeneca, Avaxia Biologics, Avir Pharma, Axcan, Baxter Healthcare, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan–Biogen, EnGene, Ferring, Genentech–Roche, GiCare Pharma, Gilead Sciences, Given Imaging, GlaxoSmithKline, Ironwood, Janssen Biotech–Centocor, Janssen–Johnson & Johnson, Kyowa Hakko Kirin, Eli Lilly, Merck, Mesoblast Pharma, Millennium, Nestlé, Novo Nordisk, Novartis, Pfizer, Prometheus, Protagonist, Receptos Salix, Sanofi, Shire, Sigmoid Pharma, Synergy Pharma, Takeda, Teva, TiGenix, Tillotts Pharma, UCB Pharma, Vertex, VHsquared, Wyeth, Zealand, and Zygenia; lecture fees from AbbVie, Janssen–Johnson & Johnson, Takeda, and UCB Pharma, and grant support from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen Biotech–Centocor, Janssen–Johnson & Johnson, Pfizer, Receptos, Sanofi, and Takeda, and is the Senior Scientific Officer of Alimentiv Inc. VJ has received has received consulting/advisory board fees from AbbVie, Alimentiv (formerly Robarts Clinical Trials), Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert; speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Quantifying placebo rates and the factors influencing them are essential to inform trial design. We provide a contemporary summary of clinical, endoscopic, histological and safety placebo rates in induction and maintenance clinical trials of ulcerative colitis, and identify factors influencing them., Methods: MEDLINE, EMBASE and the Cochrane library were searched from April 2014 to April 2020, updating a prior meta-analysis that searched from inception to April 2014. We included placebo-controlled trials of aminosalicylates, corticosteroids, immunosuppressives, small-molecules and biologics in adults with ulcerative colitis. Placebo rates were pooled using random-effects and mixed-effects meta-regression models to assess the associated study-level., Results: In 119 trials [92 induction, 27 maintenance] clinical, endoscopic and histological remission placebo rates for induction trials were 11% (95% confidence interval [CI] 9-13%), 19% [95% CI 15-23%] and 15% [95% CI 11-19%], respectively; for maintenance trials, clinical and endoscopic placebo remission rates were 18% [95% CI 12-25%] and 20% [95% CI 15-25%], respectively. Higher endoscopic subscore and a higher rate of exposure to prior biologic therapy at enrolment were associated with lower clinical and endoscopic placebo remission rates. Absence of central reading was associated with an increase in placebo endoscopic response and remission rates. More follow-up visits and increasing trial duration were associated with higher clinical placebo rates., Conclusions: Placebo rates in ulcerative colitis trials vary according to the endpoint assessed, whether it is for assessment of response or remission, and whether the trial is designed for induction or maintenance. These contemporary rates across different endpoints and drug classes will help to inform trial design., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Early life exposure to environmental lead (Pb) has been linked to decreased IQ, behavior problems, lower lifetime earnings, and increased criminal activity. Beginning in the 1970s, limits on Pb in paint, gasoline, food cans, and regulated water utilities sharply curtailed US environmental Pb exposure. Nonetheless, hundreds of thousands of US children remain at risk. This study reports on how unregulated private well water is an underrecognized Pb exposure source that is associated with an increased risk of teenage juvenile delinquency. We build a longitudinal dataset linking blood Pb measurements for 13,580 children under age 6 to their drinking water source, individual- and neighborhood-level demographics, and reported juvenile delinquency records. We estimate how early life Pb exposure from private well water influences reported delinquency. On average, children in homes with unregulated private wells had 11% higher blood Pb than those with community water service. This higher blood Pb was significantly associated with reported delinquency. Compared to children with community water service, those relying on private wells had a 21% (95% CI: 5 to 40%) higher risk of being reported for any delinquency and a 38% (95% CI: 10 to 73%) increased risk of being reported for serious delinquency after age 14. These results suggest that there could be substantial but as-yet-unrecognized social benefits from intervention programs to prevent children's exposure to Pb from private wells, on which 13% of the US population relies., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

Competing Interests: The authors declare no conflicts of interest.

Background: Although there is interest in developing pharmacotherapies for the treatment of immune checkpoint inhibitor-associated enterocolitis (ICIC), there is currently no consensus on how to optimally measure disease activity in this condition., Aims: To identify all scoring indices used for the measurement of disease activity in ICIC, assess their operating properties, and explore their potential utility as outcome measures., Methods: We searched MEDLINE, EMBASE and the Cochrane Library from inception to November 2020 to identify studies that evaluated disease activity and severity in patients with ICI-associated enterocolitis. These scoring tools could be designed specifically for ICIC or adapted from other diseases, and assessed clinical, endoscopic, or histologic disease activity., Results: Sixty-four studies were included. The Common Terminology Criteria for Adverse Events is commonly used to describe symptoms, although has only been partially validated and was not designed as a disease activity index. Endoscopic and histologic indices used in inflammatory bowel disease have been adopted for ICIC including the Mayo Endoscopic Subscore, Ulcerative Colitis Endoscopic Index of Severity, Simple Endoscopic Score for Crohn's Disease, Nancy Histological Index, Robarts Histopathological Index, and Geboes Score, among others. None of these indices has been validated for use in ICIC, and all lacked content validity and responsiveness., Conclusions: There are no validated clinical, endoscopic, or histologic outcomes to assess disease activity in ICIC. Development and validation of reliable and responsive outcome measures that can be used to measure disease activity will be paramount for both clinical practice and for the development of treatments., (© 2021 John Wiley & Sons Ltd.)

The pedestrian-induced instability of the London Millennium Bridge is a widely used example of Kuramoto synchronisation. Yet, reviewing observational, experimental, and modelling evidence, we argue that increased coherence of pedestrians' foot placement is a consequence of, not a cause of the instability. Instead, uncorrelated pedestrians produce positive feedback, through negative damping on average, that can initiate significant lateral bridge vibration over a wide range of natural frequencies. We present a simple general formula that quantifies this effect, and illustrate it through simulation of three mathematical models, including one with strong propensity for synchronisation. Despite subtle effects of gait strategies in determining precise instability thresholds, our results show that average negative damping is always the trigger. More broadly, we describe an alternative to Kuramoto theory for emergence of coherent oscillations in nature; collective contributions from incoherent agents need not cancel, but can provide positive feedback on average, leading to global limit-cycle motion., (© 2021. The Author(s).)

Importance: The root causes of violent crime in Black urban neighborhoods are structural, including residential racial segregation and concentrated poverty. Previous work suggests that simple and scalable place-based environmental interventions can overcome the legacies of neighborhood disinvestment and have implications for health broadly and crime specifically., Objective: To assess whether structural repairs to the homes of low-income owners are associated with a reduction in nearby crime., Design, Setting, and Participants: This cross-sectional study using difference-in-differences analysis included data from the City of Philadelphia Basic Systems Repair Program (BSRP) from January 1, 2006, through April 30, 2013. The unit of analysis was block faces (single street segments between 2 consecutive intersecting streets) with or without homes that received the BSRP intervention. The blocks of homes that received BSRP services were compared with the blocks of eligible homes that were still on the waiting list. Data were analyzed from December 1, 2019, to February 28, 2021., Exposures: The BSRP intervention includes a grant of up to $20 000 provided to low-income owners for structural repairs to electrical, plumbing, heating, and roofing damage. Eligible homeowners must meet income guidelines, which are set by the US Department of Housing and Urban Development and vary yearly., Main Outcomes and Measures: The main outcome was police-reported crime across 7 major categories of violent and nonviolent crimes (homicide, assault, burglary, theft, robbery, disorderly conduct, and public drunkenness)., Results: A total of 13 632 houses on 6732 block faces received the BSRP intervention. Owners of these homes had a mean (range) age of 56.5 (18-98) years, were predominantly Black (10 952 [78.6%]) or Latino (1658 [11.9%]) individuals, and had a mean monthly income of $993. These census tracts compared with those without BSRP intervention had a substantially larger Black population (49.5% vs 12.2%; |D| = 0.406) and higher unemployment rate (17.3% vs 9.3%; |D| = 0.357). The main regression analysis demonstrated that the addition to a block face of a property that received a BSRP intervention was associated with a 21.9% decrease in the expected count of total crime (incidence rate ratio [IRR], 0.78; 95% CI, 0.76-0.80; P < .001), 19.0% decrease in assault (IRR, 0.81; 95% CI, 0.79-0.84; P < .001), 22.6% decrease in robbery (IRR, 0.77; 95% CI, 0.75-0.80; P < .001), and 21.9% decrease in homicide (IRR, 0.78; 95% CI, 0.71-0.86; P < .001). When restricting the analysis to blocks with properties that had ever received a BSRP intervention, a total crime reduction of 25.4% was observed for each additional property (IRR, 0.75; 95% CI, 0.73-0.77; P < .001). A significant dose-dependent decrease in total crime was found such that the magnitude of association increased with higher numbers of homes participating in the BSRP on a block., Conclusions and Relevance: This study found that the BSRP intervention was associated with a modest but significant reduction in crime. These findings suggest that intentional and targeted financial investment in structural, scalable, and sustainable place-based interventions in neighborhoods that are still experiencing the lasting consequences of structural racism and segregation is a vital step toward achieving health equity.

A single-centre retrospective observational study aimed at observing the outcomes of using DEB in ACS patients. All-comer ninety patients were included with a follow-up of 12-36 months. DEBs were deployed successfully yielding TIMI 3 without significant coronary dissection. MACE was 1.1% and 3.3% for 30 days and 12-36 months respectively., Competing Interests: Declaration of competing interest Authors have no conflict of interest., (Copyright © 2021 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: The goal of this consensus conference, sponsored by the American Association of Plastic Surgeons, was to perform a systematic review and meta-analysis of controlled trials to examine both the benefits and risks of surgical treatment and surgical prevention of upper and lower extremity lymphedema., Methods: The panel met in Boston for a 3-day, face-to-face meeting in July of 2017. After an exhaustive review of the existing literature, the authors created consensus recommendations using the Grading of Recommendations, Assessment, Development and Evaluation criteria. Important directions for future research were also identified., Results: There is evidence to support that lymphovenous anastomosis can be effective in reducing severity of lymphedema (grade 1C). There is evidence to support that vascular lymph node transplantation can be effective in reducing severity of lymphedema (grade 1B). Currently, there is no consensus on which procedure (lymphovenous bypass versus vascular lymph node transplantation) is more effective (grade 2C). A few studies show that prophylactic lymphovenous bypass in patients undergoing extremity lymphadenectomy may reduce the incidence of lymphedema (grade 1B). More studies with longer follow-up are required to confirm this benefit. Debulking procedures such as liposuction are effective in addressing a nonfluid component such as fat involving lymphedema (grade 1C). There is a role for liposuction combined with physiologic procedures although the timing of each procedure is currently unresolved (grade 1C)., Conclusions: Many studies seem to support some efficacy of lymphovenous bypass and vascular lymph node transplantation. Many studies show the important role of lymphedema therapy and other procedures such as liposuction and debulking. The management of lymphedema is a challenging field with many promising advances. However, many questions remain unanswered., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Background: Oral 5-aminosalicylic acid (5-ASA; also known as mesalazine or mesalamine) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. In an earlier version of this review, we found that 5-ASA drugs were more effective than placebo for maintenance of remission of ulcerative colitis (UC), but had a significant therapeutic inferiority relative to SASP. In this version, we have rerun the search to bring the review up to date., Objectives: To assess the efficacy, dose-responsiveness, and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for maintenance of remission in quiescent UC and to compare the efficacy and safety of once-daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens., Search Methods: We performed a literature search for studies on 11 June 2019 using MEDLINE, Embase, and the Cochrane Library. In addition, we searched review articles and conference proceedings., Selection Criteria: We included randomized controlled trials with a minimum treatment duration of six months. We considered studies of oral 5-ASA therapy for treatment of participants with quiescent UC compared with placebo, SASP, or other 5-ASA formulations. We also included studies that compared once-daily 5-ASA treatment with conventional dosing of 5-ASA and 5-ASA dose-ranging studies., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. The primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes were adherence, adverse events (AE), serious adverse events (SAE), withdrawals due to AEs, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus SASP, once-daily dosing versus conventional dosing, 5-ASA (balsalazide, Pentasa, and olsalazine) versus comparator 5-ASA formulation (Asacol and Salofalk), and 5-ASA dose-ranging. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each outcome. We analyzed data on an intention-to-treat basis, and used GRADE to assess the overall certainty of the evidence., Main Results: The search identified 44 studies (9967 participants). Most studies were at low risk of bias. Ten studies were at high risk of bias. Seven of these studies were single-blind and three were open-label. 5-ASA is more effective than placebo for maintenance of clinical or endoscopic remission. About 37% (335/907) of 5-ASA participants relapsed at six to 12 months compared to 55% (355/648) of placebo participants (RR 0.68, 95% CI 0.61 to 0.76; 8 studies, 1555 participants; high-certainty evidence). Adherence to study medication was not reported for this comparison. SAEs were reported in 1% (6/550) of participants in the 5-ASA group compared to 2% (5/276) of participants in the placebo group at six to 12 months (RR 0.60, 95% CI 0.19 to 1.84; 3 studies, 826 participants; low-certainty evidence). There is probably little or no difference in AEs at six to 12 months' follow-up (RR 0.93, 95% CI 0.73 to 1.18; 5 studies, 1132 participants; moderate-certainty evidence). SASP is more effective than 5-ASA for maintenance of remission. About 48% (416/871) of 5-ASA participants relapsed at six to 18 months compared to 43% (336/784) of SASP participants (RR 1.14, 95% CI 1.03 to 1.27; 12 studies, 1655 participants; high-certainty evidence). Adherence to study medication and SAEs were not reported for this comparison. There is probably little or no difference in AEs at six to 12 months' follow-up (RR 1.07, 95% CI 0.82 to 1.40; 7 studies, 1138 participants; moderate-certainty evidence). There is little or no difference in clinical or endoscopic remission rates between once-daily and conventionally dosed 5-ASA. About 37% (717/1939) of once-daily participants relapsed over 12 months compared to 39% (770/1971) of conventional-dosing participants (RR 0.94, 95% CI 0.88 to 1.01; 10 studies, 3910 participants; high-certainty evidence). There is probably little or no difference in medication adherence rates. About 10% (106/1152) of participants in the once-daily group failed to adhere to their medication regimen compared to 8% (84/1154) of participants in the conventional-dosing group (RR 1.18, 95% CI 0.72 to 1.93; 9 studies, 2306 participants; moderate-certainty evidence). About 3% (41/1587) of participants in the once-daily group experienced a SAE compared to 2% (35/1609) of participants in the conventional-dose group at six to 12 months (RR 1.20, 95% CI 0.77 to 1.87; moderate-certainty evidence). There is little or no difference in the incidence of AEs at six to 13 months' follow-up (RR 0.98, 95% CI 0.92 to 1.04; 8 studies, 3497 participants; high-certainty evidence). There may be little or no difference in the efficacy of different 5-ASA formulations. About 44% (158/358) of participants in the 5-ASA group relapsed at six to 18 months compared to 41% (142/349) of participants in the 5-ASA comparator group (RR 1.08, 95% CI 0.91 to 1.28; 6 studies, 707 participants; low-certainty evidence)., Authors' Conclusions: There is high-certainty evidence that 5-ASA is superior to placebo for maintenance therapy in UC. There is high-certainty evidence that 5-ASA is inferior compared to SASP. There is probably little or no difference between 5-ASA and placebo, and 5-ASA and SASP in commonly reported AEs such as flatulence, abdominal pain, nausea, diarrhea, headache, and dyspepsia. Oral 5-ASA administered once daily has a similar benefit and harm profile as conventional dosing for maintenance of remission in quiescent UC., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Oral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. It was previously found that 5-ASA drugs in doses of at least 2 g/day were more effective than placebo but no more effective than SASP for inducing remission in ulcerative colitis (UC). This review is an update of a previously published Cochrane Review., Objectives: To assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators (i.e. other formulations of 5-ASA) for induction of remission in active UC. A secondary objective was to compare the efficacy and safety of once-daily dosing of oral 5-ASA versus conventional dosing regimens (two or three times daily)., Search Methods: We searched MEDLINE, Embase and the Cochrane Library on 11 June 2019. We also searched references, conference proceedings and study registers to identify additional studies., Selection Criteria: We considered randomized controlled trials (RCTs) including adults (aged 18 years or more) with active UC for inclusion. We included studies that compared oral 5-ASA therapy with placebo, SASP, or other 5-ASA formulations. We also included studies that compared once-daily to conventional dosing as well as dose-ranging studies., Data Collection and Analysis: Outcomes include failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, endoscopic improvement, adherence, adverse events (AEs), serious adverse events (SAEs), withdrawals due to AEs, and withdrawals or exclusions after entry. We analyzed five comparisons: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once-daily dosing versus conventional dosing, 5-ASA (e.g. MMX mesalamine, Ipocol, Balsalazide, Pentasa, Olsalazine and 5-ASA micropellets) versus comparator 5-ASA (e.g. Asacol, Claversal, Salofalk), and 5-ASA dose-ranging. We calculated the risk ratio (RR) and 95% confidence interval (95% CI) for each outcome. We analyzed data on an intention-to-treat basis, and used GRADE to assess the overall certainty of the evidence., Main Results: We include 54 studies (9612 participants). We rated most studies at low risk of bias. Seventy-one per cent (1107/1550) of 5-ASA participants failed to enter clinical remission compared to 83% (695/837) of placebo participants (RR 0.86, 95% CI 0.82 to 0.89; 2387 participants, 11 studies; high-certainty evidence). We also observed a dose-response trend for 5-ASA. There was no difference in clinical remission rates between 5-ASA and SASP. Fifty-four per cent (150/279) of 5-ASA participants failed to enter remission compared to 58% (144/247) of SASP participants (RR 0.90, 95% CI 0.77 to 1.04; 526 participants, 8 studies; moderate-certainty evidence). There was no difference in remission rates between once-daily dosing and conventional dosing. Sixty per cent (533/881) of once-daily participants failed to enter clinical remission compared to 61% (538/880) of conventionally-dosed participants (RR 0.99, 95% CI 0.93 to 1.06; 1761 participants, 5 studies; high-certainty evidence). Eight per cent (15/179) of participants dosed once daily failed to adhere to their medication regimen compared to 6% (11/179) of conventionally-dosed participants (RR 1.36, 95% CI 0.64 to 2.86; 358 participants, 2 studies; low-certainty evidence). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Fifty per cent (507/1022) of participants in the 5-ASA group failed to enter remission compared to 52% (491/946) of participants in the 5-ASA comparator group (RR 0.94, 95% CI 0.86 to 1.02; 1968 participants, 11 studies; moderate-certainty evidence). There was no evidence of a difference in the incidence of adverse events and serious adverse events between 5-ASA and placebo, once-daily and conventionally-dosed 5-ASA, and 5-ASA and comparator 5-ASA formulation studies. Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache and worsening UC. SASP was not as well tolerated as 5-ASA. Twenty-nine per cent (118/411) of SASP participants experienced an AE compared to 15% (72/498) of 5-ASA participants (RR 0.48, 95% CI 0.36 to 0.63; 909 participants, 12 studies; moderate-certainty evidence)., Authors' Conclusions: There is high-certainty evidence that 5-ASA is superior to placebo, and moderate-certainty evidence that 5-ASA is not more effective than SASP. Considering relative costs, a clinical advantage to using oral 5-ASA in place of SASP appears unlikely. High-certainty evidence suggests 5-ASA dosed once daily appears to be as efficacious as conventionally-dosed 5-ASA. There may be little or no difference in efficacy or safety among the various 5-ASA formulations., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Although the Flint, Michigan, water crisis renewed concerns about lead (Pb) in city drinking water, little attention has been paid to Pb in private wells, which provide drinking water for 13% of the US population. This study evaluates the risk of Pb exposure in children in households relying on private wells. It is based on a curated dataset of blood Pb records from 59,483 North Carolina children matched with household water source information. We analyze the dataset for statistical associations between children's blood Pb and household drinking water source. The analysis shows that children in homes relying on private wells have 25% increased odds (95% CI 6.2 to 48%, P < 0.01) of elevated blood Pb, compared with children in houses served by a community water system that is regulated under the Safe Drinking Water Act. This increased Pb exposure is likely a result of corrosion of household plumbing and well components, because homes relying on private wells rarely treat their water to prevent corrosion. In contrast, corrosion control is required in regulated community water systems. These findings highlight the need for targeted outreach to prevent Pb exposure for the 42.5 million Americans depending on private wells for their drinking water., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Critical to the success of establishing a sustainable human presence on Mars is the ability to economically grow crop plants. Several environmental factors make it difficult to fully rely on local resources for agriculture. These include nutrient sparse regolith, low and fluctuating temperatures, a high amount of ultraviolet radiation, and water trapped locally in the form of ice or metal oxides. While the 96% CO 2 martian atmosphere is ideal to support photosynthesis, high CO 2 concentrations inhibit germination. An added difficulty is the fact that a vast majority of crop plants require oxygen for germination. Here, we report the production of a polymer-based oxygen delivery system that supports the germination and growth of cress seeds ( Lepidium sativum ) in a martian regolith simulant under a martian atmosphere at 101 kPa. The oxygen-donating system is based on a low-density lightly cross-linked polyacrylate that is foamed and converted into a dry powder. It is lightweight, added in low amounts to regolith simulant, and efficiently donates enough oxygen throughout the volume of hydrated regolith simulant to fully support seed germination and plant growth. Germination rates, plant development, and plant mass are nearly identical for L. sativum grown in 100% CO 2 in the presence of the oxygen-donating lightly cross-linked polyacrylate compared with plants grown in air. The polymer system also serves to protect root structures and better anchors plants in the regolith simulant.