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Background Pre-resection biopsy (PRB) of large nonpedunculated colorectal polyps (LNPCPs, ≥ 20 mm) is often performed before referral for endoscopic mucosal resection (EMR). How this affects the EMR procedure is unknown. Methods This was a retrospective analysis of a prospectively collected cohort of patients with LNPCPs referred for EMR between 2013 to 2016 at an Australian tertiary center. Outcomes were differences between PRB and EMR histology, and effects of PRB on the EMR procedure. Results Among 586 LNPCPs, lesions that underwent PRB were larger (median 35 vs. 30 mm; P Conclusions Routine PRB of LNPCP did not reliably detect advanced histology and may have affected EMR complexity. PRB should be utilized with caution in guiding endoscopic management of LNPCPs.

Summary tiny-count is a highly flexible counting tool that allows for hierarchical classification and quantification of small RNA reads from high-throughput sequencing data. Selection rules can be used to filter reads by 5’ nucleotide, length, position of alignments in relation to reference features, and by the number of mismatches to reference sequences. tiny-count can quantify reads aligned to a genome or directly to small RNA or transcript sequences. With tiny-count, users can quantify a single class of small RNAs or multiple classes in parallel. tiny-count can resolve distinct classes of small RNAs, for example piRNAs and siRNAs, produced from the same locus. It can distinguish small RNAs variants, such as miRNAs and isomiRs, with single-nucleotide precision. tRNA, rRNA, and other RNA fragments can also be quantified. tiny-count can be run alone or as part of tinyRNA, a workflow that provides a basic all-in-one command line-based solution for small RNA-seq data analysis, with documentation and statistics generated at each step for accurate and reproducible results. Availability tiny-count and other tinyRNA tools are implemented in Python, C ++, Cython, and R, and the workflow is coordinated with CWL. tiny-count and tinyRNA are free and open-source software distributed under the GPLv3 license. tiny-count can be installed via Bioconda (https://anaconda.org/bioconda/tiny-count) and both tiny-count and tinyRNA documentation and software downloads are available at https://github.com/MontgomeryLab/tinyRNA. Supplementary information Reference data, including genome sequences and features tables, for certain species can be found at https://www.MontgomeryLab.org.

Introduction The frequency and severity of abdominal pain after endoscopic mucosal resection (EMR) of colonic laterally spreading lesions (LSLs) of ≥ 20 mm is unknown, as are the risk factors to predict its occurrence. We aimed to prospectively characterize pain after colonic EMR , determine the rapidity and frequency of its resolution after analgesia, and estimate the frequency of needing further intervention. Methods Procedural and lesion data on consecutive patients with LSLs who underwent EMR at a single tertiary referral center were prospectively collected. If pain after colonic EMR, graded using a visual analogue scale (VAS), lasted > 5 minutes, 1 g of paracetamol was administered. Pain lasting > 30 minutes lead to clinical review and upgrade to opiate analgesics. Investigations and interventions for pain were recorded. Results 67/336 patients (19.9 %, 95 %CI 16.0 %–24.5 %) experienced pain after colonic EMR (median VAS 5, interquartile range 3–7). Multivariable predictors of pain were: lesion size ≥ 40 mm, odds ratio [OR] 2.15 (95 %CI 1.22–3.80); female sex, OR 1.99 (95 %CI 1.14–3.48); and intraprocedural bleeding requiring endoscopic control, OR 1.77 (95 %CI 0.99–3.16). Of 67 patients with pain, 51 (76.1 %, 95 %CI 64.7 %–84.7 %) had resolution of their “mild pain” after paracetamol and were discharged without sequelae. The remaining 16 (23.9 %) required opiate analgesia (fentanyl), after which 11/16 patients (68.8 %; “moderate pain”) could be discharged. The 5/67 patients (7.5 %) with “severe pain” had no resolution despite fentanyl; all settled during hospital admission (median duration 2 days), intravenous analgesia, and antibiotics. Conclusion Pain after colonic EMR occurs in approximately 20 % of patients and resolves rapidly and completely in the majority with administration of intravenous paracetamol. Pain despite opiates heralds a more serious scenario and further investigation should be considered.

Isotropic phase de-wetting of discotic liquid crystals on a surface patterned with alternating ~5-10 μm wide wetting and de-wetting stripes results in the formation of long narrow droplets. On slow...

Background and Aims Laterally spreading lesions (LSLs) in the duodenum are conventionally treated by EMR. Recurrence is commonly encountered and can be difficult to treat safely due to the unique anatomic characteristics of the duodenum. Auxiliary techniques designed to prevent recurrence have not been described. Methods We sought to evaluate the effectiveness of thermal ablation of the defect margin after EMR (EMR-T) in reducing recurrence at first surveillance endoscopy (SE1, scheduled at 6 months) in a single tertiary referral center. All duodenal LSLs ≥10 mm referred for EMR were eligible. After successful EMR, thermal ablation was performed using snare-tip soft coagulation around the entire circumference of the resection defect. The primary outcome was the frequency of recurrence at SE1. A previous, well-characterized, prospective cohort of duodenal LSLs ≥10 mm treated by conventional EMR was the comparator. Results Over 43 months up to October 2019, 54 LSLs underwent EMR-T. One hundred twenty-five LSLs underwent conventional EMR in the comparator group. Patient and lesion characteristics were similar between the groups. Recurrence was significantly lower in the EMR-T group compared with the conventional EMR group (1 of 49 [2.3%] vs 19 of 108 [17.6%]; P = .01). No difference in technical success, EMR-related adverse outcomes, or referral to surgery were identified between the groups. Conclusions EMR-T significantly reduces the frequency of recurrence for duodenal LSLs. This technique is safe in the duodenum and has the potential to significantly improve the effectiveness of duodenal EMR. (Clinical trial registration number: NCT02306603.)

Background Gold nanocages have been widely used as multifunctional platforms for drug and gene delivery, as well as photothermal agents for cancer therapy. However, their potential as gene delivery systems for cancer treatment has been reported in combination with chemotherapeutics and photothermal therapy, but not in isolation so far. The purpose of this work was to investigate whether the conjugation of gold nanocages with the cancer targeting ligand lactoferrin, polyethylene glycol and polyethylenimine could lead to enhanced transfection efficiency on prostate cancer cells in vitro, without assistance of external stimulation. Methods Novel lactoferrin-bearing gold nanocages conjugated to polyethylenimine and polyethylene glycol have been synthesized and characterized. Their transfection efficacy and cytotoxicity were assessed on PC-3 prostate cancer cell line following complexation with a plasmid DNA. Results Lactoferrin-bearing gold nanocages, alone or conjugated with polyethylenimine and polyethylene glycol, were able to condense DNA at conjugate:DNA weight ratios 5:1 and higher. Among all gold conjugates, the highest gene expression was obtained following treatment with gold complex conjugated with polyethylenimine and lactoferrin, at weight ratio 40:1, which was 1.71-fold higher than with polyethylenimine. This might be due to the increased DNA cellular uptake observed with this conjugate, by up to 8.65-fold in comparison with naked DNA. Conclusion Lactoferrin-bearing gold nanocages conjugates are highly promising gene delivery systems to prostate cancer cells., Graphical Abstract

Background and Purpose: The DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) randomized clinical trial demonstrated the efficacy of endovascular therapy in treating ischemic stroke 6 to 16 hours after onset, resulting in better functional outcomes than standard medical therapy alone. The objective of this secondary analysis is to analyze the effect of late-window endovascular treatment of ischemic stroke on quality of life (QoL) outcomes. Methods: Patients (n=182) who presented between 6 and 16 hours after they were last known to be well with acute anterior circulation ischemic stroke were randomized to endovascular thrombectomy plus standard medical therapy or standard medical therapy alone and followed-up through 90 days poststroke. QoL at day 90 was assessed with the QoL in Neurological Disorders measurement tool. Results: Of the 146 subjects alive at day 90, 136 (95%) filled out QoL in Neurological Disorders short forms. Patients treated with endovascular therapy had better QoL scores in each domain: mobility, social participation, cognitive function, and depression ( P 2 =0.82), a moderate proportion in social participation (Rs 2 =0.62), and a low proportion in cognition (Rs 2 =0.31) and depression (Rs 2 =0.19). Conclusions: Patients treated with endovascular therapy 6 to 16 hours after stroke have better QoL than patients treated with medical therapy alone, including better mobility, more social participation, superior cognition, and less depression. The modified Rankin Scale fails to capture patients’ outcomes in cognition and depression, which should therefore be assessed with dedicated QoL tools. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02586415.

Background and Aims Although sporadic duodenal and/or ampullary adenomas (DAs) are uncommon, they are increasingly diagnosed during upper endoscopy. These patients have a 3- to 7-fold increased risk of colonic neoplasia compared with the normal population. It is unknown, however, whether they also have an increased risk of additional small-bowel (SB) polyps. Our aim was to establish the prevalence of SB polyps in patients with DA. Methods In a single-center, prospective study, we used video capsule endoscopy (VCE) to investigate the prevalence of SB polyps in patients with a DA compared with patients undergoing VCE for obscure GI bleeding or iron deficiency anemia. Results Over 25 months, 201 patients were enrolled in the study; the mean age was 65 years and 47% were male. There were 101 control patients and 100 cases of DA cases (mean size, 30 mm (range, 10-80 mm)). We did not identify any SB polyps in either group. Colonic polyps were found more frequently in the DA group compared with controls (61% versus 37%, respectively (P =.002)). Advanced colonic adenoma (high-grade dysplasia, >10 mm, villous histology) were found in 18% of the DA group and 5% of the control group (P =.018). Conclusion Our data suggest that patients with a DA are not at risk for additional SB polyps and hence do not support screening with VCE. However, colonoscopy is mandatory due to the significantly higher risk of colonic polyps including advanced adenomas. (Clinical trial registration number: NCT02470416.)

SummarytinyRNA performs precision analysis of small RNAs, including miRNAs, piRNAs, and siRNAs, from high-throughput sequencing experiments. At the core of tinyRNA is a highly flexible counting utility, tiny-count, that allows for hierarchical assignment of small RNA reads to features based on positional information, extent of feature overlap, 5’ nucleotide, length, and strandedness. tinyRNA provides an all-in-one solution for small RNA-seq data analysis, with documentation and statistics generated at each step for accurate, reproducible results.Availability and ImplementationtinyRNA tools are implemented in Python and R, and the pipeline workflow is coordinated with CWL. tinyRNA is free and open-source software distributed under the GPLv3 license. tinyRNA is available at https://github.com/MontgomeryLab/tinyRNA.Contacttai.montgomery@colostate.eduSupplementary informationReference data, including genome sequences and features tables, for certain species can be found at https://www.MontgomeryLab.org.

In the midst of the SARS-CoV-2 pandemic, the US Association of American Medical Colleges (AAMC) required residency programme transition from in-person to virtual interviews for all applicants. The new virtual format upended a system that has relied on programmes and applicants balancing the likelihood of acceptance with the financial and time demands of cross-country travel. In this commentary, we address the history of residency interviewing in the USA and the emerging changes that are taking place in light of virtual interviews. We discuss the advantages of the new online format, including the reduced cost for applicants and programmes, as well as the decreased carbon footprint. We also discuss the inequities of virtual interviewing, involving a national maldistribution of interviews to only the top-tier candidates. We share previously unpublished data on the number of virtual interviews accepted by Stanford's 2020 residency applicants, compared with those conducted in person in 2019. We find Stanford applicants in all fields accepted more interviews: from a mean of 8 in 2019 to 14 in 2020, a change of 160% on average. Despite this, only half of Stanford 2020 applicants interviewing in the virtual format thought they had accepted more interviews than they would have in person. We comment on how transitions to online interviewing may be affecting medical schools and applicants disproportionately. Ultimately, we highlight the need and offer ideas for additional regulation on behalf of the AAMC to ensure a more equitable distribution of interview opportunities.

INTRODUCTION Endoscopic mucosal resection (EMR) is an effective therapy for naive large nonpedunculated colorectal polyps (N-LNPCPs). The best approach for the treatment of previously attempted LNPCPs (PA-LNPCPs) is undetermined. METHODS EMR performance for PA-LNPCPs was evaluated in a prospective observational cohort of LNPCPs ≥20 mm. Efficacy was measured by technical success (removal of all visible polypoid tissue during index EMR) and recurrence at first surveillance colonoscopy (SC1). Safety was assessed by clinically significant intraprocedural bleeding, deep mural injury types III-V, clinically significant post-EMR bleeding, and delayed perforation. RESULTS From January 2012 to October 2019, 158 PA-LNPCPs and 1,134 N-LNPCPs underwent EMR. Median PA-LNPCP size was 30 mm (interquartile range 25-46 mm). Technical success was 93.0% and increased to 95.6% after adjusting for 2-stage EMR. Cold-forceps avulsion with adjuvant snare-tip soft coagulation (CAST) was required for nonlifting polypoid tissue in 73 (46.2%). Median time to SC1 was 6 months (interquartile range 5-7 months). Recurrence occurred in 9 (7.8%). No recurrence was identified among 65 PA-LNPCPs which underwent margin thermal ablation at SC1 vs 9 (18.0%; P < 0.001) which did not. There were significant differences in resection duration (35 vs 25 minutes; P < 0.001), technical success (93.0% vs 96.6%; P = 0.026), and use of CAST (46.2% vs 7.6%; P < 0.001), between PA-LNPCPs and N-LNPCPs. When adjusting for 2-stage EMR, no difference in technical success was identified (95.6% vs 97.8%; P = 0.100). No differences in adverse events or recurrence were identified. DISCUSSION EMR, using auxillary techniques where necessary, can achieve high technical success and low recurrence frequencies for PA-LNPCPs.

The synthesis of donor–acceptor di-, tri- and tetrablock copolymers via sequential ROMP of electron rich and electron deficient paracyclophanediene monomers using Grubbs ruthenium carbene initiator, G3, is discussed. Block copolymers were initially formed with a cis/trans alkene geometry and these can be readily photoisomerised to the all trans forms. The optical and electrochemical properties of these block copolymers were examined by theory and experiment, and it was found that the HOMO and LUMO energy levels are localised on the donor and acceptor blocks, respectively.

ObjectiveLarge (≥20 mm) sessile serrated lesions (L-SSL) are premalignant lesions that require endoscopic removal. Endoscopic mucosal resection (EMR) is the existing standard of care but carries some risk of adverse events including clinically significant post-EMR bleeding and deep mural injury (DMI). The respective risk-effectiveness ratio of piecemeal cold snare polypectomy (p-CSP) in L-SSL management is not fully known.DesignConsecutive patients referred for L-SSL management were treated by p-CSP from April 2016 to January 2020 or by conventional EMR in the preceding period between July 2008 and March 2016 at four Australian tertiary centres. Surveillance colonoscopies were conducted at 6 months (SC1) and 18 months (SC2). Outcomes on technical success, adverse events and recurrence were documented prospectively and then compared retrospectively between the subsequent time periods.ResultsA total of 562 L-SSL in 474 patients were evaluated of which 156 L-SSL in 121 patients were treated by p-CSP and 406 L-SSL in 353 patients by EMR. Technical success was equal in both periods (100.0% (n=156) vs 99.0% (n=402)). No adverse events occurred in p-CSP, whereas delayed bleeding and DMI were encountered in 5.1% (n=18) and 3.4% (n=12) of L-SSL treated by EMR, respectively. Recurrence rates following p-CSP were similar to EMR at 4.3% (n=4) versus 4.6% (n=14) and 2.0% (n=1) versus 1.2% (n=3) for surveillance colonoscopy (SC)1 and SC2, respectively.ConclusionsIn a historical comparison on the endoscopic management of L-SSL, p-CSP is technically equally efficacious to EMR but virtually eliminates the risk of delayed bleeding and perforation. p-CSP should therefore be considered as the new standard of care for L-SSL treatment.

Blood parasites can impact host fitness and can, thus, act as selective agents in their host’s evolution. The melanocortin system linked to colouration of vertebrates may infer higher parasite resistance via pleiotropic properties of the genes involved. Black Sparrowhawks (Accipiter melanoleucus) are colour polymorphic (dark and light morph adults) and distributed clinally in South Africa, with more dark morphs in the Southwest where the breeding season coincides with the rainy season. There, dark morphs have lower infections of haemosporidian parasites Haemoproteus nisi, suggesting a higher parasitic resistance. Thus, it is hypothesized that the morph distribution may be an adaptive response to coping with varying parasite prevalence associated with rainfall levels, which may regulate the parasites’ invertebrate vectors. This hypothesis assumes a fitness cost of high parasite burden, which could be specifically important during the energy-demanding breeding season. To explore this, we (1) quantified Black Sparrowhawk H. nisi infections across South Africa, and explored (2) breeding performance and apparent annual survival of adults, and (3) nestling body condition in Cape Town in relation to infection levels. In contrast to the predictions, we found that parasite prevalence did not vary across the country, we found no fitness costs of higher infection levels for breeding birds, and also nestling body condition was independent of infection levels. Thus, we found no support for our hypothesis. Black Sparrowhawk polymorphism is unlikely to be driven by an adaptive function linked to dealing with higher infections with H. nisi in regions with wetter breeding seasons.

Waterbirds in stochastic environments exhibit nomadism in order to cater for the unpredictable availability of water resources. Lesser flamingos Phoeniconaias minor have long been thought to be nomadic waterbirds. In southern Africa, conservation efforts for lesser flamingos are hampered by a lack of knowledge about their movement trajectories. To investigate their movement ecology in southern Africa, we fitted GPS–GSM transmitters to 12 adults and tracked their movements over four years, from March 2016 to February 2020. Net squared displacement (NSD) was used in nonlinear least squares models classifying trajectories as nomadic, migratory, mixed-migratory, home range restricted or dispersal movement types. Data from eight of the 12 birds met the criteria for the NSD analysis. Model success was good; only 8 out of 120 (6.7%) movement type models failed to reach convergence. Goodness of fit statistics from the NSD models supported migratory and mixed migratory movement types (concordance criteria coefficient (CC) = 0.78) for more than half of the annual trajectories investigated (57.2%). Dispersal, home range-restricted and nomadic movements best described 28.6, 9.5 and 4.8% of annual trajectories, respectively, but all resulted in a mean CC of < 0.4 and thus did not fit observed NSD patterns as well as the migratory movement types. We then used nonlinear mixed effects models to account for annual and individual differences in migration parameters. Variation in the timing and duration of all migrations were more important than variation in migration distance, indicating well-established summer and winter ‘ranges’ and routes between Kamfers Dam (South Africa) and Sua Pan (Botswana). We propose that lesser flamingos in central southern Africa may be partial migrants, not true nomads, as most of their movements followed a regular, repeated pattern between two primary locations.

Disassortative mating in color-polymorphic raptors is a proposed mechanism for the maintenance of color polymorphism in populations. Selection for such a mating system may occur if there are fitness advantages of mating with a contrasting morph. In the black sparrowhawk (Accipiter melanoleucus), mixed-morph pairs may have a selective advantage because they produce offspring that have higher survival rates. Two hypotheses, which may explain the mechanism, are the “avoidance-image” and “complementarity” hypotheses. The first suggests that, within a predator’s territory, prey develop a search image for the more commonly encountered parental morph, for example, the male morph during incubation and brooding. Females of a contrasting morph to their partner would then have higher capture rates once they commence hunting in the later nestling phase. Thus, the “avoidance-image” hypothesis predicts higher provisioning rates for mixed-morph pairs. Alternatively, the “complementarity” hypothesis posits that different color morphs exploit different environmental conditions, allowing mixed-morph pairs to hunt under a wider range of conditions and predicts that food is delivered more consistently. We test these hypotheses using nest cameras to record prey delivery rates during the late nestling phase when both parents are hunting. We found support for the “complementarity” hypothesis, with mixed-morph pairs delivering food more consistently but not at a higher rate. This higher consistency in prey deliveries may explain the improved survival of the offspring of mixed-morph pairs and could, therefore, play a role in maintaining the stability of color polymorphism in this system.

The Southern Ocean surrounding Antarctica is a region that is key to a range of climatic and oceanographic processes with worldwide effects, and is characterised by high biological productivity and biodiversity. Since 2013, the International Bathymetric Chart of the Southern Ocean (IBCSO) has represented the most comprehensive compilation of bathymetry for the Southern Ocean south of 60°S. Recently, the IBCSO Project has combined its efforts with the Nippon Foundation – GEBCO Seabed 2030 Project supporting the goal of mapping the world’s oceans by 2030. New datasets initiated a second version of IBCSO (IBCSO v2). This version extends to 50°S (covering approximately 2.4 times the area of seafloor of the previous version) including the gateways of the Antarctic Circumpolar Current and the Antarctic circumpolar frontal systems. Due to increased (multibeam) data coverage, IBCSO v2 significantly improves the overall representation of the Southern Ocean seafloor and resolves many submarine landforms in more detail. This makes IBCSO v2 the most authoritative seafloor map of the area south of 50°S.

Background The European Society of Gastrointestinal Endoscopy (ESGE) has developed a core curriculum for high quality optical diagnosis training for practice across Europe. The development of easy-to-measure competence standards for optical diagnosis can optimize clinical decision-making in endoscopy. This manuscript represents an official Position Statement of the ESGE aiming to define simple, safe, and easy-to-measure competence standards for endoscopists and artificial intelligence systems performing optical diagnosis of diminutive colorectal polyps (1 – 5 mm). Methods A panel of European experts in optical diagnosis participated in a modified Delphi process to reach consensus on Simple Optical Diagnosis Accuracy (SODA) competence standards for implementation of the optical diagnosis strategy for diminutive colorectal polyps. In order to assess the clinical benefits and harms of implementing optical diagnosis with different competence standards, a systematic literature search was performed. This was complemented with the results from a recently performed simulation study that provides guidance for setting alternative competence standards for optical diagnosis. Proposed competence standards were based on literature search and simulation study results. Competence standards were accepted if at least 80 % agreement was reached after a maximum of three voting rounds. Recommendation 1 In order to implement the leave-in-situ strategy for diminutive colorectal lesions (1–5 mm), it is clinically acceptable if, during real-time colonoscopy, at least 90 % sensitivity and 80 % specificity is achieved for high confidence endoscopic characterization of colorectal neoplasia of 1–5 mm in the rectosigmoid. Histopathology is used as the gold standard.Level of agreement 95 %. Recommendation 2 In order to implement the resect-and-discard strategy for diminutive colorectal lesions (1–5 mm), it is clinically acceptable if, during real-time colonoscopy, at least 80 % sensitivity and 80 % specificity is achieved for high confidence endoscopic characterization of colorectal neoplasia of 1–5 mm. Histopathology is used as the gold standard.Level of agreement 100 %. Conclusion The developed SODA competence standards define diagnostic performance thresholds in relation to clinical consequences, for training and for use when auditing the optical diagnosis of diminutive colorectal polyps.

Hypoxia is associated with neoplastic tissue, protecting cancer cells from death by irradiation and chemotherapy. Identification of hypoxic volume of tumors could optimize patient selection for hypoxia-directed medical, immunological, and radiation therapies. Clostridium novyi-NT (CNV-NT) is an oncolytic bacterium derived from attenuated wild-type Clostridium novyi spores, which germinates exclusively in the anaerobic core of tumors with low-oxygen content. The hypothesis was that 64Cu-ATSM would localize to regions of hypoxia, and that greater hypoxic volume would result in greater germination of Clostridium novyi-NT (CNV-NT). Tumor-bearing companion dogs were recruited to a veterinary clinical trial. Dogs received a CT scan, 18F-FDG PET scan (74 MBq) and 64Cu-ATSM PET scan (74 MBq). Scan regions of interest were defined as the highest 20% of counts/voxel for each PET scan, and regions with voxels overlapping between the two scans. Maximum standardized uptake value (MaxSUV) and threshold volume were calculated. Direct oximetry was performed in select tumors. Tumor types evaluated included nerve sheath tumor (10), apocrine carcinoma (1), melanoma (3) and oral sarcoma (6). MaxSUVATSM ranged from 0.3-6.6. Measured oxygen tension ranged from 0.05-89.9 mmHg. Inverse of MaxSUVATSM had a linear relationship with oxygen tension (R2 = 0.53, P = 0.0048). Hypoxia8 mmHg was associated with an SUVATSM1.0. Hypoxic volume ranged from 0 to 100% of gross tumor volume (GTV) and MaxSUVATSM was positively correlated with hypoxic volume (R = 0.674; P = 0.0001), but not GTV (P = 0.182). Tumor hypoxic volume was heterogeneous in location and distribution. 64Cu-ATSM-avid regions were associated with differential CT attenuation. Hypoxic volume did not predict CNV-NT germination. 64Cu-ATSM PET scanning predicts hypoxia patterns within spontaneously occurring tumors of dogs as measured by direct oxymetry. Total tumor volume does not accurately predict degree or proportion of tumor hypoxia.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are complementary techniques for large (≥20 mm) nonpedunculated rectal polyps (LNPRPs). A mechanism for appropriate technique selection has not been described.We evaluated the performance of a selective resection algorithm (SRA) (August 2017 to April 2021) compared with a universal EMR algorithm (UEA) (July 2008 to July 2017) for LNPRPs within a prospective observational study. In the SRA, LNPRPs with features of superficial submucosal invasive cancer (SMIC) (1000 μm; Kudo pit pattern Vi), or with an increased risk of SMIC (Paris 0-Is or 0-IIa+Is nongranular, 0-IIa+Is granular with a dominant nodule ≥10 mm) underwent ESD. The remaining LNPRPs underwent EMR. Algorithm performance was evaluated by SMIC identified after EMR, curative oncologic resection (R0 resection, superficial SMIC, absence of negative histologic features), technical success, adverse events, and recurrence at first surveillance colonoscopy.A total of 480 LNPRPs were evaluated (290 UEA, 190 SRA). Median lesion size was 40 (interquartile range, 30-60) mm. SMIC was identified in 56 (11.7%) LNPRPs. Significant differences in SMIC after EMR (SRA 1 [1.0%] vs UEA 35 [12.1%]; P = .001) and curative oncologic resection (SRA n = 7 [33.3%] vs UEA n = 2 [5.7%]; P = .010) were identified. No significant differences in technical success or adverse events were identified (all P.137). Among LNPRPs with SMIC amenable to curative oncologic resection and which underwent ESD, 100% (n = 7 of 7) were cured.A rectum-specific SRA optimizes oncologic outcomes for LNPRPs and mitigates the risk of piecemeal resection of cancers.

BackgroundThere is an emerging understanding that coronavirus disease 2019 (COVID-19) is associated with increased incidence of pneumomediastinum (PTM). We aimed to determine its incidence among patients hospitalised with COVID-19 in the UK and describe factors associated with outcome.MethodsA structured survey of PTM and its incidence was conducted from September 2020 to February 2021. UK-wide participation was solicitedviarespiratory research networks. Identified patients had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and radiologically proven PTM. The primary outcomes were to determine incidence of PTM in COVID-19 and to investigate risk factors associated with patient mortality.Results377 cases of PTM in COVID-19 were identified from 58 484 inpatients with COVID-19 at 53 hospitals during the study period, giving an incidence of 0.64%. Overall 120-day mortality in COVID-19 PTM was 195 out of 377 (51.7%). PTM in COVID-19 was associated with high rates of mechanical ventilation. 172 out of 377 patients (45.6%) were mechanically ventilated at the point of diagnosis. Mechanical ventilation was the most important predictor of mortality in COVID-19 PTM at the time of diagnosis and thereafter (pConclusionsPTM appears to be a marker of severe COVID-19 pneumonitis. The majority of patients in whom PTM was identified had not been mechanically ventilated at the point of diagnosis.

In yeast physiology, a commonly used reference condition for many experiments, including those involving nitrogen catabolite repression (NCR), is growth in synthetic complete (SC) medium. Four SC formulations, SCCSH,1990, SCCSH,1994, SCCSH,2005, and SCME, have been used interchangeably as the nitrogen-rich medium of choice [Cold Spring Harbor Yeast Course Manuals (SCCSH) and a formulation in the methods in enzymology (SCME)]. It has been tacitly presumed that all of these formulations support equivalent responses. However, a recent report concluded that (i) TorC1 activity is downregulated by the lower concentration of primarily leucine in SCME relative to SCCSH. (ii) The Whi2–Psr1/2 complex is responsible for this downregulation. TorC1 is a primary nitrogen-responsive regulator in yeast. Among its downstream targets is control of NCR-sensitive transcription activators Gln3 and Gat1. They in turn control production of catabolic transporters and enzymes needed to scavenge poor nitrogen sources (e.g., Proline) and activate autophagy (ATG14). One of the reporters used in Chen et al. was an NCR-sensitive DAL80-GFP promoter fusion. This intrigued us because we expected minimal if any DAL80 expression in SC medium. Therefore, we investigated the source of the Dal80-GFP production and the proteomes of wild-type and whi2Δ cells cultured in SCCSH and SCME. We found a massive and equivalent reorientation of amino acid biosynthetic proteins in both wild-type and whi2Δ cells even though both media contained high overall concentrations of amino acids. Gcn2 appears to play a significant regulatory role in this reorientation. NCR-sensitive DAL80 expression and overall NCR-sensitive protein production were only marginally affected by the whi2Δ. In contrast, the levels of 58 proteins changed by an absolute value of log2 between 3 and 8 when Whi2 was abolished relative to wild type. Surprisingly, with only two exceptions could those proteins be related in GO analyses, i.e., GO terms associated with carbohydrate metabolism and oxidative stress after shifting a whi2Δ from SCCSH to SCME for 6 h. What was conspicuously missing were proteins related by TorC1- and NCR-associated GO terms.

Phosphorus (P) losses from agricultural fields through leaching are the main contributors to eutrophication of lakes and rivers in North America. Adoption of P-retaining strategies is essential to improve the environmental quality of water bodies. The main objective of this study is to evaluate lime as a soil amendment in reducing phosphorus concentration in the leachate from three common soil textures with neutral to alkaline pH. Phosphorus leaching from undisturbed soil columns (10 cm in diameter and 20 cm deep) as well as small repacked columns was investigated and compared in this study. Lime (high calcium hydrated lime) at the rate of 1% by air-dried soil mass was applied to the topsoil of the columns. Both sets of experiments followed a full factorial design with two factors of soil texture at three levels (sandy loam, loam, and clay loam) and treatment at two levels (control and limed) with three replicates. Scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy was performed on the control and limed soil samples to confirm the formation of calcium phosphate compounds. For both intact and repacked columns, dissolved reactive phosphorus (DRP) concentrations in the leachates from limed sandy loam and limed loam soil columns was significantly reduced, while DRP in the limed clay loam column leachates was not changed. Elemental mapping demonstrated that in limed sandy loam and loam soils, the calcium loadings on the soil surface were always linked with phosphorus. The formation of calcium phosphate compounds and the increased phosphate adsorption on the soil surface through Ca bridging could be the two main phosphorus-lime retention mechanisms. Total dissolved phosphorus (TDP) in the leachates of limed loam and limed clay loam indoor intact and repacked columns was reduced, while there was no change in that of the sandy loam soil. In finer textured soils, lime can increase TDP retention through the immobilization of organic phosphates. The impact of lime application on DRP and TDP varied with the soil texture. The lime-induced reduction in the DRP and TDP was variable between the intact and repacked columns demonstrating the importance of soil structure on phosphorus and lime interactions in the soil. Overall, lime application at the studied rate can be considered a promising soil amendment in mitigating phosphorus loss from non-calcareous neutral to alkaline soils.

Old world vultures are the most threatened group of raptors globally. Supplementary feeding sites (SFS) are a popular conservation tool, widely used to assist vulture populations. Despite their popularity, the impact of SFS on vultures remains largely unstudied. A lack of knowledge on the number, distribution and management of SFS is a key factor hindering such research. In this study, we compile records of SFS in South Africa and conduct questionnaires with SFS managers to characterize SFS. We identify 143 currently active SFS. Our data suggest that SFS numbers have been stable over the last decade. The average provisioning rate for all SFS was 64.6 kg day(-1). Overall SFS provide an estimated 3301 tonnes of food to scavengers each year, the equivalent of 83% of the energetic needs of all vultures in the region. This contribution was highly skewed, however, with just 17% of active SFS sites providing 69% of all food. Furthermore, these resources were not equally distributed, with SFS in Limpopo, North West and Kwazulu-Natal provinces providing 83% of the total meat provisioned. The three most common meat types provided at SFS were beef (39%), pork (33%) and game (19%). Worryingly, we found that 68% and 28% of SFS managers were unaware of the potential harmful effects of lead and veterinary drugs, respectively, which highlights potential poisoning risks associated with SFS. Examining exposure to SFS by different vulture species, we found that whilst SFS are accessible across the distribution range of vultures with large home ranges (e.g. African white-backed and Cape vultures), those species with smaller home ranges have relatively poor accessibility. With this study, we demonstrate the potential importance, but also associated risks, of SFS to vultures in South Africa, and provide the information base to assess the impacts of this popular but as yet largely unassessed conservation tool.

Dialkoxy- and dialkyl-substituted phenylene benzothiadiazole paracyclophane-1,9-diene monomers undergo living ring-opening metathesis polymerization using ruthenium carbene initiators (G3) to give ...

Debates concerning residential population displacement in the context of gentrification remain vociferous, but are hampered by a lack of empirical evidence of the extent of the displacement occurring. The lack of quantitative evidence on gentrification-induced displacement and the difficulties in collecting it has long hampered the fight against it. Based on a systematic review of quantitative studies of the displacement associated with gentrification, this article considers how researchers have attempted to measure displacement using a range of statistical and mapping techniques reflecting the multi-dimensional character of gentrification. We note that these techniques often struggle to provide meaningful estimates of the number of individuals and households displaced by gentrification, something compounded by the lack of data available on a sufficiently granular temporal and spatial scale. Noting the limitations of extant methods, we conclude by considering the potential of more novel data sources and emergent methods involving the processing of larger amounts of (micro)data, as well as participatory GIS methods that involve affected communities themselves. This implies that whilst the quantitative study of displacement remains difficult, patterns and processes of displacement can be inferred through existing data sources, as well as data generated from those who themselves have experienced displacement.

Background and Aims Clinically significant post-EMR bleeding (CSPEB) is the most-frequent serious adverse event after EMR of large laterally spreading colonic lesions (LSLs). There is no proven prophylactic therapy, and it remains a significant drawback of EMR. We aimed to systematically describe and evaluate the features of the post-EMR mucosal defect (PED) and their relationship to CSPEB. Methods A prospective study of LSLs referred for EMR at a tertiary center was performed. PEDs without visible features were recorded as bland blue. Nonbland blue (NBB) PED features included size, number, and herniation of submucosal vessels and presence of submucosal hemorrhage, fibrosis, fat, and exposed muscle. NBB PEDs were analyzed for association with CSPEB, defined as bleeding occurring after completion of the procedure necessitating readmission or reintervention. Results From April 2012 to May 2017, 501 lesions in 501 patients were eligible for analysis. The frequency of CSPEB was 30 of 501 (6.0%). More than or equal to 3 visible vessels was a significant predictor of CSPEB (P = .016). None of the following showed a significant correlation with CSPEB: presence of visible vessels, their diameter, herniation, or other nonvascular PED features. Submucosal vessels were more common in the left-sided colon segment (88.6% vs 78.3%, P = .004) and were significantly larger (20.8% vs 12.1% ≥1 mm, P = .037), more numerous (median 4 vessels [interquartile range, 2-7] vs 2 vessels [interquartile range, 1-4], P Conclusions More than or equal to 3 visible vessels within the PED may be predictive for CSPEB and may define a target group for real-time prophylactic intervention. No other endoscopically visible features of the PEDs were predictive of CSPEB. (Clinical trial registration number: NCT03117400 .)

* Abbreviations: CI — : confidence interval COVID-19 — : coronavirus disease 2019 PCR — : polymerase chain reaction SARS-CoV-2 — : severe acute respiratory syndrome coronavirus 2 Abbott BinaxNOW (a bedside lateral flow immunoassay intended for the qualitative detection of nucleocapsid protein antigen) is widely available under US Food and Drug Administration emergency use authorization for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in symptomatic patients within 7 days of symptom onset. Its diagnostic performance in symptomatic children has not been evaluated. Cross-sectional study of symptomatic children ≤20 years presenting for care to 1 of 2 primary care practices in December 2020, during which time coronavirus disease 2019 (COVID-19) rates were … Address correspondence to Nader Shaikh, MD, MPH, University of Pittsburgh Medical Center, Children’s Hospital of Pittsburgh, 1 Children’s Hospital Dr, 4401 Penn Ave, Pittsburgh, PA 15224. E-mail: nader.shaikh{at}chp.edu

Objective: Ultrasound-guided peripheral intravenous (USPIV) catheters are being placed in emergency department (ED) patients with increasing frequency. USPIV catheters have been shown to improve the success rates of cannulation. It is unknown what the long-term effect of USPIV placement will be on fistula creation in chronic kidney disease (CKD) patients considering these ultrasound-guided peripheral lines often target the same deeper vessels used for fistulas. This study aimed to survey whether emergency medicine programs place restrictions on USPIV placement in patients with CKD stages 3–5. Methods: This was a survey study encompassing all 110 emergency ultrasound fellowship directors in the United States at the time the survey was conducted. Data was collected on an anonymous and voluntary basis. The primary outcome was the number of programs with restrictions on USPIV placement in patients with CKD stage 3 or greater. Results: Of the 56 programs that responded, 21% reported having policies limiting which patients were appropriate for USPIV. Despite this, only one program reported placing restrictions on USPIV in CKD stage 3 or greater ( p Conclusions: Emergency departments do not have or follow restrictions placed on USPIV placement in patients with CKD stage 3 or greater. The use of these veins in the ED may result in thrombosis as well as inflammation and permanent scarring which could negatively impact the ability to utilize those vessels for fistula creation. Future studies are needed to further characterize the impact of USPIV on fistula creation.

Epilepsy is an ancient disease, which has fascinated and frightened scientists and laymen alike. Before the working knowledge of the central nervous system, seizures were shrouded in mystery. In antiquity, this disease was accredited to gods and demonic possession, causing those with epilepsy to be feared and isolated. Epilepsy patients continued to face discrimination through the mid-20th century. This discrimination ranged from lack of access to health insurance, jobs, and marriage equality to forced sterilizations. Despite the strides that have been made, there are still many misconceptions globally regarding epilepsy. Studies show that patients with epilepsy in communities that understand the pathology and cause of seizures are generally more successful in social and educational environments. While there has been progress, there is more work which needs to be done to educate people across the globe about the pathology of epilepsy.

The Ionospheric Data Assimilation Four-Dimensional (IDA4D) technique has been coupled to Sami3, which is another model of the ionosphere (SAMI3). In this application, ground-based and space-based GPS total electron content (TEC) data have been assimilated into SAMI3, while in-situ electron densities, autoscaled ionosonde NmF2, and reference GPS stations have been used for validation. IDA4D/SAMI3 shows that night-time ionospheric localized enhancements (NILE) are formed following geomagnetic storms in November 2003 and August 2018. The NILE phenomenon appears as a moderate, longitudinally extended enhancement of NmF2 at 30°-40°N MLAT, occurring in the late evening (20-24 LT) following much larger enhancements of the equatorial anomaly crests in the main phase of the storms. The NILE appears to be caused by upward and northward plasma transport around the dusk terminator, which is consistent with eastward polarization electric fields. Independent validation confirms the presence of the NILE, and indicates that IDA4D is effective in correcting random errors and systematic biases in SAMI3. In all cases, biases and root-mean-square errors are reduced by the data assimilation, typically by a factor of 2 or more. During the most severe part of the November 2003 storm, the uncorrected ionospheric error on a GPS 3D position at 1LSU (Louisiana) is estimated to exceed 34 m. The IDA4D/SAMI3 specification is effective in correcting this down to 10 m.

IDA4D/SAMI3 model output for the associated JGR Space Physics publication.&nbsp

Gln3 activates Nitrogen Catabolite Repression, NCR-sensitive expression of the genes required for Saccharomyces cerevisiae to scavenge poor nitrogen sources from its environment. The global TorC1 kinase complex negatively regulates nuclear Gln3 localization, interacting with an α-helix in the C-terminal region of Gln3, Gln3656–666. In nitrogen replete conditions, Gln3 is sequestered in the cytoplasm, whereas when TorC1 is down-regulated, in nitrogen restrictive conditions, Gln3 migrates into the nucleus. In this work, we show that the C-terminal Gln3–Tor1 interaction site is required for wild type, rapamycin-elicited, Sit4-dependent nuclear Gln3 localization, but not for its dephosphorylation. In fact, truncated Gln31-384 can enter the nucleus in the absence of Sit4 in both repressive and derepressive growth conditions. However, Gln31-384 can only enter the nucleus if a newly discovered second positively-acting Gln3–Tor1 interaction site remains intact. Importantly, the N- and C-terminal Gln3–Tor1 interaction sites function both autonomously and collaboratively. The N-terminal Gln3–Tor1 interaction site, previously designated Gln3URS contains a predicted α-helix situated within an unstructured coiled-coil region. Eight of the thirteen serine/threonine residues in the Gln3URS are dephosphorylated 3–15-fold with three of them by 10–15-fold. Substituting phosphomimetic aspartate for serine/threonine residues in the Gln3 URS abolishes the N-terminal Gln3–Tor1 interaction, rapamycin-elicited nuclear Gln3 localization, and ½ of the derepressed levels of nuclear Gln3 localization. Cytoplasmic Gln3 sequestration in repressive conditions, however, remains intact. These findings further deconvolve the mechanisms that achieve nitrogen-responsive transcription factor regulation downstream of TorC1.

Stimuli-responsive nanocarriers have become increasingly important for nucleic acid and drug delivery in cancer therapy. Here, we report the synthesis, characterization and evaluation of disulphide-linked, octadecyl (C18 alkyl) chain-bearing PEGylated generation 3-diaminobutyric polypropylenimine dendrimer-based vesicles (or dendrimersomes) for gene delivery. The lipid-bearing PEGylated dendrimer was successfully synthesized through in situ two-step reaction. It was able to spontaneously self-Assemble into stable, cationic, nanosized vesicles, with low critical aggregation concentration value, and also showed redox-responsiveness in presence of a glutathione concentration similar to that of the cytosolic reducing environment. In addition, it was able to condense more than 70% of DNA at dendrimer: DNA weight ratios of 5 : 1 and higher. This dendriplex resulted in an enhanced cellular uptake of DNA at dendrimer: DNA weight ratios of 10 : 1 and 20 : 1, by up to 16-fold and by up to 28-fold compared with naked DNA in PC-3 and DU145 prostate cancer cell lines respectively. At a dendrimer: DNA weight ratio of 20 : 1, it led to an increase in gene expression in PC-3 and DU145 cells, compared with DAB dendriplex. These octadecyl chain-bearing, PEGylated dendrimer-based vesicles are therefore promising redox-sensitive drug and gene delivery systems for potential applications in combination cancer therapy. This journal is

ObjectiveManagement of covert submucosal invasive cancer (SMIC) discovered after piecemeal endoscopic mucosal resection (pEMR) of large (>20 mm) non-pedunculated colorectal polyps is challenging. The residual cancer risk is largely unknown. We sought to evaluate this in a large tertiary referral cohort.DesignCases of covert SMIC following pEMR were identified and followed. Oncological outcomes after surgery were divided based on residual intramural cancer, lymph node metastases (LNM) or both. Risk factors for residual intramural cancer and LNM were analysed based on the original pEMR histological variables. Risk parameters were analysed with respect to low and high-risk variables for residual intramural cancer and LNM.ResultsAmong 3372 cases of large non-pedunculated colorectal polyps, 143 cases of covert SMIC (4.2%) were identified. 109 underwent surgical resection. Histological analysis of pEMR histology was available in 98 of 109 (90%) cases. 62 cases (63%) had no residual malignancy. 36 cases had residual malignancy (residual intramural cancer n=24; LNM n=5; both n=7). All cases of residual intramural cancer could be identified by a R1 histological deep margin. Cases with poor differentiation (PD) and/or lymphovascular invasion (LVI) had a high risk of LNM (12/33), with a very low risk without these criteria (ConclusionThe majority of cases of large non-pedunculated colorectal polyps with covert SMIC following pEMR will have no residual malignancy. The risk of residual malignancy can be ascertained from three key variables: PD, LVI and R1 deep margin.

The most important causes of hereditary colorectal cancer are Lynch syndrome (LS) and the adenomatous polyposis syndromes (familial adenomatous poly- posis syndrome or FAP, attenuated FAP or AFAP and MUTYH associated polyposis syndrome or MAP). The aim of this study was to investigate whether all patients with a hereditary syndrome within one center receive uniform advice regarding surveillance and treatment.A retrospective analysis was performed of all electronic patient health records of patients with LS, FAP, AFAP and MAP who received genetic counselling or were followed by a health care specialist at the University Hospital in Ghent.Data from 122 patients were collected. For all patients, recommendations from the medical genetics department were highly consistent. Adherence to their recommendations was good within the center for the management of colon polyps. There was a lack of consistency in the screening and surveillance advice for other tumors in departments other than gastroenterology. Only 33 patients had systematic follow-up consultations to check results and organize surveillance.Previously, small studies have suggested that patients with hereditary gastrointestinal cancer syndromes infrequently have surveillance as specified in the guidelines. This study shows almost uniform recommendations and good adherence for surveillance of the colon, but incomplete or contradictory advice for surveillance of other organs. The need for an integrated approach from a multidisciplinary team will only increase in the future, because more families with hereditary cancer are likely to be found due to the increased use of next generation sequencing in cancer diagnostics.