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IntroductionIn 2012 we presented a poster to the Digestive Disorders Foundation Meeting, we analysed 5162 colonoscopies and noted a significant difference in caecal intubation rates (CIR) of male and female patients (92.73% v 87.63%, p < 0.0001, NNH 19.57).1 Gender differences in colonoscopy have been published previously in the 1990s.2,3 Several theories were mooted for this difference; such as female patients undergoing previous hysterectomy,2 and having longer colons.3 We have revisited this topic to identify causes of the difference relevant to modern colonoscopic practice.MethodsData was analysed from 8324 colonoscopies at Kettering General Hospital 2008-13. Incomplete colonoscopies' reports were scrutinised to record the causes of failure.ResultsAbstract PWE-027 Table 1 Number of colonoscopies Reached caecum/TI/anastomosis Incomplete CIR 95% CI Female3886353235490.89%89.94-91.76Male4438421921995.07%94.39 -95.66Total8324775157393.12%92.55-93.64Reason for failed colonoscopy (females v males, p value)Poor bowel preparation (16.38 vs. 24.66%, 0.09), tight bend (6.21 vs. 0.91%, <0.03)Intolerance/pain (27.97 vs. 19.63%, 0.11), looping (18.36 vs. 18.72%)Obstructing lesion (8.19 vs. 15.53%, 0.06), previous surgery (5.37 vs. 0.46%, <0.03)Diverticular disease (9.32 vs. 5.02%, 0.18), withdrew consent (5.93 vs. 2.28%, 0.14)ConclusionThe data reveals significant differences in CIR between female and male patients (90.89 vs. 95.07%, p < 0.0001, NNH 24). Analysis of the reasons recorded for failure shows a strong trend in males for poor bowel preparation and obstructing lesion. In females, a strong trend was shown for pain/intolerance, diverticular disease and withdrawal of consent. Statistical significance was shown for previous (abdominal) surgery and tight bend. Looping is a common reason for failing colonoscopy with no gender difference.This is an important observation that females are significantly less likely to have complete colonoscopy. Perhaps endoscopy units should outline the potential for missed lesions as a consequence when consenting female patients - in particular those with known diverticular disease or previous abdominal surgery. Other reasons of failure could also be addressed e.g. higher doses of analgesia for females as required.References1 Verma AM, McGrath N, Dixon A, Chilton AP. Gender differences: analysis of 5162 colonoscopies over 4years reveals higher caecal intubation rates in male patients. Gut 2012; 61:Suppl 2 A150-A1512 Church JM. Complete colonoscopy: How often? And if not, why not? Am J Gastroenterol 1994; 89:556-60.3 Saunders BP, Fukumoto M, Halligan S, et al. Why is colonoscopy more difficult in women? Gastrointestinal Endoscopy 1996; 43:124-6.Disclosure of InterestNone Declared.

Few disciplines in contemporary clinical research have experienced the high expectations directed at the gene therapy field. However, gene therapy has been challenging to translate to the clinic, often because the therapeutic gene is expressed at insufficient levels in the patient or because the gene delivery vector integrates near protooncogenes, which can cause leukemia (see the Perspective by Verma ). Biffi et al. ( 1233158 , published online 11 July) and Aiuti et al. ( 1233151 ; published online 11 July) report progress on both fronts in gene therapy trials of three patients with metachromatic leukodystrophy (MLD), a neurodegenerative disorder, and three patients with Wiskott-Aldrich syndrome (WAS), an immunodeficiency disorder. Optimized lentiviral vectors were used to introduce functional MLD or WAS genes into the patients' hematopoietic stem cells (HSCs) ex vivo, and the transduced cells were then infused back into the patients, who were then monitored for up to 2 years. In both trials, the patients showed stable engraftment of the transduced HSC and high expression levels of functional MLD or WAS genes. Encouragingly, there was no evidence of lentiviral vector integration near proto-oncogenes, and the gene therapy treatment halted disease progression in most patients. A longer follow-up period will be needed to further validate efficacy and safety. Lentivirus-mediated gene therapy produces encouraging results in three children with a rare immunodeficiency disorder. [Also see Perspective by Verma ] Wiskott-Aldrich syndrome (WAS) is an inherited immunodeficiency caused by mutations in the gene encoding WASP, a protein regulating the cytoskeleton. Hematopoietic stem/progenitor cell (HSPC) transplants can be curative, but, when matched donors are unavailable, infusion of autologous HSPCs modified ex vivo by gene therapy is an alternative approach. We used a lentiviral vector encoding functional WASP to genetically correct HSPCs from three WAS patients and reinfused the cells after a reduced-intensity conditioning regimen. All three patients showed stable engraftment of WASP-expressing cells and improvements in platelet counts, immune functions, and clinical scores. Vector integration analyses revealed highly polyclonal and multilineage haematopoiesis resulting from the gene-corrected HSPCs. Lentiviral gene therapy did not induce selection of integrations near oncogenes, and no aberrant clonal expansion was observed after 20 to 32 months. Although extended clinical observation is required to establish long-term safety, lentiviral gene therapy represents a promising treatment for WAS.

Few disciplines in contemporary clinical research have experienced the high expectations directed at the gene therapy field. However, gene therapy has been challenging to translate to the clinic, often because the therapeutic gene is expressed at insufficient levels in the patient or because the gene delivery vector integrates near protooncogenes, which can cause leukemia (see the Perspective by Verma ). Biffi et al. ( 1233158 , published online 11 July) and Aiuti et al. ( 1233151 ; published online 11 July) report progress on both fronts in gene therapy trials of three patients with metachromatic leukodystrophy (MLD), a neurodegenerative disorder, and three patients with Wiskott-Aldrich syndrome (WAS), an immunodeficiency disorder. Optimized lentiviral vectors were used to introduce functional MLD or WAS genes into the patients' hematopoietic stem cells (HSCs) ex vivo, and the transduced cells were then infused back into the patients, who were then monitored for up to 2 years. In both trials, the patients showed stable engraftment of the transduced HSC and high expression levels of functional MLD or WAS genes. Encouragingly, there was no evidence of lentiviral vector integration near proto-oncogenes, and the gene therapy treatment halted disease progression in most patients. A longer follow-up period will be needed to further validate efficacy and safety. Lentivirus-mediated gene therapy produces encouraging results in three children with a rare lysosomal storage disease. [Also see Perspective by Verma ] Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disease caused by arylsulfatase A (ARSA) deficiency. Patients with MLD exhibit progressive motor and cognitive impairment and die within a few years of symptom onset. We used a lentiviral vector to transfer a functional ARSA gene into hematopoietic stem cells (HSCs) from three presymptomatic patients who showed genetic, biochemical, and neurophysiological evidence of late infantile MLD. After reinfusion of the gene-corrected HSCs, the patients showed extensive and stable ARSA gene replacement, which led to high enzyme expression throughout hematopoietic lineages and in cerebrospinal fluid. Analyses of vector integrations revealed no evidence of aberrant clonal behavior. The disease did not manifest or progress in the three patients 7 to 21 months beyond the predicted age of symptom onset. These findings indicate that extensive genetic engineering of human hematopoiesis can be achieved with lentiviral vectors and that this approach may offer therapeutic benefit for MLD patients.

Bayesian network models with latent variables are widely used in statistics and machine learning. In this paper, we provide a complete algebraic characterization of these models when the observed variables are discrete and no assumption is made about the state-space of the latent variables. We show that it is algebraically equivalent to the so-called nested Markov model, meaning that the two are the same up to inequality constraints on the joint probabilities. In particular, these two models have the same dimension, differing only by inequality constraints for which there is no general description. The nested Markov model is therefore the closest possible description of the latent variable model that avoids consideration of inequalities. A consequence of this is that the constraint finding algorithm of Tian and Pearl [In Proceedings of the 18th Conference on Uncertainty in Artificial Intelligence (2002) 519–527] is complete for finding equality constraints. Latent variable models suffer from difficulties of unidentifiable parameters and nonregular asymptotics; in contrast the nested Markov model is fully identifiable, represents a curved exponential family of known dimension, and can easily be fitted using an explicit parameterization.

This paper presents a classification of all simple Harish-Chandra modules for the $N=1$ Heisenberg–Virasoro superalgebra, which turn out to be highest weight modules, lowest weight modules, and evaluation modules of the intermediate series (all weight spaces are one dimensional). Moreover, a characterization of the tensor product of highest weight modules with intermediate series modules is obtained.

Disease resistance strategies are powerful approaches to sustainable agriculture because they reduce chemical input into the environment. Recently, Piriformospora indica, a plant-root-colonizing basidiomycete fungus, has been discovered in the Indian Thar desert and was shown to provide strong growth-promoting activity during its symbiosis with a broad spectrum of plants [Verma, S. et al. (1998) Mycologia 90, 896-903]. Here, we report on the potential of P. indica to induce resistance to fungal diseases and tolerance to salt stress in the monocotyledonous plant barley. The beneficial effect on the defense status is detected in distal leaves, demonstrating a systemic induction of resistance by a root-endophytic fungus. The systemically altered \"defense readiness\" is associated with an elevated antioxidative capacity due to an activation of the glutathione-ascorbate cycle and results in an overall increase in grain yield. Because P. indica can be easily propagated in the absence of a host plant, we conclude that the fungus could be exploited to increase disease resistance and yield in crop plants.

According to oncologist Vinay Prasad (Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA), information about out-of-pocket health-care expenses would be more helpful for patients than hospitals' list prices, which do not always predict how much insurers will actually pay. Asked if the American Hospital Association will offer guidance to hospitals to help patients understand chargemasters and out-of-pocket costs, a spokeswoman replied that US hospitals are “committed to improving patients' access to information on the price of their care, and, specifically, on what the patient will pay out-of-pocket”. For the US Government's fact sheet on hospital price-list transparency see https://www.cms.gov/newsroom/fact-sheets/fiscal-year-fy-2019-medicare-hospital-inpatient-prospective-payment-system-ipps-and-long-term-acute-0 For the proposed US government mandate on television advertisements see https://www.washingtonpost.com/national/health-science/tv-ads-for-drugs-will-send-patients-to-websites-with-pricing-information/2018/10/15/b74ac344-d090-11e8-b2d2-f397227b43f0_story.html?utm_term=.de373ac90627 For the CMS National CAR-T Cell Coverage announcement see https://www.cms.gov/medicare-coverage-database/details/nca-tracking-sheet.aspx?NCAId=291 For the news reports on CMS National Coverage Analysis see https://www.biopharmadive.com/news/cms-car-t-national-coverage-decision-kymriah-yescarta/523777/ Burger/Phanie/Science Photo Library

We compare the $K$-theory stable bases of the Springer resolution associated to different affine Weyl alcoves. We prove that (up to relabelling) the change of alcoves operators are given by the Demazure–Lusztig operators in the affine Hecke algebra. We then show that these bases are categorified by the Verma modules of the Lie algebra, under the localization of Lie algebras in positive characteristic of Bezrukavnikov, Mirković, and Rumynin. As an application, we prove that the wall-crossing matrices of the $K$-theory stable bases coincide with the monodromy matrices of the quantum cohomology of the Springer resolution.