| 1. |
- Su, Zhan, et al.
(författare)
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Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
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Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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| 2. |
- Agirre, Jon, et al.
(författare)
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The CCP4 suite: integrative software for macromolecular crystallography
- 2023
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Ingår i: Acta Crystallographica Section D. - : INT UNION CRYSTALLOGRAPHY. - 2059-7983. ; 79, s. 449-461
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Tidskriftsartikel (refereegranskat)abstract
- The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.
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| 3. |
- Balasubramanian, Ishwarya, et al.
(författare)
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Out-Patient Management of Mild or Uncomplicated Diverticulitis: A Systematic Review
- 2017
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Ingår i: Digestive Surgery. - : S. Karger AG. - 0253-4886 .- 1421-9883. ; 34, s. 151-160
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Forskningsöversikt (refereegranskat)abstract
- © 2016 S. Karger AG, Basel. Background: Management of diverticular disease has undergone a paradigm shift, with movement towards a less invasive management strategy. In keeping with this, outpatient management of uncomplicated diverticulitis (UD) has been advocated in several studies, but concerns still remain regarding the safety of this practice. Aim: To assess outcomes of out-patient management of acute UD. Methods: A comprehensive search for published studies using the search terms 'uncomplicated diverticulitis', 'mild diverticulitis' and 'out-patient' was performed. The primary outcomes were failure of medical treatment. Secondary outcomes were recurrence rate at follow up and medical cost savings. Results: The search yielded 192 publications. Of these, 10 studies met the inclusion criteria including 1 randomized controlled trial, 6 clinical controlled trials and 3 case series. There was no difference in failure rates of medical treatment (6.5 vs. 4.6%, p = 0.32) or in recurrence rates (13.0 vs. 12.1%, p = 0.81) between those receiving ambulatory care and in-patient care for UD. Ambulatory treatment is associated with an estimated daily cost savings of between 600 and 1,900 euros per patient treated. Meta-analysis of data was not possible due to heterogeneity in study designs and inclusion criteria. Conclusion: Ambulatory management of acute UD is reasonable in selected patients.
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| 4. |
- Bass, Gary Alan, 1979-, et al.
(författare)
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Techniques for mesoappendix transection and appendix resection: insights from the ESTES SnapAppy study
- 2023
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 17-32
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Surgically managed appendicitis exhibits great heterogeneity in techniques for mesoappendix transection and appendix amputation from its base. It is unclear whether a particular surgical technique provides outcome benefit or reduces complications. Material and methods: We undertook a pre-specified subgroup analysis of all patients who underwent laparoscopic appendectomy at index admission during SnapAppy (ClinicalTrials.gov Registration: NCT04365491). We collected routine, anonymized observational data regarding surgical technique, patient demographics and indices of disease severity, without change to clinical care pathway or usual surgeon preference. Outcome measures of interest were the incidence of complications, unplanned reoperation, readmission, admission to the ICU, death, hospital length of stay, and procedure duration. We used Poisson regression models with robust standard errors to calculate incident rate ratios (IRRs) and 95% confidence intervals (CIs). Results: Three-thousand seven hundred sixty-eight consecutive adult patients, included from 71 centers in 14 countries, were followed up from date of admission for 90days. The mesoappendix was divided hemostatically using electrocautery in 1564(69.4%) and an energy device in 688(30.5%). The appendix was amputated by division of its base between looped ligatures in 1379(37.0%), with a stapler in 1421(38.1%) and between clips in 929(24.9%). The technique for securely dividing the appendix at its base in acutely inflamed (AAST Grade 1) appendicitis was equally divided between division between looped ligatures, clips and stapled transection. However, the technique used differed in complicated appendicitis (AAST Grade 2 +) compared with uncomplicated (Grade 1), with a shift toward transection of the appendix base by stapler (58% vs. 38%; p < 0.001). While no statistical difference in outcomes could be detected between different techniques for division of appendix base, decreased risk of any [adjusted IRR (95% CI): 0.58 (0.41–0.82), p = 0.002] and severe [adjusted IRR (95% CI): 0.33 (0.11–0.96), p = 0.045] complications could be detected when using energy devices. Conclusions: Safe mesoappendix transection and appendix resection are accomplished using heterogeneous techniques. Technique selection for both mesoappendix transection and appendix resection correlates with AAST grade. Higher grade led to more ultrasonic tissue transection and stapled appendix resection. Higher AAST appendicitis grade also correlated with infection-related complication occurrence. Despite the overall well-tolerated heterogeneity of approaches to acute appendicitis, increasing disease acuity or complexity appears to encourage homogeneity of intraoperative surgical technique toward advanced adjuncts.
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| 5. |
- Chenouard, Nicolas, et al.
(författare)
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Objective comparison of particle tracking methods
- 2014
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 11:3, s. 281-U247
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Tidskriftsartikel (refereegranskat)abstract
- Particle tracking is of key importance for quantitative analysis of intracellular dynamic processes from time-lapse microscopy image data. Because manually detecting and following large numbers of individual particles is not feasible, automated computational methods have been developed for these tasks by many groups. Aiming to perform an objective comparison of methods, we gathered the community and organized an open competition in which participating teams applied their own methods independently to a commonly defined data set including diverse scenarios. Performance was assessed using commonly defined measures. Although no single method performed best across all scenarios, the results revealed clear differences between the various approaches, leading to notable practical conclusions for users and developers.
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| 6. |
- Forssten, Maximilian Peter, 1996-, et al.
(författare)
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Surgical management of acute appendicitis during the European COVID-19 second wave: safe and effective
- 2023
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Ingår i: European Journal of Trauma and Emergency Surgery. - : Springer Science and Business Media LLC. - 1863-9933 .- 1615-3146 .- 1863-9941. ; 49, s. 57-67
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The COVID-19 (SARS-CoV-2) pandemic drove acute care surgeons to pivot from long established practice patterns. Early safety concerns regarding increased postoperative complication risk in those with active COVID infection promoted antibiotic-driven non-operative therapy for select conditions ahead of an evidence-base. Our study assesses whether active or recent SARS-CoV-2 positivity increases hospital length of stay (LOS) or postoperative complications following appendectomy. Methods: Data were derived from the prospective multi-institutional observational SnapAppy cohort study. This preplanned data analysis assessed consecutive patients aged ≥ 15years who underwent appendectomy for appendicitis (November 2020–May 2021). Patients were categorized based on SARS-CoV-2 seropositivity: no infection, active infection, and prior infection. Appendectomy method, LOS, and complications were abstracted. The association between SARS-CoV-2 seropositivity and complications was determined using Poisson regression, while the association with LOS was calculated using a quantile regression model. Results: Appendectomy for acute appendicitis was performed in 4047 patients during the second and third European COVID waves. The majority were SARS-CoV-2 uninfected (3861, 95.4%), while 70 (1.7%) were acutely SARS-CoV-2 positive, and 116 (2.8%) reported prior SARS-CoV-2 infection. After confounder adjustment, there was no statistically significant association between SARS-CoV-2 seropositivity and LOS, any complication, or severe complications. Conclusion: During sequential SARS-CoV-2 infection waves, neither active nor prior SARS-CoV-2 infection was associated with prolonged hospital LOS or postoperative complication. Despite early concerns regarding postoperative safety and outcome during active SARS-CoV-2 infection, no such association was noted for those with appendicitis who underwent operative management.
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| 7. |
- Gemmell, Neil J., et al.
(författare)
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The tuatara genome reveals ancient features of amniote evolution
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 584:7821, s. 403-409
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Tidskriftsartikel (refereegranskat)abstract
- The tuatara (Sphenodon punctatus)—the only living member of the reptilian order Rhynchocephalia (Sphenodontia), once widespread across Gondwana1,2—is an iconic species that is endemic to New Zealand2,3. A key link to the now-extinct stem reptiles (from which dinosaurs, modern reptiles, birds and mammals evolved), the tuatara provides key insights into the ancestral amniotes2,4. Here we analyse the genome of the tuatara, which—at approximately 5 Gb—is among the largest of the vertebrate genomes yet assembled. Our analyses of this genome, along with comparisons with other vertebrate genomes, reinforce the uniqueness of the tuatara. Phylogenetic analyses indicate that the tuatara lineage diverged from that of snakes and lizards around 250 million years ago. This lineage also shows moderate rates of molecular evolution, with instances of punctuated evolution. Our genome sequence analysis identifies expansions of proteins, non-protein-coding RNA families and repeat elements, the latter of which show an amalgam of reptilian and mammalian features. The sequencing of the tuatara genome provides a valuable resource for deep comparative analyses of tetrapods, as well as for tuatara biology and conservation. Our study also provides important insights into both the technical challenges and the cultural obligations that are associated with genome sequencing.
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| 8. |
- Netterberg, Ida, et al.
(författare)
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The tumor time-course predicts overall survival in non-small cell lung cancer patients treated with atezolizumab : dependency on follow-up time
- 2020
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Ingår i: CPT. - : Wiley. - 2163-8306. ; 9:2, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- The large heterogeneity in response to immune checkpoint inhibitors is driving the exploration of predictive biomarkers to identify patients who will respond to such treatment. We extended our previously suggested modeling framework of atezolizumab pharmacokinetics, IL18, and tumor size (TS) dynamics, to also include overall survival (OS). Baseline and model‐derived variables were explored as predictors of OS in 88 patients with non‐small cell lung cancer treated with atezolizumab. To investigate the impact of follow‐up length on the inclusion of predictors of OS, four different censoring strategies were applied. The time‐course of TS change was the most significant predictor in all scenarios, whereas IL18 was not significant. Identified predictors of OS were similar regardless of censoring strategy, although OS was underpredicted when patients were censored 5 months after last dose. The study demonstrated that the tumor‐time course‐OS relationship could be identified based on early phase I data.
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| 9. |
- Reulen, Raoul C, et al.
(författare)
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Risk Factors for Primary Bone Cancer After Childhood Cancer : A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study
- 2023
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 41:21, s. 3735-3746
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.METHODS: Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship.RESULTS: The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation ( P trend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m 2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer. CONCLUSION: To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m 2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.
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| 10. |
- Roura-Pascual, Núria, et al.
(författare)
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Alternative futures for global biological invasions
- 2021
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Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 16:5, s. 1637-1650
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Tidskriftsartikel (refereegranskat)abstract
- Scenario analysis has emerged as a key tool to analyze complex and uncertain future socio-ecological developments. However, currently existing global scenarios (narratives of how the world may develop) have neglected biological invasions, a major threat to biodiversity and the economy. Here, we use a novel participatory process to develop a diverse set of global biological invasion scenarios spanning a wide range of plausible global futures through to 2050. We adapted the widely used two axes scenario analysis approach to develop four families of four scenarios each, resulting in 16 scenarios that were later clustered into four contrasting sets of futures. Our analysis highlights that socioeconomic developments and technological innovation have the potential to shape biological invasions, in addition to well-known drivers, such as climate and human land use change and global trade. Our scenarios partially align with the shared socioeconomic pathways created by the climate change research community. Several factors that drive differences in biological invasions were underrepresented in the shared socioeconomic pathways; in particular, the implementation of biosecurity policies. We argue that including factors related to public environmental awareness and technological and trade development in global scenarios and models is essential to adequately consider biological invasions in global environmental assessments and thereby obtain a more integrative picture of future social-ecological developments.
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