The Abdominal Aortic Aneurysm Statistically Corrected Operative Risk Evaluation (AAA SCORE) for predicting mortality after open and endovascular interventions

BackgroundAccurate adjustment of surgical outcome data for risk is vital in an era of surgeon-level reporting. Current risk prediction models for abdominal aortic aneurysm (AAA) repair are suboptimal. We aimed to develop a reliable risk model for in-hospital mortality after intervention for AAA, using rigorous contemporary statistical techniques to handle missing data.MethodsUsing data collected during a 15-month period in the United Kingdom National Vascular Database, we applied multiple imputation methodology together with stepwise model selection to generate preoperative and perioperative models of in-hospital mortality after AAA repair, using two thirds of the available data. Model performance was then assessed on the remaining third of the data by receiver operating characteristic curve analysis and compared with existing risk prediction models. Model calibration was assessed by Hosmer-Lemeshow analysis.ResultsA total of 8088 AAA repair operations were recorded in the National Vascular Database during the study period, of which 5870 (72.6%) were elective procedures. Both preoperative and perioperative models showed excellent discrimination, with areas under the receiver operating characteristic curve of .89 and .92, respectively. This was significantly better than any of the existing models (area under the receiver operating characteristic curve for best comparator model, .84 and .88; P < .001 and P = .001, respectively). Discrimination remained excellent when only elective procedures were considered. There was no evidence of miscalibration by Hosmer-Lemeshow analysis.ConclusionsWe have developed accurate models to assess risk of in-hospital mortality after AAA repair. These models were carefully developed with rigorous statistical methodology and significantly outperform existing methods for both elective cases and overall AAA mortality. These models will be invaluable for both preoperative patient counseling and accurate risk adjustment of published outcome data

Historical roots of Agile methods: where did “Agile thinking” come from?

The appearance of Agile methods has been the most noticeable change to software process thinking in the last fifteen years [16], but in fact many of the “Agile ideas” have been around since 70’s or even before. Many studies and reviews have been conducted about Agile methods which ascribe their emergence as a reaction against traditional methods. In this paper, we argue that although Agile methods are new as a whole, they have strong roots in the history of software engineering. In addition to the iterative and incremental approaches that have been in use since 1957 [21], people who criticised the traditional methods suggested alternative approaches which were actually Agile ideas such as the response to change, customer involvement, and working software over documentation. The authors of this paper believe that education about the history of Agile thinking will help to develop better understanding as well as promoting the use of Agile methods. We therefore present and discuss the reasons behind the development and introduction of Agile methods, as a reaction to traditional methods, as a result of people's experience, and in particular focusing on reusing ideas from histor

Refining Vision Videos

[Context and motivation] Complex software-based systems involve several stakeholders, their activities and interactions with the system. Vision videos are used during the early phases of a project to complement textual representations. They visualize previously abstract visions of the product and its use. By creating, elaborating, and discussing vision videos, stakeholders and developers gain an improved shared understanding of how those abstract visions could translate into concrete scenarios and requirements to which individuals can relate. [Question/problem] In this paper, we investigate two aspects of refining vision videos: (1) Refining the vision by providing alternative answers to previously open issues about the system to be built. (2) A refined understanding of the camera perspective in vision videos. The impact of using a subjective (or "ego") perspective is compared to the usual third-person perspective. [Methodology] We use shopping in rural areas as a real-world application domain for refining vision videos. Both aspects of refining vision videos were investigated in an experiment with 20 participants. [Contribution] Subjects made a significant number of additional contributions when they had received not only video or text but also both - even with very short text and short video clips. Subjective video elements were rated as positive. However, there was no significant preference for either subjective or non-subjective videos in general.Comment: 15 pages, 25th International Working Conference on Requirements Engineering: Foundation for Software Quality 201

Proteogenomic analysis of mycobacterium smegmatis using high resolution mass spectrometry

Biochemical evidence is vital for accurate genome annotation. The integration of experimental data collected at the proteome level using high resolution mass spectrometry allows for improvements in genome annotation by providing evidence for novel gene models, while validating or modifying others. Here, we report the results of a proteogenomic analysis of a reference strain of Mycobacterium smegmatis (mc2155), a fast growing model organism for the pathogenic Mycobacterium tuberculosis—the causative agent for Tuberculosis. By integrating high throughput LC/MS/MS proteomic data with genomic six frame translation and ab initio gene prediction databases, a total of 2887 ORFs were identified, including 2810 ORFs annotated to a Reference protein, and 63 ORFs not previously annotated to a Reference protein. Further, the translational start site (TSS) was validated for 558 Reference proteome gene models, while upstream translational evidence was identified for 81. In addition, N-terminus derived peptide identifications allowed for downstream TSS modification of a further 24 gene models. We validated the existence of six previously described interrupted coding sequences at the peptide level, and provide evidence for four novel frameshift positions. Analysis of peptide posterior error probability (PEP) scores indicates high-confidence novel peptide identifications and shows that the genome of M. smegmatis mc2155 is not yet fully annotated. Data are available via ProteomeXchange with identifier PXD003500

What factors indicate prognosis for adults with depression in primary care? A protocol for meta-analyses of individual patient data using the Dep-GP database [version 2; peer review: 2 approved]

BACKGROUND: Pre-treatment severity is a key indicator of prognosis for those with depression. Knowledge is limited on how best to encompass severity of disorders. A number of non-severity related factors such as social support and life events are also indicators of prognosis. It is not clear whether this holds true after adjusting for pre-treatment severity as a) a depressive symptom scale score, and b) a broader construct encompassing symptom severity and related indicators: “disorder severity”. In order to investigate this, data from the individual participants of clinical trials which have measured a breadth of “disorder severity” related factors are needed. AIMS: 1) To assess the association between outcomes for adults seeking treatment for depression and the severity of depression pre-treatment, considered both as i) depressive symptom severity only and ii) “disorder severity” which includes depressive symptom severity and comorbid anxiety, chronicity, history of depression, history of previous treatment, functional impairment and health-related quality of life. 2) To determine whether i) social support, ii) life events, iii) alcohol misuse, and iv) demographic factors (sex, age, ethnicity, marital status, employment status, level of educational attainment, and financial wellbeing) are prognostic indicators of outcomes, independent of baseline “disorder severity” and the type of treatment received. METHODS: Databases were searched for randomised clinical trials (RCTs) that recruited adults seeking treatment for depression from their general practitioners and used the same diagnostic and screening instrument to measure severity at baseline – the Revised Clinical Interview Schedule; outcome measures could differ between studies. Chief investigators of all studies meeting inclusion criteria were contacted and individual patient data (IPD) were requested. CONCLUSIONS: In total 15 RCTs met inclusion criteria. The Dep-GP database will include the 6271 participants from the 13 studies that provided IPD. This protocol outlines how these data will be analysed. REGISTRATION: PROSPERO CRD42019129512 (01/04/2019

Improving Risk Adjustment for Mortality After Pediatric Cardiac Surgery: The UK PRAiS2 Model

BACKGROUND: Partial Risk Adjustment in Surgery (PRAiS), a risk model for 30-day mortality after children's heart surgery, has been used by the UK National Congenital Heart Disease Audit to report expected risk-adjusted survival since 2013. This study aimed to improve the model by incorporating additional comorbidity and diagnostic information. METHODS: The model development dataset was all procedures performed between 2009 and 2014 in all UK and Ireland congenital cardiac centers. The outcome measure was death within each 30-day surgical episode. Model development followed an iterative process of clinical discussion and development and assessment of models using logistic regression under 25 × 5 cross-validation. Performance was measured using Akaike information criterion, the area under the receiver-operating characteristic curve (AUC), and calibration. The final model was assessed in an external 2014 to 2015 validation dataset. RESULTS: The development dataset comprised 21,838 30-day surgical episodes, with 539 deaths (mortality, 2.5%). The validation dataset comprised 4,207 episodes, with 97 deaths (mortality, 2.3%). The updated risk model included 15 procedural, 11 diagnostic, and 4 comorbidity groupings, and nonlinear functions of age and weight. Performance under cross-validation was: median AUC of 0.83 (range, 0.82 to 0.83), median calibration slope and intercept of 0.92 (range, 0.64 to 1.25) and -0.23 (range, -1.08 to 0.85) respectively. In the validation dataset, the AUC was 0.86 (95% confidence interval [CI], 0.82 to 0.89), and the calibration slope and intercept were 1.01 (95% CI, 0.83 to 1.18) and 0.11 (95% CI, -0.45 to 0.67), respectively, showing excellent performance. CONCLUSIONS: A more sophisticated PRAiS2 risk model for UK use was developed with additional comorbidity and diagnostic information, alongside age and weight as nonlinear variables

Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial. A multicentre, randomised controlled trial: design and methodology

PURPOSE: The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT). DESIGN: The LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis. CONCLUSIONS: The LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication. TRIAL REGISTRATION NUMBER: ISRCTN32038223, Pre-results

Different Transport Pathways of Individual Precursor Proteins in Mitochondria

Transport of mitochondrial precursor proteins into mitochondria of Neurospora crassa was studied in a cellfree reconstituted system. Precursors were synthesized in a reticulocyte lysate programmed with Neurospora mRNA and transported into isolated mitochondria in the absence of protein synthesis. Uptake of the following precursors was investigated: apocytochrome c, ADP/ATP carrier and subunit 9 of the oligomycin-sensitive ATPase. Addition of high concentrations of unlabelled chemically prepared apocytochrome c (1–10 μM) inhibited the appearance in the mitochondrial of labelled cytochrome c synthesized in vitro because the unlabelled protein dilutes the labelled one and because the translocation system has a limited capacity [apparent V is 1–3 pmol × min−1× (mg mitochondrial protein)−1]. Concentrations of added apocytochrome c exceeding the concentrations of precursor proteins synthesized in vitro by a factor of about 104 did not inhibit the transfer of ADP/ATP carrier or ATPase subunit 9 into mitochondria. Carbonylcyanide m-chlorophenylhydrazone, an uncoupler of oxidative phosphorylation, inhibited transfer in vitro of ADP/ATP carrier and of ATPase subunit 9, but not of cytochrome c. These findings suggest that cytochrome c and the other two proteins have different import pathways into mitochondria. It can be inferred from the data presented that different 'receptors' on the mitochondrial surface mediate the specific recognition of precursor proteins by mitochondria as a first step in the transport process

Incidence and Outcomes of Severe Renal Impairment Following Ruptured Abdominal Aortic Aneurysm Repair

IntroductionAcute kidney injury (AKI) following ruptured abdominal aortic aneurysm (rAAA) repair is common and multifactorial. A standard definition of AKI after endovascular repair (EVAR), the Aneurysm Renal Injury Score (ARISe), has been proposed to facilitate standardised reporting and thus improve understanding of this issue.MethodsData were collected retrospectively on AKI in a prospectively maintained database of all patients treated for rAAA in a single tertiary referral centre since the availability of routine out of hours emergency EVAR. The ARISe score was used to describe the degree of AKI and factors which correlated with poor renal outcomes were assessed.ResultsTwo-hundred and five patients were treated between January 2006 and April 2014. Of these, 125 were treated with open repair (OSR) and 80 were treated with EVAR. Severe AKI (defined as ARISe score ≥3) occurred in 36% of patients. After correction for confounders, patients treated with OSR were significantly more likely to develop severe AKI (43% vs. 26%, p = .02). There was no significant difference in preoperative serum creatinine between groups, but increased preoperative serum creatinine was strongly associated with severe AKI postoperatively (p < .001). Age, sex, endograft type, and preoperative CT scanning were not associated with differences in renal outcomes. Clamp position above renal arteries was predictive of severe AKI in patients treated with OSR (p < .01). Patients suffering severe AKI had significantly higher mortality at 30 days and 12 months (28% vs. 5% and 44% vs. 13%, p < .001 for both comparisons).ConclusionSevere AKI is common following successful repair of rAAA. In this large case series of high-risk patients, OSR was associated with significantly higher rates of severe AKI compared with EVAR, despite the increased dose of contrast involved in EVAR and the older age of these patients. In turn, severe AKI was associated with higher mortality rates