The spreadsheet paradigm: a basis for powerful and accessible programming

This paper takes a cognition-centric approach for programming languages. It promotes the spreadsheet paradigm, with two concrete goals. First, it calls for the design and implementation of several language features to enhance the expressiveness of spreadsheet programming. Second, it describes a plan for rigorous empirical studies to retain the learnability of spreadsheet programming

Measuring Interaction Design before Building the System: a Model-Based Approach

Early prototyping of user interfaces is an established good practice in interactive system development. However, prototypes cover only some usage scenarios, and questions dealing with number of required steps, possible interaction paths or impact of possible user errors can be answered only for the specific scenarios and only after tedious manual inspection. We present a tool (MIGTool) that transforms models of the behavior of a user interface into a graph, upon which usage scenarios can be easily specified, and used by MIGTool to compute possible interaction paths. Metrics based on possible paths, with or without user navigation errors, can then be computed. For example, when analyzing four mail applications, we show that Gmail has 3 times more shortest routes, has twice more routes that include a single user error, has routes with 13\ufewer steps, but has also optimal routes with the smallest probability to be chosen. Without MIGTool, this kind of analysis could only be done after building some prototype of the system, and then only for specific scenarios by manually tracing user actions and relative changes to the screens. With MIGTool the exploration of suitability of a design with respect to different scenarios, or comparison of different design alternatives against a single scenario, can be done with just a partial specification of the user interface behavior. This is made possible by the ability to associate scenarios steps to required user actions as defined in the model, by an efficient strategy to identify complete execution traces that users can follow, and by computing a range of diverse metrics on these results

Umbrella review and meta‐analysis of antiplatelet therapy for peripheral artery disease

Background The literature on antiplatelet therapy for peripheral artery disease has historically been summarized inconsistently, leading to conflict between international guidelines. An umbrella review and meta‐analysis was performed to summarize the literature, allow assessment of competing safety risks and clinical benefits, and identify weak areas for future research. Methods MEDLINE, Embase, DARE, PROSPERO and Cochrane databases were searched from inception until January 2019. All meta‐analyses of antiplatelet therapy in peripheral artery disease were included. Quality was assessed using AMSTAR scores, and GRADE analysis was used to quantify the strength of evidence. Data were pooled using random‐effects models. Results Twenty‐eight meta‐analyses were included. Thirty‐three clinical outcomes and 41 antiplatelet comparisons in 72 181 patients were analysed. High‐quality evidence showed that antiplatelet monotherapy reduced non‐fatal strokes (3 (95 per cent c.i. 0 to 6) fewer per 1000 patients), In symptomatic patients, it reduced cardiovascular deaths (8 (0 to 16) fewer per 1000 patients), but increased the risk of major bleeding (7 (3 to 14) more events per 1000). In asymptomatic patients, monotherapy reduced non‐fatal strokes (5 (0 to 8) fewer per 1000), but had no other clinical benefit. Dual antiplatelet therapy caused more major bleeding after intervention than monotherapy (37 (8 to 102) more events per 1000), with very low‐quality evidence of improved endovascular patency (risk ratio 4·00, 95 per cent c.i. 0·91 to 17·68). Conclusion Antiplatelet monotherapy has minimal clinical benefit for asymptomatic peripheral artery disease, and limited benefit for symptomatic disease, with a clear risk of major bleeding. There is a lack of evidence to guide antiplatelet prescribing after peripheral endovascular intervention

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

Acute corticospinal tract diffusion tensor imaging predicts 6-month functional outcome after intracerebral haemorrhage

INTRODUCTION: Diffusion tensor imaging (DTI) can assess the structural integrity of the corticospinal tract (CST) in vivo. We aimed to investigate whether CST DTI metrics after intracerebral haemorrhage (ICH) are associated with 6-month functional outcome and can improve the predictive performance of the existing ICH score. METHODS: We retrospectively included 42 patients with DTI performed within 5 days after deep supratentorial spontaneous ICH. Ipsilesional-to-contralesional ratios were calculated for fractional anisotropy (rFA) and mean diffusivity (rMD) in the pontine segment (PS) of the CST. We determined the most predictive variables for poor 6-month functional outcome [modified Rankin Scale (mRS) > 2] using the least absolute shrinkage and selection operator (LASSO) method. We calculated discrimination using optimism-adjusted estimation of the area under the curve (AUC). RESULTS: Patients with 6-month mRS > 2 had lower rFA (0.945 [± 0.139] vs 1.045 [± 0.130]; OR 0.004 [95% CI 0.00-0.77]; p =  0.04) and higher rMD (1.233 [± 0.418] vs 0.963 [± 0.211]; OR 22.5 [95% CI 1.46-519.68]; p = 0.02). Discrimination (AUC) values were: 0.76 (95% CI 0.61-0.91) for the ICH score, 0.71 (95% CI 0.54-0.89) for rFA, and 0.72 (95% CI 0.61-0.91) for rMD. Combined models with DTI and non-DTI variables offer an improvement in discrimination: for the best model, the AUC was 0.82 ([95% CI 0.68-0.95]; p = 0.15). CONCLUSION: In our exploratory study, PS-CST rFA and rMD had comparable predictive ability to the ICH score for 6-month functional outcome. Adding DTI metrics to clinical-radiological scores might improve discrimination, but this needs to be investigated in larger studies

Whole-brain diffusion tensor imaging predicts 6-month functional outcome in acute intracerebral haemorrhage

Introduction: Small vessel disease (SVD) causes most spontaneous intracerebral haemorrhage (ICH) and is associated with widespread microstructural brain tissue disruption, which can be quantified via diffusion tensor imaging (DTI) metrics: mean diffusivity (MD) and fractional anisotropy (FA). Little is known about the impact of whole-brain microstructural alterations after SVD-related ICH. We aimed to investigate: (1) association between whole-brain DTI metrics and functional outcome after ICH; and (2) predictive ability of these metrics compared to the pre-existing ICH score. Methods: Sixty-eight patients (38.2% lobar) were retrospectively included. We assessed whole-brain DTI metrics (obtained within 5 days after ICH) in cortical and deep grey matter and white matter. We used univariable logistic regression to assess the associations between DTI and clinical-radiological variables and poor outcome (modified Rankin Scale > 2). We determined the optimal predictive variables (via LASSO estimation) in: model 1 (DTI variables only), model 2 (DTI plus non-DTI variables), model 3 (DTI plus ICH score). Optimism-adjusted C-statistics were calculated for each model and compared (likelihood ratio test) against the ICH score. Results: Deep grey matter MD (OR 1.04 [95% CI 1.01–1.07], p = 0.010) and white matter MD (OR 1.11 [95% CI 1.01–1.23], p = 0.044) were associated (univariate analysis) with poor outcome. Discrimination values for model 1 (0.67 [95% CI 0.52–0.83]), model 2 (0.71 [95% CI 0.57–0.85) and model 3 (0.66 [95% CI 0.52–0.82]) were all significantly higher than the ICH score (0.62 [95% CI 0.49–0.75]). Conclusion: Our exploratory study suggests that whole-brain microstructural disruption measured by DTI is associated with poor 6-month functional outcome after SVD-related ICH. Whole-brain DTI metrics performed better at predicting recovery than the existing ICH score

Association between Triglyceride-Glucose Index and Early Neurological Outcomes after Thrombolysis in Patients with Acute Ischemic Stroke

Background: The triglyceride-glucose (TyG) index is a novel biomarker of insulin resistance which might plausibly influence endogenous fibrinolysis and thus early neurological outcomes in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis using recombinant tissue-plasminogen activator. Methods: We included consecutive AIS patients within 4.5 h of symptom onset undergoing intravenous thrombolysis between January 2015 and June 2022 in this multi-center retrospective observational study. Our primary outcome was early neurological deterioration (END), defined as ≥2 (END2) or ≥ 4 (END4) National Institutes of Health Stroke Scale (NIHSS) score worsening compared to the initial NIHSS score within 24 h of intravenous thrombolysis. Our secondary outcome was early neurological improvement (ENI), defined as a lower NIHSS score at discharge. TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. We evaluated the association of END and ENI with TyG index using a logistic regression model. Results: A total of 676 patients with AIS were evaluated. The median age was 68 (Interquartile range, IQR (60–76) years old), and 432 (63.9%) were males. A total of 89 (13.2%) patients developed END2, 61 (9.0%) patients developed END4, and 492 (72.7%) experienced ENI. In multivariable logistic regression analysis, after adjustment for confounding factors, TyG index was significantly associated with increased risks of END2 (categorical variable, vs. lowest tertile, medium tertile odds ratio [OR] 1.05, 95% confidence interval, CI 0.54–2.02, highest tertile OR 2.94, 95%CI 1.64–5.27, overall p < 0.001) and END4 (categorical variable, vs. lowest tertile, medium tertile OR 1.21, 95%CI 0.54–2.74, highest tertile OR 3.80, 95%CI 1.85–7.79, overall p < 0.001), and a lower probability of ENI (categorical variable, vs. lowest tertile, medium tertile OR 1.00, 95%CI 0.63–1.58, highest tertile OR 0.59, 95%CI 0.38–0.93, overall p = 0.022). Conclusions: Increasing TyG index was associated with a higher risk of END and a lower probability of ENI in patients with acute ischemic stroke treated with intravenous thrombolysis

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

Sea WiFS Technical Report Series: The fourth SeaWIFS Intercalibration Round-Robin Experiment (SIRREX-4), May 1995

This report documents the fourth Sea-viewing Wide Field-of-view Sensor (SeaWiFS) Intercalibration Round-Robin Experiment (SIRREX-4), which was held at the National Institute of Standards and Technology (NIST) on 3-10 May 1995. The agenda for SIRREX-4 was established by a consensus reached at the conclusion of SIRREX-3: there should be an emphasis on training and work to foster and encourage uniform use of accepted protocols for calibrating radiometric instruments in the laboratory. The goal was to host the activity in a setting where proper techniques could be discussed and demonstrated. It seemed appealing to split the day between morning lectures and afternoon laboratory exercises or practicals. The former gave the user community a chance to present what was important to them and discuss it with acknowledged experts in radiometry, while the latter presented a unique opportunity for training and evaluation in the presence of these same experts. The five laboratory sessions were concerned with (1) determining the responsivity of a spectroradiometer and the spectral radiance of an unknown integrating sphere source, (2) demonstrating spectral field calibration procedures for an integrating sphere using three different instruments, (3) measuring spectral radiance using the plaque method, (4) setting up and aligning lamp calibration transfer standards using the NIST specifications for irradiance measurements, and (5) characterizing radiometric instruments. In addition to documenting some supplemental studies performed outside the laboratory sessions, this report includes an evaluation of the hardware that has been used during the SIRREX activities plus a critical evaluation of SIRREX objectives

Randomised controlled trial of the clinical and cost-effectiveness of a peer delivered self-management intervention to prevent relapse in crisis resolution team users: study protocol

Introduction: Crisis resolution teams (CRTs) provide assessment and intensive home treatment in a crisis, aiming to offer an alternative for people who would otherwise require a psychiatric inpatient admission. They are available in most areas in England. Despite some evidence for their clinical and cost-effectiveness, recurrent concerns are expressed regarding discontinuity with other services and lack of focus on preventing future relapse and readmission to acute care. Currently evidence on how to prevent readmissions to acute care is limited. Self management interventions, involving supporting service users in recognising and managing signs of their own illness and in actively planning their recovery, have some supporting evidence, but have not been tested as a means of preventing readmission to acute care in people leaving community crisis care. We thus proposed the current study to test the effectiveness of such an intervention. We selected peer support workers as the preferred staff to deliver such an intervention, as they are well-placed to model and encourage active and autonomous recovery from mental health problems. Methods and analysis: The CORE (CRT Optimisation and Relapse Prevention) self management trial compares the effectiveness of a peer provided self-management intervention for people leaving CRT care, with treatment as usual supplemented by a booklet on self-management. The planned sample is 440 participants, including 40 participants in an internal pilot. The primary outcome measure is whether participants are readmitted to acute care over 1 year of follow-up following entry to the trial. Secondary outcomes include self-rated recovery at 4 and at 18 months following trial entry, measured using the Questionnaire on the Process of Recovery. Analysis will follow an intention to treatment principle. Random effects logistic regression modelling with adjustment for clustering by peer support worker will be used to test the primary hypothesis