A Composite Likelihood-based Approach for Change-point Detection in Spatio-temporal Process

This paper develops a unified, accurate and computationally efficient method for change-point inference in non-stationary spatio-temporal processes. By modeling a non-stationary spatio-temporal process as a piecewise stationary spatio-temporal process, we consider simultaneous estimation of the number and locations of change-points, and model parameters in each segment. A composite likelihood-based criterion is developed for change-point and parameters estimation. Asymptotic theories including consistency and distribution of the estimators are derived under mild conditions. In contrast to classical results in fixed dimensional time series that the asymptotic error of change-point estimator is $O_{p}(1)$, exact recovery of true change-points is guaranteed in the spatio-temporal setting. More surprisingly, the consistency of change-point estimation can be achieved without any penalty term in the criterion function. A computational efficient pruned dynamic programming algorithm is developed for the challenging criterion optimization problem. Simulation studies and an application to U.S. precipitation data are provided to demonstrate the effectiveness and practicality of the proposed method

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Automatic Optimal Batch Size Selection for Recursive Estimators of Time-Average Covariance Matrix

<p>The time-average covariance matrix (TACM) <math><mrow><mrow><mi></mi><mi>Σ</mi></mrow><mo>:</mo><mo>=</mo><msub><mo>∑</mo><mrow><mi>k</mi><mo>∈</mo><mi>Z</mi></mrow></msub><msub><mrow><mi></mi><mi>Γ</mi></mrow><mi>k</mi></msub></mrow></math>, where <b><i>Γ</i></b>_<i>k</i> is the auto-covariance function, is an important quantity for the inference of the mean of an <math><mi>R</mi><mi>d</mi></math>-valued stationary process (<i>d</i> ⩾ 1). This article proposes two recursive estimators for <b><i>Σ</i></b> with optimal asymptotic mean square error (AMSE) under different strengths of serial dependence. The optimal estimator involves a batch size selection, which requires knowledge of a smoothness parameter <math><mrow><msub><mrow><mi></mi><mi>ϒ</mi></mrow><mi>β</mi></msub><mo>:</mo><mo>=</mo><msub><mo>∑</mo><mrow><mi>k</mi><mo>∈</mo><mi>Z</mi></mrow></msub><mrow><mo>|</mo><mi>k</mi><mo>|</mo></mrow><mi>β</mi><msub><mrow><mi></mi><mi>Γ</mi></mrow><mi>k</mi></msub></mrow></math>, for some β. This article also develops recursive estimators for <b><i>ϒ</i></b>_β. Combining these two estimators, we obtain a fully automatic procedure for optimal online estimation for <b><i>Σ</i></b>. Consistency and convergence rates of the proposed estimators are derived. Applications to confidence region construction and Markov chain Monte Carlo convergence diagnosis are discussed. Supplementary materials for this article are available online.</p

Likelihood Inferences for High-Dimensional Factor Analysis of Time Series With Applications in Finance

<p>This article investigates likelihood inferences for high-dimensional factor analysis of time series data. We develop a matrix decomposition technique to obtain expressions of the likelihood functions and its derivatives. With such expressions, the traditional delta method that relies heavily on score function and Hessian matrix can be extended to high-dimensional cases. We establish asymptotic theories, including consistency and asymptotic normality. Moreover, fast computational algorithms are developed for estimation. Applications to high-dimensional stock price data and portfolio analysis are discussed. The technical proofs of the asymptotic results and the computer codes are available online.</p