Approximating Markov Chains for Bootstrapping and Simulation

In this work we develop a bootstrap method based on the theory of Markov chains. The method moves from the two competing objectives that a researcher pursues when performing a bootstrap procedure: (i) to preserve the structural similarity -in statistical sense- between the original and the bootstrapped sample; (ii) to assure a diversification of the latter with respect to the former. The original sample is assumed to be driven by a Markov chain. The approach we follow is to implement an optimization problem to estimate the memory of a Markov chain (i.e. its order) and to identify its relevant states. The basic ingredients of the model are the transition probabilities, whose distance is measured through a suitably defined functional. We apply the method to the series of electricity prices in Spain. A comparison with the Variable Length Markov Chain bootstrap, which is a well established bootstrap method, shows the superiority of our proposal in reproducing the dependence among data

A Tabu Search Heuristic Procedure in Markov Chain Bootstrapping

Markov chain theory is proving to be a powerful approach to bootstrap nite states processes, especially where time dependence is non linear. In this work we extend such approach to bootstrap discrete time continuous-valued processes. To this purpose we solve a minimization problem to partition the state space of a continuous-valued process into a nite number of intervals or unions of intervals (i.e. its states) and identify the time lags which provide \memory" to the process. A distance is used as objective function to stimulate the clustering of the states having similar transition probabilities. The problem of the exploding number of alternative partitions in the solution space (which grows with the number of states and the order of the Markov chain) is addressed through a Tabu Search algorithm. The method is applied to bootstrap the series of the German and Spanish electricity prices. The analysis of the results conrms the good consistency properties of the method we propose

Children with Cerebral Palsy can imagine actions like their normally developed peers

The present study aimed at assessing whether children with Cerebral Palsy (CP) can imagine object directed actions similarly to their normally developed peers. We asked children with CP (n = 12) and paired healthy controls (n = 12) to imagine in first person perspective eight daily actions, after observing them through videoclips presented on a computer screen. During motor imagery (MI) children were interrupted at a specific timepoint (e.g., at 2.5 s) from the start. Two frames extracted from the videoclips were then presented on the screen. One of the two depicted the correct timepoint at which the imagined action was interrupted, while the other represented an earlier or later timepoint. Children had to respond by pressing the key associated to the correct frame. Children also underwent VMIQ-2 questionnaire. Both groups performed similarly in the questionnaire and in the requested task, where they showed the same error rate. Errors mainly concerned the later frame, suggesting a similar strategy to solve the task in the two groups. The results support the view that children with CP can imagine actions similarly to their normally developed peers. This encourages the use of MI as a rehabilitative tool in children with motor impairment

Droplet Self-Propulsion on Slippery Liquid-Infused Surfaces with Dual Lubricant Wedge-Shaped Wettability Patterns

Young’s equation is fundamental to the concept of the wettability of a solid surface. It defines the contact angle for a droplet on a solid surface through a local equilibrium at the three-phase contact line. Recently, the concept of a liquid Young’s law contact angle has been developed to describe the wettability of slippery liquid-infused porous surfaces (SLIPS) by droplets of an immiscible liquid. In this work, we present a new method to fabricate biphilic SLIP surfaces and show how the wettability of the composite SLIPS can be exploited with a macroscopic wedge-shaped pattern of two distinct lubricant liquids. In particular, we report the development of composite liquid surfaces on silicon substrates based on lithographically patterning a Teflon AF1600 coating and a superhydrophobic coating (Glaco Mirror Coat Zero), where the latter selectively dewets from the former. This creates a patterned base surface with preferential wetting to matched liquids: the fluoropolymer PTFE with a perfluorinated oil Krytox and the hydrophobic silica-based GLACO with olive oil (or other mineral oils or silicone oil). This allows us to successively imbibe our patterned solid substrates with two distinct oils and produce a composite liquid lubricant surface with the oils segregated as thin films into separate domains defined by the patterning. We illustrate that macroscopic wedge-shaped patterned SLIP surfaces enable low-friction droplet self-propulsion. Finally, we formulate an analytical model that captures the dependence of the droplet motion as a function of the wettability of the two liquid lubricant domains and the opening angle of the wedge. This allows us to derive scaling relationships between various physical and geometrical parameters. This work introduces a new approach to creating patterned liquid lubricant surfaces, demonstrates long-distance droplet self-propulsion on such surfaces, and sheds light on the interactions between liquid droplets and liquid surfaces

Cerebral blood flow and cerebrovascular reactivity correlate with severity of motor symptoms in Parkinson’s disease

Background: Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder that is mainly characterized by movement dysfunction. Neurovascular unit (NVU) disruption has been proposed to be involved in the disease, but its role in PD neurodegenerative mechanisms is still unclear. The aim of this study was to investigate cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) within the regions belonging to the motor network, in patients with mild to moderate stages of PD. Methods: Twenty-eight PD patients (66.6 \ub1 8.6 years, 22 males, median [interquartile range, IQR] Hoehn & Yahr = 1.5 [1\u20131.9]) and 32 age- and sex-matched healthy controls (HCs) were scanned with arterial spin labeling (ASL) magnetic resonance imaging (MRI) for CBF assessment. ASL MRI was also acquired in hypercapnic conditions to induce vasodilation and subsequently allow for CVR measurement in a subgroup of 13 PD patients and 13 HCs. Median CBF and CVR were extracted from cortical and subcortical regions belonging to the motor network and compared between PD patients and HCs. In addition, the correlation between these parameters and the severity of PD motor symptoms [quantified with Unified Parkinson\u2019s Disease Rating Scale part III (UPDRS III)] was assessed. The false discovery rate (FDR) method was used to correct for multiple comparisons. Results: No significant differences in terms of CBF and CVR were found between PD patients and HCs. Positive significant correlations were observed between CBF and UPDRS III within the precentral gyrus, postcentral gyrus, supplementary motor area, striatum, pallidum, thalamus, red nucleus, and substantia nigra (pFDR < 0.05). Conversely, significant negative correlation between CVR and UPDRS III was found in the corpus striatum (pFDR < 0.05). Conclusion: CBF and CVR assessment provides information about NVU integrity in an indirect and noninvasive way. Our findings support the hypothesis of NVU involvement at the mild to moderate stages of PD, suggesting that CBF and CVR within the motor network might be used as either diagnostic or prognostic markers for PD

Feasibility and Predictive Performance of a Triage System for Patients with Cancer During the COVID-19 Pandemic

Background: Triage procedures have been implemented to limit hospital access and minimize infection risk among patients with cancer during the coronavirus disease (COVID-19) outbreak. In the absence of prospective evidence, we aimed to evaluate the predictive performance of a triage system in the oncological setting. Materials and Methods: This retrospective cohort study analyzes hospital admissions to the oncology and hematology department of Udine, Italy, during the COVID-19 pandemic (March 30 to April 30, 2020). A total of 3,923 triage procedures were performed, and data of 1,363 individual patients were reviewed. Results: A self-report triage questionnaire identified 6% of triage-positive procedures, with a sensitivity of 66.7% (95% confidence interval [CI], 43.0%–85.4%), a specificity of 94.3% (95% CI, 93.5%–95.0%), and a positive predictive value of 5.9% (95% CI, 4.3%–8.0%) for the identification of patients who were not admitted to the hospital after medical review. Patients with thoracic cancer (odds ratio [OR], 1.69; 95% CI, 1.13–2.53, p =.01), younger age (OR, 1.52; 95% CI, 1.15–2.01, p <.01), and body temperature at admission ≥37°C (OR, 9.52; 95% CI, 5.44–16.6, p <.0001) had increased risk of positive triage. Direct hospital access was warranted to 93.5% of cases, a further 6% was accepted after medical evaluation, whereas 0.5% was refused at admission. Conclusion: A self-report questionnaire has a low positive predictive value to triage patients with cancer and suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms. Differential diagnosis with tumor- or treatment-related symptoms is always required to avoid unnecessary treatment delays. Body temperature measurement improves the triage process's overall sensitivity, and widespread SARS-CoV-2 testing should be implemented to identify asymptomatic carriers. Implications for Practice: This is the first study to provide data on the predictive performance of a triage system in the oncological setting during the coronavirus disease outbreak. A questionnaire-based triage has a low positive predictive value to triage patients with cancer and suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms, and a differential diagnosis with tumor- or treatment-related symptoms is mandatory to avoid unnecessary treatment delays. Consequently, adequate recourses should be reallocated for a triage implementation in the oncological setting. Of note, body temperature measurement improves the overall sensitivity of the triage process, and widespread testing for SARS-CoV-2 infection should be implemented to identify asymptomatic carriers

Modified percutaneous ethanol injection of parathyroid adenoma in primary hyperparathyroidism.

Surgery is the treatment of choice for symptomatic primary hyperparathyroidism; unlikely few patients do not meet established surgical criteria or have comorbid conditions that prohibit surgery. In these subjects, medical therapy alone offers little hope for a sustained long normocalcemic period. However percutaneous ethanol injection (PEI) may represent an alternative therapeutic procedure. It is currently in use for the treatment of secondary or tertiary hyperparathyroidism, however, few studies or case reports suggest it for the treatment of primary hyperparathyroidism. Moreover, little information is available about the long-term follow-up, where incomplete necrosis or the spreading of ethanol in the surrounding tissues is often reported. We believe that many of the side effects could be correlated to procedure itself. Taking these experiences into account, we have reasoned that in order to limit these side effects, we had to modify the standard PEI procedure. We reported this preliminary experience describing our modified PEI procedure

Drug holidays and overall survival of patients with metastatic colorectal cancer

Different de-escalation strategies have been proposed to limit the risk of cumulative toxicity and guarantee quality of life during the treatment trajectory of patients with metastatic colorectal cancer (mCRC). Programmed treatment interruptions, defined as drug holidays (DHs), have been implemented in clinical practice. We evaluated the association between DHs and overall survival (OS). This was a retrospective study, conducted at the University Hospital of Udine and the IRCCS CRO of Aviano. We retrieved records of 608 consecutive patients treated for mCRC from 1 January 2005 to 15 March 2017 and evaluated the impact of different de-escalation strategies (maintenance, DHs, or both) on OS through uni-and multivariate Cox regression analyses. We also looked at attrition rates across treatment lines according to the chosen strategy. In our study, 19.24% of patients received maintenance therapy, 16.12% DHs, and 9.87% both, while 32.07% continued full-intensity first-line treatment up to progression or death. In uni-and multivariate analyses first-line continuous treatment and early discontinuation (treatment for less than 3 months) were associated to worse OS compared to non-continuous strategies (HR, 1.68; 95% CI, 1.22\u20132.32; p = 0.002 and HR,4.89; 95% CI, 3.33\u20137.19; p < 0.001, respectively). Attrition rates were 22.8%, 20.61%, and 19.64% for maintenance, DHs, or both, respectively. For continuous therapy and for treatment of less than 3 months it was 21.57% and 49%. De-escalation strategies are safe and effective options. DHs after initial induction chemotherapy may be considered in clinically selected patients with metastatic colorectal cancer