An Exact Formula for the Average Run Length to False Alarm of the Generalized Shiryaev-Roberts Procedure for Change-Point Detection under Exponential Observations

We derive analytically an exact closed-form formula for the standard minimax Average Run Length (ARL) to false alarm delivered by the Generalized Shiryaev-Roberts (GSR) change-point detection procedure devised to detect a shift in the baseline mean of a sequence of independent exponentially distributed observations. Specifically, the formula is found through direct solution of the respective integral (renewal) equation, and is a general result in that the GSR procedure's headstart is not restricted to a bounded range, nor is there a "ceiling" value for the detection threshold. Apart from the theoretical significance (in change-point detection, exact closed-form performance formulae are typically either difficult or impossible to get, especially for the GSR procedure), the obtained formula is also useful to a practitioner: in cases of practical interest, the formula is a function linear in both the detection threshold and the headstart, and, therefore, the ARL to false alarm of the GSR procedure can be easily computed.Comment: 9 pages; Accepted for publication in Proceedings of the 12-th German-Polish Workshop on Stochastic Models, Statistics and Their Application

Remote Electrical Stimulation by Means of Implanted Rectifiers

Miniaturization of active implantable medical devices is currently compromised by the available means for electrically powering them. Most common energy supply techniques for implants – batteries and inductive couplers – comprise bulky parts which, in most cases, are significantly larger than the circuitry they feed. Here, for overcoming such miniaturization bottleneck in the case of implants for electrical stimulation, it is proposed to make those implants act as rectifiers of high frequency bursts supplied by remote electrodes. In this way, low frequency currents will be generated locally around the implant and these low frequency currents will perform stimulation of excitable tissues whereas the high frequency currents will cause only innocuous heating. The present study numerically demonstrates that low frequency currents capable of stimulation can be produced by a miniature device behaving as a diode when high frequency currents, neither capable of thermal damage nor of stimulation, flow through the tissue where the device is implanted. Moreover, experimental evidence is provided by an in vivo proof of concept model consisting of an anesthetized earthworm in which a commercial diode was implanted. With currently available microelectronic techniques, very thin stimulation capsules (diameter <500 µm) deliverable by injection are easily conceivable

Thoracoscopic Left Atrial Appendage Clipping: a multicenter cohort analysis

Objectives: This study sought to document the closure rate, safety, and stroke rate after thoracoscopic left atrial appendage (LAA) clipping. Background: The LAA is the main source of stroke in patients with atrial fibrillation, and thoracoscopic clipping may provide a durable and safe closure technique. Methods: The investigators studied consecutive patients undergoing clipping as part of a thoracoscopic maze procedure in 4 referral centers (the Netherlands and the United States) from 2012 to 2016. Completeness of LAA closure was assessed by either computed tomography (n = 100) or transesophageal echocardiography (n = 122). The primary outcome was complete LAA closure (absence of residual LAA flow and pouch <10 mm). The secondary outcomes were 30-day complications; the composite of ischemic stroke, hemorrhagic stroke, or transient ischemic attack; and all-cause mortality. Results: A total of 222 patients were included, with a mean age of 66 ± 9 years, and 68.5% were male. The mean CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65 to 74 years, sex category [female]) score was 2.3 ± 1.0. Complete LAA closure was achieved in 95.0% of patients. There were no intraoperative or clip-related complications, and the overall 30-day freedom from any complication rate was 96.4%. The freedom from cerebrovascular events after surgery was 99.1% after median follow-up of 20 months (interquartile range: 14 to 25 months; 369 patient-years of follow-up), and overall survival was 98.6%. The observed rate of cerebrovascular events after LAA clipping was low (0.5 per 100 patient-years). Conclusions: LAA clipping during thoracoscopic ablation is a feasible and safe technique for closure of the LAA in patients with atrial fibrillation. The lower than expected rate of cerebrovascular events after deployment was likely multifactorial, including not only LAA closure, but also the effect of oral anticoagulation and rhythm control

Tetramethylpyrazine attenuates spinal cord ischemic injury due to aortic cross-clamping in rabbits

BACKGROUND: Lower limb paralysis occurs in 11% of patients after surgical procedure of thoracic or thoracoabdominal aneurysms and is an unpredictable and distressful complication. The aim of this study was to investigate the effects of tetramethylpyrazine (TMP), an intravenous drug made from traditional Chinese herbs, on the neurologic outcome and hisotpathology after transient spinal cord ischemia in rabbits. METHODS: Forty-five male New Zealand white rabbits were anesthetized with isoflurane and spinal cord ischemia was induced for 20 min by infrarenal aortic occlusion. Animals were randomly allocated to one of five groups (n = 8 each). Group C received no pharmacologic intervention. Group P received intravenous infusion of 30 mg·kg(-1) TMP within 30 min before aortic occlusion. Group T(1), Group T(2) and Group T(3) received intravenous infusion of 15, 30 and 60 mg·kg(-1) TMP respectively within 30 min after reperfusion. In the sham group (n = 5), the animals underwent the same procedures as the control group except infrarental aortic unocclusion. Neurologic status was scored by using the Tarlov criteria (in which 4 is normal and 0 is paraplegia) at 4 h, 8 h, 12 h, 24 h, and 48 h after reperfusion. All animals were sacrificed at 48 h after reperfusion and the spinal cords (L(5)) were removed immediately for histopathologic study. RESULTS: All animals in the control group became paraplegic. Neurologic status and histopathology (48 h) in the Groups P, T(2) and T(3) were significantly better than those in the control group (P < 0.05). There was a strong correlation between the final neurologic scores and the number of normal neurons in the anterior spinal cord (r = 0.776, P < 0.01). CONCLUSION: Tetramethylpyrazine significantly reduces neurologic injury related to spinal cord ischemia and reperfusion after aortic occlusion within a certain range of dose

Modulation of colony stimulating factor release and apoptosis in human colon cancer cells by anticancer drugs

Modulation of the immune response against tumour cells is emerging as a valuable approach for cancer treatment. Some experimental studies have shown that secretion of colony stimulating factors by cancer cells reduces their tumorigenicity and increases their immunogenicity probably by promoting the cytolitic and antigen presenting activities of leukocytes. We have observed that human colon cancer cells (HT-29) are able to secrete granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor when stimulated with cytokines (IL-1β and TNF-α). In this study we assessed, for the first time, the effects of several anticancer drugs on colony stimulating factor release or apoptosis in HT-29 cells. Cytokine-induced release of granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor was significantly increased by cisplatin and 6-mercaptopurine. Taxol only increased macrophage-colony stimulating factor release while reduced that of granulocyte-colony stimulating factor. No changes in colony stimulating factor secretion were observed after treatment with methotrexate. Only cisplatin and taxol induced apoptosis in these cells. Secretion of colony stimulating factors by colon cancer cells may contribute to the immune host response against them. Anticancer drugs such as cisplatin and 6-mercaptopurine increase colony stimulating factor secretion by cytokine stimulated cancer cells probably through mechanisms different to those leading to cell apoptosis, an effect that may contribute to their anti-neoplasic action

The environmental impact of fertilizer embodied in a wheat-to-bread supply chain

Food production and consumption cause approximately one-third of total greenhouse gas emissions, and therefore delivering food security challenges not only the capacity of our agricultural system, but also its environmental sustainability. Knowing where and at what level environmental impacts occur within particular food supply chains is necessary if farmers, agri-food industries and consumers are to share responsibility to mitigate these impacts. Here we present an analysis of a complete supply chain for a staple of the global diet, a loaf of bread. We obtained primary data for all the processes involved in the farming, production and transport systems that lead to the manufacture of a particular brand of 800 g loaf. The data were analysed using an advanced life cycle assessment (LCA) tool, yielding metrics of environmental impact, including greenhouse gas emissions. We show that more than half of the environmental impact of producing the loaf of bread arises directly from wheat cultivation, with the use of ammonium nitrate fertilizer alone accounting for around 40%. These findings reveal the dependency of bread production on the unsustainable use of fertilizer and illustrate the detail needed if the actors in the supply chain are to assume shared responsibility for achieving sustainable food production

Soundscape assessment: Towards a validated translation of perceptual attributes in different languages

The recently published ISO/TS 12913-2:2018 standard aims to provide researchers and practitioners around the world with a reliable questionnaire for soundscape characterization. The ISO Technical Specifications report protocols and attributes grounded in the soundscape literature, but only includes an English version. The applicability and reliability of these attributes in non-English speaking regions remains an open question, as research investigating translations of soundscape attributes is limited. To address this gap, an international collaboration was initiated with soundscape researchers from all over the world. Translation into 15 different languages, obtained through focus groups and panels of experts in soundscape studies, are proposed. The main challenges and outcomes of this preliminary exercise are discussed. The long-term objective is to validate the proposed translations using standardized listening experiments in different languages and geographical regions as a way to promote a widespread use of the soundscape attributes, both in academia and practice, across locations, populations and languages

Search for the Θ+\Theta^+ pentaquark in the reaction γd→pK−K+n\gamma d \to p K^- K^+ n

A search for the \thp in the reaction $\gamma d \to pK^-K^+n$ was completed using the CLAS detector at Jefferson Lab. A study of the same reaction, published earlier, reported the observation of a narrow \thp resonance. The present experiment, with more than 30 times the integrated luminosity of our earlier measurement, does not show any evidence for a narrow pentaquark resonance. The angle-integrated upper limit on \thp production in the mass range of 1.52 to 1.56 GeV/c$^2$ for the $\gamma d \to pK^-\Theta^+$ reaction is 0.3 nb (95% CL). This upper limit depends on assumptions made for the mass and angular distribution of \thp production. Using \lamstar production as an empirical measure of rescattering in the deuteron, the cross section upper limit for the elementary $\gamma n \to K^-\Theta^+$ reaction is estimated to be a factor of 10 higher, {\it i.e.}, $\sim 3$ nb (95% CL).Comment: 5 figures, submitted to PRL, revised for referee comment

Real-time algorithm for changes detection in depth of anesthesia signals

This paper presents a real-time algorithm for changes detection in depth of anesthesia signals. A Page-Hinkley test (PHT) with a forgetting mechanism (PHT-FM) was developed. The samples are weighted according to their "age" so that more importance is given to recent samples. This enables the detection of the changes with less time delay than if no forgetting factor was used. The performance of the PHT-FM was evaluated in a two-fold approach. First, the algorithm was run offline in depth of anesthesia (DoA) signals previously collected during general anesthesia, allowing the adjustment of the forgetting mechanism. Second, the PHT-FM was embedded in a real-time software and its performance was validated online in the surgery room. This was performed by asking the clinician to classify in real-time the changes as true positives, false positives or false negatives. The results show that 69 % of the changes were classified as true positives, 26 % as false positives, and 5 % as false negatives. The true positives were also synchronized with changes in the hypnotic or analgesic rates made by the clinician. The contribution of this work has a high impact in the clinical practice since the PHT-FM alerts the clinician for changes in the anesthetic state of the patient, allowing a more prompt action. The results encourage the inclusion of the proposed PHT-FM in a real-time decision support system for routine use in the clinical practice. © 2012 Springer-Verlag

The Cognitive Role of the Globus Pallidus interna; Insights from Disease States.

The motor symptoms of both Parkinson's disease and focal dystonia arise from dysfunction of the basal ganglia, and are improved by pallidotomy or deep brain stimulation of the Globus Pallidus interna (GPi). However, Parkinson's disease is associated with a greater degree of basal ganglia-dependent learning impairment than dystonia. We attempt to understand this observation in terms of a comparison of the electrophysiology of the output of the basal ganglia between the two conditions. We use the natural experiment offered by Deep Brain Stimulation to compare GPi local field potential responses in subjects with Parkinson's disease compared to subjects with dystonia performing a forced-choice decision-making task with sensory feedback. In dystonic subjects, we found that auditory feedback was associated with the presence of high gamma oscillations nestled on a negative deflection, morphologically similar to sharp wave ripple complexes described in human rhinal cortex. These were not present in Parkinson's disease subjects. The temporal properties of the high gamma burst were modified by incorrect trial performance compared to correct trial performance. Both groups exhibited a robust low frequency response to 'incorrect' trial performance in dominant GPi but not non-dominant GPi at theta frequency. Our results suggest that cellular processes associated with striatum-dependent memory function may be selectively impaired in Parkinson's disease even if dopaminergic drugs are administered, but that error detection mechanisms are preserved