A k-out-of-n reliability system with an unreliable server and phase type repairs and services: the (N, T) policy

In this paper we study a k-out-of-n reliability system in which a single unreliable server maintains n identical components. The reliability system is studied under the (N,T) policy. An idle server takes a vacation for a random amount of time T and then attends to any failed component waiting in line upon completion of the vacation. The vacationing server is recalled instantaneously upon the failure of the Nth component. The failure times of the components are assumed to follow an exponential distribution. The server is subject to failure with failure times exponentially distributed. Repair times of the component, fixing times of the server, and vacationing times of the server are assumed to be of phase type. Using matrix-analytic methods we perform steady state analysis of this model. Time spent by a failed component in service, total time in the repair facility, vacation time of the server, non-vacation time of the server, and time until failure of the system are all shown to be of phase type. Several performance measures are evaluated. Illustrative numerical examples are presented

Impaired Phagocytosis in Localized Aggressive Periodontitis: Rescue by Resolvin E1

Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 µM) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A4. Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1–100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression

Architecture and roles of periplasmic adaptor proteins in tripartite efflux assemblies.

Recent years have seen major advances in the structural understanding of the different components of tripartite efflux assemblies, which encompass the multidrug efflux (MDR) pumps and type I secretion systems. The majority of these investigations have focused on the role played by the inner membrane transporters and the outer membrane factor (OMF), leaving the third component of the system - the Periplasmic Adaptor Proteins (PAPs) - relatively understudied. Here we review the current state of knowledge of these versatile proteins which, far from being passive linkers between the OMF and the transporter, emerge as active architects of tripartite assemblies, and play diverse roles in the transport process. Recognition between the PAPs and OMFs is essential for pump assembly and function, and targeting this interaction may provide a novel avenue for combating multidrug resistance. With the recent advances elucidating the drug efflux and energetics of the tripartite assemblies, the understanding of the interaction between the OMFs and PAPs is the last piece remaining in the complete structure of the tripartite pump assembly puzzle

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Epidemiology and assessment of psychiatric disorders in epilepsy

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Infinite Server Queueing-Inventory Models

In this paper, we study an MAP/M/∞ role= presentation style= box-sizing: inherit; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; \u3eMAP/M/∞MAP/M/∞ queue associated with an inventory system. The inventory is replenished according to an (s, S)-policy. The (self) service and lead times are assumed to be exponentially distributed. No arriving customer is allowed to enter into the system (of infinite capacity) when there is no inventory available for servicing the customer. Thus, every customer in service is attached with an inventory at the time of entering into the system. We employ an algorithmic approach for the computation of various quantities of interest and derive some explicit expressions in some cases. An illustrative example and an optimization problem are presented

On a customer induced interruption in a service system

Server induced interruptions such as server break downs, server attending a high priority customer, and server taking a vacation in queues have been extensively studied in the literature. However, customer-induced interruptions such as customers leaving in the middle of a service due to not having enough information for completing a service and customer breakdowns have not been studied so far. The purpose of this work is to introduce customer interruptions in queueing systems. We consider an infinite capacity queueing system with a single server to which customers arrive according to a Poisson process and the service time follows an exponential distribution. The customer interruption while in service occurs according to a Poisson process and the interruption duration follows an exponential distribution. The self-interrupted customers will enter into a finite buffer of size K. Any interrupted customer, finding the buffer full, is considered lost. Those interrupted customers who complete their interruptions will be placed into another buffer of same size. The interrupted customers waiting for service are given non-preemptive priority over new customers. We investigate the behavior of this queuing system. Several performance measures are evaluated. Numerical illustrations of the system behavior are also provided. An optimization problem of interest will be discussed through an illustrative example

Peri-Ictal and Ictal Cognitive Dysfunction in Epilepsy

Disturbances in cognitive function, particularly memory, are a common complaint of patients with epilepsy. Factors contributing to cognitive dysfunction are the type of epilepsy, type and frequency of seizures, anti-epileptic drugs and the location of underlying brain lesions. Whilst a great deal of attention has been paid to permanent cognitive impairment, the nature and underlying mechanisms of ictal and peri-ictal cognitive changes are poorly understood. In-depth investigation of seizure related cognitive dysfunction is of great clinical relevance, as these changes are potentially reversible and treatable, thus reducing the cumulative effect of frequent seizures Greater knowledge of peri-ictal and ictal cognitive dysfunction would improve seizure prediction, localization of seizure focus and assessment of treatment effectiveness, greatly reducing distress and disability. This paper will review current understanding of peri-ictal and ictal cognitive dysfunction and discuss future directions for research

MAP/PH/1 queue with working vacations, vacation interruptions and N Policy

In this paper we study a MAP/PH/1 queueing model in which the server is subject to taking vacations and offering services at a lower rate during those times. The service is returned to normal rate whenever the vacation gets over or when the queue length hits a specific threshold value. This model is analyzed in steady state using matrix analytic methods. An illustrative numerical example is discussed