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We consider a parallel server queueing system consisting of a bank of buffers for holding incoming jobs and a bank of flexible servers for processing these jobs. Incoming jobs are classified into one of several different classes (or buffers). Jobs within a class are processed on a first-in-first-out basis, where the processing of a given job may be performed by any sever from a given (class dependent) subset of the bank of servers. The random service time of a job may depend on both its class and the server providing the service. Each job departs the system after receiving service from one server. The system manager seeks to minimize holding costs by dynamically scheduling waiting jobs to available servers. We consider a parameter regime in which the system satisfies both a heavy traffic and a complete resource pooling condition. Our cost function is an expected cumulative discounted cost of holding jobs in the system, where the (undiscounted) cost per unit time is a linear function of normalized (with heavy traffic scaling) queue length. In a prior work [42], the second author proposed a continuous review threshold control policy for use in such a parallel server system. This policy was advanced as an "interpretation" of the analytic solution to an associated Brownian control problem (formal heavy traffic diffusion approximation). In this paper we show that the policy proposed in [42] is asymptotically optimal in the heavy traffic limit and that the limiting cost is the same as the optimal cost in the Brownian control problem.

To explore a side of lesion differences in Meniere's disease (MD). A retrospective review (2019–2021) was conducted of patients with definite MD, as defined by 2015 Bárány Society diagnostic criteria. Testing information included pure tone audiometry, tympanometry, and extra-tympanic electrocochleography (ECochG). Normative ECochG data from healthy subjects determined the 95% cut-off value for clinical abnormality. 107 patients with definite MD were included in the study and 40 healthy controls. The review identified 75 patients with unilateral MD and 32 patients with bilateral MD according to their clinical histories. 79% of unilateral cases were found to have MD on the L ear. 94% of bilateral MD cases had L ears more affected than R ears. Objective ECochG testing indicated a greater incidence of elevated SP/AP area curve and amplitude ratios in L ears. On binomial testing, all results indicate a highly significant bias of MD to the L side. Unilateral MD appears more common on the L side than the R, suggesting that the disease process underlying MD is not symmetrical. MD also appears more common in females than males. It appears that there is a physiological asymmetry in the progression/cause of MD. [ABSTRACT FROM AUTHOR]

By use of student-selected consequences and an individual token reinforcement program, a special education student's habitual slouching in his chair was decreased and other positive behavior changes occurred. Procedures were carried out in the usual classroom setting, required only available school personnel and an inexpensive reward. (DS)

General anaesthesia is associated with changes in connectivity between different regions of the brain, the assessment of which has the potential to provide a novel marker of anaesthetic effect. We propose an index that quantifies the strength and direction of information flow in electroencephalographic signals collected across the scalp, assess its performance in discriminating 'wakefulness' from 'anaesthesia', and compare it with estimated bispectral index and the auditory middle latency response. We used a step-wise slow induction of anaesthesia in 10 patients to assess graded changes in electroencephalographic directional connectivity at propofol effect-site concentrations of 2 μg.ml-1 , 3 μg.ml-1 and 4 μg.ml-1 . For each stable effect-site concentration, connectivity was estimated from multichannel electroencephalograms using directed coherence, together with middle latency response and estimated bispectral index. We used a linear support vector machine classifier to compare the performance of the different electroencephalographic features in discriminating wakefulness from anaesthesia. We found a significant reduction in the strength of long-range connectivity (interelectrode distance > 10 cm) (p < 0.008), and a reversal of information flow from markedly postero-frontal to fronto-posterior (p < 0.006) between wakefulness and a propofol effect-site concentration of 2 μg.ml-1 . This then remained relatively constant as effect-site concentration increased, consistent with a step change in directed coherence with anaesthesia. This contrasted with the gradual change with increasing anaesthetic dose observed for estimated bispectral index and middle latency response. Directed coherence performed best in discriminating wakefulness from anaesthesia with an accuracy of 95%, indicating the potential of this new method (on its own or combined with others) for monitoring adequacy of anaesthesia. [ABSTRACT FROM AUTHOR]

The distribution of the squirrel glider (Petaurus norfolcensis) extends for 3,000 kilometres along the eastern coast of Australia. Human-induced habitat loss and fragmentation is a major factor resulting in the decline in distribution of this species. Records indicate the presence of the squirrel glider on a number of the islands off the coast of southeast Queensland, where the threatening processes of fragmented mainland habitat are reduced or absent. The main aims of this study were to determine the presence of the squirrel glider on southeast Queensland islands, and to estimate the density of these populations to determine whether there is any difference in density between island and mainland populations. Trapping surveys were conducted on Fraser Island, Moreton Island, North Stradbroke Island, Peel Island, South Stradbroke Island, Woogoompah Island and Coomera Island. Surveys were also conducted in three mainland patches. Results of the study confirmed that the squirrel glider exists on five of the seven islands. Density estimates for island populations ranged between 3.01 and 8.48 individuals ha-1 with an average (± s.e.) of 4.94 ± 0.55 individuals ha-1. Island population densities were not signifi cantly different from mainland populations, which had an average density (± s.e.) of 4.12 ± 0.53 individuals ha-1. Overall, the study provided up-to-date records for the squirrel glider on islands in southeast Queensland, as well as new information on population densities in this species. Results highlight the importance of retaining large areas of bushland (>700 ha) on the mainland to ensure the long-term persistence of populations of the squirrel glider. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 58-year-old man who is experiencing a difficulty of finishing a round of golf due to an abnormal sensation around his abdomen and weakness of his legs. It says that the patient has showed an evidence of cerebral lymphoma five months after presenting with acute confusion and drowsiness. It adds that five cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) chemotherapy was received by the patient.

The Auditory Brainstem Response (ABR) plays an important role in diagnosing and managing hearing loss, but can be challenging and time-consuming to measure. Test times are especially long when multiple ABR measurements are needed, e.g., when estimating hearing threshold at a range of frequencies. While many detection methods have been developed to reduce ABR test times, the majority were designed to detect the ABR at a single stimulus level and do not consider correlations in ABR waveforms across levels. These correlations hold valuable information, and can be exploited for more efficient hearing threshold estimation. This was achieved in the current work using a Gaussian Process (GP), i.e., a Bayesian approach for non-linear regression. The function to estimate with the GP was the ABR's amplitude across stimulus levels, from which hearing threshold was ultimately inferred. Active learning rules were also designed to automatically adjust the stimulus level and efficiently locate hearing threshold. Simulation results show test time reductions of up to  ∼ 50% for the GP compared to a sequentially applied Hotelling's T 2 test, which does not consider correlations across ABR waveforms. A case study was also included to briefly assess the GP approach in ABR data from an adult volunteer.

Background: Statistical detection methods are routinely used to automate auditory evoked response (AER) detection and assist clinicians with AER measurements. However, many of these methods are built around statistical assumptions that can be violated for AER data, potentially resulting in reduced or unpredictable test performances. This study explores a frequency domain bootstrap (FDB) and some FDB modifications to preserve test performance in serially correlated non-stationary data., Method: The FDB aims to generate many surrogate recordings, all with similar serial correlation as the original recording being analysed. Analysing the surrogates with the detection method then gives a distribution of values that can be used for inference. A potential limitation of the conventional FDB is the assumption of stationary data with a smooth power spectral density (PSD) function, which is addressed through two modifications., Comparisons With Existing Methods: The FDB was compared to a conventional parametric approach and two modified FDB approaches that aim to account for heteroskedasticity and non-smooth PSD functions. Hotelling's T 2 (HT2) test applied to auditory brainstem responses was the test case., Results: When using conventional HT2, false-positive rates deviated significantly from the nominal alpha-levels due to serial correlation. The false-positive rates of the modified FDB were consistently closer to the nominal alpha-levels, especially when data was strongly heteroskedastic or the underlying PSD function was not smooth due to e.g. power lines noise., Conclusion: The FDB and its modifications provide accurate, recording-dependent approximations of null distributions, and an improved control of false-positive rates relative to parametric inference for auditory brainstem response detection., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A growing body of research suggests positive links between coastal proximity, interaction, human health and wellbeing. In 2020, following the onset of the Covid-19 pandemic, many people in the UK could not engage in their usual coastal practices due to a national lockdown and associated restrictions, including government bans in entering the sea. This paper shares findings from an exploratory study examining how these restrictions shaped the recreational coastal practices, perceptions and emotions of residents in the case study region of Devon, South West England. In-depth semi-structured interviews were conducted with a purposive sample of 12 residents, with varying domestic and employment circumstances in the pandemic. We foreground three key themes identified through an inductive thematic analysis of the interviews: feeling 'at home' with the sea, experiencing a fragmented sense of home with Covid-19, and reconfiguring the coast as a therapeutic landscape. While important to understand the links between coastal proximity, health and wellbeing, we highlight the value of gaining more nuanced insights into the emotional, social, material and temporal dynamics that can re-shape the therapeutic potential of coastal encounter in the largely unprecedented situation of a global pandemic., Competing Interests: No conflicts of interest., (© 2021 Elsevier Ltd. All rights reserved.)

Aims: In recent years, the optimum primary management of primary central nervous system lymphoma (PCNSL) has evolved from combined modality chemoradiotherapy to chemotherapy alone. We describe a single-centre case series of PCNSL with a view to assessing the role of radiotherapy in primary disease management., Materials and Methods: West of Scotland PCNSL cases between 2001 and 2010 were identified by neuropathology. Observational data were collected retrospectively from case notes and electronic systems., Results: Forty-nine patients fulfilled the eligibility criteria. The median age was 61 years. Chemotherapy with a view to consolidation radiotherapy on completion was delivered to 61% (n = 30). Regimens varied, but were generally methotrexate-based. Chemotherapy was discontinued prematurely in 80% (n = 24) due to progressive disease (n = 12), intolerable toxicity (n = 7) or death (n = 4). In all patients who progressed or did not tolerate chemotherapy, treatment was changed to immediate salvage radiotherapy; modal irradiation was 40 Gy. Radiotherapy alone was delivered to those not suitable for chemotherapy (18%, n = 9) and best supportive care to those with poor performance status (18%, n = 9). The overall median survival was 8 months. In those receiving single modality radiotherapy or chemotherapy, the median survival was 5 and 8 months, respectively. For those completing chemoradiotherapy in its entirety, 3 year survival was 100%; in groups receiving salvage radiotherapy despite progressive disease or chemotherapy toxicity, moderate survival was maintained with immediate radiotherapy with 3 year survival rates of 33 and 60%, respectively., Conclusions: Although chemotherapy alone remains the optimal treatment of PCNSL, out with clinical trials only a minority of patients complete chemotherapy due to toxicity and disease progression; in such patients, immediate salvage radiotherapy provides an effective and safe alternative with maintenance of good outcomes., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: The auditory evoked potential termed the middle latency response (MLR) has been suggested as an indicator of adequacy of anaesthesia during surgery. However, the response is small and must be extracted from high levels of background noise. A key consideration in using the MLR for clinical monitoring is whether data quality is sufficient to detect small changes. The aim of this study was to investigate the quality of the MLR recorded during anaesthesia, as a rigorous analysis of data quality is lacking in many studies. MLR recordings from patients sedated in intensive care after cardiac surgery were compared to recordings from a reference group of young volunteers with normal hearing. Data quality was measured with the F(sp) parameter. A bootstrap analysis was used to measure statistical response presence and to detect within-subject changes during clinical anaesthesia. Noise levels were high in the normative group probably due to myogenic and EEG activity. With 5 Hz click stimulation, MLR presence in the normative group was below 30%. Response presence improved using stimulation paradigms with chirps or maximum length sequences and reached 100% with a combination of maximum length sequences and chirps. F(sp) values generally improved during anaesthesia as noise levels reduced and MLR presence was 100% for MLS click stimulation. Changes in the MLR amplitude with propofol infusion rate were small. Some within-subject changes in MLR amplitude were detected using the bootstrap analysis, but 100% detection was not possible., Conclusion: Obtaining good quality MLR data in awake subjects is challenging. Data quality improves during clinical anaesthesia and with advanced stimulation methods, but reliable detection of changes in the MLR for clinical monitoring remains a challenge., ((c) 2009 IPEM. Published by Elsevier Ltd. All rights reserved.)

Conclusion: The position of a subject's eyes during vestibular evoked myogenic potential (VEMP) recording significantly alters the magnitude of the response. This change is largely due to an alteration in the tonicity of the sternocleidomastoid muscle (SCM) caused by variations in the position of the eye. However, even if electromyographic (EMG) normalization is conducted effects of eye position remain., Objective: To determine if eye position has a significant effect on the magnitude of the VEMP., Subjects and Methods: VEMPs were collected from 32 ears measured on 16 healthy subjects. The recordings were made unilaterally using the head turn method. The acoustic stimuli were 500 Hz air-conduction short tone bursts. VEMPs were measured in three recording conditions: (i) eyes in the same direction as head turn, (ii) eyes straight ahead, (iii) eyes in the opposite direction to head turn., Results: All 32 ears tested showed a VEMP response with eyes in all three positions. Repeated measures analysis of variance (RM-ANOVA) verified an overall significant effect of eye position (p<0.001). Post hoc paired t tests revealed statistically significant differences between the eyes opposite and the other two conditions (p<0.001). Normalization of the VEMP magnitude using pre-stimulus EMG reduced the effect; however, some variability remained.

The middle latency response of the auditory evoked potential may be useful as an indicator of the hypnotic state during anaesthesia. However, it is difficult to record in some circumstances. This communication provides some suggestions and guidance for those not familiar with the technique.

DNA constructs based on the 534-amino-acid C-terminus of rat mucin protein Muc2 (RMC), were transfected into COS cells and the resultant (35)S-labelled dimers and monomers were detected by SDS/PAGE of immunoprecipitates. The cystine-knot construct, encoding the C-terminal 115 amino acids, appeared in cell lysates as a 45 kDa dimer, but was not secreted. A construct, devoid of the cystine knot, failed to form dimers. Site-specific mutagenesis within the cystine knot was performed on a conserved unpaired cysteine (designated Cys-X), which has been implicated in some cystine-knot-containing growth factors as being important for intermolecular disulphide-bond formation. Dimerization of RMC was effectively abolished. Each cysteine (Cys-1-Cys-6) comprising the three intramolecular disulphide bonds of the cystine knot was then mutated. Dimer formation was impaired in each case, although much less so for the Cys-3 mutant than the others. Abnormal high-molecular-mass, disulphide-dependent aggregates formed with mutations Cys-1, Cys-2, Cys-4 and Cys-5(,) and were poorly secreted. It is concluded that the intact cystine-knot domain is essential for dimerization of the C-terminal domain of rat Muc2, and that residue Cys-X in the knot plays a key role. The structural integrity of the cystine knot, maintained by intramolecular bonds Cys-1-Cys-4, Cys-2-Cys-5 and Cys-3-Cys-6, also appears to be important for dimerization, probably by allowing correct positioning of the unpaired Cys-X residue for stable intermolecular cystine-bond formation.

Earlier immunolocalization experiments showed that the extreme cationic C-terminus of the rat intestinal mucin Muc2 (RMC) was present at the base of intestinal goblet cells in the vicinity of ER and golgi compartments, but was not found with the rest of the mucin in apical storage granules. This prompted us to investigate the possibility that an early proteolytic cleavage reaction occurs post-translationally. A plasmid pRMC, encoding the C-terminal 534 amino acids of the mucin, was expressed in COS-7 cells and was shown to undergo cleavage at an R-T-R-R sequence located within the C-terminal 14 amino acids. Cleavage did not occur with the construct RMCfH, a furin site-mutated (A-T-A-A) counterpart of pRMCH (poly His6 tagged RMC). Addition of a furin inhibitor to COS-7 cell incubations also prevented cleavage of RMC and RMCH products. 35S pulse-chase kinetic experiments revealed that a truncated mutant lacking the C-terminal 14 amino acids (pRMCDeltaCT) forms faulty (doublet) dimers in the ER. These were not secreted as efficiently as the normal dimer of wild-type (pRMC) constructs. Thus the cationic C-terminus of rMuc2 apppears to facilitate the correct formation of normal Muc2 domain dimers.