On the flexibility of the design of Multiple Try Metropolis schemes

The Multiple Try Metropolis (MTM) method is a generalization of the classical Metropolis-Hastings algorithm in which the next state of the chain is chosen among a set of samples, according to normalized weights. In the literature, several extensions have been proposed. In this work, we show and remark upon the flexibility of the design of MTM-type methods, fulfilling the detailed balance condition. We discuss several possibilities and show different numerical results

Equine infectious keratitis in Finland : Associated microbial isolates and susceptibility profiles

Objective To retrospectively describe laboratory findings, treatment, and outcome associated with equine infectious keratitis in Finland. Animals and procedures Medical records of horses diagnosed with infectious keratitis in University of Helsinki Equine Hospital from January 2007 to June 2018 were reviewed. Results Forty-seven cases were included. Keratomycosis was diagnosed in 27 eyes and bacterial keratitis in 20 eyes. Aspergillus flavus was the most frequent fungal isolate (9/17, 53%), followed by Cylindrocarpon sp. (3/17, 18%) and Aspergillus fumigatus (2/17, 12%). Susceptibility was tested for 10/11 Aspergillus sp. isolates; all were susceptible to voriconazole while only two were susceptible to amphotericin B. Cylindrocarpon sp. isolates were resistant to both agents. Streptococcus equi subsp. zooepidemicus was the most frequent bacterial isolate (9/19, 47%), followed by other streptococci (4/19, 21%). All 13 Streptococcus sp. isolates were susceptible to penicillin, and all tested isolates (n = 11) were also susceptible to chloramphenicol. Mean duration of medical treatment was longer in fungal keratitis (38 days) than in bacterial keratitis (25 days) (P <.001). Twenty-six of the eyes underwent globe-sparing surgery in addition to medical therapy. Recovery was achieved in 66% (31/47) of all cases and in 59% (16/27) and 75% (15/20) (P = .264) of cases with keratomycosis and bacterial keratitis, respectively. Conclusions Although Aspergillus sp. and S zooepidemicus were the most frequently encountered isolates, cytology, culture, and susceptibility testing are essential to differentiate bacterial and fungal keratitis and guide the clinician to choose the most efficient treatment.Peer reviewe

Four patients with a history of acute exacerbations of COPD: implementing the CHEST/Canadian Thoracic Society guidelines for preventing exacerbations

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0

The PINE study: rationale and design of a randomised comparison of epidural injection of local anaesthetics and steroids versus care-as-usual to prevent postherpetic neuralgia in the elderly [ISRCTN32866390]

BACKGROUND: Postherpetic neuralgia (PHN) is by far the most common complication of herpes zoster (HZ) and one of the most intractable pain disorders. Since PHN is seen most often in the elderly, the number of patients with this disorder is expected to increase in our ageing society. PHN may last for months to years and has a high impact on the quality of life. The results of PHN treatment are rather disappointing. Epidural injection of local anaesthetics and steroids in the acute phase of HZ is a promising therapy for the prevention of PHN. Since randomised trials on the effectiveness of this intervention are lacking, the PINE (Prevention by epidural Injection of postherpetic Neuralgia in the Elderly) study was set up. The PINE study compares the effectiveness and cost-effectiveness of a single epidural injection of local anaesthetics and steroids during the acute phase of HZ with that of care-as-usual (i.e. antivirals and analgesics) in preventing PHN in elderly patients. METHODS / DESIGN: The PINE study is an open, multicenter clinical trial in which 550 elderly (age ≥ 50 yr.) patients who consult their general practitioner in the acute phase of HZ (rash < 7 days) are randomised to one of the treatment groups. The primary clinical endpoint is the presence of HZ-related pain one month after the onset of the rash. Secondary endpoints include duration and severity of pain, re-interventions aiming to treat the existing pain, side effects, quality of life, and cost-effectiveness. CONCLUSION: The PINE study is aimed to quantify the (cost-) effectiveness of a single epidural injection during the acute phase of HZ on the prevention of PHN

A multilevel analysis of neighborhood and individual effects on individual smoking and drinking in Taiwan

<p>Abstract</p> <p>Background</p> <p>We assessed direct effects of neighborhood-level characteristics and interactive effects of neighborhood-level characteristics and individual socioeconomic position on adult smoking and drinking, after consideration of individual-level characteristics in Taiwan.</p> <p>Methods</p> <p>Data on individual sociodemographic characteristics, smoking, and drinking were obtained from Taiwan Social Change Survey conducted in 1990, 1995, and 2000. The overall response rate was 67%. A total of 5883 women and men aged over 20 living in 434 neighborhoods were interviewed. Participants' addresses were geocoded and linked with Taiwan census data for measuring neighborhood-level characteristics including neighborhood education, neighborhood concentration of elderly people, and neighborhood social disorganization. The data were analyzed with multilevel binomial regression models.</p> <p>Results</p> <p>Several interaction effects between neighborhood characteristics and individual socioeconomic status (SES) were found in multilevel analyses. Our results indicated that different neighborhood characteristics led to different interaction patterns. For example, neighborhood education had a positive effect on smoking for low SES women, in contrast to a negative effect on smoking for high SES women. This result supports the hypothesis of "relative deprivation," suggesting that poor people living in affluent neighborhoods suffer from relative deprivation and relative standing. On the other hand, neighborhood social disorganization has positive effects on drinking for low SES individuals, but not for high SES individuals. These interactive effects support the hypothesis of the double jeopardy theory, suggesting that living in neighborhoods with high social disorganization will intensify the effects of individual low SES.</p> <p>Conclusion</p> <p>The findings of this study show new evidence for the effects of neighborhood characteristics on individual smoking and drinking in Taiwan, suggesting that more studies are needed to understand neighborhood effects in Asian societies.</p

Study of Peri-Articular Anaesthetic for Replacement of the Knee (SPAARK): study protocol for a patient-blinded, randomised controlled superiority trial of liposomal bupivacaine

Background: Optimising the management of peri-operative pain and recovery following knee replacement has been identified as a patient priority. Current pain relief strategies use opiate-based analgesia; however, up to 50% of patients experience significant side effects. Local anaesthetic incisional infiltration is one alternative. The length of the duration of action is a major limiting factor of current local anaesthetic techniques. Liposomal bupivacaine has been reported to be effective for up to 72 h. This randomised controlled trial will evaluate the clinical and cost effectiveness of liposomal bupivacaine. Methods: SPAARK is a patient-blinded, multi-centre, active comparator, superiority, two-arm, parallel-group randomised controlled trial. Five hundred patients undergoing knee replacement will be recruited and randomised to liposomal bupivacaine plus bupivacaine hydrochloride or bupivacaine hydrochloride alone. The co-primary outcomes are the Quality of Recovery 40 measured at 72 h post-surgery and also cumulative pain measured daily using a 0–10 visual analogue scale for the first 3 days following surgery. Secondary outcomes include cumulative opioid consumption, fitness for discharge, functional outcomes assessed using the Oxford Knee Score and American Knee Society Score, the EuroQol five dimensions instrument and complications. A cost utility analysis is also planned. Discussion: The clinical effectiveness and cost effectiveness of liposomal bupivacaine have yet to be evaluated in the National Health Service, making this trial appropriate and timely. Trial registration: ISRCTN registry, ISRCTN54191675. Registered on 14 November 2017

Analysis of CHK2 in vulval neoplasia

Structure and expression of the Rad53 homologue CHK2 were studied in vulval neoplasia. We identified the previously described silent polymorphism at codon 84 (A>G at nucleotide 252) in the germ-line of six out of 72, and somatic mutations in two out of 40 cases of vulval squamous cell carcinomas and none of 32 cases of vulval intraepithelial neoplasia. One mutation introduced a premature stop codon in the kinase domain of CHK2, whereas the second resulted in an amino acid substitution in the kinase domain. The two squamous cell carcinomas with mutations in CHK2 also expressed mutant p53. A CpG island was identified close to the putative CHK2 transcriptional start site, but methylation-specific PCR did not detect methylation in any of 40 vulval squamous cell carcinomas, irrespective of human papillomavirus or p53 status. Consistent with this observation, no cancer exhibited loss of CHK2 expression at mRNA or protein level. Taken together, these observations reveal that genetic but not epigenetic changes in CHK2 occur in a small proportion of vulval squamous cell carcinomas

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Risk Factors for Chronic Cerebrospinal Venous Insufficiency (CCSVI) in a Large Cohort of Volunteers

BACKGROUND: The role of intra- and extra-cranial venous system impairment in the pathogenesis of various vascular, inflammatory and neurodegenerative neurological disorders, as well as in aging, has not been studied in detail. Nor have risk factors been determined for increased susceptibility of venous pathology in the intra-cranial and extra-cranial veins. The aim of this study was to investigate the association between presence of a newly proposed vascular condition called chronic cerebrospinal venous insufficiency (CCSVI) and environmental factors in a large volunteer control group without known central nervous system pathology. METHODS AND FINDINGS: The data were collected in a prospective study from 252 subjects who were screened for medical history as part of the entry criteria and participated in the case-control study of CCSVI prevalence in multiple sclerosis (MS) patients, and then were analyzed post-hoc. All participants underwent physical and Doppler sonography examinations, and were assessed with a structured environmental questionnaire. Fullfilment of ≥ 2 positive venous hemodynamic (VH) criteria on Doppler sonography was considered indicative of CCSVI diagnosis. Risk and protective factors associated with CCSVI were analyzed using logistic regression analysis. Seventy (27.8%) subjects presented with CCSVI diagnosis and 153 (60.7%) presented with one or more VH criteria. The presence of heart disease (p = .001), especially heart murmurs (p = .007), a history of infectious mononucleosis (p = .002), and irritable bowel syndrome (p = .005) were associated with more frequent CCSVI diagnosis. Current or previous smoking (p = .029) showed a trend for association with more frequent CCSVI diagnosis, while use of dietary supplements (p = .018) showed a trend for association with less frequent CCSVI diagnosis. CONCLUSIONS: Risk factors for CCSVI differ from established risk factors for peripheral venous diseases. Vascular, infectious and inflammatory factors were associated with higher CCSVI frequency

Why Do Dolphins Carry Sponges?

Tool use is rare in wild animals, but of widespread interest because of its relationship to animal cognition, social learning and culture. Despite such attention, quantifying the costs and benefits of tool use has been difficult, largely because if tool use occurs, all population members typically exhibit the behavior. In Shark Bay, Australia, only a subset of the bottlenose dolphin population uses marine sponges as tools, providing an opportunity to assess both proximate and ultimate costs and benefits and document patterns of transmission. We compared sponge-carrying (sponger) females to non-sponge-carrying (non-sponger) females and show that spongers were more solitary, spent more time in deep water channel habitats, dived for longer durations, and devoted more time to foraging than non-spongers; and, even with these potential proximate costs, calving success of sponger females was not significantly different from non-spongers. We also show a clear female-bias in the ontogeny of sponging. With a solitary lifestyle, specialization, and high foraging demands, spongers used tools more than any non-human animal. We suggest that the ecological, social, and developmental mechanisms involved likely (1) help explain the high intrapopulation variation in female behaviour, (2) indicate tradeoffs (e.g., time allocation) between ecological and social factors and, (3) constrain the spread of this innovation to primarily vertical transmission