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INTRODUCTION: Monoaminergic activity modulates nociceptive transmission in the central nervous system (CNS). Although pain is the most disabling symptom of osteoarthritis (OA), limited knowledge exists regarding the CNS mechanisms that amplify pain and drive sensitization processes in humans. OBJECTIVES: The main objective of this study was to evaluate associations between cerebrospinal fluid (CSF) monoamine metabolites, pain severity, and central sensitization in patients with OA undergoing total hip arthroplasty (THA). METHODS: Patients with OA (n = 52) and pain-free controls (n = 30) provided CSF samples for measurement of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), noradrenaline (3-methoxy-4-hydroxyphenylglycol [HMPG]), and dopamine (homovanillic acid [HVA]) monoamine metabolites. Patients with OA completed longitudinal evaluation of pain using clinical measures and quantitative sensory testing. RESULTS: Patients with OA had higher HMPG levels when compared with controls (P = 0.036). Within patients with OA undergoing THA, higher 5-HIAA and HVA levels were consistently associated with higher preoperative pain severity. Higher concentrations of 5-HIAA and HVA were also associated with lower conditioned pain modulation levels, whereas higher HMPG levels were linked to more efficient conditioned pain modulation. Patients with higher levels of CSF HVA exhibited increased pressure pain sensitivity (arm pressure pain detection threshold < 250 kPa vs >/= 250 kPa, P = 0.042). Higher preoperative levels of CSF 5-HIAA predicted poorer pain control 6 months postoperatively (brief pain inventory pain severity; adjusted beta = 0.010, 95% CI 0.001-0.019). CONCLUSIONS: In OA patients with disabling pain, higher CSF levels of serotonin and dopamine metabolites are associated with increased pain severity and central sensitization. Increased noradrenergic activity may be associated with more efficient pain inhibitory capacity., Bjurstrom, Martin F Blennow, Kaj Zetterberg, Henrik Bodelsson, Mikael Walden, Markus Dietz, Nicholas Hall, Sara Hansson, Oskar Irwin, Michael R Mattsson-Carlgren, Niklas eng 2022/02/01 Pain Rep. 2022 Jan 24;7(1):e988. doi: 10.1097/PR9.0000000000000988. eCollection 2022 Jan-Feb.

Many turtle species have temperature-dependent sex determination (TSD), raising the prospect that climate change could impact population dynamics by altering sex ratios. Understanding how climate change will affect populations of animals with TSD requires a reliable and minimally invasive method of identifying the sexes of young individuals. This determination is challenging in many turtles, which often lack conspicuous external sexual dimorphism until years after hatching. Here, we explore four alternatives for sexing three age classes of captive-reared young gopher tortoises (Gopherus polyphemus), a terrestrial turtle of conservation concern native to the southeastern United States: (1) naive testosterone levels, (2) testosterone levels following a follicle stimulating hormone (FSH) challenge, (3) linear morphological measurements, and (4) geometric morphometrics. Unlike some other turtle species, male and female neonatal gopher tortoises have overlapping naive testosterone concentration distributions, justifying more complicated methods. We found that sex of neonates (<7 days old) is best predicted by a "random forest" machine learning model with naive testosterone levels and morphological measurements (8% out-of-bag error). Sex of hatchlings (4-8 months old) was predicted with 11% error using a simple threshold on naive testosterone levels, or with 4% error using a simple threshold on post-FSH testosterone levels. Sex of juveniles (approximately 3.5 years old) was perfectly predicted using a simple threshold on naive testosterone levels. Sexing hatchlings at >4 months of age is the easiest and most reliable non-surgical method for sex identification. Given access to a rearing facility and equipment to perform hormone assays, these methods have the potential to supplant laparoscopic surgery as the method of choice for sexing young gopher tortoises.

Neuroinflammation is implicated in the development and maintenance of persistent pain states, but there are limited data linking cerebrospinal fluid (CSF) inflammatory mediators with neurophysiological pain processes in humans. In a prospective observational study, CSF inflammatory mediators were compared between patients with osteoarthritis (OA) who were undergoing total hip arthroplasty due to disabling pain symptoms (n = 52) and pain-free comparison controls (n = 30). In OA patients only, detailed clinical examination and quantitative sensory testing were completed. Cerebrospinal fluid samples were analyzed for 10 proinflammatory mediators using Meso Scale Discovery platform. Compared to controls, OA patients had higher CSF levels of interleukin 8 (IL-8) (P = 0.002), intercellular adhesion molecule 1 (P = 0.007), and vascular cell adhesion molecule 1 (P = 0.006). Osteoarthritis patients with central sensitization possibly indicated by arm pressure pain detection threshold <250 kPa showed significantly higher CSF levels of Fms-related tyrosine kinase 1 (Flt-1) (P = 0.044) and interferon gamma-induced protein 10 (IP-10) (P = 0.024), as compared to subjects with PPDT above that threshold. In patients reporting pain numerical rating scale score >/=3/10 during peripheral venous cannulation, Flt-1 was elevated (P = 0.025), and in patients with punctate stimulus wind-up ratio >/=2, CSF monocyte chemoattractant protein 1 was higher (P = 0.011). Multiple logistic regression models showed that increased Flt-1 was associated with central sensitization, assessed by remote-site PPDT and peripheral venous cannulation pain, and monocyte chemoattractant protein-1 with temporal summation in the area of maximum pain. Multiple proinflammatory mediators measured in CSF are associated with persistent hip OA-related pain. Pain phenotype may be influenced by specific CSF neuroinflammatory profiles., Bjurstrom, Martin Flores Bodelsson, Mikael Montgomery, Agneta Harsten, Andreas Walden, Markus Janelidze, Shorena Hall, Sara Hansson, Oskar Irwin, Michael R Mattsson-Carlgren, Niklas eng Observational Study Research Support, Non-U.S. Gov't 2020/05/10 Pain. 2020 Sep 1;161(9):2142-2154. doi: 10.1097/j.pain.0000000000001903.

Facing the media after a reported 5.6 per cent swing against him in the Brisbane seat of Dickson, Australian Minister for Immigration and Border Protection Peter Dutton defiantly declared that the Coalition was ‘a victim of our own success’.1 ‘The fact that we stopped boats and got children out of detention’, Dutton asserted, meant the ‘issue’ of ‘border protection’ and people arriving in Australia unauthorised by boat to seek asylum ‘had gone off the radar’ (quoted in Hutchens 2016). The minister’s assertion was certainly provocative, if a little misleading. While Australia’s policies towards refugees and asylum seekers did not appear to feature prominently in the 2016 election campaign, this was largely due to a confluence of circumstances, not all of which were of the Coalition’s making. These circumstances primarily included the bipartisan support for the three key pillars of Australia’s increasingly draconian deterrence model (namely, boat turn backs, regional processing and the mandatory detention of certain asylum seekers) and the exceptional government censorship of information from inside immigration detention centres and the official secrecy surrounding the implementation of Australia’s military-led Operation Sovereign Borders (OSB). This meant that the Coalition and Labor had both orchestrated a situation where there seemed to be little political mileage to be gained from foregrounding the issue of Australia’s refugee laws and policies during the campaign. Instead, the election contest predominantly played out across more traditional issues of economic and social policy, such as job creation and the funding of healthcare. Despite being a highly volatile political issue, refugee policy could rarely be seen to determine the outcome of elections—perhaps with the exception of the Coalition’s major 2001 electoral victory in the wake of the Tampa affair. Since 2004, fewer than 10 per cent of surveyed voters have ranked the issue of ‘refugees and asylum seekers’

AIM: To prospectively validate 3 T magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) for preoperative lymph node (LN) staging in a clinical setting, in intermediate- and high-risk prostate cancer (PCa) patients using laparoscopic extended LN dissection (ePLND) as the reference standard. MATERIALS AND METHODS: Between August 2011 and May 2013, 40 newly diagnosed intermediate and high-risk PCa patients underwent preoperative LN staging with 3 T MRI DWI using histopathology of ePLND as the reference standard. The sensitivity, specificity, and accuracy of MRI DWI were calculated. A subgroup analysis of proven LN-positive patients was made to investigate differences in PSA, Gleason score, number, and size of LN metastases, estimated risk of LN involvement, and if curative treatment was indicated, between the true-positive and the false-negative groups. RESULTS: A total of 728 LN were harvested from six anatomical regions per patient (external, obturator, internal) with a mean number of 18 LNs per patient (range 11-40). Twenty patients had histologically proven LN-positive disease. MRI DWI was true positive in 11 patients, false negative in nine patients, false positive in two patients, and true negative in 18 patients, resulting in 90% specificity, 55% sensitivity, and 72.5% accuracy. The true-positive patients had significantly more involved LNs (mean 6.9 versus 2.7, p = 0.017), with larger diameter (mean 12.3 versus 5.2 mm, p = 0.048) and fewer were treated with curative intent (six versus nine, p = 0.03), compared with the false-negative group. CONCLUSION: MRI DWI LN staging has a low sensitivity but high specificity. The true-positive patients have a considerably higher burden of LN metastases compared to false-negative patients.

The size and complexity of Simulink models is constantly increasing, just as the systems which they represent. Therefore, it is beneficial to control them already at the design phase. In this paper we establish a set of complexity metrics for Simulink models to capture diverse aspects of complexity by proposing new and redefining existing metrics. To evaluate the applicability of our metrics, we compare them with the closed-source metric proposed by Mathworks. Moreover, through a case study from the automotive domain, we relate such metrics to quality attributes as determined by domain experts, and correlate them to known faults. Preliminary assessment suggests that complexity is closely related to analysability, understandability, and testability.