A quantification of the relationship between neuronal responses in the rat rostral ventromedial medulla and noxious stimulation-evoked withdrawal reflexes

The rostral ventromedial medulla (RVM) regulates a range of involuntary behaviours but is most often associated with nociception via the action of pronociceptive ON cells and antinociceptive OFF cells. The phasic responses of ON and OFF cells determine whether or not incoming noxious signals provoke a withdrawal reflex, and previous studies have suggested that reflex RVM activity patterns actively shape motor output. Here we challenged the model by using juvenile rats, which are known to exhibit markedly different reflex responses compared with adults. By recording single-cell activity in the RVM and the electromyography responses of hindlimb flexor muscles to noxious thermal stimulation we found that the juvenile reflex had a shorter onset latency, was larger in amplitude and exhibited a decreased rise time compared with the adult reflex. The responses of ON and OFF cells faithfully tracked the shorter onset latency of the reflex by also responding earlier and, thus, still preceded the reflex. However, neither the reflex amplitude nor the ongoing response profile was predicted by the firing rate of RVM cells in either age group. Instead we found a close correspondence between RVM activity and the reflex only during the initiation of the response. Furthermore, the short rise time of the juvenile reflex was reflected in higher rates of change of both ON and OFF cell firing. Our data suggest that the RVM is associated only with the initiation of reflexes and does not shape ongoing muscle activity, which is more likely to be subserved by downstream spinal processes

20,000 years of societal vulnerability and adaptation to climate change in southwest Asia.

The Fertile Crescent, its hilly flanks and surrounding drylands has been a critical region for studying how climate has influenced societal change, and this review focuses on the region over the last 20,000 years. The complex social, economic, and environmental landscapes in the region today are not new phenomena and understanding their interactions requires a nuanced, multidisciplinary understanding of the past. This review builds on a history of collaboration between the social and natural palaeoscience disciplines. We provide a multidisciplinary, multiscalar perspective on the relevance of past climate, environmental, and archaeological research in assessing present day vulnerabilities and risks for the populations of southwest Asia. We discuss the complexity of palaeoclimatic data interpretation, particularly in relation to hydrology, and provide an overview of key time periods of palaeoclimatic interest. We discuss the critical role that vegetation plays in the human-climate-environment nexus and discuss the implications of the available palaeoclimate and archaeological data, and their interpretation, for palaeonarratives of the region, both climatically and socially. We also provide an overview of how modelling can improve our understanding of past climate impacts and associated change in risk to societies. We conclude by looking to future work, and identify themes of "scale" and "seasonality" as still requiring further focus. We suggest that by appreciating a given locale's place in the regional hydroscape, be it an archaeological site or palaeoenvironmental archive, more robust links to climate can be made where appropriate and interpretations drawn will demand the resolution of factors acting across multiple scales. This article is categorized under:Human Water > Water as Imagined and RepresentedScience of Water > Water and Environmental ChangeWater and Life > Nature of Freshwater Ecosystems

Strong constraints on aerosol-cloud interactions from volcanic eruptions.

Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify aerosol-cloud interactions. Here we show that the massive 2014-2015 fissure eruption in Holuhraun, Iceland, reduced the size of liquid cloud droplets-consistent with expectations-but had no discernible effect on other cloud properties. The reduction in droplet size led to cloud brightening and global-mean radiative forcing of around -0.2 watts per square metre for September to October 2014. Changes in cloud amount or cloud liquid water path, however, were undetectable, indicating that these indirect effects, and cloud systems in general, are well buffered against aerosol changes. This result will reduce uncertainties in future climate projections, because we are now able to reject results from climate models with an excessive liquid-water-path response

Canine models of copper toxicosis for understanding mammalian copper metabolism

Hereditary forms of copper toxicosis exist in man and dogs. In man, Wilson’s disease is the best studied disorder of copper overload, resulting from mutations in the gene coding for the copper transporter ATP7B. Forms of copper toxicosis for which no causal gene is known yet are recognized as well, often in young children. Although advances have been made in unraveling the genetic background of disorders of copper metabolism in man, many questions regarding disease mechanisms and copper homeostasis remain unanswered. Genetic studies in the Bedlington terrier, a dog breed affected with copper toxicosis, identified COMMD1, a gene that was previously unknown to be involved in copper metabolism. Besides the Bedlington terrier, a number of other dog breeds suffer from hereditary copper toxicosis and show similar phenotypes to humans with copper storage disorders. Unlike the heterogeneity of most human populations, the genetic structure within a purebred dog population is homogeneous, which is advantageous for unraveling the molecular genetics of complex diseases. This article reviews the work that has been done on the Bedlington terrier, summarizes what was learned from studies into COMMD1 function, describes hereditary copper toxicosis phenotypes in other dog breeds, and discusses the opportunities for genome-wide association studies on copper toxicosis in the dog to contribute to the understanding of mammalian copper metabolism and copper metabolism disorders in man

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements