Subjects are at substantial increased odds of developing CWP if they display features of somatization, health-seeking behaviour and poor sleep. Psychosocial distress has a strong aetiological influence on CWP.

Objective. To test the hypothesis that abnormalities in the hypothalamic-pituitary-adrenal (HPA) stress-response system would act as an effect moderator between HPA function and the onset of chronic widespread pain (CWP).Methods. We conducted a population-based prospective cohort study. Current pain and psychosocial status were ascertained in 11,000 subjects. Of the 768 eligible subjects free of CWP but at future risk based on their psychosocial profile, 463 were randomly selected, and 267 (57.7%) consented to assessment of their HPA axis function. Diurnal function was measured by assessing levels of salivary cortisol in the morning (9:00 AM) and evening (10:00 PM). Serum cortisol levels were measured after an overnight low-dose (0.25 mg) dexamethasone suppression test and a potentially stressful clinical examination. All subjects were followed up 15 months later to identify cases of new-onset CWP.Results. A total of 241 subjects (94.9%) completed the followup study, and 28 (11. Conclusion. Among a group of psychologically at-risk subjects, dysfunction of the HPA axis helps to distinguish those who will and will not develop newonset CWP.6%Chronic widespread pain (CWP) affecting the musculoskeletal system, the principal symptom of fibromyalgia, is common, with a 1-month population prevalence of ϳ11% (1). It is associated with loss of function and considerable disability, may be associated with increased mortality rates (2), and is a major cause of health care utilization both in primary and secondary care settings. We have previously demonstrated in the prospective Altrincham Pain Study conducted in northwest England (3) that an increased risk of CWP onset is predicted from high levels of psychological distress, other somatic symptoms, and abnormal illness behavior. These factors are indicative of the process of somatization that can be defined as the tendency to express psychological distress as physical symptoms. These results confirmed for the first time that psychosocial factors preceded the onset of CWP, rather than just

Artificial intelligence, deep convolutional neural networks, and deep learning are all niche terms that are increasingly appearing in scientific presentations as well as in the general media. In this review, we focus on deep learning and how it is applied to microscopy image data of cells and tissue samples. Starting with an analogy to neuroscience, we aim to give the reader an overview of the key concepts of neural networks, and an understanding of how deep learning differs from more classical approaches for extracting information from image data. We aim to increase the understanding of these methods, while highlighting considerations regarding input data requirements, computational resources, challenges, and limitations. We do not provide a full manual for applying these methods to your own data, but rather review previously published articles on deep learning in image cytometry, and guide the readers toward further reading on specific networks and methods, including new methods not yet applied to cytometry data. © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

To determine the relative contributions of psychological factors and sleep disturbance to reduced pain threshold we conducted a cross-sectional two-phase population-based study. A total of 424 subjects were recruited, stratified by pain and distress status. Subjects completed a postal questionnaire that asked about current pain and covered aspects of psychological status and sleep disturbance. Samples of subjects stratified by the extent of bodily pain they reported and psychological status were invited to participate in an examination of pain threshold. The association between psychological status, sleep disturbance and a low pain threshold was examined using ordinal regression. High levels of psychological distress (OR=1.6, 95% CI (1.02, 2.5)), disturbed sleep (OR=2.2, 95% CI (1.4, 3.5)) and high scores on the HAD depression scale (OR=2.1, 95% CI (1.3, 3.2)) were all associated with having a low pain threshold. In multivariate analysis disturbed sleep and depression remained independently associated with a low pain threshold. These relationships persisted after adjustment for pain status. This study had demonstrated that depression and poor sleep are associated with a reduced pain threshold.

In clinic studies, altered hypothalamic-pituitary-adrenal (HPA) axis function has been associated with fibromyalgia, a syndrome characterised by chronic widespread body pain. These results may be explained by the associated high rates of psychological distress and somatisation. We address the hypothesis that the latter, rather than the pain, might explain the HPA results. A population study ascertained pain and psychological status in subjects aged 25 to 65 years. Random samples were selected from the following three groups: satisfying criteria for chronic widespread pain; free of chronic widespread pain but with strong evidence of somatisation ('at risk'); and a reference group. HPA axis function was assessed from measuring early morning and evening salivary cortisol levels, and serum cortisol after physical (pain pressure threshold exam) and chemical (overnight 0.25 mg dexamethasone suppression test) stressors. The relationship between HPA function with pain and the various psychosocial scales assessed was modelled using appropriate regression analyses, adjusted for age and gender. In all 131 persons with chronic widespread pain (participation rate 74%), 267 'at risk' (58%) and 56 controls (70%) were studied. Those in the chronic widespread pain and 'at risk' groups were, respectively, 3.1 (95% CI (1.3, 7.3)) and 1.8 (0.8, 4.0) times more likely to have a saliva cortisol score in the lowest third. None of the psychosocial factors measured were, however, associated with saliva cortisol scores. Further, those in the chronic widespread pain (1.9 (0.8, 4.7)) and 'at risk' (1.6 (0.7, 3.6)) groups were also more likely to have the highest serum cortisol scores. High post-stress serum cortisol was related to high levels of psychological distress (p = 0.05, 95% CI (0.02, 0.08)). After adjusting for levels of psychological distress, the association between chronic widespread pain and post-stress cortisol scores remained, albeit slightly attenuated. This is the first population study to demonstrate that those with established, and those psychologically at risk of, chronic widespread pain demonstrate abnormalities of HPA axis function, which are more marked in the former group. Although some aspects of the altered function are related to the psychosocial factors measured, we conclude that the occurrence of HPA abnormality in persons with chronic widespread pain is not fully explained by the accompanying psychological stress.

Background : Tender points are a general measure of distress both in the community and in clinic subjects. It has been suggested that multiple tender points should be regarded as the early stages of somatisation of distress. Similarly, recent evidence suggests that chronic widespread pain (CWP) is one manifestation of the somatisation of distress. Objective: Given that a high tender point count and CWP are clinical hallmarks of the fibromyalgia syndrome, it was hypothesised that in somatising subjects, a high tender point count or a low pain threshold would predict the development of CWP in the future. Methods: In this population-based prospective study, 245 adults aged 25-65 years, free of CWP, were identified on the basis of a detailed questionnaire on pain and a psychosocial questionnaire comprising the Somatic Symptom Checklist and the Illness Behaviour subscale of the Illness Attitude Scales. These subjects took part in a pain threshold examination with a Fischer pressure algometer. Tender point counts were computed by including all areas with a pain threshold ,4 kg/cm 2 . Individuals were followed up at 15 months, at which time 231 (93% of subjects still living at their baseline address) provided data on pain status, using the same instruments. Results: At follow-up, 26 (11%) subjects developed new CWP. Although subjects with a low baseline pain threshold were not at increased risk of developing symptoms, a high tender point count, adjusted for age, sex, baseline pain status and other confounding factors, predicted the development of new CWP. Conclusion: Subjects free of CWP are at an increased risk of its development if they have a high tender point count. However, a low-pressure pain threshold does not predict the onset of symptoms. Data from this population-based prospective study suggest that a low pain threshold in subjects with CWP is likely to be a secondary phenomenon as a result of pain or associated distress rather than the antecedent of symptoms.

The authors conclude that the proposed CAD system can identify dissimilar nodule candidates in the multiple heterogeneous datasets. It could be considered as a useful tool to support radiologists during screening trials.

98 ACTH = adrenocorticotrophic hormone; CNS = central nervous system; CRH = corticotrophin-releasing hormone; CSF = cerebrospinal fluid; DHEA = dehydroepiandrosterone; FSH = follicle-stimulating hormone; HPA = hypothalamic-pituitary-adrenal; IGF-I = insulin-like growth factor I; LH = luteinising hormone. Arthritis Research & Therapy Vol 6 No 3 Gupta and Silman IntroductionFibromyalgia is the second most common diagnosis made in rheumatology clinics [1], yet its aetiology remains a source of controversy. It has been suggested that fibromyalgia is a functional/psychological disorder and that the symptoms of fibromyalgia are simply due to somatisation of distress [2]. In support of this construct, there is definite evidence from population-based studies that psychological distress, particularly early-life trauma such as parental loss and abuse, can predict the future development of chronic widespread pain and fibromyalgia [3,4]. However, such observations leave unanswered the question of exactly how psychological factors translate into chronic physical pain.The alternative hypothesis is that fibromyalgia has an organic basis [5]. The possible neuroendocrine origins of fibromyalgia have been extensively investigated, based on the specific hypothesis that abnormalities of various endocrine axes, and certain neurotransmitters, might be responsible for the development of the fibromyalgia syndrome [6][7][8].The present review attempts to reconcile the conflict between psychological factors and physiological factors as a basis for fibromyalgia, by determining whether there are cogent neuroendocrine pathways that explain how psychological stress could lead to the symptoms of the fibromyalgia syndrome. Although these systems are clearly interconnected, the review will consider separately the potential role of the hypothalamic-pituitary-adrenal (HPA) axis, the role of the growth hormone axis, the role of sex steroids (both androgens and oestrogens), and the role of the neurotransmitters serotonin and substance P. Schematic representations of these systems are shown in Figs 1 and 2. The HPA axis Normal physiology and response to stressThe HPA axis, along with the sympatho-adrenal system, is the principal stress-response system in the human body. Acute stress causes the hypothalamus to release corticotrophin-releasing hormone (CRH) into the hypothalamic-hypophysial portal system. AbstractThe present review attempts to reconcile the dichotomy that exists in the literature in relation to fibromyalgia, in that it is considered either a somatic response to psychological stress or a distinct organically based syndrome. Specifically, the hypothesis explored is that the link between chronic stress and the subsequent development of fibromyalgia can be explained by one or more abnormalities in neuroendocrine function. There are several such abnormalities recognised that both occur as a result of chronic stress and are observed in fibromyalgia. Whether such abnormalities have an aetiologic role remains uncertain but should be testable...