Location of the River Euphrates in the Late Miocene; dating of terrace gravel at Shireen, Syria

International audienceWe report gravel of the River Euphrates, capped by basalt that is Ar-Ar dated to ~9 Ma, at Shireen in northern Syria. This gravel, preserved by the erosion-resistant basalt, allows us for the first time to reconstruct the history of this major river during the Late Miocene. In response to progressive regional surface uplift, the Euphrates extended SE by ~800 km between the early Middle Miocene, when the coast was near Kahramanmara? in southern Turkey, and the Pliocene, when it lay in western Iraq, east of the Arabian Platform uplands

Randomized placebo-controlled trial assessing the effect of 24-week fenofibrate therapy on circulating markers of abdominal aortic aneurysm: Outcomes from the FAME-2 trial

Background-There is no drug therapy for abdominal aortic aneurysm (AAA). FAME-2 (Fenofibrate in the Management of Abdominal Aortic Aneurysm 2) was a placebo-controlled randomized trial designed to assess whether administration of 145 mg of fenofibrate/d for 24 weeks favorably modified circulating markers of AAA. Methods and Results-Patients with AAAs measuring 35 to 49 mm and no contraindication were randomized to fenofibrate or identical placebo. The primary outcome measures were the differences in serum osteopontin and kallistatin concentrations between groups. Secondary analyses compared changes in the circulating concentration of AAA-associated proteins, and AAA growth, between groups using multivariable linear mixed-effects modeling. A total of 140 patients were randomized to receive fenofibrate (n=70) or placebo (n=70). By the end of the study 3 (2.1%) patients were lost to follow-up and 18 (12.9%) patients had ceased trial medication. A total of 85% of randomized patients took =80% of allocated tablets and were deemed to have complied with the medication regimen. Patients’ allocated fenofibrate had expected reductions in serum triglycerides and estimated glomerular filtration rate, and increases in serum homocysteine. No differences in serum osteopontin, kallistatin, or AAA growth were observed between groups. Conclusions-Administering 145 mg/d of fenofibrate for 24 weeks did not significantly reduce serum concentrations of osteopontin and kallistatin concentrations, or rates of AAA growth in this trial. The findings do not support the likely benefit of fenofibrate as a treatment for patients with small AAAs. Clinical Trial Registration-URL: www.anzctr.org.au. Unique identifier: ACTRN12613001039774

Learning through social spaces: migrant women and lifelong learning in post-colonial London

This article shows how migrant women engage in learning through social spaces. It argues that such spaces are little recognised, and that there are multiple ways in which migrant women construct and negotiate their informal learning through socialising with other women in different informal modes. Additionally, the article shows how learning is shaped by the socio-political, geographical and multicultural context of living in London, outlining ways in which gendered and racialised identities shape, construct and constrain participation in lifelong learning. The article shows that one way in which migrant women resist (post)colonial constructions of difference is by engaging in informal and non-formal lifelong learning, arguing that the benefits are (at least) two-fold. The women develop skills (including language skills) but also use their informal learning to develop what is referred to in this article as 'relational capital'. The article concludes that informal lifelong learning developed through social spaces can enhance a sense of belonging for migrant women

H3K9 Methyltransferases and Demethylases Control Lung Tumor-Propagating Cells and Lung Cancer Progression

Epigenetic regulators are attractive anticancer targets, but the promise of therapeutic strategies inhibiting some of these factors has not been proven in vivo or taken into account tumor cell heterogeneity. Here we show that the histone methyltransferase G9a, reported to be a therapeutic target in many cancers, is a suppressor of aggressive lung tumor-propagating cells (TPCs). Inhibition of G9a drives lung adenocarcinoma cells towards the TPC phenotype by de-repressing genes which regulate the extracellular matrix. Depletion of G9a during tumorigenesis enriches tumors in TPCs and accelerates disease progression metastasis. Depleting histone demethylases represses G9a-regulated genes and TPC phenotypes. Demethylase inhibition impairs lung adenocarcinoma progression in vivo. Therefore, inhibition of G9a is dangerous in certain cancer contexts, and targeting the histone demethylases is a more suitable approach for lung cancer treatment. Understanding cellular context and specific tumor populations is critical when targeting epigenetic regulators in cancer for future therapeutic development

Gender studies and interdisciplinarity

In this article we consider the example of gender studies as an interdisciplinary field, and argue that gender studies, and women’s studies, from which gender studies developed, has a distinctive engagement with interdisciplinarity. By thinking about the tra- jectory of women’s studies, feminist thinking and gender studies, we suggest that this has always been an interdisciplinary field of study. We trace both the shifts and continuities in thinking between different iterations of feminist thinking to consider the three core fields of: gender, sex and sexuality; intersectionality and activism; theory and methods. The article aims to open up debate over what the constructive possibilities are of a focus upon gender, and what the relationship is between theory and activism. This article is published as part of an ongoing collection dedicated to interdisciplinary research

Increased pain intensity is associated with greater verbal communication difficulty and increased production of speech and co-speech gestures

Effective pain communication is essential if adequate treatment and support are to be provided. Pain communication is often multimodal, with sufferers utilising speech, nonverbal behaviours (such as facial expressions), and co-speech gestures (bodily movements, primarily of the hands and arms that accompany speech and can convey semantic information) to communicate their experience. Research suggests that the production of nonverbal pain behaviours is positively associated with pain intensity, but it is not known whether this is also the case for speech and co-speech gestures. The present study explored whether increased pain intensity is associated with greater speech and gesture production during face-to-face communication about acute, experimental pain. Participants (N = 26) were exposed to experimentally elicited pressure pain to the fingernail bed at high and low intensities and took part in video-recorded semi-structured interviews. Despite rating more intense pain as more difficult to communicate (t(25) = 2.21, p = .037), participants produced significantly longer verbal pain descriptions and more co-speech gestures in the high intensity pain condition (Words: t(25) = 3.57, p = .001; Gestures: t(25) = 3.66, p = .001). This suggests that spoken and gestural communication about pain is enhanced when pain is more intense. Thus, in addition to conveying detailed semantic information about pain, speech and co-speech gestures may provide a cue to pain intensity, with implications for the treatment and support received by pain sufferers. Future work should consider whether these findings are applicable within the context of clinical interactions about pain

'An interesting paper but not sufficiently theoretical’ : what does theorising in social research look like

This article explores the concept of theorising in social research: what is theorising; how does theorising look to those doing it and how can it be explained as a practice. The article draws on different sources, including accounts of theory and theorising in the literature as well as first-hand reporting by academics. A view is reached of theorising as a personal undertaking involving a commitment to comprehend the world. It is argued that theorising is driven by the identification of interesting problems (practical or theoretical or both) and a motivation to solve them. Theorising involves a shift of awareness from subsidiary to focal and such a shift allows a more abstract level of understanding. Theorising tends to be an individual undertaking which draws on personal knowledge, but it is only made possible by psychological tools which have been handed down from the past, ones which need to be accessed, understood and adapted. Theorising requires a disciplined creativity in which the imagination is channelled into finding solutions that are compatible with observed data

Psychopolitics: Peter Sedgwick’s legacy for mental health movements

This paper re-considers the relevance of Peter Sedgwick's Psychopolitics (1982) for a politics of mental health. Psychopolitics offered an indictment of ‘anti-psychiatry’ the failure of which, Sedgwick argued, lay in its deconstruction of the category of ‘mental illness’, a gesture that resulted in a politics of nihilism. ‘The radical who is only a radical nihilist’, Sedgwick observed, ‘is for all practical purposes the most adamant of conservatives’. Sedgwick argued, rather, that the concept of ‘mental illness’ could be a truly critical concept if it was deployed ‘to make demands upon the health service facilities of the society in which we live’. The paper contextualizes Psychopolitics within the ‘crisis tendencies’ of its time, surveying the shifting welfare landscape of the subsequent 25 years alongside Sedgwick's continuing relevance. It considers the dilemma that the discourse of ‘mental illness’ – Sedgwick's critical concept – has fallen out of favour with radical mental health movements yet remains paradigmatic within psychiatry itself. Finally, the paper endorses a contemporary perspective that, while necessarily updating Psychopolitics, remains nonetheless ‘Sedgwickian’

Evaluating the performance of artificial intelligence software for lung nodule detection on chest radiographs in a retrospective real-world UK population

Objectives Early identification of lung cancer on chest radiographs improves patient outcomes. Artificial intelligence (AI) tools may increase diagnostic accuracy and streamline this pathway. This study evaluated the performance of commercially available AI-based software trained to identify cancerous lung nodules on chest radiographs. Design This retrospective study included primary care chest radiographs acquired in a UK centre. The software evaluated each radiograph independently and outputs were compared with two reference standards: (1) the radiologist report and (2) the diagnosis of cancer by multidisciplinary team decision. Failure analysis was performed by interrogating the software marker locations on radiographs. Participants 5722 consecutive chest radiographs were included from 5592 patients (median age 59 years, 53.8% women, 1.6% prevalence of cancer). Results Compared with radiologist reports for nodule detection, the software demonstrated sensitivity 54.5% (95% CI 44.2% to 64.4%), specificity 83.2% (82.2% to 84.1%), positive predictive value (PPV) 5.5% (4.6% to 6.6%) and negative predictive value (NPV) 99.0% (98.8% to 99.2%). Compared with cancer diagnosis, the software demonstrated sensitivity 60.9% (50.1% to 70.9%), specificity 83.3% (82.3% to 84.2%), PPV 5.6% (4.8% to 6.6%) and NPV 99.2% (99.0% to 99.4%). Normal or variant anatomy was misidentified as an abnormality in 69.9% of the 943 false positive cases. Conclusions The software demonstrated considerable underperformance in this real-world patient cohort. Failure analysis suggested a lack of generalisability in the training and testing datasets as a potential factor. The low PPV carries the risk of over-investigation and limits the translation of the software to clinical practice. Our findings highlight the importance of training and testing software in representative datasets, with broader implications for the implementation of AI tools in imaging

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