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Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
This paper provides an up-to-date review of the problems related to the generation, detection and mitigation of strong electromagnetic pulses created in the interaction of high-power, high-energy laser pulses with different types of solid targets. It includes new experimental data obtained independently at several international laboratories. The mechanisms of electromagnetic field generation are analyzed and considered as a function of the intensity and the spectral range of emissions they produce. The major emphasis is put on the GHz frequency domain, which is the most damaging for electronics and may have important applications. The physics of electromagnetic emissions in other spectral domains, in particular THz and MHz, is also discussed. The theoretical models and numerical simulations are compared with the results of experimental measurements, with special attention to the methodology of measurements and complementary diagnostics. Understanding the underlying physical processes is the basis for developing techniques to mitigate the electromagnetic threat and to harness electromagnetic emissions, which may have promising applications.
Individual differences in cognitive responses to trauma may represent modifiable risk factors that could allow early identification, targeted early treatment and possibly prevention of chronic posttraumatic stress disorder (PTSD). Ehlers and Clark's cognitive model of PTSD suggests that negative appraisals, disjointed trauma memories, and unhelpful coping strategies maintain PTSD. These are thought to be influenced by cognitive processing during trauma. The aim of this study was to test this model prospectively with path analyses.
Participants (N = 828) were recruited from an emergency department following injury in a violent assault or road traffic collision and 700 participated in the 6-month assessments. Cognitive processing was assessed shortly after the event, negative appraisals, disjointed memories, and unhelpful coping strategies at 1 month, persistent PTSD symptom severity at 6 months, and early PTSD symptom severity at 2 weeks.
Cognitive variables, with trauma type and gender, explained 52% of the variance in PTSD symptom severity at 6 months. Including early symptom severity in the model did not explain more variance (53%). Early PTSD symptom severity, with trauma type and gender, only predicted 40%. Negative appraisals and disjointed memories predicted persistent symptom severity both directly and indirectly via unhelpful strategies. Peritraumatic processing predicted persistent symptom severity mainly indirectly. The effects of trauma type and gender were fully mediated by the cognitive factors.
The results are consistent with theoretically derived predictions and support cognitive factors as indicators of risk for chronic PTSD and as a target for the treatment and prevention of PTSD.
Refractory depression is a major contributor to the economic burden of depression. Radically open dialectical behaviour therapy (RO DBT) is an unevaluated new treatment targeting overcontrolled personality, common in refractory depression, but it is not yet known whether the additional expense of RO DBT is good value for money.
To estimate the cost-effectiveness of RO DBT plus treatment as usual (TAU) compared with TAU alone in people with refractory depression (trial registration: ISRCTN85784627).
We undertook a cost-effectiveness analysis alongside a randomised trial evaluating RO DBT plus TAU versus TAU alone for refractory depression in three UK secondary care centres. Our economic evaluation, 12 months after randomisation, adopted the perspective of the UK National Health Service (NHS) and personal social services. It evaluated cost-effectiveness by comparing the net cost of RO DBT with the net gain in quality-adjusted life-years (QALYs), estimated using the EQ-5D-3L measure of health-related quality of life.
The additional cost of RO DBT plus TAU compared with TAU alone was £7048 and was associated with a difference of 0.032 QALYs, yielding an incremental cost-effectiveness ratio (ICER) of £220 250 per QALY. This ICER was well above the National Institute for Health and Care Excellence (NICE) upper threshold of £30 000 per QALY. A cost-effectiveness acceptability curve indicated that RO DBT had a zero probability of being cost-effective compared with TAU at the NICE £30 000 threshold.
In its current resource-intensive form, RO DBT is not a cost-effective use of resources in the UK NHS.
Declaration of interest
R.H. is co-owner and director of Radically Open Ltd, the RO DBT training and dissemination company. D.K. reports grants outside the submitted work from the National Institute for Health Research (NIHR). T.L. receives royalties from New Harbinger Publishing for sales of RO DBT treatment manuals, speaking fees from Radically Open Ltd, and a grant outside the submitted work from the Medical Research Council. He was co-director of Radically Open Ltd between November 2014 and May 2015 and is married to Erica Smith-Lynch, the principal shareholder and one of two directors of Radically Open Ltd. H.O'M. reports personal fees outside the submitted work from the Charlie Waller Institute and Improving Access to Psychological Therapy. S.R. provides RO DBT supervision through her company S C Rushbrook Ltd. I.R. reports grants outside the submitted work from NIHR and Health & Care Research Wales. M. Stanton reports personal fees outside the submitted work from British Isles DBT Training, Stanton Psychological Services Ltd and Taylor & Francis. M. Swales reports personal fees outside the submitted work from British Isles DBT Training, Guilford Press, Oxford University Press and Taylor & Francis. B.W. was co-director of Radically Open Ltd between November 2014 and February 2015.
Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression.
To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627).
RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated.
After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94–9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI –2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI –2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group.
The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these.
We present the characteristics of a high temperature CMOS integrated circuit process based on 4H silicon carbide designed to operate at temperatures beyond 300°C. N-channel and P-channel transistor characteristics at room and elevated temperatures are presented. Both channel types show the expected low values of field effect mobility well known in SiC MOSFETS. However the performance achieved is easily capable of exploitation in CMOS digital logic circuits and certain analogue circuits, over a wide temperature range.
Data is also presented for the performance of digital logic demonstrator circuits, in particular a 4 to 1 analogue multiplexer and a configurable timer operating over a wide temperature range. Devices are packaged in high temperature ceramic dual in line (DIL) packages, which are capable of greater than 300°C operation. A high temperature “micro-oven” system has been designed and built to enable testing and stressing of units assembled in these package types. This system heats a group of devices together to temperatures of up to 300°C while keeping the electrical connections at much lower temperatures. In addition, long term reliability data for some structures such as contact chains to n-type and p-type SiC and simple logic circuits is summarized.
What does it mean to think “I,” to say “I,” to write “I”? These foundational questions of subjectivity inform Annette von Droste-Hulshoff's literary production to such an extent that one might arguably define her oeuvre in terms of the early German Romantic notion of autopoiesis, the self-reflexive, self-critical self-creation of the subject, das Ich (the I), in and through poesy. Yet in contradistinction to the unitary structure of early Romantic subjectivity, for Droste the self frequently is presented as an object, an object often watched by—and at times watching—the subject, an object that is irreconcilable with the subject. significantly, many of these scenes of objectified self-definition are explicitly presented as aesthetic events, indicating their programmatic status in Droste's poetics, and they recur emblematically throughout her writing.
The following analysis seeks to elucidate Droste's object-driven conception of subjectivity and poetic production through a series of examples. The first section considers the early prose fragment Ledwina (1818/19–26). The second presents brief readings of a selection of her more famous poems and ballads, written between 1840 and 1844: “Das Spiegelbild” (The mirror image), “Im Moose” (In the moss), “Das Fraulein von Rodenschild” (Lady von Rodenschild), “Das erste Gedicht” (The first poem), “Das alte schloss” (The old castle), “Im Grase” (In the grass), “Die todte Lerche” (The dead lark), “Die Taxuswand” (The yew wall), “Die Mergelgrube” (The marl pit) and “Lebt wohl” (Farewell).
In 1807 Goethe formed a small chamber choir in Weimar, which he referred to on occasion as his “Singschule” (singing school), “Singechor” (singing choir), or “Singstunden” (singing class); in his diary he would often simply write that he spent time with “die Sänger” (the singers). Thanking Bettine Brentano for a packet of music she had sent him, he called the choir “meine kleine Hauscapelle” (my little chamber group) in a 24 February 1808 letter to her, and with irony he called the choir “meine kompendiose Hauskapelle” (my compendious chamber group) in a 22 April 1814 letter to his friend and musical advisor Carl Friedrich Zelter (MA 20.1:343). Years later in the Tag- und Jahreshefte he once again and more seriously referred to it as his “Hauskapelle” as he recalled its most successful season, 1810-11.
That the name recalls an earlier Hauskapelle, which Goethe created in the fictive world of Wilhelm Meisters Lehrjahre, is not accidental:
Serlo, ohne selbst Genie zur Musik zu haben, oder irgend ein Instrument zu spielen, wußte ihren hohen Wert zu schätzen; er suchte sich so oft als möglich diesen Genuß, der mit keinem andern verglichen werden kann, zu verschaffen. Er hatte wöchentlich einmal Konzert, und nun hatte sich ihm durch Mignon, den Harfenspieler und Laertes, der auf der Violine nicht ungeschickt war, eine wunderliche kleine Hauskapelle gebildet.
As many of his enemies have repeatedly emphasized, laughter is the devil. A long line of humorlessness, and especially a demonization of laughter, runs through the history of Christianity. Above all, it was the ancient Christian monkhood and the Church Fathers who accused laughter of being incompatible with human dignity. This tradition of an conservative hatred of laughter reaches from the seventeenth century's Jesuit and Jansenist critique of the comedy of the seventeenth century to Charles Baudelaire's essay De L'Essence du rire (1855), in which he reveals laughter to be the signature of fallen humanity, the trait of the satanic in mankind: “un des plus clairs signes sataniques de l'homme” (one of the clearest satanic signs of man). In paradise, laughter would have been unknown, and Christ never laughed—but he did cry—which, for Baudelaire, confirmed the antidivine character of laughter.
Two major works of modern art and literature, not least inspired by Baudelaire, have moved laughter into the sphere of evil. It is in Wagner's Parsifal that Kundry, the female main character, laughed at the cross-bearing Jesus on his journey of suffering and, as a result, was condemned like Ahasuerus, the eternal Jew, to wander through history until the end of days in “cursed laughter” (verfluchtem Lachen).