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Depression is a challenge to diagnose reliably and the current gold standard for trials of DSM-5 has been in agreement between two or more medical specialists. Research studies aiming to objectively predict depression have typically used brain scanning. Less expensive methods from cognitive neuroscience may allow quicker and more reliable diagnoses, and contribute to reducing the costs of managing the condition. In the current study we aimed to develop a novel inexpensive system for detecting elevated symptoms of depression based on tracking face and eye movements during the performance of cognitive tasks.
In total, 75 participants performed two novel cognitive tasks with verbal affective distraction elements while their face and eye movements were recorded using inexpensive cameras. Data from 48 participants (mean age 25.5 years, standard deviation of 6.1 years, 25 with elevated symptoms of depression) passed quality control and were included in a case-control classification analysis with machine learning.
Classification accuracy using cross-validation (within-study replication) reached 79% (sensitivity 76%, specificity 82%), when face and eye movement measures were combined. Symptomatic participants were characterised by less intense mouth and eyelid movements during different stages of the two tasks, and by differences in frequencies and durations of fixations on affectively salient distraction words.
Elevated symptoms of depression can be detected with face and eye movement tracking during the cognitive performance, with a close to clinically-relevant accuracy (~80%). Future studies should validate these results in larger samples and in clinical populations.
In this article, we begin to extend ontological security to third-image theorizing. We argue that the autobiographical conceptions of international agents, along with other stories told about international politics, constitute ‘the international’ as a system, society, community, or inhabitable realm beyond and between first- and second-image relations. To develop this point, we focus on the relationship between narrative, anxiety, and time. We contend that ontological security issues resound in the third image once we shift from treating the international realm as social agents' external environment to treating it as a collective project in its own right. Doing so highlights the promise of ontological security studies for further differentiating international fear and anxiety, for enabling novel explanations of international phenomena, and for elaborating third-image identity formation as a wide-ranging timing effort to surmount a dynamic, processual environment full of interconnected coordination challenges.
Cutaneous leishmaniasis (CL) is a major health problem in many countries and its current treatment involves multiple parenteral injections with toxic drugs and requires intensive health services. Previously, the efficacy of a single subcutaneous injection with a slow-release formulation consisting of poly(lactide-co-glycolide) (PLGA) microparticles loaded with an antileishmanial 3-nitro-2-hydroxy-4,6-dimethoxychalcone (CH8) was demonstrated in mice model. In the search for more easily synthesized active chalcone derivatives, and improved microparticle loading, CH8 analogues were synthesized and tested for antileishmanial activity in vitro and in vivo. The 3-nitro-2′,4′,6′-trimethoxychalcone (NAT22) analogue was chosen for its higher selectivity against intracellular amastigotes (selectivity index = 1489, as compared with 317 for CH8) and more efficient synthesis (89% yield, as compared with 18% for CH8). NAT22 was loaded into PLGA / polyvinylpyrrolidone (PVP) polymeric blend microspheres (NAT22-PLGAk) with average diameter of 1.9 μm. Although NAT22-PLGAk showed similar activity to free NAT22 in killing intracellular parasites in vitro (IC50 ~ 0.2 μm), in vivo studies in Leishmania amazonensis – infected mice demonstrated the significant superior efficacy of NAT22-PLGAk to reduce the parasite load. A single intralesional injection with NAT22-PLGAk was more effective than eight injections with free NAT22. Together, these results show that NAT22-PLGAk is a promising alternative for single-dose localized treatment of CL.
Neuroticism is associated with the onset and maintenance of a number of mental health conditions, as well as a number of deleterious outcomes (e.g. physical health problems, higher divorce rates, lost productivity, and increased treatment seeking); thus, the consideration of whether this trait can be addressed in treatment is warranted. To date, outcome research has yielded mixed results regarding neuroticism's responsiveness to treatment, perhaps due to the fact that study interventions are typically designed to target disorder symptoms rather than neuroticism itself. The purpose of the current study was to explore whether a course of treatment with the unified protocol (UP), a transdiagnostic intervention that was explicitly developed to target neuroticism, results in greater reductions in neuroticism compared to gold-standard, symptom focused cognitive behavioral therapy (CBT) protocols and a waitlist (WL) control condition.
Patients with principal anxiety disorders (N = 223) were included in this study. They completed a validated self-report measure of neuroticism, as well as clinician-rated measures of psychological symptoms.
At week 16, participants in the UP condition exhibited significantly lower levels of neuroticism than participants in the symptom-focused CBT (t(218) = −2.17, p = 0.03, d = −0.32) and WL conditions(t(207) = −2.33, p = 0.02, d = −0.43), and these group differences remained after controlling for simultaneous fluctuations in depression and anxiety symptoms.
Treatment effects on neuroticism may be most robust when this trait is explicitly targeted.
Several brain circuits are relevant in the neurobiology of addiction. Here we want to highlight symptoms related to the domains of mood, anhedonia and anxiety that may precede drug abuse and represent a specific risk factor for addiction. The mood regulation circuit that contributes to regulation of stress reactivity and the interoception circuit that contributes to awareness of drug craving and mood also participate in addiction but their involvement in the human brain has been much less investigated.
Here we aim to investigate mood and anxiety in opiate dependent, treatment-seeking patients receiving Methadone Maintenance Treatment, to test hypothesis of regional grey matter reduction correlating with mood and anxiety.
Cambridge Gambling Task (CGT) data were acquired from 30 patients receiving MMT and 23 controls. T1 weighted Magnetic Resonance Images were acquired from a representative subset of these volunteers.
MMT patients exhibited grey matter reductions in the orbito-medial prefrontal cortex and basal ganglia. Additionally, patients exhibited significant abnormalities in the clinical rating scales BDI, Anhedonia, HAD-Anxiety, IDS and Snaith Hamilton. Increased BDI, HAD-Anxiety and IDS correlated with grey matter reductions in the hippocampus, amygdala, bed nucleus of stria terminalis and insula. Increased Snaith Hamilton correlated with grey matter reductions in periaqueductal gray, ventral tegmental area and nucleus caudate.
These findings support an interpretation of a neurobiological underpinning of mood and addiction. However, the anatomically restricted correlates with mood and anxiety suggest that a rationale for adopting a mood addiction model should be further investigated.
Preclinical studies have suggested that continuous, long-term opiate exposure may be neurotoxic. There is accumulating evidence for neural and neuropsychological abnormalities in diverse human drug addiction populations. However, the structural and behavioural correlates of human opiate dependency have been less studied than other drugs.
We investigated brain structure and neuropsychological functioning in opiate dependent, treatment-seeking patients receiving Methadone Maintenance Treatment, to test hypotheses of regional grey matter reductions correlating with methadone exposure and neuropsychological measures.
Cambridge Gambling Task (CGT) data were acquired from 47 patients receiving MMT and 51 controls. T1 weighted Magnetic Resonance Images were acquired from a representative subset of these volunteers.
MMT patients exhibited grey matter reductions in the orbito-medial prefrontal cortex and basal ganglia. Additionally, patients exhibited significant abnormalities on CGT behavioural measures; risk adjustment, risk taking and impulsivity. Both the initial titration dose of methadone at the commencement of MMT following protocolised tolerance testing, and methadone dose at the time of scanning, correlated with grey matter reductions in the globus pallidus. Abnormal risk adjustment behaviour correlated with reductions in globus pallidus grey matter, increased risk taking with orbitofrontal grey matter reductions, and increased impulsivity with cingulate cortex reductions.
These findings support an interpretation of heightened risk taking and impulsivity in patients receiving MMT. However, the anatomically restricted correlates with indices of methadone exposure suggest that most structural brain abnormalities are not opiate linked, with the possible exception of the globus pallidus.
Experience of emotion is closely linked to valuation. Mood can be viewed as a bias to experience positive or negative emotions and abnormally biased subjective reward valuation and cognitions are core characteristics of major depression.
Thirty-four unmedicated subjects with major depressive disorder and controls estimated the probability that fractal stimuli were associated with reward, based on passive observations, so they could subsequently choose the higher of either their estimated fractal value or an explicitly presented reward probability. Using model-based functional magnetic resonance imaging, we estimated each subject's internal value estimation, with psychophysiological interaction analysis used to examine event-related connectivity, testing hypotheses of abnormal reward valuation and cingulate connectivity in depression.
Reward value encoding in the hippocampus and rostral anterior cingulate was abnormal in depression. In addition, abnormal decision-making in depression was associated with increased anterior mid-cingulate activity and a signal in this region encoded the difference between the values of the two options. This localised decision-making and its impairment to the anterior mid-cingulate cortex (aMCC) consistent with theories of cognitive control. Notably, subjects with depression had significantly decreased event-related connectivity between the aMCC and rostral cingulate regions during decision-making, implying impaired communication between the neural substrates of expected value estimation and decision-making in depression.
Our findings support the theory that abnormal neural reward valuation plays a central role in major depressive disorder (MDD). To the extent that emotion reflects valuation, abnormal valuation could explain abnormal emotional experience in MDD, reflect a core pathophysiological process and be a target of treatment.
Infrared (IR) spectroscopy is increasingly being used to probe the secondary structure of proteins, especially for high-concentration samples and biopharmaceuticals in complex formulation vehicles. However, the small path lengths required for aqueous protein transmission experiments, due to high water absorbance in the amide I region of the spectrum, means that the path length is not accurately known, so only the shape of the band is ever considered. This throws away a dimension of information. Attenuated total reflectance (ATR) IR spectroscopy is much easier to implement than transmission IR spectroscopy and, for a given instrument and sample, gives reproducible spectra. However, the ATR-absorbance spectrum varies with sample concentration and instrument configuration, and its wavenumber dependence differs significantly from that observed in transmission spectroscopy. In this paper, we determine, for the first time, how to transform water and aqueous protein ATR spectra into the corresponding transmission spectra with appropriate spectral shapes and intensities. The approach is illustrated by application to water, concanavalin A, haemoglobin and lysozyme. The transformation is only as good as the available water refractive index data. A hybrid of literature data provides the best results. The transformation also allows the angle of incidence of an ATR crystal to be determined. This opens the way to using both spectral shape and spectra intensity for protein structure fitting.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
The Murchison Widefield Array (MWA) is an electronically steered low-frequency (<300 MHz) radio interferometer, with a ‘slew’ time less than 8 s. Low-frequency (∼100 MHz) radio telescopes are ideally suited for rapid response follow-up of transients due to their large field of view, the inverted spectrum of coherent emission, and the fact that the dispersion delay between a 1 GHz and 100 MHz pulse is on the order of 1–10 min for dispersion measures of 100–2000 pc/cm3. The MWA has previously been used to provide fast follow-up for transient events including gamma-ray bursts (GRBs), fast radio bursts (FRBs), and gravitational waves, using systems that respond to gamma-ray coordinates network packet-based notifications. We describe a system for automatically triggering MWA observations of such events, based on Virtual Observatory Event standard triggers, which is more flexible, capable, and accurate than previous systems. The system can respond to external multi-messenger triggers, which makes it well-suited to searching for prompt coherent radio emission from GRBs, the study of FRBs and gravitational waves, single pulse studies of pulsars, and rapid follow-up of high-energy superflares from flare stars. The new triggering system has the capability to trigger observations in both the regular correlator mode (limited to ≥0.5 s integrations) and using the Voltage Capture System (VCS, 0.1 ms integration) of the MWA and represents a new mode of operation for the MWA. The upgraded standard correlator triggering capability has been in use since MWA observing semester 2018B (July–Dec 2018), and the VCS and buffered mode triggers will become available for observing in a future semester.
The chapter develops two complexes in political and social life – restraint and actionism. It introduces and draws from Carl Jung’s understanding of the libido as psychic energy, as well as his analytical concept of synchronicity.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
The chapter explores restraint in the context of security. It examines two cases where restraint proved difficult or even unsatisfying: (1) the 2013 US decision to avoid military action against Syria following the latter’s 2013 chemical weapons attack and (2) the 2014 ISIS beheadings that drew the USA into a limited use of military strikes against that transnational terrorist organization. It also applies the complexes to different Islamic movements over time. It concludes via ontological security and securitization with the reasons restraint appears to be so unsatisfying in the context of security policies.
Reviews the findings of the book. The chapter then, via Reinhold Niebuhr’s Serenity Prayer, makes a case for a strategic narrative, or set of powerful stories, regarding restraint. It applies those to the contexts of the United States and the International Relations academy.
Applies the arguments on restraint and actionism to the domains of international political economy and global public health. It explores the dynamic of racial and gendered biases found in discourses surrounding the 2008–2009 Global Financial Crisis and the 2010s European Debt Crisis. It also analyzes the transnational epistemic community of eugenics in the early twentieth century.