Magnetic resonance imaging of a randomized controlled trial investigating predictors of recovery following psychological treatment in adolescents with moderate to severe unipolar depression: study protocol for Magnetic Resonance - Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT)

Background Major depressive disorders (MDD) are a debilitating and pervasive group of mental illnesses afflicting many millions of people resulting in the loss of 110 million working days and more than 2,500 suicides per annum. Adolescent MDD patients attending NHS clinics show high rates of recurrence into adult life. A meta-analysis of recent research shows that psychological treatments are not as efficacious as previously thought. Modest treatment outcomes of approximately 65% of cases responding suggest that aetiological and clinical heterogeneity may hamper the better use of existing therapies and discovery of more effective treatments. Information with respect to optimal treatment choice for individuals is lacking, with no validated biomarkers to aid therapeutic decision-making. Methods/Design Magnetic resonance-Improving Mood with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to identify brain regions implicated in the pathophysiology of depressions and examine whether there are specific behavioural or neural markers predicting remission and/or subsequent relapse in a subsample of depressed adolescents recruited to the IMPACT randomised controlled trial (Registration # ISRCTN83033550). Discussion MR-IMPACT is an investigative biomarker component of the IMPACT pragmatic effectiveness trial. The aim of this investigation is to identify neural markers and regional indicators of the pathophysiology of and treatment response for MDD in adolescents. We anticipate that these data may enable more targeted treatment delivery by identifying those patients who may be optimal candidates for therapeutic response.

Improving mood with psychoanalytic and cognitive therapies (IMPACT): a pragmatic effectiveness superiority trial to investigate whether specialised psychological treatment reduces the risk for relapse in adolescents with moderate to severe unipolar depression: study protocol for a randomised controlled trial

Background Up to 70% of adolescents with moderate to severe unipolar major depression respond to psychological treatment plus Fluoxetine (20-50 mg) with symptom reduction and improved social function reported by 24 weeks after beginning treatment. Around 20% of non responders appear treatment resistant and 30% of responders relapse within 2 years. The specific efficacy of different psychological therapies and the moderators and mediators that influence risk for relapse are unclear. The cost-effectiveness and safety of psychological treatments remain poorly evaluated. Methods/Design Improving Mood with Psychoanalytic and Cognitive Therapies, the IMPACT Study, will determine whether Cognitive Behavioural Therapy or Short Term Psychoanalytic Therapy is superior in reducing relapse compared with Specialist Clinical Care. The study is a multicentre pragmatic effectiveness superiority randomised clinical trial: Cognitive Behavioural Therapy consists of 20 sessions over 30 weeks, Short Term Psychoanalytic Psychotherapy 30 sessions over 30 weeks and Specialist Clinical Care 12 sessions over 20 weeks. We will recruit 540 patients with 180 randomised to each arm. Patients will be reassessed at 6, 12, 36, 52 and 86 weeks. Methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, research assessors independent of treatment team and blind to randomization, analysis by intention to treat, data management using remote data entry, measures of quality assurance, advanced statistical analysis, manualised treatment protocols, checks of adherence and competence of therapists and assessment of cost-effectiveness. We will also determine whether time to recovery and/or relapse are moderated by variations in brain structure and function and selected genetic and hormone biomarkers taken at entry. Discussion The objective of this clinical trial is to determine whether there are specific effects of specialist psychotherapy that reduce relapse in unipolar major depression in adolescents and thereby costs of treatment to society. We also anticipate being able to utilise psychotherapy experience, neuroimaging, genetic and hormone measures to reveal what techniques and their protocols may work best for which patients.

An overview of Earth's global electric circuit and atmospheric conductivity

The Earth’s global atmospheric electric circuit depends on the upper and lower atmospheric boundaries formed by the ionosphere and the planetary surface. Thunderstorms and electrified rain clouds drive a DC current (∼1 kA) around the circuit, with the current carried by molecular cluster ions; lightning phenomena drive the AC global circuit. The Earth’s near-surface conductivity ranges from 10−7 S m−1 (for poorly conducting rocks) to 10−2 S m−1 (for clay or wet limestone), with a mean value of 3.2 S m−1 for the ocean. Air conductivity inside a thundercloud, and in fair weather regions, depends on location (especially geomagnetic latitude), aerosol pollution and height, and varies from ∼10−14 S m−1 just above the surface to 10−7 S m−1 in the ionosphere at ∼80 km altitude. Ionospheric conductivity is a tensor quantity due to the geomagnetic field, and is determined by parameters such as electron density and electron–neutral particle collision frequency. In the current source regions, point discharge (coronal) currents play an important role below electrified clouds; the solar wind-magnetosphere dynamo and the unipolar dynamo due to the terrestrial rotating dipole moment also apply atmospheric potential differences. Detailed measurements made near the Earth’s surface show that Ohm’s law relates the vertical electric field and current density to air conductivity. Stratospheric balloon measurements launched from Antarctica confirm that the downward current density is ∼1 pA m−2 under fair weather conditions. Fortuitously, a Solar Energetic Particle (SEP) event arrived at Earth during one such balloon flight, changing the observed atmospheric conductivity and electric fields markedly. Recent modelling considers lightning discharge effects on the ionosphere’s electric potential (∼+250 kV with respect to the Earth’s surface) and hence on the fair weather potential gradient (typically ∼130 V m−1 close to the Earth’s surface. We conclude that cloud-to-ground (CG) lightning discharges make only a small contribution to the ionospheric potential, and that sprites (namely, upward lightning above energetic thunderstorms) only affect the global circuit in a miniscule way. We also investigate the effects of mesoscale convective systems on the global circuit.

An overview of Earth’s global electric circuit and atmospheric conductivity

The Earth’s global atmospheric electric circuit depends on the upper and lower atmospheric boundaries formed by the ionosphere and the planetary surface. Thunderstorms and electrified rain clouds drive a DC current (∼1 kA) around the circuit, with the current carried by molecular cluster ions; lightning phenomena drive the AC global circuit. The Earth’s near-surface conductivity ranges from 10−7 S m−1 (for poorly conducting rocks) to 10−2 S m−1 (for clay or wet limestone), with a mean value of 3.2 S m−1 for the ocean. Air conductivity inside a thundercloud, and in fair weather regions, depends on location (especially geomagnetic latitude), aerosol pollution and height, and varies from ∼10−14 S m−1 just above the surface to 10−7 S m−1 in the ionosphere at ∼80 km altitude. Ionospheric conductivity is a tensor quantity due to the geomagnetic field, and is determined by parameters such as electron density and electron–neutral particle collision frequency. In the current source regions, point discharge (coronal) currents play an important role below electrified clouds; the solar wind-magnetosphere dynamo and the unipolar dynamo due to the terrestrial rotating dipole moment also apply atmospheric potential differences. Detailed measurements made near the Earth’s surface show that Ohm’s law relates the vertical electric field and current density to air conductivity. Stratospheric balloon measurements launched from Antarctica confirm that the downward current density is ∼1 pA m−2 under fair weather conditions. Fortuitously, a Solar Energetic Particle (SEP) event arrived at Earth during one such balloon flight, changing the observed atmospheric conductivity and electric fields markedly. Recent modelling considers lightning discharge effects on the ionosphere’s electric potential (∼+250 kV with respect to the Earth’s surface) and hence on the fair weather potential gradient (typically ∼130 V m−1 close to the Earth’s surface. We conclude that cloud-to-ground (CG) lightning discharges make only a small contribution to the ionospheric potential, and that sprites (namely, upward lightning above energetic thunderstorms) only affect the global circuit in a miniscule way. We also investigate the effects of mesoscale convective systems on the global circuit.

Farm forestry in Pakistan: an application of Theory of Planned Behaviour by probing into the measurement issues

A research has been conducted over methodological issues concerning the Theory of Planned Behaviour (TPB) by determining an appropriate measurement (direct and indirect) of constructs and selection of a plausible scaling techniques (unipolar and bipolar) of constructs: attitude, subjective norm, perceived behavioural control and intention that are important in explaining farm level tree planting in Pakistan. Unipolar scoring of beliefs showed higher correlation among the constructs of TPB than bipolar scaling technique. Both direct and indirect methods yielded significant results in explaining intention to perform farm forestry except the belief based measure of perceived behavioural control, which were analysed as statistically non-significant. A need to examine more carefully the scoring of perceived behavioural control (PBC) has been expressed

Programmable data acquisition system for research measurements from meteorological radiosondes

A programmable data acquisition system to allow novel use of meteorological radiosondes for atmospheric science measurements is described. In its basic form it supports four analogue inputs at 16 bit resolution, and up to two further inputs at lower resolution configurable instead for digital instruments. It also provides multiple instrument power supplies (+8V, +16V, +5V and -8V) from the 9V radiosonde battery. During a balloon flight encountering air temperatures from +17°C to -66°C, the worst case voltage drift in the 5V unipolar digitisation circuitry was 20mV. The system liberates a new range of low cost atmospheric research measurements, by utilising radiosondes routinely launched internationally for weather forecasting purposes. No additional receiving equipment is required. Comparisons between the specially instrumented and standard meteorological radiosondes show negligible effect of the additional instrumentation on the standard meteorological data.

Sharing power? Prospects for a U.S. concert-balance strategy

The Pax Americana and the grand strategy of hegemony (or “Primacy”) that underpins it may be becoming unsustainable. Particularly in the wake of exhausting wars, the Global Financial Crisis, and the shift of wealth from West to East, it may no longer be possible or prudent for the United States to act as the unipolar sheriff or guardian of a world order. But how viable are the alternatives, and what difficulties will these alternatives entail in their design and execution? This analysis offers a sympathetic but critical analysis of alternative U.S. National Security Strategies of “retrenchment” that critics of American diplomacy offer. In these strategies, the United States would anticipate the coming of a more multipolar world and organize its behavior around the dual principles of “concert” and “balance,” seeking a collaborative relationship with other great powers, while being prepared to counterbalance any hostile aggressor that threatens world order. The proponents of such strategies argue that by scaling back its global military presence and its commitments, the United States can trade prestige for security, shift burdens, and attain a more free hand. To support this theory, they often look to the 19th-century concert of Europe as a model of a successful security regime and to general theories about the natural balancing behavior of states. This monograph examines this precedent and measures its usefulness for contemporary statecraft to identify how great power concerts are sustained and how they break down. The project also applies competing theories to how states might behave if world politics are in transition: Will they balance, bandwagon, or hedge? This demonstrates the multiple possible futures that could shape and be shaped by a new strategy. viii A new strategy based on an acceptance of multipolarity and the limits of power is prudent. There is scope for such a shift. The convergence of several trends—including transnational problems needing collaborative efforts, the military advantages of defenders, the reluctance of states to engage in unbridled competition, and hegemony fatigue among the American people—means that an opportunity exists internationally and at home for a shift to a new strategy. But a Concert-Balance strategy will still need to deal with several potential dilemmas. These include the difficulty of reconciling competitive balancing with cooperative concerts, the limits of balancing without a forward-reaching onshore military capability, possible unanticipated consequences such as a rise in regional power competition or the emergence of blocs (such as a Chinese East Asia or an Iranian Gulf), and the challenge of sustaining domestic political support for a strategy that voluntarily abdicates world leadership. These difficulties can be mitigated, but they must be met with pragmatic and gradual implementation as well as elegant theorizing and the need to avoid swapping one ironclad, doctrinaire grand strategy for another.

Solar origin of heliospheric magnetic field inversions: evidence for coronal loop opening within pseudostreamers

The orientation of the heliospheric magnetic field (HMF) in near‒Earth space is generally a good indicator of the polarity of HMF foot points at the photosphere. There are times, however, when the HMF folds back on itself (is inverted), as indicated by suprathermal electrons locally moving sunward, even though they must ultimately be carrying the heat flux away from the Sun. Analysis of the near‒Earth solar wind during the period 1998–2011 reveals that inverted HMF is present approximately 5.5% of the time and is generally associated with slow, dense solar wind and relatively weak HMF intensity. Inverted HMF is mapped to the coronal source surface, where a new method is used to estimate coronal structure from the potential‒field source‒surface model. We find a strong association with bipolar streamers containing the heliospheric current sheet, as expected, but also with unipolar or pseudostreamers, which contain no current sheet. Because large‒scale inverted HMF is a widely accepted signature of interchange reconnection at the Sun, this finding provides strong evidence for models of the slow solar wind which involve coronal loop opening by reconnection within pseudostreamer belts as well as the bipolar streamer belt. Occurrence rates of bipolar‒ and pseudostreamers suggest that they are equally likely to result in inverted HMF and, therefore, presumably undergo interchange reconnection at approximately the same rate. Given the different magnetic topologies involved, this suggests the rate of reconnection is set externally, possibly by the differential rotation rate which governs the circulation of open solar flux.

Anhedonia and reward-circuit connectivity distinguish nonresponders from responders to dorsomedial prefrontal rTMS in major depression

Background Depression is a heterogeneous mental illness. Neurostimulation treatments, by targeting specific nodes within the brain’s emotion-regulation network, may be useful both as therapies and as probes for identifying clinically relevant depression subtypes. Methods Here, we applied 20 sessions of magnetic resonance imaging-guided repetitive transcranial magnetic stimulation (rTMS) to the dorsomedial prefrontal cortex in 47 unipolar or bipolar patients with a medication-resistant major depressive episode. Results Treatment response was strongly bimodal, with individual patients showing either minimal or marked improvement. Compared with responders, nonresponders showed markedly higher baseline anhedonia symptomatology (including pessimism, loss of pleasure, and loss of interest in previously enjoyed activities) on item-by-item examination of Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology ratings. Congruently, on baseline functional magnetic resonance imaging, nonresponders showed significantly lower connectivity through a classical reward pathway comprising ventral tegmental area, striatum, and a region in ventromedial prefrontal cortex. Responders and nonresponders also showed opposite patterns of hemispheric lateralization in the connectivity of dorsomedial and dorsolateral regions to this same ventromedial region. Conclusions The results suggest distinct depression subtypes, one with preserved hedonic function and responsive to dorsomedial rTMS and another with disrupted hedonic function, abnormally lateralized connectivity through ventromedial prefrontal cortex, and unresponsive to dorsomedial rTMS. Future research directly comparing the effects of rTMS at different targets, guided by neuroimaging and clinical presentation, may clarify whether hedonia/reward circuit integrity is a reliable marker for optimizing rTMS target selection.

Soft balancing in the Americas: Latin American opposition to U.S. intervention, 1898–1936

In the aftermath of the 2003 U.S.-led invasion of Iraq, scholars of international relations debated how to best characterize the rising tide of global opposition. The concept of “soft balancing” emerged as an influential, though contested, explanation of a new phenomenon in a unipolar world: states seeking to constrain the ability of the United States to deploy military force by using multinational organizations, international law, and coalition building. Soft balancing can also be observed in regional unipolar systems. Multinational archival research reveals how Argentina, Mexico, and other Latin American countries responded to expanding U.S. power and military assertiveness in the early twentieth century through coordinated diplomatic maneuvering that provides a strong example of soft balancing. Examination of this earlier case makes an empirical contribution to the emerging soft-balancing literature and suggests that soft balancing need not lead to hard balancing or open conflict.