Effectiveness of an online group course for adolescents and young adults with depressive symptoms: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Depression is a common condition whose first onset is usually in late adolescence or early adulthood. Internet-based interventions are an effective treatment approach to depression. The aim of this study is to investigate the effectiveness of a Dutch online cognitive-behavioural group course known as Master Your Mood (<it>Grip op Je Dip</it>) for young people reporting depressive symptoms. Secondary research questions involve maintenance of effect at 6 months, mediators, and predictors of better outcomes.</p> <p>Methods</p> <p>We will conduct a randomised controlled trial (RCT) in which 244 young people aged 16-25 are randomly allocated to the Grip op Je Dip (GOJD) online group course or to a waiting list control group. The participants will be recruited from the general population. The primary outcome measure will be the severity of depressive symptoms according to the Center for Epidemiological Studies Depression Scale (CES-D). Other outcomes will include anxiety (Hospital Anxiety and Depression Scale-Anxiety, HADS) and mastery (Mastery Scale). Assessments will take place in both groups at baseline and three months later. Effect maintenance will be studied in the GOJD group six months after baseline, with missing data imputed using the expectation-maximisation method. Mediators and predictors of better outcomes will also be identified.</p> <p>Discussion</p> <p>The trial should add to the body of knowledge on the effectiveness of Internet-based interventions for depression. To our knowledge, this will be the first RCT on an online group intervention in this field.</p> <p>Trial registration</p> <p><a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=NTR1694">NTR1694</a></p

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Rotation in [C II]-emitting gas in two galaxies at a redshift of 6.8

The earliest galaxies are thought to have emerged during the first billion years of cosmic history, initiating the ionization of the neutral hydrogen that pervaded the Universe at this time. Studying this ‘epoch of reionization’ involves looking for the spectral signatures of ancient galaxies that are, owing to the expansion of the Universe, now very distant from Earth and therefore exhibit large redshifts. However, finding these spectral fingerprints is challenging. One spectral characteristic of ancient and distant galaxies is strong hydrogen-emission lines (known as Lyman-α lines), but the neutral intergalactic medium that was present early in the epoch of reionization scatters such Lyman-α photons. Another potential spectral identifier is the line at wavelength 157.4 micrometres of the singly ionized state of carbon (the [C II] λ = 157.74 μm line), which signifies cooling gas and is expected to have been bright in the early Universe. However, so far Lyman-α-emitting galaxies from the epoch of reionization have demonstrated much fainter [C II] luminosities than would be expected from local scaling relations1,2,3,4,5, and searches for the [C II] line in sources without Lyman-α emission but with photometric redshifts greater than 6 (corresponding to the first billion years of the Universe) have been unsuccessful. Here we identify [C II] λ = 157.74 μm emission from two sources that we selected as high-redshift candidates on the basis of near-infrared photometry; we confirm that these sources are two galaxies at redshifts of z = 6.8540 ± 0.0003 and z = 6.8076 ± 0.0002. Notably, the luminosity of the [C II] line from these galaxies is higher than that found previously in star-forming galaxies with redshifts greater than 6.5. The luminous and extended [C II] lines reveal clear velocity gradients that, if interpreted as rotation, would indicate that these galaxies have similar dynamic properties to the turbulent yet rotation-dominated disks that have been observed in Hα-emitting galaxies two billion years later, at ‘cosmic noon’

Comprehensive genetic assessment of a functional TLR9 promoter polymorphism: no replicable association with asthma or asthma-related phenotypes

<p>Abstract</p> <p>Background</p> <p>Prior studies suggest a role for a variant (rs5743836) in the promoter of toll-like receptor 9 (TLR9) in asthma and other inflammatory diseases. We performed detailed genetic association studies of the functional variant rs5743836 with asthma susceptibility and asthma-related phenotypes in three independent cohorts.</p> <p>Methods</p> <p>rs5743836 was genotyped in two family-based cohorts of children with asthma and a case-control study of adult asthmatics. Association analyses were performed using chi square, family-based and population-based testing. A luciferase assay was performed to investigate whether rs5743836 genotype influences TLR9 promoter activity.</p> <p>Results</p> <p>Contrary to prior reports, rs5743836 was not associated with asthma in any of the three cohorts. Marginally significant associations were found with FEV₁and FVC (p = 0.003 and p = 0.008, respectively) in one of the family-based cohorts, but these associations were not significant after correcting for multiple comparisons. Higher promoter activity of the CC genotype was demonstrated by luciferase assay, confirming the functional importance of this variant.</p> <p>Conclusion</p> <p>Although rs5743836 confers regulatory effects on TLR9 transcription, this variant does not appear to be an important asthma-susceptibility locus.</p

Sampling-Based Approaches to Improve Estimation of Mortality among Patient Dropouts: Experience from a Large PEPFAR-Funded Program in Western Kenya

Monitoring and evaluation (M&E) of HIV care and treatment programs is impacted by losses to follow-up (LTFU) in the patient population. The severity of this effect is undeniable but its extent unknown. Tracing all lost patients addresses this but census methods are not feasible in programs involving rapid scale-up of HIV treatment in the developing world. Sampling-based approaches and statistical adjustment are the only scaleable methods permitting accurate estimation of M&E indices.In a large antiretroviral therapy (ART) program in western Kenya, we assessed the impact of LTFU on estimating patient mortality among 8,977 adult clients of whom, 3,624 were LTFU. Overall, dropouts were more likely male (36.8% versus 33.7%; p = 0.003), and younger than non-dropouts (35.3 versus 35.7 years old; p = 0.020), with lower median CD4 count at enrollment (160 versus 189 cells/ml; p<0.001) and WHO stage 3-4 disease (47.5% versus 41.1%; p<0.001). Urban clinic clients were 75.0% of non-dropouts but 70.3% of dropouts (p<0.001). Of the 3,624 dropouts, 1,143 were sought and 621 had their vital status ascertained. Statistical techniques were used to adjust mortality estimates based on information obtained from located LTFU patients. Observed mortality estimates one year after enrollment were 1.7% (95% CI 1.3%-2.0%), revised to 2.8% (2.3%-3.1%) when deaths discovered through outreach were added and adjusted to 9.2% (7.8%-10.6%) and 9.9% (8.4%-11.5%) through statistical modeling depending on the method used. The estimates 12 months after ART initiation were 1.7% (1.3%-2.2%), 3.4% (2.9%-4.0%), 10.5% (8.7%-12.3%) and 10.7% (8.9%-12.6%) respectively. CONCLUSIONS/SIGNIFICANCE ABSTRACT: Assessment of the impact of LTFU is critical in program M&E as estimated mortality based on passive monitoring may underestimate true mortality by up to 80%. This bias can be ameliorated by tracing a sample of dropouts and statistically adjust the mortality estimates to properly evaluate and guide large HIV care and treatment programs

Significant Dust-obscured Star Formation in Luminous Lyman-break Galaxies at z ∼7-8

We make use of Atacama Large Millimeter/submillimeter Array continuum observations of 15 luminous Lyman-break galaxies at z ∼7-8 to probe their dust-obscured star formation. These observations are sensitive enough to probe obscured star formation rates (SFRs) of 20 M yr-1 (3σ). Six of the targeted galaxies show significant (≥3σ) dust-continuum detections, more than doubling the number of known dust-detected galaxies at z > 6.5. Their IR luminosities range from 2.7 × 1011 L to 1.1 × 1012 L, equivalent to obscured SFRs of 25 to 101 M yr-1. We use our results to quantify the correlation of the infrared excess (IRX) on the UV-continuum slope β UV and stellar mass. Our results are most consistent with a Small Magellanic Cloud (SMC) attenuation curve for intrinsic UV-slopes βUV,intr of -2.63 and most consistent with an attenuation curve in between SMC and Calzetti for βUV,intr slopes of -2.23, assuming a dust temperature T d of 50 K. Our fiducial IRX-stellar mass results at z ∼7-8 are consistent with marginal evolution from z ∼0. We then show how both results depend on T d . For our six dust-detected sources, we estimate their dust masses and find that they are consistent with dust production from supernovae if the dust destruction is low (<90%). Finally we determine the contribution of dust-obscured star formation to the SFR density for UV luminous (H<-21.5 mag: ≥ 1.7 L ∗UV) z ∼7-8 galaxies, finding that the total SFR density at z ∼7 and z ∼8 from bright galaxies is 0.20-0.10+0.10 dex and 0.23-0.09+0.06 dex higher, respectively; i.e., ∼1/3 of the star formation in ≥ 1.7 L ∗UV galaxies at z ∼7-8 is obscured by dust

HST Imaging of the Brightest z similar to 8-9 Galaxies from UltraVISTA: The Extreme Bright End of the UV Luminosity Function

We report on the discovery of three especially bright candidate ${z}_{\mathrm{phot}}\gtrsim 8$ galaxies. Five sources were targeted for follow-up with the Hubble Space Telescope (HST)/Wide Field Camera 3 (WFC3), selected from a larger sample of 16 bright ($24.8\lesssim H\lesssim 25.5$ mag) candidate $z\gtrsim 8$ Lyman break galaxies (LBGs) identified over 1.6 degrees2 of the COSMOS/UltraVISTA field. These were selected as Y and J dropouts by leveraging the deep (Y-to-{K}_{{\rm{S}}}\sim 25.3\mbox{--}24.8 mag, $5\sigma$) NIR data from the UltraVISTA DR3 release, deep ground-based optical imaging from the CFHTLS and Suprime-Cam programs, and Spitzer/IRAC mosaics combining observations from the SMUVS and SPLASH programs. Through the refined spectral energy distributions, which now also include new HyperSuprimeCam g-, r-, i-, z-, and Y-band data, we confirm that 3/5 galaxies have robust {z}_{\mathrm{phot}}\sim 8.0\mbox{--}8.7, consistent with the initial selection. The remaining 2/5 galaxies have a nominal ${z}_{\mathrm{phot}}\sim 2$. However, with HST data alone, these objects have increased probability of being at $z\sim 9$. We measure mean UV continuum slopes $\beta =-1.74\pm 0.35$ for the three z\sim 8\mbox{--}9 galaxies, marginally bluer than similarly luminous z\sim 4\mbox{--}6 in CANDELS but consistent with previous measurements of similarly luminous galaxies at $z\sim 7$. The circularized effective radius for our brightest source is 0.9 ± 0.3 kpc, similar to previous measurements for a bright $z\sim 11$ galaxy and bright $z\sim 7$ galaxies. Finally, enlarging our sample to include the six brightest $z\sim 8$ LBGs identified over UltraVISTA (i.e., including three other sources from Labbé et al.) we estimate for the first time the volume density of galaxies at the extreme bright end (${M}_{\mathrm{UV}}\sim -22$ mag) of the $z\sim 8$ UV luminosity function. Despite this exceptional result, the still large statistical uncertainties do not allow us to discriminate between a Schechter and a double-power-law form

The Netherlands study of depression in older persons (NESDO); a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>To study late-life depression and its unfavourable course and co morbidities in The Netherlands.</p> <p>Methods</p> <p>We designed the Netherlands Study of Depression in Older Persons (NESDO), a multi-site naturalistic prospective cohort study which makes it possible to examine the determinants, the course and the consequences of depressive disorders in older persons over a period of six years, and to compare these with those of depression earlier in adulthood.</p> <p>Results</p> <p>From 2007 until 2010, the NESDO consortium has recruited 510 depressed and non depressed older persons (≥ 60 years) at 5 locations throughout the Netherlands. Depressed persons were recruited from both mental health care institutes and general practices in order to include persons with late-life depression in various developmental and severity stages. Non-depressed persons were recruited from general practices. The baseline assessment included written questionnaires, interviews, a medical examination, cognitive tests and collection of blood and saliva samples. Information was gathered about mental health outcomes and demographic, psychosocial, biological, cognitive and genetic determinants. The baseline NESDO sample consists of 378 depressed (according to DSM-IV criteria) and 132 non-depressed persons aged 60 through 93 years. 95% had a major depression and 26.5% had dysthymia. Mean age of onset of the depressive disorder was around 49 year. For 33.1% of the depressed persons it was their first episode. 41.0% of the depressed persons had a co morbid anxiety disorder. Follow up assessments are currently going on with 6 monthly written questionnaires and face-to-face interviews after 2 and 6 years.</p> <p>Conclusions</p> <p>The NESDO sample offers the opportunity to study the neurobiological, psychosocial and physical determinants of depression and its long-term course in older persons. Since largely similar measures were used as in the Netherlands Study of Depression and Anxiety (NESDA; age range 18-65 years), data can be pooled thus creating a large longitudinal database of clinically depressed persons with adequate power and a large set of neurobiological, psychosocial and physical variables from both younger and older depressed persons.</p

Cost-effectiveness of nurse-led self-help for recurrent depression in the primary care setting: design of a pragmatic randomized trial

<p>Abstract</p> <p>Background</p> <p>Major Depressive Disorder is a leading cause of disability, tends to run a recurrent course and is associated with substantial economic costs due to increased healthcare utilization and productivity losses. Interventions aimed at the prevention of recurrences may reduce patients' suffering and costs. Besides antidepressants, several psychological treatments such as preventive cognitive therapy (PCT) are effective in the prevention of recurrences of depression. Yet, many patients find long-term use of antidepressants unattractive, do not want to engage in therapy sessions and in the primary care setting psychologists are often not available. Therefore, it is important to study whether PCT can be used in a nurse-led self-help format in primary care. This study sets out to test the hypothesis that usual care plus nurse-led self-help for recurrent depression in primary care is feasible, acceptable and cost-effective compared to usual care only.</p> <p>Design</p> <p>Patients are randomly assigned to ‘nurse-led self-help treatment plus usual care’ (134 participants) or ‘usual care’ (134 participants). Randomisation is stratified according to the number of previous episodes (2 or 3 previous episodes versus 4 or more). The primary clinical outcome is the cumulative recurrence rate of depression meeting DSM-IV criteria as assessed by the Structured-Clinical-Interview-for-DSM-IV- disorders at one year after completion of the intervention. Secondary clinical outcomes are quality of life, severity of depressive symptoms, co-morbid psychopathology and self-efficacy. As putative effect-moderators, demographic characteristics, number of previous episodes, type of treatment during previous episodes, age of onset, self-efficacy and symptoms of pain and fatigue are assessed. Cumulative recurrence rate ratios are obtained under a Poisson regression model. Number-needed-to-be-treated is calculated as the inverse of the risk-difference. The economic evaluation is conducted from a societal perspective, both as a cost-effectiveness analysis (costs per depression free survival year) and as a cost-utility analysis (costs per quality adjusted life-year).</p> <p>Discussion</p> <p>The purpose of this paper is to outline the rationale and design of a nurse-led, cognitive therapy based self-help aimed at preventing recurrence of depression in a primary care setting. Only few studies have focused on psychological self-help interventions aimed at the prevention of recurrences in primary care patients.</p> <p>Trial registration</p> <p>NTR3001 (<url>http://www.trialregister.nl</url>)</p

Dissociable Modulation of Overt Visual Attention in Valence and Arousal Revealed by Topology of Scan Path

Emotional stimuli have evolutionary significance for the survival of organisms; therefore, they are attention-grabbing and are processed preferentially. The neural underpinnings of two principle emotional dimensions in affective space, valence (degree of pleasantness) and arousal (intensity of evoked emotion), have been shown to be dissociable in the olfactory, gustatory and memory systems. However, the separable roles of valence and arousal in scene perception are poorly understood. In this study, we asked how these two emotional dimensions modulate overt visual attention. Twenty-two healthy volunteers freely viewed images from the International Affective Picture System (IAPS) that were graded for affective levels of valence and arousal (high, medium, and low). Subjects' heads were immobilized and eye movements were recorded by camera to track overt shifts of visual attention. Algebraic graph-based approaches were introduced to model scan paths as weighted undirected path graphs, generating global topology metrics that characterize the algebraic connectivity of scan paths. Our data suggest that human subjects show different scanning patterns to stimuli with different affective ratings. Valence salient stimuli (with neutral arousal) elicited faster and larger shifts of attention, while arousal salient stimuli (with neutral valence) elicited local scanning, dense attention allocation and deep processing. Furthermore, our model revealed that the modulatory effect of valence was linearly related to the valence level, whereas the relation between the modulatory effect and the level of arousal was nonlinear. Hence, visual attention seems to be modulated by mechanisms that are separate for valence and arousal