FLOWERS FOR ALGERNON: THE ETHICS OF HUMAN EXPERIMENTATION ON THE INTELLECTUALLY DISABLED

Flowers for Algernon is a novel written in 1966 by Daniel Keyes. Since its publication, it has received significant critical acclaim, earning a Nebula science-fiction award, and was also adapted into a feature film. Set in the 1960s, the novel follows the story of Charlie Gordon, an intellectually disabled man who lives a simple but happy life working a cleaning job at a local bakery. Charlie’s life, however, faces an abrupt change when he is offered the opportunity to participate in a novel surgical procedure to improve his intellect. Although he doesn’t fully understand the risks of the operation, consent is provided on his behalf by his estranged sister and Charlie undergoes the experiment. The experiment is a success and Charlie develops intellectually at an alarming pace, soon surpassing the experimenters themselves. The rest of the book follows the, not all positive, changes that this intellect brings to Charlie’s life. The novel is set in a time when American scientific experimentation could often occur without fully informed consent. This article explores the ethical side of such experiments like the one performed on Charlie, namely if it is morally right to perform a potentially dangerous experimental procedure on someone who doesn’t fully understand the risks, even if it will potentially help them

Practitioner Review: Therapeutics of unipolar major depressions in adolescents.

BACKGROUND: Over the past two decades new and key randomized controlled trials have reported the efficacy, clinical and cost effectiveness of psychological and pharmacological treatments for adolescents with major depression. METHODS: The literature was searched through pubmed, psychinfo, scopus and web of science for randomized controlled trials of current major depression together with meta-analyses and systematic reviews of trials between 2000 and 2017. Those specific to the adolescent years (11-18 years) were taken as the primary source for this narrative review. Additional selected studies in adults were used to illustrate methodological issues. RESULTS: Manualized psychological therapies and the SSRI fluoxetine are more effective than active placebo in the treatment of major depressions. Mild to moderate illnesses attending community-based services are likely to benefit from psychological treatment alone. Moderately to severely ill patients attending clinic and hospital services are likely to benefit from monotherapies or combining psychological and pharmacological treatment. Antidepressants carry a small but significant side-effect risk including increased suicidality. Side effects from psychotherapies are somewhat lower but specific negative consequences remain less well characterized. There is some evidence that CBT-based approaches prevent onset of major depression episode in well adolescents at high-risk. Other psychological interventions have not been adequately studied. There has been only limited identification of treatment moderators and no clear understanding of therapeutic mechanisms. CONCLUSIONS: There is now a range of clinically effective treatments for depressed adolescents. Future research needs to reveal moderators of and mechanisms for individual differences to treatment response, determine psychotherapies of value for milder depressions, enhance our understanding of safety and side-effects for all treatments, and consider how to reduce and treat treatment-resistant cases.The IMPACT study was funded by an award to IMG from the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project number 06/05/01). IMG is also supported by a strategic award from the Wellcome Trust to the University of Cambridge and University College London (095844/Z/11/Z)

A Systematic Review of Amenable Resilience Factors That Moderate and/or Mediate the Relationship Between Childhood Adversity and Mental Health in Young People.

Background: Up to half of Western children and adolescents experience at least one type of childhood adversity. Individuals with a history of childhood adversity have an increased risk of psychopathology. Resilience enhancing factors reduce the risk of psychopathology following childhood adversity. A comprehensive overview of empirically supported resilience factors is critically important for interventions aimed to increase resilience in young people. Moreover, such an overview may aid the development of novel resilience theories. Therefore, we conducted the first systematic review of social, emotional, cognitive and/or behavioral resilience factors after childhood adversity. Methods: We systematically searched Web of Science, PsycINFO, and Scopus (e.g., including MEDLINE) for English, Dutch, and German literature. We included cohort studies that examined whether a resilience factor was a moderator and/or a mediator for the relationship between childhood adversity and psychopathology in young people (mean age 13-24). Therefore, studies were included if the resilience factor was assessed prior to psychopathology, and childhood adversity was assessed no later than the resilience factor. Study data extraction was based on the STROBE report and study quality was assessed with an adapted version of Downs and Black's scale. The preregistered protocol can be found at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016051978. Results: The search identified 1969 studies, of which 22 were included (eight nationalities, study sample n range: 59-6780). We found empirical support for 13 of 25 individual-level (e.g., high self-esteem, low rumination), six of 12 family-level (e.g., high family cohesion, high parental involvement), and one of five community-level resilience factors (i.e., high social support), to benefit mental health in young people exposed to childhood adversity. Single vs. multiple resilience factor models supported the notion that resilience factors should not be studied in isolation, and that interrelations between resilience factors should be taken into account when predicting psychopathology after childhood adversity. Conclusions: Interventions that improve individual, family, and/or social support resilience factors may reduce the risk of psychopathology following childhood adversity. Future research should scrutinize whether resilience factors function as a complex interrelated system that benefits mental health resilience after childhood adversity.AvH is supported by the Royal Society (620 DH15017 & RGF\EA\180029), and MQ (MQBFC/2). JF is supported by the Medical Research Council Doctoral Training/Sackler Fund and the Pinsent Darwin Fund. HC was supported by CLAHRC - East of England at the time of data analysis. PW’s personal unrestricted research account paid for some incidental costs of obtaining papers. Funders of the authors played no role in the conduction or reporting of the systematic review

Oxygen Moment Formation and Canting in Li2CuO2

The possibilities of oxygen moment formation and canting in the quasi-1D cuprate Li2CuO2 are investigated using single crystal neutron diffraction at 2 K. The observed magnetic intensities could not be explained without the inclusion of a large ordered oxygen moment of 0.11(1) Bohr magnetons. Least-squares refinement of the magnetic structure of Li2CuO2 in combination with a spin-density Patterson analysis shows that the magnetization densities of the Cu and O atoms are highly aspherical, forming quasi-1D ribbons of localised Cu and O moments. Magnetic structure refinements and low-field magnetization measurements both suggest that the magnetic structure of Li2CuO2 at 2 K may be canted. A possible model for the canted configuration is proposed.Comment: 10 pages, 8 figures (screen resolution

Pathways to Increasing Adolescent Physical Activity and Wellbeing: A Mediation Analysis of Intervention Components Designed Using a Participatory Approach.

We assessed which intervention components were associated with change in moderate-to-vigorous physical activity (MVPA) and wellbeing through proposed psychosocial mediators. Eight schools (n = 1319; 13-14 years) ran GoActive, where older mentors and in-class-peer-leaders encouraged classes to conduct two new activities/week; students gained points and rewards for activity. We assessed exposures: participant-perceived engagement with components (post-intervention): older mentorship, peer leadership, class sessions, competition, rewards, points entered online; potential mediators (change from baseline): social support, self-efficacy, group cohesion, friendship quality, self-esteem; and outcomes (change from baseline): accelerometer-assessed MVPA (min/day), wellbeing (Warwick-Edinburgh). Mediation was assessed using linear regression models stratified by gender (adjusted for age, ethnicity, language, school, BMI z-score, baseline values), assessing associations between (1) exposures and mediators, (2) exposures and outcomes (without mediators) and (3) exposure and mediator with outcome using bootstrap resampling. No evidence was found to support the use of these components to increase physical activity. Among boys, higher perceived teacher and mentor support were associated with improved wellbeing via various mediators. Among girls, higher perceived mentor support and perception of competition and rewards were positively associated with wellbeing via self-efficacy, self-esteem and social support. If implemented well, mentorship could increase wellbeing among adolescents. Teacher support and class-based activity sessions may be important for boys' wellbeing, whereas rewards and competition warrant consideration among girls

Measurement Invariance in Longitudinal Bifactor Models: Review and Application Based on the p Factor.

Bifactor models are increasingly being utilized to study latent constructs such as psychopathology and cognition, which change over the lifespan. Although longitudinal measurement invariance (MI) testing helps ensure valid interpretation of change in a construct over time, this is rarely and inconsistently performed in bifactor models. Our review of MI simulation literature revealed that only one study assessed MI in bifactor models under limited conditions. Recommendations for how to assess MI in bifactor models are suggested based on existing simulation studies of related models. Estimator choice and influence of missing data on MI are also discussed. An empirical example based on a model of the general psychopathology factor (p) elucidates our recommendations, with the present model of p being the first to exhibit residual MI across gender and time. Thus, changes in the ordered-categorical indicators can be attributed to changes in the latent factors. However, further work is needed to clarify MI guidelines for bifactor models, including considering the impact of model complexity and number of indicators. Nonetheless, using the guidelines justified herein to establish MI allows findings from bifactor models to be more confidently interpreted, increasing their comparability and utility

Neurodevelopment and ages of onset in depressive disorders

How and why do clinical depressive disorders emerge in adolescence? In this Personal View, we present a neurodevelopmental theory to address causes for adolescent onsets of clinical depressive disorders. We argue that theories should account for three perplexing aspects of depressive disorders in adolescence: the episodic nature of depression; differences between sexes in rates of depression across development; and age-differentiated onsets. We consider how theories such as psychosocial acceleration, heterochronic brain development, dual-process models, glucocorticoid vulnerability hypothesis linked to early life stress, and epigenetic and genetic susceptibility might explain some aspects of adolescent depressive disorders. We argue that some synthesis between existing theories might be needed to establish a sufficient neurodevelopmental theoretical framework to explain onsets of depressive disorders in adolescence

Behavioral measures of impulsivity and compulsivity in adolescents with nonsuicidal self-injury.

BACKGROUND: Nonsuicidal self-injury (NSSI) is prevalent among adolescents and research is needed to clarify the mechanisms which contribute to the behavior. Here, the authors relate behavioral neurocognitive measures of impulsivity and compulsivity to repetitive and sporadic NSSI in a community sample of adolescents. METHODS: Computerized laboratory tasks (Affective Go/No-Go, Cambridge Gambling Task, and Probabilistic Reversal Task) were used to evaluate cognitive performance. Participants were adolescents aged 15 to 17 with (n = 50) and without (n = 190) NSSI history, sampled from the ROOTS project which recruited adolescents from secondary schools in Cambridgeshire, UK. NSSI was categorized as sporadic (1-3 instances per year) or repetitive (4 or more instances per year). Analyses were carried out in a series of linear and negative binomial regressions, controlling for age, gender, intelligence, and recent depressive symptoms. RESULTS: Adolescents with lifetime NSSI, and repetitive NSSI specifically, made significantly more perseverative errors on the Probabilistic Reversal Task and exhibited significantly lower quality of decision making on the Cambridge Gambling Task compared to no-NSSI controls. Those with sporadic NSSI did not significantly differ from no-NSSI controls on task performance. NSSI was not associated with behavioral measures of impulsivity. CONCLUSIONS: Repetitive NSSI is associated with increased behavioral compulsivity and disadvantageous decision making, but not with behavioral impulsivity. Future research should continue to investigate how neurocognitive phenotypes contribute to the onset and maintenance of NSSI, and determine whether compulsivity and addictive features of NSSI are potential targets for treatment

Momentum transfer using chirped standing wave fields: Bragg scattering

We consider momentum transfer using frequency-chirped standing wave fields. Novel atom-beam splitter and mirror schemes based on Bragg scattering are presented. It is shown that a predetermined number of photon momenta can be transferred to the atoms in a single interaction zone.Comment: 4 pages, 3 figure

Toward precision therapeutics: general and specific factors differentiate symptom change in depressed adolescents.

BACKGROUND: The longitudinal course of multiple symptom domains in adolescents treated for major depression is not known. Revealing the temporal course of general and specific psychopathology factors, including potential differences between psychotherapies, may aid therapeutic decision-making. METHODS: Participants were adolescents with major depressive disorder (aged 11-17; 75% female; N = 465) who were part of the IMPACT trial, a randomized controlled trial comparing cognitive behavioral therapy, short-term psychoanalytic psychotherapy, and brief psychosocial intervention. Self-reported symptoms at baseline and 6, 12, 36, 52, and 86 weeks postrandomization were analyzed with bifactor modeling. RESULTS: General psychopathology factor scores decreased across treatment and one-year follow-up. Specific melancholic features and depressive cognitions factors decreased from baseline to 6 weeks. Conduct problems decreased across treatment and follow-up. Anxiety increased by 6 weeks and then reverted to baseline levels. Obsessions-compulsions did not change. Changes in general and specific factors were not significantly different between the three psychotherapies during treatment. During follow-up, however, conduct problems decreased more in brief psychosocial intervention versus cognitive behavioral therapy (1.02, 95% Bayes credible interval 0.25, 1.96), but not versus short-term psychoanalytic psychotherapy. CONCLUSIONS: The clinical response signature in this trial is best revealed by rapid reductions in depression symptoms and general psychopathology. Protracted improvements in general psychopathology and conduct problems subsequently occur. Psychosocial treatments for adolescent depression have comparable effects on general and specific psychopathology, although a psychoeducational, goal-focused approach may be indicated for youth with comorbid conduct problems