On Dimensionality, Measurement Invariance, and Suitability of Sum Scores for the PHQ-9 and the GAD-7.

In psychiatry, severity of mental health conditions and their change over time are usually measured via sum scores of items on psychometric scales. However, inferences from such scores can be biased if psychometric properties such as unidimensionality and temporal measurement invariance for instruments are not met. Here, we aimed to evaluate these properties for common measures of depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder Assessment-7) in a large clinical sample (N = 22,362) undergoing psychotherapy. In addition, we tested consistency in dimensionality results across different methods (parallel analysis, factor analysis, explained common variance, the partial credit model, and the Mokken model). Results showed that while both Patient Health Questionnaire-9 and Generalized Anxiety Disorder Assessment-7 are multidimensional instruments with highly correlated factors, there is justification for sum scores as measures of severity. Temporal measurement invariance across 10 therapy sessions was evaluated. Strict temporal measurement invariance was established in both scales, allowing researchers to compare sum scores as severity measures across time.NIH

Clinically significant personality traits in individuals at high risk of developing psychosis

It is still unclear to what extent personality may influence the development of psychosis. We aimed to explore significant personality traits in individuals at high-risk (HR) for psychosis. Personalities of forty HR individuals and a matched sample of 40 HVs were evaluated with the Millon Multiaxial Inventory (MCMI-III). They were also assessed with the Positive and Negative Symptoms Scale (PANSS), Beck Depression and Anxiety Inventories (BDI-II and BAI), Global Assessment of Functioning (GAF) and Mini-International Neuropsychiatric Interview (MINI 6.0.0). Fisher's exact test was employed to compare frequency of traits. Mann-Whitney U test and logistic regression were used to establish relationships between traits and symptoms, and the effect of age, sex and symptoms on such traits. Most HR individuals (97.5%) had at least one significant trait; 75% had personality disorders, mainly depressive, borderline or schizotypal. Only histrionic and narcissistic traits were more prevalent in HVs. Negative symptoms were related to schizoid and paranoid traits. Depression was more severe with borderline traits. Most HR individuals (67.6%) had more than one DSM-IV Axis I diagnosis, mainly depressive/anxiety disorders. Transition rate was low (5%). Certain personality profiles may not be markers for conversions to psychosis but contribute to high morbidity in HR individuals

Prevention of breast cancer by recapitulation of pregnancy hormone levels

At the present time, the only approved method of breast cancer prevention is use of the selective estrogen receptor modulator (SERM) tamoxifen. Many breast cancers are driven to grow by estrogen, and tamoxifen exploits this by blocking estrogen action at the estrogen receptor. A counter-intuitive and controversial approach to breast cancer prevention is administration of estrogen and progestin at an early age to achieve pregnancy levels. This approach is supported by the fact that breast cancer incidence is halved by early (≤ 20 years of age) full-term pregnancy. Moreover, it has been demonstrated in rodent models that mimicking the hormonal milieu can effectively prevent carcinogen-induced mammary cancer. In this issue of Breast Cancer Research Rajkumar and colleagues use the rodent model to further define the timing and type of hormonal therapy that is effective in preventing mammary carcinogenesis. Clearly, application of this approach in humans may be difficult, but the potential benefit is intriguing

Comparison of high and low intensity contact between secondary and primary care to detect people at ultra-high risk for psychosis: study protocol for a theory-based, cluster randomized controlled trial.

BACKGROUND: The early detection and referral to specialized services of young people at ultra-high risk (UHR) for psychosis may reduce the duration of untreated psychosis and, therefore, improve prognosis. General practitioners (GPs) are usually the healthcare professionals contacted first on the help-seeking pathway of these individuals. METHODS/DESIGN: This is a cluster randomized controlled trial (cRCT) of primary care practices in Cambridgeshire and Peterborough, UK. Practices are randomly allocated into two groups in order to establish which is the most effective and cost-effective way to identify people at UHR for psychosis. One group will receive postal information about the local early intervention in psychosis service, including how to identify young people who may be in the early stages of a psychotic illness. The second group will receive the same information plus an additional, ongoing theory-based educational intervention with dedicated liaison practitioners to train clinical staff at each site. The primary outcome of this trial is count data over a 2-year period: the yield - number of UHR for psychosis referrals to a specialist early intervention in psychosis service - per primary care practice. DISCUSSION: There is little guidance on the essential components of effective and cost-effective educational interventions in primary mental health care. Furthermore, no study has demonstrated an effect of a theory-based intervention to help GPs identify young people at UHR for psychosis. This study protocol is underpinned by a robust scientific rationale that intends to address these limitations. TRIAL REGISTRATION: Current Controlled Trials ISRCTN70185866.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Determinants of patient-reported outcome trajectories and symptomatic recovery in Improving Access to Psychological Therapies (IAPT) services.

BACKGROUND: Despite evidence for the general effectiveness of psychological therapies, there exists substantial heterogeneity in patient outcomes. We aimed to identify factors associated with baseline severity of depression and anxiety symptoms, rate of symptomatic change over the course of therapy, and symptomatic recovery in a primary mental health care setting. METHODS: Using data from a service evaluation involving 35 527 patients in England's psychological and wellbeing [Improving Access to Psychological Therapies (IAPT)] services, we applied latent growth models to explore which routinely-collected sociodemographic, clinical, and therapeutic variables were associated with baseline symptom severity and rate of symptomatic change. We used a multilevel logit model to determine variables associated with symptomatic recovery. RESULTS: Being female, younger, more functionally impaired, and more socioeconomically disadvantaged was associated with higher baseline severity of both depression and anxiety symptoms. Being older, less functionally impaired, and having more severe baseline symptomatology was associated with more rapid improvement of both depression and anxiety symptoms (male gender and greater socioeconomic disadvantage were further associated with rate of change for depression only). Therapy intensity and appointment frequency seemed to have no correlation with rate of symptomatic improvement. Patients with lower baseline symptom severity, less functional impairment, and older age had a greater likelihood of achieving symptomatic recovery (as defined by IAPT criteria). CONCLUSIONS: We must continue to investigate how best to tailor psychotherapeutic interventions to fit patients' needs. Patients who begin therapy with more severe depression and/or anxiety symptoms and poorer functioning merit special attention, as these characteristics may negatively impact recovery.NIHR, Gates Cambridge Trus

Attachment styles and clinical correlates in people at ultra high risk for psychosis.

Evidence suggests that attachment styles may influence subclinical psychosis phenotypes (schizotypy) and affective disorders and may play a part in the association between psychosis and childhood adversity. However, the role of attachment in the initial stages of psychosis remains poorly understood. Our main aim was to describe and compare attachment styles in 60 individuals at ultra high risk for psychosis (UHR) and a matched sample of 60 healthy volunteers (HV). The HV had lower anxious and avoidant attachment scores than the UHR individuals (p < .001). Sixty-nine percentage of the UHR group had more than one DSM-IV diagnosis, mainly affective and anxiety disorders. The UHR group experienced more trauma (p < .001) and more mood and anxiety symptoms (p < .001). Interestingly, in our UHR group, only schizotypy paranoia was correlated with insecure attachment. In the HV group, depression, anxiety, schizotypy paranoia, and social anxiety were correlated with insecure attachment. This difference and some discrepancies with previous studies involving UHR suggest that individuals at UHR may compose a heterogeneous group; some experience significant mood and/or anxiety symptoms that may not be explained by specific attachment styles. Nonetheless, measuring attachment in UHR individuals could help maximize therapeutic relationships to enhance recovery.This work was supported by the National Institute for Health Research (NIHR) Programme Grant RP-PG-0606-1335 ‘Understanding Causes and Developing Effective Interventions for Schizophrenia and Other Psychoses’. This work forms part of the NIHR Collaboration for Leadership in Applied Health Research & Care East of England

Autophagy in the eye:from physiology to pathophysology

Autophagy is a catabolic self-degradative pathway that promotes the degradation and recycling of intracellular material through the lysosomal compartment. Although first believed to function in conditions of nutritional stress, autophagy is emerging as a critical cellular pathway, involved in a variety of physiological and pathophysiological processes. Autophagy dysregulation is associated with an increasing number of diseases, including ocular diseases. On one hand, mutations in autophagy-related genes have been linked to cataracts, glaucoma, and corneal dystrophy; on the other hand, alterations in autophagy and lysosomal pathways are a common finding in essentially all diseases of the eye. Moreover, LC3-associated phagocytosis, a form of non-canonical autophagy, is critical in promoting visual cycle function. This review collects the latest understanding of autophagy in the context of the eye. We will review and discuss the respective roles of autophagy in the physiology and/or pathophysiology of each of the ocular tissues, its diurnal/circadian variation, as well as its involvement in diseases of the eye

Clinical effectiveness and cost-effectiveness of tailored intensive liaison between primary and secondary care to identify individuals at risk of a first psychotic illness (the LEGs study): a cluster-randomised controlled trial.

BACKGROUND: General practitioners are usually the first health professionals to be contacted by people with early signs of psychosis. We aimed to assess whether increased liaison between primary and secondary care improves the clinical effectiveness and cost-effectiveness of detection of people with, or at high risk of developing, a first psychotic illness. METHODS: Our Liaison and Education in General Practices (LEGs) study was a cluster-randomised controlled trial of primary care practices (clusters) in Cambridgeshire and Peterborough, UK. Consenting practices were randomly allocated (1:1) to a 2 year low-intensity intervention (a postal campaign, consisting of biannual guidelines to help identify and refer individuals with early signs of psychosis) or a high-intensity intervention, which additionally included a specialist mental health professional who liaised with every practice and a theory-based educational package. Practices were not masked to group allocation. Practices that did not consent to be randomly assigned comprised a practice-as-usual (PAU) group. The primary outcome was number of referrals of patients at high risk of developing psychosis to the early intervention service per practice site. New referrals were assessed clinically and stratified into those who met criteria for high risk or first-episode psychotic illness (FEP; together: psychosis true positives), and those who did not fulfil such criteria for psychosis (false positives). Referrals from PAU practices were also analysed. We assessed cost-effectiveness with decision analytic modelling in terms of the incremental cost per additional true positive identified. The trial is registered at the ISRCTN registry, number ISRCTN70185866. FINDINGS: Between Dec 22, 2009, and Sept 7, 2010, 54 of 104 eligible practices provided consent and between Feb 16, 2010, and Feb 11, 2011, these practices were randomly allocated to interventions (28 to low intensity and 26 to high intensity); the remaining 50 practices comprised the PAU group. Two high-intensity practices were excluded from the analysis. In the 2 year intervention period, high-intensity practices referred more FEP cases than did low-intensity practices (mean 1.25 [SD 1.2] for high intensity vs 0.7 [0.9] for low intensity; incidence rate ratio [IRR] 1.9, 95% CI 1.05-3.4, p=0.04), although the difference was not statistically significant for individuals at high risk of psychosis (0.9 [1.0] vs 0.5 [1.0]; 2.2, 0.9-5.1, p=0.08). For high risk and FEP combined, high-intensity practices referred both more true-positive (2.2 [1.7] vs 1.1 [1.7]; 2.0, 1.1-3.6, p=0.02) and false-positive (2.3 [2.4] vs 0.9 [1.2]; 2.6, 1.3-5.0, p=0.005) cases. Referral patterns did not differ between low-intensity and PAU practices. Total cost per true-positive referral in the 2 year follow-up was £26,785 in high-intensity practices, £27,840 in low-intensity practices, and £30,007 in PAU practices. INTERPRETATION: This intensive intervention to improve liaison between primary and secondary care for people with early signs of psychosis was clinically and cost effective. FUNDING: UK National Institute for Health Research.The authors acknowledge funding support from a National Institute for Health Research Programme Grant for Applied Research (NIHR PGfAR) programme (RP-PG-0606-1335; “Understanding Causes and Developing Effective Interventions for Schizophrenia and Other Psychoses”) awarded to PBJ. The work forms part of the NIHR Collaboration for Leadership in Applied Health Research & Care East of England (CLAHRC-EoE).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/S2215-0366(15)00157-

Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects

In gravitational-wave detection, special emphasis is put onto searches that focus on cosmic events detected by other types of astrophysical observatories. The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical telescopes and neutrino observatories, provide a trigger time for analyzing gravitational wave data coincident with the event. In certain cases the expected frequency range, source energetics, directional and progenitor information is also available. Beyond allowing the recognition of gravitational waveforms with amplitudes closer to the noise floor of the detector, these triggered searches should also lead to rich science results even before the onset of Advanced LIGO. In this paper we provide a broad review of LIGO's astrophysically triggered searches and the sources they target

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000