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Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD).
Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons.
In case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74).
Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.
We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.
We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).
Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.
Although attenuated psychotic symptoms in the psychosis clinical high-risk state (CHR-P) almost always occur in the context of a non-psychotic disorder (NPD), NPD is considered an undesired 'comorbidity' epiphenomenon rather than an integral part of CHR-P itself. Prospective work, however, indicates that much more of the clinical psychosis incidence is attributable to prior mood and drug use disorders than to psychosis clinical high-risk states per se. In order to examine this conundrum, we analysed to what degree the 'risk' in CHR-P is indexed by co-present NPD rather than attenuated psychosis per se.
We examined the incidence of early psychotic experiences (PE) with and without NPD (mood disorders, anxiety disorders, alcohol/drug use disorders), in a prospective general population cohort (n = 6123 at risk of incident PE at baseline). Four interview waves were conducted between 2007 and 2018 (NEMESIS-2). The incidence of PE, alone (PE-only) or with NPD (PE + NPD) was calculated, as were differential associations with schizophrenia polygenic risk score (PRS-Sz), environmental, demographical, clinical and cognitive factors.
The incidence of PE + NPD (0.37%) was lower than the incidence of PE-only (1.04%), representing around a third of the total yearly incidence of PE. Incident PE + NPD was, in comparison with PE-only, differentially characterised by poor functioning, environmental risks, PRS-Sz, positive family history, prescription of antipsychotic medication and (mental) health service use.
The risk in 'clinical high risk' states is mediated not by attenuated psychosis per se but specifically the combination of attenuated psychosis and NPD. CHR-P/APS research should be reconceptualised from a focus on attenuated psychotic symptoms with exclusion of non-psychotic DSM-disorders, as the 'pure' representation of a supposedly homotypic psychosis risk state, towards a focus on poor-outcome NPDs, characterised by a degree of psychosis admixture, on the pathway to psychotic disorder outcomes.
Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.
To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.
We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.
Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015–0.017), with carriers being 7.5–7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.
This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.
This study attempted to replicate whether a bias in probabilistic reasoning, or 'jumping to conclusions'(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.
Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.
JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.
These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.
It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
The 'jumping to conclusions' (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.
A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.
The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients.
Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.
Attention-deficit hyperactivity disorder (ADHD) is associated with later depression and there is considerable genetic overlap between them. This study investigated if ADHD and ADHD genetic liability are causally related to depression using two different methods.
First, a longitudinal population cohort design was used to assess the association between childhood ADHD (age 7 years) and recurrent depression in young-adulthood (age 18–25 years) in N = 8310 individuals in the Avon Longitudinal Study of Parents and Children (ALSPAC). Second, two-sample Mendelian randomization (MR) analyses examined relationships between genetic liability for ADHD and depression utilising published Genome-Wide Association Study (GWAS) data.
Childhood ADHD was associated with an increased risk of recurrent depression in young-adulthood (OR 1.35, 95% CI 1.05–1.73). MR analyses suggested a causal effect of ADHD genetic liability on major depression (OR 1.21, 95% CI 1.12–1.31). MR findings using a broader definition of depression differed, showing a weak influence on depression (OR 1.07, 95% CI 1.02–1.13).
Our findings suggest that ADHD increases the risk of depression later in life and are consistent with a causal effect of ADHD genetic liability on subsequent major depression. However, findings were different for more broadly defined depression.
Around 30% of individuals with schizophrenia remain symptomatic and significantly impaired despite antipsychotic treatment and are considered to be treatment resistant. Clinicians are currently unable to predict which patients are at higher risk of treatment resistance.
To determine whether genetic liability for schizophrenia and/or clinical characteristics measurable at illness onset can prospectively indicate a higher risk of treatment-resistant psychosis (TRP).
In 1070 individuals with schizophrenia or related psychotic disorders, schizophrenia polygenic risk scores (PRS) and large copy number variations (CNVs) were assessed for enrichment in TRP. Regression and machine-learning approaches were used to investigate the association of phenotypes related to demographics, family history, premorbid factors and illness onset with TRP.
Younger age at onset (odds ratio 0.94, P = 7.79 × 10−13) and poor premorbid social adjustment (odds ratio 1.64, P = 2.41 × 10−4) increased risk of TRP in univariate regression analyses. These factors remained associated in multivariate regression analyses, which also found lower premorbid IQ (odds ratio 0.98, P = 7.76 × 10−3), younger father's age at birth (odds ratio 0.97, P = 0.015) and cannabis use (odds ratio 1.60, P = 0.025) increased the risk of TRP. Machine-learning approaches found age at onset to be the most important predictor and also identified premorbid IQ and poor social adjustment as predictors of TRP, mirroring findings from regression analyses. Genetic liability for schizophrenia was not associated with TRP.
People with an earlier age at onset of psychosis and poor premorbid functioning are more likely to be treatment resistant. The genetic architecture of susceptibility to schizophrenia may be distinct from that of treatment outcomes.
Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.
We aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.
We called CNVs in the full UK Biobank sample and analysed data from 420 247 individuals who passed CNV quality control, reported White British or Irish ancestry and were not diagnosed with neurodevelopmental disorders. We analysed 33 pathogenic CNVs, including their reciprocal deletions/duplications, for association with seven cognitive tests and four general measures of functioning: academic qualifications, occupation, household income and Townsend Deprivation Index.
Most CNVs (24 out of 33) were associated with reduced performance on at least one cognitive test or measure of functioning. The changes on the cognitive tests were modest (average reduction of 0.13 s.d.) but varied markedly between CNVs. All 12 schizophrenia-associated CNVs were associated with significant impairments on measures of functioning.
CNVs implicated in neurodevelopmental disorders, including schizophrenia, are associated with cognitive deficits, even among unaffected individuals. These deficits may be subtle but CNV carriers have significant disadvantages in educational attainment and ability to earn income in adult life.
Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.
We examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia.
Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and – using linear regression – total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children).
Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode.
The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.
The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.
This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.
A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.
Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.
There is strong evidence that people born in winter and in spring have a small increased risk of schizophrenia. As this 'season of birth' effect underpins some of the most influential hypotheses concerning potentially modifiable risk exposures, it is important to exclude other possible explanations for the phenomenon.
Here we sought to determine whether the season of birth effect reflects gene-environment confounding rather than a pathogenic process indexing environmental exposure. We directly measured, in 136 538 participants from the UK Biobank (UKBB), the burdens of common schizophrenia risk alleles and of copy number variants known to increase the risk for the disorder, and tested whether these were correlated with a season of birth.
Neither genetic measure was associated with season or month of birth within the UKBB sample.
As our study was highly powered to detect small effects, we conclude that the season of birth effect in schizophrenia reflects a true pathogenic effect of environmental exposure.
Previous studies find that both schizophrenia and mood disorder risk alleles contribute to adult depression and anxiety. Emotional problems (depression or anxiety) begin in childhood and show strong continuities into adult life; this suggests that symptoms are the manifestation of the same underlying liability across different ages. However, other findings suggest that there are developmental differences in the etiology of emotional problems at different ages. To our knowledge, no study has prospectively examined the impact of psychiatric risk alleles on emotional problems at different ages in the same individuals.
Data were analyzed using regression-based analyses in a prospective, population-based UK cohort (the National Child Development Study). Schizophrenia and major depressive disorder (MDD) polygenic risk scores (PRS) were derived from published Psychiatric Genomics Consortium genome-wide association studies. Emotional problems were assessed prospectively at six time points from age 7 to 42 years.
Schizophrenia PRS were associated with emotional problems from childhood [age 7, OR 1.09 (1.03–1.15), p = 0.003] to mid-life [age 42, OR 1.10 (1.05–1.17), p < 0.001], while MDD PRS were associated with emotional problems only in adulthood [age 42, OR 1.06 (1.00–1.11), p = 0.034; age 7, OR 1.03 (0.98–1.09), p = 0.228].
Our prospective investigation suggests that early (childhood) emotional problems in the general population share genetic risk with schizophrenia, while later (adult) emotional problems also share genetic risk with MDD. The results suggest that the genetic architecture of depression/anxiety is not static across development.
Traditionally, personalised nutrition was delivered at an individual level. However, the concept of delivering tailored dietary advice at a group level through the identification of metabotypes or groups of metabolically similar individuals has emerged. Although this approach to personalised nutrition looks promising, further work is needed to examine this concept across a wider population group. Therefore, the objectives of this study are to: (1) identify metabotypes in a European population and (2) develop targeted dietary advice solutions for these metabotypes. Using data from the Food4Me study (n 1607), k-means cluster analysis revealed the presence of three metabolically distinct clusters based on twenty-seven metabolic markers including cholesterol, individual fatty acids and carotenoids. Cluster 2 was identified as a metabolically healthy metabotype as these individuals had the highest Omega-3 Index (6·56 (sd 1·29) %), carotenoids (2·15 (sd 0·71) µm) and lowest total saturated fat levels. On the basis of its fatty acid profile, cluster 1 was characterised as a metabolically unhealthy cluster. Targeted dietary advice solutions were developed per cluster using a decision tree approach. Testing of the approach was performed by comparison with the personalised dietary advice, delivered by nutritionists to Food4Me study participants (n 180). Excellent agreement was observed between the targeted and individualised approaches with an average match of 82 % at the level of delivery of the same dietary message. Future work should ascertain whether this proposed method could be utilised in a healthcare setting, for the rapid and efficient delivery of tailored dietary advice solutions.
It is postulated that knowledge of genotype may be more powerful than other types of personalised information in terms of motivating behaviour change. However, there is also a danger that disclosure of genetic risk may promote a fatalistic attitude and demotivate individuals. The original concept of personalised nutrition (PN) focused on genotype-based tailored dietary advice; however, PN can also be delivered based on assessment of dietary intake and phenotypic measures. Whilst dietitians currently provide PN advice based on diet and phenotype, genotype-based PN advice is not so readily available. The aim of this review is to examine the evidence for genotype-based personalised information on motivating behaviour change, and factors which may affect the impact of genotype-based personalised advice. Recent findings in PN will also be discussed, with respect to a large European study, Food4Me, which investigated the impact of varying levels of PN advice on motivating behaviour change. The researchers reported that PN advice resulted in greater dietary changes compared with general healthy eating advice, but no additional benefit was observed for PN advice based on phenotype and genotype information. Within Food4Me, work from our group revealed that knowledge of MTHFR genotype did not significantly improve intakes of dietary folate. In general, evidence is weak with regard to genotype-based PN advice. For future work, studies should test the impact of PN advice developed on a strong nutrigenetic evidence base, ensure an appropriate study design for the research question asked, and incorporate behaviour change techniques into the intervention.
Over a decade since the completion of the human genome sequence, the promise of personalised nutrition available to all has yet to become a reality. While the definition was originally very gene-focused, in recent years, a model of personalised nutrition has emerged with the incorporation of dietary, phenotypic and genotypic information at various levels. Developing on from the idea of personalised nutrition, the concept of targeted nutrition has evolved which refers to the delivery of tailored dietary advice at a group level rather than at an individual level. Central to this concept is metabotyping or metabolic phenotyping, which is the ability to group similar individuals together based on their metabolic or phenotypic profiles. Applications of the metabotyping concept extend from the nutrition to the medical literature. While there are many examples of the metabotype approach, there is a dearth in the literature with regard to the development of tailored interventions for groups of individuals. This review will first explore the effectiveness of personalised nutrition in motivating behaviour change and secondly, examine potential novel ways for the delivery of personalised advice at a population level through a metabotyping approach. Based on recent findings from our work, we will demonstrate a novel strategy for the delivery of tailored dietary advice at a group level using this concept. In general, there is a strong emerging evidence to support the effectiveness of personalised nutrition; future work should ascertain if targeted nutrition can motivate behaviour change in a similar manner.
A number of copy number variants (CNVs) have been suggested as
susceptibility factors for schizophrenia. For some of these the data
remain equivocal, and the frequency in individuals with schizophrenia is
To determine the contribution of CNVs at 15 schizophrenia-associated loci
(a) using a large new data-set of patients with schizophrenia
(n = 6882) and controls (n = 6316),
and (b) combining our results with those from previous studies.
We used Illumina microarrays to analyse our data. Analyses were
restricted to 520 766 probes common to all arrays used in the different
We found higher rates in participants with schizophrenia than in controls
for 13 of the 15 previously implicated CNVs. Six were nominally
significantly associated (P<0.05) in this new
data-set: deletions at 1q21.1, NRXN1, 15q11.2 and
22q11.2 and duplications at 16p11.2 and the Angelman/Prader–Willi
Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were
of maternal origin. When combined with published data, 11 of the 15 loci
showed highly significant evidence for association with schizophrenia
We strengthen the support for the majority of the previously implicated
CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9%
of controls carry a large, detectable CNV at one of these loci. Routine
CNV screening may be clinically appropriate given the high rate of known
deleterious mutations in the disorder and the comorbidity associated with
these heritable mutations.
Antidepressant prescribing is widespread. Nonetheless, response to antidepressants is variable. If it was possible to predict response to medication and thus tailor treatment accordingly, this would not only improve patient outcomes but may also have economic benefits.
To test the hypothesis that individuals with more severe depression would benefit more from noradrenaline reuptake inhibitors (NARIs) than selective serotonin reuptake inhibitors (SSRIs) compared with individuals with less severe depression.
Individuals recruited from UK primary care who met ICD-10 criteria for a depressive episode and scored 15 or more on the Beck Depression Inventory (BDI) were randomised to either an SSRI (citalopram 20mg daily) or a NARI (reboxetine 4mg twice daily). Randomisation was by means of a remote automated telephone system. The main outcome was depressive symptoms measured by the BDI total score 6 weeks after randomisation. (Trial registration: ISRCTN31345163.)
In total, 601 participants were randomised (citalopram: n = 298, reboxetine: n = 303). Ninety-one per cent were followed up at 6 weeks (citalopram: n = 274, reboxetine: n = 272). There was little evidence to support an interaction between treatment and severity of depression (interaction term: 0.02, 95% CI −0.59 to 0.62, P = 0.96). Adjustment for potential confounders (age, gender, employment status, history of depression, number of life events and social support) did not affect the findings (interaction term: 0.06, 95% CI −0.54 to 0.66, P = 0.85).
Treatment with NARIs does not confer any advantage over SSRI treatment for outcome in those with more severe depressive illness presenting in primary care.
Email your librarian or administrator to recommend adding this to your organisation's collection.


text: Rod Colón Rod Colón brings over 25 years of experience coaching and consulting today's professionals and executives to his role as HISPA Role Model Development Director. In this position, Colón serves as a role model to role models, focusing on the recruitment, retention, and professional development of HISPA volunteers; consulting with partner organizations; and advising on ERG best practices. A long-time HISPA supporter, Colón exemplifies what it means to lead by example: he has been an active HISPA Role Model for over eight years and has served as the New Jersey Governor's Hispanic Fellows HISPA Leadership Series Co-Lead for the past four. An in-demand executive coach and professional speaker, he reveals the depth of his experience as a corporate HR management insider, outside agency recruiter, professional networker and career coach. He aggressively challenges professionals to be relentless in building their networking skills while viewing managing their careers as a business. Colón is also an accomplished author, blogger, and radio talk show host, where he discusses career strategy, professional development, and the need for networking and human relationships as a major part of any job search. Colón's unfailing desire to mentor, coach, train and advise in all matters related to career management and personal growth has earned many awards and honors, including being inducted into the Georgian Court University Alumni Court of Honor in 2011. He has been featured on ABC-TV "Tiempo" with Joe Torres, FOX 29, NEWS12 New Jersey "It's Your Money" with Eric Landskroner, BRONXNET "Open" with Dr. Bob Lee, LatinTRENDS, Newark Examiner, Princeton Review and has received numerous recognitions and citations in both print and online media. His professional background includes over a decade serving in executive positions with JP Morgan and Bankers Trust. He also consults professional groups, colleges and corporate leaders in what it means to run a career in the same way a CEO runs a business.

subset: commoncrawl


text:
HJC Should Ask Bill Barr Why It Would Do Irreparable Harm if He Had to Explain His Actions in the Flynn Case
Unless he comes up with some new excuse, tomorrow Billy Barr will finally show up for an oversight hearing in the House Judiciary Committee.
There are a number of sets of questions that commentators have suggested for the hearing (a strategic set of four topics that will show how Barr is hurting the US, an updated set from JustSecurity, some questions about Geoffrey Berman's firing).
I could come up with similar lists. They'd be long and — by the time anyone executed them competently on the Democratic side — the big media outlets would have already filed their story on the hearing.
One thing that should be included, however, is the letter that Sidney Powell sent Barr and Jeffrey Rosen in June 2019 and Bill Barr's actions to deliver on her demands in the subsequent year, actions that DOJ itself admits would do irreparable harm if DOJ had to explain.
The letter was effectively a road map of demands, many of them based off hoaxes, almost all of them unrelated to Flynn's prosecution or false. It later became the Brady demand that Judge Emmet Sullivan rejected in a meticulous opinion last December. In it, Powell demanded that DOJ conduct a review of the prosecution and then dismiss the prosecution.
At the end of this internal review, we believe there will be ample justification for the Department to follow the precedent of the Ted Stevens case and move to dismiss the prosecution in the interest of justice — whether it be we ink a simple joint motion or sua sponte by the Department.
NYT wrote about this letter in June, calling it "little noticed" but predictably not crediting me, who did noticed it and wrote about it repeatedly.
HJC should raise this letter with Billy Barr for several reasons. First, little in the letter turned out to be true. Indeed, DOJ has asserted in court filings that even where documents Powell asked for existed, none of it was Brady material (and in fact, in spite of Timothy Shea's claim that these materials were new, that was false, meaning DOJ has no justification for flip-flopping on its call for prison time for Flynn from earlier this year). Powell should have gotten none of it, and yet Barr invented an unprecedented process to give it to her and then use it to self-sabotage the case.
More importantly, the way in which Barr has rolled out the release of these documents has served, in part, to hide the shoddiness of Timothy Shea's motion to dismiss. Based off a misrepresentation of Bill Priestap's notes, Shea pretended that the interview with Flynn focused exclusively on the Logan Act. That wasn't even an accurate reading of Priestap's own notes. Since then, DOJ has released several more documents that make it clear FBI's focus was on whether Flynn was a foreign agent (and also provide more evidence that the Flynn 302s track the Agents' description of the interview), documents that undermine their own motion to dismiss. They've either withheld a Bill Priestap 302 explaining what happened or Powell has decided it doesn't help her. And there are more records that they are sitting on that undermine the claims in their motion to dismiss.
Importantly, while DOJ was making claims that Flynn's lies were not material, John Ratcliffe was releasing documents that explained why they were. Of particular note, on February 14, 2017 — weeks after all the meetings DOJ has been focused on, Peter Strzok, in an annotation that made it clear he did not have it in for Trump or his flunkies, also made it clear that FBI didn't have any phone records yet.
We have very few call logs. NSLs have been issued for Manafort, Page, and Flynn, many of which have not yet been returned.
On February 25, notes from Tashina Gauhar make clear, Strzok and Joe Pientka believed Flynn didn't believe he had been lying. They also judged — not having phone records or much else yet — that they did not think he was an agent, but they needed to verify that.
That got translated into a later draft summary into a conclusion that Flynn wasn't a foreign agent.
But as FBI would get first call logs (which would reveal Flynn had also lied about being in contact with Mar-a-Lag0) and then his texts (which would make it clear Flynn knew well about the sanctions Obama had imposed), that would dramatically change the import of his lies. By the time he started cooperating, Flynn made it clear that he and KT McFarland had immediately set about trying to cover up the response Sergey Kislyak gave to Flynn's request.
After the briefing, Flynn and McFarland spoke over the phone. 1258 Flynn reported on the substance of his call with Kislyak, including their discussion of the sanctions. 1259 According to McFarland, Flynn mentioned that the Russian response to the sanctions was not going to be escalatory because they wanted a good relationship with the incoming Administration.1260 McFarland also gave Flynn a summary of her recent briefing with President-Elect Trump. 1261
The next day, December 30, 2016, Russian Foreign Minister Sergey Lavrov remarked that Russia would respond in kind to the sanctions. 1262 Putin superseded that comment two hours later, releasing a statement that Russia would not take retaliatory measures in response to the sanctions at that time. 1263 Hours later President-Elect Trump tweeted, "Great move on delay (by V. Putin)." 1264 Shortly thereafter, Flynn sent a text message to McFarland summarizing his call with Kislyak from the day before, which she emailed to Kushner, Bannon, Priebus, and other Transition Team members. 1265 The text message and email did not include sanctions as one of the topics discussed with Kislyak. 1266 Flynn told the Office that he did not document his discussion of sanctions because it could be perceived as getting in the way of the Obama Administration's foreign policy.1267 [my emphasis]
KT McFarland's 302s would show she told the same untruths that Flynn had told, even after he got fired for telling them. More recently, it became clear that the White House scripted Bannon to deny discussing sanctions as well.
Meanwhile, the government is still withholding the first (known) post-election transcript between Flynn and Kislyak, where he first started this game of deal-making with the country that just attacked us.
All these details may not amount to Flynn acting as an Agent of Russia.
Rather, they amount to a concerted cover-up of the White House role in this sanction discussion. That's a topic that a sentencing memorandum approved by top people in Bill Barr's DOJ argued was significant and material, because a concerted effort to undermine sanctions on Russia, "could have been evidence of links or coordination between the Trump Campaign and Russia."
The defendant's false statements to the FBI were significant. When it interviewed the defendant, the FBI did not know the totality of what had occurred between the defendant and the Russians. Any effort to undermine the recently imposed sanctions, which were enacted to punish the Russian government for interfering in the 2016 election, could have been evidence of links or coordination between the Trump Campaign and Russia.
The concerted effort to hide the extensive coordination on sanctions — involving at least Flynn, McFarland, and Bannon — was designed hide whether the Trump response to Obama's sanctions amounted to the kind of quid pro quo Mueller was appointed to investigate. A question on sanctions relief is the single one that Trump totally blew off in his responses to Mueller.
DOJ wants to claim that Flynn's conversations with Sergey Kislyak were totally normal. But not only are they still hiding at least one of them, but they were utterly material to the Mueller investigation.
But then there's the final reason why HJC should question Barr about the letter from Sidney Powell that he apparently delivered on a year after she demanded: DOJ itself admitted that explaining DOJ's actions here would do irreparable harm.
The more interesting argument came from Wall. He argued, repeatedly, that DOJ will be irreparably harmed if Sullivan is permitted to hold a hearing on DOJ's motion to dismiss. In particular, he seemed horrified that Sullivan might require sworn declarations of affidavits.
As Beth Wilkinson, arguing for Sullivan, mentioned, neither Sullivan nor Amicus John Gleeson has called for such a thing. Both are simply moving towards a hearing scheduled for July 16. Wilkinson also noted that District courts hold such hearings all the time. (And they predictably will have to in another case where DOJ has moved to end a prosecution recently, in which — unlike this case — there appears to have been prosecutorial misconduct, Ali Sadr Hashemi Nejad, which I'll return to).
Wall is literally arguing that DOJ will be permanently damaged if it has to show up and answer for its actions in this case (in particular, to explain why the prosecutors in this case didn't sign the motion to dismiss).
That Wall argued so forcibly as to the injury that DOJ would suffer if it had to show up and defend its motion to dismiss is all the crazier given that they didn't file the petition. The only harm that matters here procedurally is any harm to Flynn, not DOJ, and Powell really made no such case.
Indeed, that's the reason why the DC Circuit granted mandamus in the Flynn case — not because of any injury that Flynn might face from having Sullivan scrutinize the case, but because having to answer for what Barr did here would — simply having to show up to the kind of hearing that DOJ shows up to every day and answer questions under oath — would do grave damage to DOJ.
HJC should take DOJ at its word. DOJ has confessed their actions can't withstand the least amount of scrutiny. HJC should demand to know why.


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Even in a state accustomed to strange things washing ashore — like cocaine bricks, corpses, sharks and unexploded military ordnance — the floating contraption that beached itself in Florida over the weekend had the authorities doing a double take.
A man popped out of the top hatch of the contraption, a makeshift human hamster wheel. He had made it only 25 miles on what was supposed to be a 1,000-plus-mile journey from St. Augustine, Florida, to New York, using the power of his two legs and, if all had gone according to plan, the Gulf Stream.
The man, Reza Baluchi, said in an interview on Monday that he had spent thousands of dollars and nearly a decade on making improvements to the homemade craft, called a hydro pod. It was equipped with a satellite phone, a water filtration system, a solar array, neoprene wet suits and a stockpile of granola and ramen noodles for when he embarked from St. Augustine on Friday for what he expected would be a three-week trip.
But the next day, when Baluchi, 49, realized that his backup GPS device and charging cables were missing — he said they were stolen — he cut short his Homeric odyssey. His aborted adventure startled and bemused beachgoers.
"I open the top door and jump out," he said. "They're laughing. They're taking pictures of me. I know what I'm doing. I am not dumb."
In a Facebook post, the Flagler County Sheriff's Office said that some concerned people reported on Saturday morning that a vessel had washed shore in a part of the county known as the Hammock. The office said that it had referred the matter to the Coast Guard, which would determine if the vessel was compliant with marine safety regulations.
A spokesperson for the Coast Guard said in an email Tuesday that Baluchi would not be allowed to continue his voyage until he complied with a directive known as a captain of the port order that requires him to have an escort or support vessel, specific safety and navigation equipment, and a voyage plan.
"Failure to comply with Captain of the Port Orders is punishable by a civil penalty of up to $95,881," said the spokesperson, David Micallef. "There may also be criminal penalties for violating the order."
Baluchi, a former professional cyclist who was born in Iran and was granted asylum in the United States, said that he was hoping to use the attention from his trip to raise money to help homeless people and for other charitable causes. Over the years, he said, he has received puzzled reactions — including from the Coast Guard — after performing similar stunts on the water.
"They say, 'Why do you do this?'" said Baluchi, who lives in Boca Raton, in South Florida.
Constructed from aluminum and plastic balls that are buoyant, the hydro pod can carry several thousand pounds, according to Baluchi, who provided a copy of a vessel registration form that he said he had filed with the state of Florida.
On the form, in a box specifying what kind of propulsion system the vessel has, Baluchi wrote that it was the outboard type. He checked off "other" for the fuel type. And in the space for the odometer reading and the name of the vessel's manufacturer, he wrote, "Florida homemade boats."
The Florida Department of Highway Safety and Motor Vehicles did not immediately comment on Monday. Under state law, non-motor-powered vessels less than 16 feet in length are exempt from being titled and registered. Baluchi said his hydro pod was about 6 feet long and 10 feet wide.
Baluchi seemed unable to fathom life without the craft.
"Now, I'm dead," Baluchi said, referring to what would happen if he were to lose his hydro pod. "I don't have a car. I put everything in my life in it."
Baluchi, who is a father and was once homeless himself, is no stranger to tests of endurance. He previously drew attention for a cross-country run for charity.
In an earlier model of the hydro pod, he said, he traveled nearly 400 miles in the Pacific Ocean, reaching Santa Catalina Island. But the contraption was destroyed several years ago off the coast of Cape Canaveral, Florida, he said.
Baluchi, who has experimented with using an elliptical trainer to power his hydro pod, said it would be too costly for him to have an escort boat.
For his trip from Florida to New York, Baluchi estimated that he could have reached speeds of up to 6 knots in the current version of the vessel, which has a hammock for him to sleep in. He had planned to catch and eat fish and to chew special anti-nausea gum to manage seasickness. To protect himself from being bounced around in rough seas, he said, he had a bicycle helmet and a harness system.
To shield himself from the beating sun, Baluchi had put up a shade with a photo of Nikki Ziering, an actress and former model on "The Price Is Right" who has appeared in Playboy. Her pinup photos are featured prominently on his website, which has a page for people to track his progress.
Ziering said in an interview on Monday that mutual friends had introduced her to Baluchi.
"He said, 'Can you be my Wilson like in 'Cast Away,' the Tom Hanks movie?'" Ziering said, referring to a volleyball that was Hanks' companion on a deserted island. "I said, 'I would be honored to be your Wilson.'"
Ziering said she was impressed by Baluchi's fearlessness.
"He's going to have a spear in case there's a shark," she said. "He's going to run in a hamster wheel, basically, across the ocean."


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By Barbara Kollmeyer, MarketWatch
Getty Images
Europe's main stock gauge ended lower Friday, again weighed by worries over rising U.S. bond yields, as it posted a second consecutive weekly decline.
What are markets doing?
A day after logging the worst session in seven weeks, the Stoxx Europe 600 /zigman2/quotes/210599654/delayed XX:SXXP -0.02% declined 0.9% to end at 376.41. For the week, the pan-European gauge lost 1.8%, its weakest performance since a 2.2% drop in the week ending September 7.
Germany's DAX 30 /zigman2/quotes/210597999/delayed DX:DAX +0.01% dropped 1.1% to close at 12,111.90, while France's CAC 40 /zigman2/quotes/210597958/delayed FR:PX1 +0.08% fell 1% to 5,359.36. The U.K.'s FTSE 100 /zigman2/quotes/210598409/delayed UK:UKX +0.27% slid 1.4% to 7,318.54.
Greece's ASX Composite /zigman2/quotes/210597948/delayed GR:GD -0.23% slid 2.6% to 658.97, while Italy's FTSE MIB Italy index /zigman2/quotes/210598024/delayed IT:I945 -0.05% fell 1.3% to 20,345.96.
The euro /zigman2/quotes/210561242/realtime/sampled EURUSD +0.1346% was little changed at $1.1511, while the pound /zigman2/quotes/210561263/realtime/sampled GBPUSD -0.0165% traded at $1.3097, compared with $1.3020 late Thursday.
What is driving the market?
U.S. employers added just 134,000 new jobs in September, falling short of expectations, but the figure may have been affected by Hurricane Florence. The unemployment rate dropped to a 49-year low of 3.7%, indicating it remains tough for U.S. companies to find employers.
Led by Treasurys, global bond yields have been rising as investors pencil in the possibility of a more aggressive-than-anticipated rate-hike path by the Federal Reserve. Higher yields on bonds can make other investments such as stocks less attractive. The yield /zigman2/quotes/211347051/realtime BX:TMUBMUSD10Y 0.00% on the 10-year Treasury note was trading at a seven-year high at 3.229%.
Read: German manufacturing orders rebound in August
As for Europe, two hot spots have been grabbing the headlines, with Greek banks under pressure on concerns they can't digest a mountain of bad loans and might need fresh capital.
On Thursday evening, Italy's government, which has been in the spotlight, announced final budget targets , cutting growth targets and sticking to its plan for a budget deficit target of 2.4% of gross domestic product, or GDP, in 2019.
Elsewhere fears over rising tensions between the U.S. and China were weighing on some tech names, along with a report from Bloomberg Thursday over Chinese spying via U.S. computers.
What are strategists saying?
"As budget details emerge, targets for the deficit in 2020 and 2021 have been revised lower and markets have been somewhat reassured by a more conciliatory tone toward Brussels coming from Rome," analysts at BlueBay Asset Management wrote in a note to clients. "We continue to see Italexit risk as extremely unlikely and materially overpriced."
The China spy story plays unfortunately into the hands of U.S. President Donald Trump, and is a headache for big tech names, said Joshua Mahony, Market Analyst at IG.
"Markets care most about the potential for a resolution to U.S.-China negotiations, yet this news adds more to fuel to the fire, providing a likely extension to the timeline of any potential agreement," he told clients in a note.
Stock movers
Banks were the biggest losers on Friday, led by a 6.2% drop for Danske Bank AS after the Financial Times reported that an internal memo showed that the bank /zigman2/quotes/209678580/delayed DK:DANSKE +0.75% conducted mirror trades to allegedly launder Russian money.
Mining stocks were also a big decliner, with Anglo American PLC /zigman2/quotes/201381512/delayed UK:AAL -0.76% and Rio Tinto PLC /zigman2/quotes/208934945/delayed UK:RIO -0.52% /zigman2/quotes/202627887/composite RIO -0.62% /zigman2/quotes/202627887/composite RIO -0.62% /zigman2/quotes/202627887/composite RIO -0.62% each dropping 4%.


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Aberdeen-based Pale Blue Dot Energy has been awarded a 12 month contract by Tees Valley Unlimited, a local enterprise partnership, to develop the business case for an industrial carbon capture and storage network on Teesside – including the site of the blast furnace at the Redcar steelworks.
Part of the UK-Government supported Tees Valley City Deal Programme, the project will be significant in taking industrial carbon capture and storage forward in the UK. The Tees Valley project, which is at an early stage, will, if developed, capture CO2 emissions from major industrial sources and transport the CO2 offshore for deep underground sequestration.
This initial phase of work will take place over the next 12 months. The contract award builds upon the significant carbon-capture track record that the Pale Blue Dot Energy team has developed already from working on many of the previous UK CCS projects.
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Unless you've been living under a rock for the last few days, you' know that superheros aren't just guys anymore. Wonder Woman has taken the world by storm, and with good reason. It's one of those rare movies that offers everything – a compelling story, incredible action, and a hero that we can all cheer for. Oh, and it's the first comic book film to star AND be directed by a woman.
If you've been lucky enough to see the film already, then you no doubt know what we're talking about. If you haven't seen Wonder Woman yet, then grab some popcorn and a ticket! But don't worry, you can read this article first. We promise – no spoilers.


text:
Citrus Vinaigrette
This versatile citrus salad dressing gets a touch of natural sweetness from orange juice, which balances the acidity of the lemon juice. Use it in coleslaw for a mayo-free dressing, or drizzle it over winter greens with dried fruit and nuts.
Source: EatingWell.com, February 2018
Recipe Summary
Nutrition Profile:
To make ahead: Refrigerate dressing for up to 5 days.
Nutrition Facts
Serving Size:2 Tbsp.
Per Serving:
131 calories; protein 0.1g; carbohydrates 1.4g; dietary fiber 0.1g; sugars 0.9g; fat 14g; saturated fat 1.5g; vitamin a iu 16.7IU; vitamin c 5.8mg; folate 3.6mcg; calcium 2.6mg; iron 0.1mg; magnesium 1.6mg; potassium 25.9mg; sodium 161.9mg.
3 fat


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The Zuca Pro Travel is the perfect bag for business trips or vacations. The Pro Travel has you covered with a large insert bag and frame specifically designed for travel. Together they are FAA approved as carry-on luggage and include 5 color-coded packing pouches with a clear TSA-compliant toiletry bag. So whether you're taking product samples or bathing suits with you, everything stays organized and easy to access. Like every Zuca bag, the Pro Travel exudes quality and craftsmanship, with ballistic nylon material and aerospace-inspired aluminum alloy construction. No matter where you go, Zuca is there to protect and transport your belongings in style.
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Modern Sniper Zero
The sniper action continues with more killing, new sniper rifles, more blood, shootable body parts, better collision detection, and tons of zombie sniping. Your mission is to escort the VIP to the safe zone for extraction.Instructions:
Mouse to aim and fire. P to pause/unpause/upgrade. R to reload.Category:


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Alaska Air confirms plans to acquire Virgin America
One of the nation's oldest airlines announced plans to buy one of its newest Monday, when Alaska Airlines' parent company confirmed a $2.6 billion deal to acquire upstart Virgin America.
The move breathes life into a wave of industry consolidation that appeared to have ended after the American-US Airways merger that closed last year.
The latest deal would bring together Seattle-based Alaska Airlines and San Francisco-based Virgin America, combining airlines that each enjoy strong customer service reputations into a single West Coast juggernaut.
BOOKMARK: Go directly to the Today in the Sky blog
Branson: 'Nothing I could do to stop' Virgin America merger
It also comes after four mega-mergers since 2008, deals that took eight of the USA's biggest airlines and combined them into four larger carriers that now collectively control about 80% of the U.S. market.
"For an airline like Alaska, that says scale is relevant," Brad Tilden, CEO of the Alaska Air Group that includes Alaska Airlines, said about the backdrop under which his company made a move for Virgin America.
Alaska Airlines' iconic Eskimo gets a makeover
Alaska Airlines, which has roots tracing to 1932, is the dominant carrier in the Pacific Northwest. It's the busiest carrier at both the fast-growing Seattle-Tacoma International Airport and at Oregon's Portland International.
Virgin America began flying only in 2007, launched with the partial backing of British tycoon Sir Richard Branson and his global Virgin brand. The airline has become a major player in California, establishing its biggest hub in San Francisco as well as another in Los Angeles.
Virgin America began putting out feelers in March to test the waters for a potential buyer, which is when Alaska Air initiated its takeover bid. There was also a competing offer from JetBlue, but Alaska Air won out after what Tilden called a "hard-fought competition."
Alaska Air's 'Space Bins' come amid broader cabin upgrades
"We didn't really set out to sell the company when we were approached by Alaska," Virgin America CEO David Cush said on a Monday morning call to discuss the merger with investors and journalists. "But we are happy with the outcome of this transaction. The price paid is a big win for our shareholders. Our employees will join a vibrant, well-run company. Being part of a bigger airline offers greater job security in a highly consolidated industry."
The deal is valued at $57 per share in a deal worth about $2.6 billion.
Jim Corridore, an analyst with S&P Global Market Intelligence, says that the deal is great for Virgin America and would likely be a boon — eventually — for Alaska investors as well.
"It's a great move for Virgin's stockholders,'' he says. "Alaska is paying a very high price for these assets but they were forced into a bidding war with JetBlue. I think it's going to be a great deal for them but take a little bit for the payoff to come, based on the price they paid."
Alaska Air said its acquisition of San Francisco-based Virgin America will give it a "solid foothold in California," the USA's most populous state.
Tilden pointed to San Francisco International, where he said Alaska Airlines currently flies on only one of the top 10 routes from the airport. "With this acquisition, we'll fly to all 10," Tilden said. Also underscoring the importance of California, Tilden said picking up Virgin America's transcontinental routes affects "how much customers living in California can concentrate their travel with us."
"Our goal is to be the premier airline for people who live on the West Coast," Tilden said, calling Virgin America's California holdings "really valuable real estate."
"It gives us a shot at being your go-to airline if you live anywhere up and down the West Coast."
Combined, Alaska Airlines and Virgin America said the combined company would have 1,200 daily departures, with hubs in Seattle, San Francisco, Los Angeles, Anchorage and Portland, Ore. Its headquarters will remain in Seattle.
Virgin America's Elevate frequent-flier members would be "welcomed" into Alaska Air's MileagePlan program. And Alaska Airlines said it intended to acquire a single operating certificate for the two carriers.
Beyond that, however, the fate was not immediately clear for the Virgin America brand or for its fleet of Airbus aircraft.
Alaska Air currently uses only Boeing 737 jets for its "mainline" service, though regional partners Horizon and SkyWest fly Bombardier turboprops and regional jets for Alaska Air.
Alaska Air Chief Operating Officer Ben Minicucci said during the call it was too early to know whether Alaska Air would keep Virgin America's Airbus jets or look for ways to get rid of them.
"We're going to continue to operate the Airbus fleet in the near future. We'll decide in time whether we go to a single fleet or if we'll operate a dual fleet," Minicucci said.
Similarly, the fate of the Virgin America brand also remained uncertain. Alaska Airlines pointedly said its own brand — recently refreshed with an updated logo and airplane paint scheme — would remain.
But Alaska Air officials were less committal about the Virgin America name. They acknowledged it had become a "powerful" brand with strong customer loyalty but said only that Alaska Air will consider ways to incorporate the brand "down the road."
The most pressing next step for Alaska Air officials may be winning regulatory approval for the deal. Alaska Air and Virgin America overlap only on a small number of routes, usually a key criteria looked at by regulators in airline mergers. However, the spate of mergers during the past decade may leave Alaska Air and Virgin America facing hostile attitudes from Washington regarding yet another merger.
Kyle Levine, Alaska Air Group's vice president of legal and general counsel, said the company had not yet approached regulators about gaining approval for the deal.
"We know they're going to take a close look at it. We think we have a good story to tell about us increasing competition and better positioning us to compete against much bigger carriers," he said, noting there is "very little overlap" between the two airlines' route networks.
Analyst Corridore predicted Alaska Air will also will get a green light from regulators, who have already greenlighted much bigger mergers like United-Continental, Delta-Northwest, Southwest-AirTran and American-US Airways.
"It will be shocking if the regulators chose to focus on Alaska/Virgin rather than American/US Airways,'' Corridore says. "So I don't think that will be a problem.''
But not everyone predicted smooth sailing. Jaime Baker, an airline analyst at JP Morgan, suggested regulators may take a tougher stand than with previous mergers. He noted that the Department of Justice — which had previously signed off on the past four big mergers — opened an antitrust probe last year investigating several U.S. airlines for possible collusion,
"Setting aside empirical analysis, the reality that the DOJ and DOT are investigating recently merged entities shouldn't be ignored," Baker warned in a research note.
Contributing: Charisse Jones
TWITTER: You can follow me at twitter.com/TodayInTheSky
Alaska Airlines adds 'Premium Class,' the latest premium economy offering


text: photography, race issues, Sunday Snapshot Sunday Snapshot: breaking open the sky Date: August 27, 2017Author: Laura "We are not trapped or locked up in these bones. No, no. We are free to change. And love changes us. And if we can love one another, we can break open the sky." – Walter Mosley Share this:FacebookTwitterEmailPrintMorePinterestLinkedInTumblrLike this:Like Loading... Related


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We've been learning all about sugar and the way it interacts with the brain, then we stumbled across this gem which perfectly explains it all. Written by Kris Gunnars, BSc, from Authority Nutrition.
"No one can exert cognitive inhibition, willpower, over a biochemical drive that goes on every minute, of every day, of every year." – Dr. Robert H. Lustig
If you've ever tried to cut back on sugar, you may have realized how incredibly difficult it is. In some cases it may seem downright impossible.
It seems clear that when it comes to foods like sugar and other junk foods, that something in the brain does not function like it's supposed to.
The system in our brain that is supposed regulate our food intake and prevent us from gaining weight malfunctions. The question is: Why?
To understand why this happens, Dr. Robert H. Lustig, pediatric endocrinologist and Dr. Elissa S. Epel, psychologist, explain in the video above how sugar and other junk foods can "hijack" the brain chemistry to make us want more and more.
Overstimulation of The Reward Centers of The Brain Causes Addiction
Sugar is uniquely fattening, primarily due to its high content of fructose.
There are several ways that sugar causes us to overeat and gain weight and I will be covering all of these in the coming weeks.
Today I am going to talk about one of these mechanisms, the powerful impact sugar has on the reward centers of the brain.
When we eat foods that contain a lot of sugar, a massive amount of dopamine is released in an area of the brain called the Nucleus Accumbens.
When we eat these foods often and in large amounts, the dopamine receptors start to down-regulate. Now there are fewer receptors for the dopamine.
This means that the next time we eat these foods, their effect is blunted. We will need more junk food next time we eat in order to get the same level of reward.
Sugar and other junk foods, due to their powerful effect on the reward centers of the brain, function similarly to drugs of abuse like cocaine and nicotine (1).
The exact same brain centers are at play. People who have a certain predisposition to addiction become addicted to these foods and lose control over their consumption.
This is basically how sugar and other junk foods "hijack" the brain chemistry to make us crave more and eat more.
Sugar Has a Powerful Influence Over Our Behavior
For some people there will be anatomical changes in the brain when exposed to these sorts of foods. In many cases, this can end up in full-blown addiction (2).
I can support this idea with some personal experiences.
I am a recovering drug addict who has been to 6 rehabs. I was also a smoker for many years and it was a long battle for me to quit. You could say that I know addiction like the back of my hand.
I'm here to tell you that addiction to sugar and junk foods is exactly the same as addiction to abusive drugs like nicotine, amphetamine and cannabis.
There is no difference, except the substance of abuse is different and the consequences of relapse aren't as severe.
Since learning about this, I've spoken to several other recovering addicts and all of them say that they experience cravings for junk foods in the exact same way as they used to crave drugs and alcohol.
Yours in details,
Your Tea


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Groningen are set to sign Manchester City defender Ko Itakura on loan for the third consecutive season.
- Follow Football-Oranje on Twitter
The Japanese international has spent the last two years with Groningen with the 23-year-old making 23 appearances for the club.
Speaking to RTV Noords, Groningen director Mark-Jan Fledderus confirmed that talks with Manchester City are going well, "We are close to an agreement with Manchester City. I expect we will get clear in the coming weeks, but it looks good.
"It's not finished yet, but I have a good feeling about it. Now it is mainly about whether Ko himself wants to play for another year at FC Groningen. "


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Genamics JournalSeek
ISSN (printed): 0018-067X. ISSN (electronic): 1365-2540.
An official journal of the Genetical Society of Great BritainHeredity, now in its fiftieth year, publishes articles in all areas of genetics, focusing on the genetics of eukaryotes. The traditional strengths of the Journal lie in the fields of ecological and population genetics; biometrical and statistical genetics; animal and plant breeding; and cytogenetics. Heredity is also increasingly including articles on the new molecular genetic techniques which are now being applied by many research scientists to these areas of study.


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Super Bowl 50: NFL honors Doug Jolley and Dixie High School
Sunday's upcoming Super Bowl game between the Denver Broncos and the Carolina Panthers is still five days away, but that hasn't stopped the festivities from starting early.
Last week, Dixie High School joined an elite group of high schools all across the world after a gold football was delivered to the school.
"It was completely unexpected and caught a lot of us off guard," Dixie Athletic Director Mike Bair said of the gift. "It's really neat that the NFL did this. It's a big hit and everyone loves to look at it because it's something you don't see every day."
The NFL has gone all out for the Super Bowl's golden anniversary. From last year's draft, to uniforms, NFL logos and a golden 50-yard line this season, the league has turned this season into what seems like the California Gold Rush.
And with all of the unique ways to celebrate Super Bowl 50, high schools all over are getting in on the action thanks to the NFL's Honor Roll program.
As part of the worldwide celebration, the NFL started the Super Bowl High School Honor Roll program to acknowledge schools and communities that have directly influenced Super Bowl history.
Every high school that's had a player or coach in the Super Bowl has been recognized and given a gold football. The NFL estimates that more than 2,000 high schools and nearly 3,000 players and coaches will be recognized this season.
DHS is just one of 17 high schools in Utah to receive a football thanks to Doug Jolley.
"What an accomplishment it is for Doug and for the entire school," Bair said. "He's done a lot for us and we can't thank him enough."
Jolley was a three-sport athlete (football, basketball, baseball) during his time at DHS before starring at BYU as a tight end. After winning numerous accolades at the collegiate level, Jolley went on to have a successful NFL career after being drafted by the Oakland Raiders in the second round of the 2002 NFL Draft.
During his first year on the team, the Raiders went on to win the AFC title and a spot in Super Bowl XXXVII.
Jolley was honored at halftime when the school retired his jersey during the high school football game between Dixie and Pine View. The Flyers ended up winning the game on a last-second touchdown.
"Principal Campbell really led the way and organized everything to get his jersey retired," Bair said. "It was a lot of fun to get the community together and to honor him for all of his achievements."
With his jersey retired, Jolley now has a golden football in his name at the school that helped put him on the map.
Follow Justin Giles on Twitter @Justingiles22 or on Facebook at https://www.facebook.com/JustinGilesSportsWriter.


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A lawyer who represented former SNC-Lavalin Vice-President Sami Bebawi is accused of trying to bribe a key witness in the company's corruption trial.
SNC-Lavalin and Bebawi are currently facing fraud and bribery charges surrounding the company's operations in Libya while it was still being ruled by the dictator Muammar Gaddafi.
Constantine Kyres, allegedly bribed the company's former head of projects in Libya, Riadh Ben Aïssa, with a payment between $8 to $10 million. The offer was contingent on Aïssa changing his testimony to match that of Bebawi.
"I was offered 10 million in return for taking over Sami Bebawi's version," Aïssa testified.
An undercover RCMP officer posing as a consultant for Bebawi secretly recorded Kyres in 2013 making the offer.
"Why should we give 8 to 10 million if he does not even recognize the truth as we see it?" said Kyres.
According to Kyres, Aïssa needed to change his testimony to receive the cash.
Earlier in the trial, it was revealed that Bebawi allegedly pocketed $26 million in funds funnelled through a shell corporation for himself and his uncle. The shell corporation transferred approximately $118 million in funds used in its dealings in Libya.
Scandal has surrounded the Quebec corporation's activities since the charges were first laid. Evidence shows that the company spent millions funding sex parties for Gaddafi's son Saadi Gaddafi while in Canada.
SNC-Lavalin paid around $2 million on prostitutes, travel and entertainment expenses for the dictator's son.
The scandals have even implicated the Trudeau government after former Justice Minister and Attorney General Jody Wilson-Raybould accused the Prime Minister's Office of trying to politically interfere in the case by getting the company a deferred prosecution agreement.
Ethics Commissioner Mario Dion eventually ruled that Trudeau had broken ethics laws after directing officials to intervene in the matter.
"The authority of the Prime Minister and his office was used to circumvent, undermine and attempt to discredit the decision of the Director of Public Prosecutions as well as the authority of Ms. Wilson‑Raybould as the Crown's chief law officer," wrote Commissioner Dion.
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This is why independent media in Canada is more important than ever. If you're able, please make a tax-deductible donation to True North today. Thank you so much.


text: On Wed 20-09-17 16:17:04, Pavel Tatashin wrote:> Without deferred struct page feature (CONFIG_DEFERRED_STRUCT_PAGE_INIT),> flags and other fields in "struct page"es are never changed prior to first> initializing struct pages by going through __init_single_page().> > With deferred struct page feature enabled there is a case where we set some> fields prior to initializing:> > mem_init() {> register_page_bootmem_info();> free_all_bootmem();> ...> }> > When register_page_bootmem_info() is called only non-deferred struct pages> are initialized. But, this function goes through some reserved pages which> might be part of the deferred, and thus are not yet initialized.> > mem_init> register_page_bootmem_info> register_page_bootmem_info_node> get_page_bootmem> .. setting fields here ..> such as: page->freelist = (void *)type;> > free_all_bootmem()> free_low_memory_core_early()> for_each_reserved_mem_region()> reserve_bootmem_region()> init_reserved_page() <- Only if this is deferred reserved page> __init_single_pfn()> __init_single_page()> memset(0) <-- Loose the set fields here> > We end-up with similar issue as in the previous patch, where currently we> do not observe problem as memory is zeroed. But, if flag asserts are> changed we can start hitting issues.> > Also, because in this patch series we will stop zeroing struct page memory> during allocation, we must make sure that struct pages are properly> initialized prior to using them.> > The deferred-reserved pages are initialized in free_all_bootmem().> Therefore, the fix is to switch the above calls.> > Signed-off-by: Pavel Tatashin <firstname.lastname@example.com>> Reviewed-by: Steven Sistare <firstname.lastname@example.com>> Reviewed-by: Daniel Jordan <email@example.com>> Reviewed-by: Bob Picco <email@example.com>> Acked-by: David S. Miller <email@example.com>As you separated x86 and sparc patches doing essentially the same Iassume David is going to take this patch?Acked-by: Michal Hocko <firstname.lastname@example.com>> ---> arch/sparc/mm/init_64.c | 8 +++++++-> 1 file changed, 7 insertions(+), 1 deletion(-)> > diff --git a/arch/sparc/mm/init_64.c b/arch/sparc/mm/init_64.c> index 6034569e2c0d..310c6754bcaa 100644> --- a/arch/sparc/mm/init_64.c> +++ b/arch/sparc/mm/init_64.c> @@ -2548,9 +2548,15 @@ void __init mem_init(void)> {> high_memory = __va(last_valid_pfn << PAGE_SHIFT);> > - register_page_bootmem_info();> free_all_bootmem();> > + /* Must be done after boot memory is put on freelist, because here we> + * might set fields in deferred struct pages that have not yet been> + * initialized, and free_all_bootmem() initializes all the reserved> + * deferred pages for us.> + */> + register_page_bootmem_info();> +> /*> * Set up the zero page, mark it reserved, so that page count> * is not manipulated when freeing the page from user ptes.> -- > 2.14.1-- Michal HockoSUSE Labs


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'Thank you' is the best prayer that anyone could say. I say that one a lot. "Thank you" expresses extreme gratitude, humility and understanding. Alice Walker Pull up a chair and pour yourself a cup of coffee. Yes, I do realise that the kitchen looks as if it had just been wrecked by an untimely earthquake …
Laughter Meditation for Midlife Stress Relief
I am very grateful for the things that make me laugh. Laughter is one of the best stress-busters I know. Whenever I feel stressed and hassled, I do my best to be mindful: being100% present in the moment, my attention focused on what is happening second-by-second. Humour anchors me in the present moment. Sometimes, when …
Continue reading "Laughter Meditation for Midlife Stress Relief"
Mindful New Year's Resolution
It is the first of January, a new year awakens. The mist still hangs thick outside, but I have to go out and feed the horses. No sleeping late for me today, no matter the excesses of last night/early morning hours. As I sit down on the old wooden bench on the porch, same as …
12 Ways to deal with Midlife Stress
I found the whole experience extremely STRESSFUL. The vet may have done it a million times before, but I never have. Nor has my husband, and we are to be the vet's two essentially untrained assistants!
The Benefits of Gratitude
I woke up with a full-blown head cold. Headache, fever, muscle pains, blocked nose, sore throat, burning eyes and the overwhelming conviction that getting out of bed is a very bad idea. After feeling sorry for myself for a while, I decided to try and figure out what there is to be grateful about the situation that I find myself in.


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West Volusia chamber transportation forum rescheduled
The once-cancelled West Volusia Regional Chamber of Commerce's economic forum featuring a leader of the U.S. Department of Transportation has a new date.
The forum with Deputy Assistant Secretary Anthony Bedell will be held from 11 a.m. to 12:30 p.m. on Feb. 22 at the DeBary Golf and Country Club, 300 Plantation Club Drive, according to a release from the chamber. Lunch for members is $30 and the cost for nonmembers is $40.
The event was originally scheduled for Jan. 24, but it was delayed because of the government shutdown.
[PREVIOUS COVERAGE: Government shutdown delays West Volusia transportation meeting]
Following a talk from Bedell, a panel of local government representatives will discuss regional infrastructure challenges.
To register for the event, visit https://westvolusiaregionalchamber.org.


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For the past four years, Alex has regularly used Craigslist to set up illegal romps with prostitutes. The 28-year-old is worried that the shuttering of the site's adult services section will hurt his hobby -- only, not in the ways you might think. Online sex work isn't going anywhere, he says, but the closure is likely to make it harder for him to find his type of girl: young and inexperienced.
"A lot of the girls I've seen are ordinary college girls who wouldn't normally think of doing this," he says. "They come onto Craigslist to find roommates and buy a TV and click around and they find a post that I've written that's worded kindly and offers them help." As one john wrote in response to a question I posted on an online message board, "CL was the perfect launching pad for horny young women who wanted to give it a try without actually hitting the streets." (I'm dubious of the relevance of "horniness" in selling sex, but as a recent Salon personal essay revealed, the site certainly offers a quick in for newbies.)
While there are certainly "newbie" or "non-pro" enthusiasts like Alex, most hobbyists, as dedicated johns refer to themselves, don't seem to care all that much about the disappearance of the adult services section. The men in this crowd consider themselves sex worker connoisseurs, and turn up their noses at what one called the "low-rent" world of Craigslist. It's full of "bargain hunters" and "bottom feeders," inexperienced johns who want it quick and cheap, they tell me.
John, who requested that apt pseudonym, used Craigslist exclusively for a couple years, but found it had too many cases of "bait and switch," where an ad promises, say, a leggy blonde and you show up only to find a petite Asian girl. Escort agencies have made a practice of spamming Craigslist with generic ads; they simply send whichever girl is available when a call comes in, regardless of whether she bears any resemblance to the woman pictured in the ad.
Eventually, John, a married New Yorker in his late 40s, found The Erotic Review (TER), a site that allows users to comprehensively review sex workers' services; it's like Yelp for prostitution. The reviews allow johns to choose a reliable provider, one who is less likely to be part of a law enforcement bust or what they call a "R.O.B." (a.k.a. a "rip-off bitch" or a "cash and dash"). One john wrote me in an e-mail that "most women who advertised on CL were drug addicts, run by pimps or scam artists." Those women "will go to other sites, and men who don't know better will waste their money," he said. Another said: "The disappearance of the Craigslist Adult Services really means nothing to me OTHER than it was amusing browsing the listings. ... it was just cheap entertainment."
Craigslist is "low-hanging fruit" for law enforcement," says John. If they want to go out and make a few busts and make it look like they're doing their jobs, they're gonna go to Craigslist -- that's where all the easy people are." In other words: Most of the johns affected by this change are amateurs, guys who pay for the rare hand job in their car. He added, "The ones that screen properly, they don't get busted."


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Over the last two years, a number of microstates, mainly those located in the Pacific, have introduced a visa-free regime with Russia.
For example, two years ago, the island nation of Fiji canceled visas for Russians, while the Kremlin offered similar terms to hypothetical tourists from Fiji.
A year ago, it was Vanuatu, microstate in Melanesia, that suddenly decided to introduce visa-free regime with the Russian Federation.
And now Mauritius, a distant island in the Indian Ocean close to Madagascar, also readies to join the visa-free club. Continue reading