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Depression is one of the leading causes of mortality, disability, and loss of productivity. The World Health Organization (WHO) ranks depressive disorders as the eleventh cause of disability and mortality (1, 2). The worldwide lifetime prevalence of depression is around 12% (3). In spite of the considerable burden of depression both in terms of prevalence and public health impact, the search for more effective treatments for depression is still ongoing. Emerging evidence suggests that personalizing treatments based on individuals’ biosignature could be the “way forward” (4).
Understanding the distribution of taxa in space and time is key to understanding diversity dynamics. The fossil record provides an avenue to assess these patterns on vast timescales and through major global changes. The Eublastoidea were a conservatively plated Paleozoic echinoderm clade that range from the middle Silurian to the end-Permian. The geographic distribution of the eublastoids, as a whole, has been qualitatively assessed but has historically lacked a quantitative analysis. This is the first examination of the Eublastoidea using probabilistic methods within the R package BioGeoBEARS to assess macroevolutionary trends. Results provide an updated understanding of eublastoid diversity with new peaks and troughs in diversity through their evolutionary history. Lithology is examined in an evolutionary framework and does not have clear evolutionary trends, and there is much work to be done regarding environmental preferences. Biogeographic patterns do not recover precise group origins but do support the previous work that outlines Eublastoidea as a Laurentian clade. Sympatric speciation events dominant the clade's history but are likely exaggerated due to the highly combined areas. Vicariance events are rare and restricted to the Silurian and Devonian, and dispersal events are more common throughout the evolutionary history. Pathways allowing for lineage migrations are noted between southern Laurussia and China in the Devonian and Carboniferous and southern Laurussia and eastern Gondwana in the Carboniferous. Future work will include the addition of more non-Laurentian species into the estimated phylogeny to better estimate these global patterns.
Our research group demonstrated that vitamin A restriction affected meat quality of Angus cross and Simmental steers. Therefore, the aim of this study is to highlight the genotype variations in response to dietary vitamin A levels. Commercial Angus and Simmental steers (n = 32 per breed; initial BW = 337.2 ± 5.9 kg; ~8 months of age) were fed a low-vitamin A (LVA) (1017 IU/kg DM) backgrounding diet for 95 days to reduce hepatic vitamin A stores. During finishing, steers were randomly assigned to treatments in a 2 × 2 factorial arrangement of genotype × dietary vitamin A concentration. The LVA treatment was a finishing diet with no supplemental vitamin A (723 IU vitamin A/kg DM); the control (CON) was the LVA diet plus supplementation with 2200 IU vitamin A/kg DM. Blood samples were collected at three time points throughout the study to analyze serum retinol concentration. At the completion of finishing, steers were slaughtered at a commercial abattoir. Meat characteristics assessed were intramuscular fat concentration, color, Warner-Bratzler shear force, cook loss and pH. Camera image analysis was used for determination of marbling, 12th rib back fat and longissimus muscle area (LMA). The LVA steers had lower (P < 0.001) serum retinol concentration than CON steers. The LVA treatment resulted in greater (P = 0.03) average daily gain than the CON treatment, 1.52 and 1.44 ± 0.03 kg/day, respectively; however, there was no effect of treatment on final BW, DM intake or feed efficiency. Cooking loss and yield grade were greater and LMA was smaller in LVA steers (P < 0.05). There was an interaction between breed and treatment for marbling score (P = 0.01) and percentage of carcasses grading United States Department of Agriculture (USDA) Prime (P = 0.02). For Angus steers, LVA treatment resulted in a 16% greater marbling score than CON (683 and 570 ± 40, respectively) and 27% of LVA Angus steers graded USDA Prime compared with 0% for CON. Conversely, there was no difference in marbling score or USDA Quality Grades between LVA and CON for Simmental steers. In conclusion, feeding a LVA diet during finishing increased marbling in Angus but not in Simmental steers. Reducing the vitamin A level of finishing diets fed to cattle with a high propensity to marble, such as Angus, has the potential to increase economically important traits such as marbling and quality grade without negatively impacting gain : feed or yield grade.
Compare quetiapine+antidepressant (AD) with lithium+AD, and quetiapine monotherapy with lithium+AD in open, rater-blinded treatment.
Patients with treatment resistant depression (Thase et al 1997 stage 1 and 2) with severity of MADRS ≥25 received: quetiapine XR 300mg/day plus AD (SSRIs or venlafaxine) (n=229), lithium (monitored to between 0.6 to 1.0 meq/l) plus AD (n=221) or quetiapine XR alone (300mg/day) (n=225) for 6 weeks. Primary efficacy measure was change from baseline in MADRS total score. The pre-specified non-inferiority limit was 3 points on the MADRS.
Fewer patients discontinued on quetiapine+AD (15.2%) than lithium+AD (20.5%) and quetiapine monotherapy (21.5%). Quetiapine+AD and quetiapine monotherapy, were not inferior to lithium+AD in the primary (per protocol) analysis with a mean difference (97.5%CI) on the MADRS of -2.32 (-4.6 to -0.05) favouring add-on quetiapine and -0.97 (-3.24 to 1.31) favouring quetiapine monotherapy. This mandated superiority testing on the modified ITT population showing no significant difference at endpoint.
In a post hoc analysis discounting multiplicity, quetiapine+AD was significantly more effective than lithium+AD on the MADRS change from baseline, p=0.046. The advantage was observed at day 4 (p=0.007) and persisted throughout. Efficacy was supported by CGI-I (p=0.07). Quetiapine+AD showed a numerically greater advantage over lithium+AD in those with two failed treatments (Stage 2) rather than one (Stage 1).
Quetiapine+AD and quetiapine monotherapy, were non-inferior to lithium+AD in treatment resistant depression. There was an early significant and persistent efficacy advantage on MADRS for quetiapine augmentation compared with lithium augmentation of SSRI or venlafaxine treatment.
This pooled analysis evaluated efficacy of adjunct quetiapine XR (QTP-XR) in subgroups of patients with anxious depression and lower levels of anxiety.
Pooled data from two 6-week, double-blind, randomised, placebo-controlled trials (D1448C00006/D1448C00007) in patients with inadequate response to antidepressants were analysed. Patients received adjunct QTP-XR (150 or 300 mg/day) or placebo+antidepressant (SSRI or SNRI). Using criteria defined in the STAR*D study, analyses conducted in patients with anxious depression or lower baseline anxiety levels (HAM-D anxiety/somatic factor score >/ = 7 and < 7, respectively) included LSM change at Week 6 in: MADRS total (primary endpoint), HAM-A and CGI-S total scores.
For patients with anxious depression (n = 697; 76% patients), adjunct QTP-XR 150mg/day (-14.44, p < 0.01) and 300 mg/day (-15.09, p < 0.001) significantly improved MADRS total scores versus placebo+antidepressant (-11.78) at Week 6, with significant improvement demonstrated from Week 1 onwards. Significant improvements were seen in HAM-A (QTP-XR 150 mg/day: -9.05, p < 0.01; 300 mg/day -9.43, p < 0.01) and CGI-S total scores (QTP-XR 150 mg/day: -1.60, p< 0.001; 300 mg/day -1.63, p < 0.001) versus placebo+antidepressant (-7.40, -1.22, respectively) at Week 6.
A smaller subgroup (n = 222; 24% patients) had lower baseline anxiety levels. At Week 1, adjunct QTP-XR (150 mg/day -9.09; p < 0.01; 300 mg/day -8.60; p < 0.05) significantly improved MADRS total score versus placebo+antidepressant (-5.93). At Week 6 there were no significant changes (QTP-XR 150 mg/day -14.49; p = 0.243; 300 mg/day -14.01; p = 0.388) versus placebo+antidepressant (-12.78).
For patients with anxious depression, adjunct QTP-XR (150 and 300 mg/day) was effective at reducing symptoms of anxiety and depression, with symptom improvement observed from Week 1 onwards. AstraZeneca funded.
Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.
The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.
There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.
These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
Previous findings suggested that electrodermal hyporeactivity has a high sensitivity (up to 97%) and high raw specificity (up to 98%) for suicide.
To evaluate prevalence, sensitivity and specificity of electrodermal hyporeactivity for suicide and suicide attempt, with and without death intent and with violent method or not, in adult patients with a primary diagnosis of depression.
At each study site at least 100 patients with a primary diagnosis of depression, also in remission, will be recruited. Depressive symptomatology will be evaluated through the Montgomery-Asberg Depression Scale. Previous suicide attempts will be registered and the death intent of the worst attempt will be rated according to the first eight items of the Beck Suicide Intent Scale. The risk of suicide will be assessed according to rules and traditions at the centre. The EDOR Test (ElectroDermal Orienting Reactivity) will be performed. Two fingers are put on gold electrodes. Through headphones a moderately strong tone is presented now and then during the test. Sensors located within the electrodes are able to register the electrodermal response to those tones, measuring the skin conductance (i.e. electrodermal activity from sweat gland activity). Each patient will be followed up for one year for actions of intentional self-harm that require medical care and for suicide. The death intent will also be rated.
It is expected that the EDOR test detects a previously unknown neuropsychological dysfunction that is independent of the depressive state and can predict suicidality with a high sensitivity and specificity.
Objective: Detection of cognitive impairment suggestive of risk for Alzheimer’s disease (AD) progression is crucial to the prevention of incipient dementia. This study was performed to determine if performance on a novel object discrimination task improved identification of earlier deficits in older adults at risk for AD. Method: In total, 135 participants from the 1Florida Alzheimer’s Disease Research Center [cognitively normal (CN), Pre-mild cognitive impairment (PreMCI), amnestic mild cognitive impairment (aMCI), and dementia] completed a test of object discrimination and traditional memory measures in the context of a larger neuropsychological and clinical evaluation. Results: The Object Recognition and Discrimination Task (ORDT) revealed significant differences between the PreMCI, aMCI, and dementia groups versus CN individuals. Moreover, relative risk of being classified as PreMCI rather than CN increased as an inverse function of ORDT score. Discussion: Overall, the obtained results suggest that a novel object discrimination task improves the detection of very early AD-related cognitive impairment, increasing the window for therapeutic intervention. (JINS, 2019, 25, 688–698)
Although accumulating evidence supports the hypothesis that immune/inflammatory mechanisms are associated with the pathophysiology of bipolar disorder (BD), data about the profile of chemokines (chemotactic cytokines) and chemokine receptors are still scarce. The current study was designed to evaluate the expression of chemokine receptors on lymphocytes of patients with BD in comparison with controls.
Thirty-three patients with type I BD (N = 21 in euthymia; N = 6 in mania/hypomania; N = 6 in depression) and 22 age- and sex-matched controls were subjected to clinical evaluation and peripheral blood draw. The expression of chemokine receptors CCR3, CCR5, CXCR4, and CXCR3 on CD4+ and CD8+ lymphocytes was assessed by flow cytometry.
Patients with BD had decreased percentage of CD4+CXCR3+ (p = 0.024), CD4+CCR3+ (p = 0.042), and CD4+CCR5+ (0.013) lymphocytes in comparison with controls. The percentage of both CD4+ and CD8+ lymphocytes expressing the chemokine receptor CXCR4 was similar in patients with BD and controls. Likewise, the percentages of CD8+CXCR3+, CD8+CCR3+, and CD8+CCR5+ lymphocytes were similar in patients with BD and controls.
Our findings reinforce the hypothesis that immune pathways, especially involving CD4+ lymphocytes, are involved in the physiopathology of BD.
A core question in the debate about how to organise mental healthcare is whether in- and out-patient treatment should be provided by the same (personal continuity) or different psychiatrists (specialisation). The controversial debate drives costly organisational changes in several European countries, which have gone in opposing directions. The existing evidence is based on small and low-quality studies which tend to favour whatever the new experimental organisation is.
We compared 1-year clinical outcomes of personal continuity and specialisation in routine care in a large scale study across five European countries.
This is a 1-year prospective natural experiment conducted in Belgium, England, Germany, Italy and Poland. In all these countries, both personal continuity and specialisation exist in routine care. Eligible patients were admitted for psychiatric in-patient treatment (18 years of age), and clinically diagnosed with a psychotic, mood or anxiety/somatisation disorder.
Outcomes were assessed 1 year after the index admission. The primary outcome was re-hospitalisation and analysed for the full sample and subgroups defined by country, and different socio-demographic and clinical criteria. Secondary outcomes were total number of inpatient days, involuntary re-admissions, adverse events and patients’ social situation. Outcomes were compared through mixed regression models in intention-to-treat analyses. The study is registered (ISRCTN40256812).
We consecutively recruited 7302 patients; 6369 (87.2%) were followed-up. No statistically significant differences were found in re-hospitalisation, neither overall (adjusted percentages: 38.9% in personal continuity, 37.1% in specialisation; odds ratio = 1.08; confidence interval 0.94–1.25; p = 0.28) nor for any of the considered subgroups. There were no significant differences in any of the secondary outcomes.
Whether the same or different psychiatrists provide in- and out-patient treatment appears to have no substantial impact on patient outcomes over a 1-year period. Initiatives to improve long-term outcomes of psychiatric patients may focus on aspects other than the organisation of personal continuity v. specialisation.
Exercise during pregnancy has beneficial effects on maternal and offspring’s health in humans and mice. The underlying mechanisms remain unclear. This comparative study aimed to determine the long-term effects of an exercise program on metabolism, weight gain, body composition and changes in hormones [insulin, leptin, brain-derived neurotrophic factor (BDNF)]. Pregnant women (n=34) and mouse dams (n=44) were subjected to an exercise program compared with matched controls (period I). Follow-up in the offspring was performed over 6 months in humans, corresponding to postnatal day (P) 21 in mice (period II). Half of the mouse offspring was challenged with a high-fat diet (HFD) for 6 weeks between P70 and P112 (period III). In period I, exercise during pregnancy led to 6% lower fat content, 40% lower leptin levels and an increase of 50% BDNF levels in humans compared with controls, which was not observed in mice. After period II in humans and mice, offspring body weight did not differ from that of the controls. Further differences were observed in period III. Offspring of exercising mouse dams had significantly lower fat mass and leptin levels compared with controls. In addition, at P112, BDNF levels in offspring were significantly higher from exercising mothers while this effect was completely blunted by HFD feeding. In this study, we found comparable effects on maternal and offspring’s weight gain in humans and mice but different effects in insulin, leptin and BDNF. The long-term potential protective effects of exercise on biomarkers should be examined in human studies.
The external expression of hydrospires in blastoids has provided a basis for major and minor group classification in the clade for over a century. Unfortunately, the complete anatomy of the hydrospires has never been comprehensively studied. This study examined and described the internal hydrospires of six spiraculate species by digitally extracting hydrospire data from a legacy data set of serial acetate peels. Although only six models have been currently generated, hydrospire morphology is variable both within and between previously escribed spiraculate families. Hydrospires were found to possess novel characters that were incorporated into a phylogenetic analysis of the six digitally modeled species and several related species. The addition of internal morphology into the phylogenetic analysis provides further resolution between groupings of blastoids.
Zircon ion probe (secondary-ion mass spectrometry or SIMS) data from a set of intrusive rocks emplaced in the vicinity of major ore bodies, as well as from large igneous intrusions in the Gällivare area, gave the following results: (1) the Dundret ultramafic–mafic layered complex (1883±5 Ma), the Aitik granite (1883±5 Ma), the Nautanen diorite (1870±12 Ma), the Vassaravaara ultramafic–mafic layered complex (1798±4 Ma), the Aitik dolerite (1813±9 Ma), the Bergmästergruvan and Sikträsk syenites (1795±4 Ma and 1801±3 Ma, respectively) and the Naalojärvi granite (1782±5 Ma). These data broadly fall within the ranges 1.89–1.87 Ga (early Svecofennian) and 1.80–1.78 Ga (late Svecofennian), but geochronologically allow further subdivision into pulses at 1885–1880, 1875–1870, 1800 and 1780 Ma. During these events, large layered ultramafic–mafic and felsic plutonic rocks were generated with distinct overlap in time suggesting coeval felsic–mafic magmatism. Results also indicate the presence of inherited c. 1.87 Ga zircon crystals in the plutonic rocks at 1.78 Ga, supporting reworking of the previous crust. These data indicate the importance of mantle-derived mafic underplating in the process of crustal magma generation in the region. The c. 1.88 Ga event that generated ultramafic–mafic layered complexes is tentatively suggested to have played an important role in the formation of the Aitik Cu–Au porphyry system. The later event at c. 1.80 Ga, generating voluminous mafic–felsic units, is suggested to be coupled to the regional iron-oxide-copper-gold (IOCG) overprint.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
Systematic revision of the Late Ordovician brachiopod genera Eochonetes Reed, 1917 and Thaerodonta Wang, 1949 was conducted utilizing specimen-based morphometric and species-level phylogenetic analyses. Previous studies had recognized Thaerodonta and Eochonetes as either distinct taxonomic entities or synonyms. New multivariate and phylogenetic analyses confirm the synonymy of Thaerodonta with Eochonetes and provide a framework to assess evolutionary and ecological patterns within the clade. Multivariate analyses were employed to delineate species in morphospace and provided information on potential species relationships. Phylogenetic analysis was used to produce an evolutionary framework for taxonomic revision and identify character evolution within the clade. Most species previously assigned to Thaerodonta are transferred to Eochonetes, and three others are excluded from Eochonetes and provisionally referred to other sowerbyellid genera. Three new species (Eochonetes maearum new species, E. voldemortus new species, E. minerva new species) are described, one species (Leptaena saxea Sardeson, 1892) is synonymized with E. recedens Sardeson, 1892, and one subspecies (Thaerodonta mucronata scabra Howe, 1965) is rejected. This study demonstrates that a combination of complementary approaches and data types has the potential to advance interpretations beyond analyses confined to single analytical tools. Specifically, multivariate analyses provide constraints on species boundaries, whereas species-level phylogenetic analyses provide frameworks to examine morphological, ecological, and biogeographic evolution within a clade.
Developmental psychopathologists face the difficult task of identifying the environmental conditions that may contribute to early childhood behavior problems. Highly stressed caregivers can exacerbate behavior problems, while children with behavior problems may make parenting more difficult and increase caregiver stress. Unknown is: (a) how these transactions originate, (b) whether they persist over time to contribute to the development of problem behavior and (c) what role resilience factors, such as child executive functioning, may play in mitigating the development of problem behavior. In the present study, transactional relations between caregiving stress, executive functioning, and behavior problems were examined in a sample of 1,388 children with prenatal drug exposures at three developmental time points: early childhood (birth to age 5), middle childhood (ages 6 to 9), and early adolescence (ages 10 to 13). Transactional relations differed between caregiving stress and internalizing versus externalizing behavior. Targeting executive functioning in evidence-based interventions for children with prenatal substance exposure who present with internalizing problems and treating caregiving psychopathology, depression, and parenting stress in early childhood may be particularly important for children presenting with internalizing behavior.
Common beans (Phaseolus vulgaris L.) are a nutrient-dense, low glycemic index food that supports healthy weight management in people and was examined for dogs. The objectives of this study were to evaluate the apparent total tract digestibility (ATTD) and nutrient utilisation of navy (NB) and black (BB) bean-based diets in overweight or obese companion dogs undergoing a weight loss intervention. A nutritionally complete, dry extruded dog food was used as the control (CON) diet and two isocaloric, nutrient matched bean diets, containing either 25% w/w cooked BB or NB powder formed the test diets. Diets were fed to adult, overweight companion dogs for either four weeks (short-term study, n = 30) or for twenty-six weeks (long-term study, n = 15) at 60% of maintenance calories for ideal weight. Apparent weight loss increased over time in both the short- and long-term studies (p < 0.001) but was not different between the three study groups: apparent weight loss was between 4.05% – 6.14% for the short-term study and 14.0% – 17.9% in the long-term study. The ATTD was within expected ranges for all groups, whereby total dry matter and crude protein ATTD was 7–8% higher in the BB diet compared to CON (P < 0.05), crude fat ATTD was similar across all diets, and nitrogen free extract ATTD was 5–6% higher in both BB and NB compared to CON (P < 0.05). Metabolisable energy was similar for all diets, and ranged from 3,434–3,632 kcal/kg. At the end of each study period, dogs had haemoglobin levels ≥12 g/dl, packed cell volume ≥36%, albumin ≥2.4 g/dl, ALP ≤ 300 IU/l and all median values for each group were within defined limits for nutritional adequacy. This investigation demonstrated that BB and NB diets were safe, digestible, and supported weight loss in calorically restricted, overweight or obese, adult companion dogs.