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Common names allow species diversity to be acknowledged by experts and non-specialists alike; they are descriptors with both scientific and cultural implications. However, a lack of clarity when using a common name could risk altering perceptions of threatened species. This is the case for the Critically Endangered wild camel Camelus ferus, which, despite extensive evidence of its species status, is frequently referred to in English as wild Bactrian camel. However, the wild camel (Mongolian: хавтгай, khavtgai; Chinese: 野骆驼, ye luo tuo) is not a wild version of the domestic Bactrian camel Camelus bactrianus but a separate species near extinction, with an estimated population of c. 950. Failure to clearly separate Bactrian and wild camels in name risks masking the plight of the few remaining wild camels with the visible abundance of the domesticated species. Here we advocate the use of the accurate English common name wild camel for C. ferus ideally alongside its Indigenous names to correctly represent its cultural and conservation importance.
OBJECTIVES/GOALS: The goal of this project was to conduct a preliminary assessment of in vivo feasibility early on in the drug-discovery process in an effort to expedite the translation of novel drug scaffolds to potential clinical candidates. The data gathered in this study will be used to direct analog synthesis of our current lead compounds through rational drug design. METHODS/STUDY POPULATION: Based on virtual and physical high-throughput screening efforts and subsequent similarity searching, we identified a set of potent and selective spermine oxidase (SMOX) inhibitors adhering to a common structural scaffold. In order to address potential barriers to in vivo use, we then conducted a robust optimization analysis in an effort to identify analogs with improved drug-like characteristics. Docking simulations to predict binding were performed and visualized using molecular modeling software (MOE and PyMol). ADMET properties were calculated using a variety of software resources including SwissADME and CDD Vault. RESULTS/ANTICIPATED RESULTS: Through these optimization efforts, we were able to successfully identify analogs with improved drug-like characteristics, including increases in predicted CNS penetration, isosteric replacement of metabolically labile functional groups, increased lipophilicity, and elimination of structural attributes suggestive of off-target activity. Analogs were ranked according to predicted binding and properties of in vivo feasibility. Compounds achieving the highest scores were then selected as scaffolds to guide analog synthesis. DISCUSSION/SIGNIFICANCE: Despite evidence implicating induction of SMOX as a mechanism contributing to neuronal pathology, the lack of potent and selective inhibitors with profiles conducive for in vivo use has significantly impeded clinical investigation of this target. In this presentation, rational drug design focusing on translational optimization will be discussed.
Preliminary evidence suggests beneficial effects of cognitive remediation in depression. An update of the current evidence is needed. The aim was to systematically assess the effectiveness of cognitive remediation in depression on three outcomes.
Methods
The meta-analysis was pre-registered on PROSPERO (CRD42019124316). PubMed, PsycINFO, Embase and Cochrane Library were searched on 2 February 2019 and 8 November 2020 for peer-reviewed published articles. We included randomized and non-randomized clinical trials comparing cognitive remediation to control conditions in adults with primary depression. Random-effects models were used to calculate Hedges' g, and moderators were assessed using mixed-effects subgroup analyses and meta-regression. Main outcome categories were post-treatment depressive symptomatology (DS), cognitive functioning (CF) and daily functioning (DF).
Results
We identified 5221 records and included 21 studies reporting on 24 comparisons, with 438 depressed patients receiving cognitive remediation and 540 patients in a control condition. We found a small effect on DS (g = 0.28, 95% CI 0.09–0.46, I2 40%), a medium effect on CF (g = 0.60, 95% CI 0.37–0.83, I2 44%) and a small effect on DF (g = 0.22, 95% CI 0.06–0.39, I2 3%). There were no significant effects at follow-up. Confounding bias analyses indicated possible overestimation of the DS and DF effects in the original studies.
Conclusions
Cognitive remediation in depression improves CF in the short term. The effects on DS and DF may have been overestimated. Baseline depressive symptom severity should be considered when administering cognitive remediation.
The propagation of gradient flow structures from microscopic to macroscopic models is a topic of high current interest. In this paper, we discuss this propagation in a model for the diffusion of particles interacting via hard-core exclusion or short-range repulsive potentials. We formulate the microscopic model as a high-dimensional gradient flow in the Wasserstein metric for an appropriate free-energy functional. Then we use the JKO approach to identify the asymptotics of the metric and the free-energy functional beyond the lowest order for single particle densities in the limit of small particle volumes by matched asymptotic expansions. While we use a propagation of chaos assumption at far distances, we consider correlations at small distance in the expansion. In this way, we obtain a clear picture of the emergence of a macroscopic gradient structure incorporating corrections in the free-energy functional due to the volume exclusion.
We describe system verification tests and early science results from the pulsar processor (PTUSE) developed for the newly commissioned 64-dish SARAO MeerKAT radio telescope in South Africa. MeerKAT is a high-gain (
${\sim}2.8\,\mbox{K Jy}^{-1}$
) low-system temperature (
${\sim}18\,\mbox{K at }20\,\mbox{cm}$
) radio array that currently operates at 580–1 670 MHz and can produce tied-array beams suitable for pulsar observations. This paper presents results from the MeerTime Large Survey Project and commissioning tests with PTUSE. Highlights include observations of the double pulsar
$\mbox{J}0737{-}3039\mbox{A}$
, pulse profiles from 34 millisecond pulsars (MSPs) from a single 2.5-h observation of the Globular cluster Terzan 5, the rotation measure of Ter5O, a 420-sigma giant pulse from the Large Magellanic Cloud pulsar PSR
$\mbox{J}0540{-}6919$
, and nulling identified in the slow pulsar PSR J0633–2015. One of the key design specifications for MeerKAT was absolute timing errors of less than 5 ns using their novel precise time system. Our timing of two bright MSPs confirm that MeerKAT delivers exceptional timing. PSR
$\mbox{J}2241{-}5236$
exhibits a jitter limit of
$<4\,\mbox{ns h}^{-1}$
whilst timing of PSR
$\mbox{J}1909{-}3744$
over almost 11 months yields an rms residual of 66 ns with only 4 min integrations. Our results confirm that the MeerKAT is an exceptional pulsar telescope. The array can be split into four separate sub-arrays to time over 1 000 pulsars per day and the future deployment of S-band (1 750–3 500 MHz) receivers will further enhance its capabilities.
It has been estimated that around 10-20% of all pregnant women suffer from antenatal depressive or anxiety symptoms. These symptoms have been associated with multiple adverse child outcomes including obstetric problems, e.g. preterm delivery, Apgar score and low birth weight. Therefore, considerable health gains may be achieved if depression and anxiety during the perinatal period are adequately treated. Nevertheless, to date, no previous trials have published on the effects of Cognitive Behavioral Therapy (CBT) during pregnancy on child outcomes.
Methods
The ´Pregnancy Outcomes After a Maternity Intervention for Stressful Emotions´ (PROMISES) trial is a randomized controlled trial, which compares the effects of CBT vs. care as usual (CAU) during pregnancy among a group of women with (sub)clinically depressive and/or anxiety symptoms (n=226) on both maternal and child outcomes. Child outcomes comprise a range of obstetric outcomes including birth weight, Apgar score, and gestational age. Independent samples t-tests were performed to investigate differences in mean values.
Results
No significant differences were found between the CBT- and the CAU-groups, in gestational age (39+0 vs 39+2 weeks+days, p=.99), birth weight (3447 vs 3509 grams, p=.24), or Apgar score at 1 (8.6 vs 8.6, p=.99), 5 (9.5 vs 9.6, p=.31), and 10 minutes (9.7 vs 9.8, p=.26).
Conclusion/discussion
Although CBT as early treatment of antenatal depression and anxiety is most likely to be effective for prevention of postpartum depression, CBT seems to have no effect on major obstetric outcomes.
Prevention, identification, and treatment of maternal psychopathology may be favourable for both mother and child. Both a low socio-economic position (SEP) and adverse life events are considered risk factors for symptoms of anxiety and depression during pregnancy. It is unknown whether the effect of adverse life events is modified by SEP.
Objective
To investigate the relationship between symptoms of anxiety and depression in pregnancy and adverse life events, and how this relationship is modified by SEP.
Methods
The population based Pregnancy, Anxiety and Depression (PAD) Study is a prospective study in Dutch obstetric care. We assessed symptoms of anxiety and depression in pregnant women, SEP (educational level of mother and partner, work status of mother and partner and family income), and the number of adverse life events, categorised by period in life. The association of the number of adverse life events with anxiety and depression, as well as effect modification by SEP was tested using linear regression analyses.
Results
We included 4272 participants. The number of life events and low SEP were independantly associated with symptoms of both anxiety and depression during pregnancy. Additionally, we found that aspects of SEP: low maternal educational level, maternal unemployment, and low family income may increase the adverse effect of adverse life events.
Conclusion
A low SEP increases the adverse impact of adverse life events. In an early screening for anxiety and depression, the number of adverse life events and more important the above-mentioned aspects of SEP should play a key role.
Cognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients.
Methods
In total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes (‘normal’, ‘mixed’ and ‘impaired’) in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype.
Results
Probands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype.
Conclusions
Cross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.
According to cognitive behavioural theory, cognitive factors (i.e. underlying general dysfunctional beliefs and (situation) specific illness beliefs) are theorized to lead to outcomes like anxiety and depression. In clinical practice, general dysfunctional beliefs are generally not tackled directly in short-term-therapy.
Aims:
The goal of the present study was to investigate the associations of general versus specific illness beliefs on anxiety and depressive symptoms and psychiatric disorders among a subgroup of patients with inflammatory bowel disease (IBD) with poor mental quality of life (QoL).
Method:
This study concerns cross-sectional data, collected at baseline from a randomized clinical trial. One hundred and eighteen patients, recruited at four Dutch hospitals, with poor QoL (score ≤23 on the mental health subscale of the Short-Form 36-item Health-Survey; SF-36) were included. General dysfunctional beliefs were measured by the Dysfunctional Attitude Scale (DAS), specific illness beliefs by the Illness Perceptions Questionnaire-Revised (IPQ-R), anxiety and depressive symptoms by the Hospital Anxiety and Depression Scale (HADS), and psychiatric disorders by the Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID-I).
Results:
Univariate analyses showed associations between the level of anxiety and/or depression and general dysfunctional beliefs and four specific illness beliefs (consequences, personal control, emotional representations and treatment control). Among patients with IBD with psychiatric disorders, only the DAS was significantly associated with anxiety and depression (DAS added to IPQ-R and IPQ-R added to DAS).
Conclusions:
Psychological interventions may have to target general dysfunctional beliefs of patients with IBD with co-morbid psychiatric disorders to be effective. These patients with IBD are especially in need of psychological treatment.
As depression has a recurrent course, relapse and recurrence prevention is essential.
Aims
In our randomised controlled trial (registered with the Nederlands trial register, identifier: NTR1907), we found that adding preventive cognitive therapy (PCT) to maintenance antidepressants (PCT+AD) yielded substantial protective effects versus antidepressants only in individuals with recurrent depression. Antidepressants were not superior to PCT while tapering antidepressants (PCT/−AD). To inform decision-makers on treatment allocation, we present the corresponding cost-effectiveness, cost-utility and budget impact.
Method
Data were analysed (n = 289) using a societal perspective with 24-months of follow-up, with depression-free days and quality-adjusted life years (QALYs) as health outcomes. Incremental cost-effectiveness ratios were calculated and cost-effectiveness planes and cost-effectiveness acceptability curves were derived to provide information about cost-effectiveness. The budget impact was examined with a health economic simulation model.
Results
Mean total costs over 24 months were €6814, €10 264 and €13 282 for AD+PCT, antidepressants only and PCT/−AD, respectively. Compared with antidepressants only, PCT+AD resulted in significant improvements in depression-free days but not QALYs. Health gains did not significantly favour antidepressants only versus PCT/−AD. High probabilities were found that PCT+AD versus antidepressants only and antidepressants only versus PCT/−AD were dominant with low willingness-to-pay thresholds. The budget impact analysis showed decreased societal costs for PCT+AD versus antidepressants only and for antidepressants only versus PCT/−AD.
Conclusions
Adding PCT to antidepressants is cost-effective over 24 months and PCT with guided tapering of antidepressants in long-term users might result in extra costs. Future studies examining costs and effects of antidepressants versus psychological interventions over a longer period may identify a break-even point where PCT/−AD will become cost-effective.
Declaration of interest
C.L.H.B. is co-editor of PLOS One and receives no honorarium for this role. She is also co-developer of the Dutch multidisciplinary clinical guideline for anxiety and depression, for which she receives no remuneration. She is a member of the scientific advisory board of the National Insure Institute, for which she receives an honorarium, although this role has no direct relation to this study. C.L.H.B. has presented keynote addresses at conferences, such as the European Psychiatry Association and the European Conference Association, for which she sometimes receives an honorarium. She has presented clinical training workshops, some including a fee. She receives royalties from her books and co-edited books and she developed preventive cognitive therapy on the basis of the cognitive model of A. T. Beck. W.A.N. has received grants from the Netherlands Organisation for Health Research and Development and the European Union and honoraria and speakers' fees from Lundbeck and Aristo Pharma, and has served as a consultant for Daleco Pharma.
Mercury is surrounded by a tenuous exosphere in which particles travel on ballistic trajectories under the influence of a combination of gravity and solar radiation pressure. The densities are so small that the surface forms the exobase, and particles in the exosphere are more likely to collide with it rather than with each other. During the three flybys of Mercury by the Mariner 10 spacecraft in 1974–1975, the probe's Ultraviolet Spectrometer made measurements of hydrogen and helium and a tentative detection of oxygen. These observations were followed a decade later by discoveries with Earth-based telescopes of exospheric sodium and potassium, and still later of calcium, aluminum, and iron. In addition to characterizing sodium, calcium, and hydrogen in Mercury’s exosphere, the Mercury Atmospheric and Surface Composition Spectrometer instrument on the MESSENGER spacecraft detected magnesium, ionized calcium, aluminum, and manganese. Thus, the total inventory of confirmed exospheric neutral species now includes H, He, Na, K, Ca, Mg, Al, Fe, and Mn. This chapter summarizes both ground-based and space-based observations of Mercury’s exosphere that have been made from its discovery by Mariner 10 through the four Earth years of nearly continuous orbital observations by the MESSENGER spacecraft.
Mercury is surrounded by a tenuous exosphere in which particles travel on ballistic trajectories under the influence of a combination of gravity and solar radiation pressure. The densities are so small that the surface forms the exobase, and particles in the exosphere are more likely to collide with it rather than with each other. During the three flybys of Mercury by the Mariner 10 spacecraft in 1974–1975, the probe's Ultraviolet Spectrometer made measurements of hydrogen and helium and a tentative detection of oxygen. These observations were followed a decade later by discoveries with Earth-based telescopes of exospheric sodium and potassium, and still later of calcium, aluminum, and iron. In addition to characterizing sodium, calcium, and hydrogen in Mercury’s exosphere, the Mercury Atmospheric and Surface Composition Spectrometer instrument on the MESSENGER spacecraft detected magnesium, ionized calcium, aluminum, and manganese. Thus, the total inventory of confirmed exospheric neutral species now includes H, He, Na, K, Ca, Mg, Al, Fe, and Mn. This chapter summarizes both ground-based and space-based observations of Mercury’s exosphere that have been made from its discovery by Mariner 10 through the four Earth years of nearly continuous orbital observations by the MESSENGER spacecraft.
Hausmannite (Mn3O4), a manganese oxide with a tetragonally distorted spinel structure, is considered to be ferrimagnetic with a very low Curie temperature of 42.5 K. However, strongly magnetic hausmannite has been discovered in some of the hydrothermally altered high-grade manganese ores of the giant Kalahari manganese deposit in South Africa. EDS-electron microprobe analyses indicate magnetic hausmannite to contain on average between 3 and 11.3 wt.% Fe2O3. In contrast non-magnetic hausmannite contains on average about 1–3 wt.% Fe2O3. X-ray powder diffraction analyses reveal small changes in cell dimensions of the magnetic hausmannite related to the high iron content. Mössbauer spectroscopy suggests that all iron is in the trivalent state. Optical microscopy and scanning electron microscopy (electron back-scatter imaging) proved the magnetic hausmannite to be homogeneous in composition, containing only a few minute inclusions of hematite. Magnetic blocking temperatures of the iron-rich hausmannite, approximating the Curie temperature, are of the order of 750 K. It is suggested that the ferrimagnetic state of hausmannite is stabilized and enhanced by replacement of Mn3+ by Fe3+.
Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, little is known regarding brain functional processes mediating ECT effects.
Method
In a non-randomized prospective study, functional magnetic resonance imaging data during the automatic processing of subliminally presented emotional faces were obtained twice, about 6 weeks apart, in patients with major depressive disorder (MDD) before and after treatment with ECT (ECT, n = 24). Additionally, a control sample of MDD patients treated solely with pharmacotherapy (MED, n = 23) and a healthy control sample (HC, n = 22) were obtained.
Results
Before therapy, both patient groups equally showed elevated amygdala reactivity to sad faces compared with HC. After treatment, a decrease in amygdala activity to negative stimuli was discerned in both patient samples indicating a normalization of amygdala function, suggesting mechanisms potentially unspecific for ECT. Moreover, a decrease in amygdala activity to sad faces was associated with symptomatic improvements in the ECT sample (rspearman = −0.48, p = 0.044), and by tendency also for the MED sample (rspearman = −0.38, p = 0.098). However, we did not find any significant association between pre-treatment amygdala function to emotional stimuli and individual symptom improvement, neither for the ECT sample, nor for the MED sample.
Conclusions
In sum, the present study provides first results regarding functional changes in emotion processing due to ECT treatment using a longitudinal design, thus validating and extending our knowledge gained from previous treatment studies. A limitation was that ECT patients received concurrent medication treatment.
The authors discuss results of long-term Dutch field projects in three regions in Italy and review case studies taken from these study areas in the light of indigenous developments in early Italian centralization and urbanization. By looking at regional developments in the domains of economy, religious and funerary practice as well as that of social relationships, they arrive at the conclusion that material culture was actively used in indigenous contexts. There is a consequent need for re-definition of centralization and urbanization, which in the Italian context are often seen as non-indigenous achievements. Comparative regional research, as suggested by the authors' case studies on the Sibaritide, the Brindisino and the Pontine region, will reveal both general trends concerning the concepts discussed and regional idiosyncrasies depending on regional traditions, histories and the regional landscape. To this end, a new project was launched, known as the Regional Pathways to Complexity project, that is introduced to the reader at the end of this paper.
Feral rye is an agricultural and ruderal weed of the western United States. We investigated how it has phenotypically diverged from its cultivated ancestor, domesticated cereal rye, and across its range since the introduction of its progenitor. Vegetative growth, flowering phenology, and reproductive characters of feral populations from across a 13° range in latitude in the northwestern United States were compared to that of rye cultivars under both vernalized (cold-treated) and nonvernalized conditions. Feral populations as a whole had smaller seeds, thinner culms, and a delay in flowering relative to cultivars, regardless of cold treatment. Vernalized feral populations from northern latitudes (northern California and eastern Washington) produced more, but smaller leaves and more tillers than both vernalized rye cultivars and southern California feral populations. Northern feral populations also flowered significantly later, irrespective of vernalization treatment. We conclude that feral rye is phenotypically distinct from domesticated cereal rye and that feral populations have diverged regionally from one another. Reproductive isolation from domesticated rye, due both to the loss in popularity of the crop and to phenological shifts in feral rye relative to cultivars, may be contributing to the rapid evolution of this weed away from its domesticated ancestor in less than 120 yr since its introduction.
Current ultra-high-risk (UHR) criteria appear insufficient to predict imminent onset of first-episode psychosis, as a meta-analysis showed that about 20% of patients have a psychotic outcome after 2 years. Therefore, we aimed to develop a stage-dependent predictive model in UHR individuals who were seeking help for co-morbid disorders.
Method
Baseline data on symptomatology, and environmental and psychological factors of 185 UHR patients (aged 14–35 years) participating in the Dutch Early Detection and Intervention Evaluation study were analysed with Cox proportional hazard analyses.
Results
At 18 months, the overall transition rate was 17.3%. The final predictor model included five variables: observed blunted affect [hazard ratio (HR) 3.39, 95% confidence interval (CI) 1.56–7.35, p < 0.001], subjective complaints of impaired motor function (HR 5.88, 95% CI 1.21–6.10, p = 0.02), beliefs about social marginalization (HR 2.76, 95% CI 1.14–6.72, p = 0.03), decline in social functioning (HR 1.10, 95% CI 1.01–1.17, p = 0.03), and distress associated with suspiciousness (HR 1.02, 95% CI 1.00–1.03, p = 0.01). The positive predictive value of the model was 80.0%. The resulting prognostic index stratified the general risk into three risk classes with significantly different survival curves. In the highest risk class, transition to psychosis emerged on average ⩾8 months earlier than in the lowest risk class.
Conclusions
Predicting a first-episode psychosis in help-seeking UHR patients was improved using a stage-dependent prognostic model including negative psychotic symptoms (observed flattened affect, subjective impaired motor functioning), impaired social functioning and distress associated with suspiciousness. Treatment intensity may be stratified and personalized using the risk stratification.