Compliance of community teams with specialist service recommendations for obsessive-compulsive and body dysmorphic disorders.

Aims and method To examine how often referring community mental health teams (CMHTs) utilised treatment recommendations made by the national highly specialised service for patients with severe obsessive-compulsive disorder (OCD) and body dysmorphic disorder (BDD). We analysed all patient notes for admissions to the unit (August 2012-August 2014) and recorded how many treatment recommendations were implemented by CMHTs prior to admission and at 6 months post-discharge. Results Overall, 66% of our recommendations were met by CMHTs prior to admission and 74% after discharge. Most recommendations concerned medication and the continued need for care coordination by the CMHT. Clinical implications A significant proportion of patients in our audit did not receive optimum treatment in the community as recommended by our service. As highly specialised services are a limited resource and these patients have not responded to previous treatment, this has implications for the use of such resources

Examining psychedelic-induced changes in social functioning and connectedness in a naturalistic online sample using the five-factor model of personality.

The present study examines prospective changes in personality traits relevant to social functioning as well as perceived social connectedness in relation to the naturalistic use of psychedelic compounds in an online volunteer sample. The study also examined the degree to which demographic characteristics, social setting, baseline personality, and acute subjective factors (e.g., emotional breakthrough experiences) influenced trajectories of personality and perceived social connectedness. Participants recruited online completed self-report measures of personality and social connectedness at three timepoints (baseline, 2weeks post-experience, 4weeks post-experience). Linear mixed models were used to examine changes in outcomes and the moderation of these outcomes by covariates. The most substantive changes were reductions in the personality domains Neuroticism, and increases in Agreeableness and social connectedness. Notably, reductions in Neuroticism and increases in Agreeableness covaried over time, which may be suggestive of common processes involving emotion regulation. Preliminary evidence was found for a specific effect on a component of Agreeableness involving a critical and quarrelsome interpersonal style. Although moderation by demographic characteristics, social setting, baseline personality, and acute factors generally found limited support, baseline standing on Neuroticism, perspective taking, and social connectedness showed tentative signs of amplifying adaptive effects on each trait, respectively. Our findings hold implications for the potential use of psychedelics for treating interpersonal elements of personality pathology as well as loneliness

A partial skeleton of an enantiornithine bird from the early Cretaceous of northwestern China

Although recent discoveries from Lower Cretaceous sediments in northeastern China have greatly improved our understanding of the initial stages of avian diversification in eastern Asia, the early evolution of Aves elsewhere on the continent remains poorly understood. In 2004, a collaborative field effort directed by personnel from the Chinese Academy of Geological Sciences and Carnegie Museum of Natural History recovered multiple partial to nearly complete avian skeletons from outcrops of the Lower Cretaceous Xiagou Formation exposed in the Changma Basin of northwestern Gansu Province, China. Here we describe a thrush-sized partial skeleton comprised of a fragmentary pelvic girdle and largely complete hind limbs. A phylogenetic analysis of 20 avian ingroup taxa and 169 anatomical characters places the specimen in Enantiomithes, and within that clade, in Enenantiomithes. When coupled with additional recent discoveries from the Changma Basin, the new skeleton improves our understanding of early avian evolution and diversification in central Asia

G-quadruplex DNA motifs in the malaria parasite Plasmodium falciparum and their potential as novel antimalarial drug targets

G-quadruplexes are DNA or RNA secondary structures that can be formed from guanine-rich nucleic acids. These four-stranded structures, composed of stacked quartets of guanine bases, can be highly stable and have been demonstrated to occur in vivo in the DNA of human cells and other systems, where they play important biological roles, influencing processes such as telomere maintenance, DNA replication and transcription, or, in the case of RNA G-quadruplexes, RNA translation and processing. We report for the first time that DNA G-quadruplexes can be detected in the nuclei of the malaria parasite Plasmodium falciparum, which has one of the most A/T-biased genomes sequenced and therefore possesses few guanine-rich sequences with the potential to form G-quadruplexes. We show that despite this paucity of putative G-quadruplex-forming sequences, P. falciparum parasites are sensitive to several G-quadruplex-stabilizing drugs, including quarfloxin, which previously reached phase 2 clinical trials as an anticancer drug. Quarfloxin has a rapid initial rate of kill and is active against ring stages as well as replicative stages of intraerythrocytic development. We show that several G-quadruplex-stabilizing drugs, including quarfloxin, can suppress the transcription of a G-quadruplex-containing reporter gene in P. falciparum but that quarfloxin does not appear to disrupt the transcription of rRNAs, which was proposed as its mode of action in both human cells and trypanosomes. These data suggest that quarfloxin has potential for repositioning as an antimalarial with a novel mode of action. Furthermore, G-quadruplex biology in P. falciparum may present a target for development of other new antimalarial drugs

Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246

TP53 mutants (mutp53) are involved in the pathogenesis of most human cancers. Specific mutp53 proteins gain oncogenic functions (GOFs) distinct from the tumor suppressor activity of the wild-type protein. Tumor-associated macrophages (TAMs), a hallmark of solid tumors, are typically correlated with poor prognosis. Here, we report a non-cell-autonomous mechanism, whereby human mutp53 cancer cells reprogram macrophages to a tumor supportive and anti-inflammatory state. The colon cancer cells harboring GOF mutp53 selectively shed miR-1246-enriched exosomes. Uptake of these exosomes by neighboring macrophages triggers their miR-1246-dependent reprogramming into a cancerpromoting state. Mutp53-reprogammed TAMs favor anti-inflammatory immunosuppression with increased activity of TGF-β. These findings, associated with poor survival in colon cancer patients, strongly support a microenvironmental GOF role for mutp53 in actively engaging the immune system to promote cancer progression and metastasis

Structural similarity assessment for drug sensitivity prediction in cancer

<p>Abstract</p> <p>Background</p> <p>The ability to predict drug sensitivity in cancer is one of the exciting promises of pharmacogenomic research. Several groups have demonstrated the ability to predict drug sensitivity by integrating chemo-sensitivity data and associated gene expression measurements from large anti-cancer drug screens such as NCI-60. The general approach is based on comparing gene expression measurements from sensitive and resistant cancer cell lines and deriving drug sensitivity profiles consisting of lists of genes whose expression is predictive of response to a drug. Importantly, it has been shown that such profiles are generic and can be applied to cancer cell lines that are not part of the anti-cancer screen. However, one limitation is that the profiles can not be generated for untested drugs (i.e., drugs that are not part of an anti-cancer drug screen). In this work, we propose using an existing drug sensitivity profile for drug A as a substitute for an untested drug B given high structural similarities between drugs A and B.</p> <p>Results</p> <p>We first show that structural similarity between pairs of compounds in the NCI-60 dataset highly correlates with the similarity between their activities across the cancer cell lines. This result shows that structurally similar drugs can be expected to have a similar effect on cancer cell lines. We next set out to test our hypothesis that we can use existing drug sensitivity profiles as substitute profiles for untested drugs. In a cross-validation experiment, we found that the use of substitute profiles is possible without a significant loss of prediction accuracy if the substitute profile was generated from a compound with high structural similarity to the untested compound.</p> <p>Conclusion</p> <p>Anti-cancer drug screens are a valuable resource for generating omics-based drug sensitivity profiles. We show that it is possible to extend the usefulness of existing screens to untested drugs by deriving substitute sensitivity profiles from structurally similar drugs part of the screen.</p

Soccer Team Vectors

In this work we present STEVE - Soccer TEam VEctors, a principled approach for learning real valued vectors for soccer teams where similar teams are close to each other in the resulting vector space. STEVE only relies on freely available information about the matches teams played in the past. These vectors can serve as input to various machine learning tasks. Evaluating on the task of team market value estimation, STEVE outperforms all its competitors. Moreover, we use STEVE for similarity search and to rank soccer teams.Comment: 11 pages, 1 figure; This paper was presented at the 6th Workshop on Machine Learning and Data Mining for Sports Analytics at ECML/PKDD 2019, W\"urzburg, Germany, 201

Depressive disorders in caregivers of dementia patients: a systematic review.

Although depressive symptomatology has been well studied in caregivers of patients with dementia, depressive disorders have been examined much less. We conducted a systematic literature search in major bibliographical databases (Medline, Psychinfo, Dissertation Abstracts), and included studies examining caregivers of dementia patients that reported the prevalence of major depressive disorder, according to diagnostic criteria as assessed with a standardized psychiatric diagnostic interview. Ten studies with a total of 790 caregivers were identified (sample sizes: 22–147). In only one of the studies, a representative community sample was used. A total of 176 subjects (22.3%) had a depressive disorder (prevalence range from 0.15–0.32). In the three studies reporting differential prevalence rates for men and women somewhat smaller prevalence rates were found for men than for women. In six studies caregivers were compared to a (mostly matched) control group. The relative risks of having a depressive disorder in caregivers ranged from 2.80–38.68 (all RR’s were significant). In the three prospective studies relatively high incidence rates were found (0.48). This study made it clear that prevalence and incidence of depressive disorders are increased in caregivers of dementia patients. More research is clearly needed in this population

Changes in biomass allocation buffer low CO2 effects on tree growth during the last glaciation

Isotopic measurements on junipers growing in southern California during the last glacial, when the ambient atmospheric [CO2] (ca) was ~180 ppm, show the leaf-internal [CO2] (ci) was approaching the modern CO2 compensation point for C3 plants. Despite this, stem growth rates were similar to today. Using a coupled light-use efficiency and tree growth model, we show that it is possible to maintain a stable ci/ca ratio because both vapour pressure deficit and temperature were decreased under glacial conditions at La Brea, and these have compensating effects on the ci/ca ratio. Reduced photorespiration at lower temperatures would partly mitigate the effect of low ci on gross primary production, but maintenance of present-day radial growth also requires a ~27% reduction in the ratio of fine root mass to leaf area. Such a shift was possible due to reduced drought stress under glacial conditions at La Brea. The necessity for changes in allocation in response to changes in [CO2] is consistent with increased below-ground allocation, and the apparent homoeostasis of radial growth, as ca increases today

Changes in Treatment Content of Services During Trauma-informed Integrated Services for Women with Co-occurring Disorders

The experience of trauma is highly prevalent in the lives of women with mental health and substance abuse problems. We examined how an intervention targeted to provide trauma-informed integrated services in the treatment of co-occurring disorders has changed the content of services reported by clients. We found that the intervention led to an increased provision of integrated services as well as services addressing each content area: trauma, mental health and substance abuse. There was no increase in service quantity from the intervention. Incorporation of trauma-specific element in the treatment of mental health and substance abuse may have been successfully implemented at the service level thereby better serve women with complex behavioral health histories