Global climate change is altering community composition across many ecosystems due to nonrandom species turnover, typically characterized by the loss of specialist species and increasing similarity ...of biological communities across spatial scales. As anthropogenic disturbances continue to alter species composition globally, there is a growing need to identify how species responses influence the establishment of distinct assemblages, such that management actions may be appropriately assigned. Here, we use trait‐based analyses to compare temporal changes in five complementary indices of reef fish assemblage structure among six taxonomically distinct coral reef habitats exposed to a system‐wide thermal stress event. Our results revealed increased taxonomic and functional similarity of previously distinct reef fish assemblages following mass coral bleaching, with changes characterized by subtle, but significant, shifts toward predominance of small‐bodied, algal‐farming habitat generalists. Furthermore, while the taxonomic or functional richness of fish assemblages did not change across all habitats, an increase in functional originality indicated an overall loss of functional redundancy. We also found that prebleaching coral composition better predicted changes in fish assemblage structure than the magnitude of coral loss. These results emphasize how measures of alpha diversity can mask important changes in the structure and functioning of ecosystems as assemblages reorganize. Our findings also highlight the role of coral species composition in structuring communities and influencing the diversity of responses of reef fishes to disturbance. As new coral species configurations emerge, their desirability will hinge upon the composition of associated species and their capacity to maintain key ecological processes in spite of ongoing disturbances.
The 2016 pantropical coral bleaching event caused widespread coral loss, and the reorganization of species. Our trait‐based analyses of temporal changes in reef fish assemblage structure revealed increased taxonomic and functional similarity of previously distinct reef fish assemblages following mass coral bleaching, characterized by subtle, but significant, shifts toward predominance of small‐bodied, algal‐farming habitat generalists. While the taxonomic or functional richness of fish assemblages did not change across all habitats, an increase in functional originality indicated an overall loss of functional redundancy. Finally, results showed that prebleaching coral composition better predicted changes in fish assemblage structure than the magnitude of coral loss
Up to 20% of adolescents experience an episode of major depression by age 18 years yet few receive evidence-based treatments for their depression.
To determine whether a collaborative care ...intervention for adolescents with depression improves depressive outcomes compared with usual care.
Randomized trial with blinded outcome assessment conducted between April 2010 and April 2013.
Nine primary care clinics in the Group Health system in Washington State.
Adolescents (aged 13-17 years) who screened positive for depression (Patient Health Questionnaire 9-item PHQ-9 score ≥10) on 2 occasions or who screened positive and met criteria for major depression, spoke English, and had telephone access were recruited. Exclusions included alcohol/drug misuse, suicidal plan or recent attempt, bipolar disorder, developmental delay, and seeing a psychiatrist.
Twelve-month collaborative care intervention including an initial in-person engagement session and regular follow-up by master's-level clinicians. Usual care control youth received depression screening results and could access mental health services through Group Health.
The primary outcome was change in depressive symptoms on a modified version of the Child Depression Rating Scale-Revised (CDRS-R; score range, 14-94) from baseline to 12 months. Secondary outcomes included change in Columbia Impairment Scale score (CIS), depression response (≥50% decrease on the CDRS-R), and remission (PHQ-9 score <5).
Intervention youth (n = 50), compared with those randomized to receive usual care (n = 51), had greater decreases in CDRS-R scores such that by 12 months intervention youth had a mean score of 27.5 (95% CI, 23.8-31.1) compared with 34.6 (95% CI, 30.6-38.6) in control youth (overall intervention effect: F2,747.3 = 7.24, P < .001). Both intervention and control youth experienced improvement on the CIS with no significant differences between groups. At 12 months, intervention youth were more likely than control youth to achieve depression response (67.6% vs 38.6%, OR = 3.3, 95% CI, 1.4-8.2; P = .009) and remission (50.4% vs 20.7%, OR = 3.9, 95% CI, 1.5-10.6; P = .007).
Among adolescents with depression seen in primary care, a collaborative care intervention resulted in greater improvement in depressive symptoms at 12 months than usual care. These findings suggest that mental health services for adolescents with depression can be integrated into primary care.
clinicaltrials.gov Identifier: NCT01140464.
The purpose of this study was to examine the performance characteristics and validity of the Patient Health Questionnaire-9 Item (PHQ-9) as a screening tool for depression among adolescents.
The ...PHQ-9 was completed by 442 youth (aged 13-17 years) who were enrolled in a large health care-delivery system and participated in a study on depression outcomes. Criterion validity and performance characteristics were assessed against an independent structured mental health interview (the Child Diagnostic Interview Schedule DISC-IV). Construct validity was tested by examining associations between the PHQ-9 and a self-report measure of functional impairment, as well as parental reports of child psychosocial impairment and internalizing symptoms.
A PHQ-9 score of 11 or more had a sensitivity of 89.5% and a specificity of 77.5% for detecting youth who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression on the DISC-IV. Receiver-operator-curve analysis revealed that the PHQ-9 had an area under the curve of 0.88 (95% confidence interval: 0.82-0.94), and the cut point of 11 was optimal for maximizing sensitivity without loss of specificity. Increasing PHQ-9 scores were significantly correlated with increasing levels of functional impairment, as well as parental report of internalizing symptoms and psychosocial problems.
Although the optimal cut point is higher among adolescents, the sensitivity and specificity of the PHQ-9 are similar to those of adult populations. The brief nature and ease of scoring of this instrument make this tool an excellent choice for providers and researchers seeking to implement depression screening in primary care settings.
Abstract Purpose Previous studies in adults have suggested concussion and other brain injury presents a risk factor for depression. The goal of our study was to analyze the association between ...previous concussion and current depression diagnosis in a large nationally representative adolescent data set. Methods Retrospective cohort study using the National Survey of Children's Health 2007–2008, a nationally representative survey conducted via random digit dialing. Data were obtained by parental report. We included youth 12–17 years old without a current concussion (N = 36,060), and evaluated the association between previous concussion (binary) and current depression diagnosis (binary) using multiple logistic regression to control for age, sex, parental mental health, and socioeconomic status. Results After controlling for age, sex, parental mental health, and socioeconomic status, history of concussion was associated with a 3.3-fold greater risk for depression diagnosis (95% CI: 2.0–5.5). Other factors significantly associated with depression diagnosis included poor or fair parental mental health (OR: 3.7, 95% CI: 2.8–4.9), and older age (15–17 years vs. 12–14 years, OR: 1.4, 95% CI: 1.1–1.8). Sex of the subject was not significantly related to depression diagnosis. Being above 200% of the poverty level was associated with approximately a 50% decreased risk of depression diagnosis (95% CI: 35%–70%). Conclusions History of concussion was associated with a higher prevalence of diagnosed depression in a large nationally representative adolescent data set. Clinicians should screen for depression in their adolescent patients with concussion. Future studies should confirm this association using prospective methodology and examine potential treatment approaches.
Adolescents' wide use of technology opens up opportunities to integrate technology into health visits and health care. In particular, technology has the potential to influence adolescent behavior ...change by offering new avenues for provider communication and support for healthy choices through many different platforms. However, little information exists to guide the integration of technology into adolescent health care, especially adolescents' perspectives and preferences for what they find useful.
This qualitative study aimed to take a broad approach to understanding adolescents' use of technology for supporting their overall health and to understand whether and how adolescents envision using technology to enhance their health and clinical care, particularly in communicating with their provider.
Adolescents (13-18 years) were recruited to participate in semi-structured, in-depth individual interviews. Potential participants were approached in-person through the Seattle Children's Hospital Adolescent Medicine Clinic while they were waiting for consultation appointments, through outreach to youth who expressed interest in other local research study activities, and via flyers in waiting rooms. Interviews were recorded, transcribed, and analyzed using a thematic analysis approach.
Thirty-one adolescents (58% female, M= 15.2 years) were interviewed and described 3 main uses of technology: (1) to gather information, (2a) to share their own experiences and (2b) view others' experiences in order to gain social support or inspiration, and (3) to track behaviors and health goals. Perceived benefits and potential downsides were identified for technology use. Teens desired to use technology with their provider for 3 main reasons: (1) have questions answered outside of visits, (2) have greater access to providers as a way to build relationship/rapport, and (3) share data regarding behaviors in between visits. Social media was not a preferred method for communicating with providers for any of the youth due to concerns about privacy and intrusiveness.
Although youth are avid users of technology in general, in regard to technology for health, they display specific use preferences especially in how they wish to use it to communicate with their primary care provider. Healthcare providers should offer guidance to youth with regard to how they have used and plan to use technology and how to balance potential positives and negatives of use. Technology developers should take youth preferences into account when designing new health technology and incorporate ways they can use it to communicate with their healthcare provider.
Abstract Despite the recognition that behavioral and medical health conditions are frequently intertwined, the existing health care system divides management for these issues into separate settings. ...This separation results in increased barriers to receipt of care and contributes to problems of underdetection, inappropriate diagnosis, and lack of treatment engagement. Adolescents and young adults with mental health conditions have some of the lowest rates of treatment for their conditions of all age groups. Integration of behavioral health into primary care settings has the potential to address these barriers and improve outcomes for adolescents and young adults. In this paper, we review the current research literature for behavioral health integration in the adolescent and young adult population and make recommendations for needed research to move the field forward.
Systematic studies of cancer genomes have provided unprecedented insights into the molecular nature of cancer. Using this information to guide the development and application of therapies in the ...clinic is challenging. Here, we report how cancer-driven alterations identified in 11,289 tumors from 29 tissues (integrating somatic mutations, copy number alterations, DNA methylation, and gene expression) can be mapped onto 1,001 molecularly annotated human cancer cell lines and correlated with sensitivity to 265 drugs. We find that cell lines faithfully recapitulate oncogenic alterations identified in tumors, find that many of these associate with drug sensitivity/resistance, and highlight the importance of tissue lineage in mediating drug response. Logic-based modeling uncovers combinations of alterations that sensitize to drugs, while machine learning demonstrates the relative importance of different data types in predicting drug response. Our analysis and datasets are rich resources to link genotypes with cellular phenotypes and to identify therapeutic options for selected cancer sub-populations.
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•We integrate heterogeneous molecular data of 11,289 tumors and 1,001 cell lines•We measure the response of 1,001 cancer cell lines to 265 anti-cancer drugs•We uncover numerous oncogenic aberrations that sensitize to an anti-cancer drug•Our study forms a resource to identify therapeutic options for cancer sub-populations
A look at the pharmacogenomic landscape of 1,001 human cancer cell lines points to new treatment applications for hundreds of known anti-cancer drugs.
It is not fully understood why COVID-19 is typically milder in children
. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed ...paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.
Combinations of anti-cancer drugs can overcome resistance and provide new treatments
. The number of possible drug combinations vastly exceeds what could be tested clinically. Efforts to ...systematically identify active combinations and the tissues and molecular contexts in which they are most effective could accelerate the development of combination treatments. Here we evaluate the potency and efficacy of 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines. We show that synergy between drugs is rare and highly context-dependent, and that combinations of targeted agents are most likely to be synergistic. We incorporate multi-omic molecular features to identify combination biomarkers and specify synergistic drug combinations and their active contexts, including in basal-like breast cancer, and microsatellite-stable or KRAS-mutant colon cancer. Our results show that irinotecan and CHEK1 inhibition have synergistic effects in microsatellite-stable or KRAS-TP53 double-mutant colon cancer cells, leading to apoptosis and suppression of tumour xenograft growth. This study identifies clinically relevant effective drug combinations in distinct molecular subpopulations and is a resource to guide rational efforts to develop combinatorial drug treatments.
Inpatient pediatric mental health is a priority topic for national quality measurement and improvement, but nationally representative data on the patients admitted or their diagnoses are lacking. Our ...objectives were: to describe pediatric mental health hospitalizations at general medical facilities admitting children nationally; to assess which pediatric mental health diagnoses are frequent and costly at these hospitals; and to examine whether the most frequent diagnoses are similar to those at free-standing children's hospitals.
We examined all discharges in 2009 for patients aged 3 to 20 years in the nationally representative Kids' Inpatient Database (KID) and in the Pediatric Health Information System (free-standing children's hospitals). Main outcomes were frequency of International Classification of Diseases, Ninth Revision, Clinical Modification-defined mental health diagnostic groupings (primary and nonprimary diagnosis) and, using KID, resource utilization (defined by diagnostic grouping aggregate annual charges).
Nearly 10% of pediatric hospitalizations nationally were for a primary mental health diagnosis, compared with 3% of hospitalizations at free-standing children's hospitals. Predictors of hospitalizations for a primary mental health problem were older age, male gender, white race, and insurance type. Nationally, the most frequent and costly primary mental health diagnoses were depression (44.1% of all mental health admissions; $1.33 billion), bipolar disorder (18.1%; $702 million), and psychosis (12.1%; $540 million).
We identified the child mental health inpatient diagnoses with the highest frequency and highest costs as depression, bipolar disorder, and psychosis, with substance abuse an important comorbid diagnosis. These diagnoses can be used as priority conditions for pediatric mental health inpatient quality measurement.
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