Excitability and irritability in preschoolers predicts later psychopathology: The importance of positive and negative emotion dysregulation

Emotion dysregulation is a risk factor for the development of a variety of psychopathologic outcomes. In children, irritability, or dysregulated negative affect, has been the primary focus, as it predicts later negative outcomes even in very young children. However, dysregulation of positive emotion is increasingly recognized as a contributor to psychopathology. Here we used an exploratory factor analysis and defined four factors of emotion dysregulation: irritability, excitability, sadness, and anhedonia, in the preschool-age psychiatric assessment collected in a sample of 302 children ages 3-5 years enriched for early onset depression. The irritability and excitability factor scores defined in preschoolers predicted later diagnosis of mood and externalizing disorders when controlling for other factor scores, social adversity, maternal history of mood disorders, and externalizing diagnoses at baseline. The preschool excitability factor score predicted emotion lability in late childhood and early adolescence when controlling for other factor scores, social adversity, and maternal history. Both excitability and irritability factor scores in preschoolers predicted global functioning into the teen years and early adolescence, respectively. These findings underscore the importance of positive, as well as negative, affect dysregulation as early as the preschool years in predicting later psychopathology, which deserves both further study and clinical consideration

Rift kinematics preserved in deep-time erosional landscape below the northern North Sea

Our understanding of continental rifting is, in large parts, derived from the stratigraphic record. This record is, however, incomplete as it does not often capture the geomorphic and erosional signal of rifting. New 3D seismic reflection data reveal a Late Permian-Early Triassic landscape incised into the pre-rift basement of the northern North Sea. This landscape, which covers at least 542 km2, preserves a drainage system bound by two major tectonic faults. A quantitative geomorphic analysis of the drainage system reveals 68 catchments, with channel steepness and knickpoint analysis of catchment-hosted palaeo-rivers showing that the landscape preserved a >2 Myr long period of transient tectonics. We interpret that this landscape records a punctuated uplift of the footwall of a major rift-related normal fault (Vette Fault) at the onset of rifting. The landscape was preserved by a combination of relatively rapid subsidence in the hangingwall of a younger fault (Øygarden Fault) and burial by post-incision sediments. As such, we show how and why erosional landscapes are preserved in the stratigraphic record, and how they can help us understand the tectono-stratigraphic evolution of ancient continental rifts.publishedVersio

Searching for Signatures of Cosmic Superstrings in the CMB

Because cosmic superstrings generically form junctions and gauge theoretic strings typically do not, junctions may provide a signature to distinguish between cosmic superstrings and gauge theoretic cosmic strings. In cosmic microwave background anisotropy maps, cosmic strings lead to distinctive line discontinuities. String junctions lead to junctions in these line discontinuities. In turn, edge detection algorithms such as the Canny algorithm can be used to search for signatures of strings in anisotropy maps. We apply the Canny algorithm to simulated maps which contain the effects of cosmic strings with and without string junctions. The Canny algorithm produces edge maps. To distinguish between edge maps from string simulations with and without junctions, we examine the density distribution of edges and pixels crossed by edges. We find that in string simulations without Gaussian noise (such as produced by the dominant inflationary fluctuations) our analysis of the output data from the Canny algorithm can clearly distinguish between simulations with and without string junctions. In the presence of Gaussian noise at the level expected from the current bounds on the contribution of cosmic strings to the total power spectrum of density fluctuations, the distinction between models with and without junctions is more difficult. However, by carefully analyzing the data the models can still be differentiated.Comment: 15 page

Gender-Affirming Mastectomy Trends and Surgical Outcomes in Adolescents

BackgroundThere are over 150,000 transgender adolescents in the United States, yet research on outcomes following gender-affirming mastectomy in this age group is limited. We evaluated gender-affirming mastectomy incidence, as well as postoperative complications, including regret, in adolescents within our integrated health care system.MethodsGender-affirming mastectomies performed from January 1, 2013 - July 31, 2020 in adolescents 12-17 years of age at the time of referral were identified. The incidence of gender-affirming mastectomy was calculated by dividing the number of patients undergoing these procedures by the number of adolescents assigned female at birth ages 12-17 within our system at the beginning of each year and amount of follow-up time within that year. Demographic information, clinical characteristics (comorbidities, mental health history, testosterone use), surgical technique, and complications, including mention of regret, of patients who underwent surgery were summarized. Patients with and without complications were compared to evaluate for differences in demographic or clinical characteristics using chi-squared tests.ResultsThe incidence of gender-affirming mastectomy increased 13-fold (3.7 to 47.7 per 100,000 person-years) during the study period. Of the 209 patients who underwent surgery, the median age at referral was 16 years (range 12-17) and the most common technique was double-incision (85%). For patients with greater than 1-year follow-up (n=137, 65.6%), at least one complication was found in 7.3% (n=10), which included hematoma (3.6%), infection (2.9%), hypertrophic scars requiring steroid injection (2.9%), seroma (0.7%), and suture granuloma (0.7%); 10.9 % underwent revision (n=15). There were no statistically significant differences in patient demographics and clinical characteristics between those with and without complications (p>0.05). Two patients (0.95%) had documented postoperative regret but neither underwent reversal surgery at follow-up of 3 and 7 years postoperatively.ConclusionBetween 2013-2020, we observed a marked increase in gender-affirming mastectomies in adolescents. The prevalence of surgical complications was low and of over 200 adolescents who underwent surgery, only two expressed regret, neither of which underwent a reversal operation. Our study provides useful and positive guidance for adolescent patients, their families, and providers regarding favorable outcomes with gender-affirming mastectomy

History of Adverse Pregnancy Outcomes, Blood Pressure, and Subclinical Vascular Measures in Late Midlife: SWAN (Study of Women’s Health Across the Nation)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142563/1/jah32800_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142563/2/jah32800.pd

Preventing male suicide through a psychosocial intervention that provides psychological support and tackles financial difficulties:a mixed method evaluation

BACKGROUND: To help resolve high suicide rates in Bristol, North Somerset and South Gloucestershire, the charity Second Step was commissioned to roll-out the Hope service offering a psychosocial intervention for men, supporting them through acute distress and addressing financial difficulties. This study evaluated the impact of the Hope service on men at risk of suicide experiencing financial and other difficulties. METHODS: Mixed methods study using: (i) a prospective cohort study design to compare depression, suicidal ideation and financial self-efficacy scores of men aged 30–64, referred to the service between October 2018 and July 2020, at baseline and 6 months follow-up and between low and moderate to high-intensity service users; and (ii) a qualitative interview study to evaluate the acceptability and impact of the Hope service to Hope service users. RESULTS: There was a 49% reduction in depression score (mean reduction − 10.0, 95% CI − 11.7 to − 8.3) and in the proportion of service users with suicidal ideation (percent reduction − 52.5, 95% CI − 64.1% to − 40.9%) at 6 months follow-up compared to baseline. Financial self-efficacy scores increased by 26% (mean increase 2.9, 95% CI 1.8 to 3.9). Qualitative accounts illustrated how ‘Hope saved my life’ for several men interviewed; most respondents described being able to move forward and tackle challenges with more confidence following the Hope intervention. Professional advice to tackle financial and other difficulties such as housing helped to relieve anxiety and stress and enable practical issues to be resolved. CONCLUSIONS: The Hope service offered practical and emotional support to men who have experienced suicidal feelings, redundancy, homelessness and poverty and occupies an important space between mental health and social care provision. Hope demonstrates the value of an intervention which cuts across traditional boundaries between psychiatric care and social advice agencies to provide, what is, in effect, an integrated care service. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12888-022-03973-5

Loss of Cyclin C or CDK8 provides ATR inhibitor resistance by suppressing transcription-associated replication stress.

The protein kinase ATR plays pivotal roles in DNA repair, cell cycle checkpoint engagement and DNA replication. Consequently, ATR inhibitors (ATRi) are in clinical development for the treatment of cancers, including tumours harbouring mutations in the related kinase ATM. However, it still remains unclear which functions and pathways dominate long-term ATRi efficacy, and how these vary between clinically relevant genetic backgrounds. Elucidating common and genetic-background specific mechanisms of ATRi efficacy could therefore assist in patient stratification and pre-empting drug resistance. Here, we use CRISPR-Cas9 genome-wide screening in ATM-deficient and proficient mouse embryonic stem cells to interrogate cell fitness following treatment with the ATRi, ceralasertib. We identify factors that enhance or suppress ATRi efficacy, with a subset of these requiring intact ATM signalling. Strikingly, two of the strongest resistance-gene hits in both ATM-proficient and ATM-deficient cells encode Cyclin C and CDK8: members of the CDK8 kinase module for the RNA polymerase II mediator complex. We show that Cyclin C/CDK8 loss reduces S-phase DNA:RNA hybrid formation, transcription-replication stress, and ultimately micronuclei formation induced by ATRi. Overall, our work identifies novel biomarkers of ATRi efficacy in ATM-proficient and ATM-deficient cells, and highlights transcription-associated replication stress as a predominant driver of ATRi-induced cell death

Are conservation organizations configured for effective adaptation to global change?

© The Ecological Society of America. Conservation organizations must adapt to respond to the ecological impacts of global change. Numerous changes to conservation actions (eg facilitated ecological transitions, managed relocations, or increased corridor development) have been recommended, but some institutional restructuring within organizations may also be needed. Here we discuss the capacity of conservation organizations to adapt to changing environmental conditions, focusing primarily on public agencies and nonprofits active in land protection and management in the US. After first reviewing how these organizations anticipate and detect impacts affecting target species and ecosystems, we then discuss whether they are sufficiently flexible to prepare and respond by reallocating funding, staff, or other resources. We raise new hypotheses about how the configuration of different organizations enables them to protect particular conservation targets and manage for particular biophysical changes that require coordinated management actions over different spatial and temporal scales. Finally, we provide a discussion resource to help conservation organizations assess their capacity to adapt