Cultivating Curiosity and Collaboration: Mentalizing as a Modality of Intervention in Attention-Deficit/Hyperactivity Disorder

Parents and caregivers who are able to understand their own mental states are better able to hold a child’s mental states in mind, an important consideration for moderating negative perceptions of ADHD behavior. In this thesis, I discuss how mentalizing-focused treatment for parents and caregivers strengthens attachment bonds in families where a child is diagnosed with ADHD. I explore the effectiveness of mentalizing-focused treatment to parents, some of whom experience difficulty in understanding their own mental states, and all of whom experience challenges in interpreting the intentions and mental states of their children, particularly in families where a child has been diagnosed with ADHD. In addition, I define how mentalizing relates to the important developmental theories, including attachment, as a means of promoting autonomy and resilience for a child as well as the potential negative effects when mentalizing breaks down

New Reports of Exotic and Native Ambrosia and Bark Beetle Species (Coleoptera: Curculionidae: Scolytinae) From Ohio

In a 2007 survey of ambrosia and bark beetles (Coleoptera: Curculionidae: Scolytinae) along a transect in northeastern Ohio, we collected six exotic and three native species not previously reported from the state. These species include the exotic ambrosia beetles Ambrosiodmus rubricollis (Eichhoff), Dryoxylon onoharaensum (Murayama), Euwallacea validus (Eichhoff), Xyleborus californicus Wood, Xyleborus pelliculosusEichhoff, and Xylosandrus crassiusculus (Motschulsky). The native ambrosia beetle Corthylus columbianus Hopkins, and the native bark beetles Dryocoetes autographus (Ratzeburg) and Hylastes tenuis Eichhoff are also reported from Ohio for the first time. Our study suggests a northward range expansion for five of the six exotic species including, X. crassiusculus, which is an important pest of nursery and orchard crops in the southeastern United States

Functional Role of Kallikrein 6 in Regulating Immune Cell Survival

Kallikrein 6 (KLK6) is a newly identified member of the kallikrein family of secreted serine proteases that prior studies indicate is elevated at sites of central nervous system (CNS) inflammation and which shows regulated expression with T cell activation. Notably, KLK6 is also elevated in the serum of multiple sclerosis (MS) patients however its potential roles in immune function are unknown. Herein we specifically examine whether KLK6 alters immune cell survival and the possible mechanism by which this may occur.Using murine whole splenocyte preparations and the human Jurkat T cell line we demonstrate that KLK6 robustly supports cell survival across a range of cell death paradigms. Recombinant KLK6 was shown to significantly reduce cell death under resting conditions and in response to camptothecin, dexamethasone, staurosporine and Fas-ligand. Moreover, KLK6-over expression in Jurkat T cells was shown to generate parallel pro-survival effects. In mixed splenocyte populations the vigorous immune cell survival promoting effects of KLK6 were shown to include both T and B lymphocytes, to occur with as little as 5 minutes of treatment, and to involve up regulation of the pro-survival protein B-cell lymphoma-extra large (Bcl-XL), and inhibition of the pro-apoptotic protein Bcl-2-interacting mediator of cell death (Bim). The ability of KLK6 to promote survival of splenic T cells was also shown to be absent in cell preparations derived from PAR1 deficient mice.KLK6 promotes lymphocyte survival by a mechanism that depends in part on activation of PAR1. These findings point to a novel molecular mechanism regulating lymphocyte survival that is likely to have relevance to a range of immunological responses that depend on apoptosis for immune clearance and maintenance of homeostasis

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

COVID-19 Disruptions to Endoscopic Surveillance in Lynch Syndrome

Disruptions in cancer screening due to the COVID-19 pandemic may disproportionally affect patients with inherited cancer predisposition syndromes, including Lynch syndrome. Herein, we study the effect of the COVID-19 pandemic on endoscopic surveillance in Lynch syndrome through a prospective study of patients with Lynch syndrome at a tertiary referral center who were scheduled for endoscopic surveillance during the COVID-19 pandemic shutdown between March 16, 2020 and June 4, 2020. Of our cohort of 302 individuals with Lynch syndrome, 34 (11%) had endoscopic procedures scheduled during the COVID-19 pandemic shutdown. Of the 27 patients whose endoscopic surveillance was canceled during this period, 85% rescheduled procedures within 6 months with a median delay of 72 days [interquartile range (IQR), 55-84 days], with identification of an advanced adenoma or gastrointestinal cancer in 13%. Individuals who did not have a rescheduled endoscopic procedure were significantly younger than those with a rescheduled procedure [age 35 (IQR, 26-43) vs. age 55 (IQR, 43-63), P = 0.018]. Male sex was also suggestive of increasing likelihood of not having a rescheduled procedure. Taken together, our study demonstrates that the COVID-19 pandemic shutdown led to delayed endoscopic surveillance in Lynch syndrome, with potentially impactful delays among young patients. These data also emphasize the importance of timely surveillance in Lynch syndrome during this current, as well as potential future, global pandemics. Prevention Relevance: The COVID-19 pandemic has led to unprecedented disruptions in cancer screening, which may have disproportionate effects on individuals at increased cancer risk, including those with Lynch syndrome. Herein, we show that the COVID-19 pandemic led to significant disruptions in Lynch syndrome surveillance with potentially impactful delays, thus highlighting the importance of ensuring timely surveillance among this high-risk cohort

Evaluating genotyping‐in‐thousands by sequencing as a genetic monitoring tool for a climate sentinel mammal using non‐invasive and archival samples

Abstract Genetic tools for wildlife monitoring can provide valuable information on spatiotemporal population trends and connectivity, particularly in systems experiencing rapid environmental change. Multiplexed targeted amplicon sequencing techniques, such as genotyping‐in‐thousands by sequencing (GT‐seq), can provide cost‐effective approaches for collecting genetic data from low‐quality and quantity DNA samples, making them potentially useful for long‐term wildlife monitoring using non‐invasive and archival samples. Here, we developed a GT‐seq panel as a potential monitoring tool for the American pika (Ochotona princeps) and evaluated its performance when applied to traditional, non‐invasive, and archival samples, respectively. Specifically, we optimized a GT‐seq panel (307 single nucleotide polymorphisms (SNPs)) that included neutral, sex‐associated, and putatively adaptive SNPs using contemporary tissue samples (n = 77) from the Northern Rocky Mountains lineage of American pikas. The panel demonstrated high genotyping success (94.7%), low genotyping error (0.001%), and excellent performance identifying individuals, sex, relatedness, and population structure. We subsequently applied the GT‐seq panel to archival tissue (n = 17) and contemporary fecal pellet samples (n = 129) collected within the Canadian Rocky Mountains to evaluate its effectiveness. Although the panel demonstrated high efficacy with archival tissue samples (90.5% genotyping success, 0.0% genotyping error), this was not the case for the fecal pellet samples (79.7% genotyping success, 28.4% genotyping error) likely due to the exceptionally low quality/quantity of recovered DNA using the approaches implemented. Overall, our study reinforced GT‐seq as an effective tool using contemporary and archival tissue samples, providing future opportunities for temporal applications using historical specimens. Our results further highlight the need for additional optimization of sample and genetic data collection techniques prior to broader‐scale implementation of a non‐invasive genetic monitoring tool for American pikas

Morphologically normal-appearing mammary epithelial cells obtained from high-risk women exhibit methylation silencing of INK4a/ARF.

Purposep16(INK4a) has been appreciated as a key regulator of cell cycle progression and senescence. Cultured human mammary epithelial cells that lack p16(INK4a) activity have been shown to exhibit premalignant phenotypes, such as telomeric dysfunction, centrosomal dysfunction, a sustained stress response, and, most recently, a dysregulation of chromatin remodeling and DNA methylation. These data suggest that cells that lack p16(INK4a) activity would be at high risk for breast cancer development and may exhibit an increased frequency of DNA methylation events in early cancer.Experimental designTo test this hypothesis, the frequencies of INK4a/ARF promoter hypermethylation, as well as four additional selected loci, were tested in the initial random periareolar fine needle aspiration samples from 86 asymptomatic women at high risk for development of breast cancer, stratified using the Masood cytology index.ResultsINK4a/ARF promoter hypermethylation was observed throughout all early stages of intraepithelial neoplasia and, importantly, in morphologically normal-appearing mammary epithelial cells; 29 of 86 subjects showed INK4a/ARF promoter hypermethylation in at least one breast. Importantly, INK4a/ARF promoter hypermethylation was not associated with atypia, and the frequency of hypermethylation did not increase with increasing Masood cytology score. The frequency of INK4a/ARF promoter hypermethylation was associated with the combined frequency of promoter hypermethylation of retinoic acid receptor-beta2, estrogen receptor-alpha, and breast cancer-associated 1 genes (P = 0.001).ConclusionsBecause INK4a/ARF promoter hypermethylation does not increase with age but increases with the frequency of other methylation events, we predict that INK4a/ARF promoter hypermethylation may serve as a marker of global methylation dysregulation