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Clinical course in attention-deficit/hyperactivity disorder (ADHD) is highly heterogeneous with respect to both core symptoms and associated features and impairment. Onset of comorbid anxiety and mood disorders during later childhood and adolescence is one critical aspect of divergent outcomes in ADHD. Characterizing heterogeneity in onset of anxiety and depression and identifying prospective predictors of these divergent courses may facilitate early identification of the children most at risk.A total of 849 children recruited for a case-control study of ADHD development, aged 7-12 years at baseline, completed up to six annual waves of comprehensive clinical and cognitive assessment, including multi-informant behavior ratings, parent semi-structured clinical diagnostic interviews, and measures of executive function (EF). Latent class growth curve analyses (LCGAs) characterized patterns of anxiety and depression over time. Trajectories were predicted from baseline parent-rated child temperament, lab-measured child EF, coded parental criticism, and child-reported self-blame for inter-parental conflict.Latent class growth curve analyses separately identified three trajectories for anxiety and three for depression: persistently high, persistently low, and increasing. Temperamental fear/sadness and irritability were independent predictors that interacted with family characteristics. Baseline parental criticism and self-blame for inter-parental conflict exerted influence but only in the context of low temperamental risk. Better baseline child working memory was associated with delayed onset of depression.The interaction of baseline child emotional features with EF or family environment predicted divergent courses of both anxiety and depression from middle-childhood to mid-adolescence. Results suggest modifiable risk factors associated with prospective differences in long-term outcomes.

Objective This study aimed to qualitatively explore how partner support for health behaviours is perceived, received, and utilised in people living with and beyond cancer (LWBC). Methods Semi-structured audio interviews were conducted with 24 participants, 15 men and nine women, living with and beyond breast, prostate, and colorectal cancer. Inductive and deductive Thematic Analysis was used to analyse the data. Results Three key themes with six subthemes were identified relating to partner support for health behaviours: (1) Interdependence (Reciprocity, Overt Control, Influence & Motivation) (2) Concordance (Shared Attitudes & Health Beliefs, Shared Health Behaviour) and (3) Communal Coping (Communal Orientation towards Health and Decision Making, Co-operative Action in Health Behaviour). Conclusions Partner support plays a unique and significant role in the health behaviours of people LWBC. Partners play a collaborative role in managing health and facilitating health behaviours, while the high level of concordance in couples may represent a potential barrier to change via the reinforcement of maladaptive health beliefs and behaviours. Implications for Cancer Survivors Overall, findings demonstrate that partners should be considered and included where possible when designing future behaviour change interventions for people LWBC.

Primary-care providers, clinic staff, and nurses play an important role in reducing child obesity; yet time restraints and clinical demands compete with effective pediatric weight management and prevention.To investigate the potential impact of an electronic health record (EHR) enabled tool to assist primary care teams in addressing child obesity, we conducted a controlled effectiveness study of FitTastic compared with usual care on the BMI pattern of 291 children (2 to 17 years) up to 4 years later.Per χStudy findings suggest that EHR-enabled tools to assist primary care teams in managing child obesity may be useful for helping to address the weight in children with overweight/obesity, especially in younger children (2 to 5 years). Digital and EHR-enabled technologies may prove useful for partnering health care teams and families in the important tasks of setting positive, family-centered healthy lifestyle behavioral goals and managing child overweight and obesity.

Supplemental Methods

ElasticNet Tables for PF-06939999 in NSCLC

Supplemental Figures S1-S8

MHC-I expression in re-isolated MC703-KLL tumor cells

Purpose: The persistent expression of Merkel cell polyomavirus (MCPyV) oncoproteins in Merkel cell carcinoma (MCC) provides a unique opportunity to characterize immune evasion mechanisms in human cancer. We isolated MCPyV-specific T cells and determined their frequency and functional status.Experimental Design: Multiparameter flow cytometry panels and HLA/peptide tetramers were used to identify and characterize T cells from tumors (n = 7) and blood (n = 18) of patients with MCC and control subjects (n = 10). PD-1 ligand (PD-L1) and CD8 expression within tumors were determined using mRNA profiling (n = 35) and immunohistochemistry (n = 13).Results: MCPyV-specific CD8 T cells were detected directly ex vivo from the blood samples of 7 out of 11 (64%) patients with MCPyV-positive tumors. In contrast, 0 of 10 control subjects had detectable levels of these cells in their blood (P < 0.01). MCPyV-specific T cells in serial blood specimens increased with MCC disease progression and decreased with effective therapy. MCPyV-specific CD8 T cells and MCC-infiltrating lymphocytes expressed higher levels of therapeutically targetable PD-1 and Tim-3 inhibitory receptors compared with T cells specific to other human viruses (P < 0.01). PD-L1 was present in 9 of 13 (69%) MCCs and its expression was correlated with CD8-lymphocyte infiltration.Conclusions: MCC-targeting T cells expand with tumor burden and express high levels of immune checkpoint receptors PD-1 and Tim-3. Reversal of these inhibitory pathways is therefore a promising therapeutic approach for this virus-driven cancer. Clin Cancer Res; 19(19); 5351–60. ©2013 AACR.

Purpose: The causative agent of most cases of Merkel cell carcinoma (MCC) has been identified as the Merkel cell polyomavirus (MCV). MCV-encoded T antigens (Tag) are essential not only for virus-mediated tumorigenesis but also for maintaining MCC cell lines in vitro. MCV Tags are thus an appealing target for viral oncoprotein-directed T-cell therapy for MCC. With this study, we aimed to isolate and characterize Tag-specific T-cell receptors (TCR) for potential use in gene therapy clinical trials.Experimental Design: T-cell responses against MCV Tag epitopes were investigated by immunizing transgenic mice that express a diverse human TCR repertoire restricted to HLA-A2. Human lymphocytes genetically engineered to express Tag-specific TCRs were tested for specific reactivity against MCC cell lines. The therapeutic potential of Tag-specific TCR gene therapy was tested in a syngeneic cancer model.Results: We identified naturally processed epitopes of MCV Tags and isolated Tag-specific TCRs. T cells expressing these TCRs were activated by HLA-A2–positive cells loaded with cognate peptide or cells that stably expressed MCV Tags. We showed cytotoxic potential of T cells engineered to express these TCRs in vitro and demonstrated regression of established tumors in a mouse model upon TCR gene therapy.Conclusions: Our findings demonstrate that MCC cells can be targeted by MCV Tag-specific TCRs. Although recent findings suggest that approximately half of MCC patients benefit from PD-1 pathway blockade, additional patients may benefit if their endogenous T-cell response can be augmented by infusion of transgenic MCV-specific T cells such as those described here. Clin Cancer Res; 24(15); 3644–55. ©2018 AACR.

Supplementary Data - PDF file 227K, Supplementaty Data Figure S1. Representative flow cytometry gating scheme for TIL and PBMC surface marker analysis. Figure S2. Representative data showing IFN-y production in response to no stimulation (top row) or to PMA/ionomycin stimulation (bottom row)

V-J segment usage as well as CDR3 sequences of TCRs isolated from ABabDII mice after immunization with SMF or KLL epitope petide, respectively.

Protein arginine methyltransferase 5 (PRMT5) overexpression in hematologic and solid tumors methylates arginine residues on cellular proteins involved in important cancer functions including cell-cycle regulation, mRNA splicing, cell differentiation, cell signaling, and apoptosis. PRMT5 methyltransferase function has been linked with high rates of tumor cell proliferation and decreased overall survival, and PRMT5 inhibitors are currently being explored as an approach for targeting cancer-specific dependencies due to PRMT5 catalytic function. Here, we describe the discovery of potent and selective S-adenosylmethionine (SAM) competitive PRMT5 inhibitors, with in vitro and in vivo characterization of clinical candidate PF-06939999. Acquired resistance mechanisms were explored through the development of drug resistant cell lines. Our data highlight compound-specific resistance mutations in the PRMT5 enzyme that demonstrate structural constraints in the cofactor binding site that prevent emergence of complete resistance to SAM site inhibitors. PRMT5 inhibition by PF-06939999 treatment reduced proliferation of non–small cell lung cancer (NSCLC) cells, with dose-dependent decreases in symmetric dimethyl arginine (SDMA) levels and changes in alternative splicing of numerous pre-mRNAs. Drug sensitivity to PF-06939999 in NSCLC cells associates with cancer pathways including MYC, cell cycle and spliceosome, and with mutations in splicing factors such as RBM10. Translation of efficacy in mouse tumor xenograft models with splicing mutations provides rationale for therapeutic use of PF-06939999 in the treatment of splicing dysregulated NSCLC.

PurposeSocial support facilitated healthy behaviours in people living with and beyond cancer (LWBC) before the COVID-19 pandemic. Little is known about how social support impacted their health behaviours during the pandemic when social restrictions were imposed. The aim of this study was to qualitatively explore how social support impacted the health behaviours of people LWBC during the COVID-19 pandemic.MethodsSemi-structured interviews were conducted via telephone with 24 adults living with and beyond breast, prostate and colorectal cancer. Inductive and deductive framework analysis was used to analyse the data. ResultsSix themes developed. These were 1) Companionship and accountability as motivators for physical activity, 2) Familial social influence increasing alcohol consumption, 3) Importance of friends, communities and government in maintenance of food security, 4) Partner support in food practices, 5) Informational support as important for behaviour change, and 6) Validation of health behaviours from immediate social networks. ConclusionThis study found that companionship, social influence, instrumental support, informational support and validation impacted the health behaviours of people LWBC during the COVID-19 pandemic. Interventions for people LWBC could recommend co-participation in exercise with friends and family; promote the formation of collaborative implementation intentions with family to reduce alcohol consumption; and encourage supportive communication between partners about health behaviours. These interventions would be useful during pandemics and at other times. Government policies to help support clinically extremely vulnerable groups of people LWBC during pandemics should focus on providing access to healthier foods.

Background There are multiple health benefits from participating in physical activity after a cancer diagnosis, but many people living with and beyond cancer (LWBC) are not meeting physical activity guidelines. App-based interventions offer a promising platform for intervention delivery. This trial aims to pilot a theory-driven, app-based intervention that promotes brisk walking among people living with and beyond cancer. The primary aim is to investigate the feasibility and acceptability of study procedures before conducting a larger randomised controlled trial (RCT). Methods This is an individually randomised, two-armed pilot RCT. Patients with localised or metastatic breast, prostate, or colorectal cancer, who are aged 16 years or over, will be recruited from a single hospital site in South Yorkshire in the UK. The intervention includes an app designed to encourage brisk walking (Active 10) supplemented with habit-based behavioural support in the form of two brief telephone/video calls, an information leaflet, and walking planners. The primary outcomes will be feasibility and acceptability of the study procedures. Demographic and medical characteristics will be collected at baseline, through self-report and hospital records. Secondary outcomes for the pilot (assessed at 0 and 3 months) will be accelerometer measured and self-reported physical activity, body mass index (BMI) and waist circumference, and patient-reported outcomes of quality of life, fatigue, sleep, anxiety, depression, self-efficacy, and habit strength for walking. Qualitative interviews will explore experiences of participating or reasons for declining to participate. Parameters for the intended primary outcome measure (accelerometer measured average daily minutes of brisk walking (≥ 100 steps/min)) will inform a sample size calculation for the future RCT and a preliminary economic evaluation will be conducted. Discussion This pilot study will inform the design of a larger RCT to investigate the efficacy and cost-effectiveness of this intervention in people LWBC. Trial registration ISRCTN registry, ISRCTN18063498. Registered 16 April 2021.

Purpose Social support facilitated healthy behaviours in people living with and beyond cancer (LWBC) before the COVID-19 pandemic. Little is known about how social support impacted their health behaviours during the pandemic when social restrictions were imposed. The aim of this study was to qualitatively explore how social support was perceived to impact the health behaviours of people LWBC during the COVID-19 pandemic. Methods Semi-structured interviews were conducted via telephone with 24 adults living with and beyond breast, prostate and colorectal cancer. Inductive and deductive framework analysis was used to analyse the data. Results Five themes developed. These were (1) Companionship and accountability as motivators for physical activity, (2) Social influences on alcohol consumption, (3) Instrumental support in food practices, (4) Informational support as important for behaviour change and (5) Validation of health behaviours from immediate social networks. Conclusion This study described how companionship, social influence, instrumental support, informational support and validation were perceived to impact the health behaviours of people LWBC during the COVID-19 pandemic. Interventions for people LWBC could recommend co-participation in exercise with friends and family; promote the formation of collaborative implementation intentions with family to reduce alcohol consumption; and encourage supportive communication between partners about health behaviours. These interventions would be useful during pandemics and at other times. Government policies to help support clinically extremely vulnerable groups of people LWBC during pandemics should focus on providing access to healthier foods.

Escherichia coli ST131 is a globally dispersed extraintestinal pathogenic E. coli lineage contributing significantly to hospital and community acquired urinary tract and bloodstream infections. Here we describe a detailed phylogenetic analysis of the whole genome sequences of 284 Australian ST131 E. coli isolates from diverse sources, including clinical, food and companion animals, wildlife and the environment. Our phylogeny and the results of single nucleotide polymorphism (SNP) analysis show the typical ST131 clade distribution with clades A, B and C clearly displayed, but no niche associations were observed. Indeed, interspecies relatedness was a feature of this study. Thirty-five isolates (29 of human and six of wild bird origin) from clade A (32 fimH41, 2 fimH89, 1 fimH141) were observed to differ by an average of 76 SNPs. Forty-five isolates from clade C1 from four sources formed a cluster with an average of 46 SNPs. Within this cluster, human sourced isolates differed by approximately 37 SNPs from isolates sourced from canines, approximately 50 SNPs from isolates from wild birds, and approximately 52 SNPs from isolates from wastewater. Many ST131 carried resistance genes to multiple antibiotic classes and while 41 (14 %) contained the complete class one integron–integrase intI1, 128 (45 %) isolates harboured a truncated intI1 (462–1014 bp), highlighting the ongoing evolution of this element. The module intI1–dfrA17–aadA5–qacEΔ1–sul1–ORF–chrA–padR–IS1600–mphR–mrx–mphA, conferring resistance to trimethoprim, aminoglycosides, quaternary ammonium compounds, sulphonamides, chromate and macrolides, was the most common structure. Most (73 %) Australian ST131 isolates carry at least one extended spectrum β-lactamase gene, typically bla CTX-M-15 and bla CTX-M-27. Notably, dual parC-1aAB and gyrA-1AB fluoroquinolone resistant mutations, a unique feature of clade C ST131 isolates, were identified in some clade A isolates. The results of this study indicate that the the ST131 population in Australia carries diverse antimicrobial resistance genes and plasmid replicons and indicate cross-species movement of ST131 strains across diverse reservoirs.

The present study investigated the relationship between self-reported creativity and current symptoms of depression and mania. Three hundred and ninety-seven participants previously diagnosed with BD completed an online questionnaire that included demographic and clinical information questions, creativity and self-report measures of depression and hypo/mania over the past week. Those reporting clinically significant depressive symptoms had significantly lower creativity scores than those in the hypo/mania and no current symptom groups. There were no significant differences between those reporting clinically significant hypo/mania and no current symptom groups, however they reported significantly higher creativity scores than those who reported symptoms of both hypo/mania and depression in the past week. Furthermore, subscales of the creativity measure demonstrated significant differences between some of the groups on the drama, interaction and maths/science subscales. These findings suggest that there is a relationship between mood and how people with BD understand and experience creativity. Further research is needed to better understand the role of creativity in the management of bipolar disorder and how this may be associated with well-being outcomes such as recovery, and also how it may be incorporated into treatment.

Introduction One of the most common surgical procedures performed annually is inguinal hernia repair. Inguinal hernias are traditionally known to be caused by a weakening in the abdominal wall and precipitated by increased intraabdominal pressure. Recently, intra-abdominal cancer producing the increased intraabdominal pressure, along with metastasis directly into the inguinal canal, have been identified in more studies as causes of inguinal hernias. Presentation of case This case focuses on a unique presentation of small-cell neuroendocrine carcinoma presenting as an inguinal hernia. Discussion This patient's rapid demise and advanced metastatic disease upon presentation is alarming, but his advanced disease process presenting as a routine inguinal hernia is noteworthy. Upon literature analysis, the number of advanced disease processes – most notably cancer – presenting as hernias is significant. Conclusion This case emphasis the importance of perioperative screening, and presents the question, should hernias indicate further workup in the appropriate, at-risk patient populations., Highlights • Small cell neuroendocrine carcinoma is a highly malignant, poorly defined cancer with a wide variety of metastasis sites. • The clinical presentation of intra-abdominal cancer within inguinal hernia has mounting supporting evidence. • Late metastatic small cell lung carcinoma developed in inguinal hernia from an increase in intra-abdominal pressure. • Further screening for malignancies in those who present for an evaluation of a hernia may be merited.

Transmission of tuberculosis typically requires close and prolonged contact with an infected individual. However, several cases of transmission between elephants and from elephants to humans or other animals without direct contact or over long distances have been reported. Elephants have been shown to be capable of producing aerosolized bacterial droplets, suggesting a possible route of transmission that is magnified by the size and force of the elephant respiratory tract. To investigate the dispersion and viability of aerosolized bacteria generated from the elephant respiratory tract, a pre-existing model with a proxy organism was used. A six-stage Andersen sampler was used to detect the proxy organism, a commensal elephant respiratory bacterium, at different locations around an elephant barn at a zoo. The amount of proxy organism detected at various time points and distances from the elephants indicates they are capable of dispersing viable bacterial aerosols further than humans can. The concentration of these aerosols is dependent on proximity to the elephants and does not remain at a high level for prolonged periods of time. These findings support the model of aerosol-mediated transmission of bacteria from elephants and can be used to improve disease management practices and prevent the spread of pathogens from elephants in zoos and other facilities.

Organizational and technical approaches have proven successful in increasing the performance and preventing risks at socio-technical systems at all scales. Nevertheless, damaging events are often unavoidable due to a wide and dynamic threat landscape and enabled by the increasing complexity of modern systems. For overall performance and risk control at the system level, resilience can be a versatile option, in particular for reducing resources needed for system development, maintenance, reuse, or disposal. This paper presents a framework for a resilience assessment and management process that builds on existing risk management practice before, during, and after potential and real events. It leverages tabular and matrix correlation methods similar as standardized in the field of risk analysis to fulfill the step-wise resilience assessment and management for critical functions of complex systems. We present data needs for the method implementation and output generation, in particular regarding the assessment of threats and the effects of counter measures. Also included is a discussion of how the results contribute to the advancement of functional risk control and resilience enhancement at system level as well as related practical implications for its efficient implementation. The approach is applied in the domains telecommunication, gas networks, and indoor localization systems. Results and implications are further discussed.

These are initial findings of ongoing, phase 1 multiple ascending-dose gene transfer trial of ≤9 LGMD2E patients who received rAAVrh74.MHCK7.SGCB (NCT03652259). Participants: patients 4–15y, confirmed β-sarcoglycan (SGCB) mutation (both alleles), negative for rAAVrh74 antibodies, >40%n on 100-meter timed test. Patients received single IV infusion of 5x1013 vg/kg rAAVrh74.MHCK7.SGCB. Prednisone 1 mg/kg/day was initiated 1d before gene delivery, tapering after 30d. Primary endpoints: ≥20% SGCB-positive fibers (Day-60 muscle biopsy) and safety (Day 270). Secondary endpoints: CK decrease and functional endpoints (Day 270). First 3 patients enrolled (age 13[n=2]; age 4[n=1]): robust SGCB expression observed by immunohistochemistry (IHC), with a mean of 51% SGCB positive fibers (range 42–63%) expressing a mean 47% intensity (range 38–57%). Co-localization of β-sarcoglycan observed (IHC). Western blot showed a mean 36.1% SGCB expression vs normal (range 34–39%). Mean CK levels reduced by 82%, suggesting slowed muscle destruction. Two patients had elevated liver enzymes (1 serious) and 1 had elevated bilirubin following oral steroid taper, which returned to baseline. Two patients had transient mild nausea, corresponding with increased steroid dosing. No other clinically significant lab findings. Gene transfer in LGMD2E patients following rAAVrh74.MHCK7.SGCB infusion was positive for defined endpoints, demon- strating potential benefits of a rationally designed delivery system.jrichardson@sarepta.com

Scatterplots and scatterplot matrix methods have been popularly used for showing statistical graphics and for exposing patterns in multivariate data. A recent technique, called Linkable Scatterplots, provides an interesting idea for interactive visual exploration which provides a set of necessary plot panels on demand together with interaction, linking and brushing. This article presents a controlled study with a mixed-model design to evaluate the effectiveness and user experience on the visual exploration when using a Sequential-Scatterplots who a single plot is shown at a time, Multiple-Scatterplots who number of plots can be specified and shown, and Simultaneous-Scatterplots who all plots are shown as a scatterplot matrix. Results from the study demonstrated higher accuracy using the Multiple-Scatterplots visualization, particularly in comparison with the Simultaneous-Scatterplots.​ While the time taken to complete tasks was longer in the Multiple-Scatterplots technique, compared with the simpler Sequential-Scatterplots, Multiple-Scatterplots is inherently more accurate. Moreover, the Multiple-Scatterplots technique is the most highly preferred and positively experienced technique in this study. Overall, results support the strength of Multiple-Scatterplots and highlight its potential as an effective data visualization technique for exploring multivariate data.

Protein arginine methyltransferase 5 (PRMT5) overexpression in hematological and solid tumors promotes symmetrical di-methyl arginine (SDMA) on cellular proteins involved in important cancer functions including cell cycle regulation, mRNA splicing, cell differentiation, cell signaling, and apoptosis. PRMT5 methyltransferase function has been linked with high rates of tumor cell proliferation and decreased overall survival, and PRMT5 inhibitors are currently being explored as an approach for targeting cancer-specific dependencies due to PRMT5 catalytic function. Here we describe the discovery of potent and selective S-adenosylmethionine (SAM) competitive PRMT5 inhibitors, including the clinical candidate PF-06939999. Acquired resistance mechanisms were explored through the development of drug resistant cell lines. Our data highlight compound-specific resistance mutations in the PRMT5 enzyme that demonstrate structural constraints in the co-factor binding site that prevent emergence of complete resistance to SAM site inhibitors. PRMT5 inhibition by PF-06939999 treatment reduced proliferation of NSCLC cancer cells, with dose-dependent decreases in SDMA levels and changes in alternative splicing of numerous pre-mRNAs. Drug sensitivity associates with cancer pathways including MYC, cell cycle and splicing. Translation of efficacy in mouse tumor xenograft models with splicing mutations provides rationale for therapeutic use of PF-06939999 for treatment of splicing dysregulated NSCLC. Citation Format: Kristen Jensen-Pergakes, John Tatlock, Karen Maegley, Indrawan McAlpine, Michele McTigue, Tao Xie, Christopher Dillon, Yuli Wang, Shinji Yamazaki, Noah Spiegel, Manli Shi, Amy Nemeth, Natalie Miller, Eleanore Hendrickson, Hieu Lam, John Sherrill, Wei Liu, Ya-Li Deng, Chi-Yeh Chung, Elizabeth A. McMillan, Prakash Palde, Alexei Brooun, John Braganza, Susan E. Kephart, Robert Kumpf, Ryan Patman, Eugene Rui, Stephanie Scales, Michelle Tran-Dube, Fen Wang, Martin Wythes, Thomas Paul. SAM competitive PRMT5 inhibitor PF06939999 demonstrates antitumor activity in splicing dysregulated NSCLC with decreased liability of drug resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1160.

Background:\ud Pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment.\ud \ud Objective:\ud We sought to estimate the effectiveness of topical therapies in the treatment of patients with PG.\ud \ud Methods:\ud This was a retrospective cohort study of UK secondary care patients with a clinical diagnosis of PG that was suitable for topical treatment (recruited between July 2009 and June 2012). Participants received topical therapy after normal clinical practice (primarily topical corticosteroids [classes I-III] and tacrolimus 0.03% or 0.1%). The primary outcome was speed of healing at 6 weeks. Secondary outcomes included the following: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality of life; treatment failure; and recurrence.\ud \ud Results:\ud Sixty-six patients (22-85 years of age) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28 of 66 (43.8%) ulcers healed by 6 months. The median time to healing was 145 days (95% confidence interval, 96 days to ∞). Initial ulcer size was a significant predictor of time to healing (hazard ratio, 0.94 [95% confidence interval, 0.88-1.00); P = .043). Four patients (15%) had a recurrence.\ud \ud Limitations:\ud Our study did not include a randomized comparator.\ud \ud Conclusion:\ud Topical therapy is potentially an effective first-line treatment for PG that avoids the possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone.

Date Presented 03/28/20 This qualitative descriptive study examined students’ perceptions of the impacts of simulation on preparation for OT Level II fieldwork. Participants indicated ways in which thoughtfully designed simulations can help enhance confidence as well as interprofessional relationships, role delineation, and communication skills. Outcomes provided insight into considerations for the design of future simulations emphasizing professional-skill development. Primary Author and Speaker: Ellen Herlache-Pretzer Additional Authors and Speakers: Jean Prast Contributing Authors: Rachel Andrzejewski, Sara Gapski, Brittany Raisanen, Monica Wilds, Natalie Miller

3021Background: MCC is an aggressive skin cancer with suboptimal therapies. Despite persistent expression of Merkel cell polyomavirus in ~80% of pts, MCC tumors are able to evade host immunity. G10...

3083 Background: MCC is an aggressive skin cancer with suboptimal therapeutic options. Despite persistent expression of Merkel cell polyomavirus (MCPyV) proteins in ~80% of cases, these tumors are ...

Chlamydiae traffic along microtubules to the microtubule organizing center (MTOC) to establish an intracellular niche within the host cell. Trafficking to the MTOC is dynein dependent although the activating and cargo-linking function of the dynactin complex is supplanted by unknown chlamydial protein(s). We demonstrate that once localized to the MTOC, the chlamydial inclusion maintains a tight association with cellular centrosomes. This association is sustained through mitosis and leads to a significant increase in supernumerary centrosomes, abnormal spindle poles, and chromosomal segregation defects. Chlamydial infection thus can lead to chromosome instability in cells that recover from infection.