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Many approaches to identify therapeutically relevant neoantigens couple tumor sequencing with bioinformatic algorithms and inferred rules of tumor epitope immunogenicity. However, there are no reference data to compare these approaches, and the parameters governing tumor epitope immunogenicity remain unclear. Here, we assembled a global consortium wherein each participant predicted immunogenic epitopes from shared tumor sequencing data. 608 epitopes were subsequently assessed for T cell binding in patient-matched samples. By integrating peptide features associated with presentation and recognition, we developed a model of tumor epitope immunogenicity that filtered out 98% of non-immunogenic peptides with a precision above 0.70. Pipelines prioritizing model features had superior performance, and pipeline alterations leveraging them improved prediction performance. These findings were validated in an independent cohort of 310 epitopes prioritized from tumor sequencing data and assessed for T cell binding. This data resource enables identification of parameters underlying effective anti-tumor immunity and is available to the research community.

PurposePatients with SCLC rarely undergo biopsies at relapse. When pursued, tissue obtained can be inadequate for molecular testing, posing a challenge in identifying potentially targetable alterations in a clinically meaningful time frame. We examined the feasibility of circulating tumor DNA (ctDNA) testing in identifying potentially targetable alterations in SCLC.Experimental designctDNA test results were prospectively collected from patients with SCLC between 2014 and 2017 and analyzed. ctDNA profiles of SCLC at diagnosis and relapse were also compared.ResultsA total of 609 samples collected from 564 patients between 2014 and 2017 were analyzed. The median turnaround time for test results was 14 days. Among patients with data on treatment status, there were 61 samples from 59 patients and 219 samples from 206 patients collected at diagnosis and relapse, respectively. The number of mutations or amplifications detected per sample did not differ by treatment status. Potentially targetable alterations in DNA repair, MAPK and PI3K pathways, and genes such as MYC and ARID1A were identifiable through ctDNA testing. Furthermore, our results support that it may be possible to reconstruct the clonal relationship between detected variants through ctDNA testing.ConclusionsPatients with relapsed SCLC rarely undergo biopsies for molecular testing and often require prompt treatment initiation. ctDNA testing is less invasive and capable of identifying alterations in relapsed disease in a clinically meaningful timeframe. ctDNA testing on an expanded gene panel has the potential to advance our knowledge of the mechanisms underlying treatment resistance in SCLC and aid in the development of novel treatment strategies.

After decades of multiyear defoliation episodes in southern New England, Lymantria dispar dispar (previously gypsy moth) populations diminished with the appearance of the L. dispar fungus in 1989. Multiyear defoliations did not occur again until 2015-2018. To assess the impact of the return of multiyear defoliations, we examined 3095 oaks on 29 permanent study areas in Connecticut and Rhode Island that were established at least 11 years before the latest outbreaks. Pre-defoliation stand-level oak mortality averaged 2% (3-year basis). Post-defoliation mortality did not differ between managed and unmanaged stands but was much higher in severely defoliated stands (36%) than in stands with moderate (7%) or low to no defoliation (1%). Pre-defoliation mortality of individual trees differed among species, was lower for larger diameter trees and on unmanaged than managed stands. Post-defoliation mortality on plots with no to moderate defoliation was similar to pre-defoliation mortality levels. Following multiyear defoliations, white oak (Quercus alba L.) mortality was higher than for northern red oak (Quercus rubra L.) and black oak (Q. velutina Lam.). There was weak evidence that mortality was elevated on stands with higher basal area following severe defoliation. Natural resource managers should not assume that oaks that survived earlier multiyear defoliations episodes will survive future multiyear outbreaks, possibly because trees are older. Key words: Quercus, disturbance, gypsy moth, Lymantria dispar, drought. Apres plusieurs decennies d'episodes de defoliation pluriannuelle dans le sud de la Nouvelle-Angleterre, les populations de Lymantria dispar dispar (anterieurement appelee spongieuse) ont diminue avec l'apparition du champignon parasite de L. dispar en 1989. Les defoliations pluriannuelles ne sont pas survenues a nouveau jusqu'en 2015-2018. Pour evaluer l'impact du retour des defoliations pluriannuelles, nous avons examine 3095 chenes dans 29 zones d'etude permanentes etablies au Connecticut et au Rhode Island au moins 11 ans avant les dernieres epidemies. La mortalite du chene a l'echelle du peuplement anterieurement a la defoliation atteignait en moyenne 2 % (sur la base de trois annees). La mortalite qui a suivi la defoliation ne differait pas, que les peuplements soient amenages ou non, mais elle etait beaucoup plus elevee dans les peuplements severement defolies (36 %) que dans les peuplements moderement (7 %) ou legerement (1 %) a non defolies. Anterieurement a la defoliation, la mortalite differait selon l'espece d'arbre, etait plus faible parmi les arbres de fort diametre ainsi que dans les peuplements non amenages comparativement aux peuplements amenages. La mortalite qui a suivi une defoliation nulle a moderee etait semblable au niveau de mortalite qui existait avant que survienne la defoliation. A la suite de defoliations pluriannuelles, la mortalite du chene blanc (Quercus alba L.) etait plus elevee que celle du chene rouge (Quercus rubra L.) et du chene des teinturiers (Quercus velutina Lam.). A la suite d'une defoliation severe il y avait vraisemblablement plus de mortalite dans les peuplements dont la surface terriere etait plus elevee. Les gestionnaires des ressources naturelles ne devraient pas prendre pour acquis que les chenes qui ont deja survecu a des episodes de defoliation pluriannuelle vont survivre a des epidemies pluriannuelles dans le futur, possiblement parce que les arbres seront alors plus vieux. [Traduit par la Redaction] Mots-cles: Quercus, perturbation, spongieuse, Lymantria dispar, secheresse., Introduction Since its escape in eastern Massachusetts in the 1860s, Lymantria dispar dispar L. (L. dispar; formerly known as gypsy moth) has spread to 19 US states and five Canadian [...]

The purpose of this survey study was to examine current admissions processes and assessment practices for music programs of National Association of Schools of Music member institutions. Representatives from 95 institutions responded to a researcher-designed questionnaire. Music education programs were perceived as being comparable to performance programs on admissions standards. We describe the current state of candidate assessment practices from matriculation through degree conferral, consider a range of assessment measures including gateway or barrier instruments, and pose critical questions about the use of such assessments to determine whether music education candidates are appropriately qualified to become P-12 music educators.

Author(s): Stephen T. Ferris [sup.1] , Vivek Durai [sup.1] [sup.10] , Renee Wu [sup.1] , Derek J. Theisen [sup.1] , Jeffrey P. Ward [sup.1] [sup.2] , Michael D. Bern [sup.3] [...], Conventional type 1 dendritic cells (cDC1).sup.1 are thought to perform antigen cross-presentation, which is required to prime CD8.sup.+ T cells.sup.2,3, whereas cDC2 are specialized for priming CD4.sup.+ T cells.sup.4,5. CD4.sup.+ T cells are also considered to help CD8.sup.+ T cell responses through a variety of mechanisms.sup.6-11, including a process whereby CD4.sup.+ T cells 'license' cDC1 for CD8.sup.+ T cell priming.sup.12. However, this model has not been directly tested in vivo or in the setting of help-dependent tumour rejection. Here we generated an Xcr1.sup.Cre mouse strain to evaluate the cellular interactions that mediate tumour rejection in a model requiring CD4.sup.+ and CD8.sup.+ T cells. As expected, tumour rejection required cDC1 and CD8.sup.+ T cell priming required the expression of major histocompatibility class I molecules by cDC1. Unexpectedly, early priming of CD4.sup.+ T cells against tumour-derived antigens also required cDC1, and this was not simply because they transport antigens to lymph nodes for processing by cDC2, as selective deletion of major histocompatibility class II molecules in cDC1 also prevented early CD4.sup.+ T cell priming. Furthermore, deletion of either major histocompatibility class II or CD40 in cDC1 impaired tumour rejection, consistent with a role for cognate CD4.sup.+ T cell interactions and CD40 signalling in cDC1 licensing. Finally, CD40 signalling in cDC1 was critical not only for CD8.sup.+ T cell priming, but also for initial CD4.sup.+ T cell activation. Thus, in the setting of tumour-derived antigens, cDC1 function as an autonomous platform capable of antigen processing and priming for both CD4.sup.+ and CD8.sup.+ T cells and of the direct orchestration of their cross-talk that is required for optimal anti-tumour immunity. Conventional type 1 dendritic cells perform antigen processing and priming of CD4.sup.+ and CD8.sup.+ T cells against tumour antigens, orchestrating their cross-talk to effect anti-tumour immunity.

This study examines the consequences of a policy shock to the criminal legal system through the prisms of the lived experiences of incarcerated persons. The study draws on a qualitative analysis of 159 unsolicited letters from incarcerated individuals in the Pennsylvania Department of Corrections written during the 2008–2009 Moratorium on prison releases. The results indicate that the moratorium eroded their trust and exacerbated an already existing crisis in procedural justice and legitimacy for discretionary parole, underscoring both direct and collateral consequences of this policy shock on the lived experiences of those most directly affected. Several policy implications emerge that can help improve or restore procedural justice and legitimacy of discretionary parole and corrections, more generally. [ABSTRACT FROM AUTHOR]

A growing proportion of forested landscapes are interspersed with human infrastructure, such as utility lines and roads, increasing the potential for tree-failure consequences due to storms and other causes. Utilities and other institutions have strong incentives to reduce such interactions and allocate substantial resources to risk reduction, but trees and forests in densely populated landscapes also provide significant amenities to society. We present a generalized framework for "Stormwise" forest management, focused on resistance of roadside forests to storms, based on elements of arboricultural and silvicultural practice and tree biomechanics and architecture. We detail results of a multidisciplinary research program focused on management outcomes, opportunities and barriers to implementation, and allocation of investment based on physical and social landscape characteristics. We discuss initial findings, the potential for widespread adoption of resilience-focused management in roadside and infrastructure-adjacent forests, and the importance of such work, considering a changing climate. Study Implications: The research and implementation program we detail here illustrates the potential for "Stormwise" forest management to reduce storm-damage recovery costs, result in fewer and shorter-duration power and transportation interruptions, and allow for low-investment ground-based management in future forest entries. We illustrate a multifaceted, interdisciplinary research program that links the geospatial, social, and biophysical components of understanding forest infrastructure systems. We illustrate how implementation of Stormwise management has the potential to benefit stakeholders such as residents and utilities, offset the substantial economic costs of tree-related power outages, and reduce societal disruptions associated with interactions between trees and infrastructure during storms. [ABSTRACT FROM AUTHOR]