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Simple Summary: This study explored the current practices in the real world for grade 2 glioma, an uncommon primary brain cancer. Leveraging the prospective BRAIN registry, this study demonstrates that whilst sequential radiotherapy and chemotherapy improve progression-free survival in high-risk grade 2 glioma, the majority of patients are observed following surgery. In high-risk patients who are observed, 61% remain progression-free at 12 months, with 10% being progression-free at 5 years. This clinically meaningful progression-free survival suggests that validated biomarkers beyond the usual definition of high-risk are required to better inform patient management. Factors contributing to decision-making are underway. Background: Grade-2 gliomas (G2-glioma) are uncommon. In 2016, RTOG9802 established the addition of chemotherapy after radiation (CRT) as a new standard of care for patients with high-risk G2-glioma, defined as subtotal resection or age ≥40 yrs. Here, we report current practices using real-world data. Methods: Patients diagnosed with G2-glioma from 1 January 2016 to 31 December 2022 were identified in BRAIN, a prospective clinical registry collecting data on patients with brain tumours. High- and low-risk were defined as per RTOG9802. Two time periods, January 2016–December 2019 (TP1) and January 2020–December 2022 (TP2), were defined. Survival was estimated using the Kaplan–Meier method. Results: 224 patients were identified. Overall, 38 (17%) were low-risk, with 35 (91%) observed without further treatment. A total of 186 (83%) were high-risk, with 96 (52%) observed, 63 (34%) receiving CRT, and 19 (10%) receiving radiation. Over time, CRT use increased (TP1 vs. TP2: 22% vs. 36%, p = 0.004), and the rate of biopsy (TP1 vs. TP2: 35% vs. 20%, p = 0.02) and radiotherapy alone (TP1 vs. TP2: 14% vs. 4%, p = 0.01) decreased. Median progression-free survival (PFS) was significantly longer in high-risk patients who received CRT (NR) over observation (39 months) (HR 0.49, p = 0.007). In high-risk patients who were observed, 59 (61%) were progression-free at 12 months and 10 (10%) at 5 years. OS data remains immature. Conclusion: Congruent with RTOG9802, real-world BRAIN data shows CRT is associated with improved PFS compared to observation in high-risk G2-glioma. Whilst CRT use has increased over time, observation after surgery remains the most common strategy, with some high-risk patients achieving clinically meaningful PFS. Validated biomarkers are urgently required to better inform patient management. [ABSTRACT FROM AUTHOR]

AMG 256 is a bi-specific, heteroimmunoglobulin molecule with an anti-PD-1 antibody domain and a single IL-21 mutein domain on the C-terminus. Nonclinical studies in cynomolgus monkeys revealed that AMG 256 administration led to the development of immunogenicity-mediated responses and indicated that the IL-21 mutein domain of AMG 256 could enhance the antidrug antibody response directed toward the monoclonal antibody domain. Anti- AMG 256 IgE were also observed in cynomolgus monkeys. A first-in-human (FIH) study in patients with advanced solid tumors was designed with these risks in mind. AMG 256 elicited ADA in 28 of 33 subjects (84.8%). However, ADA responses were only robust and exposure-impacting at the 2 lowest doses. At mid to high doses, ADA responses remained low magnitude and all subjects maintained exposure, despite most subjects developing ADA. Limited drugspecific IgE were also observed during the FIH study. ADA responses were not associated with any type of adverse event. The AMG 256 program represents a unique case where nonclinical studies informed on the risk of immunogenicity in humans, due to the IL-21-driven nature of the response. [ABSTRACT FROM AUTHOR]

Little is known about the process by which children disclose adult wrongdoing, a topic of considerable debate and controversy. In the current study, we investigated children's evaluations of disclosing adult wrongdoing by focusing on children's preferences for particular disclosure recipients and perceptions of the consequences of disclosure in hypothetical vignettes. We tested whether children thought that disclosure recipients would believe a story child as a truth teller and what actions the recipients would take against the "instigator" who committed the transgression. Maltreated and non-maltreated 4- to 9-year-olds (N=235) responded to questions about vignettes that described a parent's or stranger's transgression. Older children preferred caregiver recipients over police officer recipients when disclosing a parent's transgression but not a stranger's transgression. Maltreated children's preference for caregiver recipients over police officer recipients developed more gradually than that of non-maltreated children. Older children expected disclosure recipients to be more skeptical of the story child's account, and older children and maltreated children expected disclosure recipients to intervene formally less often when a parent, rather than a stranger, was the instigator. Results contribute to understanding vulnerable children's development and highlight the developmental, experiential, and socio-contextual factors underlying children's disclosure patterns.

This study tested the effects of narrative practice rapport building (asking open-ended questions about a neutral event) and a putative confession (telling the child an adult "told me everything that happened and he wants you to tell the truth") on 4- to 9-year-old maltreated and nonmaltreated children's reports of an interaction with a stranger who asked them to keep toy breakage a secret (n = 264). Only one third of children who received no interview manipulations disclosed breakage; in response to a putative confession, one half disclosed. Narrative practice rapport building did not affect the likelihood of disclosure. Maltreated children and nonmaltreated children responded similarly to the manipulations. Neither narrative practice rapport building nor a putative confession increased false reports.

Prior research has found that children disclosing physical abuse appear more reticent and less consistent than children disclosing sexual abuse. Although this has been attributed to differences in reluctance, it may also be due to differences in the process by which abuse is suspected and investigated. Disclosure may play a larger role in arousing suspicions of sexual abuse, while other evidence may play a larger role in arousing suspicions of physical abuse. As a result, children who disclose physical abuse in formal investigations may be doing so for the first time, and they may be more reluctant to provide details of the abuse. We examined abuse disclosure and evidence in comparable samples of court-substantiated physical (n = 33) and sexual (n = 28) abuse. Consistent with predictions, the likelihood that the child had disclosed abuse before an investigation began was lower in physical (27%) than that in sexual (67%) abuse cases, and there was more nondisclosure evidence of abuse in physical abuse cases. These findings have implications for understanding the dynamics and meaning of disclosure in cases involving different types of abuse.

We describe a Bayesian approach to evaluating children's abuse disclosures and review research demonstrating that children's disclosure of genital touch can be highly probative of sexual abuse, with the probative value depending on disclosure spontaneity and children's age. We discuss how some commentators understate the probative value of children's disclosures by: confusing the probability of abuse given disclosure with the probability of disclosure given abuse, assuming that children formally questioned about sexual abuse have a low prior probability of sexual abuse, misstating the probative value of abuse disclosure, and confusing the distinction between disclosure and nondisclosure with the distinction between true and false disclosures. We review interviewing methods that increase the probative value of disclosures, including interview instructions, narrative practice, noncontingent reinforcement, and questions about perpetrator/caregiver statements and children's reactions to the alleged abuse. (Contains 3 notes.)

This study examined the origins of children's ability to make consciously false statements, a necessary component of lying. Children 2 to 5 years of age were rewarded for claiming that they saw a picture of a bird when viewing pictures of fish. They were asked outcome questions ("Do you win/lose?"), recognition questions ("Do you have a bird/fish?"), and recall questions ("What do you have?"), which were hypothesized to vary in difficulty depending on the need for consciousness of falsity (less for outcome questions) and self-generation of an appropriate response (more for recall questions). The youngest children (2 1/2 to 3 1/2 years old) were above chance on outcome questions, but it was not until age 3 1/2 that children performed above chance on recognition questions or were capable of maintaining false claims across question types. Findings have implications for understanding the emergence of deception in young children. (Contains 2 tables and 1 figure.)

A total of two hundred ninety-nine 4- to 9-year-old maltreated and nonmaltreated children of comparable socioeconomic status and ethnicity judged whether children should or would disclose unspecified transgressions of adults (instigators) to other adults (recipients) in scenarios varying the identity of the instigator (stranger or parent), the identity of the recipient (parent, police, or teacher), and the severity of the transgression ("something really bad" or "something just a little bad"). Children endorsed more disclosure against stranger than parent instigators and less disclosure to teacher than parent and police recipients. The youngest maltreated children endorsed less disclosure than nonmaltreated children, but the opposite was true among the oldest children. Older maltreated children distinguished less than nonmaltreated children between parents and other types of instigators and recipients.

Malnutrition and sarcopenia are prevalent in patients with head and neck squamous cell carcinoma (HNSCC). Pre-treatment sarcopenia and adverse oncological outcomes in this population are well described. The impact of myosteatosis and post-treatment sarcopenia is less well known. Patients with HNSCC (n = 125) undergoing chemoradiotherapy, radiotherapy alone and/or surgery were assessed for sarcopenia and myosteatosis, using cross-sectional computed tomography (CT) imaging at the third lumbar (L3) vertebra, at baseline and 3 months post-treatment. Outcomes were overall survival (OS) at 12 months and 5 years post-treatment. One hundred and one participants had a CT scan evaluable at one or two time points, of which sixty-seven (66 %) participants were sarcopenic on at least one time point. Reduced muscle attenuation affected 93 % (n = 92) pre-treatment compared with 97 % (n = 90) post-treatment. Five-year OS favoured those without post-treatment sarcopenia (hazard ratio, HR 0·37, 95 % CI 0·16, 0·88, P = 0·06) and those without both post-treatment myosteatosis and sarcopenia (HR 0·33, 95 % CI 0·13, 0·83, P = 0·06). Overall, rates of myosteatosis were high at both pre- and post-treatment time points. Post-treatment sarcopenia was associated with worse 5-year OS, as was post-treatment sarcopenia in those who had myosteatosis. Post-treatment sarcopenia should be evaluated as an independent risk factor for decreased long-term survival post-treatment containing radiotherapy (RT) for HNSCC. [ABSTRACT FROM AUTHOR]