Double strand breaks (DSBs) as indicators of genomic instability in PATRR-mediated translocations.

Genomic instability contributes to a variety of potentially damaging conditions, including DNA-based rearrangements. Breakage in the form of double strand breaks (DSBs) increases the likelihood of DNA damage, mutations and translocations. Certain human DNA regions are known to be involved in recurrent translocations, such as the palindrome-mediated rearrangements that have been identified at the breakpoints of several recurrent constitutional translocations: t(11;22)(q23;q11), t(17;22)(q11;q11) and t(8;22) (q24;q11). These breakpoints occur at the center of palindromic AT-rich repeats (PATRRs), which suggests that the structure of the DNA may play a contributory role, potentially through the formation of secondary cruciform structures. The current study analyzed the DSB propensity of these PATRR regions in both lymphoblastoid (mitotic) and spermatogenic cells (meiotic). Initial results found an increased association of sister chromatid exchanges (SCEs) at PATRR regions in experiments that used SCEs to assay DSBs, combining SCE staining with fluorescence in situ hybridization (FISH). Additional experiments used chromatin immunoprecipitation (ChIP) with antibodies for either markers of DSBs or proteins involved in DSB repair along with quantitative polymerase chain reaction to quantify the frequency of DSBs occurring at PATRR regions. The results indicate an increased rate of DSBs at PATRR regions. Additional ChIP experiments with the cruciform binding 2D3 antibody indicate an increased rate of cruciform structures at PATRR regions in both mitotic and meiotic samples. Overall, these experiments demonstrate an elevated rate of DSBs at PATRR regions, an indication that the structure of PATRR containing DNA may lead to increased breakage in multiple cellular environments.

Clinician Perspectives on Specifications for Metrics to Inform Pediatric Alarm Management.

Background: Ongoing management of monitor alarms is important for reducing alarm fatigue among clinicians (e.g., nurses, physicians). Strategies to enhance clinician engagement in active alarm management in pediatric acute care have not been well explored. Access to alarm summary metrics may enhance clinician engagement. Objective: To lay the foundation for intervention development, we sought to identify functional specifications for formulating, packaging, and delivering alarm metrics to clinicians. Methods: Our team of clinician scientists and human factors engineers conducted focus groups with clinicians from medical-surgical inpatient units in a children's hospital. We inductively coded transcripts, developed codes into themes, and grouped themes into "current state" and "future state." Results: We conducted five focus groups with 13 clinicians (eight registered nurses and five doctors of medicine). In the current state, information exchanged among team members about alarm burden is initiated by nurses on an ad hoc basis. For a future state, clinicians identified ways in which alarm metrics could help them manage alarms and described specific information, such as alarm trends, benchmarks, and contextual data, that would support decision-making. Conclusion: We developed four recommendations for future strategies to enhance clinicians' active management of patient alarms: (1) formulate alarm metrics for clinicians by categorizing alarm rates by type and summarizing alarm trends over time, (2) package alarm metrics with contextual patient data to facilitate clinicians' sensemaking, (3) deliver alarm metrics in a forum that facilitates interprofessional discussion, and (4) provide clinician education to establish a shared mental model about alarm fatigue and evidence-based alarm-reduction strategies.

IQ and hemizygosity for the Val158 Met functional polymorphism of COMT in 22q11DS.

22q11.2 Deletion Syndrome (22q11DS) is a multisystem disorder caused by a hemizygous deletion within 22q11.2. Patients with the deletion display a wide range of cognitive deficits. The gene catechol-O-methyl-transferase (COMT) resides in the typically deleted region of 22q11.2 and is rendered hemizygous in individuals affected by the 22q11DS. COMT is a critical enzyme in the degradation of catecholamine neurotransmitters in the brain. A functional polymorphism, Val158 Met, has been associated with a variety of neurocognitive outcomes. In this study, 159 patients with 22q11DS were analyzed for a potential association between intelligence quotient (IQ) and COMT genotype. We performed a univariate analysis for overall influence and modified our analysis to focus on possible differences between average, borderline, and intellectually impaired patients. No correlation between COMT genotype and IQ performance was found. © 2016 Wiley Periodicals, Inc.

Observing sources of system resilience using in situ alarm simulations.

Alarm fatigue (and resultant alarm nonresponse) threatens the safety of hospitalized patients. Historically threats to patient safety, including alarm fatigue, have been evaluated using a Safety I perspective analyzing rare events such as failure to respond to patients' critical alarms. Safety II approaches call for learning from the everyday adaptations clinicians make to keep patients safe. To identify such sources of resilience in alarm systems, we conducted 59 in situ simulations of a critical hypoxemic-event alarm in medical/surgical and intensive care units at a tertiary care pediatric hospital between December 2019 and May 2022. Response timing, observations of the environment, and postsimulation debrief interviews were captured. Four primary means of successful alarm responses were mapped to domains of Systems Engineering Initiative for Patient Safety framework to inform alarm system design and improvement.

The Context-Variable Self and Autonomy: Exploring Surveillance Experience, (Mis)recognition, and Action at Airport Security Checkpoints.

This paper critiques and extends the notion of autonomy by examining how common autonomy definitions construct selfhood, with the support of an analysis of airport surveillance experiences. In psychology, autonomy is (1) often oriented around volition and action rather than the-self-that-acts and (2) the-self-that-acts is construed in singular terms. This neglects the multiple, context-variable self: while others may confirm our self-definitions (recognition), identity claims may also be rejected (misrecognition). The autonomy critique is sustained through an ethnographic analysis of airport security accounts (N = 156) in multiple nations with comparable security procedure (e.g., identification checks, luggage screening, questioning). Such procedures position people in multiple ways (e.g., as safe/dangerous, human/object, respectable/trash). Where respondents felt recognized, they experienced the security procedures positively, actively assisted in the screening process (engaged participation), and did not adapt their behaviors. Where respondents felt misrecognized, they experienced surveillance negatively, were alienated, and responded by either accommodating their behavior to avoid scrutiny, seeking to disrupt the process, or else withdrawing from screening sites. In misrecognition, the strategies that are open to the subject are incompatible with autonomy, if autonomy is defined solely in terms of volition. Accordingly, the concept of autonomy needs to be analyzed on two levels: in terms of the subject's ability freely to determine their own sense of self, as well as the actor's ability freely to enact selfhood.