Impact of target degradation on the 6FFF output of a Varian TrueBeam Linac.

The dosimetric output of a 6FFF beam, produced from a Varian TrueBeam linac exhibited an unexpected downward trend over time that was contrary to well-established expectations. To elucidate the cause of this uncharacteristic trend, a review of the linac's quality control results over its lifetime was performed, including, constancy checks of the dosimetric output, beam energy, flatness and symmetry, and percentage depth dose characteristics. These results were supplemented with a comprehensive series of measurements including flatness and symmetry measurements with a 1D-diode array, high-resolution measurements of the photon beam's build-up region with a parallel-plate chamber and measurement of the beam's output as a function of the x-ray target position.

Fragment-Based Discovery of a Series of Allosteric-Binding Site Modulators of β-Glucocerebrosidase.

β-Glucocerebrosidase (GBA/GCase) mutations leading to misfolded protein cause Gaucher's disease and are a major genetic risk factor for Parkinson's disease and dementia with Lewy bodies. The identification of small molecule pharmacological chaperones that can stabilize the misfolded protein and increase delivery of degradation-prone mutant GCase to the lysosome is a strategy under active investigation. Here, we describe the first use of fragment-based drug discovery (FBDD) to identify pharmacological chaperones of GCase.

Resurgence of ethanol seeking following voluntary abstinence produced by nondrug differential reinforcement of other behavior.

Resurgence refers to the relapse of a target behavior following the worsening of a source of alternative reinforcement that was made available during response elimination. Most laboratory analyses of resurgence have used a combination of extinction and alternative reinforcement to reduce target behavior. In contingency-management treatments for alcohol use disorder, however, alcohol use is not placed on extinction.

Evaluation of tumour motion and internal/external correlation in lung SABR.

Objective: This study aims to analyse lung tumour motion and to investigate the correlation between the internal tumour motion acquired from four-dimensional computed tomography (4DCT) and the motion of an external surrogate.

Methods: A data set of 363 4DCT images was analysed. Tumours were classified based on their anatomical lobes.

What If You Can't Ask Them? Psychometric Properties of a Behavioral Assessment of Sibling Relationship Quality.

Building on studies of preferences for social interaction in children with autism spectrum disorder (ASD) we sought to provide a way for siblings with ASD to express their perspective about the quality of their sibling relationships. We developed a behavioral assessment of sibling relationship preference (Sibling Relationship Assessment [SRA]) and examined the psychometric properties of test-retest reliability, inter-rater reliability, and convergent validity. The SRA was feasible to administer and revealed expected differences between sibling dyads with one sibling with ASD compared to typically-developing sibling dyads.

CNPY4 inhibits the Hedgehog pathway by modulating membrane sterol lipids.

The Hedgehog (HH) pathway is critical for development and adult tissue homeostasis. Aberrant HH signaling can lead to congenital malformations and diseases including cancer. Although cholesterol and several oxysterol lipids have been shown to play crucial roles in HH activation, the molecular mechanisms governing their regulation remain unresolved.

An Investigation of Multileaf Collimator Performance Dependence on Gantry Angle Using Machine Log Files.

Background: Quality assurance of linear accelerators (linacs) is an important part of ensuring accurate radiotherapy treatment deliveries. The aim of this study is to investigate the role of gravity on the positional accuracy of multileaf collimator (MLC) leaves during complex radiotherapy treatments on linacs. This investigation is based on the analysis of the machine log files from five different linacs in multiple centers.

Targetable HER3 functions driving tumorigenic signaling in HER2-amplified cancers.

Effective inactivation of the HER2-HER3 tumor driver has remained elusive because of the challenging attributes of the pseudokinase HER3. We report a structure-function study of constitutive HER2-HER3 signaling to identify opportunities for targeting. The allosteric activation of the HER2 kinase domain (KD) by the HER3 KD is required for tumorigenic signaling and can potentially be targeted by allosteric inhibitors.

Stratified Care vs Stepped Care for Depression: A Cluster Randomized Clinical Trial.

Importance: Depression is a major cause of disability worldwide. Although empirically supported treatments are available, there is scarce evidence on how to effectively personalize psychological treatment selection.

Objective: To compare the clinical effectiveness and cost-effectiveness of 2 treatment selection strategies: stepped care and stratified care.

Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization.

Upon ligand binding, bone morphogenetic protein (BMP) receptors form active tetrameric complexes, comprised of two type I and two type II receptors, which then transmit signals to SMAD proteins. The link between receptor tetramerization and the mechanism of kinase activation, however, has not been elucidated. Here, using hydrogen deuterium exchange mass spectrometry (HDX-MS), small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, combined with analysis of SMAD signaling, we show that the kinase domain of the type I receptor ALK2 and type II receptor BMPR2 form a heterodimeric complex via their C-terminal lobes.

Dealing with loss in the face of disasters and crises: Integrating interpersonal theories of couple adaptation and functioning.

The COVID-19 pandemic has highlighted the significant and varied losses that couples can experience during times of global and regional disasters and crises. What factors determine how couples navigate their close relationships during times of loss? In this paper, we elaborate and extend on one of the most influential frameworks in relationship science-the Vulnerability Stress Adaptation Model (VSAM, Karney and Bradbury, 1995)-to enhance the model's power to explain relationships during loss-themed disasters/crises. We do so by elaborating on attachment theory and integrating interdependence theory (emphasizing partner similarities and differences).

Reducing treatment machine downtime with a preventative MLC maintenance procedure.

The persistent use of MLCs through VMAT and IMRT is causing additional wear and tear on these mechanical parts, leading to an increase in MLC interlocks, breakdowns and failures. This study investigates the effect of an MLC clean and service procedure on MLC performance and positional accuracy demonstrated through in-house service logbook reports, Varian MLC backlash test results, daily MLC position QC results and Varian TrueBeam trajectory log file data. A service and clean of each individual MLC leaf was carried out on 3 standard MLC and 2 high definition MLC (HDMLC) Varian TrueBeam linacs.

Health promotion interventions to improve oral health of adolescents: A systematic review and meta-analysis.

Objectives: To evaluate the effectiveness of health promotion interventions on oral health knowledge, behaviour and status of healthy adolescents.

Methods: This review included randomized controlled trials (RCTs) of oral health promotion interventions targeting adolescents. Primary clinical outcomes (gingival health, plaque scores, caries) and secondary proxy outcomes were evaluated.

Family Impact of Child Oro-Facial Cleft.

Objective: To describe the association between children's orofacial cleft (OFC) and families' quality of life (QoL), using the short-form Family Impact Scale questionnaire (FIS-SF). Also assessed were the psychometric properties of the FIS-SF, as well as whether certain demographic and clinical variables impacted the family.

Design: Observational cross-sectional study.

Laboratory misdiagnosis of von Willebrand disease in post-menarchal females: A multi-center study.

Increased awareness of von Willebrand Disease (VWD) has led to more frequent diagnostic laboratory testing, which insurers often dictate be performed at a facility with off-site laboratory processing, instead of a coagulation facility with onsite processing. Off-site processing is more prone to preanalytical variables causing falsely low levels of von Willebrand Factor (VWF) due to the additional transport required. Our aim was to determine the percentage of discordance between off-site and onsite specimen processing for VWD in this multicenter, retrospective study.

Commitment strength versus commitment bolstering: Uncertainty undermines and promotes relationship success.

Little research has examined factors that might weaken or strengthen commitment effects on relationship outcomes. The current research integrates attitude strength and investment model perspectives to identify uncertainty as a new moderator of commitment's predictive ability. Consistent with an attitude strength perspective, having doubt associated with commitment undermines commitment's predictive power.

Adaptive radiotherapy for head and neck cancer reduces the requirement for rescans during treatment due to spinal cord dose.

Background: Patients treated with radiotherapy for head and neck (H&N) cancer often experience anatomical changes. The potential compromises to Planning Target Volume (PTV) coverage or Organ at Risk (OAR) sparing has prompted the use of adaptive radiotherapy (ART) for these patients. However, implementation of ART is time and resource intensive.

The crystal structure of the protein kinase HIPK2 reveals a unique architecture of its CMGC-insert region.

The homeodomain-interacting protein kinase (HIPK) family is comprised of four nuclear protein kinases, HIPK1-4. HIPK proteins phosphorylate a diverse range of transcription factors involved in cell proliferation, differentiation, and apoptosis. HIPK2, thus far the best-characterized member of this largely understudied family of protein kinases, plays a role in the activation of p53 in response to DNA damage.

Seeking and Ensuring Interdependence: Desiring Commitment and the Strategic Initiation and Maintenance of Close Relationships.

The current research offers and examines the concept of , defined as the subjective desire to be involved in a committed romantic relationship at a given time. In pursuing their desire for a committed romance, how do individuals high in commitment desirability strategically ensure success? We suggest that high perceived partner commitment is sought by individuals who themselves desire to be involved in a committed relationship. In three studies involving individuals both currently involved and not involved in a relationship, we found support for the hypothesized interactive effect of commitment desirability and perceived partner commitment, such that greater commitment desirability was associated with more positive relationship outcomes, especially when partners were perceived to be high in commitment.

Functional role of PGAM5 multimeric assemblies and their polymerization into filaments.

PGAM5 is a mitochondrial protein phosphatase whose genetic ablation in mice results in mitochondria-related disorders, including neurodegeneration. Functions of PGAM5 include regulation of mitophagy, cell death, metabolism and aging. However, mechanisms regulating PGAM5 activation and signaling are poorly understood.

An evaluation of techniques for dose calculation on cone beam computed tomography.

Objective:: To assess the accuracy and efficiency of four different techniques, thus determining the optimum method for recalculating dose on cone beam CT (CBCT) images acquired during radiotherapy treatments.

Methods:: Four established techniques were investigated and their accuracy assessed via dose calculations: (1) applying a standard planning CT (pCT) calibration curve, (2) applying a CBCT site-specific calibration curve, (3) performing a density override and (4) using deformable registration. Each technique was applied to 15 patients receiving volumetric modulated arc therapy to one of three treatment sites, head and neck, lung and prostate.

Commitment Readiness and Relationship Formation.

The concept of being ready for a relationship is pervasive in popular culture, but theoretical and empirical research on readiness is lacking. We offer a conceptualization of commitment readiness and provide some of the first empirical work examining readiness among single individuals-specifically how this construct shapes various aspects of relationship formation. Using data from five independent samples of individuals not involved in romantic relationships, we first establish that commitment readiness is associated with more interest in developing a close romantic relationship (Studies 1a, 1b, 2) and with active pursuit of relationship initiation (Study 2).

Improvement of off-axis SABR plan verification results by using adapted dose reconstruction algorithms for the Octavius 4D system.

Purpose: Stereotactic ablative body radiotherapy (SABR) for lung patients can be performed with volumetric-modulated arc therapy (VMAT) plans using off-axis target geometry to allow treatment in their CBCT verified position. For patient-specific quality assurance measurements using the PTW Octavius 4D phantom (PTW, Freiburg, Germany) (OCT4D) in conjunction with an Octavius 1000SRS array (OCT1000) (PTW, Freiburg, Germany), repositioning the phantom off-axis is required to ensure the measurement area coincides with the tumor. The aim of this work is to quantify delivery errors using an array repositioned off-axis and evaluate new software which incorporates corrections for off-axis phantom measurements.

Contraceptive Method Choice Among Young Adults: Influence of Individual and Relationship Factors.

Because decisions related to contraceptive behavior are often made by young adults in the context of specific relationships, the relational context likely influences use of contraceptives. Data presented here are from in-person structured interviews with 536 Black, Hispanic, and White young adults from East Los Angeles, California. We collected partner-specific relational and contraceptive data on all sexual partnerships for each individual, on four occasions, over one year.