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ABSTRACT: Objective: To evaluate the impact of the COVID-19 pandemic on the psychosocial functioning of individuals with cleft lip and/or palate (CL/P). Methods: Patients with CL/P ≥ 6 years old were prospectively recruited from the Cleft and Craniofacial Clinic of a tertiary children's hospital. From July-October 2021, eligible patients (or their parent/guardian) were sent a survey regarding their psychosocial functioning before and after the start of the pandemic. Main Outcome Measure: The difference between prepandemic and intrapandemic patient-reported outcome scores. Results: Thirty-six patients (20 female, age: 15.9 ± 9.8 years) responded. Most had cleft lip and palate (77.8%), responded online (69.4%), interacted remotely via both voice- and video-conferencing (62.9%), and wore masks routinely (77.1%). Similar numbers of patients responded independently (27.8%), responded with the help of a parent/guardian (36.1%), or had a parent/guardian respond on their behalf (36.1%). General social-emotional well-being (p = 0.004, rrb = 0.659) and satisfaction with facial appearance (p = 0.044, rrb = 0.610) significantly improved after the start of the pandemic. Compared to their general intrapandemic social-emotional well-being scores, patients reported higher scores while wearing a mask (rrb = 0.827) and lower scores while interacting remotely (rrb = 0.605), although all were still significantly improved compared to their prepandemic scores (p ≤ 0.010). Patients also reported significant improvement in social functioning while wearing a mask (p = 0.036, rrb = 0.519), whereas they did not when considering their general intrapandemic feelings/experiences (p = 0.269, rrb = 0.211). Conclusion: Patients with CL/P demonstrated significant improvement in overall social-emotional well-being, satisfaction with facial appearance, and social functioning after the start of the COVID-19 pandemic, particularly when wearing a mask.

Background: To address unknown risk for readmission among patients with COVID-19 and persistent capacity strain, hospital systems used postdischarge contact and monitoring to facilitate safe discharge and recovery. However, little work has systematically documented how hospitals implemented changes to hospitalization postdischarge contact practices during COVID-19. Research Question: How did hospitals’ innovate and adapt postdischarge telephone follow-up and remote monitoring strategies to assess discharged patients with COVID-19 for risk of readmission and recovery progress? Study Design and Methods: Semistructured interviews were conducted (January 2022 to March 2023) with 70 inpatient and outpatient providers and administrators (5-12 per site) in nine health systems that varied by size, region, rurality, proportion of Medicaid patients, and estimated scale of post-COVID-19 care organization. Participants described innovation in and implementation of discharge and postdischarge care processes used to assess patients with COVID-19 for readmission risk and recovery progress. The primary analysis was site-level case comparative analysis. Results: Respondents described hospital systems’ motivations for adapting preexisting resources and innovating new postdischarge programs, including postdischarge telephone follow-up and remote monitoring programs, to facilitate safe hospital discharge and transitions to ambulatory care for patients with COVID-19. Respondents also explained various factors that influenced the implementation and use of postdischarge contact practices. Participants perceived that these practices mitigated postdischarge risks and alleviated capacity strain. Respondents described retiring or adapting remote monitoring programs for other conditions as COVID-19 demands declined. Interpretation: Our results show that hospitals implemented and adapted postdischarge practices to help facilitate recovery and address unknown risk for readmission during the pandemic. Some efforts may present opportunities to manage readmission concerns and capacity strain more generally.

Objective: To describe Kaiser Permanente Northern California's (KPNC) systematic implementation of universal tobacco screening, evidence-based interventions, and performance measures to achieve long-term smoking cessation success. Methods: We outline seven key components of KPNC's tobacco screening and intervention program that contributed to a significant decline in smoking prevalence. We also report changes in the prevalence of current smokers within KPNC from 2014 to 2023 using linear regression analyses. Results: Key factors driving the success of the tobacco cessation program included risk-based screening algorithms, alert prompts for at-risk patients, system-wide medical champions, performance tracking, virtual coaching, widespread messaging, and comprehensive medication management. Implementing this multifaceted approach across all facilities was associated with a significant reduction in smoking prevalence, from 8.6% in 2014 to 5.8% in 2023 (p < 0.0001). Conclusion: Our comprehensive, system-wide approach resulted in substantial public health gains and highlights the potential of similar preventive strategies as healthcare systems transition toward value-based care.

Objective: Given the high burden and increasing prevalence of post-traumatic osteoarthritis (PTOA), identifying clinically beneficial strategies to prevent or delay its onset could improve the quality of life of those at high risk of developing the disease. Methods: Preventing Injured Knees from OsteoArthritis: Severity Outcomes (PIKASO) is a multicenter blinded, parallel, two-arm randomized controlled trial of 512 individuals aged 18–45 years undergoing anterior cruciate ligament reconstruction (ACLR). This study is designed to evaluate the efficacy of a 12-month intervention of oral metformin vs. placebo in decreasing the rate of structural knee changes and pain. Participants will be asked to take up to 1500 ​mg/day of either metformin or placebo as tolerated. The primary outcomes are Knee injury and Osteoarthritis Outcome Score (KOOS) Pain subscale scores averaged between 12 and 24 months after randomization, and MRI derived cartilage structural change at 24 months. The trial will be deemed successful if at least one of the two primary outcomes reaches the preplanned effect size with sufficient statistical certainty. In this paper, we describe PIKASO elements according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Results: Our multidisciplinary team developed the methods and statistical analysis plan for a placebo controlled, randomized clinical trial to determine whether metformin alters pain and early osteoarthritic changes after ACLR. Discussion: This manuscript outlines the rationale, study design, and implementation of the PIKASO trial aiming to prevent the onset of PTOA after ACLR. Trial registration: clinicaltrials.gov NCT06096259.

Viruses are infectious agents that cause various diseases worldwide. The recent COVID-19 pandemic has shown the need for rapid and reliable tests to confirm viral infections, aiming at the rapid isolation, treatment, and identification of high-incidence regions. Rapid antigen tests based on lateral flow immunochromatography have proven to be very useful. However, they are not accurate in patients with low viral loadings. The gold standard test is RT-PCR, which identifies parts of the viral genome by detecting specific DNA or RNA sequences. RT-PCR or similar tests such as RT-LAMP involve several steps for sample preparation and amplification of target sequences, require trained personnel to be performed, and can be time-consuming and expensive, limiting their point-of-care application. Biosensors are promising analytical devices for detecting nucleic acids, mainly RNA from viruses, offering advantages such as rapid results, high sensitivity, and low cost compared with the RT-PCR test since the amplification of target sequences is not necessary. Recently, several biosensors have been developed to detect RNA viruses without sequence amplification. Here, we present a review on the design and technology of amplification-free biosensors for the detection of viral RNA as an alternative for diagnosing infectious diseases. The challenges and advances for the point-of-care electrochemical, electrical, and optical biosensors will be addressed.

Summary: Here, we show that a NOT gated cell therapy (Tmod) can exploit antigens such as epidermal growth factor receptor (EGFR) and human leukocyte antigen-E (HLA-E) which are widely expressed on cancer cells. Noncancerous cells—despite high expression of these antigens—are protected from cytotoxicity by the action of an inhibitory receptor (“blocker”) via a mechanism that involves blocker modulation of CAR surface expression. The blocker is triggered by the product of a polymorphic HLA allele (e.g., HLA-A∗02) deleted in a significant subset of solid tumors via loss of heterozygosity. Moreover, Tmod constructs that target mouse homologs of EGFR or HLA-E for activation, and a mouse-equivalent of HLA-A∗02 for inhibition, protect mice from toxicity caused by the CAR alone. The blocker also controls graft vs. host response in allogeneic T cells in vitro, consistent with the use of Tmod cells for off-the-shelf therapy without additional gene-editing.

Summary: The gastrointestinal (GI) tract is innervated by intrinsic neurons of the enteric nervous system (ENS) and extrinsic neurons of the central nervous system and peripheral ganglia. The GI tract also harbors a diverse microbiome, but interactions between the ENS and the microbiome remain poorly understood. Here, we activate choline acetyltransferase (ChAT)-expressing or tyrosine hydroxylase (TH)-expressing gut-associated neurons in mice to determine effects on intestinal microbial communities and their metabolites as well as on host physiology. The resulting multi-omics datasets support broad roles for discrete peripheral neuronal subtypes in shaping microbiome structure, including modulating bile acid profiles and fungal colonization. Physiologically, activation of either ChAT+ or TH+ neurons increases fecal output, while only ChAT+ activation results in increased colonic contractility and diarrhea-like fluid secretion. These findings suggest that specific subsets of peripherally activated neurons differentially regulate the gut microbiome and GI physiology in mice without involvement of signals from the brain.

Summary: Aging increases the risk of age-related diseases, imposing substantial healthcare and personal costs. Targeting fundamental aging mechanisms pharmacologically can promote healthy aging and reduce this disease susceptibility. In this work, we employed transcriptome-based drug screening to identify compounds emulating transcriptional signatures of long-lived genetic interventions. We discovered compound 60 (Cmpd60), a selective histone deacetylase 1 and 2 (HDAC1/2) inhibitor, mimicking diverse longevity interventions. In extensive molecular, phenotypic, and bioinformatic assessments using various cell and aged mouse models, we found Cmpd60 treatment to improve age-related phenotypes in multiple organs. Cmpd60 reduces renal epithelial-mesenchymal transition and fibrosis in kidney, diminishes dementia-related gene expression in brain, and enhances cardiac contractility and relaxation for the heart. In sum, our two-week HDAC1/2 inhibitor treatment in aged mice establishes a multi-tissue, healthy aging intervention in mammals, holding promise for therapeutic translation to promote healthy aging in humans.

Objectives: This study was designed to understand the experience and needs surrounding advance care planning (ACP) discussions for surrogate decision-makers of persons with advanced dementia (PWAD). Methods: Semi-structured qualitative interviews based on end-of-life communication models with a convenience sample of 17 clinicians, and 15 surrogates of PWAD. We used a hybrid approach of deductive and inductive thematic analysis. Results: Two main themes emerged. 1)Deficits in communication: Often surrogates did not fully comprehend the disease trajectory or medical treatments, like the likelihood of pneumonia and use of mechanical ventilation, nor concepts related to ACP, particularly legal documents and orders such as Do Not Hospitalize, which made decision-making challenging as perceived by clinicians. 2)Decision-making conflicts: Clinicians perceived a disconnect between surrogates' understanding of their loved one's preferences and knowing how or when to operationalize them. Conclusions: Significant gaps in knowledge surrounding disease trajectory and complications, such as pneumonia, and aspects of ACP, exist. These gaps create decision-making challenges for surrogates and clinicians alike. Innovation: This study assessed both clinicians and surrogate decision-makers' perspectives on communication and decision-making concerning care preferences, goals, and ACP. The study findings from a national cohort can inform decision-support interventions for clinicians and surrogate decision-makers of PWAD.

Recurrent patellar instability is a rare complication after patellofemoral arthroplasty (PFA) and usually involves a traumatic injury. Medial patellofemoral ligament (MPFL) reconstruction after arthroplasty is a complicated and technically challenging surgical procedure because the lack of patellar bone stock due to resurfacing significantly increases the risk of patellar fracture. We present our surgical technique for revision MPFL reconstruction for recurrent instability after PFA. This technical note describes the use of 1.8-mm all-suture anchors for revision MPFL reconstruction in patients with decreased patellar bone stock after PFA. This technique reduces the risk of patellar fracture without compromising the integrity of the MPFL graft.

Purpose: Head and neck (HN) radiation (RT) treatment planning is complex and resource intensive. Deviations and inconsistent plan quality significantly affect clinical outcomes. We sought to develop a novel automated virtual integrative (AVI) knowledge-based planning application to reduce planning time, increase consistency, and improve baseline quality. Methods and Materials: An in-house write-enabled script was developed from a library of 668 previously treated HN RT plans. Prospective hazard analysis was performed, and mitigation strategies were implemented before clinical release. The AVI-planner software was retrospectively validated in a cohort of 52 recent HN cases. A physician panel evaluated planning limitations during initial deployment, and feedback was enacted via software refinements. A final second set of plans was generated and evaluated. Kolmogorov-Smirnov test in addition to generalized evaluation metric and weighted experience score were used to compare normal tissue sparing between final AVI planner versus respective clinically treated and historically accepted plans. A t test was used to compare the interactive time, complexity, and monitor units for AVI planner versus manual optimization. Results: Initially, 86% of plans were acceptable to treat, with 10% minor and 4% major revisions or rejection recommended. Variability was noted in plan quality among HN subsites, with high initial quality for oropharynx and oral cavity plans. Plans needing revisions were comprised of sinonasal, nasopharynx, P-16 negative squamous cell carcinoma unknown primary, or cutaneous primary sites. Normal tissue sparing varied within subsites, but AVI planner significantly lowered mean larynx dose (median, 18.5 vs 19.7 Gy; P < .01) compared with clinical plans. AVI planner significantly reduced interactive optimization time (mean, 2 vs 85 minutes; P < .01). Conclusions: AVI planner reliably generated clinically acceptable RT plans for oral cavity, salivary, oropharynx, larynx, and hypopharynx cancers. Physician-driven iterative learning processes resulted in favorable evolution in HN RT plan quality with significant time savings and improved consistency using AVI planner.

Purpose: While disparities in the inclusion and advancement of women and minorities in science, technology, engineering, mathematics, and medical fields have been well documented, less work has focused on medical physics specifically. In this study, we evaluate historical and current diversity within the medical physics workforce, in cohorts representative of professional advancement (PA) in the field, and within National Institutes of Health (NIH)–funded medical physics research activities. Methods and Materials: The 2020 American Association of Physicists in Medicine (AAPM) membership was queried as surrogate for the medical physics workforce. Select subsets of the AAPM membership were queried as surrogate for PA and early career professional advancement (ECPA) in medical physics. Self-reported AAPM-member demographics data representative of study analysis groups were identified and analyzed. Demographic characteristics of the 2020 AAPM membership were compared with those of the PA and ECPA cohorts and United States (US) population. The AAPM-NIH Research Database was appended with principal investigator (PI) demographics data and analyzed to evaluate trends in grant allocation by PI demographic characteristics. Results: Women, Hispanic/Latinx/Spanish individuals, and individuals reporting a race other than White or Asian alone comprised 50.8%, 18.7%, and 32.4% of the US population, respectively, but only 23.9%, 9.1%, and 7.9% of the 2020 AAPM membership, respectively. In general, representation of women and minorities was further decreased in the PA cohort; however, significantly higher proportions of women (P < .001) and Hispanic/Latinx/Spanish members (P < .05) were observed in the ECPA cohort than the 2020 AAPM membership. Analysis of historical data revealed modest increases in diversity within the AAPM membership since 2002. Across NIH grants awarded to AAPM members between 1985 and 2020, only 9.4%, 5.3%, and 1.7% were awarded to women, Hispanic/Latinx/Spanish, and non-White, non-Asian PIs, respectively. Conclusions: Diversity within medical physics is limited. Proactive policy should be implemented to ensure diverse, equitable, and inclusive representation within research activities, roles representative of PA, and the profession at large.

Objective: Evidence-based decision support resources do not exist for persons with lung cancer. We sought to develop and refine a treatment decision support, or conversation tool, to improve shared decision-making (SDM). Methods: We conducted a multi-site study among patients with stage I-IV non-small cell lung cancer (NSCLC) who completed or had ongoing lung cancer treatment using semi-structured, cognitive qualitative interviews to assess participant understanding of content. We used an integrated approach of deductive and inductive thematic analysis. Results: Twenty-seven patients with NSCLC participated. Participants with prior cancer experiences or those with family members with prior cancer experiences reported better preparedness for cancer treatment decision-making. All participants agreed the conversation tool would be helpful to clarify their thinking about values, comparisons, and goals of treatment, and to help patients communicate more effectively with their clinicians. Conclusion: Participants reported that the tool may empower them with confidence and agency to actively participate in cancer treatment SDM. The conversation tool was acceptable, comprehensible, and usable. Next steps will test effectiveness on patient-centered and decisional outcomes. Innovation: A personalized conversation tool using consequence tables and core SDM components is novel in that it can encourage a tailored, conversational dynamic and includes patient-centered values along with traditional decisional outcomes.

Perceptual narrowing is a domain-general process in which infants move from a broad sensitivity to a wide range of stimuli to developing expertise within often experienced native stimuli (Maurer & Werker, 2014). One outcome of this is the own-race bias, characterized by an increasing difficulty in discriminating other-race faces with age and experience for those raised in a racially homogenous environment (Anzures, Quinn, Pascalis, Slater, Tanaka, & Lee, 2013). Theorists have proposed that this is due to a categorization-individuation process, wherein infants begin to categorize non-native stimuli but continue to individuate native stimuli (Hugenberg, Young, Bernstein, & Sacco, 2010; Nelson, 2001). Exposure to multiple exemplars during initial learning has been found to facilitate infant categorization of other-species faces while exposure to a single exemplar does not (Dixon, Reynolds, Romano, Roth, Stumpe, Guy, & Mosteller, 2019). The goal of this study was to investigate the effects of initial learning conditions on infants' ability to individuate and categorize own- and other-race faces. Ten-month-old infants were familiarized with a single exemplar or multiple exemplars of own- or other-race faces. Event-related potentials (ERPs) were recorded while infants were presented with the familiar face(s) they were exposed to during familiarization, novel faces from the same race used during familiarization, and novel faces from a race other than the one used in familiarization. Infants familiarized with a single exemplar, regardless of race, showed significant differences in both the Nc component (Negative central, associated with visual attention) and the LSW (late slow wave, associated with recognition memory) between familiar and novel faces at the subordinate-level category of race. No differences were found across familiarization conditions for the P400 component associated with face processing. Infants familiarized with multiple exemplars showed no evidence of discriminating faces at the categorical or individual level. Results suggest that, in contrast to other-species faces, infants at this age may process human faces more efficiently when familiarized with a single exemplar. The implications of the current findings are discussed in relation to the impact of initial learning conditions on infants' ability to individuate and categorize own- and other-species faces and social implications of infants' processing of other-race faces.

Recently, increased number of studies have demonstrated a relationship between the oral microbiome and development of head and neck cancer, however, there are few studies to investigate the role of oral bacteria in the context of the tumor microenvironment in a single head and neck subsite. Here, paired tumor and adjacent normal tissues from thirty-seven oral tongue squamous cell carcinoma (SCC) patients were subjected to 16S rRNA gene sequencing and whole exome sequencing (WES), in addition to RNA sequencing for tumor samples. We observed that Fusobacterium was significantly enriched in oral tongue cancer and that Rothia and Streptococcus were enriched in adjacent normal tissues. A decrease in alpha diversity was found in tumor when compared to adjacent normal tissues. While increased Fusobacterium in tumor samples was not associated with changes in immune cell infiltration, it was associated with increased PD-L1 mRNA expression. Therefore, we examined the effects of Fusobacterium on PD-L1 expression in head and neck SCC cell lines. We demonstrated that infection with Fusobacterium species can increase both PD-L1 mRNA and surface PD-L1 protein expression on head and neck cancer cell lines. The correlation between Fusobacterium and PD-L1 expression in oral tongue SCC, in conjunction with the ability of the bacterium to induce PD-L1 expression in vitro suggests a potential role for Fusobacterium on modulation of the tumor immune microenvironment in head and neck cancer.

Background & Aims: Alpha-1 antitrypsin deficiency is caused by mutations in SERPINA1, most commonly homozygosity for the Pi∗Z variant, and can present as liver disease. While heterozygosity for Pi∗Z (Pi∗MZ) is linked to increased risk of cirrhosis, whether the Pi∗MZ genotype is associated with an increased rate of decompensation among patients who already have compensated cirrhosis is not known. Methods: This was a retrospective study of Michigan Genomics Initiative participants with baseline compensated cirrhosis. The primary predictors were Pi∗MZ or Pi∗MS genotype (vs. Pi∗MM). The primary outcomes were hepatic decompensation with ascites, hepatic encephalopathy, or variceal bleeding, or the combined endpoint of liver-related death or liver transplant, both modeled with Fine-Gray competing risk models. Results: We included 576 patients with baseline compensated cirrhosis who had undergone genotyping, of whom 474 had Pi∗MM, 49 had Pi∗MZ, and 52 had Pi∗MS genotypes. Compared to Pi∗MM genotype, Pi∗MZ was associated with increased rates of hepatic decompensation (hazard ratio 1.81; 95% CI 1.22-2.69; p = 0.003) and liver transplant or liver-related death (hazard ratio 2.07; 95% CI 1.21-3.52; p = 0.078). These associations remained significant after adjustment for severity of underlying liver disease, and were robust across subgroup analyses based on etiology, sex, obesity, and diabetes status. Pi∗MS was not associated with decompensation or death/transplantation. Conclusions: The SERPINA1 Pi∗MZ genotype is associated with an increased rate of hepatic decompensation and decreased transplant-free survival among patients with baseline compensated cirrhosis. Lay summary: There is a mutation in the gene SERPINA1 called Pi∗MZ which increases risk of liver scarring (cirrhosis); however, it is not known what effect Pi∗MZ has if someone already has cirrhosis. In this study, we found that people who had cirrhosis and Pi∗MZ developed complications from cirrhosis faster than those who did not have the mutation.

Cannabis use among individuals before and during pregnancy is increasing alongside the proliferation of new products with various modes of administration. Preconception cannabis use is a strong predictor of prenatal cannabis use. Yet little is known about how individuals administer cannabis during the preconception period, particularly in socioeconomically vulnerable populations. This study examined the prevalence and correlates of modes of cannabis administration (smoke, vape, blunts, edible/oral, dabs/wax, lotion/topical) during the year before conception, among patients who self-reported preconception cannabis use during universal screening in prenatal care. Descriptive statistics included sociodemographic characteristics, preconception cannabis use frequency, and modes of administration. Chi-square tests examined whether mode was associated with sociodemographic characteristics and use frequency. The sample (N = 11,936, screened from February 2020-May 2021) was 59.8% non-White and 26.1% were

Solar selective coatings can improve the performance of solar collectors by reducing heat losses by thermal radiation, so that the surface selectively absorbs solar radiation with wavelengths specific to solar thermal conversion. The demand for low carbon and more sustainable products has evolved rapidly in recent years and selective surfaces are expected to play an important role in the development of solar energy technologies. The objective of this study is to assess the production process of selective surfaces with Black Chrome (CrxOy) obtained by two deposition techniques (sputtering and electrodeposition), using the Life Cycle Assessment (LCA) methodology. To this end, real data were collected from experiments, and detailed inventories of energy and material flows were built to support a LCA that quantified the carbon footprint of each manufacturing process. Per process, the results demonstrated that electrodeposition presented a higher overall carbon footprint (16.912 g CO2-eq) than sputtering (14.271 g CO2-eq). Electricity consumption associated with both processes was responsible for a significant share of the total carbon footprint: 77% for the electrodeposition technique and 59% for sputtering. The prospective LCA presented herein helped identify the hotspots of the processes that have margins for improvement, providing guidance regarding process upscaling.

Purpose: Due to a gap in published guidance, we describe our robust cycle of in-house clinical software development and implementation, which has been used for years to facilitate the safe treatment of all patients in our clinics. Methods and Materials: Our software development and implementation cycle requires clarity in communication, clearly defined roles, thorough commissioning, and regular feedback. Cycle phases include design requirements and use cases, development, physics evaluation testing, clinical evaluation testing, and full clinical release. Software requirements, release notes, test suites, and a commissioning report are created and independently reviewed before clinical use. Software deemed to be high-risk, such as those that are writable to a database, incorporate the use of a formal, team-based hazard analysis. Incident learning is used to both guide initial development and improvements as well as to monitor the safe use of the software. Results: Our standard process builds in transparency and establishes high expectations in the development and use of custom software to support patient care. Since moving to a commercial planning system platform in 2013, we have applied our team-based software release process to 16 programs related to scripting in the treatment planning system for the clinic. Conclusions: The principles and methodology described here can be implemented in a range of practice settings regardless of whether or not dedicated resources are available for software development. In addition to teamwork with defined roles, documentation, and use of incident learning, we strongly recommend having a written policy on the process, using phased testing, and incorporating independent oversight and approval before use for patient care. This rigorous process ensures continuous monitoring for and mitigatation of any high risk hazards.

Purpose: To generate an understanding of the primary concerns facing medical physicists regarding integration of a demanding technical career with their personal lives. Methods and Materials: In 2019, we recruited 32 medical physics residents, faculty, and staff via emails to US medical physics residency program directors to participate in a 1-hour, semistructured interview that elicited their thoughts on several topics, including work–life integration. Standard techniques of qualitative thematic analysis were used to generate the research findings. Results: Of the participants, 50% were women and 69% were non-Hispanic White individuals, with a mean (SD) age of 37.5 (7.4) years. They were evenly split between residents and faculty or staff. Participant responses centered around 5 primary themes: the gendered distribution of household responsibilities, the effect of career or work on home and family life, the effect of family on career or work, support and strategies for reconciling work–life conflicts, and the role of professional societies in addressing work–life integration. Participants expressed concern about the effect of heavy workloads on home life, with female respondents more likely to report carrying the majority of the household burden. Conclusions: Medical physicists experience challenges in managing work–life conflict amid a diverse array of personal and professional responsibilities. Further investigations are needed to quantitatively assess the division of work and household labor by gender in medical physics, particularly after the outbreak of the COVID-19 pandemic, but this study's qualitative findings suggest that the profession should consider ways to address root causes of work–life conflict to promote the future success and well-being of all medical physicists, and perhaps women in particular.

This paper reports 2 cases of female carriers of the FMR1 premutation for developing spontaneous coronary artery dissection (SCAD). These women had classical presentations of premutation symptoms, including anxiety, depression, and connective tissue problems, all of which can contribute to SCAD. These cases suggest a possible connection between the fragile X premutation and a predisposition to SCAD. (Level of Difficulty: Intermediate.)

Purpose: To present a systematic approach to the reirradiation special medical physics consult (ReRT-SMPC) process. Materials and Methods: An in-house reirradiation committee of physicians and physicists was formed to develop a streamlined and well-documented approach to ReRT-SMPCs. Dosimetric goals and considerations for tissue repair were generated by the committee with input from the literature, clinical trial guidelines, and physician experience. Procedural workflow was also defined. Results: The total number of ReRT-SMPCs performed in our department in 2018 was 401, corresponding to 369 unique patients and 16% of the total number of patients receiving external beam radiation in our department that year. This constituted a large increase over the 183 ReRT-SMPCs performed in 2017. We have found that a standardized ReRT-SMPC workflow helps to safeguard patients, documents the clinical decision-making process for medical and legal purposes, and facilitates the peer-review process. The data being collected from each consult along with toxicity and outcomes data can be used to help inform future re-treatment guidelines. Conclusions: As the number of patients returning for additional courses of radiation continues to increase, a uniform method for the ReRT-SMPC workflow and analysis is a powerful tool for ensuring patient safety, understanding and predicting treatment toxicity, and refining reirradiation dosimetric limits.

T2 quantification is commonly attempted by applying an exponential fit to proton density (PD) and transverse relaxation (T2)-weighted fast spin echo (FSE) images. However, inter-site studies have noted systematic differences between vendors in T2 maps computed via standard exponential fitting due to imperfect slice refocusing, different refocusing angles and transmit field (B1+) inhomogeneity. We examine T2 mapping at 3T across 13 sites and two vendors in healthy volunteers from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using both a standard exponential and a Bloch modelling approach. The standard exponential approach resulted in highly variable T2 values across different sites and vendors. The two-echo fitting method based on Bloch equation modelling of the pulse sequence with prior knowledge of the nominal refocusing angles, slice profiles, and estimated B1+ maps yielded similar T2 values across sites and vendors by accounting for the effects of indirect and stimulated echoes. By modelling the actual refocusing angles used, T2 quantification from PD and T2-weighted images can be applied in studies across multiple sites and vendors.

Declining auditory spatial processing is hypothesized to contribute to the difficulty older adults have detecting, locating, and selecting a talker from among others in noisy listening environments. Though auditory spatial processing has been associated with several cortical structures, little is known regarding the underlying white matter architecture or how age-related changes in white matter microstructure may affect it. The arcuate fasciculus is a target for understanding age-related differences in auditory spatial attention based on normative spatial attention findings in humans. Similarly, animal and human clinical studies suggest that the corpus callosum plays a role in the cross-hemispheric integration of auditory spatial information important for spatial localization and attention. The current investigation used diffusion imaging to examine the extent to which age-group differences in the identification of spatially cued speech were accounted for by individual differences in the white matter microstructure of the right arcuate fasciculus and the corpus callosum. Higher right arcuate and callosal fractional anisotropy (FA) predicted better segregation and identification of spatially cued speech across younger and older listeners. Further, individual differences in callosal microstructure mediated age-group differences in auditory spatial processing. Follow-up analyses suggested that callosal tracts connecting left and right pre-frontal and posterior parietal cortex are particularly important for auditory spatial processing. The results are consistent with previous work in animals and clinical human samples and provide a cortical mechanism to account for age-related deficits in auditory spatial processing. Further, the results suggest that both intrahemispheric and interhemispheric mechanisms are involved in auditory spatial processing.

Selenium is a metalloid trace element essential for maintaining the optimal redox environment in cells and tissues. It is structurally incorporated into over 25 selenoproteins and enzymes. The glutathione peroxidase (GPx) family of enzymes has a critical role in human health because of its antioxidant function. The recommended daily allowance (RDA) for selenium intake in humans was established to maximize the activity of GPx in plasma. Suboptimal availability of selenium can limit the expression and activities of GPxs leading to a compromised redox environment. This can cause detrimental oxidative distress that could be prevented by increasing the availability of selenium. In cell culture studies, the medium is typically deficient in selenium; supplementation with selenium can increase selenoenzyme activities. However, the optimal level of supplementation in cell culture media has not been well characterized. We performed dose-response experiments for the activities of GPx1 and GPx4 vs. the level of selenium supplementation in cell culture medium. For this, we advanced an assay to determine the activities of both GPx1 and GPx4 efficiently in a single run. During the optimization process, we found that the observed activities of GPx1 and GPx4 depend greatly on the pH of the assay buffer; the observed activities increase with increasing pH, with pH 8 being optimal. Using the combination assay, we also found that the expression and activities for both GPx1 and GPx4 can be maximized in exponentially growing cells by supplementing cell culture media with ≈ 200 nM seleno-l-methionine, without concerns for toxicity. Optimizing the availability of selenium in cell culture to maximize the expression and activities GPx1 and GPx4 may allow for better translation of information from cell culture work to in vivo settings.

As the global burden of cardiovascular disease (CVD) rises, public health-related interventions aimed at prevention of heart disease have gained medical attention. Clinical research reports that exercise is a protective risk factor associated with CVD and that clinicians need to provide exercise recommendations to patients. Nevertheless, physical inactivity remains a public health problem. In certain populations, like firefighters (FF), increased risk of CVD is especially concerning. The workload FF face is extreme, 50% of line-of-duty deaths (LODD) in FF are cardiac-related, and research on the volunteer FF population is scarce. Government regulations do not require volunteer FF companies to have fitness testing or programming, so exercise intervention studies are necessary to improve the burden of CVD risk in this population. Therefore, this study examined the effects of a 4-week exercise circuit training (CT) intervention on vascular health and fitness in volunteer FF (N = 27) from the Philadelphia PA area compared to a control group of Non-FF (N = 25). Carotid artery intima-media thickness (IMT), brachial artery flow-mediated dilation (FMD), augmentation index, and pulse pressure (PP), brachial and central blood pressure (BP) and fitness were measured pre- and post- intervention. Overall, volunteer FF had more significant improvements (p

Pharmacological doses (> 1 mM) of ascorbate (a.k.a., vitamin C) have been shown to selectively kill cancer cells through a mechanism that is dependent on the generation of H2O2 at doses that are safely achievable in humans using intravenous administration. The process by which ascorbate oxidizes to form H2O2 is thought to be mediated catalytically by redox active metal ions such as iron (Fe). Because intravenous iron sucrose is often administered to colon cancer patients to help mitigate anemia, the current study assessed the ability of pharmacological ascorbate to kill colon cancer cells in the presence and absence of iron sucrose.In vitro survival assays showed that 10 mM ascorbate exposure (2 h) clonogenically inactivated 40â80% of exponentially growing colon cancer cell lines (HCT116 and HT29). When the H2O2 scavenging enzyme, catalase, was added to the media, or conditionally over-expressed using a doxycycline inducible vector, the toxicity of pharmacological ascorbate was significantly blunted. When colon cancer cells were treated in the presence or absence of 250 µM iron sucrose, then rinsed, and treated with 10 mM ascorbate, the cells demonstrated increased levels of labile iron that resulted in significantly increased clonogenic cell killing, compared to pharmacological ascorbate alone. Interestingly, when colon cancer cells were treated with iron sucrose for 1 h and then 10 mM ascorbate was added to the media in the continued presence of iron sucrose, there was no enhancement of toxicity despite similar increases in intracellular labile iron. The combination of iron chelators, deferoxamine and diethylenetriaminepentaacetic acid, significantly inhibited the toxicity of either ascorbate alone or ascorbate following iron sucrose. These observations support the hypothesis that increasing intracellular labile iron pools, using iron sucrose, can be used to increase the toxicity of pharmacological ascorbate in human colon cancer cells by a mechanism involving increased generation of H2O2. Keywords: Oxidative stress, Redox active iron, Iron sucrose, Catalase, Deferoxamine, Chelators

In this work, we study and characterize 20%- and 30%-reinforced rubber tire powder and polypropylene composite to apply it in the engine encapsulation of commercial vehicles. We produce a prototype with 20% of rubber tire powder due to its better processability and carry out external noise analysis and the results show it is similar to the already available material and within the limits established by law, besides presenting a substantial 54-weight% decrease. In addition, the material guarantees a minimization of sound pollution – through the attenuation of noise by the composite – and environmental, by the reduction of inappropriate disposal of waste tires.

The Affordable Care Act (ACA) promised to narrow smoking disparities by expanding access to healthcare and mandating comprehensive coverage for tobacco treatment starting in 2014. We examined whether two years after ACA implementation disparities in receiving clinician advice to quit and smokers' knowledge and use of treatment resources remained.We conducted telephone interviews in 2016 with a stratified random sample of self-reported smokers newly enrolled in the Kaiser Permanente Northern California's (KPNC) integrated healthcare delivery system in 2014 (N = 491; 50% female; 53% non-white; 6% Spanish language). We used Poisson regression with robust standard errors to test whether sociodemographics, insurance type, comorbidities, smoking status in 2016 (former, light/nondaily [

Background: While attention has been paid to physical risks in the work environment and the promotion of individual employee health, mental health protection and promotion have received much less focus. Psychosocial risk management has not yet been fully incorporated in such efforts. This paper presents good practices in promoting mental health in the workplace in line with World Health Organization (WHO) guidance by identifying barriers, opportunities, and the way forward in this area. Methods: Semistructured interviews were conducted with 17 experts who were selected on the basis of their knowledge and expertise in relation to good practice identified tools. Interviewees were asked to evaluate the approaches on the basis of the WHO model for healthy workplaces. Results: The examples of good practice for Workplace Mental Health Promotion (WMHP) are in line with the principles and the five keys of the WHO model. They support the third objective of the WHO comprehensive mental health action plan 2013–2020 for multisectoral implementation of WMHP strategies. Examples of good practice include the engagement of all stakeholders and representatives, science-driven practice, dissemination of good practice, continual improvement, and evaluation. Actions to inform policies/legislation, promote education on psychosocial risks, and provide better evidence were suggested for higher WMHP success. Conclusion: The study identified commonalities in good practice approaches in different countries and stressed the importance of a strong policy and enforcement framework as well as organizational responsibility for WMHP. For progress to be achieved in this area, a holistic and multidisciplinary approach was unanimously suggested as a way to successful implementation.

This study investigated human-induced pluripotent stem cell (hiPSC) -derived neurons for their ability to secrete neurotransmitters in an activity-dependent manner, the fundamental property required for chemical neurotransmission. Cultured hiPSC neurons showed KCl stimulation of activity-dependent secretion of catecholamines—dopamine (DA), norepinephrine (NE), and epinephrine (Epi)—and the peptide neurotransmitters dynorphin and enkephlain. hiPSC neurons express the biosynthetic enzymes for catecholamines and neuropeptides. Because altered neurotransmission contributes to schizophrenia (SZ), we compared SZ to control cultures of hiPSC neurons and found that SZ cases showed elevated levels of secreted DA, NE, and Epi. Consistent with increased catecholamines, the SZ neuronal cultures showed a higher percentage of tyrosine hydroxylase (TH)-positive neurons, the first enzymatic step for catecholamine biosynthesis. These findings show that hiPSC neurons possess the fundamental property of activity-dependent neurotransmitter secretion and can be advantageously utilized to examine regulation of neurotransmitter release related to brain disorders.