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Breast cancer surgeries have traditionally been documented in narrative reports. Narrative reports have been shown to be incomplete. Synoptic reports utilize standardized templates to record data and have emerged as an alternative to narrative reports. This study evaluates the uptake and impact of synoptic reporting for breast cancer surgery in a community care setting. A retrospective review of operative reports documenting breast cancer surgeries over a consecutive 3-year period. 772 narrative reports and 158 synoptic reports were reviewed. Synoptic reports were associated with a higher degree of overall completeness (60% vs 45%) when compared to narrative reports. 6 out of 7 surgeons that produced at least 5 synoptic and 5 narrative reports had increases in completeness with use of synoptic reporting. Use of synoptic reporting improves breast cancer operative report completeness and decreases superfluous content when compared to narrative reports. While synoptic report uptake during the study period was suboptimal there exists several means by which it can be improved, including investment in information technology infrastructure and emphasis on stakeholder engagement. •Synoptic reports improve operative report completeness.•Synoptic reports may document more efficiently than narrative reports.•Efficacy of synoptic reporting depends on implementation.•Uptake of synoptic reporting depends on practice setting and implementation.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impaired social interactions, difficulty with communication, and repetitive behavior patterns. In humans affected by ASD, there is a male pre-disposition towards the condition with a male to female ratio of 4:1. In part due to the complex etiology of ASD including genetic and environmental interplay, there are currently no available medical therapies to improve the social deficits of ASD. Studies in rodent models and humans have shown promising therapeutic effects of oxytocin in modulating social adaptation. One pharmacological approach to stimulating oxytocinergic activity is the melanocortin receptor 4 agonist Melanotan-II (MT-II). Notably the effects of oxytocin on environmental rodent autism models has not been investigated to date. We used a maternal immune activation (MIA) mouse model of autism to assess the therapeutic potential of MT-II on autism-like features in adult male mice. The male MIA mice exhibited autism-like features including impaired social behavioral metrics, diminished vocal communication, and increased repetitive behaviors. Continuous administration of MT-II to male MIA mice over a seven-day course resulted in rescue of social behavioral metrics. Normal background C57 male mice treated with MT-II showed no significant alteration in social behavioral metrics. Additionally, there was no change in anxiety-like or repetitive behaviors following MT-II treatment of normal C57 mice, though there was significant weight loss following subacute treatment. These data demonstrate MT-II as an effective agent for improving autism-like behavioral deficits in the adult male MIA mouse model of autism.

The Healthcare Cost and Utilization Project reported that 5.2% of all inpatient hospital stays had alcohol abuse listed as a comorbidity, and 5.2% had drug abuse (Owens, 2022). ABOUT THE AUTHOR Jordan Lang, PT, DPT, is currently practicing in the inpatient rehabilitation setting at Encompass Health Rehabilitation Hospital of Rock Hill in South Carolina. SAMHSA Announces National Survey on Drug Use and Health (NSDUH) Results Detailing Mental Illness and Substance Use Levels in 2021. (https://www.ncbi.nlm. nih.gov/pmc/articles/PMC5525418/ ) * Owens, P; Liang, L; Barrett, M; Finger, K. (2022) Comorbidities Associated With Adult Inpatient Stays, 2019.

The expression of the gut tumor suppressor gene adenomatous polyposis coli (Apc) and its role in the oligodendroglial lineage are poorly understood. APC is a multi-functional protein serving as a negative regulator of Wnt/β-catenin signaling and as a cytoskeletal regulator during process extension, migration, and mitosis. This dissertation is organized into two chapters: 1) a review of Wnt/β-catenin regulation of the oligodendroglial lineage, 2) a report of novel experimental findings demonstrating that APC promotes oligodendroglial development in the spinal cord and that endogenous β-catenin is not required for spinal oligodendroglial development. In the review chapter, the current literature of Wnt/β-catenin regulation of oligodendroglial progenitor cell (OPC) generation from radial glia and oligodendrocyte differentiation is closely examined. The spinal cord and brain are independently considered, as recent findings indicate unique roles for Wnt/β-catenin signaling in these tissues. Additionally, Wnt/β-catenin signaling appears to have different effects on oligodendrogenesis at different developmental stages, in particular when comparing cortical subventricular zone oligodendrogenesis in the embryonic, postnatal and adult stages. In the research report chapter, we report that immunoreactive APC is transiently induced in the oligodendroglial lineage during both normal myelination and remyelination following toxin-induced and genetic murine demyelination models. Using the Cre/loxP system to conditionally ablate Apc from the oligodendroglial lineage, we determined that APC is essential for oligodendrocyte differentiation in a cell-autonomous manner. Additionally, Apc disruption resulted in decreased numbers of actively proliferating PDGFRa+/Ki67 + OPCs. Biallelic Apc disruption caused translocation of β-catenin into the nucleus and upregulated β-catenin-mediated Wnt signaling in early postnatal but not adult oligodendroglial lineage cells. However, conditional ablation of Apc resulting in one-allele deficiency was not sufficient to dysregulate β-catenin-mediated Wnt signaling in oligodendroglial lineage cells. Additionally, conditional ablation of Ctnnb1 (the gene encoding β-catenin) revealed that β-catenin is dispensable for postnatal oligodendroglial differentiation. Together, our data support the hypothesis that APC promotes oligodendrocyte differentiation and developmental myelination and reject the hypothesis that endogenous β-catenin promotes postnatal oligodendroglial development.

To move beyond 50% efficiency multijunction solar cells, additional higher energy junctions are needed, and none of the conventional semiconductors can fill this role. Because of a large absorption coefficient (α ~10 5 cm-1 for GaN) and a wide diode depletion (~300 nm), the potential for significant optical absorption in the depletion of a p-i-n diode is promising for a drift-based solar cell based on the III-nitride system. The work described in this thesis covers the development of InGaN material growth by ammonia molecular beam epitaxy (MBE) and its incorporation into photovoltaic devices. A new regime of high V/III ratio and modulated growth was explored in ammonia MBE, leading to device quality material layers. It was observed that increasing ammonia overpressure during growth dramatically increased the indium incorporation efficiency for a given group-III flux and substrate growth temperature. Upon increasing the ammonia pressure, however, the growth rate was observed to decrease. The growth rate reduction was explained by a free-space particle scattering model wherein group-III source beams are attenuated through collisions with the high density of ammonia molecules above the surface of the substrate. By modulating the ammonia flow and substrate temperature during alternating growth of InGaN and GaN layers, the growth of high quality InGaN/GaN superlattice and multiquantum-well (MQW) structures was achieved. These observations and techniques allowed the extension of device quality layers to smaller bandgap quantum wells through the increased incorporation of indium. The InGaN layers grown by this method were then incorporated into photovoltaic (PV) device structures. The physics of quasi-bulk and MQW PV devices was explored through empirical and theoretical means. The short minority carrier diffusion length in highly n and especially p-type GaN was predicted to result in poor collection efficiency for photogenerated carriers. Experiments with varying the p-window layer thickness resulted in dramatically increased short-wavelength external quantum efficiency improvement. EQE simulations of these devices confirm these results and give estimates of minority carrier diffusion lengths in p-GaN. Very high internal quantum efficiency (IQE) was confirmed, however, for material within the depletion region of a p-i-n diode, as measured by comparing device EQE data to measured optical absorption. To extend the PV spectral response to longer wavelengths, a change to the MQW-based structures was found to prevent morphological breakdown and result in much higher open-circuit voltages. A significant barrier-thickness dependent behavior was observed in these devices, with increasing IQE for decreasing barrier thickness. Temperature-dependent L-I-V curves and temperature-dependent biased EQE curves were measured to probe this behavior. A reduction in carrier escape times was suggested to explain the increase in IQE for reduced barrier devices. For thin barriers, a temperature-independent mechanism was observed. Calculations of tunneling and thermionic emission carrier escape corroborated the measured results and suggested tunneling dominated for all devices at room temperature and lower, while thermionic emission dominated for thicker-barrier samples at elevated temperatures. The dramatically increased performance of the thinner barrier samples suggested a future direction for practical performance devices for multijunction integration.

It was around December first when my family and I put up our Christmas tree. We put in Christmas music and everything. While my dad set up the fake tree, my friend, Breanna and I set up our Christmas village. The time seemed to inch by. Finally, as me and Breanna started to get bored, my dad finished putting up the angel.

Background The standing broad jump (SBJ) is an excellent functional measure of explosive lower-body strength that is significantly related to health among children and adolescents. Objectives The aim of this study was to estimate national (country-level) and international (pooled global data) temporal trends in SBJ performance for children and adolescents, and to examine the relationships between national trends in SBJ performance and national trends in health-related and socioeconomic/demographic indicators. Methods Data were obtained from a systematic search of studies reporting temporal trends in SBJ performance for 9- to 17-year-olds, and by examining national fitness datasets. Sample-weighted regression models estimated trends at the study/dataset-country-sex-age level, with national and international trends estimated by a post-stratified population-weighting procedure. Pearson’s correlations quantified relationships between national trends in SBJ performance and national trends in health-related and socioeconomic/demographic indicators. Results Data from 34 studies/datasets were extracted to estimate trends for 10,940,801 children and adolescents from 24 high-, 4 upper-middle-, and 1 low-income countries between 1960 and 2017. Collectively, there was a negligible (per decade) improvement in SBJ performance of 1.73 cm (95% CI 1.71–1.75), 0.99% (95% CI 0.97–1.01) or a standardized effect size of 0.07 (0.07–0.07) over the entire period, with the rate of improvement steady from the 1960s to the 1980s, slowing in the 1990s, before declining. Sex- and age-related temporal differences were negligible. Trends differed between countries, with most countries experiencing declines. National trends in SBJ performance were not significantly related to national trends in health-related and socioeconomic/demographic indicators. Conclusions SBJ performance of children and adolescents has declined since 2000 (at least among most of the countries in this analysis) and is suggestive of a modern decline in functional explosive lower-body strength. Growing recognition of the importance of muscular fitness as a marker of population health highlights the need for continued tracking of temporal trends in SBJ, especially among low- and lower-middle-income countries for which temporal data are lacking. PROSPERO Registration Number CRD42013003657.

Objective To estimate national and international temporal trends in handgrip strength for children and adolescents, and to examine relationships between trends in handgrip strength and trends in health-related and sociodemographic indicators. Methods Data were obtained through a systematic search of studies reporting temporal trends in the handgrip strength for apparently healthy 9–17-year-olds, and by examining large national fitness datasets. Temporal trends at the country–sex–age level were estimated by sample-weighted regression models relating the year of testing to mean handgrip strength. International and national trends were estimated by a post-stratified population-weighting procedure. Pearson’s correlations quantified relationships between national trends in handgrip strength and national trends in health-related/sociodemographic indicators. Results 2,216,320 children and adolescents from 13 high-, 5 upper-middle-, and 1 low-income countries/special administrative regions between 1967 and 2017 collectively showed a moderate improvement of 19.4% (95% CI 18.4–20.4) or 3.8% per decade (95% CI 3.6–4.0). The international rate of improvement progressively increased over time, with more recent values (post-2000) close to two times larger than those from the 1960s/1970s. Improvements were larger for children (9–12 years) compared to adolescents (13–17 years), and similar for boys and girls. Trends differed between countries, with relationships between national trends in handgrip strength and national trends in health-related/sociodemographic indicators negligible-to-weak and not statistically significant. Conclusions There has been a substantial improvement in absolute handgrip strength for children and adolescents since 1967. There is a need for improved international surveillance of handgrip strength, especially in low- and middle-income countries, to more confidently determine true international trends. PROSPERO Registration Number CRD42013003657.

Background The measurement of physical fitness has a history that dates back nearly 200 years. Recently, there has been an increase in international research and surveillance on physical fitness creating a need for setting international priorities that could help guide future efforts. Objective This study aimed to produce a list of the top 10 international priorities for research and surveillance on physical fitness among children and adolescents. Methods Using a twin-panel Delphi method, two independent panels consisting of 46 international experts were identified (panel 1 = 28, panel 2 = 18). The panel participants were asked to list up to five priorities for research or surveillance (round 1), and then rated the items from their own panel on a 5-point Likert scale of importance (round 2). In round 3, experts were asked to rate the priorities identified by the other panel. Results There was strong between-panel agreement (panel 1: r s  = 0.76, p  < 0.01; panel 2: r s  = 0.77, p  < 0.01) in the priorities identified. The list of the final top 10 priorities included (i) “conduct longitudinal studies to assess changes in fitness and associations with health”. This was followed by (ii) “use fitness surveillance to inform decision making”, and (iii) “implement regular and consistent international/national fitness surveys using common measures”. Conclusions The priorities identified in this study provide guidance for future international collaborations and research efforts on the physical fitness of children and adolescents over the next decade and beyond.

Background The success of agents that reverse T-cell inhibitory signals, such as anti-PD-1/PD-L1 therapies, has reinvigorated cancer immunotherapy research. However, since only a minority of patients respond to single-agent therapies, methods to test the potential anti-tumor activity of rational combination therapies are still needed. Conventional murine xenograft models have been hampered by their immune-compromised status; thus, we developed a hematopoietic humanized mouse model, hu-CB-BRGS, and used it to study anti-tumor human immune responses to triple-negative breast cancer (TNBC) cell line and patient-derived colorectal cancer (CRC) xenografts (PDX). Methods BALB/c-Rag2 null Il2rγ null SIRPα NOD (BRGS) pups were humanized through transplantation of cord blood (CB)-derived CD34+ cells. Mice were evaluated for human chimerism in the blood and assigned into experimental untreated or nivolumab groups based on chimerism. TNBC cell lines or tumor tissue from established CRC PDX models were implanted into both flanks of humanized mice and treatments ensued once tumors reached a volume of ~150mm 3 . Tumors were measured twice weekly. At end of study, immune organs and tumors were collected for immunological assessment. Results Humanized PDX models were successfully established with a high frequency of tumor engraftment. Humanized mice treated with anti-PD-1 exhibited increased anti-tumor human T-cell responses coupled with decreased Treg and myeloid populations that correlated with tumor growth inhibition. Combination therapies with anti-PD-1 treatment in TNBC-bearing mice reduced tumor growth in multi-drug cohorts. Finally, as observed in human colorectal patients, anti-PD-1 therapy had a strong response to a microsatellite-high CRC PDX that correlated with a higher number of human CD8+ IFNγ+ T cells in the tumor. Conclusion Hu-CB-BRGS mice represent an in vivo model to study immune checkpoint blockade to human tumors. The human immune system in the mice is inherently suppressed, similar to a tumor microenvironment, and thus allows growth of human tumors. However, the suppression can be released by anti-PD-1 therapies and inhibit tumor growth of some tumors. The model offers ample access to lymph and tumor cells for in-depth immunological analysis. The tumor growth inhibition correlates with increased CD8 IFNγ+ tumor infiltrating T cells. These hu-CB-BRGS mice provide a relevant preclinical animal model to facilitate prioritization of hypothesis-driven combination immunotherapies.