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Background:Asynchronous virtual patient care is increasingly used; however, the effectiveness of virtually delivering guideline-concordant care in conjunction with antibiotic stewardship initiatives remains uncertain. We developed a bundled stewardship intervention to improve antibiotic use in E-visits for upper respiratory tract infections (URTIs).Methods:In this before-and-after study, adult patients who completed E-visits for “cough,” “flu,” or “sinus symptoms” at Michigan Medicine between January 1, 2018, and September 30, 2020, were included. Patient demographics, diagnoses, and antibiotic details were collected. The multifaceted intervention occurred over 6 months. Segmented linear regression was performed to estimate the effect of the intervention on appropriate antibiotic use for URTI diagnoses (defined as no antibiotic prescribed) and sinusitis (defined as guideline-concordant antibiotic selection and duration). Regression lines were fit to data before the bundled intervention (January 2019) and after the bundled intervention (May 2019).Results:In total, 5,151 E-visits were included. The intervention decreased the number of visits for flu, cough, or sinus symptoms prescribed antibiotics from 43.2% to 28.9% (P < .001). Guideline concordance of antibiotic prescriptions improved following the intervention: first-line amoxicillin-clavulanate rose from 37.9% of prescriptions to 66.1% of prescriptions (P < .001), second-line doxycycline rose from 13.8% to 22.7% (P < .001); and median duration of antibiotics decreased from 10 days to 5 days (P < .001).Conclusions:A multifaceted stewardship bundle for E-visits involving both changes in the EMR and audit and feedback improved guideline-concordant antibiotic use for URTIs. This approach can aid stewardship efforts in the ambulatory care setting with regard to telemedicine.

Although cigars pose health risks similar to cigarettes, their packaging/marketing is not subject to commensurate regulation in the US. In a 2000 agreement with the Federal Trade Commission, seven major manufacturers agreed to use some form of cigar warning. In 2016, the Food and Drug Administration passed a rule requiring larger standardized warnings, but the requirement was successfully challenged in court. Here, we examined U.S. population-level trends in noticing existing cigarillo, traditional and filtered cigar warnings. We analyzed Wave 5 Population Assessment of Tobacco and Health adult data to assess prevalence of past-30 day warning noticing and associations with socio-demographic and tobacco use variables. Noticing was higher among current users of cigarillos (27%), filtered (34%) and traditional cigars (21%), than non-users (8% for each product, p < 0.0001), and among every-day vs. some-day users, established vs. experimental users, and past-30 day users vs. those without past-30 day use. Results varied by product, but generally indicated lower noticing among non-Hispanic Whites and dual cigarette users, but higher noticing among those purchasing cigars by the box/pack (vs. not purchasing for themselves). Low overall noticing but higher prevalence among frequent users underscores a need for a stronger, uniform cigar warning label policy in the US.

Introduction E-cigarette advertising may benefit young adult cigarette smokers in transitioning to using e-cigarettes. We assessed whether e-cigarette advertising exposure was associated with subsequent e-cigarette use among young adult cigarette smokers. Aims and Methods Data were from Waves 4 (2016–2018) and 5 (2018–2019) of the nationally representative Population Assessment of Tobacco and Health (PATH) study adult survey. Respondents were young adult established cigarette smokers at Wave 4 (18–34 years; n = 3391) and a subsample of those who tried to quit smoking cigarettes completely in the past year at Wave 5 (n = 1235). Multivariable logistic regressions were used to examine the associations between e-cigarette advertising exposure (by channel of exposure) and subsequent past-year e-cigarette use in general and e-cigarette use to quit smoking cigarettes, controlling for covariates. Results At Wave 5, 43.4% of smokers reported past-year use of e-cigarettes; and 14.8% of smokers who tried to completely quit smoking reported past-year use of e-cigarettes to quit. E-cigarette advertising exposure was associated with subsequent past-year e-cigarette use (adjusted odds ratio [AOR] = 1.53, p Discussion Exposure to e-cigarette advertising among U.S. young adult established cigarette smokers may be associated with subsequent e-cigarette use and use to quit smoking. More research is needed to understand the features of e-cigarette advertising (eg, discounts, flavors, smoker-targeted claims) that may shape perception and behavior related to e-cigarette use among young adult smokers. Implications Little is known about the associations between e-cigarette advertising exposure and e-cigarette use among young adult cigarette smokers who may benefit from switching to e-cigarettes. This study found that e-cigarette advertising exposure was positively associated with (1) subsequent e-cigarette use among U.S. young adult established cigarette smokers and (2) subsequent e-cigarette use to quit smoking cigarettes among those who tried to completely quit in the past year. These observed associations were driven by smokers who did not currently use e-cigarettes at baseline. E-cigarette advertising exposure through brick-and-mortar stores or websites/social media was also positively associated with subsequent e-cigarette use behaviors.

Limited data exist on the awareness, beliefs, and use of heated tobacco products (HTPs). Data from 1583 U.S. adult (age ≥ 21 years) current tobacco users were collected in 2021. Participants self-reported HTP awareness, beliefs, use, and susceptibility, as well as current tobacco product use and sociodemographics. We used weighted logistic and multinomial regression models to explore their associations. Overall, 23.6% were aware of, 8.9% had ever used, and 3.0% currently used HTPs. Younger individuals (vs. 61+ years), those with annual income $50,000+ (vs. 0.05). Holding favorable HTP beliefs was associated with susceptibility to and more advanced HTP use statuses (p < 0.05). Sociodemographics associated with HTP use may reflect HTP marketing strategies. The lack of association with cigarette smoking suggests HTPs may be unlikely cigarette substitutes. Addressing favorable HTP-related beliefs may prevent dual use.

Oral presentation is a popular type of assessment in undergraduate degree programs. However, presentation delivery and grading pose considerable challenges to students and faculty alike. For the former, many students who learn English as an additional language may fear giving oral presentations in English due to a lack of confidence. For the latter, faculty who teach multiple classes and have many students may find it difficult to spend adequate time helping students refine their communication skills. This study examines an AI-assisted presentation platform that was built to offer students more opportunities for presentation training without the need for faculty intervention. Surveys with students and teachers were conducted to inform the design of the platform. After a preliminary platform was developed, two methods were employed to evaluate its reliability: a beta test with 24 students and a comparison of AI and human scoring of the presentation performance of 36 students. It was found that students are highly receptive to the platform, but there are noticeable differences between AI and human scoring abilities. The results reveal some limitations of AI and human raters, and emphasize the potential benefit of exploring collaborative AI–human intelligence.

With the adoption of inhibitors of cyclin dependent kinases 4 and 6 (CDK4/6i) in combination with endocrine therapy as standard of care for the treatment of advanced and metastatic estrogen receptor positive (ER+) breast cancer, the search is now on for novel therapeutic options to manage the disease after the inevitable development of resistance to CDK4/6i. In this review we will consider the integral role that the p53/MDM2 axis plays in the interactions between CDK4/6, ERα, and inhibitors of these molecules, the current preclinical evidence for the efficacy of MDM2 inhibitors in ER+ breast cancer, and discuss the possibility of targeting the p53/MDM2 via inhibition of MDM2 in the CDK4/6i resistance setting.

Idiopathic normal pressure hydrocephalus (iNPH) is an uncommon yet potentially reversible cause of dementia in the elderly. It is characterized by cognitive deterioration, urinary incontinence, ventriculomegaly (enlarged cerebral ventricles) and gait apraxia. The diagnosis and management of iNPH requires an organized approach, starting with a comprehensive history and neurologic examination, a review of neuroimaging, and an evaluation of diagnosis. It is important to treat comorbidities in patients prior to specific iNPH testing, which includes testing patient responses to temporary CSF removal and assessing CSF hydrodynamics. In carefully selected patients, all physiological and neurological symptoms improved with a ventriculoperitoneal (VP) shunt surgery, which allows for a gradual adjustment in pressure to prevent complications caused by over-drainage.

Purpose This study aims to explore disciplinary differences in completing blended learning tasks in an academic literacy course and the feasibility of adopting a blended learning analytics approach to explore disciplinary differences. Design/methodology/approach Following a learning analytics approach, this study blends data from the learning management system and timetabling arrangements. Findings Results suggest that online behaviors of design students and accounting students are different in terms of starting day and completion rate. Blending data sources also provides a new perspective to our learning analytics study. Originality/value This study is an important contribution to the field because studies on learning analytics with multiple data sources are rare, and most disciplinary studies rely on survey data; students’ actual behaviors are under-explored.

In 2020, California passed a flavored tobacco sales restriction (FTSR), but the tobacco companies filed a referendum, and the ban will not be implemented unless approved by voters in November 2022. This study examined the percentage of the California population covered by a city FTSR and identified groups more likely to be covered. Mean demographics as well as tobacco use and control measures were compared for California cities with (n = 93) and without (n = 389) a FTSR, and t tests were used to examine the differences. We calculated adjusted odds ratios using logistic regression models. City FTSR policies covered 20.7% of the California population. Adjusted predictors of having a FTSR included the American Lung Association tobacco control score (odds ratio [OR] = 1.27, 95% confidence interval [CI]: [1.17, 1.38]), voting democratic (OR = 1.06, 95% CI: [1.02, 1.10]). and having a lower adult smoking prevalence (OR = 0.84, 95% CI: [0.72, 0.99]). A state-level policy would cover all populations in California.

E-cigarette marketing tactics to reach and appeal to youth are rapidly changing. This study examined to what extent youth e-cigarette marketing exposure was associated with e-cigarette use behavior change one year later, during a time when youth e-cigarette use was starting to surge in the U.S. Using nationally representative longitudinal public-use data from the Population Assessment of Tobacco and Health (PATH) Study, we examined associations between recalled e-cigarette marketing exposure (2016-2018) at Wave (W) 4 and e-cigarette use harm perception and behavior change (ever, current, and regular use) one year later (W4.5; 2017-2018) among W4 never tobacco users (n = 9405). Recall of exposure to e-cigarette marketing through different channels was also examined in multivariable models controlling for socio-demographic factors and established e-cigarette use risk factors. Results show that the most frequently recalled channels of e-cigarette marketing exposure were retail stores (50.3%), television (22.2%), and websites/social media (20.2%). Over one year, 21.2%, 7.8%, 3.4%, and 1.2% of respondents reported reduced harm perceptions, and ever, current, and regular use of e-cigarettes, respectively, at follow-up. Recalled exposure to e-cigarette marketing was associated with reduced e-cigarette harm perception (AOR = 1.20; 95% CI = 1.05-1.37) and ever (AOR = 1.26; 95% CI = 1.01-1.56) and current use (AOR = 1.40; 95% CI = 1.02-1.92) at follow-up. E-cigarette marketing exposure through websites/social media was associated with reduced harm perceptions and all stages of e-cigarette use change, including regular use. Identifying marketing techniques and channels that change youth e-cigarette harm perceptions and influence e-cigarette use progression is essential to inform e-cigarette regulatory policies and prevention campaigns.

Here, we report the genome sequence of bacteriophage Elbi, which infects the cyanobacterium Anabaena sp. strain PCC 7120, a model organism for prokaryotic multicellular development. The 68,626 bp encode 108 proteins, of which 31 can be assigned a function. Elbi is similar to two Anabaena myophages, namely, A-1 and N-1, isolated in the 1970s.

Here, we report the genome sequence of bacteriophage Elbi that infects the cyanobacterium Anabaena sp. strain PCC 7120, a model organism for prokaryotic multicellular development. The 68,626 bp encode 108 proteins, of which 31 can be assigned a function. Elbi is similar to two Anabaena myophages, namely, A-1 and N-1, isolated in the 1970s.

Background Most health insurance organizations reimbursed both video and audio-only (i.e., phone) visits during the COVID-19 pandemic, but may discontinue phone visit coverage after the pandemic. The impact of discontinuing phone visit coverage on various patient subgroups is uncertain. Objective Identify patient subgroups that are more probable to access telehealth through phone versus video. Design Retrospective cohort. Patients All patients at a U.S. academic medical center who had an outpatient visit that was eligible for telehealth from April through June 2020. Main Measures The marginal and cumulative effect of patient demographic, socioeconomic, and geographic characteristics on the probability of using video versus phone visits. Key Results A total of 104,204 patients had at least one telehealth visit and 45.4% received care through phone visits only. Patient characteristics associated with lower probability of using video visits included age (average marginal effect [AME] −6.9% for every 10 years of age increase, 95%CI −7.8, −4.5), African-American (AME −10.2%, 95%CI −11.4, −7.6), need an interpreter (AME −19.3%, 95%CI −21.8, −14.4), Medicaid as primary insurance (AME −12.1%, 95%CI −13.7, −9.0), and live in a zip code with low broadband access (AME −7.2%, 95%CI −8.1, −4.8). Most patients had more than one factor which further reduced their probability of using video visits. Conclusions Patients who are older, are African-American, require an interpreter, use Medicaid, and live in areas with low broadband access are less likely to use video visits as compared to phone. Post-pandemic policies that eliminate insurance coverage for phone visits may decrease telehealth access for patients who have one or more of these characteristics. Supplementary Information The online version contains supplementary material available at 10.1007/s11606-021-07172-y.

IntroductionYoung adults new to tobacco (including e-cigarettes) are at an increased risk of e-cigarette use after e-cigarette exposure. This study examined the association between noticing e-cigarette advertising features and perceived product appeal among non-tobacco-using young adults.MethodsA sample of non-tobacco-using young adults (ages 18–29 years; n=1993) completed an online survey in 2021. We content analysed visible features from 12 e-cigarette ads that represented commonly used e-cigarette brands. Participants viewed the ads and clicked on the areas of the ads that drew their attention. Participants reported e-cigarette product appeal for each ad, including ad liking, product curiosity and use interest. We used generalised estimating equations to examine within-person associations between noticing specific ad features and reporting each and any type of product appeal, adjusting for noticing other features and participant characteristics.ResultsNoticing people, discounts, non-tobacco (menthol and mint/fruit) flavours, positive experience claims or product images was positively associated with having any e-cigarette product appeal. Noticing discounts or mint/fruit flavours was also positively associated with e-cigarette use interest. In contrast, noticing nicotine warnings or smoking cessation claims was negatively associated with ad liking and product curiosity.ConclusionsAttention to several e-cigarette ad features (eg, people, discounts, non-tobacco flavours) was associated with increased e-cigarette product appeal, whereas attention to nicotine warnings and smoking cessation claims was associated with reduced appeal among non-tobacco-using young adults. Restricting appeal-promoting features while strengthening the effects of nicotine warnings and smoker-targeted claims in e-cigarette ads may potentially reduce e-cigarettes’ overall appeal among this priority population.

We present the case of a 16-year-old female with systemic lupus erythematosus who presented with shock of unclear etiology, refractory to fluid resuscitation and triple vasopressors. She suffered pulseless electrical activity and underwent cannulation onto veno-arterial extracorporeal membrane oxygenation (ECMO). After cannulation, it was discovered she had intentionally overdosed on her home medication, amlodipine, a calcium channel blocker (CCB). She was supported on ECMO, treated with IV calcium and insulin, and was able to be weaned off ECMO after 4 days. She developed oligoanuric acute kidney injury, treated with continuous renal replacement therapy followed by intermittent hemodialysis. At discharge, she was neurologically intact and did not require dialysis. Herein, we review the treatment of CCB overdose, review the literature on the use of ECMO in refractory shock due to cardiovascular medication overdose, and highlight the utility of ECMO in pediatric refractory shock and/or cardiac arrest of unclear etiology.

Background. Query a single institution computed tomography (CT) database to assess the prevalence of aortic arch anomalies in general adult population and their potential association with thoracic aortopathies. Methods. CT chest scan reports of patients aged 50-85 years old performed for any indication at a single health system between 2013 and 2016 were included in the analysis. Characteristics of patients with and without aortic arch anomalies were compared by t-test and Fisher exact tests. Logistic regression analysis was performed to assess for independent risk factors of thoracic aortic aneurysm. Results. Of 21,336 CT scans, 603 (2.8%) described arch anomalies. Bovine arch (n=354, 58.7%) was the most common diagnosis. Patients with arch anomalies were more likely to be female (p

Congenital diaphragmatic hernias rarely present after 2 months of age and are typically diagnosed in the perinatal period. Moderate to severe diaphragmatic hernias present with respiratory symptoms, while late-onset hernias have a more varied presentation, depending on the age and content of the hernia. Very rarely, such hernias are found on incidental imaging, in which surgical repair is frequently recommended. A young girl with Loeys-Dietz syndrome and prior abdominal surgeries presents with 1-year history of increasingly severe, intermittent, abdominal and left shoulder pain. Prior imaging incidentally revealed a left diaphragmatic hernia with omentum protruding into the thoracic cavity. This was managed expectantly due to her other medical and surgical issues. Serial imaging revealed that the herniated omentum was increasing in size and symptoms began to develop. An uncomplicated primary thoracoscopic repair was performed. We report the first case of a congenital diaphragmatic hernia in a patient with Loeys-Dietz syndrome.

Patients with clinically progressive metastatic ERTen women (mean age 57 years) underwent imaging. 8/10 demonstrated disease on both DOTA and FDG. 2/10 positive on conventional imaging, but DOTAWhilst we have not demonstrated DOTA to be superior to FDG in staging of ER

ICERI2020 : 13th Annual International Conference of Education, Research and Innovation, Online Conference, 9-10 November 2020

Squamous cell carcinoma of the vulva is a rare gynecologic cancer that is associated with significant patient morbidity and mortality, particularly for recurrent disease. This review summarizes the evidence and continued challenges, regarding the traditional clinicopathologic factors used to prognosticate vulvar squamous cell carcinoma. Articles published within the last 10 years (2010-2020) were identified. Relevant articles concerning the following fifteen prognostic factors were reviewed: HPV/p16 status, vulvar intraepithelial neoplasia, patient age, tumor stage, tumor grade, tumor size, depth of invasion, stromal changes, histologic patterns of invasion, lymphovascular space invasion (LVSI), perineural invasion, lymph node metastases, tumour focality, margin status and lichen sclerosus (LS). The relationship between each prognostic factor and progression-free survival (PFS) and overall survival (OS), including hazard ratios, 95% confidence intervals and p-values, were extracted.

New therapeutic strategies are needed for the growing unmet clinical needs in liver disease and fibrosis. Platelet activation and PDGF activity are recognized as important therapeutic targets; however, no therapeutic approach has yet addressed these two upstream drivers of liver fibrosis. We therefore designed a matrix-targeting glycan therapeutic, SBR-294, to inhibit collagen-mediated platelet activation while also inhibiting PDGF activity. Herein we describe the synthesis and characterization of SBR-294 and demonstrate its potential therapeutic benefits in vitro and in vivo. In vitro SBR-294 was found to bind collagen (EC50 = 23 nM), thereby inhibiting platelet-collagen engagement (IC50 = 60 nM). Additionally, SBR-294 was found to bind all PDGF homodimeric isoforms and to inhibit PDGF-BB mediated hepatic stellate cell activation and proliferation. Translating these mechanisms in vivo, SBR-294 reduced fibrosis by up to 54% in the CCl4 mouse model (p = 0.0004), as measured by Sirius red histological analysis. Additional fibrosis measurements were also supportive of the therapeutic benefit in this model. These results support the therapeutic benefit of platelet and PDGF antagonism and warrant further investigation of SBR-294 as a potential treatment for liver fibrosis.

Pediatric patients with medically refractory ulcerative colitis (UC) often undergo an initial subtotal colectomy end ileostomy (STC-I). The role of fecal diversion in the subsequent completion proctectomy/ileal-pouch anal anastomosis (CP-IPAA) remains controversial. A multi-institutional retrospective review was performed of pediatric UC patients who underwent an STC-I followed by CP-IPAA from 2008 to 2016. 37 patients were included [diverted (n = 20), undiverted (n = 17)]. Children who underwent undiverted CP-IPAA had a longer length of stay (days) compared to the diverted group (9, 6.5–13 vs. 6, 5–6, p = 0.002). The 30-day complication rate was significantly higher in the undiverted group (p = 0.003) although the difference in anastomotic leak, readmission rate, unplanned computer tomography use, and reoperation was not statistically significant. Three patients with undiverted CP-IPAA required additional surgery in the perioperative period for fecal diversion. The mean long-term follow-up was 25.68 ± 21.56 months. There were no significant differences in functional pouch outcomes. Patients who underwent an undiverted CP-IPAA after initial STC-I had significantly more complications in the immediate postoperative period compared to diverted patients, although this did not translate into long-term differences in functional outcomes. Questions remain regarding careful patient selection and counseling for undiverted pouches in the pediatric UC population.

The recent literature has shown that vulvar squamous cell carcinoma (VSCC) can be stratified into two prognostically relevant groups based on human papillomavirus (HPV) status. The prognostic value of p53 for further sub-stratification, particularly in the HPV-independent group, has not been agreed upon. This disagreement is likely due to tremendous variations in p53 immunohistochemical (IHC) interpretation. To address this problem, we sought to compare p53 IHC patterns with TP53 mutation status. We studied 61 VSCC (48 conventional VSCC, 2 VSCC with sarcomatoid features, and 11 verrucous carcinomas) and 42 in situ lesions (30 differentiated vulvar intraepithelial neoplasia [dVIN], 9 differentiated exophytic vulvar intraepithelial lesions [deVIL], and 3 high-grade squamous intraepithelial lesions or usual vulvar intraepithelial neoplasia [HSIL/uVIN]). IHC for p16 and p53, and sequencing of TP53 exons 4-9 were performed. HPV in situ hybridization (ISH) was performed in selected cases. We identified six major p53 IHC patterns, two wild-type patterns: (1) scattered, (2) mid-epithelial expression (with basal sparing), and four mutant patterns: (3) basal overexpression, (4) parabasal/diffuse overexpression, (5) absent, and (6) cytoplasmic expression. These IHC patterns were consistent with TP53 mutation status in 58/61 (95%) VSCC and 39/42 (93%) in situ lesions. Cases that exhibited strong scattered staining and those with a weak basal overexpression pattern could be easily confused. The mid-epithelial pattern was exclusively observed in p16-positive lesions; the basal and parabasal layers that had absent p53 staining, appeared to correlate with the cells that were positive for HPV-ISH. This study describes a pattern-based p53 IHC interpretation framework, which can be utilized as a surrogate marker for TP53 mutational status in both VSCC and vulvar in situ lesions.

Background Asynchronous virtual patient care is growing in popularity; however, the effectiveness of virtually delivering guideline-concordant care in conjunction with antibiotic stewardship initiatives remains uncertain. We developed a bundled stewardship intervention aimed at improving antibiotic use in E-visits for upper respiratory tract infections (URTIs). Methods In this pre-post study, adult patients who completed an E-visit for “cough,” “flu,” or “sinus symptoms” at Michigan Medicine between 1/1/2018 and 9/30/2020 were included. Patient demographics, diagnoses, and antibiotic details were collected. The multi-faceted intervention occurred over 6 months (Figure 1). We performed segmented linear regression to estimate the effect of the intervention on the level and trend of appropriate antibiotic use for URTI diagnosis (defined as no antibiotic prescribed) and sinusitis (defined as guideline-concordant antibiotic selection and duration). Regression lines were fit to data before (March 2019) and after (May 2019) the physician championing period. Results Among 5151 E-visits, the mean age was 46 years old, and most patients were female (71.3%, N=3674). 3405/5151 E-visits were for URTI. Inappropriate antibiotic use for URTI was stable in trend prior to the audit and feedback intervention (Figure 2), followed by a 12% (P-value = 0.01) decrease in inappropriate antibiotic use post-intervention. The trend in inappropriate antibiotic use continued to decrease after the intervention by 1.1%/month (P-value = 0.02) (Figure 2a). Of 2493/5151 E-visits specifically for sinus symptoms, guideline-concordant antibiotic use was low (intercept = 8%) pre-intervention (Figure 2b). Post-intervention, there was an estimated 47% increase (P-value < 0.001) in patients receiving guideline-concordant antibiotics. Solid line represents time of the webinar, dashed line represents time of modified questionnaire roll out and electronic medical record “nudges”, and shaded area is time of physician champion intervention. Guideline-concordant antibiotic prescribing for sinusitis included amoxicillin/clavulanate or doxycycline prescribed for a duration of 5-7 days Conclusion A multifaceted stewardship bundle for E-visits improved guideline-concordant antibiotic use for URTIs. Changes implemented in the EMR are most beneficial after a period of audit and feedback. This approach can aid stewardship efforts in the ambulatory care setting particularly with regards to telemedicine. Disclosures Tejal N. Gandhi, MD, Blue Cross Blue Shield of Michigan (Individual(s) Involved: Self): Grant/Research Support Lindsay A. Petty, MD, Nothing to disclose

The International Fetal Medicine and Surgery Society was created in 1982 and proposed guidelines for fetal interventions that required demonstrations of the safety and feasibility of intended interventions in animal models prior to application in humans. Because of their short gestation and low cost, small animal models are useful in early investigation of fetal strategies. However, owing to the anatomic and physiologic differences between small animals and humans, repeated studies in large animal models are usually needed to facilitate translation to humans. Ovine (sheep) models have been used the most extensively to study the pathophysiology of congenital abnormalities and to develop techniques for fetal interventions. However, nonhuman primates have uterine and placental structures that most closely resemble those of humans. Thus, the nonhuman primate is the ideal model to develop surgical and anesthetic techniques that minimize obstetrical complications.

Purpose The purpose of this study is to determine the feasibility of fetal surgical repair of myelomeningocele (MMC) in a rodent model using human placental mesenchymal stromal cells (PMSCs) seeded onto extracellular matrix (ECM) and to characterize the resulting changes in spinal cord tissue. Methods Fetal rodents with retinoic acid (RA) induced MMC underwent surgical repair of the MMC defect using an ECM patch on embryonic age (EA) 19 and were collected via caesarean section on EA 21. Various seeding densities of PMSC-ECM and ECM only controls were evaluated. Cross-sectional compression (width/height) and apoptotic cell density of the lumbosacral spinal cord were analyzed. Results 67 dams treated with 40mg/kg of RA resulted in 352 pups with MMC defects. 121 pups underwent MMC repair, and 105 (86.8%) survived to term. Unrepaired MMC pups had significantly greater cord compression and apoptotic cell density compared to normal non-MMC pups. Pups treated with PMSC-ECM had significantly less cord compression and demonstrated a trend towards decreased apoptotic cell density compared to pups treated with ECM only. Conclusion Surgical repair of MMC with a PMSC-seeded ECM disc is feasible with a postoperative survival rate of 86.8%. Fetal rodents repaired with PMSC-ECM have significantly less cord deformity and decreased histological evidence of apoptosis compared to ECM only controls.

The treatment of children with myelomeningocele (MMC) has improved over time, from supportive management to early postnatal closure to prenatal repair of the defect. The Management of Myelomeningocele Study (MOMS) showed that prenatal repair of MMC resulted in improved neurological outcomes compared to postnatal closure. Follow-up studies showed that prenatal repair was, as with any other fetal intervention, associated with higher rates of obstetrical complications. There was no significant difference in urological outcomes. Long-term follow-up of ambulatory status, executive functioning, and urological outcomes is needed to determine the durable effects of fetal MMC repair on mobility, functional independence, and the prevalence of renal insufficiency in patients with MMC who survive to adulthood. The future of fetal MMC repair consists of developing strategies to reduce maternal morbidity and improve infant outcomes. Fetoscopic MMC repair has been suggested as an alternative to open repair that may reduce obstetrical complications and the need for cesarean delivery in subsequent pregnancies. Translational research using mesenchymal stromal cells to augment fetal repair of ovine MMC has shown improvement in motor function.

We have recently encountered p53 immunohistochemical (IHC) patterns in human papillomavirus (HPV)-associated carcinomas of the gynecologic tract, which were confused with absent (null) or overexpression TP53 mutational staining. We therefore evaluated p53 and p16 IHC in 25 squamous cell carcinomas (SCC) (16 vulva, 4 Bartholin's gland, and 5 cervix), 20 endocervical adenocarcinomas (EDAC), 14 high-grade squamous intraepithelial lesions (HSIL), 2 adenocarcinoma in situ (AIS), all of which exhibited morphologic features of HPV. Only cases showing diffuse/strong block-like p16 staining were included for further study. All EDACs underwent TP53 sequencing and HPV in situ hybridization (ISH) was performed in selected cases. p53 IHC staining fell into two main patterns. The most common was designated as "markedly reduced (null-like)" (absence or significantly attenuated staining in70% of cells), which could be confused with true null mutational pattern. This was present in 14/25 (56%) SCCs, 7/14 (50%) HSILs, and 18/20 (90%) EDACs. The second notable pattern was "mid-epithelial (basal sparing)" (distinct absence of staining in basal cells juxtaposed with strong staining in parabasal cells), seen in 10/25 (40%) SCC, 7/14 (50%) HSIL, and none of the EDACs. There was scattered weak to moderate p53 staining (conventional wild type) in 1/25 (4%) SCC and 2/20 (10%) EDAC. No cases showed strong/diffuse overexpression. One EDAC had a TP53 missense mutation and exhibited "markedly reduced (null-like)" staining. HPV ISH revealed an inverse relationship with p53, cells positive for HPV mRNA were negative for p53. Knowledge of these patterns can help pathologists avoid misinterpreting p53 status in the setting of HPVA cancers.

This chapter explores changes in learner motivation associated with policy changes in an academic English course. This chapter contributes to the field in two ways: (1) large-scale mixed-method studies of blended learning courses are rare and (2) motivation in computer-assisted language learning has seldom been explored using a data-driven approach. The study employed learning analytics to examine the learning behavioral patterns of 9500+ students, and the results were supplemented by student interviews to further our understanding of student motivation. The study explored the effect of staggered deadlines and single deadlines for online components and suggested that the goal theory of motivation can best describe students’ behavioral and psychological processes. These results verify the need to address goal-oriented behaviors of students when designing online activities for students.

This chapter defines the concept of innovation in the context of higher education by discussing the implementation of a dashboard in a university English program. A dashboard is a personalized feedback tool and a common “big data” application. The challenges arising in the process of developing and implementing such innovations have seldom been explored. However, in this study, the English Language Centre of a Hong Kong university developed a dashboard called course diagnostic reports (CDR) that was piloted with over 400 students from 39 classes. This chapter reports the findings of both a questionnaire evaluating the CDR and 14 interviews that were conducted with course leaders, subject teachers, and students. Discussions of the tool revealed the complex process of innovation. It was found that, for stakeholders, innovation is a continuous process that requires compromises and that an innovation must cross a minimum usability threshold before continuing through the innovation process.

Objectives We evaluated how well phase II trials in locally advanced and metastatic pancreatic cancer (LAMPC) meet current recommendations for trial design. Methods We conducted a systematic review of phase II first-line treatment trial for LAMPC. We assessed baseline characteristics, type of comparison, and primary end point to examine adherence to the National Cancer Institute recommendations for trial design. Results We identified 148 studies (180 treatment arms, 7505 participants). Forty-seven (32%) studies adhered to none of the 5 evaluated National Cancer Institute recommendations, 62 (42%) followed 1, 31 (21%) followed 2, and 8 (5%) followed 3 recommendations. Studies varied with respect to the proportion of patients with good performance status (range, 0%-80%) and locally advanced disease (range, 14%-100%). Eighty-two (55%) studies concluded that investigational agents should progress to phase III testing; of these, 24 (16%) had documented phase III trials. Three (8%) phase III trials demonstrated clinically meaningful improvements for investigational agents. One of 38 phase II trials that investigated biological investigational agents was enriched for a biomarker. Conclusions Phase II trials do not conform well to current recommendations for trial design in LAMPC.

In their ranges on east and south coasts of the Americas as well as their established invasions in the Adriatic and Baltic, blue crabs, Callinectis sapidus, inhabit estuaries, sounds and coastal oceans and are commercially and ecologically important. How crabs move in response to physical variables is important to management. We monitored life stages at canal control structures, assessed gender ratios with recreational crabbing, learned from crabbers, and studied movements of tagged crabs in a canal connecting Lake Mattamuskeet to the Pamlico sound. Juveniles enter the lake through two of 4 canals connecting to the sounds. Females migrate out through one canal. The lake standing population is about 70% male. Movements of 240 crabs in August 2012 and 102 crabs in October 2014 were quantified using RFID tags with co-located meteorological and oceanographic devices. Non-spawning females and males are nomadic. Crabs released in the canal move in response to changes in water depth and go with the flow, toward the Pamlico Sound (summer 76% and fall 78%). What crabbers describe as a fall migration appears to be concentration of crabs in warmer deeper canals and then southern movement with flow generated by strong north winds. To be effective, management strategies like migratory corridors require understanding of crab movements.

Window of opportunity therapies, which involve short-term administration of systemic therapy between cancer diagnosis and surgery, have raised significant interest in recent years as a mean of assessing the sensitivity of a patient's cancer to therapy prior to surgery. There is now compelling evidence that in patients with early stage hormone-receptor positive breast cancer, a 2-week preoperative treatment with standard hormone therapies in a preoperative window period provides important prognostic information, which in turn helps to aid decision-making regarding treatment options. Changes in short-term biomarker endpoints such as cell proliferation measured by Ki-67 can act as surrogate markers of long-term outcomes. Paired tissues obtained pre- and post-investigational treatment, without having to subject the patient to additional biopsies, can then be used to conduct translational research to investigate predictive biomarkers and pharmacodynamics. In this review, we will examine the utility and challenges of window of opportunities therapies in breast cancer in the current literature, and the current Australian and international trial landscape in this clinical space.

// Daniel Brungs 1, 2, 3, 4 , Julia Chen 5 , Morteza Aghmesheh 1, 3, 4 , Kara L. Vine 1, 2, 4 , Therese M. Becker 4, 6, 7, 8 , Martin G. Carolan 1, 3, 4 , Marie Ranson 1, 2, 4 1 Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, Australia 2 School of Biological Sciences, University of Wollongong, Wollongong, Australia 3 Illawarra Cancer Centre, Wollongong Hospital, Wollongong, Australia 4 CONCERT-Translational Cancer Research Centre, New South Wales, Australia 5 St George Cancer Centre, St George Hospital, Sydney, Australia 6 Ingham Institute for Applied Medical Research, Liverpool Hospital, Australia 7 School of Medicine, University of Western Sydney, Liverpool, Australia 8 South Western Medical School, University of New South Wales, Liverpool, Australia Correspondence to: Daniel Brungs, email: Daniel.brungs@health.nsw.gov.au Keywords: stomach neoplasms, gastrointestinal neoplasms, urokinase-type plasminogen activator, urokinase plasminogen activator Received: November 30, 2016 Accepted: February 07, 2017 Published: February 18, 2017 ABSTRACT Background: The urokinase plasminogen activation (uPA) system is a crucial pathway for tumour invasion and establishment of metastasis. Although there is good evidence that uPA system expression is a clinically relevant biomarker in some solid tumours, its role in gastroesophageal cancer is uncertain. Results: We identified 22 studies encompassing 1966 patients which fulfilled the inclusion criteria. uPA, uPAR, or PAI-1 expression is significantly associated with high risk clinicopathological features. High uPA expression is associated with a shorter RFS (HR 1.90 95% 1.16–3.11, p = 0.01) and OS (HR 2.21 95% CI 1.74–2.80, p < 0.0001). High uPAR expression is associated with poorer OS (HR 2.21 95%CI 1.82–2.69, p < 0.0001). High PAI-1 expression is associated with shorter RFS (HR 1.96 96% CI 1.07–3.58, p = 0.03) and OS (HR 1.84 95%CI 1.28–2.64, p < 0.0001). There was no significant association between PAI-2 expression and OS (HR 0.97 95%CI 0.48–1.94, p < 0.92) although data was limited. Materials and Methods: We undertook a systematic review evaluating expression of uPA, urokinase plasminogen activator receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1/SerpinE1) and plasminogen activator inhibitor-2 (PAI-2/SerpinB2) on primary oesophageal, gastro-oesophageal junction, and gastric adenocarcinomas. We performed a meta-analysis of clinicopathological associations, overall survival (OS) and recurrence free survival (RFS). Conclusions: We conclude that the uPA system is a clinically relevant biomarker in primary gastroesophageal cancer, with higher expression of uPA, uPAR and PAI-1 associated with higher risk disease and poorer prognosis. This also highlights the potential utility of the uPA system as a therapeutic target for improved treatment strategies.

Background Multimodal pain management strategies are used for analgesia following pectus excavatum repair. However, the optimal regimen has not been identified. We describe our early experience with intercostal cryoablation for pain management in children undergoing the Nuss procedure and compare early cryoablation outcomes to our prior outcomes using thoracic epidural analgesia. Methods A multi-institutional, retrospective review of fifty-two patients undergoing Nuss bar placement with either intercostal cryoablation ( n =26) or thoracic epidural analgesia ( n =26) from March 2013 to January 2016 was conducted. The primary outcome was hospital length of stay. Secondary outcomes included telemetry unit monitoring time, total intravenous narcotic use, duration of intravenous narcotic use, and postoperative complications. Results Patients who underwent intercostal cryoablation had a significant reduction in the mean hospital length of stay, time in a monitored telemetry bed, total use of intravenous narcotics, and the duration of intravenous narcotic administration when compared to thoracic epidural patients. Cryoablation patients had a slightly higher rate of postoperative complications. Conclusion Intercostal cryoablation is a promising technique for postoperative pain management in children undergoing repair of pectus excavatum. This therapy results in reduced time to hospital discharge, decreased intravenous narcotic utilization, and has eliminated epidurals from our practice. Level of evidence Retrospective study – level III.