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usc Refereed/Peer-reviewed Purpose: Genetic variants causing aberrant premessenger RNA splicing are increasingly being recognized as causal variants in genetic disorders. In this study, we devise standardized practices for polymerase chain reaction (PCR)-based RNA diagnostics using clinically accessible specimens (blood, fibroblasts, urothelia, biopsy). Methods: A total of 74 families with diverse monogenic conditions (31% prenatal-congenital onset, 47% early childhood, and 22% teenage-adult onset) were triaged into PCR-based RNA testing, with comparative RNA sequencing for 19 cases. Results: Informative RNA assay data were obtained for 96% of cases, enabling variant reclassification for 75% variants that can be used for genetic counseling (71%), to inform clinical care (32%) and prenatal counseling (41%). Variant-associated mis-splicing was highly reproducible for 28 cases with samples from ≥2 affected individuals or heterozygotes and 10 cases with ≥2 biospecimens. PCR amplicons encompassing another segregated heterozygous variant was vital for clinical interpretation of 22 of 79 variants to phase RNA splicing events and discern complete from partial mis-splicing. Conclusion: RNA diagnostics enabled provision of a genetic diagnosis for 64% of recruited cases. PCR-based RNA diagnostics has capacity to analyze 81.3% of clinically significant genes, with long amplicons providing an advantage over RNA sequencing to phase RNA splicing events. The Australasian Consortium for RNA Diagnostics (SpliceACORD) provide clinically-endorsed, standardized protocols and recommendations for interpreting RNA assay data.

Introduction Accurate assessment of hypersomnia depends upon consideration of several factors, including use of medications that affect alertness and sleep organization. Urine drug screens (UDS) are recommended when assessing hypersomnia, but there is little standardization with respect to screening methods, types of substances detected, and use in maintenance of wakefulness test (MWT) interpretation, in part because there is scant literature relating UDS results to patients’ characteristics, MWT findings and implications. Methods A retrospective analysis was performed in adolescents evaluated at Cincinnati Children's Sleep Center between 2008 and 2021 who underwent MWT with concurrent UDS to determine the adequacy of hypersomnia treatment. UDS in our laboratory were performed by Qualitative Immunoassay/Gas Chromatography-Mass Spectrometry/Liquid Chromatography-Tandem Mass Spectrometry. Results A total of 109 MWTs were accompanied by UDS in 79 patients. Patients were 17.7 [16.6, 18.6] years old (median, [IQ range]), 41.3% female, 68.8% White, 25.7% Black, 5.5% Other, with a BMI of 25.8 [22.1, 31.8] kg/m2. 85.3% had narcolepsy. In addition to prescribed medications, caffeine was positive in 54.1% of UDS, and diphenhydramine was positive in 58.7%. No patients reported use of caffeine or diphenhydramine on the day of MWT. There were no significant demographic differences between those who tested positive and negative for caffeine. The median sleep latency in those with caffeine-positive UDS was longer than those with caffeine-negative UDS, although it did not reach statistical significance (27.3 [14.7, 38.3] vs 19.1 [9.8, 36.1] minutes; P=0.15). Patients with a positive UDS for diphenhydramine all took modafinil/armodafinil. In addition, 80% of patients taking modafinil/armodafinil had diphenhydramine-positive results. Nicotine and cannabinoids were detected in 2 UDS. Conclusion Two unexpected substances (caffeine and diphenhydramine) were found on UDS during MWTs in a significant proportion of our cohort. Caffeine may influence the results of MWTs, although further investigations are warranted. The unexpected presence of diphenhydramine is a false positive for those patients on modafinil/armodafinil (supported by literature and confirmed by our laboratory director). Sleep clinicians should be aware of these findings and the implications of unexpected substances when interpreting MWTs. Support (If Any) Cincinnati Children's Hospital Research Fund

Introduction CPAP Adherence in children with OSA is often sub-optimal and there is concern for worsening during the COVID-19 pandemic. Although telehealth has been used in sleep clinics during the pandemic, there is little known about telemedicine’s effectiveness in specialized care. The purpose of this study is to compare CPAP adherence and related outcome metrics in pediatric OSA patients seen before and during the COVID-19 pandemic and between those seen in person and by telemedicine. Methods This retrospective cohort consisted of patients who were diagnosed with OSA, prescribed CPAP, and were seen in a CPAP clinic between 1/1/2018 and 9/31/2021. CPAP adherence data and outcome metrics including the Epworth Sleepiness Scale (ESS), Michigan Sleep-disordered Breathing (PSQ) and Pediatric Quality of Life questionnaires (Ped-QOL) were collected. Only patients with one pre-pandemic and at least one post-pandemic visit were included. All variables were reported as mean± SD. Statistical comparison was performed using the mixed-effects model. Results 147 patients met criteria with 353 total visits. 147 were before the pandemic (pre) and 206 were during the pandemic (post). Demographic data indicated 57% male, 82% white, and 63% 12 years and older. Post-pandemic visits consisted of 78% telemedicine. Comparison between pre and post pandemic data demonstrated no statistically significant differences in % CPAP usage>4hrs (71±31% [pre] vs 73±33% [post], p=0.95), ESS (6.4±5.5 [pre] vs 5.9±5.8 [post], p=0.27), or PSQ (0.38±0.22 [pre] vs 0.36±0.22 [post] p=0.90). However, there was a significant difference in Psychosocial Health domain of Ped-QOL (68.6±19.4 [pre] vs 74.5±17.9 [post], p=0.012). Comparison between telemedicine and in-person visits during the pandemic showed no differences in %CPAP usage>4hrs (73±31% [Tele] vs 73±37%, p=0.73), ESS, PSQ, or Ped-QOL. Conclusion In our cohort, children with OSA had no significant changes in CPAP adherence, sleepiness, or OSA symptoms during the COVID-19 pandemic. CPAP telehealth visits provided the same effectiveness as in-person visits, as evidenced by similar adherences and outcome metrics. Interestingly, patients reported higher psychosocial health during the pandemic despite no difference in CPAP adherence. Factors not related to OSA management may contribute to the improvement of quality of life in this population. Support (If Any) Cincinnati Children’s Research Fund

Introduction Children with central hypersomnia often have residual daytime sleepiness despite treatment with medical therapies. The Maintenance of Wakefulness Test (MWT) is an objective measure used to assess daytime alertness and responsiveness to treatment in patients with hypersomnia. There are limited data on MWT characteristics among pediatric populations. The purpose of this study was to: (1.) Compare MWT characteristics and subjective assessment between patients who passed and failed the MWT; (2.) Determine clinical management changes following MWT. Methods A retrospective review was conducted of all children who underwent MWT at Cincinnati Children’s Hospital Medical Center from September, 2008 to June, 2021. Pass and fail assessment designations were determined by the clinician as recorded in the medical record. Demographics, Epworth Sleepiness Scores (ESS), MWT characteristics, and pharmacological modifications were recorded. A majority of patients underwent MWT prior to driving. Descriptive statistics as well as Chi-square, Fisher’s exact, and Wilcoxon rank-sum testing were utilized. All variables were reported as medians with interquartile ranges. Results 109 MWTs were performed on 79 children with a median age of 17.7 years [16.6, 18.6]. MWTs were indicated for 4 primary diagnoses: hypersomnia (n=5), idiopathic hypersomnia (n=11), narcolepsy type 1 (n=56), and narcolepsy type 2 (n=37). 55 (50.5%) were documented as pass (P) and 54 as fail (F). No differences in age (17.5 years) [16.2,18.5] (P) vs. (17.8) [16.9,18.9] (F) (p=NS) or other demographics existed between the two groups. As expected, mean sleep latency was significantly higher among those who passed (37.3 minutes) [31.2,40.0] (P) vs. (10.8) [7.9,16.6] (F) (p Conclusion MWT provides useful objective assessment and often leads to management changes in adolescents with central hypersomnia. A subjective sleepiness assessment (ESS) does not correlate with objective MWT assessments. We speculate that an altered perception of sleepiness in children with hypersomnia may play a role in the inaccuracy of subjective assessments commonly utilized in clinical practice. Support (If Any) Cincinnati Children’s Research Foundation.

The National Ebola Training and Education Center (NETEC) was established in 2015 in response to the 2014–2016 Ebola virus disease outbreak in West Africa. The US Department of Health and Human Services office of the Assistant Secretary for Preparedness and Response and the US Centers for Disease Control and Prevention sought to increase the competency of healthcare and public health workers, as well as the capability of healthcare facilities in the United States, to deliver safe, efficient, and effective care to patients infected with Ebola and other special pathogens nationwide. NYC Health + Hospitals/Bellevue, Emory University, and the University of Nebraska Medical Center/Nebraska Medicine were awarded this cooperative agreement, based in part on their experience in safely and successfully evaluating and treating patients with Ebola virus disease in the United States. In 2016, NETEC received a supplemental award to expand on 3 initial primary tasks: (1) develop metrics and conduct peer review assessments; (2) develop and provide educational materials, resources, and tools, including exercise design templates; (3) provide expert training and technical assistance; and, to add a fourth task, create a special pathogens clinical research network.

The 2013-2016 epidemic of Ebola virus disease (EVD) that originated in West Africa underscored many of the challenges to conducting clinical research during an ongoing infectious disease epidemic, both in the most affected countries of Guinea, Liberia, and Sierra Leone, as well as in the United States and Europe, where a total of 27 patients with EVD received care in biocontainment units. The Special Pathogens Research Network (SPRN) was established in the United States in November 2016 to provide an organizational structure to leverage the expertise of the 10 Regional Ebola and Other Special Pathogen Treatment Centers (RESPTCs); it was intended to develop and support infrastructure to improve readiness to conduct clinical research in the United States. The network enables the rapid activation and coordination of clinical research in the event of an epidemic and facilitates opportunities for multicenter research when the RESPTCs are actively caring for patients requiring a biocontainment unit. Here we provide an overview of opportunities identified in the clinical research infrastructure during the West Africa EVD epidemic and the SPRN activities to meet the ongoing challenges in the context of Ebola virus and other special pathogens.

Objectives/Hypothesis Numerous symptoms may arise that prevent mother-infant dyads from maintaining desired breastfeeding intervals. Investigations into treatments that positively influence breastfeeding outcomes allow for improved patient counseling for treatment decisions to optimize breastfeeding quality. This investigation aimed to determine the impact of surgical tongue-tie/lip-tie release on breastfeeding impairment. Study Design Prospective, cohort study from June 2014 to April 2015 in a private practice setting. Methods Study participants consisted of breastfeeding mother–infant (0–12 weeks of age) dyads with untreated ankyloglossia and/or tethered maxillary labial frenula who completed preoperative, 1 week, and 1 month postoperative surveys consisting of the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF), visual analog scale (VAS) for nipple pain severity, and the revised Infant Gastroesophageal Reflux Questionnaire (I-GERQ-R). Breastmilk intake was measured preoperatively and 1 week postoperatively. Results A total of 237 dyads were enrolled after self-electing laser lingual frenotomy and/or maxillary labial frenectomy. Isolated posterior tongue-tie was identified in 78% of infants. Significant postoperative improvements were reported between mean preoperative scores compared to 1 week and 1 month scores of the BSES-SF (F(2) = 212.3; P < .001), the I-GERQ-R (F(2) = 85.3; P < .001), and VAS pain scale (F(2) = 259.8; P < .001). Average breastmilk intake improved 155% from 3.0 (2.9) to 4.9 (4.5) mL/min (P < .001). Conclusions Surgical release of tongue-tie/lip-tie results in significant improvement in breastfeeding outcomes. Improvements occur early (1 week postoperatively) and continue to improve through 1 month postoperatively. Improvements were demonstrated in both infants with classic anterior tongue-tie and less obvious posterior tongue-tie. This study identifies a previously under-recognized patient population that may benefit from surgical intervention if abnormal breastfeeding symptoms exist. Level of Evidence 2c Laryngoscope, 127:1217–1223, 2017

Introduction We present a patient with chronic insomnia, excessive daytime sleepiness, and sleep-related hypoventilation that improved with a wake promoting agent in conjunction with BPAP. Report of Case A 15-year-old male with Cystic Fibrosis (single F508del mutation, positive sweat test, FEV1% of 98%) and Autism who presented with frequent headaches, chronic insomnia, and daytime sleepiness (PDSS of 22). Current medications included albuterol as needed. Sleep history was significant for restless leg symptoms. Labs revealed low serum ferritin. Sleep study two years prior showed an AHI of 3.4 and PMLD of 18.4. After completion of iron therapy and initiation of gabapentin, his chronic insomnia and serum ferritin improved. However, patient continued to have aggressive behavior, headaches, and snoring. Sleep study was repeated and revealed mild OSA with hypoventilation (AHI of 6.41, >28% of total sleep time with TCO2 above 50 mm Hg). Initial serum bicarbonate was 29 mmol/L and progressively increased to 34 mmol/L. Due to evidence of persistent chronic hypoventilation, patient was trialed on BPAP. Subsequent sleep study with BPAP showed an AHI of 0, but with worsening sleep related hypoventilation (TCO2 of 56mmHg, > 70% total sleep time with TCO2 above 50 mm Hg). Genetic, endocrine, and neurological work up for hypoventilation was negative. Due to persistent daytime sleepiness (PDSS of 24), MSLT was performed and showed evidence of hypersomnia. Modafinil was then initiated. With the combination of nocturnal BPAP use and Modafinil, daytime sleepiness improved (PDSS of 15) and he had normalization of CO2 and bicarbonate levels. Conclusion We present a patient with CF, with minimal lung disease, who demonstrated a negative work up for sleep related hypoventilation, in which dysregulation of control of breathing improved with the use of a wake promoting agent in conjunction with BPAP.

Background: Lingual frenotomy improves patient-reported outcome measures, including infant reflux and maternal nipple pain, and prolongs the nursing relationship; however, many mother–infant dyads continue to experience breastfeeding difficulty despite having had a frenotomy. Research aim: The aim of this study was to determine how incomplete release of the tethered lingual frenulum may result in persistent breastfeeding difficulties. Methods: A one-group, observational, prospective cohort study was conducted. The sample consisted of breastfeeding mother–infant (0-9 months of age) dyads ( N = 54) after the mothers self-elected completion lingual frenotomy and/or maxillary labial frenectomy following prior lingual frenotomy performed elsewhere. Participants completed surveys preoperatively, 1-week postoperatively, and 1-month postoperatively consisting of the Breastfeeding Self-Efficacy Scale–Short-Form (BSES-SF), Visual Analog Scale (VAS) for nipple pain severity, and the Revised Infant Gastroesophageal Reflux Questionnaire (I-GERQ-R). Results: Significant postoperative improvements were reported between mean preoperative scores compared with 1-week and 1-month scores of the BSES-SF, F(2) = 41.2, p < .001; the I-GERQ-R, F(2) = 22.7, p < .001; and VAS pain scale, F(2) = 46.1, p < .001. Conclusion: We demonstrated that besides nipple pain, measures of infant reflux symptoms and maternal breastfeeding self-confidence can improve following full release of the lingual frenulum. Additionally, a patient population was identified that could benefit from increased scrutiny of infant tongue function when initial frenotomy fails to improve breastfeeding symptoms.

Percutaneous coronary intervention (PCI) in patients with spontaneous coronary artery dissection is associated with high rates of complications and suboptimal long-term outcomes. Coronary artery fenestration with cutting balloon angioplasty prior to stenting can prevent the expansion of intramural hematoma and optimize PCI outcomes in this patient population. © 2015 Wiley Periodicals, Inc.

For some mothers, insufficient milk supply impacts their ability to fully breastfeed their infants. Many of these mothers seek holistic options to increase their milk supply. Placenta medicine, or postpartum placenta consumption as a purported galactogogue, appears to be a practice on the rise in the United States. There is some limited historical research, and more recently some phenomenological data, about the practice of placenta as a galactogogue. However, little is truly known about the benefits and risks of placentophagy, in general, or specifically as a galactogogue. This article reviews existing literature and proposes a further call for research regarding the safety and efficacy of placenta consumption.

This research aims to design an educational mobile game for home computer users to protect against phishing attacks. Phishing is an online identity theft which aims to steal sensitive information such as username, password and online banking details from victims. To prevent this, phishing education needs to be considered. Mobile games could facilitate to embed learning in a natural environment. The paper introduces a mobile game design based on a story which is simplifying and exaggerating real life. We use a theoretical model derived from Technology Threat Avoidance Theory (TTAT) to address the game design issues and game design principles were used as a set of guidelines for structuring and presenting information. The overall mobile game design was aimed to enhance avoidance motivation and behaviour of home computer users to protect against phishing threats. The prototype game design is presented on Google App Inventor Emulator. We believe by training home computer users to protect against phishing attacks, would be an aid to enable the cyberspace as a secure environment.

After losing an infant, grieving mothers may still have to cope with postpartum issues, including lactation. This article reviews and addresses care options for lactation concerns after pregnancy, neonatal, or infant loss. Currently, lactation care and advice after loss varies greatly. Lactation consultants are instrumental in providing mothers with anticipatory guidance and evidence-based care. Implementing system-wide training and education regarding this topic will help families receive the information they need to deal with the physiological aftermath of infant loss.

This paper reports on a failed experiment to use Wiki technology to support student engagement with the subject matter of a third year undergraduate module. Using qualitative data, the findings reveal that in an educational context, social technologies such as Wiki's, are perceived differently compared with ordinary personal use and this discourages student adoption. A series of insights are then offered which help HE teachers understand the pitfalls of integrating social technologies in educational contexts.

Background Poor hand hygiene on college campuses can be improved by promoting handwashing behavior. This observational study was conducted to evaluate gender and race/ethnic differences in hand hygiene practices among college students. Methods Hand hygiene practices in college students were evaluated in 4 settings (soap and water; soap and water and visual prompts; soap and water and hand sanitizers; and soap and water, hand sanitizers, and visual prompts). The degree of hand hygiene (ie, adequate handwashing time, use of hand sanitizer, and hand-drying method) also was evaluated at various locations on campus. Results Overall, 72.9% of students washed their hands, 58.3% practiced hand hygiene (using either soap or hand sanitizer), and 26.1% washed their hands adequately. Hand sanitizer use was low when students were given the option, and paper towel was the most common hand-drying method. In general, hand hygiene practices were better in academic buildings than in the student recreation center. Visual prompts improved handwashing behavior only among students in the "other" ethnic category, but not by gender. Conclusions Handwashing is the most effective way of preventing the spread of infectious diseases, and our findings have implications for the design of effective hand hygiene education programs in college students.

This paper puts forward a case for using hermeneutics in information systems (IS) research. Unlike case study and action research, which could now be described as ‘mainstream’ interpretive research in IS, hermeneutics is neither well accepted nor much practiced in IS research. A suitable hermeneutic approach is described in detail. A brief account of hermeneutics in action is provided through a description of research investigating notions of convenience in home Internet shopping. The hermeneutic circle enabled the researcher to reveal unexpectedly the practice of using surrogates in Internet shopping and this example illustrates some of the potential of the approach in IS research.

Proteomics is one of the important new disciplines to emerge from the genome sequencing projects of the last decade. In order to introduce our students to the techniques and promise of this emerging field, a capstone laboratory experience has been developed. The exercise involves multiple aspects of proteomics research including microbial culturing methods, two-dimensional gel electrophoresis techniques, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, and database mining. Over a 12-week semester, students design their own experiments and apply a proteomic approach to investigate the heat shock response in Escherichia coli. In the trial presented in this article, students successfully identified several major heat shock proteins. The laboratory outlined here can be readily adapted to explore a wide variety of responses in metabolic pathways or responses resulting from other environmental insults or stresses. Additionally, the laboratory can be modified to explore the proteomes of organelles, tissues, and other model organisms.

Understanding how different cultures use the Net---as well as perceive the same Web sites---can translate to truly global e-commerce.

The consumer interface, whereby consumers interact through the World Wide Web to transact consumer commerce, is a vital component of electronic commerce. We are attempting to understand this interface from a perspective that combines concepts from marketing, human?computer interaction and culture.We have conducted an extensive experiment comparing the reactions of subjects in the United Kingdom, United States and Hong Kong to web sites. We used the web sites for the automobile manufacturers VW, Ford and Toyota so we could vary the origin of the site. We used well-known constructs from advertising and marketing research to measure various aspects of the subjects and their reactions to the web site.Our basic finding is that there are fewer differences between subjects than have typically been observed by paper-based marketing experiments. There is no evidence that the origin of the site interacts with the individual. However, after performing a factor analysis on how subjects reported their purpose for using the Internet, we found considerable differences in purpose of use between US and Hong Kong subjects. American subjects are inclined to use the Internet for information search purposes, and the Hong Kong subjects are more inclined to use the Internet for social communication purposes. Further, in both countries there is a relationship between these purposes and subjects having their views on the product transformed.

Business success requires that advances in technology be designed and applied within a human context. Too often technological advance has occurred without reference to human behavior. While research appreciates that electronic consumers are computer users, and vice-versa, few understand exactly how this is transforming consumer behavior. In other words, technological imagination has surpassed our knowledge of media-based consumer behavior. This paper seeks to re-dress the balance of understanding. By (i) integrating themes in human-computer interaction (HCI) with consumer behavior models and (ii) placing the results within a framework of relevant research issues, we present the conceptual foundations for a consumer interface.

Electronic commerce implies global reach, increased connectivity and interdependence, and technological advancement across cultural boundaries. Development of these aspects, however, has not occurr...

Proposes that, in the chaotic organizational environments of the 1990s, managers must be able to design winning competitive paradigms and then change these continuously and sometimes discontinuously if their organization is at least to stay crisis‐averse and ideally grow and prosper. Indicates that to achieve this they must understand their environment and the keys to a successful and sustained match ‐ this requires that they stay aware and think strategically. States that awareness and thinking implies learning and sharing information ‐ both inside the organization and with important stakeholders and influencers. To this end, managers must realize just what information is important and how to deal with it. Reports that the important information relates to those specific organizational competences which, unique to the individual organization, are critical for their current and future competitive and strategic success. Driven by the strategic leader organizations must, therefore, first, establish their unique mix of competences. Second, they must ensure attention is focused on these competences ‐ rather than others which are less important for adding value ‐ and that this attention fosters improvement. Third, these improvements must be measured. In addition organizations must, over time, develop (internally) or acquire (by buying in) new competences. Concludes that research indicates that learning and competence development along these lines is not happening widely.

Interface usability is critical to the successful adoption of information systems. The aim of this study is to evaluate interface of Facebook's advertising tool Beacon by using privacy heuristics [4]. Beacon represents an interesting case study because of the negative media and user backlash it received. The findings of heuristic evaluation suggest violation of privacy heuristics [4]. Here, analysis identified concerns about user choice and consent, integrity and security of data, and awareness and notice. Beacon was an innovative tool, therefore, its systematic evaluation was needed in order to identify privacy problems, their causes and subsequent consequences. The study provides useful insights to human computer interaction (HCI) designers of online social networks.

The Nepal Safer Motherhood Project (1997-2004) was one of the first large-scale projects to focus on access to emergency obstetric care, covering 15% of Nepal. Six factors for success in reducing maternal mortality are applied to assess the project. There was an average annual increase of 1.3% per year in met need for emergency obstetric care, reaching 14% in public sector facilities in project districts in 2004. Infrastructure and equipment to achieve comprehensive-level care were improved, but sustained functioning, availability of a skilled doctor, blood and anaesthesia, were greater challenges. In three districts, 70% of emergency procedures were managed by nurses, with additional training. However, major shortages of skilled professionals remain. Enhancement of the weak referral system was beyond the project's scope. Instead, it worked to increase information in the community about danger signs in pregnancy and delivery and taking prompt action. A key initiative was establishing community emergency funds for obstetric complications. Efforts were also made to develop a positive shift in attitudes towards patient-centred care. Supply-side interventions are insufficient for reducing the high level of maternal deaths. In Nepal, this situation is complicated by social norms that leave women undervalued and disempowered, especially those from lower castes and certain ethnic groups, a pattern reflected in use of maternity services. Programming also needs to address the social environment.