Iowa City Research Articles

Progressive Tinnitus Management at Two Veterans Affairs Medical Centers: Clinical Implementation With Modified Protocols.

Purpose This is a description of the clinical implementation and outcomes of progressive tinnitus management (PTM) at 2 Veterans Affairs (VA) medical centers: Both programs modified the protocol originally described by PTM developers. Method Modifications at both sites were classified according to an evidence-based framework set forth by Stirman, Miller, Toder, and Calloway (2013) . The Iowa City VA PTM program clinicians made 2 modifications and the Asheville, North Carolina, VA PTM program clinicians made 6 modifications to the standard PTM protocol. Pre-post outcome measures were analyzed for 20 veterans who completed the Iowa City program and for 200 veterans who completed the Asheville program. Results Veterans who completed the Iowa City program showed a statistically significant decrease in the average Tinnitus Handicap Inventory score ( Newman, Jacobson, & Spitzer, 1996 ). Veterans who completed the Asheville PTM program showed a statistically significant decrease in the average Tinnitus Functional Index (TFI) score. Outcomes in Asheville were compared to outcomes of a clinical trial of PTM conducted by the developers of PTM. The clinical work in Asheville resulted in a greater mean reduction on the TFI and a larger effect size using the TFI as compared to the results of the PTM clinical trial. Conclusions Clinician-directed modifications to PTM that are made to address the unique needs and circumstances of an individual clinic have potential to result in positive outcomes for patients. Clinicians providing care for patients with tinnitus using PTM who modify the protocol to meet the needs of their local setting are encouraged to collect and report the outcomes of their modifications to improve understanding of the impact of various types of modifications to PTM and other evidence-based practices.

The Sports Preparticipation Evaluation.

1. Shane M. Miller, MD, FAAP* 2. Andrew R. Peterson, MD, MSPH, FAAP† 1. *Departments of Orthopaedics and Pediatrics, UT Southwestern, and Texas Scottish Rite Hospital for Children Sports Medicine Center, Dallas, TX 2. †Departments of Pediatrics and Orthopaedics/Rehabilitation, University of Iowa, Iowa City, IA * Abbreviations: AAP: : American Academy of Pediatrics AAS: : anabolic-androgenic steroid AHA: : American Heart Association BP: : blood pressure CDC: : Centers for Disease Control and Prevention DM: : diabetes mellitus ECG: : electrocardiography FDA: : Food and Drug Administration LVH: : left ventricular hypertrophy PES: : performance-enhancing substance PPE: : preparticipation physical evaluation SCAT5: : Sports Concussion Assessment Tool, Version 5 SCD: : sickle cell disease SCT: : sickle cell trait Lack of familiarity with current recommendations diminishes the confidence to perform a preparticipation physical evaluation (PPE). In a 2014 survey, Madsen et al (1) reported, “Only 37% of physicians reported an awareness of the PPE Monograph.” (2) Clinicians should be aware of current guidelines for performing a PPE and identify children who may be at increased risk from sport participation. After completing this article, readers should be able to: 1. Perform a preparticipation history and physical examination and identify children and adolescents who may be at increased risk for morbidity or mortality from sport participation. 2. Recognize that the mandatory preparticipation physical evaluation serves as an opportunity to address medical and psychosocial issues not necessarily associated with sport participation and as an entry point for healthy adolescents into the health-care system. 3. Recognize the cardiac risks associated with sport participation and when additional cardiac evaluation is required. 4. Understand the importance of assessing and documenting neurocognitive function before sport participation. 5. Identify which sports are appropriate for athletes with some common medical conditions. 6. Recognize the effect of a febrile illness on sport participation. In the United States, sport participation is increasing, with more than 60 million children and adolescents competing in organized sports every year. The number of high school athletes has increased from 7.2 million to 7.9 million during the past 10 years. (3) The physical and psychosocial benefits of sport participation are well-documented, and pediatricians serve a vital role …

Poverty and Charity in Early Modern Theater and Performance. By Robert Henke. Iowa City: University of Iowa Press, 2015. Pp. xiii + 202. $55 Hb.

Poverty and Charity in Early Modern Theater and Performance. By Robert Henke. Iowa City: University of Iowa Press, 2015. Pp. xiii + 202. $55 Hb.

The Heritability of Pigment Dispersion Syndrome and Pigmentary Glaucoma

Pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) are presumed to be inherited in an autosomal dominant manner. We examine relatives of patients with PDS and PG in order to determine the heritability of these diseases. This was a prospective, cross-sectional study. One hundred and one patients with PDS were prospectively recruited over 11months. Four of the patients had PDS without ocular hypertension or glaucoma, 6 had PDS and ocular hypertension, and 91 had PG. Criteria for PDS were 2 of 3 signs: Krukenberg spindle, midperipheral iris transillumination defects, and/or heavy trabecular meshwork pigmentation. Criteria for PG were PDS and 2 of 3 signs: intraocular pressure >21mm Hg, glaucomatous optic nerve damage, and/or glaucomatous visual field loss. Ninety-nine first-degree relatives living within a 100-mile radius of Iowa City, Iowa were examined in the clinic to determine the probability of familial transmission. A total of 10 of 99 (10.10%) first-degree relatives were diagnosed with PDS (1 with PDS alone, 2 with PDS and ocular hypertension, and 7 with PG). Seven families with ≥2 affected members were identified. The majority of affected family members (8/10) showed moderate to heavy trabecular meshwork pigmentation and either Krukenberg spindle or transillumination defects. Most of the cases of PDS in our study were sporadic, and the risk to first-degree relatives is lower than previously reported. However, there are families with apparent autosomal dominant inheritance of PDS in which the risk to relatives may be high.

Wild bees and urban agriculture: assessing pollinator supply and demand across urban landscapes

Growing interest in urban agriculture has increased demand for pollination services. Most studies map pollination supply broadly, and do not consider the impacts of fine-scale urban land-use practices on the dynamics of pollination delivery, leaving a critical gap in our understanding of the pollinator supply-demand balance in urban landscapes. This study demonstrates a spatially-explicit framework, using Iowa City, IA (USA) as the case study region, for assessing the capacity of urban ecosystems to produce pollinator services in support of demand from urban agriculture. We estimate pollinator supply using the InVEST pollination model with detailed land-cover data produced through field survey and Bayesian hierarchical analysis, and we validate modeling results with bee abundance and richness data. We map social demand for pollinators using a kernel density estimation of urban agricultural sites and evaluate supply-demand budgets through spatial overlay analysis. Our results show that incorporating high-thematic-resolution urban land-use data substantially improves the performance of pollination supply modeling. Pollinator supply meets demand in 72% of the city. Surpluses occur in natural areas and heavily-vegetated, established residential neighborhoods, whereas deficits occur in resource-poor lawns. Our mapping framework stresses the key role of humans in modifying resource availability and pollinator services, and demonstrates the effectiveness of using disaggregated socio-economic data in urban land-cover classification for predicting pollinator supply. Our improved ability to identify spatial congruence and disparities in urban pollinator supply and demand can be used to inform pollinator conservation to support sustainable urban agriculture.

Playful Letters: A Study in Early Modern Alphabetics. Erika Mary Boeckeler. Impressions: Studies in the Art, Culture, and Future of Books. Iowa City: University of Iowa Press, 2017. xiv + 286 pp. $75.

Playful Letters: A Study in Early Modern Alphabetics. Erika Mary Boeckeler. Impressions: Studies in the Art, Culture, and Future of Books. Iowa City: University of Iowa Press, 2017. xiv + 286 pp. $75. - Volume 72 Issue 2

Organosulfates in the Midwestern United States: abundance, composition and stability

Environmental contextOrganosulfates in the atmosphere are an indicator that particulate matter has formed from gases in the presence of anthropogenic pollution. By characterising organosulfates in atmospheric fine particulate matter from the Midwestern USA, we found that organosulfates account for a significant fraction of organic carbon and that they are associated with both plant-derived and anthropogenic gases. Our results demonstrate that anthropogenic pollution significantly influences atmospheric particle concentrations and composition. AbstractOrganosulfates are components of secondary organic aerosol resulting from the oxidation of volatile organic compounds in the presence of acidic sulfate. This study characterises organosulfates in the Midwestern United States for the first time. In fine particulate matter (PM2.5) collected in Iowa City, IA, in September 2017, organosulfates were analysed using liquid chromatography coupled to high-resolution and tandem mass spectrometry (MS) to identify and quantify (or semi-quantify) major species. Among the 22 identified species, methyltetrol sulfate (m/z 215; C5H11SO7−) had the largest contribution to the bisulfate (m/z 97) product ion, as determined by precursor-ion MS/MS (59.5% of signal), followed by ten other isoprene-derived organosulfates (15.2%), seven monoterpene-derived organosulfates (5.6%), three anthropogenic organosulfates (4.3%) and one species of unknown origin (0.6%). Among the quantified species were hydroxyacetone sulfate (4.8±1.1ngm−3), glycolic acid sulfate (21.0±1.5ngm−3), 2-methylgyceric acid sulfate (15.1±0.8ngm−3), C5H7SO7− (m/z 211; 17.9±0.9ngm−3), C5H9SO7− (m/z 213; 16.0±1.0ngm−3), and methyltetrol sulfate (214±8ngm−3); together, these species accounted for 4.4% of organic carbon. To further validate the measurement of organic species in PM using filter samples, the stability of organosulfates on filters frozen at −20°C was evaluated over the course of 1 year. The stored samples revealed no degradation of organosulfates, indicating their stability on filters stored frozen for extended periods of time. This study provides new insight into the abundance and identity of organosulfates in the Midwestern US and demonstrates that isoprene-derived organosulfates, in particular, are a significant contributor to PM2.5 organic carbon.

Looking Back to Look Forward: The Promising Profession of Academic Librarianship

Looking Back to Look Forward:The Promising Profession of Academic Librarianship Rebecca S. Albitz (bio) In a Forbes op-ed piece in July 2018, Panos Mourdoukoutas, an economics professor from Long Island University in New York, suggested that Amazon bookstores should replace our local public libraries to save taxpayer dollars.1 He was not, by any stretch of the imagination, the first nor the last to predict the demise of libraries, and by association, the passing of the librarian. But, if my professional history is any indication, librarians' career opportunities continue to grow. We in academic libraries have an amazing array of options when we create a career trajectory that is uniquely our own. We can choose to work in small colleges or large universities, either public or private. We can consider a position that offers the opportunity to earn faculty rank and tenure. Do you want to become a manager? You can select roles that will prepare you to become a department head or even a head librarian. In the following essay, I explore the three areas mentioned—large and small libraries, tenure, and management roles—through the lens of my varying experiences to consider the ever-evolving opportunities available to an academic librarian. To offer context to this perspective, I need to provide a brief outline of my career thus far. My first position was media services librarian at the University of Iowa in Iowa City, which included managing the media and microforms department, building and cataloging the video collection, providing reference services for media and film studies, and serving as liaison with the film program. This was truly a unique position: I did everything—acquisitions, cataloging, reference, collections, microforms, department management, and instruction—in a large research library. My next position, archivist for media and the performing arts at New York University (NYU), was more focused on video, collection building, reference, and instruction for all the performing arts departments except music. Following two positions focused on media and reference/instruction, my next role was the first shift in my career. I became the head librarian (and the only librarian for [End Page 1] part of my tenure) at Penn State Shenango, a regional campus in Sharon, Pennsylvania. The differences in this role from my previous positions were numerous, but the most obvious was the type of campus. Shenango was nonresidential, with a student body split between traditional undergraduates and returning adults. Although four-year programs were just being established, most students either earned an associate's degree or took core courses with the intent of transferring to Penn State's main campus for their junior and senior years. In addition, librarians at Penn State have faculty rank and status. The tenure process closely follows that of teaching faculty, with an expectation of publication, presentation, and professional service along with librarianship, which takes the place of credit teaching in the dossier. My husband's career prompted me to apply for my next position—the inaugural electronic resources and copyright librarian for Penn State. The job required that I move from Sharon to University Park and involved a dramatic change in the library's size and scope of services. I no longer had management responsibilities, and my public service duties diminished dramatically (though for much of my tenure in this position, I did provide copyright instruction programs for the entire university). I went from being a public services generalist in a small library to a highly specialized technical services librarian in one of the largest research libraries in the country. After 11 years, my next position took me once again to a small library at Bates College in Lewiston, Maine, where I was responsible for collections and budgeting. From Bates, I moved to my current position as library director at Marist College in Poughkeepsie, New York, a master's-level institution with a focus on graduate professional education. Size of Institution I have worked in small and large libraries, both public and private, and am now employed at a master's-level institution. Size does make a difference in work environment and upward mobility, as I discovered. Large Research Library In a study of job-hopping, Kelly Steenackers and...

Kitchen Sink Realisms: Domestic Labor, Dining, and Drama in American Theatre

Book Review| January 01 2019 Kitchen Sink Realisms: Domestic Labor, Dining, and Drama in American Theatre Kitchen Sink Realisms: Domestic Labor, Dining, and Drama in American Theatre. By Dorothy Chansky. Iowa City: University of Iowa Press, 2015. x + 291 pp. Cloth, $55.00; ebook, $55.00. Brenda Murphy Brenda Murphy University of Connecticut Search for other works by this author on: This Site Google American Literary Realism (2019) 51 (2): 182–183. https://doi.org/10.5406/amerlitereal.51.2.0182 Cite Icon Cite Share Icon Share Facebook Twitter LinkedIn MailTo Permissions Search Site Citation Brenda Murphy; Kitchen Sink Realisms: Domestic Labor, Dining, and Drama in American Theatre. American Literary Realism 1 January 2019; 51 (2): 182–183. doi: https://doi.org/10.5406/amerlitereal.51.2.0182 Download citation file: Zotero Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All Scholarly Publishing CollectiveUniversity of Illinois PressAmerican Literary Realism Search Advanced Search The text of this article is only available as a PDF. Copyright 2018 by the Board of Trustees of the University of Illinois2018 Article PDF first page preview Close Modal Issue Section: Reviews You do not currently have access to this content.

The Small-Town Midwest: Resilience and Hope in the Twenty-First Century by Julianne Couch

Reviewed by: The Small-Town Midwest: Resilience and Hope in the Twenty-First Century by Julianne Couch Emily Prifogle Julianne Couch, The Small-Town Midwest: Resilience and Hope in the Twenty-First Century. Iowa City: University of Iowa Press, 2016. 230 pp. $35.00. Since at least the early nineteenth century, travelers, politicians, and reformers, as well as urban and rural residents alike, have claimed that the small midwestern town was disappearing, for better or worse. The decline of small-town communities is discussed today most frequently in the context of the rural opioid crisis and the voting patterns of the 2016 presidential election. The message is clear: rural communities are struggling in terms of economics, health, and education. Yet, Julianne Couch's The Small-Town Midwest: Resilience and Hope in the Twenty-First Century examines small communities that are surviving, some even thriving, in the Great Plains region. [End Page 142] Her travelogue visits nine small-town communities to seek out "the qualities that make people stick to small, rural places" (3). Couch's nine chapters, each devoted to a particular community, take her reader on a journey from Wyoming, where she lived until recently, through Kansas, Missouri, Nebraska, and then finally to Iowa, where she now resides. Couch tends to use the term small town more than rural to describe the communities she visits, and she focuses on using population size and access to goods and services to define what counts as "small." Couch implicitly recognizes the diversity among small towns. She likewise recognizes that the nine communities in her book might not be representative of even the Great Plains region, let alone the census-designated midwestern states. But that seems to be—at least partially—the point. There is far more variation across, and less harmony within, heartland small communities than many might expect. Moreover, Couch approaches the towns and her writing as "an interested traveler." While her work is informed by social science research, she does not purport to engage in academic analysis (9). Indeed, those looking for a sharp-eyed account of the underbelly of midwestern small towns will not find it here. The reader encounters most frequently the successful town boosters that have managed to keep a small community afloat, and that is the book's strength. Couch takes residents and their communities on their own terms with a healthy dose of skepticism but without condescension. From this perspective, she reveals the hope and resilience that remains within small midwestern towns. The reader meanders through the towns with Couch, being passed from one store owner to another, or from the local historian to the director of the local development organization. As the reader meets the towns' boosters, many recurring issues will be familiar to those who have studied or lived in small towns: outmigration, conservative politics, local history and tourism, homogenizing pressures, infrastructure challenges, aging populations, lack of healthcare services, and the centrality of local schools. One of the most striking themes is the mobility of rural residents. We know that many rural people travel long distances to work in more densely populated hubs, but in Couch's travels, the reader finds a different type of mobility. Many, perhaps even most, of the civic leaders Couch interviews have not lived in the same small town for their entire lives. Some were born into a rural community but moved away for education or a career only to find that employment, family, or retirement brought them back to the same [End Page 143] or a similar small town. Still others have left their city life to "escape" to the country. Couch herself is one of the latter type of rural itinerants, many of whom (like Couch) are creative individuals who provide rural communities with art, music, and theater. These residents add dynamism to the communities chronicled here, and it is primarily through their eyes that Couch explores the qualities of small towns that draw people to them. This dynamism, however, is matched by a "social-norming machinery" in the communities that sanctions transgressive behavior, including holding liberal political views, living outside of a heterosexual nuclear family, not attending a Christian church, or even proposing too bold...

Here on Earth

Here on Earth Chad Abushanab (bio) The field behind our house tonightreminds me of an empty bedwith drifts of snow like wrinkled sheetsand shadows where you laid your head. A month and six days since you left,and night is when I feel you most.Sleep won’t come. I sit outsidetrying to ignore your ghost. Instead, the snow piles up. The woodsbeyond the field grow darker still.I shut my eyes against the cold,swallow another sleeping pill, and brace myself to face the numbwhite space, the bed you’re missing from. [End Page 128] Chad Abushanab chad abushanab is the author of The Last Visit, winner of the Donald Justice Poetry Prize, published by Autumn House Press in 2019. His poems have appeared in the New York Times Magazine, Southern Poetry Review, Shenandoah, Best New Poets, the Believer, and 32 Poems. He earned his PhD in English and creative writing at Texas Tech University. He lives in Iowa City. Copyright © 2019 University of North Carolina Wilmington

Susan Glaspell's Poetics and Politics of Rebellion. By Emeline Jouve. Studies in Theatre History and Culture. Iowa City: University of Iowa Press, 2017; pp. xiii + 258. $65 paper, $65 e-book.

Susan Glaspell's Poetics and Politics of Rebellion. By Emeline Jouve. Studies in Theatre History and Culture. Iowa City: University of Iowa Press, 2017; pp. xiii + 258. $65 paper, $65 e-book.

Traveler, There Is No Road: Theatre, the Spanish Civil War, and the Decolonial Imagination in the Americas. By Lisa Jackson-Schebetta. Studies in Theatre History and Culture. Iowa City: University of Iowa Press, 2017; pp. ix + 252, 15 illustrations. $65 paper, $65 e-book.

Traveler, There Is No Road: Theatre, the Spanish Civil War, and the Decolonial Imagination in the Americas. By Lisa Jackson-Schebetta. Studies in Theatre History and Culture. Iowa City: University of Iowa Press, 2017; pp. ix + 252, 15 illustrations. $65 paper, $65 e-book.

2018 AHA Late-Breaking Basic Science Abstracts.

2018 AHA Late-Breaking Basic Science Abstracts.

<em>The Simpsons</em> Do the Nineties

<em>The Simpsons</em> Do the Nineties

Temporal Trends in ADHD Prevalence, 1997–2016

Research Article| December 01 2018 Temporal Trends in ADHD Prevalence, 1997–2016 AAP Grand Rounds (2018) 40 (6): 67. https://doi.org/10.1542/gr.40-6-67 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Temporal Trends in ADHD Prevalence, 1997–2016. AAP Grand Rounds December 2018; 40 (6): 67. https://doi.org/10.1542/gr.40-6-67 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Source: Xu G, Strathearn L, Liu B, et al. Twenty-year trends in diagnosed attention-deficit/hyperactivity disorder among US children and adolescents, 1997–2016. JAMA Network Open. 2018; 1(4): e181471; doi: https://doi.org/10.1001/jamanetworkopen.2018.1471Google Scholar Investigators from the University of Iowa, Iowa City, and Shenzhen Children’s Hospital, Shenzhen, Guangdong, China, analyzed data from the National Health Interview Survey (NHIS) to estimate the current prevalence of diagnosed ADHD among US youth and evaluate trends in prevalence during the period 1997–2016. NHIS is a cross-sectional in-person survey conducted annually by the CDC and is used to generate nationally representative data on the health of the US population. For households with children, one child is randomly chosen for the survey, with survey responses provided by caregivers. For the current study, the investigators abstracted data on children 4–17 years old who were included in the NHIS between 1997–2016. The primary outcome was a diagnosis of ADHD, based on response to the question, “Has a doctor or health care professional ever told you that [sample child] had…ADHD?” Demographic data, including race/ethnicity, gender, household income and region of the country, were also abstracted. A nationally representative estimated overall prevalence of ADHD and prevalence of ADHD in subgroups during 2015–2016 were calculated. Regression analysis was used to assess changes in prevalence between 1997 and 2016, and chisquare tests were used to assess differences among subgroups. Overall, data were collected on 186,457 children during the study period. The nationally estimated prevalence of a diagnosis of ADHD among children 4–17 years old in 2015–2016 was 10.2% (95% CI, 9.6%, 10.8%). The prevalence was significantly higher in boys than girls (14.0% vs 6.3%, P<.001) and more common among non-Hispanic white and non-Hispanic black youth than in those of Hispanic ethnicity (12.0%, 12.8%, and 6.1%, respectively; P<.001). There was a significant difference in diagnosed ADHD prevalence in different regions of the country (Northeast 10.3%, Midwest 12.2%, South 11.1%, and West 7.0%). Children living in poverty were significantly more likely to be diagnosed with ADHD than those in wealthier households. During the entire study period, there was a significant increase in prevalence of ADHD from 6.1% in 1997–1998, to 10.2% in 2015–2016 (P<.001 for trend). There were also significant increases during this time among all subgroups assessed. The authors conclude that the prevalence of diagnosed ADHD increased significantly between 1997 and 2016. Dr Doherty has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. ADHD is an umbrella category that encompasses individuals with hyperactivity, impulsivity, and/or inattention beyond what is expected for their overall developmental stage. Rather than a discrete disorder, ADHD likely represents the end of a spectrum of executive function resulting from combined genetic and environmental factors. Nonetheless, categorical diagnosis of ADHD is important because children with ADHD are at increased risk for other neurodevelopmental issues, such as learning disabilities, anxiety, depression, and oppositional defiant... You do not currently have access to this content.

High Expression of NEK2 Mediated By p53 Contributes to Progression and Relapse of Multiple Myeloma

High expression of NEK2 mediated by p53 contributes to progression and relapse of multiple myelomaXiangling Feng1,2, Jiaojiao Guo1, Bowen Ouyang2, Yinghong Zhu1,Gang An3, Hao Zhen1, Jiliang Xia1, Yongjun Guan1, Xinying Zhao2, Lugui Qiu3, Jiaxi Zhou3, Fenghuang Zhan4,Wen Zhou11, Cancer Research Institute,Central South University, Changsha 410078, China. 2Xiang Ya School of Public Health, Central South University, Changsha, Hunan, China. USA. 3State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, China. 4Department of Internal Medicine, Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, USA. E-mail: wenzhou@csu.edu.cn.Background: Loss of p53 is an independent prognostic factor in patients with multiple myeloma (MM). Our previous studies found abnormal high expression of NEK2 was closely related to the poor prognosis and drug resistance of myeloma patients. However, it's unclear how NEK2 was up-regulated in MM. Through bioinformatics analysis, the binding site of p53 protein is found in NEK2 promoter, but the relationship and function of p53 and NEK2 in MM are poorly understood.Materials and Methods: In this study, p53-/- MM cell lines (ARP1 and KMS11) and p53 p53+/+ MM cell lines (MM1S and H929) were used for investigating the role of NEK2 in p53-/- MM cell. FISH was performed on interphase nuclei of MM primary cells to detect p53 and NEK2 copy numbers. Chromatin immunoprecipitation and fluorescence reporter system were applied for examining the binding site of p53 protein in the distal NEK2 promoter. CGH and RNA-seq were performed to validate copy number changes and variations in the expression of several transcripts.Results: The top 10% of MM patients with the highest NEK2 expression and lowest p53 had a significantly inferior OS (P<0.001) in TT2 and TT3 patients (GSE2658) and the expression of NEK2 increased significantly in myeloma cells during chemotherapy(GSE19554), while p53 decreased with the disease progression, suggesting a strong relationship with drug resistance. Single cell PCR showed increased NEK2 expression correlated with decreased p53 expression in single CD138+ plasma cell. FISH confirmed the loss of p53 in CD138+ plasma cells with amplification of NEK2 copies. Furthermore, NEK2 was also high expressed in p53 low expressed MM cells by Immunofluorescence (IF) (P<0.01). In addition, NEK2 was upregulated in p53-/- MM cell lines and HEK293 cells by deleted p53 gene with CRISPR technique both on mRNA and protein level (P<0.01), suggesting a negative correlation between the p53 and the expression level of NEK2. Meanwhile, when p53 deletion and NEK2 overexpression occur simultaneously, the phenomena of asymmetric mitosis and multipolar division are more obvious (P<0.001), suggested that the double hit of p53 deletion and NEK2 overexpression increases the chromosomal instability. Further in vivo study indicated the subcutaneous tumorigenesis in p53 deletion and NEK2 overexpression group was significantly greater than that of the single overexpression of NEK2 and deletion of p53 group (P<0.001), suggested that NEK2 overexpression and p53 deletion enhances the tumorigenic ability in vivo. While down-regulation of NEK2 by shRNA in p53 deletion cells, cell growth was inhibited in vitro and in vivo.To explore the relationship between p53 and NEK2, chromatin immunoprecipitation and fluorescence reporter system showed that p53 could bind to the promoter region of NEK2 and regulate its transcriptional expression. Further CGH analysis of the deletion of p53 expression in HEK293 cells can cause 1q21.4-44 amplification of the chromosome region of the NEK2 directly, which further confirmed by FISH. Finally, RNA-seq revealed several chromosome instability genes were abnormal expressed in NEK2 overexpression and p53 deletion double-hit group.Conclusion: In summary, p53 deletion and NEK2 overexpression induced cancer cell drug resistance, proliferation and chromosomal instability. p53 could bind to the promoter region of NEK2 and cause NEK2 amplification. Down-regulation of NEK2 by shRNA in p53 deletion cells inhibited cell growth in vitro and in vivo. Thus,The significance of this study will provide the pre-clinical application of the NEK2 inhibitor to overcome the drug resistance induced by p53 in MM. DisclosuresNo relevant conflicts of interest to declare.

A fully 3-D numerical model to predict flood wave propagation and assess efficiency of flood protection measures

Abstract This paper discusses development and validation of a 3-D, non-hydrostatic, Reynolds-Averaged Navier–Stokes (RANS) model using the Volume of Fluid (VOF) approach to simulate flooding events in natural environments. A series of validation simulations in simple and complex geometries are performed to test the different modules of the flow solver. The paper also discusses the differences between simulation results obtained using the 3-D model and those obtained using a standard, 2-D hydrostatic, depth-averaged model. The predictions by the two models show fairly large differences in regions where 3-D effects are expected to be significant (e.g., in regions containing highly-curved river reaches and near hydraulic structures). Then, the validated 3-D model is employed to investigate the efficiency of using flood-protection walls to reduce adverse effects of flooding in the Iowa River near Iowa City, Iowa, USA. Finally, the propagation of a flood wave in a reach of the Iowa River containing a bridge is simulated and the effects of the flow becoming pressurized beneath the bridge deck are discussed. For such applications, in which the regime can change locally between open channel and pressurized flow, the use of fully 3-D, non-hydrostatic models may be the only viable option to accurately predict flow hydrodynamics and its effects on bed shear stresses and sediment entrainment potential, especially around locations where the flow becomes pressurized.

Editorial introductions

Editorial introductions

Adaptive elastic net for group testing.

For disease screening, group (pooled) testing can be a cost-saving alternative to one-at-a-time testing, with savings realized through assaying pooled biospecimen (eg, urine, blood, saliva). In many group testing settings, practitioners are faced with the task of conducting disease surveillance. That is, it is often of interest to relate individuals' true disease statuses to covariate information via binary regression. Several authors have developed regression methods for group testing data, which is challenging due to the effects of imperfect testing. That is, all testing outcomes (on pools and individuals) are subject to misclassification, and individuals' true statuses are never observed. To further complicate matters, individuals may be involved in several testing outcomes. For analyzing such data, we provide a novel regression methodology which generalizes and extends the aforementioned regression techniques and which incorporates regularization. Specifically, for model fitting and variable selection, we propose an adaptive elastic net estimator under the logistic regression model which can be used to analyze data from any group testing strategy. We provide an efficient algorithm for computing the estimator along with guidance on tuning parameter selection. Moreover, we establish the asymptotic properties of the proposed estimator and show that it possesses "oracle" properties. We evaluate the performance of the estimator through Monte Carlo studies and illustrate the methodology on a chlamydia data set from the State Hygienic Laboratory in Iowa City.