• JUNCTIONAL ARMADILLO (β-CATENIN) MAINTAINS PROPER TISSUE ARCHITECTURE DURINGDROSOPHILAEYE DEVELOPMENT

      Pignoni, Francesca; DeSantis, Dana F (2020)
      Formation of thecompoundeye of Drosophilarequires carefully orchestrated developmental events that occur in its progenitor epithelium, the eye imaginal disc.This tissue is composed of two continuous, apposed epithelia: the disc proper epithelium (DpE), which forms the retina, and the peripodial epithelium (PE), which ultimately forms head cuticle. In this work, I describe an armadillo (b-catenin)loss-of-function condition in which the developing DpEis disrupted and displays a phenotype that I call“retinalshift”. This developmental phenotype ultimately results in abnormal fly eye morphology that is incompatible with compound eye vision.I uncover a role for the PE in maintaining proper retinal epithelium morphology during eye formation and trace the molecular mechanism to the regulation of Hippo-Yki pathway in PE cells by the function of Armadillo at the adherens junctions.
    • Knee dislocation with popliteal artery disruption: A nationwide analysis from 2005 to 2013.

      Naziri, Qais; Beyer, George A; Shah, Neil V; Solow, Maximillian; Hayden, Andrew J; Nadarajah, Vidushan; Ho, Derek; Newman, Jared M; Boylan, Matthew R; Basu, Niladri N; et al. (2018-08-16)
      Objective: Few have compared short-term outcomes following knee dislocations with or without concomitant popliteal artery disruption (PAD). Methods: The Nationwide Inpatient Sample was used to identify 2175 patients admitted for knee dislocation from 2005 to 2013 (concomitant PAD: n = 210/9.7%; without: n = 1965/90.3%). Results: Patients with PAD were younger, more often male, Black and Hispanic, and with Medicaid (all p ≤ 0.013). PADs were associated with 11.0-times higher odds of increased LOS (95%CI, 6.6-18.4) and 2.8-times higher odds of experiencing any complication (95%CI, 2.03-3.92). Female sex was a protective factor against increased LOS, (OR = 0.65; 95%CI, 0.48-0.88). Conclusion: High suspicion index should be maintained for concomitant vascular injuries following knee dislocations.
    • Knowledge Documentation - From Text to Graphics: Can this improve help desk knowledge transfer?

      Gage, Teresa J. (2007-08-01)
      This thesis was designed to find out if graphics could improve help desk knowledge transfer. Four Web prototype presentation styles were analyzed via the Delphi Method (Michalski 2003) utilizing a panel of experts. The elements tested included the use of text and increasing amounts of graphics presented with different navigation systems. The results proved that graphics could improve knowledge transfer but that a combination of text and graphic may be more effective in a team-centric solution to help desk knowledge transfer.
    • Laboratory-Observed Behavioral Disinhibition in the Young Offspring of Parents With Bipolar Disorder: A High-Risk Pilot Study

      Hirshfeld-Becker, Dina R.; Biederman, Joseph; Henin, Aude; Faraone, Stephen V.; Cayton, Gabrielle A.; Rosenbaum, Jerrold F. (American Psychiatric Association Publishing, 2006-02)
      Objective: This study tested whether behavioral disinhibition is more prevalent among offspring of parents with bipolar disorder than among offspring of parents without bipolar disorder. Method: The authors conducted a secondary analysis of data from a preexisting high-risk study of offspring at risk for panic disorder and depression (N=278) that had included some children with parents who had bipolar disorder (N=34). Children (ages 2–6) had been classified as behaviorally inhibited, disinhibited, or neither in laboratory assessments. Results: Offspring of bipolar parents had significantly higher rates of behavioral disinhibition than offspring of parents without bipolar disorder. Behavioral inhibition did not differ between groups. Differences were not accounted for by parental panic disorder or major depression or by parental history of attention deficit hyperactivity disorder, conduct disorder, antisocial personality, or substance use disorders. Conclusions: Results suggest a familial link between bipolar disorder in parents and behavioral disinhibition in their offspring. Behavioral disinhibition may be a familially transmitted predisposing factor for dysregulatory distress later in life.
    • Lack of Association Between Behavioral Inhibition and Psychosocial Adversity Factors in Children at Risk for Anxiety Disorders

      Hirshfeld-Becker, Dina R.; Biederman, Joseph; Faraone, Stephen V.; Segool, Natasha; Buchwald, Jennifer; Rosenbaum, Jerrold F. (American Psychiatric Association Publishing, 2004-03)
      Objective: In a previous controlled study of offspring at risk for anxiety disorders, the authors found that parental panic disorder with comorbid major depression was associated with child behavioral inhibition, the temperamental tendency to be quiet and restrained in unfamiliar situations. To explore whether this association was mediated by environmental factors, the authors examined associations between psychosocial adversity variables and behavioral inhibition in this group of children. Method: Subjects included 200 offspring of parents with panic disorder and/or major depression and 84 comparison children of parents without mood or anxiety disorders. Behavioral inhibition was assessed through laboratory observations. The associations between behavioral inhibition and the following psychosocial factors were examined: socioeconomic status; an index of adversity factors found in previous studies to be additively associated with child psychopathology; family intactness, conflict, expressiveness, and cohesiveness; exposure to parental psychopathology; sibship size; birth order; and gender. Results: The results showed no associations between behavioral inhibition and any of the psychosocial factors in the study group as a whole, despite adequate power to detect medium effect sizes. Among low-risk comparison children only, some definitions of behavioral inhibition were associated with low socioeconomic status, low family cohesion, and female gender. Conclusions: The results suggest that the psychosocial adversity factors examined in this study do not explain the previous finding that offspring of parents with panic disorder are at high risk for behavioral inhibition.
    • Lack of Association Between Parental Alcohol or Drug Addiction and Behavioral Inhibition in Children

      Biederman, Joseph; Hirshfeld-Becker, Dina R.; Rosenbaum, Jerrold F.; Perenick, Sarah G.; Wood, Julia; Faraone, Stephen V. (American Psychiatric Association Publishing, 2001-10)
      Objective: “Behavioral inhibition to the unfamiliar” has been proposed as a precursor to anxiety. A recent study proposed that it may also be a precursor to alcoholism. The authors sought to replicate the latter finding through a secondary analysis of data from a large study of young children (age 2–6 years)—offspring of parents with panic and depressive disorders—who had been assessed for behavioral inhibition through laboratory-based observations. Method: The offspring were stratified on the basis of presence or absence of parental lifetime history of DSM-III-R alcohol dependence (N=115 versus N=166, respectively) or drug dependence (N=78 versus N=203). The rates of behavioral inhibition were then compared between groups. Results: Despite adequate power to detect associations, neither parental alcohol dependence nor drug dependence was associated with a higher risk for behavioral inhibition in the offspring. Conclusions: These results are not consistent with the hypothesis linking behavioral inhibition to addictions
    • Laminins regulate retinal angiogenesis

      Brunken, William J.; Biswas,Saptarshi (2017)
      Vascular pathologies are the leading causes of acquired blindness in the developed world. While many studies sought to unravel cell-intrinsic and growth factor-mediated regulations of angiogenesis, it is only recently that the role of the basement membrane (BM) components in angiogenesis began to be explored. Several diseases with ocular manifestations are known to alter vascular BM compositions. Therefore, a detailed knowledge of the BM-mediated signals that regulate angiogenesis is of great importance. Laminins, a critical component of the BM, have been shown to regulate several aspects of angiogenesis in the retina. Our laboratory previously demonstrated that the laminin composition of the inner limiting membrane (ILM) regulates astrocyte migration, and consequently vascular expansion along the retinal surface. Here, I examined the role of γ3- and β2-containing laminins in two specific aspects of angiogenesis: 1) vascular branching and endothelial cell proliferation in the nascent vascular plexus, and 2) arterial morphogenesis in the remodeling zone. Results presented in Chapter 2 and Appendix 1 demonstrate that laminin composition of the BM is a critical regulator of microglial recruitment to the growing nascent plexus, where microglia facilitate vascular branching. Furthermore, microglia interact with the astrocyte-derived layer of the vascular BM, and that this interaction regulates iii microglial activation. The activation state of microglia, in turn, regulates endothelial cell proliferation. Results presented in Chapter 3 and Appendix 2 demonstrate that vascular BM laminins are critical regulators of arterial morphogenesis. Specifically, my results reveal a novel mechanism where γ3- containing laminins signal through dystroglycan to induce Dll4/Notch signaling in arterial endothelial cells, regulating proper arterial morphogenesis. Finally, in Appendix 3, I examined the coordinated expression of different laminin chains in the vascular BM. My preliminary results suggest that expressions of laminin α2-, α5- and γ3-chains in the retinal vascular BM are coordinately regulated with the expression of laminin β2-chain. In conclusion, this study sheds light on hitherto unexplored mechanisms by which BM laminins regulate retinal vascular development.
    • Laptop’s In Education – Hype or Help?

      Cronn, Patrick (2006-12-01)
      This study examines the impact of introducing a laptop program for educational teaching in the classroom. By interviewing experts in the field, teachers, administrators, and students at a college level, a phenomenology was completed on the impact of laptops in pedagogy. These ideals were then applied to the Human-Centered Design Theory. “It was not until twenty years ago that serious progress was achieved in applying the available computer and internet technology to support teaching and learning in schools and institutions of higher education. The technology that was previously only available to large corporations and organizations began to be available in homes, schools and universities. This new shift in technology application has provided both students and educators many new advantages and learning possibilities (Altalib, 4).” The numerous ways in which professors and their students interact has always been a critical issue in higher educational institutes. With the increase in technological enhancements over the past several years, study is needed on how collaboration between faculty and students advance.
    • Library renovation: From setbacks to success.

      Wells, Elaine (Research Caucus of the Medical Library Association, 2021-02-25)
      The journey started at a 2016 meeting of the college’s Learning Resources Committee, which I chair as Library Director, A student representative casually commented that our Library looked “dated”. Not that we actually WERE dated, we have electronic resources, 24/7 remote access, printers, scanners, wireless, and a state-of-the-art Library Management System. However, through the eyes of our young student, the Library looked “like something from the 1970s.” Anyone who has lived through that decade’s will know that was not meant as a compliment. The student’s criticism prompted the Dean of Academic Affairs, who sat in on the meeting, to ask when the Library had had its last “facelift.” That was an easy one to answer - as far as I knew…never. And I’ve been here over 20 years. Just like that, a renovation was born. How hard could this be? I would query the students on what a suitable update might look like, get a budget, buy some new furniture, and go back to the business of being a librarian rather than an interior designer. Spoiler alert: not so fast.
    • Limb Salvage Versus Amputation in Conventional Appendicular Osteosarcoma: a Systematic Review.

      Jauregui, Julio J; Nadarajah, Vidushan; Munn, Joseph; Pivec, Robert; Kapadia, Bhaveen H; Lerman, Daniel M; Maheshwari, Aditya V (2018-01-20)
      The overall survivorship in patients with appendicular osteosarcoma has increased in the past few decades. However, controversies and questions about performing an amputation or a limb salvage procedure still remain. Using three peer-reviewed library databases, a systematic review of the literature was performed to evaluate all studies that have evaluated the outcomes of appendicular osteosarcoma, either with limb salvage or amputation. The mean 5-year overall survivorship was 62% for salvage and 58% for amputation (p > 0.05). At mean 6-year follow-up, the local recurrence rates were 8.2% for salvage and 3.0% for amputation (p > 0.05). Additionally, at mean 6-year follow-up, the rate for metastasis was 33% for salvage and 38% for amputation (p > 0.05). The revision rates were higher with salvage (31 vs. 28%), and there were more complications in the salvage groups (52 vs. 34%; p > 0.05). Despite the heterogeneity of studies available for review, we observed similar survival rates between the two procedures. Although there was no significant statistical difference between rates of recurrence and metastasis, the local recurrence rate and risk of complications were higher for limb salvage as compared to amputation. Cosmetic satisfaction is often higher with limb salvage, whereas long-term expense is higher with amputation. Overall, current literature supports limb salvage procedures when wide surgical margins can be achieved while still retaining a functional limb.
    • Linkage of chromosome 13q32 to schizophrenia in a large veterans affairs cooperative study sample

      Faraone, Stephen V.; Skol, Andrew D.; Tsuang, Debby W.; Bingham, Stephen; Young, Keith A.; Prabhudesai, Sarita; Haverstock, Susan L.; Mena, Felicitas; Menon, Aerath Sri Kumar; Bisset, Darren; et al. (Wiley, 2002-07-29)
      Several prior reports have suggested that chromosomal region 13q32 may harbor a schizophrenia susceptibility gene. In an attempt to replicate this finding, we assessed linkage between chromosome 13 markers and schizophrenia in 166 families, each with two or more affected members. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Studies Program, included 392 sampled affected subjects and 216 affected sib pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizoaffective disorder, depressed. The families had mixed ethnic backgrounds. The majority were northern European-American families (n = 62, 37%), but a substantial proportion were African-American kindreds (n = 60, 36%). Chromosome 13 markers, spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the 13q32 region were genotyped and the data analyzed using semi-parametric affected only linkage analysis. For the combined sample (with race broadly defined and schizophrenia narrowly defined) the maximum LOD score was 1.43 (Z-score of 2.57; P = 0.01) at 79.0 cM between markers D13S1241 (76.3 cM) and D13S159 (79.5 cM). Both ethnic groups showed a peak in this region. The peak is within 3 cM of the peak reported by Brzustowicz et al.
    • Live Tweet Map with Sentimental Analysis

      Kotrika, Rohila; Chen-Fu Chiang; Reviewer; Saumendra, Sengupta; Advisor; Andriamanalimanana, Bruno; Reviewer (2016-05-01)
      This project basically aims to build a system for the real-time analysis of the trends and public views around the whole world by storing and analyzing the stream of tweets from the Twitter live API which produces a huge amount of data . The tweets, tweet ID, time and other relevant elements are stored into a database and are represented in a map that is being updated in near real time with the help of Google map API. This project also aims to achieve the sentimental analysis of the tweets by sending the tweets to the natural language processing API which in turn processes the tweets using the natural language processing and gives a result If those tweets are positive, negative or neutral in nature. The map clusters tweet as to show where people are tweeting most from according to the sample tweets we get from the streaming API. These clusters will be shown in different colors according to the sentimental evaluation we receive from the sentiment API by Vivek Narayanan which works by examining individual words and short sequences of words (n-grams) and comparing them with a probability model. The probability model is built on a pre labeled test set of IMDb movie reviews. It can also detect negations in phrases, i.e., the phrase "not bad" will be classified as positive despite having two individual words with a negative sentiment. The web service uses a co routine server based on event, so that the trained database can be loaded into shared memory for all requests, which makes it quite scalable and fast. The API is specified here, it supports batch calls so that network latency isn't the main bottleneck. For Instance, if a tweet is negative in evaluation then it is shown in a red color marker on the map, green for positive and grey for the neutral. This analytic will also demonstrate the heat map for all the tweets that are stored in the database which gives a satisfying answer demonstrating from which part of the world are most of the tweets from. In this project we create a dynamic web application with the target runtime environment as Apache Tomcat Server. The server will also be initialized with the context listener which starts running the code to get the tweets into the database till the server is stopped. The most popular trends among worldwide and citywide would be provided in a drop down to be selected from which gives a clear perspective on how each trend behaves. It also offers the public, the media, politicians and scholars a new and timely perspective on the dynamics of the world wide trends and public opinion.
    • Liver-specific glucocorticoid action in alcoholic liver disease

      Lu, Hong; Wang, Yazheng (2021)
      The number of deaths due to alcoholic liver disease is increasing every year. Glucocorticoids (GCs) are the only first-line drugs for alcoholic hepatitis (AH) treatment but have limited efficacy. Long-term high-dose GC use can cause various side effects on extrahepatic tissues, such as immunosuppression and neuromuscular side effects, which may be a limiting factor for GC treatment of AH. Therefore, liver-specific GC-targeted therapy may have multiple advantages compared with systemic GC for AH. This research explored the role of liver-specific deficiency of glucocorticoid receptor (GR) in AH induced by a high-fat diet (HFD) plus ethanol binge. Females are less prone to AH induced by HFD plus acute binge drinking, likely due to sex differences in estrogen (E2) signaling. We found that hepatic GR deficiency worsened steatosis in both genders of AH mice but only aggravated the liver injury in male AH mice. Multiple signaling pathways were dysregulated in GR knockout AH mice. Interestingly, hepatic expression of estrogen receptor (ERα) was induced, and the E2-inactivating enzyme was markedly down-regulated in GR knockout AH mice, suggesting enhanced E2 signaling in these mice. Our data mining found marked dysregulation of many GR-target genes important for lipid catabolism, cytoprotection, and inflammation in patients with severe AH. These key GR-target genes were similarly induced or down-regulated by our liver-targeting GC prodrugs and the parent drug at 1μM in primary human hepatocytes. In contrast, GC prodrugs had much weaker inhibitory effects than the parent drug on LPS-induction of IL-1B in mouse macrophages, suggesting a good liver selectivity of our liver-targeting GC prodrugs. The ultimate goal of this study is to determine the mechanistic role of GR in alcoholic fatty liver disease and develop targeted drug therapies to treat alcoholic hepatitis.
    • Local Diversification of Methicillin- Resistant Staphylococcus aureus ST239 in South America After Its Rapid Worldwide Dissemination

      Botelho, Ana Maria Nunes; Cerqueira e Costa, Maiana Oliveira; Moustafa, Ahmed M.; Beltrame, Cristiana Ossaille; Ferreira, Fabienne Antunes; Côrtes, Marina Farrel; Costa, Bruno Souza Scramignon; Silva, Deborah Nascimento Santos; Bandeira, Paula Terra; Lima, Nicholas Costa Barroso; et al. (Frontiers Media SA, 2019-02-27)
      The global spread of specific clones of methicillin-resistant Staphylococcus aureus (MRSA) has become a major public health problem, and understanding the dynamics of geographical spread requires worldwide surveillance. Over the past 20 years, the ST239 lineage of MRSA has been recognized as an emerging clone across the globe, with detailed studies focusing on isolates from Europe and Asia. Less is known about this lineage in South America, and, particularly, Brazil where it was the predominant lineage of MRSA in the early 1990s to 2000s. To gain a better understanding about the introduction and spread of ST239 MRSA in Brazil we undertook a comparative phylogenomic analysis of ST239 genomes, adding seven completed, closed Brazilian genomes. Brazilian ST239 isolates grouped in a subtree with those from South American, and Western, romance-language-speaking, European countries, here designated the South American clade. After an initial worldwide radiation in the 1960s and 1970s, we estimate that ST239 began to spread in South America and Brazil in approximately 1988. This clone demonstrates specific genomic changes that are suggestive of local divergence and adaptational change including agrC single-nucleotide polymorphisms variants, and a distinct pattern of virulence-associated genes (mainly the presence of the chp and the absence of sea and sasX). A survey of a geographically and chronologically diverse set of 100 Brazilian ST239 isolates identified this virulence genotype as the predominant pattern in Brazil, and uncovered an unexpectedly high prevalence of agr-dysfunction (30%). ST239 isolates from Brazil also appear to have undergone transposon (IS256) insertions in or near global regulatory genes (agr and mgr) that likely led to rapid reprogramming of bacterial traits. In general, the overall pattern observed in phylogenomic analyses of ST239 is of a rapid initial global radiation, with subsequent local spread and adaptation in multiple different geographic locations. Most ST239 isolates harbor the ardA gene, which we show here to have in vivo anti-restriction activity. We hypothesize that this gene may have improved the ability of this lineage to acquire multiple resistance genes and distinct virulence-associated genes in each local context. The allopatric divergence pattern of ST239 also may suggest strong selective pressures for specific traits in different geographical locations.
    • Localization of sarcomeric proteins during muscle assembly in mouse cardiomyocytes and skeletal myotubes

      Sanger, Jean; Sanger, Joseph; Welchons, Matthew J (2017)
      This study seeks to investigate the role of contractions in myofibrillogenesis, and structure of nascent myofibrils. The model system employed in these experiments was cultured quail myotubes. In order to determine the role of contractions in myofibrillogensis, contractions were indirectly inhibited with elevated KCl, and directly inhibited with 2,3 butanedione monoxime (BDM), a small cell-permeable inhibitor of actin & muscle myosin interactions. Myotubes were treated with contraction inhibitors at 2½days –soon after the main fusion event. On the 6thculture day, there was significant delay in myofibrillogensis in myotubes exposed to elevated KCl. This delay was characterized by the expansion of nascent myofibrils at the spreading edges of myotubes. This delay in myofibrillogenesis was not accompanied by diminished accumulations of muscle myosin. On the 4thculture day, there was complete arrest of myofibrillogenesis at the nascent step with the treatment of BDM. As a result, it is concluded that contractions are necessary for the progression of nascent myofibrils to mature myofibrils. The structure of nascent myofibrils was further investigated with super resolution microscopy. Structured illumination microscopy (SIM) and stimulated emission depletion (STED) microscopy revealed mini-A-bands –shorter than 1.5 μmin length –associated with nascent myofibrils. These structures were spaced at varying intervals, and oriented at angles deviating the from the actin superstructure of the nascent myofibril. Mini-A-bands were also observed to progressively in expand in length distal to the spreading edges of myotubes. STED imaging indicates that some mini-A-band are adjacent to, and not integrated within, the actin superstructure of nascent myofibrils.
    • Long-term outcome of pediatric obsessive-compulsive disorder: a meta-analysis and qualitative review of the literature

      Stewart, S. E.; Geller, D. A.; Jenike, M.; Pauls, D.; Shaw, D.; Mullin, B.; Faraone, Stephen V. (Wiley, 2004-07)
      Objective: To review the extant literature on the long-term outcome of child/adolescent-onset obsessive–compulsive disorder (OCD). Method: Medline and Psychlit databases were systematically searched for articles regarding long-term outcomes of child/adolescent-onset OCD. Meta-analysis regression was applied to evaluate predictors and persistence of OCD. Results: Sixteen study samples (n ¼ 6–132; total ¼ 521 participants) in 22 studies had follow-up periods ranging between 1 and 15.6 years. Pooled mean persistence rates were 41% for full OCD and 60% for full or subthreshold OCD. Earlier age of OCD onset (z ¼ )3.26, P ¼ 0.001), increased OCD duration (z ¼ 2.22, P ¼ 0.027) and inpatient vs. out-patient status (z ¼ 2.94, P ¼ 0.003) predicted greater persistence. Comorbid psychiatric illness and poor initial treatment response were poor prognostic factors. Although psychosocial function was frequently compromised, most studies lacked comprehensive outcome measures. Conclusion: Long-term persistence of pediatric OCD may be lower than believed. Future studies should include broader measures of outcome including symptomatic persistence and functional impairment in multiple domains.
    • Longitudinal Viral Load Monitoring Using Home-Collected Dried Blood Spot Specimens of MSM Living with HIV: Results from a Feasibility Pilot Study.

      Teran, Richard A; Sobieszczyk, Magdalena E; Chiasson, Mary Ann; Uhlemann, Anne-Catrin; Weidler, Jessica; Shah, Jayesh G; Chang, Jennifer Y; Otto, Caitlin; Hirshfield, Sabina
      Novel viral load monitoring strategies are needed to help individuals maintain an undetectable viral load (UVL). In 2018, U.S. MSM living with HIV with a past detectable VL received a dried blood spot (DBS) kit at baseline and 3-month follow-up and returned specimens to a research laboratory. Of 56 consenting participants, 91% returned specimens at baseline and 77% at 3-month follow-up; 74% who returned two specimens had UVL at both time points. At-home DBS collection and longitudinal VL monitoring is feasible among U.S. MSM with fluctuating viral load. This complementary approach to clinical care could improve viral suppression maintenance.
    • Lost Memories: Exploring Childhood Amnesia and Nostalgia Through Autoethnographic Research

      Lizardi, Ryan; Thesis Advisor; Stam, Kathryn; Second Reader; Danielle, Pastore (2021-04)
      Memory, especially at a young age, is unstable. Memories can easily be remapped and misremembered. Generally, memory retention follows a predictable pattern, known as the reminiscence bump, and memory retention reaches its peak around twenty years old. While memory retention does increase exponentially as a child ages, there is a tendency for early childhood memories to vanish - a phenomenon known formally as childhood amnesia. Photographs and videos can act as memory aids to assist recall, but can lead to misremembering. People also view photographs and videos (especially physical versions such as photo albums) as memory storage devices, and often experience a great deal of nostalgia when flipping through and reminiscing. However, just as society experienced a shift from analogue to digital film and video, users shifted their intentions of photography from memory to communication. To further explore these topics I performed extensive autoethnographic research. In the hopes of shedding light on lost or forgotten memories and to better understand personal nostalgia, I had twenty-eight rolls of undeveloped childhood film developed, which I then personally scanned. Additionally, I digitally transferred and watched eighty-six never-before-seen childhood home video cassettes. Using both written, photo, and video footage-based context clues, I assembled a video timeline to represent my lost memories. Video Link: https://youtu.be/7OCfjgm1YkU
    • Machine Learning And MRI-Based Diagnostic Models For ADHD: Are We There Yet?

      Zhang-James, Yanli; Hoogman, Martine; Franke, Barbara; Faraone, Stephen V. (Cold Spring Harbor Laboratory, 2020-10-23)
      Machine learning (ML) has been applied to develop magnetic resonance imaging (MRI)-based diagnostic classifiers for attention-deficit/hyperactivity disorder (ADHD). This systematic review examines this literature to clarify its clinical significance and to assess the implications of the various analytic methods applied. We found that, although most of studies reported the classification accuracies, they varied in choice of MRI modalities, ML models, cross-validation and testing methods, and sample sizes. We found that the accuracies of cross-validation methods inflated the performance estimation compared with those of a held-out test, compromising the model generalizability. Test accuracies have increased with publication year but were not associated with training sample sizes. Improved test accuracy over time was likely due to the use of better ML methods along with strategies to deal with data imbalances. Ultimately, large multi-modal imaging datasets, and potentially the combination with other types of data, like cognitive data and/or genetics, will be essential to achieve the goal of developing clinically useful imaging classification tools for ADHD in the future.
    • Machine-Learning Prediction of Comorbid Substance Use Disorders in ADHD Youth Using Swedish Registry Data

      Zhang-James, Yanli; Chen, Qi; Kuja-Halkola, Ralf; Lichtenstein, Paul; Larsson, Henrik; Faraone, Stephen V. (Cold Spring Harbor Laboratory, 2019-06-06)
      Background: Children with attention-deficit/hyperactivity disorder (ADHD) have a high risk for substance use disorders (SUDs). Early identification of at-risk youth would help allocate scarce resources for prevention programs. Methods: Psychiatric and somatic diagnoses, family history of these disorders, measures of socioeconomic distress, and information about birth complications were obtained from the national registers in Sweden for 19,787 children with ADHD born between 1989 and 1993. We trained (a) a cross-sectional random forest (RF) model using data available by age 17 to predict SUD diagnosis between ages 18 and 19; and (b) a longitudinal recurrent neural network (RNN) model with the Long Short-Term Memory (LSTM) architecture to predict new diagnoses at each age. Results: The area under the receiver operating characteristic curve (AUC) was 0.73(95%CI 0.70–0.76) for the random forest model (RF). Removing prior diagnosis from the predictors, the RF model was still able to achieve significant AUCs when predicting all SUD diagnoses (0.69, 95%CI 0.66–0.72) or new diagnoses (0.67, 95%CI: 0.64, 0.71) during age 18–19. For the model predicting new diagnoses, model calibration was good with a low Brier score of 0.086. Longitudinal LSTM model was able to predict later SUD risks at as early as 2 years age, 10 years before the earliest diagnosis. The average AUC from longitudinal models predicting new diagnoses 1, 2, 5 and 10 years in the future was 0.63. Conclusions: Population registry data can be used to predict at-risk comorbid SUDs in individuals with ADHD. Such predictions can be made many years prior to age of the onset, and their SUD risks can be monitored using longitudinal models over years during child development. Nevertheless, more work is needed to create prediction models based on electronic health records or linked population registers that are sufficiently accurate for use in the clinic.