University Avenue Research Articles

Finding Our Way through the Maze

Pacing and Clinical ElectrophysiologyVolume 37, Issue 2 p. 144-146 EDITORIAL Finding Our Way through the Maze MELISSA H. KONG M.D., MELISSA H. KONG M.D. Silicon Valley Cardiology, East Palo Alto, California Sequoia Hospital, Redwood City, CaliforniaSearch for more papers by this authorROGER A. WINKLE M.D., Corresponding Author ROGER A. WINKLE M.D. Silicon Valley Cardiology, East Palo Alto, California Sequoia Hospital, Redwood City, CaliforniaAddress for reprints: Roger A. Winkle, M.D., Silicon Valley Cardiology, 1950 University Avenue, Suite 160, E. Palo Alto, CA 94303. Fax: 650-327–2947; e-mail: [email protected]Search for more papers by this author MELISSA H. KONG M.D., MELISSA H. KONG M.D. Silicon Valley Cardiology, East Palo Alto, California Sequoia Hospital, Redwood City, CaliforniaSearch for more papers by this authorROGER A. WINKLE M.D., Corresponding Author ROGER A. WINKLE M.D. Silicon Valley Cardiology, East Palo Alto, California Sequoia Hospital, Redwood City, CaliforniaAddress for reprints: Roger A. Winkle, M.D., Silicon Valley Cardiology, 1950 University Avenue, Suite 160, E. Palo Alto, CA 94303. Fax: 650-327–2947; e-mail: [email protected]Search for more papers by this author First published: 14 November 2013 https://doi.org/10.1111/pace.12294 Disclosures: None. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume37, Issue2February 2014Pages 144-146 RelatedInformation

Ketotifen in the management of chronic urticaria: resurrection of an old drug

Ketotifen is an oral antiallergic drug developed in 1970 by Sandoz Pharmaceuticals of Switzerland. It is a benzocycloheptathiophene derivative and was initially marketed as an inhibitor of anaphylaxis.1 The pharmacodynamic properties of ketotifen are many, because it is an inhibitor of the release and/or activity of mast cell and basophil mediators, including histamine, neutrophil, and eosinophil chemotactic factors, arachidonic acid metabolites, prostaglandins, and leukotrienes.2 Thus, it inhibits the bronchial response to inhaled histamine, allergen, or aspirin. In addition, the ocular, nasal, and dermal responses to applied allergen in sensitized patients are attenuated with use of ketotifen.3 It also has been found to have some calcium antagonist activity and to inhibit responses to platelet-activating factor from proinflammatory cells, such as eosinophils.2 Additional possible modes of action include its ability to reverse b2-agonisteinduced decreases in b-adrenoreceptor density and to alter the affinity of these receptors and increase intracellular concentrations of cyclic adenosine monophosphate.3 Ketotifen has a chemical structure similar to some first-generation antihistamines, such as cyproheptadine and azatidene.2 With regard to the pharmacokinetic properties of ketotifen, it is readily absorbed from the gastrointestinal tract after oral administration and achieves peak plasma concentrations within 2 to 4 hours of administration. Clearance of the drug from plasma is biphasic, with a half-life of distribution of 3 hours and a half-life of elimination of 22 hours in adults.3 However, the onset of action of ketotifen is slow, and it may take 4 to 6 weeks to achieve full prophylactic value under certain conditions.4 Ketotifen was originally patented by Sandoz in the 1970s. It became very popular for management of asthma in Japan and clinical trials were initiated in the United States in the 1980s for management of asthma and other allergic conditions. One author served on the Food and Drug Administration (FDA) Pulmonarye Allergy Drugs Advisory Committee and chaired that group from 1984 to 1986. Approval for treatment of asthma was not granted, but FDA staff did recommend more extensive evaluations for management of urticaria. Unfortunately, the latter studies have not been performed in a robust fashion. However, oral ketotifen has been used in patients with asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, chronic urticaria, cold-induced urticaria, cholinergic urticaria, exercise-induced urticaria, mastocytosis, and food allergy in Canada, Europe, and Mexico. Approval was granted for ocular administration in the United States for allergic conjunctivitis and later the drug became available over the counter. A review of clintrials.gov shows evaluations of ketotifen by oral administration for fibromyalgia, atopic dermatitis, attenuation of reactions during peanut desensitization, allergic rhinitis, asthma, and post-traumatic joint contractures. The authors became aware that ketotifen could be obtained in the United States from compounding pharmacies and began prescribing it more extensively in their clinics for severe urticaria in 2011. For adults and older children with asthma or allergic disease, the recommended dose of ketotifen is 1 mg twice daily. For young children 6 months to 3 years old, the recommended dose is 0.5 mg twice daily.3 It must be noted that oral ketotifen can be safely compounded in the United States. Pharmacy compounding is a practice in which a licensed pharmacist combines, mixes, or alters ingredients in response to a prescription to create a medication tailored to the medical needs of an individual patient. Pharmacy compounding, if performed properly, can serve an important public health need if a patient cannot be treated with an FDA-approved medication. The issue of safety of compounded drugs in the FDA Compliance Policy for Pharmacy Compounding is primarily for injectable drugs and does not relate to oral compounded drugs. This policy does include a select list of compounding drugs that were withdrawn or Reprints: Kristin C. Sokol, MD, MS, MPH, Division of Allergy and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555; E-mail: Kcsokol@utmb.edu. Disclosures: Authors have nothing to disclose. Funding Sources: This study was conducted with the support of the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award (UL1T71) from the National Center for Advancing Translational Sciences, National Institutes of Health.

Making a knockout mouse: From stem cells to embryos

Janet Rossant is a Senior Scientist and the Chief of Research at The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada. e-mail: janet.rossant@sickkids.ca the underlying principles and genetic pathways of development were conserved. I was very excited by the new research horizons opened by these developments. With Alex’s arrival, our labs started working together on the next challenges — testing the function of these newly identified genes in mouse development and finding more ways to identify other key developmental genes. We knew the answer must lie with ESCs. In 1981, Martin Evans and Matt Kaufman in Cambridge and Gail Martin in San Francisco had separately isolated pluripotent stem cells directly from the mouse blastocyst. Allan Bradley and Liz Robertson, in Martin Evans’s lab, and Achim Gossler in Rolf Kemler’s lab then provided proof-of-principle studies demonstrating that any genetic alteration introduced into these cells in culture could be transmitted through the germ line in chimaeras. Alex introduced ESC concepts to Toronto from San Francisco. When Achim Gossler joined my lab as a post-doc and brought germline-competent ESCs, we had the starting material for a major assault on gene functional analysis in the mouse. But how should we attack the problem? We knew about the promise of targeted mutagenesis by homologous recombination, developed in mammalian cells by Mario Capecchi and Oliver Smithies, but it had only been demonstrated to work in ESCs for genes such as Hprt, where one could select for mutation or correction of the gene. Would it be efficient enough to work for non-selectable genes such as engrailed? We pondered instead a random retroviral insertional approach, followed by a pooled polymerase chain reaction (PCR) assay to detect mutations in genes of interest. Achim and I also started to plan an enhancer trap approach, similarly to that developed in Drosophila melanogaster, to identify novel genes by expression of their associated enhancers in ESC chimaeras. However, when we heard from Oliver Smithies that he was developing a PCR-based approach to detect targeted mutations in non-selectable genes in ESCs, we abandoned the random insertional approach and put all our efforts into targeted mutagenesis with engrailed2 as the first target. We were fortunate to have Bill Skarnes join Alex’s lab as a graduate student at that time. He developed the targeting vector for En2, which was at the same time developed into a gene trap reporter vector, using the En2 splice acceptor to trap upstream exons in a lacZ fusion that would also disrupt the gene. Alex and I started the targeting experiments, picking portions of hundreds of individual neomycin-resistant colonies and assaying for targeted integrations using PCR. We began without a PCR machine — moving tubes by hand from waterbath to water-bath. Hints of success spurred us to purchase the second PCR machine ever sold in Canada, and, as they say, the rest is history. We published one of the first reports of successful targeting of a non-selectable gene in ESCs in Nature in 1989, and reported approaches for enhancer and gene-trap screens in ESCs in Science in the same year. The field of mammalian genetics was very rapidly transformed as more and more ways of manipulating the mouse germ line were developed by different groups. But it was a special time for me in Toronto, working in a great group of talented people, all with our own personalities and quirks, but all bringing our unique skills to make a successful team. The efforts of the International Knockout Mouse Consortium have made knockout mouse ESCs available off the shelf for almost the entire mouse genome, relegating the generation of a targeted mutation to supplementary material in most papers. And it seems that classical targeted mutagenesis in ESCs may be rapidly superseded by exciting new genome editing tools. Mammalian genetics moves on and new horizons await.

Informed Consent

From the Department of Obstetrics and Gynecology, Dalhousie University, IWK Health Center, Halifax, Nova Scotia, Canada. Reprints: Alfred Bent, MD, IWK Health Centre, 5850/5980 University Avenue, P.O. Box 9700, Halifax, Nova Scotia, B3K 6R8 Canada. E-mail: [email protected]. The author has declared that there are no conflicts of interest.

IQGAP1 is a novel phosphatidylinositol 4,5 bisphosphate effector in regulation of directional cell migration

Phosphatidylinositol 4,5 bisphosphate (PIP₂) is a key lipid messenger for regulation of cell migration. PIP₂ modulates many effectors, but the specificity of PIP₂ signalling can be defined by interactions of PIP₂-generating enzymes with PIP₂ effectors. Here, we show that type Iγ phosphatidylinositol 4-phosphate 5-kinase (PIPKIγ) interacts with the cytoskeleton regulator, IQGAP1, and modulates IQGAP1 function in migration. We reveal that PIPKIγ is required for IQGAP1 recruitment to the leading edge membrane in response to integrin or growth factor receptor activation. Moreover, IQGAP1 is a PIP₂ effector that directly binds PIP₂ through a polybasic motif and PIP₂ binding activates IQGAP1, facilitating actin polymerization. IQGAP1 mutants that lack PIPKIγ or PIP₂ binding lose the ability to control directional cell migration. Collectively, these data reveal a synergy between PIPKIγ and IQGAP1 in the control of cell migration.

The impacts of invasive grasses on wildlife: An international perspective

Wildlife Society BulletinVolume 37, Issue 3 p. 467-468 Invasive Plants and Wildlife Habitat The impacts of invasive grasses on wildlife: An international perspective William P. Kuvlesky Jr., Corresponding Author William P. Kuvlesky Jr. Caesar Kleberg Wildlife Research Institute, Texas A&M University-Kingsville, MSC 218, 700 University Boulevard, Kingsville, TX, 78363 USAE-mail: william.kuvlesky@tamuk.eduSearch for more papers by this author William P. Kuvlesky Jr., Corresponding Author William P. Kuvlesky Jr. Caesar Kleberg Wildlife Research Institute, Texas A&M University-Kingsville, MSC 218, 700 University Boulevard, Kingsville, TX, 78363 USAE-mail: william.kuvlesky@tamuk.eduSearch for more papers by this author First published: 26 August 2013 https://doi.org/10.1002/wsb.326 Associate Editor/Editor-in-Chief: Ribic. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume37, Issue3September 2013Pages 467-468 RelatedInformation

Effects of body size, gender, and prey availability on diets of snow crabs in the northern Bering Sea

Jason M. Kolts*, James R. Lovvorn, Christopher A. North, Jacqueline M. Grebmeier, Lee W. Cooper Department of Zoology and Physiology, University of Wyoming, 1000 E University Avenue, Laramie, Wyoming 82071, USA Department of Zoology and Center for Ecology, Southern Illinois University, 1125 Lincoln Drive, Carbondale, Illinois 62901, USA Program in Ecology, University of Wyoming, 1000 E University Avenue, Laramie, Wyoming 82071, USA Chesapeake Biological Laboratory, University of Maryland Center for Environmental Science, 146 Williams Street, PO Box 38, Solomons, Maryland 20688, USA

Consequences of delayed therapy for sports‐related bleeds in patients with mild‐to‐moderate haemophilia and type 3 von Willebrand's disease not on prophylaxis

HaemophiliaVolume 19, Issue 4 p. e264-e267 Letter to the Editor Consequences of delayed therapy for sports-related bleeds in patients with mild-to-moderate haemophilia and type 3 von Willebrand's disease not on prophylaxis R. Kumar, R. Kumar Division of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, CanadaSearch for more papers by this authorA. M. Stain, A. M. Stain Department of Nursing, The Hospital for Sick Children, University of Toronto, Toronto, ON, CanadaSearch for more papers by this authorP. Hilliard, P. Hilliard Department of Rehabilitation Services, The Hospital for Sick Children, University of Toronto, Toronto, ON, CanadaSearch for more papers by this authorM. Carcao, Corresponding Author M. Carcao Division of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada Correspondence: Manuel Carcao, MD, FRCP., The Hospital for Sick Children, 555 University Avenue, Room 9416, Black Wing, Toronto, ON – M5G 1X8, Canada. Tel.: +(416) 237-6484 (voice); fax: +(416) 813-5327; e-mail: [email protected]Search for more papers by this author R. Kumar, R. Kumar Division of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, CanadaSearch for more papers by this authorA. M. Stain, A. M. Stain Department of Nursing, The Hospital for Sick Children, University of Toronto, Toronto, ON, CanadaSearch for more papers by this authorP. Hilliard, P. Hilliard Department of Rehabilitation Services, The Hospital for Sick Children, University of Toronto, Toronto, ON, CanadaSearch for more papers by this authorM. Carcao, Corresponding Author M. Carcao Division of Haematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada Correspondence: Manuel Carcao, MD, FRCP., The Hospital for Sick Children, 555 University Avenue, Room 9416, Black Wing, Toronto, ON – M5G 1X8, Canada. Tel.: +(416) 237-6484 (voice); fax: +(416) 813-5327; e-mail: [email protected]Search for more papers by this author First published: 07 May 2013 https://doi.org/10.1111/hae.12162Citations: 10Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume19, Issue4July 2013Pages e264-e267 RelatedInformation

When Perception Is Reality

Criminology & Public PolicyVolume 12, Issue 2 p. 283-294 POLICY ESSAY When Perception Is Reality 287(g)—A Solution in Search of a Problem Terry Coonan, Corresponding Author Terry Coonan Florida State UniversityDirect correspondence to Terry Coonan, Center for the Advancement of Human Rights, 426 West Jefferson, Florida State University, 600 W. College Avenue, Tallahassee, FL 32306 (e-mail: tcoonan@admin.fsu.edu).Search for more papers by this author Terry Coonan, Corresponding Author Terry Coonan Florida State UniversityDirect correspondence to Terry Coonan, Center for the Advancement of Human Rights, 426 West Jefferson, Florida State University, 600 W. College Avenue, Tallahassee, FL 32306 (e-mail: tcoonan@admin.fsu.edu).Search for more papers by this author First published: 21 November 2013 https://doi.org/10.1111/1745-9133.12036Citations: 2Read the full textAboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume12, Issue2May 2013Pages 283-294 RelatedInformation

Forgive Yourself, Dear WriterAlive in the Writing: Crafting Ethnography in the Company of Chekhov. By Kirin Narayan. Chicago: University of Chicago Press, 2012.

Previous articleNext article No AccessBook and Film ReviewsForgive Yourself, Dear Writer Alive in the Writing: Crafting Ethnography in the Company of Chekhov. By Kirin Narayan. Chicago: University of Chicago Press, 2012.Ruth BeharRuth BeharDepartment of Anthropology, University of Michigan, 228-A West Hall, 1085 South University Avenue, Ann Arbor, Michigan 48209-1107, U.S.A. ([email protected]). Search for more articles by this author PDFPDF PLUSFull Text Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by Current Anthropology Volume 54, Number 2April 2013 Sponsored by the Wenner-Gren Foundation for Anthropological Research Article DOIhttps://doi.org/10.1086/669935 Views: 99Total views on this site HistoryReceived January 07, 2013 For permission to reuse, please contact [email protected]PDF download Crossref reports no articles citing this article.

To write alone or not to write alone, that is the question

Correspondence: David E Vance Center for Nursing Research, School of Nursing, 1701 University Boulevard, University of Alabama at Birmingham, Birmingham, AL 35294-1210, USA Tel +1 20 59347589 Fax +1 20 5996 7183 Email devance@uab.edu Over the past 20 years, I have written and published over 150 book chapters and journal articles, with others and alone. Despite such collaborative efforts in generating articles, writing itself is a solitary act, requiring a great deal of concentration, knowledge, and dedication, along with a keen eye for detail. And it is that solitary approach that I would like to address. Since writing is such a solitary exercise, why do we write in groups? Clearly, fantastic advantages (eg, insights in conceptualization, help with interpretation and analysis of data, valuable feedback in revising the article) as well as dismal disadvantages (eg, personality clashes, extra time needed) exist for doing so. In fact, viewing scientific writing as a continuum ranging from a single/solo author to a team of multiple coauthors, a few of the pros and cons can be observed along both ends of this framework as is outlined in Figure 1; these include authorship determination, amount of workload, coordination of others, production speed, and quality checks. Starting at the solo author end of this continuum, let me begin by saying, I prefer to work on articles alone, at least initially as I’m developing the ideas, pulling the reference materials together, developing the outline, and putting pen to paper. Although I handle most of the workload when I draft the article, one reason I prefer writing alone is because when I complete a draft of the article there is no doubt that I am the first author because most of the article reflects my original thoughts and insights. Another reason I prefer to write alone is that I can be as creative and unorthodox in my reasoning as I like; likewise, I can focus on the topics that appeal to me. From a “going for promotion” perspective, I also like writing alone because I am in control of how fast the article will be written; if it does not get done, I have no one to blame but myself. But if I am writing with others, many times the production of the article is delayed as I wait on my coauthors to finish their substantial contributions which in some instances can linger for months (or in rare cases years). Yet there are several disadvantages to writing alone, such as lacking a specific skill set or knowledge base needed to improve the article. Also, let us not discount the value of balancing one’s point of view with the professional perspective of someone from another discipline; such intellectual feedback certainly can contribute to the enhancement of the article. Given these compelling reasons, I try to balance the advantages and disadvantages of both sides of the solo – team writing continuum by adopting a middle path. Once the article is drafted, I frequently invite colleagues with expertise in certain areas, to substantially contribute to the conception and interpretation of the findings of the Dovepress

Chronic Nonbacterial Osteomyelitis in a Child with Previous Juvenile Dermatomyositis

To the Editor: Chronic nonbacterial osteomyelitis (CNO) is a sterile osteitis of unknown etiology. The diagnosis is based on characteristic clinical, laboratory, and imaging features1. Currently, CNO is considered an autoinflammatory disorder. However, the association of CNO with inflammatory bowel diseases2, psoriasis3, and vasculitis suggests that both innate and adaptive immunity may contribute to pathogenesis. A 3-year-old girl presented with proximal muscle weakness, Gottron papules, and periorbital heliotrope rash. Erythrocyte sedimentation rate (ESR) was 30 mm/h (normal 0–12 mm/h); creatine kinase, aspartate aminotransferase, and lactate dehydrogenase were normal. Antinuclear autoantibody (ANA) titers were 1:320; antibodies against Jo-1, ribonuclear proteins, Smith, Ro, La, Scl-70, and double-stranded DNA were not detected. Muscle biopsy result was consistent with dermatomyositis. She was started on oral corticosteroids 1.5 mg/kg/day and methotrexate 0.5 mg/kg weekly. After 9 months, muscle strength normalized and treatment was discontinued. Family history revealed that her brother and maternal grandmother had psoriasis and a paternal uncle was diagnosed with Crohn disease (Figure 1). Figure 1. The family history of a child with chronic recurrent nonbacterial osteomyelitis and previous … Address correspondence to Dr. R.M. Laxer, Division of Rheumatology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada. E-mail: ronald.laxer{at}sickkids.ca

Biologic Drug Access and Juvenile Idiopathic Arthritis in Canada: Improving Collaboration Between Clinician Experts and Funders

To the Editor: We read with great interest the article by LeBlanc, et al , “ Access to Biologic Therapies in Canada for Children with Juvenile Idiopathic Arthritis”1. We congratulate the authors for highlighting the challenges for Canada’s healthcare system in delivering equitable drug access across the country when healthcare is provincially delivered and there is still no national pharmaceutical program. This is particularly important in areas such as juvenile idiopathic arthritis (JIA), where because of the rarity of the underlying condition, the development of different funding decisions across provinces and territories leads to inefficient drug policy. Provincial governments should be encouraged to review the advice of national organizations such as the Canadian Agency for Drugs and Technologies in Health (CADTH) and the pan-Canadian Oncology Drug Review (pCODR). These organizations provide evidence-based information about health technologies, including drugs, with the goal of harmonizing drug funding across the country. We would like to clarify a few misconceptions in the LeBlanc article. First, the authors stated … Address correspondence to Dr. E. Cohen, Department of Pediatrics and Institute of Health Policy, Management and Evaluation, University of Toronto, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada; E-mail: eyal.cohen{at}sickkids.ca

Ms Hassanzadeh, et al reply

To the Editor: We thank Dr. Kapoor for his interest1 in our recent article on the use of subcutaneous methotrexate (MTX)2. He lists the rare side effects of this drug but fails to point out … Address correspondence to Dr. R. Hassanzadeh, University of Glasgow – Medical School, Wolfson Medical School Building, University Avenue, Glasgow G12 8QQ, UK. E-mail: royahmr{at}googlemail.com

Crystal ball – 2013

Crystal ball – 2013

Treatment of attention deficit hyperactivity disorder insomnia with blue wavelength light-blocking glasses

Correspondence: Rachel Fargason 3rd Floor Callahan Eye Foundation Hospital, 1720 University Boulevard, Birmingham, AL 35294, USA Tel +1 205 934 4301 Fax +1 205 975 9600 Email Rfargason@uab.edu Background: The aim of this study was to examine a nonmedical treatment alternative to medication in attention deficit hyperactivity disorder (ADHD) insomnia, in which blue wavelength light-blocking glasses are worn during the evening hours to counteract the phase-delaying effect of light. Outcome measures included sleep quality and midsleep time. The capacity of ADHD subjects to comply with treatment using the glasses was assessed. Methods: Daily bedtime, wake-up time, and compliance diaries were used to assess sleep quality and timing during a baseline observation week and a 2-week intervention period. The Pittsburgh Sleep Quality Index (PSQI) was administered following baseline and intervention. The intervention protocol consisted of use of blue wavelength-blocking glasses and a moderate lighting environment during evening hours. Results: Partial and variable compliance were noted, with only 14 of 22 subjects completing the study due to nonadherence with wearing the glasses and diary completion. Despite the minimum 3-hour recommendation, glasses were worn, on average, for 2.4 hours daily. Lighting was reduced for only 58.7% of the evening. Compared with baseline, the intervention resulted in significant improvement in global PSQI scores, PSQI subcomponent scores, and sleep diary measures of morning refreshment after sleep (P = 0.037) and night-time awakenings (P = 0.015). Global PSQI scores fell from 11.15 to 4.54, dropping below the cut-off score of 5 for clinical insomnia. The more phase-delayed subjects, ie, those with an initial midsleep time after 4:15 am, trended towards an earlier midsleep time by 43.2 minutes following the intervention (P = 0.073). Participants reported less anxiety following the intervention (P = 0.048). Conclusions: Despite only partial compliance with intervention instructions, subjects completing the study showed subjectively reduced anxiety and improved sleep quality on multiple measures. The more sleep-delayed subjects trended toward an earlier sleep period following use of the glasses. Blue-blocking glasses are a potential insomnia treatment for more compliant subjects with ADHD insomnia, especially those with prominent sleep delay. Larger studies of blue light-blocking glasses in more phase-delayed groups could reveal significant advances in chronotherapeutics.

Dramatic Response to Sirolimus in Lymphangioleiomyomatosis

Depatrment of Respirology, University of Toronto, Toronto General Hospital, Toronto, Ontario Correspondence: Dr Dmitry Rozenberg, Depatrment of Respirology, Toronto General Hospital, 9N 965 – 585 University Avenue, Toronto, Ontario M5G 2N2. Telephone 416-340-4591, fax 416-340-3109, e-mail dmitry.rozenberg@uhn.ca A 41-year-old woman presented with a one-year history of progressive dyspnea, early satiety and abdominal cramping. A clinical diagnosis of lymphangioleiomyomatosis (LAM) was made based on a confirmed right-sided chylous effusion (milky, exudative and triglyceride level of 52.6 mmol/L) and characteristic cystic changes on a highresolution computed tomography scan of the chest (Figure 1). A large left-sided retroperitoneal lymphangioleiomyoma supported the diagnosis (Figure 2), with no renal angiomyolipoma or clinical evidence of tuberous sclerosis. She was started on sirolimus therapy, which resolved her dyspnea and abdominal symptoms within six months. Her forced expiratory volume in 1 s (FEV1) (1.6 L) and FVC (2.1 L) had markedly improved during this time interval to 2.6 L and 4.2 L, respectively. Her chest x-ray demonstrated almost complete resolution of the right pleural effusion (Figure 3) and the lymphangioleiomyoma had also decreased in size (Figure 4). The patient remains clinically stable on sirolimus with few side effects and her FEV1 and FVC on therapy at nine months increased to 3.3 L (96%) and 4.8 L (118%), respectively. The present case is a dramatic example of a chylous pleural effusion and massive intra-abdominal lymphangioleiomyoma responding to sirolimus therapy. images in respiratory meDicine

Central nervous system juvenile xanthogranuloma after langerhans cell histiocytosis

Pediatric Blood & CancerVolume 60, Issue 2 p. 342-343 Letter to the Editor Central nervous system juvenile xanthogranuloma after langerhans cell histiocytosis Oussama Abla MD, Corresponding Author Oussama Abla MD oussama.abla@sickkids.ca Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, CanadaDivision of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.===Search for more papers by this authorWilliam Halliday MD, William Halliday MD Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, CanadaSearch for more papers by this authorSuzanne Laughlin MD, Suzanne Laughlin MD Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, CanadaSearch for more papers by this authorSheila Weitzman MD, FRCP, Sheila Weitzman MD, FRCP Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, CanadaSearch for more papers by this author Oussama Abla MD, Corresponding Author Oussama Abla MD oussama.abla@sickkids.ca Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, CanadaDivision of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.===Search for more papers by this authorWilliam Halliday MD, William Halliday MD Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, CanadaSearch for more papers by this authorSuzanne Laughlin MD, Suzanne Laughlin MD Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, CanadaSearch for more papers by this authorSheila Weitzman MD, FRCP, Sheila Weitzman MD, FRCP Division of Haematology/Oncology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, CanadaSearch for more papers by this author First published: 25 October 2012 https://doi.org/10.1002/pbc.24379Citations: 8Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume60, Issue2February 2013Pages 342-343 RelatedInformation

Healthy Child Uganda survey of knowledge, attitude and behaviour of village health team members toward their health care responsibilities in southwest Uganda

1Department of Psychiatry, Mbarara University of Science and Technology; 2Healthy Child Uganda (HCU); 3Department of Paediatrics, Mbarara University of Science and Technology, Mbarara, Uganda; 4Department of Paediatrics, Dalhousie University, Halifax, Nova Scotia; 5CPS/CCHCSP Mentor Correspondence: Dr Noni MacDonald, Department of Paediatrics, IWK Health Centre, 5850/5980 University Avenue, Halifax, Nova Scotia B3K 6R8. Website www.microresearch.ca Accepted for publication July 12, 2012 The village health team (VHT) program was started in 2001 by the Ministry of Health in Uganda and later supported by Healthy Child Uganda (HCU) (www.healthychilduganda.org), a collaboration between a Ugandan and several Canadian universities and the Canadian Paediatric Society, with a goal of improving maternal child health in southwest Uganda. VHT members are volunteers with brief, VHT-specific training who work together to promote healthy practices in sanitation, immunization and good nutrition in the community and at the household level, as well as appropriate use of District Health Centres. The aim of the present study was to determine the knowledge, attitudes and behaviours of VHT members toward their village health care responsibilities comparing HCUsupported versus Ugandan government (UG)-supported VHTs.

Data falsification should be a criminal offence

Dear Sir, I read with interest the two articles on academic fraud in the August 2012 issue of Bone & Joint360 .1,2 They are well-written, thought-provoking and a must read for researchers and clinicians. Written by two highly respected medical professionals, they have a slightly different perspective and emphasis. Marcovitch’s article focuses more on fraud, the falsification of data to support invalid conclusions, and gives examples of this in the literature. To some degree he also talks about plagiarism but the article by Rajasekaran puts more of an emphasis on this and in particular about what he feels is the underlying cause (i.e. publish to flourish) of this problem. Cheating in publishing should be divided into fraud and plagiarism and not grouped together. Both are forms of cheating with some overlap …