Publications by authors named "James Connell"

44 Publications

Xanthogranuloma of the external auditory canal-an atypical anatomical manifestation.

J Surg Case Rep 2021 Mar 31;2021(3):rjaa536. Epub 2021 Mar 31.

Department of Otolaryngology Head and Neck Surgery, Modbury Hospital, Adelaide, South Australia, Australia.

Juvenile xanthogranuloma is a proliferative cutaneous manifestation encountered in the paediatric population. Adult cases are uncommon, but have been reported. Lesions are prevalent in the head and neck region, but rarely observed in the external auditory canal. We present the case of a 39-year-old female with a rapidly progressing obstructive soft tissue lesion of the external auditory canal. Surgical excision diagnosed the lesion as a rarely observed otological manifestation of juvenile xanthogranuloma. Surgical excision was curative with no locoregional recurrence. Otolaryngologists should consider juvenile xanthogranuloma as a differential for atypical soft tissue cutaneous lesions of the head and neck, including in divergent populations.
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http://dx.doi.org/10.1093/jscr/rjaa536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023365PMC
March 2021

Sexual Health Knowledge, Attitudes, and Perceptions Among Men Who Have Sex With Men During Co-Occurring Sexually Transmitted Infection Epidemics in Toronto, Canada: A Qualitative Study.

Sex Transm Dis 2020 10;47(10):658-662

School of Population and Public Health, University of British Columbia, Vancouver, Canada.

Background: Our objective was to explore the sexual health knowledge, attitudes, and perceptions of men who have sex with men (MSM).

Methods: In-depth interviews were conducted with 31 MSM who lived, worked, or socialized in Toronto in June and July 2016. Participants were asked about concepts of risky sex and knowledge of, and attitudes toward, sexually transmitted infections (STIs), especially syphilis, and potential interventions. Thematic analysis was used to analyze interview transcripts.

Results: The prevention of STI relied on HIV prevention strategies. No one used condoms for oral sex, nor did they intend to. Pre-exposure prophylaxis was perceived as both threatening and liberating. Concepts of risky sex included emotional risk. Conversations with partners about STI testing were easier than STI status. Stigma and concealment of sexual identity were barriers to sexual health care. None of the participants recommended sexual behavior or sexual health interventions. Instead, recommendations centered on social changes to reduce or eliminate shame, embarrassment, stigma, and discrimination around both STIs and sexual orientation.

Conclusion: Participants were thinking about sexual risk and using a variety of ways to prevent STI transmission, although most relied on HIV prevention strategies, possibly because they knew little about other STIs, and other STIs were perceived as curable, especially syphilis. Interventions promoting conversations about STI testing may be promising and will also reduce stigma as STI testing is normalized. Social and clinic interventions focused on creating psychologically safe spaces to disclose sexual identity and providing sexual orientation affirming health care may reduce STIs and improve sexual health for MSM.
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http://dx.doi.org/10.1097/OLQ.0000000000001237DOI Listing
October 2020

'… if U equals U what does the second U mean?': sexual minority men's accounts of HIV undetectability and untransmittable scepticism.

Cult Health Sex 2020 Jul 23:1-17. Epub 2020 Jul 23.

BC Centre for Disease Control, Faculty of Medicine, University of British Columbia, Vancouver, Canada.

The everyday meaning and use of HIV 'undetectability' raises significant questions about the social and sexual significance of this state of viral suppression. We conducted in-depth, semi-structured interviews with 25 sexual minority men living in Vancouver, Canada, including men living with HIV. Interviews were audio-recorded, transcribed verbatim and analysed using grounded theory. Most participants understood being undetectable to signify that someone living with HIV is at a 'low,' 'lower,' or 'slim to no' risk of sexually transmitting HIV, as opposed to meaning 'uninfectious' or 'untransmittable'. Men discussed how undetectability was communicated in-person and online, including via sexual networking apps, and revealed how it is sometimes confused or conflated with another biomedical advance in HIV-prevention, namely pre-exposure prophylaxis (PrEP). HIV-negative men expressed significant scientific scepticism, a reluctance to incorporate a partner's low viral load or undetectable HIV status into their sexual decision-making, and an enduring fear associated with knowingly having sex with someone who is HIV-positive. We describe this as a form of . While international campaigns have worked to communicate the scientific message that 'undetectable equals untransmittable' (U = U), the sexual stigma attached to HIV remains durable among some gay, bisexual, queer and other men who have sex with men.
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http://dx.doi.org/10.1080/13691058.2020.1776397DOI Listing
July 2020

Knowledge and attitudes of syphilis and syphilis pre-exposure prophylaxis (PrEP) among men who have sex with men in Vancouver, Canada: a qualitative study.

BMJ Open 2019 11 21;9(11):e031239. Epub 2019 Nov 21.

Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada

Objectives: In British Columbia, Canada, syphilis is at record-high rates, with over 80% of cases in 2017 seen in gay, bisexual and other men who have sex with men (GBM). The syphilis epidemic is of particular concern for those living with HIV, since syphilis may lead to more serious complications in this population. We sought to explore syphilis-related knowledge and attitudes around biomedical prevention options for syphilis, with the goal of informing effective strategies to prevent syphilis.

Design: We conducted a qualitative study consisting of in-depth, individual interviews from December 2016 to June 2017. Our interviews focused on participants' knowledge about syphilis and perceptions regarding syphilis pre-exposure prophylaxis (PrEP). Interviews were analysed using Grounded Theory.

Participants: Twenty-five GBM were interviewed (64% white; median age: 43 years), including men living with HIV and/or with a history of syphilis.

Setting: Vancouver, British Columbia.

Results: Five interrelated themes emerged. First, GBM were aware of the local syphilis epidemic. Second, syphilis-related knowledge differed according to syphilis and HIV serostatus. Third, competing ideas emerged regarding men's concerns about syphilis. While our participants expressed concern about getting syphilis, they also described the importance of sexual pleasure. Fourth, many participants said that syphilis was not perceived to be alarming; preventing HIV infection remained a primary concern for many. Finally, while syphilis PrEP was appealing to those living with HIV or a prior syphilis diagnosis, others were concerned about antibiotic resistance, cost and side effects.

Conclusions: Our participants organised their safer sex strategies around HIV, not syphilis. Although syphilis-related knowledge was relatively high among GBM living with HIV and those with a prior syphilis diagnosis, this knowledge did not appear to be related with safer sexual practices, such as increased condom use. This work highlights the importance of examining other potential prevention solutions, such as syphilis PrEP.
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http://dx.doi.org/10.1136/bmjopen-2019-031239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886914PMC
November 2019

The Social Geography of Partner Selection in Toronto, Canada: A Qualitative Description of "Convection Mixing".

Arch Sex Behav 2020 07 18;49(5):1839-1851. Epub 2019 Oct 18.

Department of Social and Preventative Medicine, School of Public Health, University of Montreal, Montreal, PQ, Canada.

The geographic distribution of sexually transmitted infections reflects the underlying social process of sexual partner selection. This qualitative study explored the social geography of partner selection among sexual minority men and used the results to develop a mid-range theory of STI transmission. In-depth interviews with 31 sexual minority men who lived, worked, or socialized in Toronto, Canada, occurred in June and July 2016. Participants were asked how they found sexual partners and reconstructed their egocentric sexual networks for the previous 3 months. Participants described an iterative process of partner selection involving intention (sex versus dating), connecting with community, and selecting a partner based on intersecting partner characteristics (external, internal, and emergent feelings when interacting with potential partners) and personal preferences. Geography influenced partner selection three ways: (1) participant search patterns maximized the number of potential partners in the shortest distance possible; (2) the density of sexual minority men in a participant's community directly impacted participant's social and sexual isolations; and (3) geosexual isolation influenced sexual mixing patterns. Participants described "convection mixing," where assortative urban mixing nested within disassortative suburban mixing resulted in movement from the suburbs to downtown and back to the suburbs. We theorize that convection mixing may be contributing to the persistence of STI epidemics in core and outbreak areas by creating STI reservoirs outside of, and connected to, core and outbreak areas.
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http://dx.doi.org/10.1007/s10508-019-01484-1DOI Listing
July 2020

ESCRT-III-associated proteins and spastin inhibit protrudin-dependent polarised membrane traffic.

Cell Mol Life Sci 2020 Jul 5;77(13):2641-2658. Epub 2019 Oct 5.

Department of Medical Genetics and Cambridge Institute for Medical Research, The Keith Peters Building, Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0XY, UK.

Mutations in the gene encoding the microtubule severing ATPase spastin are the most frequent cause of hereditary spastic paraplegia, a genetic condition characterised by length-dependent axonal degeneration. Here, we show that HeLa cells lacking spastin and embryonic fibroblasts from a spastin knock-in mouse model become highly polarised and develop cellular protrusions. In HeLa cells, this phenotype was rescued by wild-type spastin, but not by forms unable to sever microtubules or interact with endosomal ESCRT-III proteins. Cells lacking the spastin-interacting ESCRT-III-associated proteins IST1 or CHMP1B also developed protrusions. The protrusion phenotype required protrudin, a RAB-interacting protein that interacts with spastin and localises to ER-endosome contact sites, where it promotes KIF5-dependent endosomal motility to protrusions. Consistent with this, the protrusion phenotype in cells lacking spastin also required KIF5. Lack or mutation of spastin resulted in functional consequences for receptor traffic of a pathway implicated in HSP, as Bone Morphogenetic Protein receptor distribution became polarised. Our results, therefore, identify a novel role for ESCRT-III proteins and spastin in regulating polarised membrane traffic.
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http://dx.doi.org/10.1007/s00018-019-03313-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320071PMC
July 2020

Teaching an Adult With Autism Spectrum Disorder to Use an Activity Schedule During a Vocational Beekeeping Task.

Behav Anal Pract 2019 Jun 30;12(2):435-439. Epub 2018 Oct 30.

AJ Drexel Autism Institute, Drexel University, 3020 Market Street, Suite 560, Philadelphia, PA 19104 USA.

Recent federal legislation passed supports investment in sustainable green jobs. Beekeeping is one type of sustainable vocation. Activity schedules have shown effectiveness in increasing the independence of children with autism engaged in various tasks. This study investigated the effects of a treatment package consisting of an activity schedule plus contingent reinforcement on increasing the number of steps completed independently by an adult with autism employed at an apiary. The data demonstrate that the treatment package led to a higher percentage of steps completed correctly.
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http://dx.doi.org/10.1007/s40617-018-00306-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745568PMC
June 2019

Acute peritonsillar swelling: a unique presentation for Kawasaki disease in adolescence.

BMJ Case Rep 2018 Jul 24;2018. Epub 2018 Jul 24.

Women's & Children's Hospital, Adelaide, South Australia, Australia.

We report the case of a 14-year-old man with unilateral peritonsillar swelling, airway compromise and fever. On physical examination, the patient was pyrexic with trismus, dysphonia, uvula deviation, exudative unilateral peritonsillar swelling and unilateral cervical lymphadenopathy. Attempts at aspirating the prominent peritonsillar region were unsuccessful. CT head and neck identified a large inflammatory mass arising from the left palatine tonsil. The patient was treated for presumptive peritonsillar abscess. After failing to respond to intravenous antimicrobials, he progressively developed the classical sequale of Kawasaki's Disease. Echocardiogram identified coronary arteritis. Intravenous immunoglobulin and high-dose aspirin were initiated and his clinical picture improved. Kawasaki's disease mimicking an acute infective process can pose a diagnostic dilemma. It is an uncommon differential in the adolescent population. Prompt recognition and initiation of appropriate therapy are imperative to minimise morbidity.
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http://dx.doi.org/10.1136/bcr-2018-224441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059251PMC
July 2018

Conceptualizing Geosexual Archetypes: Mapping the Sexual Travels and Egocentric Sexual Networks of Gay and Bisexual Men in Toronto, Canada.

Sex Transm Dis 2018 06;45(6):368-373

From the Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Background: There are complex, synergistic, and persistent sexually transmitted infection (STI) epidemics affecting gay, bisexual and other men who have sex with men (gbMSM) in every major urban centre across North America. We explored the spatial architecture of egocentric sexual networks for gbMSM in Toronto, Canada.

Methods: Our integrative mixed methods study included in-depth interviews with 31 gbMSM between May and July 2016. During interviews, participants mapped their egocentric sexual network for the preceding 3 months geographically. At the end, a self-administered survey was used to collect sociodemographic characteristics, online technology use, and STI testing and history.

Results: We identified 6 geosexual archetypes: hosters, house-callers, privates, rovers, travellers, and geoflexibles. Hosters always, or almost always (≥80%), hosted sex at their home. House-callers always, or almost always (≥80%), had sex at their partner's home. Rovers always or almost always (≥80%) had sex at public venues (eg, bath houses, sex clubs) and other public spaces (eg, parks, cruising sites). Privates had sex in private-their own home or their partner's (part hoster, part house-caller). Travellers had sex away from their home, either at a partner's home or some other venue or public space (part house-caller, part rover). Geoflexibles had sex in a variety of locations-their home, their partner's home, or public venues. All hosters and rovers, and to a lesser extent, geoflexibles, reported a history of syphilis and human immunodeficiency virus.

Conclusions: Prioritizing interventions to hosters, rovers, and geoflexibles may have an important impact on reducing STI transmission.
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http://dx.doi.org/10.1097/OLQ.0000000000000752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959212PMC
June 2018

The medical home for children with autism spectrum disorder: an essential element whose time has come.

Curr Opin Pediatr 2018 04;30(2):311-317

Department of Pediatrics, St. Christopher's Hospital for Children.

Purpose Of Review: The purpose of this review is to describe the role of the medical home in children with autism spectrum disorder (ASD). A high-quality medical home is essential, given the increase in prevalence of ASD and the array of services, community partners, specialists, therapists, and healthcare team members needed to care for this population.

Recent Findings: Providing care through the medical home model results in fewer unmet needs. Care coordination and integration are the aspects of the medical home currently most lacking. Navigating the healthcare landscape for children with ASD may be enhanced with patient navigators, integration of physical and behavioral health, and telehealth services.

Summary: Children with ASD have an increased number of medical and mental health needs. Obtaining care via a medical home has been shown to decrease unmet healthcare needs. However, they are less likely to receive care through the medical home model compared with other children with special healthcare needs. Barriers identified by families include a lack of early identification, limited knowledge on educational plans, and unknown community resources. Barriers identified by providers include lack of time, training, and resources. Providing care coordination and family-centered care in a medical home model are essential for children with ASD.
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http://dx.doi.org/10.1097/MOP.0000000000000605DOI Listing
April 2018

Expression characterization of the herbicide tolerance gene Aryloxyalkanoate Dioxygenase (aad-1) controlled by seven combinations of regulatory elements.

BMC Plant Biol 2018 01 15;18(1):14. Epub 2018 Jan 15.

Dow AgroSciences, LLC, 9330 Zionsville Rd, Indianapolis, IN, 46268, USA.

Background: Availability of well characterized maize regulatory elements for gene expression in a variety of tissues and developmental stages provides effective alternatives for single and multigene transgenic concepts. We studied the expression of the herbicide tolerance gene aryloxyalkanoate dioxygenase (aad-1) driven by seven different regulatory element construct designs including the ubiquitin promoters of maize and rice, the actin promoters of melon and rice, three different versions of the Sugarcane Bacilliform Badnavirus promoters in association with other regulatory elements of gene expression.

Results: Gene expression of aad-1 was characterized at the transcript and protein levels in a collection of maize tissues and developmental stages. Protein activity against its target herbicide was characterized by herbicide dosage response. Although differences in transcript and protein accumulation were observed among the different constructs tested, all events were tolerant to commercially relevant rates of quizalafop-P-ethyl compared to non-traited maize under greenhouse conditions.

Discussion: The data reported demonstrate how different regulatory elements affect transcript and protein accumulation and how these molecular characteristics translate into the level of herbicide tolerance. The level of transcript detected did not reflect the amount of protein quantified in a particular tissue since protein accumulation may be influenced not only by levels of transcript produced but also by translation rate, post-translational regulation mechanisms and protein stability. The amount of AAD-1 enzyme produced with all constructs tested showed sufficient enzymatic activity to detoxify the herbicide and prevent most herbicidal damage at field-relevant levels without having a negative effect on plant health.

Conclusions: Distinctive profiles of aad-1 transcript and protein accumulation were observed when different regulatory elements were utilized in the constructs under study. The ZmUbi and the SCBV constructs showed the most consistent robust tolerance, while the melon actin construct provided the lowest level of tolerance compared to the other regulatory elements used in this study. These data provide insights into the effects of differing levels of gene expression and how these molecular characteristics translate into the level of herbicide tolerance. Furthermore, these data provide valuable information to optimize future designs of single and multiple gene constructs for maize research and crop improvement.
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http://dx.doi.org/10.1186/s12870-018-1227-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5769356PMC
January 2018

Behavior Skills Training with Voice-Over Video Modeling.

J Organ Behav Manage 2018 3;38(2-3):258-273. Epub 2018 May 3.

University of Pennsylvania.

The present study used behavior skills training (BST) to teach three adult participants to implement a video modeling intervention aimed at teaching social skills to adults with autism spectrum disorder (ASD). During baseline trials, participants were given access to written instructions before role-play with two actors (who simulated a quiet conversation) and one confederate (who played the role of an adult with ASD). During treatment, participants were given a video model with voiceover instruction depicting how to implement the video modeling intervention to teach social skills, repeated roleplay trials, and feedback following their performance. All participant scores (percentage of steps correctly implemented in each session) increased from baseline to treatment, and generalization was demonstrated with an actual consumer diagnosed with ASD. Additionally, after training participants to use a video model to teach one social skill, there was generalization to teaching as many as three additional novel social skills. Participants showed maintenance of skills during a treatment study that involved training adult clients with ASD to engage in the social skills.
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http://dx.doi.org/10.1080/01608061.2018.1454871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768417PMC
May 2018

Saphenovenous Graft Aneurysm: A Rare Complication of CABG.

Case Rep Cardiol 2017 18;2017:8101489. Epub 2017 May 18.

Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia.

Saphenovenous graft aneurysm is a rare complication of coronary artery bypass grafts that is likely underdiagnosed. It is typically asymptomatic, slow growing, and often diagnosed incidentally on angiography or following catastrophic rupture. There is no consensus on best management but PCI and surgery appear to have more favourable mortality outcomes relative to conservative management. We present the case of a 48-year-old male with a cardiovascular risk profile hallmarked by diabetes mellitus, end stage renal failure, recalcitrant hyperlipidaemia, and IHD previously treated with CABG. 11 years following his CABG, he was retrieved from remote Australia to a tertiary cardiology centre with stabbing chest pain. Serial cardiac enzymes were negative. Echocardiogram identified a mass compressing the right ventricular wall. Noncontrast coronary angiogram ultimately identified a large aneurysm at the proximal end of SVG to PDA. He was managed with aggressive risk factor modification prior to planned surgical intervention once medically optimized. His case supports the role of aggressive medical management combined with surgical intervention.
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http://dx.doi.org/10.1155/2017/8101489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451847PMC
May 2017

Sleep in Children with Autism Spectrum Disorder.

Curr Psychiatry Rep 2017 Jun;19(6):34

University of Pennsylvania School of Nursing, 418 Curie Blvd, Philadelphia, PA, 19104, USA.

The purposes of this paper are to provide an overview of the state of the science of sleep in children with autism spectrum disorder (ASD), present hypotheses for the high prevalence of insomnia in children with ASD, and present a practice pathway for promoting optimal sleep. Approximately two thirds of children with ASD have chronic insomnia, and to date, the strongest evidence on promoting sleep is for sleep education, environmental changes, behavioral interventions, and exogenous melatonin. The Sleep Committee of the Autism Treatment Network (ATN) developed a practice pathway, based on expert consensus, to capture best practices for screening, identification, and treatment for sleep problems in ASD in 2012. An exemplar case is presented to integrate key constructs of the practice pathway and address arousal and sensory dysregulation in a child with ASD and anxiety disorder. This paper concludes with next steps for dissemination of the practice pathway and future directions for research of sleep problems in ASD.
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http://dx.doi.org/10.1007/s11920-017-0782-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5846201PMC
June 2017

Defects in ER-endosome contacts impact lysosome function in hereditary spastic paraplegia.

J Cell Biol 2017 05 7;216(5):1337-1355. Epub 2017 Apr 7.

Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, England, UK

Contacts between endosomes and the endoplasmic reticulum (ER) promote endosomal tubule fission, but the mechanisms involved and consequences of tubule fission failure are incompletely understood. We found that interaction between the microtubule-severing enzyme spastin and the ESCRT protein IST1 at ER-endosome contacts drives endosomal tubule fission. Failure of fission caused defective sorting of mannose 6-phosphate receptor, with consequently disrupted lysosomal enzyme trafficking and abnormal lysosomal morphology, including in mouse primary neurons and human stem cell-derived neurons. Consistent with a role for ER-mediated endosomal tubule fission in lysosome function, similar lysosomal abnormalities were seen in cellular models lacking the WASH complex component strumpellin or the ER morphogen REEP1. Mutations in , , or cause hereditary spastic paraplegia (HSP), a disease characterized by axonal degeneration. Our results implicate failure of the ER-endosome contact process in axonopathy and suggest that coupling of ER-mediated endosomal tubule fission to lysosome function links different classes of HSP proteins, previously considered functionally distinct, into a unifying pathway for axonal degeneration.
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http://dx.doi.org/10.1083/jcb.201609033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412567PMC
May 2017

Obstacles to torture rehabilitation at Guantánamo Bay.

Torture 2017 ;27(2):62-78

United States Department of Defense, Military Commissions Defense Organization.

This article sets out the legal duty of the United States of America to provide victims of torture and cruel, inhumane and degrading treatment (CIDT) the right to full rehabilitation under international law, including those still detained at the facility at Guantánamo Bay. After an examination of some of the torture methods used on these detainees, while they were in the custody of the CIA and arguably afterwards, it goes on to indicate the current obstacles to rehabilitation, including on-going incarceration, lack of impunity, classification of medical documents and limited access to non-military staff. Limited options for possible psychological assistance towards the right to rehabilitation are considered.
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January 2017

Transoral robotic surgery base of tongue mucosectomy for head and neck cancer of unknown primary.

ANZ J Surg 2017 Dec 17;87(12):E281-E284. Epub 2016 Nov 17.

Department of Otolaryngology Head and Neck Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

Background: Head and neck cancer of unknown primary (HNCUP) is a source of diagnostic uncertainty. Patients presenting with cytologically positive neck lumps without a clinically identifiable primary, require extensive investigation including imaging, tonsillectomy, panendoscopy and tissue biopsy. Treatment typically involves neck dissection, wide field radiotherapy and chemotherapy. Transoral robotic surgery (TORS) has emerged as an expanding surgical technique for resecting tumours of the oropharynx. Its role in base of tongue (BOT) mucosectomy for HNCUP can alleviate diagnostic uncertainty and provide an adjunct treatment modality with few complications.

Methods: We conducted a 7-year chart review of consecutive patients presenting with HNCUP that were treated with TORS BOT mucosectomy. We examined the efficacy, diagnostic rates and complications associated with TORS BOT mucosectomy when used for treating HNCUP.

Results: TORS BOT mucosectomy was performed in seven cases of squamous cell carcinoma of unknown primary. Robotic mucosectomy diagnosed BOT as the primary tumour site in five cases (71.4%). All five cases were p16 positive. Average time before return to normal swallowing function was 2.7 days. There were no major surgical complications.

Conclusion: TORS BOT mucosectomy is an expanding surgical technique with a key role in head and neck surgery. It can be utilized to good effect where head and neck cancer is diagnosed without an identifiable primary. Incorporating robotic surgery in the diagnostic and treatment pathway offers low complication rates, reduced morbidity and improved tumour identification.
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http://dx.doi.org/10.1111/ans.13741DOI Listing
December 2017

Quantitative Gait Analysis Using a Motorized Treadmill System Sensitively Detects Motor Abnormalities in Mice Expressing ATPase Defective Spastin.

PLoS One 2016 28;11(3):e0152413. Epub 2016 Mar 28.

Department of Medical Genetics and Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.

The hereditary spastic paraplegias (HSPs) are genetic conditions in which there is progressive axonal degeneration in the corticospinal tract. Autosomal dominant mutations, including nonsense, frameshift and missense changes, in the gene encoding the microtubule severing ATPase spastin are the most common cause of HSP in North America and northern Europe. In this study we report quantitative gait analysis using a motorized treadmill system, carried out on mice knocked-in for a disease-associated mutation affecting a critical residue in the Walker A motif of the spastin ATPase domain. At 4 months and at one year of age homozygous mutant mice had a number of abnormal gait parameters, including in stride length and stride duration, compared to heterozygous and wild-type littermates. Gait parameters in heterozygous animals did not differ from wild-type littermates. We conclude that quantitative gait analysis using the DigiGait system sensitively detects motor abnormalities in a hereditary spastic paraplegia model, and would be a useful method for analyzing the effects of pharmacological treatments for HSP.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152413PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4809716PMC
August 2016

Dismantling the Active Ingredients of an Intervention for Children with Autism.

J Autism Dev Disord 2015 Sep;45(9):2917-27

Perelman School of Medicine, University of Pennsylvania, 3535 Market St, 3rd Floor, Philadelphia, PA, 19104, USA,

This study evaluated the association of fidelity to each of the components of the Strategies for Teaching based on Autism Research (STAR) program, a comprehensive treatment package for children with autism that includes discrete trial training, pivotal response training, and teaching in functional routines, on outcomes for 191 students ages 5-8 years in a large public school district. Fidelity to all components was relatively low, despite considerable training and support, suggesting the need to develop new implementation strategies. Fidelity to pivotal response training, but not discrete trial training or functional routines, was positively associated with gains in cognitive ability despite low levels of fidelity, and may be an effective intervention choice in under-resourced settings.
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http://dx.doi.org/10.1007/s10803-015-2455-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770807PMC
September 2015

Child characteristics associated with outcome for children with autism in a school-based behavioral intervention.

Autism 2016 Apr 24;20(3):321-9. Epub 2015 Apr 24.

University of Pennsylvania, USA.

This study examined the extent to which clinical and demographic characteristics predicted outcome for children with autism spectrum disorder. Participants included 152 students with autism spectrum disorder in 53 kindergarten-through-second-grade autism support classrooms in a large urban public school district. Associations between child characteristics (including age, language ability, autism severity, social skills, adaptive behavior, co-occurring psychological symptoms, and restrictive and repetitive behavior) and outcome, as measured by changes in cognitive ability following one academic year of an intervention standardized across the sample were evaluated using linear regression with random effects for classroom. While several scales and subscales had statistically significant bivariate associations with outcome, in adjusted analysis, only age and the presence of symptoms associated with social anxiety, such as social avoidance and social fearfulness, as measured through the Child Symptom Inventory-4, were associated with differences in outcome. The findings regarding the role of social anxiety are new and have important implications for treatment. Disentangling the construct of social anxiety to differentiate between social fearfulness and social motivation has important implications for shifting the focus of early treatment for children with autism spectrum disorder.
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http://dx.doi.org/10.1177/1362361315577518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4766053PMC
April 2016

Training Teachers to use Evidence-Based Practices for Autism: Examining Procedural Implementation fidelity.

Psychol Sch 2015 Feb;52(2):181-195

Penn Medicine, Dept. of Psychiatry, The Children's Hospital of Philadelphia Center for Autism Research, 3535 Market Street, 8th floor, Philadelphia, PA 19104.

The purpose of this study was to examine the extent to which public school teachers implemented evidence-based interventions for students with autism in the way these practices were designed. Evidence-based practices for students with autism are rarely incorporated into community settings, and little is known about the quality of implementation. An indicator of intervention quality is procedural implementation fidelity (the degree to which a treatment is implemented as prescribed). Procedural fidelity likely affects student outcomes. This project examined procedural implementation fidelity of three evidence-based practices used in a randomized trial of a comprehensive program for students with autism in partnership with a large, urban school district. Results indicate that teachers in public school special education classrooms can learn to implement evidence-based strategies; however they require extensive training, coaching, and time to reach and maintain moderate procedural implementation fidelity. Procedural fidelity over time, and across intervention strategies is examined.
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http://dx.doi.org/10.1002/pits.21815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290214PMC
February 2015

Identification and use of the sugarcane bacilliform virus enhancer in transgenic maize.

BMC Plant Biol 2014 Dec 19;14:359. Epub 2014 Dec 19.

Background: Transcriptional enhancers are able to increase transcription from heterologous promoters when placed upstream, downstream and in either orientation, relative to the promoter. Transcriptional enhancers have been used to enhance expression of specific promoters in transgenic plants and in activation tagging studies to help elucidate gene function.

Results: A transcriptional enhancer from the Sugarcane Bacilliform Virus - Ireng Maleng isolate (SCBV-IM) that can cause increased transcription when integrated into the the genome near maize genes has been identified. In transgenic maize, the SCBV-IM promoter was shown to be comparable in strength to the maize ubiquitin 1 promoter in young leaf and root tissues. The promoter was dissected to identify sequences that confer high activity in transient assays. Enhancer sequences were identified and shown to increase the activity of a heterologous truncated promoter. These enhancer sequences were shown to be more active when arrayed in 4 copy arrays than in 1 or 2 copy arrays. When the enhancer array was transformed into maize plants it caused an increase in accumulation of transcripts of genes near the site of integration in the genome.

Conclusions: The SCBV-IM enhancer can activate transcription upstream or downstream of genes and in either orientation. It may be a useful tool to activate enhance from specific promoters or in activation tagging.
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http://dx.doi.org/10.1186/s12870-014-0359-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302606PMC
December 2014

Localization of sunitinib in in vivo animal and in vitro experimental models by MALDI mass spectrometry imaging.

Anal Bioanal Chem 2015 Mar 26;407(8):2245-53. Epub 2014 Nov 26.

Clinical Protein Science & Imaging, Department of Biomedical Engineering, Lund University, Biomedical Center D13, 221 84, Lund, Sweden.

The spatial distribution of an anticancer drug and its intended target within a tumor plays a major role on determining how effective the drug can be at tackling the tumor. This study provides data regarding the lateral distribution of sunitinib, an oral antiangiogenic receptor tyrosine kinase inhibitor using an in vitro animal model as well as an in vitro experimental model that involved deposition of a solution of sunitinib onto tissue sections. All tumor sections were analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging and compared with subsequent histology staining. Six tumors at four different time points after commencement of in vivo sunitinib treatment were examined to observe the patterns of drug uptake. The levels of sunitinib present in in vivo treated tumor sections increased continuously until day 7, but a decrease was observed at day 10. Furthermore, the in vitro experimental model was adjustable to produce a drug level similar to that obtained in the in vivo model experiments. The distribution of sunitinib in tissue sections treated in vitro appeared to agree with the histological structure of tumors, suggesting that this approach may be useful for testing drug update.
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http://dx.doi.org/10.1007/s00216-014-8350-2DOI Listing
March 2015

Teaching helping to adolescents with autism.

J Appl Behav Anal 2014 29;47(4):850-5. Epub 2014 Aug 29.

Temple University.

This study is a replication and extension of Reeve, Reeve, Townsend, and Poulson (2007) evaluating the effects of a treatment package that included multiple-exemplar training, video modeling, prompting, and reinforcement on helping of 3 adolescents with autism. Results demonstrated that all participants acquired the helping responses. Probes before and after intervention also demonstrated generalization of helping across settings and categories of helping behavior.
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http://dx.doi.org/10.1002/jaba.156DOI Listing
August 2015

An ESCRT-spastin interaction promotes fission of recycling tubules from the endosome.

J Cell Biol 2013 Aug 29;202(3):527-43. Epub 2013 Jul 29.

Department of Medical Genetics, University of Cambridge, Cambridge CB2 0XY, England, UK.

Mechanisms coordinating endosomal degradation and recycling are poorly understood, as are the cellular roles of microtubule (MT) severing. We show that cells lacking the MT-severing protein spastin had increased tubulation of and defective receptor sorting through endosomal tubular recycling compartments. Spastin required the ability to sever MTs and to interact with ESCRT-III (a complex controlling cargo degradation) proteins to regulate endosomal tubulation. Cells lacking IST1 (increased sodium tolerance 1), an endosomal sorting complex required for transport (ESCRT) component to which spastin binds, also had increased endosomal tubulation. Our results suggest that inclusion of IST1 into the ESCRT complex allows recruitment of spastin to promote fission of recycling tubules from the endosome. Thus, we reveal a novel cellular role for MT severing and identify a mechanism by which endosomal recycling can be coordinated with the degradative machinery. Spastin is mutated in the axonopathy hereditary spastic paraplegia. Zebrafish spinal motor axons depleted of spastin or IST1 also had abnormal endosomal tubulation, so we propose this phenotype is important for axonal degeneration.
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http://dx.doi.org/10.1083/jcb.201211045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3734076PMC
August 2013

Transcriptional activation of Brassica napus β-ketoacyl-ACP synthase II with an engineered zinc finger protein transcription factor.

Plant Biotechnol J 2012 Sep 23;10(7):783-91. Epub 2012 Apr 23.

Dow AgroSciences, Indianapolis, IN, USA.

Targeted gene regulation via designed transcription factors has great potential for precise phenotypic modification and acceleration of novel crop trait development. Canola seed oil composition is dictated largely by the expression of genes encoding enzymes in the fatty acid biosynthetic pathway. In the present study, zinc finger proteins (ZFPs) were designed to bind DNA sequences common to two canola β-ketoacyl-ACP Synthase II (KASII) genes downstream of their transcription start site. Transcriptional activators (ZFP-TFs) were constructed by fusing these ZFP DNA-binding domains to the VP16 transcriptional activation domain. Following transformation using Agrobacterium, transgenic events expressing ZFP-TFs were generated and shown to have elevated KASII transcript levels in the leaves of transgenic T(0) plants when compared to 'selectable marker only' controls as well as of T(1) progeny plants when compared to null segregants. In addition, leaves of ZFP-TF-expressing T(1) plants contained statistically significant decreases in palmitic acid (consistent with increased KASII activity) and increased total C18. Similarly, T(2) seed displayed statistically significant decreases in palmitic acid, increased total C18 and reduced total saturated fatty acid contents. These results demonstrate that designed ZFP-TFs can be used to regulate the expression of endogenous genes to elicit specific phenotypic modifications of agronomically relevant traits in a crop species.
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http://dx.doi.org/10.1111/j.1467-7652.2012.00695.xDOI Listing
September 2012

Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12.

J Clin Invest 2012 Feb 9;122(2):538-44. Epub 2012 Jan 9.

Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.

Hereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous neurodegenerative conditions. They are characterized by progressive spastic paralysis of the legs as a result of selective, length-dependent degeneration of the axons of the corticospinal tract. Mutations in 3 genes encoding proteins that work together to shape the ER into sheets and tubules - receptor accessory protein 1 (REEP1), atlastin-1 (ATL1), and spastin (SPAST) - have been found to underlie many cases of HSP in Northern Europe and North America. Applying Sanger and exome sequencing, we have now identified 3 mutations in reticulon 2 (RTN2), which encodes a member of the reticulon family of prototypic ER-shaping proteins, in families with spastic paraplegia 12 (SPG12). These autosomal dominant mutations included a complete deletion of RTN2 and a frameshift mutation predicted to produce a highly truncated protein. Wild-type reticulon 2, but not the truncated protein potentially encoded by the frameshift allele, localized to the ER. RTN2 interacted with spastin, and this interaction required a hydrophobic region in spastin that is involved in ER localization and that is predicted to form a curvature-inducing/sensing hairpin loop domain. Our results directly implicate a reticulon protein in axonopathy, show that this protein participates in a network of interactions among HSP proteins involved in ER shaping, and further support the hypothesis that abnormal ER morphogenesis is a pathogenic mechanism in HSP.
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http://dx.doi.org/10.1172/JCI60560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266795PMC
February 2012

The AAA ATPase spastin links microtubule severing to membrane modelling.

Biochim Biophys Acta 2012 Jan 25;1823(1):192-7. Epub 2011 Aug 25.

Department of Medical Genetics and Cambridge Institute for Medical Research, University of Cambridge, UK.

In 1999, mutations in the gene encoding the microtubule severing AAA ATPase spastin were identified as a major cause of a genetic neurodegenerative condition termed hereditary spastic paraplegia (HSP). This finding stimulated intense study of the spastin protein and over the last decade, a combination of cell biological, in vivo, in vitro and structural studies have provided important mechanistic insights into the cellular functions of the protein, as well as elucidating cell biological pathways that might be involved in axonal maintenance and degeneration. Roles for spastin have emerged in shaping the endoplasmic reticulum and the abscission stage of cytokinesis, in which spastin appears to couple membrane modelling to microtubule regulation by severing.
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http://dx.doi.org/10.1016/j.bbamcr.2011.08.010DOI Listing
January 2012

We're all in this together now: group performance feedback to increase classroom team data collection.

J Sch Psychol 2011 Aug 20;49(4):411-31. Epub 2011 Apr 20.

Temple University, USA.

This study's primary goal was to evaluate the use of performance feedback procedures delivered to a classroom team to increase daily data collection. Performance feedback (PFB) was delivered to four classroom teams responsible for the daily collection of data representing student performance during prescribed instructional activities. Using a multiple-baseline design, the effects of the team performance-feedback were evaluated for the target student, and for generalization to data collection for all classroom students. A secondary question evaluated if student on-task behavior correlated with increased data collection. Finally, social validity was investigated to evaluate team satisfaction with the PFB intervention. The results demonstrate improved data collection across all four classroom teams for the target student in each classroom and generalization within classrooms to all remaining students. Slight increases in student on-task behavior were observed in three of the four classrooms, and teacher satisfaction ratings were high.
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http://dx.doi.org/10.1016/j.jsp.2011.04.003DOI Listing
August 2011