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21.
Victoria Grahame Lisa Stuart Emma Honey Mark Freeston 《Child and Adolescent Mental Health》2020,25(2):71-73
This paper is in response to the commentary written by Richard Woods in which he attempts to provide support for his Monotropism autism theory and the research indicating that Demand Avoidance Phenomena may not be developmentally persistent (Woods, 2019). We acknowledge the continuing controversy around the proposed construct of PDA and the clinical dilemma faced by professionals, within the United Kingdom, following increased demand from families seeking assessment and support. We appreciate that research on this topic is scarce and understanding of PDA behaviours remains limited and that methodological improvements are required. However, it is important to remember that anxiety, which often has an onset in middle childhood and adolescence, is a major risk factor for mental health difficulties. Therefore, treatments targeting underlying and potentially modifiable mechanisms rather than anxiety symptoms may be more likely to be effective. 相似文献
22.
Connie J. Chen Stuart Kaufman Kirk Packo Heidi Stöhr Bernhard H. F. Weber Morton F. Goldberg 《Ophthalmic genetics》2016,37(1):102-108
Background: Mutations in BEST1 account for autosomal dominant vitreoretinochoroidopathy (ADVIRC), a rare inherited retinal dystrophy with presenile cataracts and incomplete anterior segment development. The long-term clinical findings and visual prognosis of these patients continues to evolve over time.Materials and Methods: The retina was assessed by fundus photography, fluorescein angiography, and spectral domain optical coherence tomography. Sanger dideoxy chain-termination sequencing identified mutations in BEST1. Bioinformatic tools were used to predict changes in splicing. An in vitro splicing assay was applied to evaluate for altered pre-mRNA splicing.Results: Long-term follow up of the first ever reported ADVIRC proband revealed progressive foveal atrophy in both eyes 3 decades after his initial presentation. Progressive retinal ischemia, bilateral iris atrophy, and pseudophakodnesis were observed on follow up. The patient was heterozygous for a c.248G?>?A missense mutation in exon 4 of BEST1, affecting a highly conserved transmembrane domain. Although computational prediction models suggest a change in the binding probability of splicing-associated SR proteins, in vitro splicing assays failed to demonstrate an effect of the c.248G?>?A mutation on splicing of BEST1 exon 3 or exon 4.Conclusions: Progressive posterior chorioretinal changes occurred over time in the initial ADVIRC proband, leading to visual loss. The causative mutation in this patient falls in the transmembrane domain of the BEST1 protein, with unclear functional consequences. Although previous studies showed alteration in pre-mRNA splicing, in vitro splicing assays failed to demonstrate this in our patient. 相似文献
23.
Jay A. Graham Julia Torabi Maria Ajaimy Enver Akalin Luz E. Liriano Yorg Azzi Cindy Pynadath Stuart M. Greenstein Doctor Y. Goldstein Amy S. Fox Jeffery M. Weiss Tia P. Powell John F. Reinus Milan M. Kinkhabwala Juan P. Rocca 《Clinical transplantation》2020,34(4):e13833
The advent of direct-acting antivirals (DAAs) has provided the impetus to transplant kidneys from hepatitis C virus-positive donors into uninfected recipients (D+/R−). Thirty D+/R− patients received DAA treatment. Sustained virologic response (SVR12) was defined as an undetectable viral load in 12 weeks after treatment. An age-matched cohort of uninfected donor and recipient pairs (D−/R−) transplanted during same time period was used for comparison. The median day of viral detection was postoperative day (POD) 2. The detection of viremia in D+/R− patients was 100%. The initial median viral load was 531 copies/μL (range: 10-1 × 108 copies/μL) with a median peak viral load of 3.4 × 105 copies/μL (range: 804-1.0 × 108 copies/μL). DAAs were initiated on median POD 9 (range: 5-41 days). All 30 patients had confirmed SVR12. During a median follow-up of 10 months, patient and graft survival was 100%, and acute rejection was 6.6% with no major adverse events related to DAA treatment. Delayed graft function was significantly decreased in D+/R− patients as compared to the age-matched cohort (27% vs 60%; P = .01). D+/R− transplantation offers patients an alternative strategy to increase access. 相似文献
24.
Mehdi Kordi Jonathan Folland Stuart Goodall Nicos Haralabidis Tom Maden-Wilkinson Tejal Sarika Patel Jonathan Leeder Paul Barratt Glyn Howatson 《Scandinavian journal of medicine & science in sports》2020,30(2):227-237
Mechanical peak power output (PPO) is a determinant of performance in sprint cycling. The purpose of this study was to examine the relationship between PPO and putative physiological determinants of PPO in elite cyclists, and to compare sprint performance between elite sprint and endurance cyclists. Thirty-five elite cyclists (18 endurance; 17 sprint) performed duplicate sprint cycling laboratory tests to establish PPO and its mechanical components. Quadriceps femoris (QVOL) and hamstring muscle volume (HAMVOL) were assessed with MRI, vastus lateralis pennation angle (PθVL) and fascicle length (FLVL) were determined with ultrasound imaging, and neuromuscular activation of three muscles was assessed using EMG at PPO during sprint cycling. For the whole cohort, there was a wide variability in PPO (range 775-2025 W) with very large, positive, bivariate relationships between PPO and QVOL (r = .87), HAMVOL (r = .71), and PθVL (r = .81). Step-wise multiple regression analysis revealed that 87% of the variability in PPO between cyclists was explained by two variables QVOL (76%) and PθVL (11%). The sprint cyclists had greater PPO (+61%; P < .001 vs endurance), larger QVOL (P < .001), and BFVOL (P < .001) as well as more pennate vastus lateralis muscles (P < .001). These findings emphasize the importance of quadriceps muscle morphology for sprint cycling events. 相似文献
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28.
Stuart J. Dilley Tracey J. Weiland Robert O’Brien Neil J. Cunningham Julian E. Van Dijk Rosie M. Mahoney 《Teaching and learning in medicine》2015,27(1):71-79
Theory: Immersive simulation is a common mode of education for medical students. Observation of clinical simulations prior to participation is believed to be beneficial, though this is often a passive process. Active observation may be more beneficial. Hypotheses: The hypothesis tested in this study was that the active use of a simple checklist during observation of an immersive simulation would result in better participant performance in a subsequent scenario compared with passive observation alone. Methods: Medical students were randomized to either passive or active (with checklist) observation of an immersive simulation involving cardiac arrest prior to participating in their own simulation. Performance measures included time to cardiopulmonary resuscitation (CPR) and time to defibrillation and were compared between first and second scenarios as well as between passive and active observers. Results: Seventy-nine simulations involving 232 students were conducted. Mean time to CPR was 18 seconds (SD = 11.6) for those using the checklist and 24 seconds (SD = 15.8) for those who observed passively (M difference = 6 seconds), t(35) = 1.46, p =.153. Time to defibrillation was 94 seconds (SD = 26.4) for those using the checklist and 92 seconds (SD = 23.8) for those who observed passively (M difference = –2 seconds), t(38) =.21, p =.837. Time to CPR was 24 seconds (SD = 15.8) for passive observers and 31 seconds (SD = 21.0; M difference = 7 seconds), t(35) = 1.13, p =.265, for their first scenario counterparts. Time to CPR was 18 seconds (SD = 11.6) for active observers and 36 seconds (SD = 26.2; M difference = 18 seconds), t(24) = 2.81, p =.010, for their first scenario counterparts. Time to defibrillation was 92 seconds (SD = 23.8) for passive observers and 125 seconds (SD = 32.2; M difference = 33 seconds), t(33) = 3.63, p =.001, for their first scenario counterparts. Time to defibrillation was 94 seconds (SD = 26.4) for the active observers and 132 seconds (SD = 52.9; M difference = 38 seconds), t(28) =.46, p =.008, for their first scenario counterparts. Conclusions: Observation alone leads to improved performance in the management of a simulated cardiac arrest. The active use of a simple skills-based checklist during observation did not appear to improve performance over passive observation alone. 相似文献
29.
Luke Boulter Rachel V. Guest Timothy J. Kendall David H. Wilson Davina Wojtacha Andrew J. Robson Rachel A. Ridgway Kay Samuel Nico Van Rooijen Simon T. Barry Stephen J. Wigmore Owen J. Sansom Stuart J. Forbes 《The Journal of clinical investigation》2015,125(3):1269-1285
Cholangiocarcinoma (CC) is typically diagnosed at an advanced stage and is refractory to surgical intervention and chemotherapy. Despite a global increase in the incidence of CC, little progress has been made toward the development of treatments for this cancer. Here we utilized human tissue; CC cell xenografts; a p53-deficient transgenic mouse model; and a non-transgenic, chemically induced rat model of CC that accurately reflects both the inflammatory and regenerative background associated with human CC pathology. Using these systems, we determined that the WNT pathway is highly activated in CCs and that inflammatory macrophages are required to establish this WNT-high state in vivo. Moreover, depletion of macrophages or inhibition of WNT signaling with one of two small molecule WNT inhibitors in mouse and rat CC models markedly reduced CC proliferation and increased apoptosis, resulting in tumor regression. Together, these results demonstrate that enhanced WNT signaling is a characteristic of CC and suggest that targeting WNT signaling pathways has potential as a therapeutic strategy for CC. 相似文献
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