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Lauren B Navrady, Yanni Zeng, Toni-Kim Clarke, Mark J Adams, David M Howard, Ian J Deary, Andrew M McIntosh
Background: Twin studies indicate that genetic and environmental factors contribute to both psychological resilience and coping style, but estimates of their relative molecular and shared environmental contributions are limited. The degree of overlap in the genetic architectures of these traits is also unclear. Methods: Using data from a large population- and family-based cohort Generation Scotland (N = 8,734), we estimated the genetic and shared environmental variance components for resilience, task-, emotion-, and avoidance-oriented coping style in a linear mixed model (LMM)...
2018: Wellcome Open Research
Pascale Guitera, Helena Collgros, Christine M Madronio, Christopher Goumas, Graham J Mann, Caroline G Watts, Amanda R Pereira, Bruce K Armstrong, Martin Drummond, Rachael L Morton, Richard A Scolyer, Scott W Menzies, John F Thompson, Anne E Cust
BACKGROUND/OBJECTIVES: There are limited population-based data documenting the incidence and management of lentigo maligna (LM) and invasive lentigo maligna melanoma (LMM). We report the data on occurrence and management of LM and LMM in an Australian population. METHODS: Prospective collection of incidence and clinician-reported management of melanoma in situ (MIS; n = 450, capped) and localised invasive melanoma (n = 3251) notified to the New South Wales Cancer Registry over 12-months in 2006-2007...
October 9, 2018: Australasian Journal of Dermatology
J Michael Reed, David R Harris, L Michael Romero
There is broad interest in determining repeatability of individual responses. Current methods calculate repeatability of individual points (initial and/or peak), time to peak value, or a single measure of the integrated total response (area under the curve), rather than the shape of the response profile. Repeatability estimates of response profiles using linear mixed models (LMM) generate an average repeatability for an aggregate of individuals, rather than an estimate of individual repeatability. Here we use a novel ad hoc method to calculate repeatability of individual response profiles and demonstrate the need for a more rigorous assessment protocol...
September 28, 2018: General and Comparative Endocrinology
T Gambichler, M Doerler, J Kempka, F G Bechara, M Stücker
Recurrence rates of both lentigo maligna (LM) and lentigo maligna melanoma (LMM) following conventional surgery are usually relatively high. We aimed to assess the frequencies of melanocytes in tumour-free margins around LM/LMM using soluble adenylyl cyclase (sAC) immunohistochemistry, and to compare these with those of matched healthy contralateral skin. Using the primary mouse-anti-human sAC antibody R21, we evaluated pan-nuclear melanocytic R21 immunostaining, and found that it was significantly (P < 0...
September 27, 2018: Clinical and Experimental Dermatology
J Zhang, J R Liang, R Duan, S Qin, M Xiao, H Q Jing, X Wang
Objective: In this study, we analyze the regulation mechanisms of the expression of ampD in AmpC β-lactamase and the regulation mechanism of β-N-acetylglucosaminidase (NagZ) in Yersinia enterocolitica . Methods: We construct the mutation strains of Yersinia enterocolitica AmpD (AmpD1-3) gene ( ampD 1-3), Low-Molecular-Mass Penicillin-Binding Proteins (LMM PBPs) gene ( pbp 4, pbp 5 a , pbp 5 b , pbp 7), NagZ gene ( nagZ ), and ampR gene by deleting and complementing genes, and induce them by cefoxitin. We determined the activity of AmpC β-lactamase activity (U) of mutant strains (basal level and induce level) by using cephalothiophene hydrolysis method, the promoter activity of AmpC β-lactamase ((relative light unit (RLU)) was detected by the luxCDABE reporter system, and the activity of β-N-acetylglucosaminidase (nmol/L) was determined by by using 4-nitrophenyl N-acetyl-β-D-glucosaminide as the chromogenic substrate...
June 6, 2018: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
Xulong Wang, Vivek M Philip, Guruprasad Ananda, Charles C White, Ankit Malhotra, Paul J Michalski, Krishna R Murthy Karuturi, Sumana R Chintalapudi, Casey Acklin, Michael Sasner, David A Bennett, Philip L De Jager, Gareth R Howell, Gregory W Carter
Recent technical and methodological advances have greatly enhanced genome-wide association studies (GWAS). The advent of low-cost, whole-genome sequencing facilitates high-resolution variant identification, and the development of linear mixed models (LMM) allows improved identification of putatively causal variants. While essential for correcting false positive associations due to sample relatedness and population stratification, LMMs have commonly been restricted to quantitative variables. However, phenotypic traits in association studies are often categorical, coded as binary case-control or ordered variables describing disease stages...
May 2018: Genetics
Andrey Ziyatdinov, Miquel Vázquez-Santiago, Helena Brunel, Angel Martinez-Perez, Hugues Aschard, Jose Manuel Soria
BACKGROUND: Quantitative trait locus (QTL) mapping in genetic data often involves analysis of correlated observations, which need to be accounted for to avoid false association signals. This is commonly performed by modeling such correlations as random effects in linear mixed models (LMMs). The R package lme4 is a well-established tool that implements major LMM features using sparse matrix methods; however, it is not fully adapted for QTL mapping association and linkage studies. In particular, two LMM features are lacking in the base version of lme4: the definition of random effects by custom covariance matrices; and parameter constraints, which are essential in advanced QTL models...
February 27, 2018: BMC Bioinformatics
Clara Matas-Nadal, Xavier Sòria, María R García-de-la-Fuente, Valentín Huerva, Eugenia Ortega, Felip Vilardell, Sònia Gatius, Josep M Casanova, Rosa M Martí
The incidence of lentigo maligna (LM), in situ (LM) or invasive (lentigo maligna melanoma, LMM), has increased during the last decades. Due to functional or cosmetic outcomes, optimal treatment with surgical excision may not be appropriate in some cases. We tried less invasive therapy, immunocryosurgery, as a single treatment for LM or combined with surgery for LMM, with better aesthetic results. Three patients with LM or LMM not amenable to complete surgical excision were selected. LMM patients underwent limited surgical resection of the invasive area...
May 2018: Journal of Dermatology
Luke R Lloyd-Jones, Matthew R Robinson, Jian Yang, Peter M Visscher
Genome-wide association studies (GWAS) have identified thousands of loci that are robustly associated with complex diseases. The use of linear mixed model (LMM) methodology for GWAS is becoming more prevalent due to its ability to control for population structure and cryptic relatedness and to increase power. The odds ratio (OR) is a common measure of the association of a disease with an exposure ( e.g. , a genetic variant) and is readably available from logistic regression. However, when the LMM is applied to all-or-none traits it provides estimates of genetic effects on the observed 0-1 scale, a different scale to that in logistic regression...
April 2018: Genetics
D Tio, C A C Prinsen, B Dréno, R Hoekzema, M Augustin, C van Montfrans
BACKGROUND: Lentigo maligna (LM), a form of melanoma in situ, is treated to prevent progression to lentigo maligna melanoma (LMM). Surgical treatment is the gold standard. However, treatment guidelines are based on expert opinion, and comparative studies are lacking. OBJECTIVE: The objective of this study was to assess the diagnostic methods and clinical management of LM patients among European dermatologists and residents. METHODS: A survey consisting of 29 questions about diagnostic methods and treatment options used for LM patients was sent to 3308 members of the European Association of Dermatologists and Venereologists (EADV)...
September 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Outi Kaarre, Marja Äikiä, Elisa Kallioniemi, Mervi Könönen, Virve Kekkonen, Noora Heikkinen, Petri Kivimäki, Tommi Tolmunen, Sara Määttä, Eila Laukkanen
The most thoroughly studied transcranial magnetic stimulation (TMS)-evoked electroencephalogram (EEG) potential (TEP), N100, is often defined as a measure of cortical inhibition. We explored the association of the N100 amplitude with attention in 51 young healthy adults. Navigated TMS with simultaneous EEG registering was applied over the left primary motor cortex at the intensity of 110% of the resting motor threshold. Attention was assessed with the Paced Auditory Serial Addition Test (PASAT). We found a negative Pearson correlation (p = ...
April 2018: Brain and Cognition
E Cinotti, B Labeille, S Debarbieux, C Carrera, F Lacarrubba, A M Witkowski, E Moscarella, E Arzberger, H Kittler, P Bahadoran, S Gonzalez, P Guitera, M Agozzino, F Farnetani, R Hofmann-Wellenhof, M Ardigò, P Rubegni, L Tognetti, J Łudzik, I Zalaudek, G Argenziano, C Longo, S Ribero, J Malvehy, G Pellacani, F Cambazard, J L Perrot
BACKGROUND: Several dermoscopic and in vivo reflectance confocal microscopy (RCM) diagnostic criteria of lentigo maligna (LM)/lentigo maligna melanoma (LMM) have been identified. However, no study compared the diagnostic accuracy of these techniques. OBJECTIVE: We evaluated the diagnostic accuracy of dermoscopy and RCM for LM/LMM using a holistic assessment of the images. METHODS: A total of 223 facial lesions were evaluated by 21 experts...
January 17, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Rohit R Singh, James W Dunn, Motamed M Qadan, Nakiuda Hall, Kathy K Wang, Douglas D Root
The mechanical stability of the myosin subfragment-2 (S2) was tested with simulated force spectroscopy (SFS) and gravitational force spectroscopy (GFS). Experiments examined unzipping S2, since it required less force than stretching parallel to the coiled coil. Both GFS and SFS demonstrated that the force required to destabilize the light meromyosin (LMM) was greater than the force required to destabilize the coiled coil at each of three different locations along S2. GFS data also conveyed that the mechanical stability of the S2 region is independent from its association with the myosin thick filament using cofilaments of myosin tail and a single intact myosin...
January 15, 2018: Archives of Biochemistry and Biophysics
E B Yerkes, C Halline, G Yoshiba, T A Meyer, I Rosoklija, R Bowman, D McLone, E Y Cheng
INTRODUCTION: The primary urologic objectives for lipomyelomeningocele (LMM) and myelomeningocele (MM) are preserving renal integrity and achieving continence. Due to this common ground, LMM and MM are urologically treated the same. However, unlike MM, LMM may present with no evident functional concerns. Indications for and timing of tethered cord release (TCR) in LMM are therefore controversial. Long-term urologic outcomes are not well defined. OBJECTIVE: Expectations for continence and potential for intermittent catheterization (CIC) following TCR in LMM are important for realistically counseling families regarding future needs...
August 2017: Journal of Pediatric Urology
Akhilesh Kaushal, Hongmei Zhang, Wilfried J J Karmaus, Meredith Ray, Mylin A Torres, Alicia K Smith, Shu-Li Wang
BACKGROUND: Whole blood is frequently utilized in genome-wide association studies of DNA methylation patterns in relation to environmental exposures or clinical outcomes. These associations can be confounded by cellular heterogeneity. Algorithms have been developed to measure or adjust for this heterogeneity, and some have been compared in the literature. However, with new methods available, it is unknown whether the findings will be consistent, if not which method(s) perform better. RESULTS: Methods: We compared eight cell-type correction methods including the method in the minfi R package, the method by Houseman et al...
April 14, 2017: BMC Bioinformatics
Luke R Lloyd-Jones, Matthew R Robinson, Gerhard Moser, Jian Zeng, Sandra Beleza, Gregory S Barsh, Hua Tang, Peter M Visscher
Genetic association studies in admixed populations are underrepresented in the genomics literature, with a key concern for researchers being the adequate control of spurious associations due to population structure. Linear mixed models (LMMs) are well suited for genome-wide association studies (GWAS) because they account for both population stratification and cryptic relatedness and achieve increased statistical power by jointly modeling all genotyped markers. Additionally, Bayesian LMMs allow for more flexible assumptions about the underlying distribution of genetic effects, and can concurrently estimate the proportion of phenotypic variance explained by genetic markers...
June 2017: Genetics
Leslie R Euceda, Deborah K Hill, Endre Stokke, Rana Hatem, Rania El Botty, Ivan Bièche, Elisabetta Marangoni, Tone F Bathen, Siver A Moestue
Patients with triple-negative breast cancer (TNBC) are unresponsive to endocrine and anti-HER2 pharmacotherapy, limiting their therapeutic options to chemotherapy. TNBC is frequently associated with abnormalities in the PI3K/AKT/mTOR signaling pathway; drugs targeting this pathway are currently being evaluated in these patients. However, the response is variable, partly due to heterogeneity within TNBC, conferring a need to identify biomarkers predicting response and resistance to targeted therapy. In this study, we used a metabolomics approach to assess response to the mTOR inhibitor everolimus in a panel of TNBC patient-derived xenografts (PDX) (n = 103 animals)...
May 5, 2017: Journal of Proteome Research
Shashwath A Meda, Ralitza V Gueorguieva, Brian Pittman, Rivkah R Rosen, Farah Aslanzadeh, Howard Tennen, Samantha Leen, Keith Hawkins, Sarah Raskin, Rebecca M Wood, Carol S Austad, Alecia Dager, Carolyn Fallahi, Godfrey D Pearlson
BACKGROUND: Alcohol and marijuana are the two most abused substances in US colleges. However, research on the combined influence (cross sectional or longitudinal) of these substances on academic performance is currently scant. METHODS: Data were derived from the longitudinal 2-year Brain and Alcohol Research in College Students (BARCS) study including 1142 freshman students who completed monthly marijuana use and alcohol consumption surveys. Subjects were classified into data-driven groups based on their alcohol and marijuana consumption...
2017: PloS One
R Burrows, P Correa-Burrows, M Reyes, E Blanco, C Albala, S Gahagan
BACKGROUND: Increased cardiometabolic risk (CMR) is documented in obese and non-obese adolescents with low muscular fitness. However, the association of low muscle mass (LMM) with CMR, independent of weight status, has not been examined. We analyzed the relationship of LMM with CMR in adolescents, regardless of their weight status. MATERIALS AND METHODS: Observational study in 660 adolescents. BMI, waist circumference (WC), arterial blood pressures (ABP) were measured...
December 2017: Pediatric Diabetes
Stefan Smesny, Berko Milleit, Miriam R Schaefer, Jana Hesse, Monika Schlögelhofer, Kerstin Langbein, Uta-Christina Hipler, Maximus Berger, David R Cotter, Heinrich Sauer, Patrick D McGorry, G Paul Amminger
Alterations of immune function have been reported in ultra-high risk (UHR) for psychosis patients causing expectations in terms of predictive meaningfulness and benefits of anti-inflammatory agents. According to a RCT in UHR-patients supplementation of omega-3 polyunsaturated fatty acids (PUFA) was effective in reducing transition to psychosis risk and to improve symptomatology. Based on preclinical findings, we now investigated state marker properties of and the influence of PUFA on immune markers in a RCT (clinical trials...
October 2017: Schizophrenia Research
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