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1.
Nature ; 590(7845): 290-299, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33568819

RESUMO

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1. In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%.


Assuntos
Variação Genética/genética , Genoma Humano/genética , Genômica , National Heart, Lung, and Blood Institute (U.S.) , Medicina de Precisão , Citocromo P-450 CYP2D6/genética , Haplótipos/genética , Heterozigoto , Humanos , Mutação INDEL , Mutação com Perda de Função , Mutagênese , Fenótipo , Polimorfismo de Nucleotídeo Único , Densidade Demográfica , Medicina de Precisão/normas , Controle de Qualidade , Tamanho da Amostra , Estados Unidos , Sequenciamento Completo do Genoma/normas
2.
Plant Biotechnol J ; 22(2): 472-483, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37870930

RESUMO

The native, perennial shrub American hazelnut (Corylus americana) is cultivated in the Midwestern United States for its significant ecological benefits, as well as its high-value nut crop. Implementation of modern breeding methods and quantitative genetic analyses of C. americana requires high-quality reference genomes, a resource that is currently lacking. We therefore developed the first chromosome-scale assemblies for this species using the accessions 'Rush' and 'Winkler'. Genomes were assembled using HiFi PacBio reads and Arima Hi-C data, and Oxford Nanopore reads and a high-density genetic map were used to perform error correction. N50 scores are 31.9 Mb and 35.3 Mb, with 90.2% and 97.1% of the total genome assembled into the 11 pseudomolecules, for 'Rush' and 'Winkler', respectively. Gene prediction was performed using custom RNAseq libraries and protein homology data. 'Rush' has a BUSCO score of 99.0 for its assembly and 99.0 for its annotation, while 'Winkler' had corresponding scores of 96.9 and 96.5, indicating high-quality assemblies. These two independent assemblies enable unbiased assessment of structural variation within C. americana, as well as patterns of syntenic relationships across the Corylus genus. Furthermore, we identified high-density SNP marker sets from genotyping-by-sequencing data using 1343 C. americana, C. avellana and C. americana × C. avellana hybrids, in order to assess population structure in natural and breeding populations. Finally, the transcriptomes of these assemblies, as well as several other recently published Corylus genomes, were utilized to perform phylogenetic analysis of sporophytic self-incompatibility (SSI) in hazelnut, providing evidence of unique molecular pathways governing self-incompatibility in Corylus.


Assuntos
Corylus , Corylus/genética , Filogenia , Melhoramento Vegetal , Cromossomos , Genômica
3.
Ann Neurol ; 94(4): 727-735, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37314750

RESUMO

OBJECTIVE: This study was undertaken to investigate factors associated with aquaporin-4 (AQP4)-IgG serostatus change using a large serological database. METHODS: This retrospective study utilizes Mayo Clinic Neuroimmunology Laboratory data from 2007 to 2021. We included all patients with ≥2 AQP4-IgG tests (by cell-based assay). The frequency and clinical factors associated with serostatus change were evaluated. Multivariable logistic regression analysis examined whether age, sex, or initial titer was associated with serostatus change. RESULTS: There were 933 patients who had ≥2 AQP4-IgG tests with an initial positive result. Of those, 830 (89%) remained seropositive and 103 (11%) seroreverted to negative. Median interval to seroreversion was 1.2 years (interquartile range [IQR] = 0.4-3.5). Of those with sustained seropositivity, titers were stable in 92%. Seroreversion was associated with age ≤ 20 years (odds ratio [OR] = 2.25; 95% confidence interval [CI] = 1.09-4.63; p = 0.028) and low initial titer of ≤1:100 (OR = 11.44, 95% CI = 3.17-41.26, p < 0.001), and 5 had clinical attacks despite seroreversion. Among 62 retested after seroreversion, 50% returned to seropositive (median = 224 days, IQR = 160-371). An initial negative AQP4-IgG test occurred in 9,308 patients. Of those, 99% remained seronegative and 53 (0.3%) seroconverted at a median interval of 0.76 years (IQR = 0.37-1.68). INTERPRETATION: AQP4-IgG seropositivity usually persists over time with little change in titer. Seroreversion to negative is uncommon (11%) and associated with lower titers and younger age. Seroreversion was often transient, and attacks occasionally occurred despite prior seroreversion, suggesting it may not reliably reflect disease activity. Seroconversion to positive is rare (<1%), limiting the utility of repeat testing in seronegative patients unless clinical suspicion is high. ANN NEUROL 2023;94:727-735.


Assuntos
Aquaporina 4 , Imunoglobulina G , Soroconversão , Adulto , Humanos , Adulto Jovem , Autoanticorpos , Estudos Retrospectivos
4.
Phys Rev Lett ; 132(5): 056002, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38364146

RESUMO

We investigated the high energy spin excitations in electron-doped La_{2-x}Ce_{x}CuO_{4}, a cuprate superconductor, by resonant inelastic x-ray scattering (RIXS) measurements. Efforts were paid to disentangle the paramagnon signal from non-spin-flip spectral weight mixing in the RIXS spectrum at Q_{∥}=(0.6π,0) and (0.9π,0) along the (1 0) direction. Our results show that, for doping level x from 0.07 to 0.185, the variation of the paramagnon excitation energy is marginal. We discuss the implication of our results in connection with the evolution of the electron correlation strength in this system.

5.
J Evol Biol ; 37(8): 877-890, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38900077

RESUMO

Mate choice is a key trait that determines fitness for most sexually reproducing organisms, with females often being the choosy sex. Female preference often results in strong selection on male traits that can drive rapid divergence of traits and preferences between lineages, leading to reproductive isolation. Despite this fundamental property of female mate choice, very few loci have been identified that contribute to mate choice and reproductive isolation. We used a combination of population genetics, quantitative complementation tests, and behavioural assays to demonstrate that alan shepard and Neuroglian contribute to female mate choice, and could contribute to partial reproductive isolation between populations of Drosophila melanogaster. Our study is among the first to identify genes that contribute to female mate preference in this historically important system, where female preference is an active premating barrier to reproduction. The identification of loci that are primarily known for their roles in neurodevelopment provides intriguing questions of how female mate preference evolves in populations via changes in sensory system and higher learning brain centres.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Preferência de Acasalamento Animal , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Feminino , Proteínas de Drosophila/genética , Masculino , Isolamento Reprodutivo
6.
J Eukaryot Microbiol ; : e13050, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39019843

RESUMO

Dinoflagellates are an abundant and diverse group of protists representing a wealth of unique biology and ecology. While many dinoflagellates are photosynthetic or mixotrophic, many taxa are heterotrophs, often with complex feeding strategies. Compared to their photosynthetic counterparts, heterotrophic dinoflagellates remain understudied, as they are difficult to culture. One exception, a long-cultured isolate originally classified as Amphidinium but recently reclassified as Oxytoxum, has been the subject of a number of feeding, growth, and chemosensory studies. This lineage was recently determined to be closely related to Prorocentrum using phylogenetics of ribosomal RNA gene sequences, but the exact nature of this relationship remains unresolved. Using transcriptomes sequenced from culture and three single cells from the environment, we produce a robust phylogeny of 242 genes, revealing Oxytoxum is likely sister to the Prorocentrum clade, rather than nested within it. Molecular investigations uncover evidence of a reduced, nonphotosynthetic plastid and proteorhodopsin, a photoactive proton pump acquired horizontally from bacteria. We describe the ultrastructure of O. lohmannii, including densely packed trichocysts, and a new type of mucocyst. We observe that O. lohmannii feeds preferentially on cryptophytes using myzocytosis, but can also feed on various phytoflagellates using conventional phagocytosis. O. lohmannii is amenable to culture, providing an opportunity to better study heterotrophic dinoflagellate biology and feeding ecology.

7.
Arch Sex Behav ; 53(3): 1091-1105, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38277097

RESUMO

There is scarce empirical evidence examining whether sexual initiation and power are associated with each other. Utilizing latent profile analyses, we examined in a nationally representative sample of US newlywed heterosexual couples (N = 1,948 couples) whether wives' and husbands' sexual initiation patterns and satisfaction with these patterns were associated with membership in different profiles of wives' and husbands' perceptions of shared relational power while accounting for both partner's satisfaction with sexual frequency. We found four profiles of wives' and husbands' perceptions of power. The most common profile was when both wives and husbands perceived high levels of power compared to other profiles, but wives had significantly higher reports of perceived power than husbands (High Power, Wife Higher; 40.8%). Husbands' sexual initiation patterns were not associated with profile membership. Wives who reported equal sexual initiation patterns had a higher probability of being in the High Power, Wife Higher profile compared to the Wife Low Power, Husband Moderate Power profile. Both wives' and husbands' satisfaction with sexual initiation patterns were associated with profile membership. Wives and husbands that were satisfied with sexual initiation patterns had a higher probability of being in the High Power, Wife Higher profile compared to the profile where both wives and husbands had high perceptions of shared relational power compared to other profiles, but their scores were not significantly different from each other (High Power, Equal).


Assuntos
Comportamento Sexual , Cônjuges , Humanos , Casamento , Heterossexualidade
8.
Artigo em Inglês | MEDLINE | ID: mdl-38482939

RESUMO

OBJECTIVE: The purpose of this study was to identify the cerebral physiologic response to aerobic exercise in individuals with a symptomatic concussion, highlighting available knowledge and knowledge gaps in the literature. DESIGN: A systematic scoping review was conducted and reported in keeping with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. A search of EMBASE, MEDLINE, SCOPUS, BIOSIS, and Cochrane libraries was conducted on June 15, 2023 (from database inception). An online systematic/scoping review management system was used to remove duplicates, and the remaining articles were screened for inclusion by 2 researchers. Inclusion criteria required articles to be original research published in peer-reviewed journals. Additionally, studies were required to have an aerobic exercise component, include a measure of cerebral physiology during a bout of aerobic exercise, exclude moderate and/or severe traumatic brain injury (TBI) populations, and be in the English language. Both human and animal studies were included, with participants of any age who were diagnosed with a mild TBI/concussion only (ie, Glasgow Coma Scale score ≥ 13). Studies could be of any design as long as a measure of cerebral physiologic response to a bout of aerobic exercise was included. RESULTS: The search resulted in 1773 articles to be screened and data from 3 eligible studies were extracted. CONCLUSIONS: There are currently too few studies investigating the cerebral physiologic response to aerobic exercise following concussion or mild TBI to draw definitive conclusions. Further research on this topic is necessary since understanding the cerebral physiologic response to aerobic exercise in the concussion and mild TBI populations could assist in optimizing exercise-based treatment prescription and identifying other targeted therapies.

9.
J Sports Sci ; : 1-10, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39206749

RESUMO

The relationship between heart rate variability (HRV) and training load in team-sport is unknown. We therefore assessed relations between completed training-load in the previous 1-, 3- and 7-days and waking HRV in professional Australian Rules Football. Linear-mixed models analysed changes in HRV, considering training load from the previous 1-, 3- and 7-days. Total Distance (TD), distance >14.4 km ‧ h-1 (HSR) and >24.9 km ‧ h-1 (Sprint-Distance), duration >85% max heart rate and Rating of Perceived Exertion were included as independent variables. Sub-group analysis of season-phase and years of professional experience was also conducted. Increased three-day Sprint-Distance reduced HRV in the first 8-weeks of pre-season (-13.1 ms, p = 0.03) and across the data collection period (-3.75 ms, p = 0.01). In first-year players, higher previous-day (-63.3 ms, p=0.04) and seven-day TD (-38.2 ms, p = 0.02) reduced HRV, whilst higher seven-day HSR increased HRV (34.5 ms, p = 0.01). In players with five-to-seven years of professional experience, higher three-day (-14.4 ms, p = 0.02) and seven-day TD (-15.7 ms, p = 0.01) reduced HRV, while higher three-day HSR increased HRV (12.5 ms, p = 0.04). In players with greater than eight years of professional experience, higher previous-day Sprint-Distance reduced HRV (-13.1 ms, p < 0.008). Completed training load across the previous 7-days influences HRV, but the relation between variables is complex and influenced by professional experience and season-phase.

10.
Fam Process ; 63(1): 130-150, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37431218

RESUMO

Two types of sexual beliefs, growth and destiny, have been found in past research to be differentially associated with sexual and relationship outcomes; however, past research has not explored these beliefs with dyadic data nor considered common intervening variables that might be pathways through which beliefs influence outcomes. Consequently, using the sexual wholeness model, we analyzed how couples' specific sexual beliefs (growth and destiny) influenced their sexual mindfulness, communication, and functioning within their couple relationships and how each of these variables influenced sexual satisfaction and harmonious sexual passion. Using a national sample of dyadic data from 964 sexually active individuals (482 heterosexual couples) who had been in a committed relationship for at least 2 years, we evaluated an actor/partner structural equation model with distinguishable dyads. We found that while sexual growth and destiny beliefs had a significant association with sexual mindfulness, communication, and functioning for both partners, sexual beliefs had no direct association with sexual satisfaction and harmonious sexual passion. Because growth beliefs had strong associations with sexual communication, it may be beneficial to help couples identify their implicit beliefs and encourage the development of sexual growth beliefs.


Assuntos
Atenção Plena , Parceiros Sexuais , Humanos , Comportamento Sexual , Satisfação Pessoal , Comunicação
11.
J Am Chem Soc ; 145(36): 19422-19439, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37642501

RESUMO

Wastewater is an underleveraged resource; it contains pollutants that can be transformed into valuable high-purity products. Innovations in chemistry and chemical engineering will play critical roles in valorizing wastewater to remediate environmental pollution, provide equitable access to chemical resources and services, and secure critical materials from diminishing feedstock availability. This perspective envisions electrochemical wastewater refining─the use of electrochemical processes to tune and recover specific products from wastewaters─as the necessary framework to accelerate wastewater-based electrochemistry to widespread practice. We define and prescribe a use-informed approach that simultaneously serves specific wastewater-pollutant-product triads and uncovers a mechanistic understanding generalizable to broad use cases. We use this approach to evaluate research needs in specific case studies of electrocatalysis, stoichiometric electrochemical conversions, and electrochemical separations. Finally, we provide rationale and guidance for intentionally expanding the electrochemical wastewater refining product portfolio. Wastewater refining will require a coordinated effort from multiple expertise areas to meet the urgent need of extracting maximal value from complex, variable, diverse, and abundant wastewater resources.

12.
Mol Biol Evol ; 39(11)2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36251862

RESUMO

Despite a century of genetic analysis, the evolutionary processes that have generated the patterns of exceptional genetic and phenotypic variation in the model organism Drosophila melanogaster remains poorly understood. In particular, how genetic variation is partitioned within its putative ancestral range in Southern Africa remains unresolved. Here, we study patterns of population genetic structure, admixture, and the spatial structuring of candidate incompatibility alleles across a global sample, including 223 new accessions, predominantly from remote regions in Southern Africa. We identify nine major ancestries, six that primarily occur in Africa and one that has not been previously described. We find evidence for both contemporary and historical admixture between ancestries, with admixture rates varying both within and between continents. For example, while previous work has highlighted an admixture zone between broadly defined African and European ancestries in the Caribbean and southeastern USA, we identify West African ancestry as the most likely African contributor. Moreover, loci showing the strongest signal of introgression between West Africa and the Caribbean/southeastern USA include several genes relating to neurological development and male courtship behavior, in line with previous work showing shared mating behaviors between these regions. Finally, while we hypothesized that potential incompatibility loci may contribute to population genetic structure across the range of D. melanogaster; these loci are, on average, not highly differentiated between ancestries. This work contributes to our understanding of the evolutionary history of a key model system, and provides insight into the partitioning of diversity across its range.


Assuntos
Evolução Biológica , Drosophila melanogaster , Animais , Drosophila melanogaster/genética , Alelos , África , Índias Ocidentais , Genética Populacional , Variação Genética
13.
Ann Surg ; 278(3): 417-425, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37334712

RESUMO

OBJECTIVES: We aimed to report efficacy, safety, and health-related quality of life (HRQoL) outcomes of a multidisciplinary treatment approach including supraclavicular thoracic outlet decompression among patients with thoracic outlet syndrome (TOS). BACKGROUND: TOS is a challenging condition where controversy remains in diagnosis and treatment, primarily given a lack of data exploring various treatment approaches and associated patient outcomes. METHODS: Patients who underwent unilateral, supraclavicular thoracic outlet decompression, or pectoralis minor tenotomy for neurogenic, venous, or arterial TOS were identified from a prospectively maintained database. Demography, use of preoperative botulinum toxin injection, and participation in multidisciplinary evaluation were measured. The primary endpoints were composite postoperative morbidity and symptomatic improvement compared with baseline. RESULTS: Among 2869 patients evaluated (2007-2021), 1032 underwent surgery, including 864 (83.7%) supraclavicular decompressions and 168 (16.3%) isolated pectoralis minor tenotomies. Predominant TOS subtypes among surgical patients were neurogenic (75.4%) and venous TOS (23.4%). Most patients (92.9%) with nTOS underwent preoperative botulinum toxin injection; 56.3% reported symptomatic improvement. Before surgical consultation, few patients reported participation in physical therapy (10.9%). The median time from first evaluation to surgery was 136 days (interquartile range: 55, 258). Among 864 patients who underwent supraclavicular thoracic outlet decompression, complications occurred in 19.8%; the most common complication was chyle leak (8.3%). Four patients (0.4%) required revisional thoracic outlet decompression. At a median follow-up of 420 days (interquartile range: 150, 937) 93.3% reported symptomatic improvement. CONCLUSION: Based on low composite morbidity, need for very few revisional operations, and high rates of symptomatic improvement, a multidisciplinary treatment approach including primarily supraclavicular thoracic outlet decompression is safe and effective for patients with TOS.


Assuntos
Toxinas Botulínicas , Síndrome do Desfiladeiro Torácico , Humanos , Resultado do Tratamento , Qualidade de Vida , Descompressão Cirúrgica/efeitos adversos , Síndrome do Desfiladeiro Torácico/cirurgia , Síndrome do Desfiladeiro Torácico/diagnóstico , Síndrome do Desfiladeiro Torácico/etiologia , Estudos Retrospectivos
14.
J Neurol Neurosurg Psychiatry ; 95(1): 14-18, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-37221051

RESUMO

INTRODUCTION: Limited data exist on brain MRI enhancement in myelin-oligodendrocyte-glycoprotein (MOG) antibody-associated disease (MOGAD) and differences from aquaporin-4-IgG-positive-neuromyelitis-optica-spectrum-disorder (AQP4+NMOSD), and multiple sclerosis (MS). METHODS: In this retrospective observational study, we identified 122 Mayo Clinic MOGAD patients (1 January 1996-1 July 2020) with cerebral attacks. We explored enhancement patterns using a discovery set (n=41). We assessed enhancement frequency and Expanded Disability Status Scale scores at nadir and follow-up in the remainder (n=81). Two raters assessed T1-weighted-postgadolinium MRIs (1.5T/3T) for enhancement patterns in MOGAD, AQP4+NMOSD (n=14) and MS (n=26). Inter-rater agreement was assessed. Leptomeningeal enhancement clinical correlates were analysed. RESULTS: Enhancement occurred in 59/81 (73%) MOGAD cerebral attacks but did not influence outcome. Enhancement was often patchy/heterogeneous in MOGAD (33/59 (56%)), AQP4+NMOSD (9/14 (64%); p=0.57) and MS (16/26 (62%); p=0.63). Leptomeningeal enhancement favoured MOGAD (27/59 (46%)) over AQP4+NMOSD (1/14 (7%); p=0.01) and MS (1/26 (4%); p<0.001) with headache, fever and seizures frequent clinical correlates. Ring enhancement favoured MS (8/26 (31%); p=0.006) over MOGAD (4/59 (7%)). Linear ependymal enhancement was unique to AQP4+NMOSD (2/14 (14%)) and persistent enhancement (>3 months) was rare (0%-8%) across all groups. Inter-rater agreement for enhancement patterns was moderate. CONCLUSIONS: Enhancement is common with MOGAD cerebral attacks and often has a non-specific patchy appearance and rarely persists beyond 3 months. Leptomeningeal enhancement favours MOGAD over AQP4+NMOSD and MS.


Assuntos
Esclerose Múltipla , Neuromielite Óptica , Humanos , Instituições de Assistência Ambulatorial , Aquaporina 4 , Cefaleia , Neuroimagem , Neuromielite Óptica/diagnóstico por imagem , Glicoproteína Mielina-Oligodendrócito
15.
J Neurol Neurosurg Psychiatry ; 94(9): 757-768, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37221052

RESUMO

OBJECTIVE: To investigate relationships between serum neurofilament light chain (sNfL), ubiquitin C-terminal hydrolase L1 (sUCHL1), tau (sTau) and glial fibrillary acidic protein (sGFAP) levels and disease activity/disability in neuromyelitis optica spectrum disorder (NMOSD), and the effects of inebilizumab on these biomarkers in N-MOmentum. METHODS: N-MOmentum randomised participants to receive inebilizumab or placebo with a randomised controlled period (RCP) of 28 weeks and an open-label follow-up period of ≥2 years. The sNfL, sUCHL1, sTau and sGFAP were measured using single-molecule arrays in 1260 scheduled and attack-related samples from N-MOmentum participants (immunoglobulin G (IgG) autoantibodies to aquaporin-4-positive, myelin oligodendrocyte glycoprotein-IgG-positive or double autoantibody-negative) and two control groups (healthy donors and patients with relapsing-remitting multiple sclerosis). RESULTS: The concentration of all four biomarkers increased during NMOSD attacks. At attack, sNfL had the strongest correlation with disability worsening during attacks (Spearman R2=0.40; p=0.01) and prediction of disability worsening after attacks (sNfL cut-off 32 pg/mL; area under the curve 0.71 (95% CI 0.51 to 0.89); p=0.02), but only sGFAP predicted upcoming attacks. At RCP end, fewer inebilizumab-treated than placebo-treated participants had sNfL>16 pg/mL (22% vs 45%; OR 0.36 (95% CI 0.17 to 0.76); p=0.004). CONCLUSIONS: Compared with sGFAP, sTau and sUCHL1, sNfL at attack was the strongest predictor of disability worsening at attack and follow-up, suggesting a role for identifying participants with NMOSD at risk of limited post-relapse recovery. Treatment with inebilizumab was associated with lower levels of sGFAP and sNfL than placebo. TRIAL REGISTRATION NUMBER: NCT02200770.


Assuntos
Neuromielite Óptica , Humanos , Neuromielite Óptica/sangue , Neuromielite Óptica/tratamento farmacológico , Biomarcadores , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-Cego
16.
Mult Scler ; 29(8): 945-955, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37282545

RESUMO

BACKGROUND: The N-MOmentum trial investigated safety and efficacy of inebilizumab in participants with neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: Evaluate the attack identification process and adjudication committee (AC) performance in N-MOmentum. METHODS: Adults (n = 230) with NMOSD and Expanded Disability Status Scale score ⩽8 were randomized (3:1) to inebilizumab 300 mg or placebo. The randomized controlled period was 28 weeks or until adjudicated attack. Attacks were adjudicated according to 18 predefined criteria. Magnetic resonance imaging (MRI) and biomarker (serum glial fibrillary acidic protein [sGFAP]) analyses were performed. RESULTS: A total of 64 participant-reported neurological events occurred; 51 (80%) were investigator-determined to be attacks. The AC confirmed 43 of the investigator-determined attacks (84%). There was high inter- and intra-AC-member agreement. In 25/64 events (39%) and 14/43 AC-adjudicated attacks (33%), MRI was reviewed during adjudication. Retrospective analysis revealed new domain-specific T1 and T2 MRI lesions in 90% of adjudicated attacks. Increased mean sGFAP concentrations (>2-fold change) from baseline were observed in 56% of adjudicated attacks versus 14% of investigator-determined attacks rejected by the AC and 31% of participant-reported events determined not to be attacks. CONCLUSION: AC adjudication of NMOSD attacks according to predefined criteria appears robust. MRI lesion correlates and sGFAP elevations were found in most adjudicated attacks.


Assuntos
Anticorpos Monoclonais Humanizados , Neuromielite Óptica , Neuromielite Óptica/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética , Biomarcadores/sangue , Proteína Glial Fibrilar Ácida/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos Retrospectivos
17.
J Sex Med ; 20(4): 525-535, 2023 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-36779553

RESUMO

BACKGROUND: We based this study on the sexual wholeness model, which considers emotional, physical, and meaning elements of sexuality, and previous research that indicates variability in the associations among orgasm consistency, relational satisfaction, and sexual satisfaction. AIM: We performed a person-based latent class approach to examine variables linked with the trifecta of orgasm consistency, relational satisfaction, and sexual satisfaction. METHODS: We used a Mechanical Turk sample that consisted of 1645 sexually active participants (1032 women) to evaluate classes and related variables. OUTCOMES: Women divided into 5 classes and men into 3 classes. High orgasm consistency alone did not ensure sexual or relational satisfaction. RESULTS: We found that 5 groups emerged for women: high orgasm/low satisfaction (6%), low trifecta (8%), low orgasm/high satisfaction (16%), moderate orgasm/high satisfaction (15%), and high trifecta (55%). For men, 3 groups emerged: lower orgasm/high satisfaction (12%), moderate trifecta (14%), and high trifecta (74%). We also found that high orgasm consistency for women did not guarantee relational and sexual satisfaction, nor did lower orgasm consistency for men or women guarantee problematic relational and sexual satisfaction. CLINICAL IMPLICATIONS: Communication, attachment, and sexual harmony were key elements associated with positive trifecta outcomes. Clinicians and educators may emphasize the importance of these variables when individuals encounter sexual or relational distress. STRENGTHS AND LIMITATIONS: Data analytic techniques revealed a variety of groups for men and women and associations between a host of physical, psychological, and meaning variables and the trifecta of orgasm consistency, relational satisfaction, and sexual satisfaction. However, this study is cross-sectional and correlational, which limits the conclusions that we can draw from it. CONCLUSION: While the variables of orgasm consistency, relational satisfaction, and sexual satisfaction are each informative, together they help clinicians, educators, and researchers better understand the complexity of sex.


Assuntos
Orgasmo , Comportamento Sexual , Masculino , Humanos , Feminino , Estudos Transversais , Comportamento Sexual/psicologia , Sexualidade , Satisfação Pessoal , Parceiros Sexuais/psicologia , Inquéritos e Questionários
18.
J Sex Marital Ther ; 49(2): 229-241, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35796519

RESUMO

Sexuality is a highly complex aspect of a human's existence with several elements contributing to a quality sexual relationship. This study examined a broad scope of sexuality encompassing physical, emotional, and meaning aspects of sex, or sexual wholeness. Sexual wholeness is grounded in the idea that a self-determined sexual relationship in which three innate human needs (autonomy, competence, and relatedness) are met is more likely to promote sexual well-being. Using a sample of 884 adults in long-term relationships, we used structural equation modeling to estimate the association between each of the three self-determination theory (SDT) needs and the physical, emotional, and meaning aspects of sex. We found that overall, greater SDT needs satisfaction predicted sexual wholeness, though some needs held more bearing than others and the associations with components of sexual wholeness varied. For women, the physical aspect of sex was predicted by autonomy (predicted comfort) and competence (predicted sexual knowledge) but for the physical aspects of sex for men, no significant associations were found. The emotional aspect of sex was associated with all three SDT needs for both men and women and sexual meaning was associated with competence and relatedness for both men and women.


Assuntos
Emoções , Comportamento Sexual , Masculino , Adulto , Humanos , Feminino , Comportamento Sexual/psicologia , Autonomia Pessoal , Sexualidade , Satisfação Pessoal
19.
Proc Natl Acad Sci U S A ; 117(30): 17551-17557, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32647062

RESUMO

The rational creation of two-component conjugated polymer systems with high levels of phase purity in each component is challenging but crucial for realizing printed soft-matter electronics. Here, we report a mixed-flow microfluidic printing (MFMP) approach for two-component π-polymer systems that significantly elevates phase purity in bulk-heterojunction solar cells and thin-film transistors. MFMP integrates laminar and extensional flows using a specially microstructured shear blade, designed with fluid flow simulation tools to tune the flow patterns and induce shear, stretch, and pushout effects. This optimizes polymer conformation and semiconducting blend order as assessed by atomic force microscopy (AFM), transmission electron microscopy (TEM), grazing incidence wide-angle X-ray scattering (GIWAXS), resonant soft X-ray scattering (R-SoXS), photovoltaic response, and field effect mobility. For printed all-polymer (poly[(5,6-difluoro-2-octyl-2H-benzotriazole-4,7-diyl)-2,5-thiophenediyl[4,8-bis[5-(2-hexyldecyl)-2-thienyl]benzo[1,2-b:4,5-b']dithiophene-2,6-diyl]-2,5-thiophenediyl]) [J51]:(poly{[N,N'-bis(2-octyldodecyl)naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)}) [N2200]) solar cells, this approach enhances short-circuit currents and fill factors, with power conversion efficiency increasing from 5.20% for conventional blade coating to 7.80% for MFMP. Moreover, the performance of mixed polymer ambipolar [poly(3-hexylthiophene-2,5-diyl) (P3HT):N2200] and semiconducting:insulating polymer unipolar (N2200:polystyrene) transistors is similarly enhanced, underscoring versatility for two-component π-polymer systems. Mixed-flow designs offer modalities for achieving high-performance organic optoelectronics via innovative printing methodologies.

20.
Proc Natl Acad Sci U S A ; 117(31): 18231-18239, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32703807

RESUMO

The field-effect electron mobility of aqueous solution-processed indium gallium oxide (IGO) thin-film transistors (TFTs) is significantly enhanced by polyvinyl alcohol (PVA) addition to the precursor solution, a >70-fold increase to 7.9 cm2/Vs. To understand the origin of this remarkable phenomenon, microstructure, electronic structure, and charge transport of IGO:PVA film are investigated by a battery of experimental and theoretical techniques, including In K-edge and Ga K-edge extended X-ray absorption fine structure (EXAFS); resonant soft X-ray scattering (R-SoXS); ultraviolet photoelectron spectroscopy (UPS); Fourier transform-infrared (FT-IR) spectroscopy; time-of-flight secondary-ion mass spectrometry (ToF-SIMS); composition-/processing-dependent TFT properties; high-resolution solid-state 1H, 71Ga, and 115In NMR spectroscopy; and discrete Fourier transform (DFT) analysis with ab initio molecular dynamics (MD) liquid-quench simulations. The 71Ga{1H} rotational-echo double-resonance (REDOR) NMR and other data indicate that PVA achieves optimal H doping with a Ga···H distance of ∼3.4 Å and conversion from six- to four-coordinate Ga, which together suppress deep trap defect localization. This reduces metal-oxide polyhedral distortion, thereby increasing the electron mobility. Hydroxyl polymer doping thus offers a pathway for efficient H doping in green solvent-processed metal oxide films and the promise of high-performance, ultra-stable metal oxide semiconductor electronics with simple binary compositions.

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