Huts and History Geier, Clarence R; Orr, David G; Reeves, Matthew B
2006, 20060101
eBook
Explores the fascinating history of encampments, while establishing new models for their study, emphasizing innovative and non-traditional methods to delve into the data sets that really give us ...insight into a soldier's life in the field.
A novel series of imidazolidinone-based matrix metalloproteinase (MMP) inhibitors was discovered by structural modification of pyrrolidinone
1a. Potent inhibition of MMP-13 was exhibited by the ...analogues having 4-(4-fluorophenoxy)phenyl (
4a, IC
50=3
nM) and 4-(naphth-2-yloxy)phenyl (
4h, IC
50=4
nM) as P1′ groups.
Graphic
Cancer cachexia is a multifactorial syndrome characterised by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support alone. Cachexia has a high ...prevalence in cancer and a major impact on patient physical function, morbidity and mortality. Despite the consequences of cachexia, there is no licensed treatment for cachexia and no accepted standard of care. It has been argued that the multifactorial genesis of cachexia lends itself to therapeutic targeting through a multimodal treatment. Following a successful phase II trial, a phase III randomised controlled trial of a multimodal cachexia intervention is under way. Termed the MENAC trial (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia), this intervention is based on evidence to date and consists of non-steroidal anti-inflammatory drugs and eicosapentaenoic acid to reduce inflammation, a physical exercise programme using resistance and aerobic training to increase anabolism, as well as dietary counselling and oral nutritional supplements to promote energy and protein balance. Herein we describe the development of this trial.
NCT02330926.
When Professor Cornelius Conway Felton of Harvard was laid to rest in the spring of 1862, he was remembered as a man of warmth and wit, with a sense of humour which, though easily animated, never ...undermined the "manliness of his character" (Woolsey 1862, 16). "The spirit of Aristopha- nes lodged in Professor Felton," remarked Theodore Woolsey, president of Yale College; "he had the same sense of the ludicrous, the same keen judgment of character, the same underlying earnestness of patriotism, the same political conservatism" (8). Like many of his Harvard colleagues, Fel- ton was also a "reverent and devout" Unitarian, a conservative Whig, and a lively and prolific contributor to the staid organ of the Boston intellectual aristocracy, the North American Review (19).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Medically underserved people with type 2 diabetes mellitus face limited access to group-based diabetes care, placing them at risk for poor disease control and complications. Immersive technology and ...telemedicine solutions could bridge this gap.
The purpose of this study was to compare the effectiveness of diabetes medical group visits (DMGVs) delivered in an immersive telemedicine platform versus an in-person (IP) setting and establish the noninferiority of the technology-enabled approach for changes in hemoglobin A
(HbA
) and physical activity (measured in metabolic equivalent of task MET) at 6 months.
This study is a noninferiority randomized controlled trial conducted from February 2017 to December 2019 at an urban safety net health system and community health center. We enrolled adult women (aged ≥18 years) who self-reported African American or Black race or Hispanic or Latina ethnicity and had type 2 diabetes mellitus and HbA
≥8%. Participants attended 8 weekly DMGVs, which included diabetes self-management education, peer support, and clinician counseling using a culturally adapted curriculum in English or Spanish. In-person participants convened in clinical settings, while virtual world (VW) participants met remotely via an avatar-driven, 3D VW linked to video teleconferencing. Follow-up occurred 6 months post enrollment. Primary outcomes were mean changes in HbA
and physical activity at 6 months, with noninferiority margins of 0.7% and 12 MET-hours, respectively. Secondary outcomes included changes in diabetes distress and depressive symptoms.
Of 309 female participants (mean age 55, SD 10.6 years; n=195, 63% African American or Black; n=105, 34% Hispanic or Latina; n=151 IP; and n=158 in VW), 207 (67%) met per-protocol criteria. In the intention-to-treat analysis, we confirmed noninferiority for primary outcomes. We found similar improvements in mean HbA
by group at 6 months (IP: -0.8%, SD 1.9%; VW: -0.5%, SD 1.8%; mean difference 0.3, 97.5% CI -∞ to 0.3; P<.001). However, there were no detectable improvements in physical activity (IP: -6.5, SD 43.6; VW: -9.6, SD 44.8 MET-hours; mean difference -3.1, 97.5% CI -6.9 to ∞; P=.02). The proportion of participants with significant diabetes distress and depressive symptoms at 6 months decreased in both groups.
In this noninferiority randomized controlled trial, immersive telemedicine was a noninferior platform for delivering diabetes care, eliciting comparable glycemic control improvement, and enhancing patient engagement, compared to IP DMGVs.
ClinicalTrials.gov NCT02726425; https://clinicaltrials.gov/ct2/show/NCT02726425.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Post-traumatic stress disorder (PTSD) is a debilitating disorder defined by the onset of intrusive, avoidant, negative cognitive or affective, and/or hyperarousal symptoms after ...witnessing or experiencing a traumatic event. Previous voxel-based morphometry studies have provided insight into structural brain alterations associated with PTSD with notable heterogeneity across these studies. Furthermore, how structural alterations may be associated with brain function, as measured by task-free and task-based functional connectivity, remains to be elucidated.
Methods
Using emergent meta-analytic techniques, we sought to first identify a consensus of structural alterations in PTSD using the anatomical likelihood estimation (ALE) approach. Next, we generated functional profiles of identified convergent structural regions utilizing resting-state functional connectivity (rsFC) and meta-analytic co-activation modeling (MACM) methods. Finally, we performed functional decoding to examine mental functions associated with our ALE, rsFC, and MACM brain characterizations.
Results
We observed convergent structural alterations in a single region located in the medial prefrontal cortex. The resultant rsFC and MACM maps identified functional connectivity across a widespread, whole-brain network that included frontoparietal and limbic regions. Functional decoding revealed overlapping associations with attention, memory, and emotion processes.
Conclusions
Consensus-based functional connectivity was observed in regions of the default mode, salience, and central executive networks, which play a role in the tripartite model of psychopathology. Taken together, these findings have important implications for understanding the neurobiological mechanisms associated with PTSD.
Objective: There is a pressing need to elucidate the brain-behavior interactions underlying autism spectrum disorders (ASD) given the marked rise in ASD diagnosis over the past decade. Functional ...magnetic resonance imaging (fMRI) has begun to address this need, but few fMRI studies have evaluated age-related changes in ASD. Therefore, we conducted a developmental analysis of activation likelihood estimation (ALE) meta-analysis to compare child versus adult ASD fMRI studies. We hypothesized that children and adolescents with ASD (less than 18 years old) would rely less on prefrontal cortex structures than adults (greater than or equal to = 18 years old). Method: PubMed and PsycInfo literature searches were conducted to identify task-dependent fMRI studies of children or adults with ASD. Then recent GingerALE software improvements were leveraged to perform direct comparisons of child (n = 18) versus adult (n = 24) studies. Results: ALE meta-analyses of social tasks showed that children and adolescents with ASD versus adults had significantly greater hyperactivation in the left post-central gyrus, and greater hypoactivation in the right hippocampus and right superior temporal gyrus. ALE meta-analyses of nonsocial tasks showed that children with ASD versus adults had significantly greater hyperactivation in the right insula and left cingulate gyrus, and hypoactivation in the right middle frontal gyrus. Conclusion: Our data suggest that the neural alterations associated with ASD are not static, occurring only in early childhood. Instead, children with ASD have altered neural activity compared to adults during both social and nonsocial tasks, especially in fronto-temporal structures. Longitudinal neuroimaging studies are required to examine these changes prospectively, as potential targets for brain-based treatments for ASD. (Contains 7 figures and 4 tables.)
We previously identified missense mutations in the U2AF1 splicing factor affecting codons S34 (S34F and S34Y) or Q157 (Q157R and Q157P) in 11% of the patients with de novo myelodysplastic syndrome ...(MDS). Although the role of U2AF1 as an accessory factor in the U2 snRNP is well established, it is not yet clear how these mutations affect splicing or contribute to MDS pathophysiology. We analyzed splice junctions in RNA-seq data generated from transfected CD34+ hematopoietic cells and found significant differences in the abundance of known and novel junctions in samples expressing mutant U2AF1 (S34F). For selected transcripts, splicing alterations detected by RNA-seq were confirmed by analysis of primary de novo MDS patient samples. These effects were not due to impaired U2AF1 (S34F) localization as it co-localized normally with U2AF2 within nuclear speckles. We further found evidence in the RNA-seq data for decreased affinity of U2AF1 (S34F) for uridine (relative to cytidine) at the e-3 position immediately upstream of the splice acceptor site and corroborated this finding using affinity-binding assays. These data suggest that the S34F mutation alters U2AF1 function in the context of specific RNA sequences, leading to aberrant alternative splicing of target genes, some of which may be relevant for MDS pathogenesis.
Abstract
We use observations with the infrared-optimized Magellan Adaptive Optics (MagAO) system and Clio camera in 3.9
μ
m light to place stringent mass constraints on possible undetected companions ...to Sirius A. We suppress the light from Sirius A by imaging it through a grating vector-apodizing phase plate coronagraph with a 180° dark region (gvAPP-180). To remove residual starlight in postprocessing, we apply a time-domain principal-components-analysis-based algorithm we call PCA-Temporal, which uses eigen time series rather than eigenimages to subtract starlight. By casting the problem in terms of eigen time series, we reduce the computational cost of postprocessing the data, enabling the use of the fully sampled data set for improved contrast at small separations. We also discuss the impact of retaining fine temporal sampling of the data on final contrast limits. We achieve postprocessed contrast limits of 1.5 × 10
−6
–9.8 × 10
−6
outside of 0.″75, which correspond to planet masses of 2.6–8.0
M
J
. These are combined with values from the recent literature of high-contrast imaging observations of Sirius to synthesize an overall completeness fraction as a function of mass and separation. After synthesizing these recent studies and our results, the final completeness analysis rules out 99% of ≥9
M
J
planets from 2.5 to 7 au.
The cerebellum historically has been thought to mediate motor and sensory signals between the body and cerebral cortex, yet cerebellar lesions are also associated with altered cognitive behavioral ...performance. Neuroimaging evidence indicates that the cerebellum contributes to a wide range of cognitive, perceptual, and motor functions. Here, we used the BrainMap database to investigate whole-brainco-activation patterns between cerebellar structures and regions of the cerebral cortex, as well as associations with behavioral tasks. Hierarchical clustering was performed to meta-analytically identify cerebellar structures with similar cortical co-activation, and independently, with similar correlations to specific behavioral tasks. Strong correspondences were observed in these separate but parallel analyses of meta-analytic connectivity and behavioral metadata. We recovered differential zones of cerebellar co-activation that are reflected across the literature. Furthermore, the behaviors and tasks associated with the different cerebellar zones provide insight into the specialized function of the cerebellum, relating to high-order cognition, emotion, perception, interoception, and action. Taken together, these task-basedmeta-analytic results implicate distinct zones of the cerebellum as critically involved in the monitoring and mediation of psychological responses to internal and external stimuli.
•Cerebellar organization was investigated through meta-analytic methods.•Co-activation and behavioral clustering analyses yielded four clusters.•Clusters demonstrated co-activation with pre-frontal and motor cortices.•Results supported cerebellar involvement in both cognitive and motor functions.•This model elaborated on theories about cerebellar monitoring of mental processes.
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