Robust Machine Learning-Based Correction on Automatic Segmentation of the Cerebellum and Brainstem.

Automated segmentation is a useful method for studying large brain structures such as the cerebellum and brainstem. However, automated segmentation may lead to inaccuracy and/or undesirable boundary. The goal of the present study was to investigate whether SegAdapter, a machine learning-based method, is useful for automatically correcting large segmentation errors and disagreement in anatomical definition. We further assessed the robustness of the method in handling size of training set, differences in head coil usage, and amount of brain atrophy. High resolution T1-weighted images were acquired from 30 healthy controls scanned with either an 8-channel or 32-channel head coil. Ten patients, who suffered from brain atrophy because of fragile X-associated tremor/ataxia syndrome, were scanned using the 32-channel head coil. The initial segmentations of the cerebellum and brainstem were generated automatically using Freesurfer. Subsequently, Freesurfer's segmentations were both manually corrected to serve as the gold standard and automatically corrected by SegAdapter. Using only 5 scans in the training set, spatial overlap with manual segmentation in Dice coefficient improved significantly from 0.956 (for Freesurfer segmentation) to 0.978 (for SegAdapter-corrected segmentation) for the cerebellum and from 0.821 to 0.954 for the brainstem. Reducing the training set size to 2 scans only decreased the Dice coefficient ≤0.002 for the cerebellum and ≤ 0.005 for the brainstem compared to the use of training set size of 5 scans in corrective learning. The method was also robust in handling differences between the training set and the test set in head coil usage and the amount of brain atrophy, which reduced spatial overlap only by <0.01. These results suggest that the combination of automated segmentation and corrective learning provides a valuable method for accurate and efficient segmentation of the cerebellum and brainstem, particularly in large-scale neuroimaging studies, and potentially for segmenting other neural regions as well

Evaluation of human acellular dermis versus porcine acellular dermis in an in vivo model for incisional hernia repair

Incisional hernias commonly occur following abdominal wall surgery. Human acellular dermal matrices (HADM) are widely used in abdominal wall defect repair. Xenograft acellular dermal matrices, particularly those made from porcine tissues (PADM), have recently experienced increased usage. The purpose of this study was to compare the effectiveness of HADM and PADM in the repair of incisional abdominal wall hernias in a rabbit model. A review from earlier work of differences between human allograft acellular dermal matrices (HADM) and porcine xenograft acellular dermal matrices (PADM) demonstrated significant differences (P < 0.05) in mechanical properties: Tensile strength 15.7 MPa vs. 7.7 MPa for HADM and PADM, respectively. Cellular (fibroblast) infiltration was significantly greater for HADM vs. PADM (Armour). The HADM exhibited a more natural, less degraded collagen by electrophoresis as compared to PADM. The rabbit model surgically established an incisional hernia, which was repaired with one of the two acellular dermal matrices 3 weeks after the creation of the abdominal hernia. The animals were euthanized at 4 and 20 weeks and the wounds evaluated. Tissue ingrowth into the implant was significantly faster for the HADM as compared to PADM, 54 vs. 16% at 4 weeks, and 58 vs. 20% for HADM and PADM, respectively at 20 weeks. The original, induced hernia defect (6 cm2) was healed to a greater extent for HADM vs. PADM: 2.7 cm2 unremodeled area for PADM vs. 1.0 cm² for HADM at 20 weeks. The inherent uniformity of tissue ingrowth and remodeling over time was very different for the HADM relative to the PADM. No differences were observed at the 4-week end point. However, the 20-week data exhibited a statistically different level of variability in the remodeling rate with the mean standard deviation of 0.96 for HADM as contrasted to a mean standard deviation of 2.69 for PADM. This was significant with P < 0.05 using a one tail F test for the inherent variability of the standard deviation. No significant differences between the PADM and HADM for adhesion, inflammation, fibrous tissue or neovascularization were noted

Tracking Assaultâ injured, Drugâ using Youth in Longitudinal Research: Followâ up Methods

ObjectivesViolence is one of the leading causes of death among youth ages 14 to 24. Hospitalâ and emergency department (ED)â based violence prevention programs are increasingly becoming a critical part of public health efforts; however, evaluation of prevention efforts is needed to create evidenceâ based best practices. Retention of study participants is key to evaluations, although little literature exists regarding optimizing followâ up methods for violently injured youth. This study aims to describe the methods for retention in youth violence studies and the characteristics of hardâ toâ reach participants.MethodsThe Flint Youth Injury (FYI) Study is a prospective study following a cohort of assaultâ injured, drugâ using youth recruited in an urban ED, and a comparison population of drugâ using youth seeking medical or nonâ violenceâ related injury care. Validated survey instruments were administered at baseline and four followâ up time points (6, 12, 18, and 24 months). Followâ up contacts used a variety of strategies and all attempts were coded by type and level of success. Regression analysis was used to predict contact difficulty and followâ up interview completion at 24 months.ResultsA total of 599 patients (ages 14â 24) were recruited from the ED (mean ± SD age = 20.1 ± 2.4 years, 41.2% female, 58.2% African American), with followâ up rates at 6, 12, 18, and 24 months of 85.3%, 83.7% 84.2%, and 85.3%, respectively. Participant contact efforts ranged from two to 53 times per followâ up time frame to complete a followâ up appointment, and more than 20% of appointments were completed off site at community locations (e.g., participantsâ homes, jail/prison). Participants who were younger (p < 0.05) and female (p < 0.01) were more likely to complete their 24â month followâ up interview. Participants who sought care in the ED for assault injury (p < 0.05) and had a substance use disorder (p < 0.01) at baseline required fewer contact attempts to complete their 24â month followâ up, while participants reporting a fight within the immediate 3 months before their 24â month followâ up (p < 0.01) required more intensive contact efforts.ConclusionsThe FYI study demonstrated that achieving high followâ up rates for a difficultâ toâ track, violentlyâ injured ED population is feasible through the use of established contact strategies and a variety of interview locations. Results have implications for followâ up strategies planned as part of other violence prevention studies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146571/1/acem13495_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146571/2/acem13495.pd

Near-infrared Emission Spectrum of WASP-103b Using Hubble Space Telescope/Wide Field Camera 3

We present here our observations and analysis of the dayside emission spectrum of the hot Jupiter WASP-103b. We observed WASP-103b during secondary eclipse using two visits of the Hubble Space Telescope with the G141 grism on Wide Field Camera 3 in spatial scan mode. We generated secondary eclipse light curves of the planet in both blended white-light and spectrally binned wavechannels from 1.1-1.7 µm and corrected the light curves for flux contamination from a nearby companion star. We modeled the detector systematics and secondary eclipse spectrum using Gaussian process regression and found that the near-IR emission spectrum of WASP-103b is featureless across the observed near-IR region to down to a sensitivity of 175 ppm, and shows a shallow slope toward the red. The atmosphere has a single brightness temperature of T_B = 2890 K across this wavelength range. This region of the spectrum is indistinguishable from isothermal, but may not manifest from a physically isothermal system, i.e., pseudo-isothermal. A solar-metallicity profile with a thermal inversion layer at 10^(−2) bar fits the spectrum of WASP-103b with high confidence, as do an isothermal profile with solar metallicity and a monotonically decreasing atmosphere with C/O > 1. The data rule out a monotonically decreasing atmospheric profile with solar composition, and we rule out a low-metallicity decreasing profile as unphysical for this system. The pseudo-isothermal profile could be explained by a thermal inversion layer just above the layer probed by our observations, or by clouds or haze in the upper atmosphere. Transmission spectra at optical wavelengths would allow us to better distinguish between potential atmospheric models

Organic matter composition and the protist and nematode communities around anecic earthworm burrows

By living in permanent burrows and incorporating organic detritus from the soil surface, anecic earthworms contribute to soil heterogeneity, but their impact is still under-studied in natural field conditions. We investigated the effects of the anecic earthworm Lumbricus centralis on fresh carbon (C) incorporation, soil organic matter composition, protists, and nematodes of a Cambisol under grassland. We used plant material labelled with stable isotope tracers to detect fresh C input around earthworm-occupied burrows or around burrows from which the earthworm had been removed. After 50 days, we sampled soil (0–10 cm depth) in concentric layers around the burrows, distinguishing between drilosphere (0–8 mm) and bulk soil (50–75 mm). L. centralis effectively incorporated fresh C into the drilosphere, and this shifted soil organic matter amount and chemistry: total soil sugar content was increased compared to unoccupied drilosphere and bulk soil, and the contribution of plant-derived sugars to soil organic matter was enhanced. Earthworms also shifted the spatial distribution of soil C towards the drilosphere. The total abundance of protists and nematodes was only slightly higher in earthworm-occupied drilosphere, but strong positive effects were found for some protist clades (e.g. Stenamoeba spp.). Additional data for the co-occurring anecic earthworm species Aporrectodea longa showed that it incorporated fresh C less than L. centralis, suggesting that the two species may have different effects on soil C distribution and organic matter quality

Inhibition of HIV Env binding to cellular receptors by monoclonal antibody 2G12 as probed by Fc-tagged gp120

During natural HIV infection, an array of host receptors are thought to influence virus attachment and the kinetics of infection. In this study, to probe the interactions of HIV envelope (Env) with various receptors, we assessed the inhibitory properties of various anti-Env monoclonal antibodies (mAbs) in binding assays. To assist in detecting Env in attachment assays, we generated Fc fusions of full-length wild-type gp120 and several variable loop-deleted gp120s. Through investigation of the inhibition of Env binding to cell lines expressing CD4, CCR5, DC-SIGN, syndecans or combinations thereof, we found that the broadly neutralizing mAb, 2G12, directed to a unique carbohydrate epitope of gp120, inhibited Env-CCR5 binding, partially inhibited Env-DC-SIGN binding, but had no effect on Env-syndecan association. Furthermore, 2G12 inhibited Env attachment to primary monocyte-derived dendritic cells, that expressed CD4 and CCR5 primary HIV receptors, as well as DC-SIGN, and suggested that the dual activities of 2G12 could be valuable in vivo for inhibiting initial virus dissemination and propagation

Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 12-month analysis of the phase 3 ILLUMINATE-B trial

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that causes progressive kidney damage and systemic oxalosis due to hepatic overproduction of oxalate. Lumasiran demonstrated efficacy and safety in the 6-month primary analysis period of the phase 3, multinational, open-label, single-arm ILLUMINATE-B study of infants and children < 6 years old with PH1 (ClinicalTrials.gov: NCT03905694 (4/1/2019); EudraCT: 2018–004,014-17 (10/12/2018)). Outcomes in the ILLUMINATE-B extension period (EP) for patients who completed ≥ 12 months on study are reported here. METHODS: Of the 18 patients enrolled in the 6-month primary analysis period, all entered the EP and completed ≥ 6 additional months of lumasiran treatment (median (range) duration of total exposure, 17.8 (12.7–20.5) months). RESULTS: Lumasiran treatment was previously reported to reduce spot urinary oxalate:creatinine ratio by 72% at month 6, which was maintained at 72% at month 12; mean month 12 reductions in prespecified weight subgroups were 89%, 68%, and 71% for patients weighing < 10 kg, 10 to < 20 kg, and ≥ 20 kg, respectively. The mean reduction from baseline in plasma oxalate level was reported to be 32% at month 6, and this improved to 47% at month 12. Additional improvements were also seen in nephrocalcinosis grade, and kidney stone event rates remained low. The most common lumasiran-related adverse events were mild, transient injection-site reactions (3 patients (17%)). CONCLUSIONS: Lumasiran treatment provided sustained reductions in urinary and plasma oxalate through month 12 across all weight subgroups, with an acceptable safety profile, in infants and young children with PH1. GRAPHICAL ABSTRACT: A higher resolution version of the Graphical abstract is available as Supplementary information

In vivo Hypoxia and a Fungal Alcohol Dehydrogenase Influence the Pathogenesis of Invasive Pulmonary Aspergillosis

Currently, our knowledge of how pathogenic fungi grow in mammalian host environments is limited. Using a chemotherapeutic murine model of invasive pulmonary aspergillosis (IPA) and 1H-NMR metabolomics, we detected ethanol in the lungs of mice infected with Aspergillus fumigatus. This result suggests that A. fumigatus is exposed to oxygen depleted microenvironments during infection. To test this hypothesis, we utilized a chemical hypoxia detection agent, pimonidazole hydrochloride, in three immunologically distinct murine models of IPA (chemotherapeutic, X-CGD, and corticosteroid). In all three IPA murine models, hypoxia was observed during the course of infection. We next tested the hypothesis that production of ethanol in vivo by the fungus is involved in hypoxia adaptation and fungal pathogenesis. Ethanol deficient A. fumigatus strains showed no growth defects in hypoxia and were able to cause wild type levels of mortality in all 3 murine models. However, lung immunohistopathology and flow cytometry analyses revealed an increase in the inflammatory response in mice infected with an alcohol dehydrogenase null mutant strain that corresponded with a reduction in fungal burden. Consequently, in this study we present the first in vivo observations that hypoxic microenvironments occur during a pulmonary invasive fungal infection and observe that a fungal alcohol dehydrogenase influences fungal pathogenesis in the lung. Thus, environmental conditions encountered by invading pathogenic fungi may result in substantial fungal metabolism changes that influence subsequent host immune responses

The Role of Pathological Aging in Cardiac and Pulmonary Fibrosis

Aging promotes a range of degenerative pathologies characterized by progressive losses of tissue and/or cellular function. Fibrosis is the hardening, overgrowth and scarring of various tissues characterized by the accumulation of extracellular matrix components. Aging is an important predisposing factor common for fibrotic heart and respiratory disease. Age-related processes such as senescence, inflammaging, autophagy and mitochondrial dysfunction are interconnected biological processes that diminish the regenerative capacity of the aged heart and lung and have been shown to play a crucial role in cardiac fibrosis and idiopathic pulmonary fibrosis. This review focuses on these four processes of aging in relation to their role in fibrosis. It has long been established that the heart and lung are linked both functionally and anatomically when it comes to health and disease, with an ever-expanding aging population, the incidence of fibrotic disease and therefore the number of fibrosis-related deaths will continue to rise. There are currently no feasible therapies to treat the effects of chronic fibrosis therefore highlighting the importance of exploring the processes of aging and its role in inducing and exacerbating fibrosis of each organ. The focus of this review may help to highlight potential avenues of therapeutic exploration</p