Remediation of disfiguring scratches and abrasions on aging plastics challenges even the most experienced conservator. This study assesses the effect of three NOVUS polishing products on remediation ...of poly (methyl methacrylate) (PMMA). Samples were prepared to mimic the depth and type of scratches observed during conservation treatment performed on vacuum-formed reliefs from the 1960s. The study compares samples of new/unaged PMMA to naturally aged PMMA samples. Two different methods were successfully used to assess the polishing efficacy, which is notoriously challenging to document in transparent and reflective media: (1) image segmentation analysis of photographs to yield scratched area fractions, using three approaches (Li-thresholding, random forest, and convolution neural network); and (2) optical profilometry measurements, which provide surface root-mean-square roughness (R
RMS
) values. Both methods support the qualitative observations that polishing with the abrasive NOVUS products significantly reduced the surface damage; scratch area fractions decreased from 50-60% to 1-5% across the aged PMMA types after treatment, corresponding to an ∼85% decrease in surface roughness. Critically, the two methods are complementary: the image segmentation results demonstrated a greater visible difference between two degrees of polishing treatments on the new material, while profilometry results were able to parse differences in the degree of scratch reduction between the aged and new materials.
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BFBNIB, NMLJ, NUK, PILJ, SAZU, UL, UM, UPUK, ZRSKP
RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in ...influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat. In this study, we identified 553 patients carrying biallelic RFC1 expansions and measured the repeat expansion size in 392 cases. Pearson's coefficient was calculated to assess the correlation between the repeat size and age at disease onset. A Cox model with robust cluster standard errors was adopted to describe the effect of repeat size on age at disease onset, on age at onset of each individual symptoms, and on disease progression. A quasi-Poisson regression model was used to analyse the relationship between phenotype and repeat size. We performed multivariate linear regression to assess the association of the repeat size with the degree of cerebellar atrophy. Meiotic stability was assessed by Southern blotting on first-degree relatives of 27 probands. Finally, somatic instability was investigated by optical genome mapping on cerebellar and frontal cortex and unaffected peripheral tissue from four post-mortem cases. A larger repeat size of both smaller and larger allele was associated with an earlier age at neurological onset smaller allele hazard ratio (HR) = 2.06, P < 0.001; larger allele HR = 1.53, P < 0.001 and with a higher hazard of developing disabling symptoms, such as dysarthria or dysphagia (smaller allele HR = 3.40, P < 0.001; larger allele HR = 1.71, P = 0.002) or loss of independent walking (smaller allele HR = 2.78, P < 0.001; larger allele HR = 1.60; P < 0.001) earlier in disease course. Patients with more complex phenotypes carried larger expansions smaller allele: complex neuropathy rate ratio (RR) = 1.30, P = 0.003; cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) RR = 1.34, P < 0.001; larger allele: complex neuropathy RR = 1.33, P = 0.008; CANVAS RR = 1.31, P = 0.009. Furthermore, larger repeat expansions in the smaller allele were associated with more pronounced cerebellar vermis atrophy (lobules I-V β = -1.06, P < 0.001; lobules VI-VII β = -0.34, P = 0.005). The repeat did not show significant instability during vertical transmission and across different tissues and brain regions. RFC1 repeat size, particularly of the smaller allele, is one of the determinants of variability in RFC1 disease and represents a key prognostic factor to predict disease onset, phenotype and severity. Assessing the repeat size is warranted as part of the diagnostic test for RFC1 expansion.
Aims:
In order to improve self- efficacy and clinical outcomes for people with diabetes, new approaches using more interactive methods of group education are being promoted. We report results of an ...educator evaluation of IDEA to assist others who may be interested in starting similar groups in their care settings.
Methods:
A qualitative analysis was conducted as part of an ongoing randomized trial comparing two different educational interventions (Group IDEA and Individual Education) to Usual Care. As part of the study, educators at HealthPartners clinics in Minneapolis, MN and ABQ Health Partners in Albuquerque, NM were trained on how to use Conversation Maps (CM). All educators completed a Likert scale questionnaire after each CM session with responses from 1–10 (10 being the best). An open- ended evaluation form was also used to solicit positive and negative opinions about the sessions.
Analysis:
The data consisted of 48 nurse and dietitian evaluations from two sites. The mean Likert scores of the educational experience were calculated and compared for each site and for each of the four CM topics (general information, monitoring, nutrition, and complications). All eight research team members also reviewed answers to the open-ended questions and group consensus was used to describe positive and negative themes.
Results:
Educator rated Likert scores of map sessions were excellent (mean scores for Maps 1, 2, 3, 4: Overall success 8.3, 7.6, 7.7, 8.8; Ease and comfort levels in facilitation 8.9, 8.9, 9.2, 9.5; Patient motivation to self-manage 7.7, 6.9, 8, 8.8). Scores did not differ significantly across sites or between maps. Positive comments on the maps outweighed the negatives. The challenges identified were:
Disruptive (especially angry or negative) people;
Distracting topics raised by patients and late arrivals;
Variable reading levels among patients (too hard or too easy); and
Not enough time to cover the content (especially nutrition).
Conclusions:
The IDEA method was perceived positively by educators due to its ability to promote patient interaction, sharing, and meaningful discussion. To be successful, however, educators need tips and practice on handling disruptive patients, distractions, variance in literacy, and covering intended nutritional content in a group context.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The IDEA Study, a multisite randomized trial, is underway, conducted by researchers at HealthPartners Research Foundation (HP) in Minneapolis, Minn., and LCF Research (LCF), in Albuquerque, N.M. The ...study aims to evaluate the effectiveness of two methods of education: 1 a traditional individual educational approach and 2 a more novel group-based, interactive learning experience called IDEA (Interactive Dialogue to Educate and Activate) using the U.S. Diabetes Conversation Map education program (created by Healthy Interactions in collaboration with the American Diabetes Association ADA and sponsored by Merck & Co.). Using six components, including a map visual, conversation questions, discussion cards, group interaction, facilitation, and an action plan, the overall purpose of the group visit was to empower individuals with diabetes to take responsibility for their own health and well-being.3-4 Each map, a laminated 3-by-5-foot table-top visual with colorful drawings as metaphors of situations familiar to people with diabetes, is placed on a table with participants gathered around it.
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CMK, NUK, UL, UM, UPUK, VSZLJ
Cells from patients with the human genetic disorder ataxia-telangiectasia (A-T) are defective in the activation of cell cycle checkpoints in response to ionizing radiation damage. In order to ...understand the role of ATM in checkpoint control we investigated whether Schizosaccaromyces pombe chk1, a protein kinase implicated in controlling the G2 DNA damage checkpoint, might alter the radiosensitive phenotype in A-T cells. The fission yeast chkl gene was cloned into an EBV-based vector under the control of a metallothionein promoter and transfected into A-T lymphoblastoid cells. Induction of chk1 enhanced the survival of an A-T cell line in response to radiation exposure as determined by cell viability and reduction of radiation-induced chromosome aberrations. This can be accounted for at least in part by the restoration of the G2 checkpoint to chk1 expressing cells. There was no evidence that chk1 expression corrected either the G1/S checkpoint or radioresistant DNA synthesis in S phase in these cells. These results suggest that chk1 when overexpressed acts downstream from ATM to restore the G2 checkpoint in these cells and correct the radiosensitive phenotype. These data allow us to dissociate individual checkpoint events and relate them to the radiosensitive phenotype in A-T cells.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Brown rot decay removes cellulose and hemicellulose from wood—residual lignin contributing up to 30% of forest soil carbon—and is derived from an ancestral white rot saprotrophy in which both lignin ...and cellulose are decomposed. Comparative and functional genomics of the "dry rot" fungus Serpula lacrymans, derived from forest ancestors, demonstrated that the evolution of both ectomycorrhizal biotrophy and brown rot saprotrophy were accompanied by reductions and losses in specific protein families, suggesting adaptation to an intercellular interaction with plant tissue. Transcriptome and proteome analysis also identified differences in wood decomposition in S. lacrymans relative to the brown rot Postia placenta. Furthermore, fungal nutritional mode diversification suggests that the boreal forest biome originated via genetic coevolution of above- and below-ground biota.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract
Cochlear implants (CIs) have proven to be a useful treatment option for individuals with severe-to-profound hearing loss by providing improved access to one's surrounding auditory ...environment. CIs differ from traditional acoustic amplification by providing information to the auditory system via electrical stimulation. Both postlingually deafened adults and prelingually deafened children can benefit from a CI; however, outcomes with a CI can vary. Numerous factors can impact performance outcomes with a CI. It is important for the audiologist to understand what factors might play a role and impact performance outcomes with a CI so that they can effectively counsel the recipient and their family, as well as establish appropriate and realistic expectations with a CI. This review article will discuss the CI candidacy process, CI programming and postoperative follow-up care, as well as considerations across the lifespan that may affect performance outcomes with a CI.
Manipulation of the gut microbiome using live biotherapeutic products shows promise for clinical applications but remains challenging to achieve. Here, we induced dysbiosis in 56 healthy volunteers ...using antibiotics to test a synbiotic comprising the infant gut microbe, Bifidobacterium longum subspecies infantis (B. infantis), and human milk oligosaccharides (HMOs). B. infantis engrafted in 76% of subjects in an HMO-dependent manner, reaching a relative abundance of up to 81%. Changes in microbiome composition and gut metabolites reflect altered recovery of engrafted subjects compared with controls. Engraftment associates with increases in lactate-consuming Veillonella, faster acetate recovery, and changes in indolelactate and p-cresol sulfate, metabolites that impact host inflammatory status. Furthermore, Veillonella co-cultured in vitro and in vivo with B. infantis and HMO converts lactate produced by B. infantis to propionate, an important mediator of host physiology. These results suggest that the synbiotic reproducibly and predictably modulates recovery of a dysbiotic microbiome.
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•B. infantis engrafts into an antibiotic-perturbed adult human gut microbiome•HMOs support engraftment of B. infantis in adults at up to 81% relative abundance•Microbiome structure and gut metabolite levels were altered in engrafted adults•B. infantis cross-fed Veillonella in adult patients, mouse models, and in vitro
Button et al. demonstrate precision microbiome engineering through human-milk-oligosaccharide-fed Bifidobacterium longum subspecies infantis in adult, antibiotic-perturbed gut microbiomes. Engraftment in adult subjects leads to reproducible changes in the microbiome, including cross-feeding of propionate-producing Veillonella spp. Reproducible positive impacts on an array of microbial metabolites point to therapeutic potential.
Abstract
Patients with ataxia-telangiectasia (A-T) lack a functional ATM kinase protein and exhibit defective repair of DNA double-stranded breaks and response to oxidative stress. We show that ...CRISPR/Cas9-assisted gene correction combined with piggyBac (PB) transposon-mediated excision of the selection cassette enables seamless restoration of functional ATM alleles in induced pluripotent stem cells from an A-T patient carrying compound heterozygous exonic missense/frameshift mutations, and from a patient with a homozygous splicing acceptor mutation of an internal coding exon. We show that the correction of one allele restores expression of ~ 50% of full-length ATM protein and ameliorates DNA damage-induced activation (auto-phosphorylation) of ATM and phosphorylation of its downstream targets, KAP-1 and H2AX. Restoration of ATM function also normalizes radiosensitivity, mitochondrial ROS production and oxidative-stress-induced apoptosis levels in A-T iPSC lines, demonstrating that restoration of a single ATM allele is sufficient to rescue key ATM functions. Our data further show that despite the absence of a functional ATM kinase, homology-directed repair and seamless correction of a pathogenic ATM mutation is possible. The isogenic pairs of A-T and gene-corrected iPSCs described here constitute valuable tools for elucidating the role of ATM in ageing and A-T pathogenesis.
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