Radiolabeling human peripheral blood stem cells for positron emission tomography (PET) imaging in young rhesus monkeys.

These studies focused on a new radiolabeling technique with copper ((64)Cu) and zirconium ((89)Zr) for positron emission tomography (PET) imaging using a CD45 antibody. Synthesis of (64)Cu-CD45 and (89)Zr-CD45 immunoconjugates was performed and the evaluation of the potential toxicity of radiolabeling human peripheral blood stem cells (hPBSC) was assessed in vitro (viability, population doubling times, colony forming units). hPBSC viability was maintained as the dose of (64)Cu-TETA-CD45 increased from 0 (92%) to 160 µCi/mL (76%, p>0.05). Radiolabeling efficiency was not significantly increased with concentrations of (64)Cu-TETA-CD45 >20 µCi/mL (p>0.50). Toxicity affecting both growth and colony formation was observed with hPBSC radiolabeled with ≥40 µCi/mL (p<0.05). For (89)Zr, there were no significant differences in viability (p>0.05), and a trend towards increased radiolabeling efficiency was noted as the dose of (89)Zr-Df-CD45 increased, with a greater level of radiolabeling with 160 µCi/mL compared to 0-40 µCi/mL (p<0.05). A greater than 2,000 fold-increase in the level of (89)Zr-Df-CD45 labeling efficiency was observed when compared to (64)Cu-TETA-CD45. Similar to (64)Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with ≥40 µCi/mL (p<0.05) (growth, colony formation). Taken together, 20 µCi/mL resulted in the highest level of radiolabeling efficiency without altering cell function. Young rhesus monkeys that had been transplanted prenatally with 25×10(6) hPBSC expressing firefly luciferase were assessed with bioluminescence imaging (BLI), then 0.3 mCi of (89)Zr-Df-CD45, which showed the best radiolabeling efficiency, was injected intravenously for PET imaging. Results suggest that (89)Zr-Df-CD45 was able to identify engrafted hPBSC in the same locations identified by BLI, although the background was high

Explaining International Differences in the Prices of Tradables and Non-Tradables (with a New Zealand Perspective)

The World Bank's International Comparison Program (ICP) data on national price levels for tradables and non-tradables (and goods compared to services) reveals that New Zealand has relatively high prices of both tradables and non-tradables when compared to a sample of over 40 OECD-Eurostat countries (Gemmell, 2013). The present paper seeks to explain both those observed international variations in non-tradables and tradables prices in general, and New Zealand's especially high prices in particular

Redbook: 1997

Advice compiled by Boston University School of Medicine students for incoming first year students and third or fourth year students preparing for clinical rotations

Increased risk of endometriosis in patients with endometritis — a nationwide cohort study involving 84,150 individuals

Objectives: To evaluate the incidence of endometriosis among endometritis patients and its association with confoundingcomorbidities.Material and methods: A population-based, retrospective cohort study of women aged between 20 to 55 years, who werenewly diagnosed with endometritis between 2000 to 2013. A total of 16,830 endometritis patients and 67,230 non-endometritisindividuals were enrolled by accessing data from the National Health Insurance Research Database of Taiwan.The comorbidities accessed were uterine leiomyoma, rheumatoid arthritis, ovarian cancer, infertility and allergic diseases.Results: The mean follow-up period was 9.15 years for the non-endometritis cohort and 9.13 years for the endometritiscohort. There were significantly higher percentages of uterine leiomyoma, rheumatoid arthritis, infertility, ovarian cancerand allergic diseases in the endometritis cohort than in the non-endometritis cohort. Patients with endometritis hada 1.5-fold increased risk of their condition advancing to endometriosis (HR 1.58, 95% CI 1.48–1.68).Conclusions: Our results suggest that patients with endometritis exhibited a positive correlation in developing endometriosis

MUC4 gene polymorphisms associate with endometriosis development and endometriosis-related infertility

<p>Abstract</p> <p>Background</p> <p>Mucin 4 (<it>MUC4</it>) plays an important role in protecting and lubricating the epithelial surface of reproductive tracts, but its role in the pathogenesis of endometriosis is largely unknown.</p> <p>Methods</p> <p>To correlate <it>MUC4 </it>polymorphism with the risk of endometriosis and endometriosis-related infertility, we performed a case-control study of 140 patients and 150 healthy women. Six unique single-nucleotide polymorphisms (SNPs) (rs882605, rs1104760, rs2688513, rs2246901, rs2258447 and rs2291652) were selected for this study. DNA fragments containing the target SNP sites were amplified by polymerase chain reaction using the TaqMan SNP Genotyping Assay System to evaluate allele frequency and distribution of genotype in <it>MUC4 </it>polymorphisms.</p> <p>Results</p> <p>Both the T/G genotype of rs882605 and the frequency of haplotype T-T (rs882605 and rs1104760) were higher in patients than in controls and were statistically significant. The frequency of the C allele at rs1104760, the C allele at rs2688513, the G allele at rs2246901 and the A allele at rs2258447 were associated with advanced stage of endometriosis. Moreover, the G allele at rs882605 was verified as a key genetic factor for infertility in patients. Protein sequence analysis indicated that amino acid substitutions by genetic variations at rs882605, rs2688513 and rs2246901 occur in the putative functional loops and the type D von Willebrand factor (VWFD) domain in the MUC4 sequence.</p> <p>Conclusions</p> <p><it>MUC4 </it>polymorphisms are associated with endometriosis development and endometriosis-related infertility in the Taiwanese population.</p

Sensitivity and uncertainty analysis of two human atrial cardiac cell models using gaussian process emulators

Biophysically detailed cardiac cell models reconstruct the action potential and calcium dynamics of cardiac myocytes. They aim to capture the biophysics of current flow through ion channels, pumps, and exchangers in the cell membrane, and are highly detailed. However, the relationship between model parameters and model outputs is difficult to establish because the models are both complex and non-linear. The consequences of uncertainty and variability in model parameters are therefore difficult to determine without undertaking large numbers of model evaluations. The aim of the present study was to demonstrate how sensitivity and uncertainty analysis using Gaussian process emulators can be used for a systematic and quantitive analysis of biophysically detailed cardiac cell models. We selected the Courtemanche and Maleckar models of the human atrial action potential for analysis because these models describe a similar set of currents, with different formulations. In our approach Gaussian processes emulate the main features of the action potential and calcium transient. The emulators were trained with a set of design data comprising samples from parameter space and corresponding model outputs, initially obtained from 300 model evaluations. Variance based sensitivity indices were calculated using the emulators, and first order and total effect indices were calculated for each combination of parameter and output. The differences between the first order and total effect indices indicated that the effect of interactions between parameters was small. A second set of emulators were then trained using a new set of design data with a subset of the model parameters with a sensitivity index of more than 0.1 (10%). This second stage analysis enabled comparison of mechanisms in the two models. The second stage sensitivity indices enabled the relationship between the L-type Ca2+ current and the action potential plateau to be quantified in each model. Our quantitative analysis predicted that changes in maximum conductance of the ultra-rapid K+ channel IKur would have opposite effects on action potential duration in the two models, and this prediction was confirmed by additional simulations. This study has demonstrated that Gaussian process emulators are an effective tool for sensitivity and uncertainty analysis of biophysically detailed cardiac cell models

Cough quality in children: a comparison of subjective vs. bronchoscopic findings

BACKGROUND: Cough is the most common symptom presenting to doctors. The quality of cough (productive or wet vs dry) is used clinically as well as in epidemiology and clinical research. There is however no data on the validity of cough quality descriptors. The study aims were to compare (1) cough quality (wet/dry and brassy/non-brassy) to bronchoscopic findings of secretions and tracheomalacia respectively and, (2) parent's vs clinician's evaluation of the cough quality (wet/dry). METHODS: Cough quality of children (without a known underlying respiratory disease) undergoing elective bronchoscopy was independently evaluated by clinicians and parents. A 'blinded' clinician scored the secretions seen at bronchoscopy on pre-determined criteria and graded (1 to 6). Kappa (K) statistics was used for agreement, and inter-rater and intra-rater agreement examined on digitally recorded cough. A receiver operating characteristic (ROC) curve was used to determine if cough quality related to amount of airway secretions present at bronchoscopy. RESULTS: Median age of the 106 children (62 boys, 44 girls) enrolled was 2.6 years (IQR 5.7). Parent's assessment of cough quality (wet/dry) agreed with clinicians' (K = 0.75, 95%CI 0.58–0.93). When compared to bronchoscopy (bronchoscopic secretion grade 4), clinicians' cough assessment had the highest sensitivity (0.75) and specificity (0.79) and were marginally better than parent(s). The area under the ROC curve was 0.85 (95%CI 0.77–0.92). Intra-observer (K = 1.0) and inter-clinician agreement for wet/dry cough (K = 0.88, 95%CI 0.82–0.94) was very good. Weighted K for inter-rater agreement for bronchoscopic secretion grades was 0.95 (95%CI 0.87–1). Sensitivity and specificity for brassy cough (for tracheomalacia) were 0.57 and 0.81 respectively. K for both intra and inter-observer clinician agreement for brassy cough was 0.79 (95%CI 0.73–0.86). CONCLUSIONS: Dry and wet cough in children, as determined by clinicians and parents has good clinical validity. Clinicians should however be cognisant that children with dry cough may have minimal to mild airway secretions. Brassy cough determined by respiratory physicians is highly specific for tracheomalacia

The effects of combined transcranial brain stimulation and a 4-week visuomotor stepping training on voluntary step initiation in persons with chronic stroke—a pilot study

PurposeEvidence suggests that transcranial direct current stimulation (tDCS) can enhance motor performance and learning of hand tasks in persons with chronic stroke (PCS). However, the effects of tDCS on the locomotor tasks in PCS are unclear. This pilot study aimed to: (1) determine aggregate effects of anodal tDCS combined with step training on improvements of the neural and biomechanical attributes of stepping initiation in a small cohort of persons with chronic stroke (PCS) over a 4-week training program; and (2) assess the feasibility and efficacy of this novel approach for improving voluntary stepping initiation in PCS.MethodsA total of 10 PCS were randomly assigned to one of two training groups, consisting of either 12 sessions of VST paired with a-tDCS (n = 6) or sham tDCS (s-tDCS, n = 4) over 4 weeks, with step initiation (SI) tests at pre-training, post-training, 1-week and 1-month follow-ups. Primary outcomes were: baseline vertical ground reaction force (B-vGRF), response time (RT) to initiate anticipatory postural adjustment (APA), and the retention of B-VGRF and RT.Resultsa-tDCS paired with a 4-week VST program results in a significant increase in paretic weight loading at 1-week follow up. Furthermore, a-tDCS in combination with VST led to significantly greater retention of paretic BWB compared with the sham group at 1 week post-training.Clinical implicationsThe preliminary findings suggest a 4-week VST results in improved paretic limb weight bearing (WB) during SI in PCS. Furthermore, VST combined with a-tDCS may lead to better retention of gait improvements (NCT04437251) (https://classic.clinicaltrials.gov/ct2/show/NCT04437251)

Experimental Efforts on Very High-Energy Cosmic Rays and their Interactions - Conference Summary

Progress reported during the XV International Symposium on Very High-Energy Cosmic-Ray Interactions is summarized. Emphasize is given to experimental work. The actual status, recent results, and their implications on the present understanding of the origin of high-energy cosmic-rays and their interactions are discussed.Comment: Invited summary of the experimental efforts discussed at the XV ISVHECR