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BACKGROUND Osteogenesis imperfecta is a skeletal disease with a range of phenotypes, depending on the genetic mutation. Individuals with osteogenesis imperfecta type I often have mutations in COL1A genes. This disease can be associated with chest wall deformities such as pectus excavatum, but the number of patients with this presentation is limited, and genetic variants associated with this phenotype have not been reported. CASE REPORT We studied the Skeletal Disorders Genetic Panel of 2 siblings with osteogenesis imperfecta type I and severe pectus excavatum requiring surgical correction. Both had severe respiratory symptoms secondary to the chest wall deformity, and the male patient had evidence of mitral valve insufficiency on an echocardiogram. Results of the genetic panel were remarkable for a homozygous copy number gain in exons 2 to 51 in gene COL1A1. Additionally, both had a heterozygous pathogenic variant in exon 7 of gene COL27A1 (replacement of a glycine with arginine in codon 697 of the protein). CONCLUSIONS Gene COL27A1 plays a role during the calcification of cartilage to bone and is associated with Steel syndrome, a skeletal disorder mainly found in the Puerto Rican population. Heterozygous carriers of the p.Gly697Arg variant in COL27A1 have not been described to have a phenotype with chest wall deformities. Additionally, a genotype-phenotype relationship regarding pectus excavatum in patients with osteogenesis imperfecta has not been described, suggesting that having COL1A gene mutations and simultaneous haploinsufficiency of COL27A1 can result in a phenotype of osteogenesis imperfecta with pectus excavatum and predispose these patients to additional phenotypic features.

Purpose To determine if a correlation exists between the medication regimen complexity index (MRCI) and quality of life (QoL) in patients with heart failure (HF) assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Methods Retrospective chart review from July 2012 through June 2018 identified patients for inclusion who completed an MLHFQ. Baseline and, if available, follow-up MLHFQ scores were collected. The medication list documented on the date of the MLHFQ was used to calculate the MRCI. Results Patients with a documented MLHFQ score were included (n = 72) in the primary analysis. No correlation existed between baseline MRCI and MLHFQ (r = 0.07; p = 0.55). A secondary analysis of correlation between change in MRCI and MLHFQ was conducted for patients (n = 30) with a follow-up MLHFQ score. A moderate, negative correlation (r = −0.47; p = 0.009) existed between change in MRCI and MLHFQ from baseline to follow-up. Conclusion No significant correlation between MRCI and MLHFQ scores were found at baseline. Patients with follow-up MLHFQ scores demonstrated improvements in QoL, despite increasingly complex medication regimens. Medication regimen complexity alone is likely an insufficient marker for predicting QoL in patients with HF.

The ‘divertorlets’ concept is a potential non-evaporative liquid metal solution for heat removal at low recycling regime. A toroidal divertorlets prototype was built and tested in LMX-U at Princeton Plasma Physics Laboratory to evaluate the performance of this configuration. In this paper, details of the design, experimental results, comparison with analytical theory and MHD numerical simulations of toroidal divertorlets are covered. Experiments, analytical model and simulations showed agreement and allowed the projection of operation properties at higher magnetic flux densities (reactor-like operation), proving the concept to be a compelling solution for divertor applications.

To compare intraocular pressure (IOP) measurements obtained using the Icare 200™ (IC200) rebound tonometer and the hand-held version of the Goldmann Applanation Tonometer (Perkins™ tonometer, GAT) in patients with primary congenital glaucoma (PCG) and in healthy subjects.A total of 42 eyes of healthy subjects (G1) and 40 patients with PCG (G2) were analysed. The following clinical data were collected: gender, age, Cup/Disc ratio, central corneal thickness (CCT). IOP was determined in the examination room using the IC200 and GAT tonometers, in the same order. Agreement between both tonometers was determined using the intraclass correlation coefficient (ICC) and Bland-Altman plot. A linear regression analysis was used to establish the IOP was affected by the studied variables.Mean IOP between both tonometers (IC200 minus GAT) was: G1=15.91 (2.57) mmHg vs. 15.06 (2.12) mmHg (mean difference, MD=0.84 (0.50) mmHg; P.101) and G2=20.10 (6.37) vs.19.12 (5.62) (MD=0.98 (1.36); P=.474). Excellent agreement was found between IC200 and GAT in both groups (ICC=G1: 0.875 (95% CI; 0.768-0.933; P.001); G2: 0.924 (95% CI; 0.852-0.961; P.001), and there was a statistically significant correlation between the IOP difference measured with IC200 and GAT and CCT in G1 (B=0.021; 95% CI; 0.005-0.037; P=.008), but was not statistically significant in G2.There was excellent agreement between the IC200 and GAT tonometers, both in healthy subjects and PCG, with a trend to overestimate IOP when measured with IC200. There was no influence by CCT on IOP measurements in patients with PGC.

Physiological communication between neurons is dependent on the exchange of neurotransmitters at the synapses. Although this chemical signal transmission targets specific receptors and allows for subtle adaptation of the action potential, in vitro neuroscience typically relies on electrical currents and potentials to stimulate neurons. The electric stimulus is unspecific and the confinement of the stimuli within the media is technically difficult to control and introduces large artifacts in electric recordings of the activity. Here, we present a local chemical stimulation platform that resembles in vivo physiological conditions and can be used to target specific receptors of synapses. Neurotransmitters were dispensed using the force-controlled fluidic force microscope (FluidFM) nanopipette, which provides exact positioning and precise liquid delivery. We show that controlled release of the excitatory neurotransmitter glutamate induces spiking activity in primary rat hippocampal neurons, as measured by concurrent electrical and optical recordings using a microelectrode array and a calcium-sensitive dye, respectively. Furthermore, we characterized the glutamate dose response of neurons by applying stimulation pulses of glutamate with concentrations from 0 to 0.5 mm. This new stimulation approach, which combines FluidFM for gentle and precise positioning with a microelectrode array read-out, makes it possible to modulate the activity of individual neurons chemically and simultaneously record their induced activity across the entire neuronal network. The presented platform not only offers a more physiological alternative compared with electrical stimulation, but also provides the possibility to study the effects of the local application of neuromodulators and other drugs.

Small-size stellarator devices with high-temperature-superconducting (HTS) magnetic coils could improve magnetic confinement performance and enable rapid diagnostics of new confinement regimes. In this context, 3D printing with acrylonitrile butadiene styrene (ABS) polymer could be a low cost and rapid manufacturing method that allows the fabrication of relatively complex shapes. However, high precision and geometric complexity are required for stellarator components. Additionally, the combined utilization of HTS magnetic coils and ABS components may require the exposure of ABS components to cryogenic environments. Therefore, this research tested the mechanical performance of additively manufactured ABS at 77 K and correlated its mechanical properties to 3D printing settings. This will allow further mechanical stability analysis about the combined implementation of HTS magnetic coils and additively manufactured ABS components. In this article, Young’s Modulus, Yield Strength and Ultimate Strength at room temperature (RT) and 77 K of additively manufactured ABS are explored while varying layer thickness, raster pattern and infill percentage as 3D printing settings. Conclusions about the influence of each 3D printing setting on each mechanical property are presented.

Copper binding motifs with their molecular mechanisms of selective copper(I) recognition are essential molecules for acquiring copper ions, trafficking copper to specific locations and controlling the potentially damaging redox activities of copper in biochemical processes. The redox activity and multiple Cu(I) binding of an analog methanobactin peptide-2 (amb2) with the sequence acetyl–His1–Cys2–Tyr3–Pro4–His5–Cys6 was investigated using ion mobility–mass spectrometry (IM-MS) and UV–Vis spectrophotometry analyses. The Cu(II) titration of amb2 showed oxidation of amb2 via the formation of intra- and intermolecular Cys–Cys disulfide bridges and the multiple Cu(I) coordination by unoxidized amb2 or the partially oxidized dimer and trimer of amb2. The principal product of these reactions was [amb2 + 3Cu(I)]+ which probably coordinates the three Cu(I) ions via two bridging thiolate groups of Cys2 and Cys6 and the δN6 of the imidazole groups of His6, as determined by geometry optimized structures at the B3LYP/LanL2DZ level of theory. The products observed by IM-MS showed direct correlation to spectral changes associated with disulfide bond formation in the UV–Vis spectrophotometric study. The results show that IM-MS analysis is a powerful technique for unambiguously determining the major ion species produced during the redox and metal binding chemistry of oligopeptides. Copyright © 2015 John Wiley & Sons, Ltd.

In this commentary we critically discuss the suitability of payments for ecosystem services and the most important challenges they face. While such instruments can play a role in improving environmental governance, we argue that over-reliance on payments as win-win solutions might lead to ineffective outcomes, similar to earlier experience with integrated conservation and development projects. Our objective is to raise awareness, particularly among policy makers and practitioners, about the limitations of such instruments and to encourage a dialogue about the policy contexts in which they might be appropriate.

Copper binding motifs with their molecular mechanisms of selective copper(I) recognition are essential molecules for acquiring copper ions, trafficking copper to specific locations and controlling the potentially damaging redox activities of copper in biochemical processes. The redox activity and multiple Cu(I) binding of an analog methanobactin peptide-2 (amb2) with the sequence acetyl-His1-Cys2-Tyr3-Pro4-His5-Cys6 was investigated using ion mobility-mass spectrometry (IM-MS) and UV-Vis spectrophotometry analyses. The Cu(II) titration of amb2 showed oxidation of amb2 via the formation of intra- and intermolecular Cys-Cys disulfide bridges and the multiple Cu(I) coordination by unoxidized amb2 or the partially oxidized dimer and trimer of amb2. The principal product of these reactions was [amb2 + 3Cu(I)](+) which probably coordinates the three Cu(I) ions via two bridging thiolate groups of Cys2 and Cys6 and the δN6 of the imidazole groups of His6, as determined by geometry optimized structures at the B3LYP/LanL2DZ level of theory. The products observed by IM-MS showed direct correlation to spectral changes associated with disulfide bond formation in the UV-Vis spectrophotometric study. The results show that IM-MS analysis is a powerful technique for unambiguously determining the major ion species produced during the redox and metal binding chemistry of oligopeptides.

We develop a new method to estimate private equity funds’ market beta from cash flows. Our methodology extends the widely known public market equivalent calculation to a cross-sectional regression. By simply regressing funds’ internal rates of return on their paired market internal rates of return, we are able to estimate private equity market betas. For venture funds, we find a high market beta. For buyout funds, we find a low beta. Though we have a small sample, our results fall in line with results recently reported in the literature.

A number of methods have been developed to link single-period arithmetic attribution results. We present the first institutional portfolio empirical study comparing the most referenced methods for producing additive multiperiod attributes from their single-period counterparts. While our findings suggest the methods typically produce similar results, we find a pattern in the way the methods’ results relate to one another. We find the Modified Frongello Method and Carino Method to produce nearly identical results, the Frongello and Carino methods to cluster and the Naive and Menchero methods to be outliers.

We extend the Brinson et al. (1986) performance attribution framework to support institutional-specific requirements, including a hierarchical structure and multiple benchmark styles. By attributing performance to four statistics (e.g. manager alpha, portfolio construction, tactical and strategic), we are able to remove the interaction term, which is a commonly referred to shortcoming of Brinson attribution. We subsequently modify Frongello (2002) linking to produce pro-rated multiperiod attributes which sum to meaningful statistics using notional portfolios of multitier excess returns.

To determine the capacity for measurement of central corneal thickness by ultrasound pachymetry and by Pentacam (pachymetry at the pupillary axis and minimum corneal pachymetry) to discriminate between healthy controls and patients with primary open-angle glaucoma.Measurements of the left eyes of 123 control subjects and 128 glaucomatous patients were taken. Differences between the two data sets for each variable were identified using a t-test for independent samples. Three univariate binary logistic regression models (to discriminate between glaucoma and controls) were constructed, in which the predictive variables were the determinations of corneal thickness.All variables showed a normal distribution. Controls and patients failed to differ significantly in terms of ultrasound pachymetry but did differ in terms of pupillary axis thickness (mean difference 22.01μm in favour of controls; 95% CI: 5.61-34.15) and minimum corneal thickness (mean difference 21.65μm in favour of controls; 95% CI: 3.05-32.25). The logistic regression model for ultrasound pachymetry was not significant (P=0.051) but significant discriminatory capacity was shown for pupillary axis thickness (expB=0.987; 95% CI: 0.99-0.993; sensitivity: 58.5%; specificity: 64.8%) and minimum corneal thickness (expB=0.987; 95% CI: 0.981-0.994; sensitivity: 61.9%; specificity: 63.1%).Central corneal thickness measurement by Pentacam, while not an ad hoc diagnostic test for glaucoma, showed a similar yet not inappreciable capacity to discriminate between glaucoma patients and controls.

The transforming growth factor beta1 (TGF-beta1) is a human cytokine which has been demonstrated to modulate cell surface integrin repertoire. In this work integrin expression in response to TGF-beta1 stimulation has been investigated on the surface of human osteoblast-like cells. We used atomic force microscopy (AFM) and confocal laser scanning microscopy to assess integrin expression and to evaluate their distribution over the dorsal side of the plasma membrane. AFM probes have been covalently functionalized with monoclonal antibodies specific to the beta1 integrin subunit. Force curves have been collected in order to obtain maps of the interaction between the immobilized antibody and the respective cell membrane receptors. Adhesion peaks have been automatically detected by means of an ad hoc developed data analysis software. The specificity of the detected interactions has been assessed by adding free antibody in the solution and monitoring the dramatic decrease in the recorded interactions. In addition, the effect of TGF-beta1 treatment on both the fluorescence signal and the adhesion events has been tested. The level of expression of the beta1 integrin subunit was enhanced by TGF-beta1. As a further analysis, the adhesion force of the single living cells to the substrate was measured by laterally pushing the cell with the AFM tip and measuring the force necessary to displace it. The treatment with TGF-beta1 resulted in a decrease of the cell/substrate adhesion force. Results obtained by AFM have been validated by confocal laser scanning microscopy thus demonstrating the high potential of the AFM technique for the investigation of cell surface receptors distribution and trafficking at the nanoscale.

The presence of anemia and renal dysfunction grants a bad prognosis for patients with heart failure and reduced ejection fraction (HFREF). The impact on patients with heart failure and normal ejection fraction (HFNEF) is not widely studied.To study the prevalence and the prognosis of anemia and renal dysfunction (RD) in patients with heart failure according to the type of ventricular dysfunction.A total of 209 patients with chronic and stable heart failure were prospectively studied. Individuals with ejection fraction50% were considered as HFREF patients. Anemia was defined, based on WHO criteria, as hemoglobin13 g/dl for men and12 g/dl for women. Renal function was calculated by means of the Simplified Modified Diet Renal Disease (sMDRD) formula. Hospitalizations, emergency admittances and obit by cardiac causes were considered as cardiac events.Ninety patients had HFREF and 119 had HFNEF. The glomerular filtration rate (GFR) was smaller in HFREF group (57.6 +/- 66.2 versus 94.8 +/- 36.6 ml/min/1.73m(2); p=0.01). There was no difference in the prevalence of anemia between groups (23.3% versus 18.5%; p=0.34). Moderate to severe RD prevalence was higher in HFREF group (32.2% versus 16.8%; p=0.01). RD was the only factor associated with anemia that was independently associated with cardiac events (HR 2.52; 95%CI=1.27-5.2; p=0.01).RD was less prevalent in HFNEF, while the prevalence of anemia did not differ between groups. RD was predictor of cardiac events independently on ejection fraction.

One of the main bottlenecks in Genetics Algorithms is the fitness evaluation for each individual. In this work, we propose a new fitness evaluation method, which will solve the bottleneck calculating a fitness on the fly.