Reduced Computational Cost, Totally Symmetric Angular Quadrature Sets for Discrete Ordinates Radiation Transport

Several new quadrature sets for use in the discrete ordinates method of solving the Boltzmann neutral particle transport equation are derived. These symmetric quadratures extend the traditional symmetric quadratures by allowing ordinates perpendicular to one or two of the coordinate axes. Comparable accuracy with fewer required ordinates is obtained. Quadratures up to seventh order are presented. The validity and efficiency of the quadratures is then tested and compared with the Sn level symmetric quadratures relative to a Monte Carlo benchmark solution. The criteria for comparison include current through the surface, scalar flux at the surface, volume average scalar flux, and time required for convergence. Appreciable computational cost was saved when used in an unstructured tetrahedral cell code using highly accurate characteristic methods. However, no appreciable savings in computation time was found using the new quadratures compared with traditional Sn methods on a regular Cartesian mesh using the standard diamond difference method. These quadratures are recommended for use in three-dimensional calculations on an unstructured mesh

Short-Term Effects of Pacifier Texture on NNS in Neurotypical Infants

The dense representation of trigeminal mechanosensitive afferents in the lip vermilion, anterior tongue, intraoral mucosa, and temporomandibular joint allows the infant’s orofacial system to encode a wide range of somatosensory experiences during the critical period associated with feed development. Our understanding of how this complex sensorium processes texture is very limited in adults, and the putative role of texture encoding in the infant is unknown.The purpose of this study was to examine the short-term effects of a novel textured pacifier experience in healthy term infants ( = 28). Nonnutritive suck (NNS) compression pressure waveforms were digitized in real time using a variety of custom-molded textured pacifiers varying in spatial array density of touch domes. MANCOVA, adjusted for postmenstrual age at test and sex, revealed that infants exhibited an increase in NNS burst attempts at the expense of a degraded suck burst structure with the textured pacifiers, suggesting that the suck central pattern generator (sCPG) is significantly disrupted and reorganized by this novel orocutaneous experience. The current findings provide new insight into oromotor control as a function of the oral somatosensory environment in neurotypically developing infants

Vinylphosphonites for staudinger-induced chemoselective peptide cyclization and functionalization

In this paper, we introduce vinylphosphonites for chemoselective Staudinger-phosphonite reactions (SPhR) with azides to form vinylphosphonamidates for the subsequent modification of cysteine residues in peptides and proteins. An electron-rich alkene is turned into an electron-deficient vinylphosphonamidate, thereby inducing electrophilic reactivity for a following thiol addition. We show that by varying the phosphonamidate ester substituent we can fine-tune the reactivity of the thiol addition and even control the functional properties of the final conjugate. Furthermore, we observed a drastic increase in thiol addition efficiency when the SPhR is carried out in the presence of a thiol substrate in a one-pot reaction. Hence, we utilize vinylphosphonites for the chemoselective intramolecular cyclization of peptides carrying an azide-containing amino acid and a cysteine in high yields. Our concept was demonstrated for the stapling of a cell-permeable peptidic inhibitor for protein–protein interaction (PPI) between BCL9 and beta-catenin, which is known to create a transcription factor complex playing a role in embryonic development and cancer origin, and for macrocyclization of cell-penetrating peptides (CPPs) to enhance the cellular uptake of proteins

Amplitude-Integrated EEG and Range-EEG Modulation Associated with Pneumatic Orocutaneous Stimulation in Preterm Infants

Background—Controlled somatosensory stimulation strategies have demonstrated merit in developing oral feeding skills in premature infants who lack a functional suck, however, the effects of orosensory entrainment stimulation on electrocortical dynamics is unknown. Objective—To determine the effects of servo-controlled pneumatic orocutaneous stimulation presented during gavage feedings on the modulation of aEEG and rEEG activity. Methods—Two-channel EEG recordings were collected during 180 sessions that included orocutaneous stimulation and non-stimulation epochs among 22 preterm infants (mean gestational age = 28.56 weeks) who were randomized to treatment and control ‘sham’ conditions. The study was initiated at around 32 weeks post-menstrual age (PMA). The raw EEG was transformed into amplitude-integrated EEG (aEEG) margins, and range-EEG (rEEG) amplitude bands measured at 1-minute intervals and subjected to a mixed models statistical analysis. Results—Multiple significant effects were observed in the processed EEG during and immediately following 3-minute periods of orocutaneous stimulation, including modulation of the upper and lower margins of the aEEG, and a reorganization of rEEG with an apparent shift from amplitude bands D and E to band C throughout the 23-minute recording period that followed the first stimulus block when compared to the sham condition. Cortical asymmetry also was apparent in both EEG measures. Conclusions—Orocutaneous stimulation represents a salient trigeminal input which has both short- and long-term effects in modulating electrocortical activity, and thus, is hypothesized to represent a form of neural adaptation or plasticity that may benefit the preterm infant during this critical period of brain maturation

Amplitude-Integrated EEG and Range-EEG Modulation Associated with Pneumatic Orocutaneous Stimulation in Preterm Infants

Background—Controlled somatosensory stimulation strategies have demonstrated merit in developing oral feeding skills in premature infants who lack a functional suck, however, the effects of orosensory entrainment stimulation on electrocortical dynamics is unknown. Objective—To determine the effects of servo-controlled pneumatic orocutaneous stimulation presented during gavage feedings on the modulation of aEEG and rEEG activity. Methods—Two-channel EEG recordings were collected during 180 sessions that included orocutaneous stimulation and non-stimulation epochs among 22 preterm infants (mean gestational age = 28.56 weeks) who were randomized to treatment and control ‘sham’ conditions. The study was initiated at around 32 weeks post-menstrual age (PMA). The raw EEG was transformed into amplitude-integrated EEG (aEEG) margins, and range-EEG (rEEG) amplitude bands measured at 1-minute intervals and subjected to a mixed models statistical analysis. Results—Multiple significant effects were observed in the processed EEG during and immediately following 3-minute periods of orocutaneous stimulation, including modulation of the upper and lower margins of the aEEG, and a reorganization of rEEG with an apparent shift from amplitude bands D and E to band C throughout the 23-minute recording period that followed the first stimulus block when compared to the sham condition. Cortical asymmetry also was apparent in both EEG measures. Conclusions—Orocutaneous stimulation represents a salient trigeminal input which has both short- and long-term effects in modulating electrocortical activity, and thus, is hypothesized to represent a form of neural adaptation or plasticity that may benefit the preterm infant during this critical period of brain maturation

Frequency-Modulated Orocutaneous Stimulation Promotes Non-nutritive Suck Development in Preterm Infants with Respiratory Distress Syndrome or Chronic Lung Disease

Background—For the premature infant, extrauterine life is a pathological condition which greatly amplifies the challenges to the brain in establishing functional oromotor behaviors. The extent to which suck can be entrained using a synthetically patterned orocutaneous input to promote its development in preterm infants who manifest chronic lung disease is unknown. Objective—To evaluate the effects of a frequency-modulated orocutaneous pulse train delivered through a pneumatically-charged pacifier capable of enhancing non-nutritive suck (NNS) activity in tube-fed premature infants. Methods—A randomized trial to evaluate the efficacy of pneumatic orocutaneous stimulation 3x/day on NNS development and length of stay (LOS) in the NICU among 160 newborn infants distributed among 3 subpopulations, including healthy preterm infants (HI), respiratory distress syndrome (RDS), and chronic lung disease (CLD). Study infants received a regimen of orocutaneous pulse trains through a PULSED pressurized silicone pacifier or a SHAM control (blind pacifier) during gavage feeds for up to 10 days. Results—Mixed modeling, adjusted for the infant’s gender, gestational age, postmenstrual age, and birth weight, was used to handle interdependency among repeated measures within subjects. A significant main effect for stimulation mode (SHAM pacifier vs PULSED orosensory) was found among preterm infants for NNS Bursts/minute (p=.003), NNS events/minute (p=.033), and for Total Oral Compressions/minute [NNS+nonNNS] (p=.016). Pairwise comparison of adjusted means using Bonferroni adjustment indicated RDS and CLD infants showed the most significant gains on these NNS performance indices. CLD infants in the treatment group showed significantly shorter LOS by an average of 2.5 days

Modulation of EEG spectral edge frequency during patterned pneumatic oral stimulation in preterm infants

Background—Stimulation of the nervous system plays a central role in brain development and neurodevelopmental outcome. Thalamocortical and corticocortical development is diminished in premature infants and correlated to electroencephalography (EEG) progression. The purpose of this study was to determine the effects of orocutaneous stimulation on the modulation of spectral edge frequency, fc=90% (SEF-90) derived from EEG recordings in preterm infants. Methods—Twenty two preterm infants were randomized to experimental and control conditions. Pulsed orocutaneous stimulation was presented during gavage feedings begun at around 32 weeks postmenstrual age (PMA). The SEF-90 was derived from 2-channel EEG recordings. Results—Compared to the control condition, the pulsed orocutaneous stimulation produced a significant reorganization of SEF-90 in the left (p = 0.005) and right (p \u3c 0.0001) hemispheres. Notably, the left and right hemisphere showed a reversal in the polarity of frequency shift, demonstrating hemispheric asymmetry in the frequency domain. Pulsed orocutaneous stimulation also produced a significant pattern of short term cortical adaptation and a long term neural adaptation manifest as a 0.5 Hz elevation in SEF-90 after repeated stimulation sessions. Conclusion—This is the first study to demonstrate the modulating effects of a servo-controlled oral somatosensory input on the spectral features of EEG activity in preterm infants

Frequency-Modulated Orocutaneous Stimulation Promotes Non-nutritive Suck Development in Preterm Infants with Respiratory Distress Syndrome or Chronic Lung Disease

Background—For the premature infant, extrauterine life is a pathological condition which greatly amplifies the challenges to the brain in establishing functional oromotor behaviors. The extent to which suck can be entrained using a synthetically patterned orocutaneous input to promote its development in preterm infants who manifest chronic lung disease is unknown. Objective—To evaluate the effects of a frequency-modulated orocutaneous pulse train delivered through a pneumatically-charged pacifier capable of enhancing non-nutritive suck (NNS) activity in tube-fed premature infants. Methods—A randomized trial to evaluate the efficacy of pneumatic orocutaneous stimulation 3x/day on NNS development and length of stay (LOS) in the NICU among 160 newborn infants distributed among 3 subpopulations, including healthy preterm infants (HI), respiratory distress syndrome (RDS), and chronic lung disease (CLD). Study infants received a regimen of orocutaneous pulse trains through a PULSED pressurized silicone pacifier or a SHAM control (blind pacifier) during gavage feeds for up to 10 days. Results—Mixed modeling, adjusted for the infant’s gender, gestational age, postmenstrual age, and birth weight, was used to handle interdependency among repeated measures within subjects. A significant main effect for stimulation mode (SHAM pacifier vs PULSED orosensory) was found among preterm infants for NNS Bursts/minute (p=.003), NNS events/minute (p=.033), and for Total Oral Compressions/minute [NNS+nonNNS] (p=.016). Pairwise comparison of adjusted means using Bonferroni adjustment indicated RDS and CLD infants showed the most significant gains on these NNS performance indices. CLD infants in the treatment group showed significantly shorter LOS by an average of 2.5 days

Retrospective study of long-term outcomes of enzyme replacement therapy in Fabry disease: Analysis of prognostic factors

Despite enzyme replacement therapy, disease progression is observed in patients with Fabry disease. Identification of factors that predict disease progression is needed to refine guidelines on initiation and cessation of enzyme replacement therapy. To study the association of potential biochemical and clinical prognostic factors with the disease course (clinical events, progression of cardiac and renal disease) we retrospectively evaluated 293 treated patients from three international centers of excellence. As expected, age, sex and phenotype were important predictors of event rate. Clinical events before enzyme replacement therapy, cardiac mass and eGFR at baseline predicted an increased event rate. eGFR was the most important predictor: hazard ratios increased from 2 at eGFR 90. In addition, men with classical disease and a baseline eGFR 60. Proteinuria was a further independent risk factor for decline in eGFR. Increased cardiac mass at baseline was associated with the most robust decrease in cardiac mass during treatment, while presence of cardiac fibrosis predicted a stronger increase in cardiac mass (3.36 gram/m2/year). Of other cardiovascular risk factors, hypertension significantly predicted the risk for clinical events. In conclusion, besides increasing age, male sex and classical phenotype, faster disease progression while on enzyme replacement therapy is predicted by renal function, proteinuria and to a lesser extent cardiac fibrosis and hypertension

Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study

BACKGROUND: Two recombinant enzymes (agalsidase alfa 0.2 mg/kg/every other week and agalsidase beta 1.0 mg/kg/every other week) have been registered for the treatment of Fabry disease (FD), at equal high costs. An independent international initiative compared clinical and biochemical outcomes of the two enzymes. METHODS: In this multicentre retrospective cohort study, clinical event rate, left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), antibody formation and globotriaosylsphingosine (lysoGb3) levels were compared between patients with FD treated with agalsidase alfa and beta at their registered dose after correction for phenotype and sex. RESULTS: 387 patients (192 women) were included, 248 patients received agalsidase alfa. Mean age at start of enzyme replacement therapy was 46 (±15) years. Propensity score matched analysis revealed a similar event rate for both enzymes (HR 0.96, P=0.87). The decrease in plasma lysoGb3 was more robust following treatment with agalsidase beta, specifically in men with classical FD (β: -18 nmol/L, P<0.001), persisting in the presence of antibodies. The risk to develop antibodies was higher for patients treated with agalsidase beta (OR 2.8, P=0.04). LVMI decreased in a higher proportion following the first year of agalsidase beta treatment (OR 2.27, P=0.03), while eGFR slopes were similar. CONCLUSIONS: Treatment with agalsidase beta at higher dose compared with agalsidase alfa does not result in a difference in clinical events, which occurred especially in those with more advanced disease. A greater biochemical response, also in the presence of antibodies, and better reduction in left ventricular mass was observed with agalsidase beta