Optimizing stimulus energy for cochlear implants with a machine learning model of the auditory nerve

Algorithms and the Foundations of Software technolog

Mathematical modeling of thermal and circulatory effects during hemodialysis.

Intradialytic hypotension (IDH) is one of the most common complications of hemodialysis (HD) treatment. The initiating factor of IDH is a decrease in blood volume which is related to an imbalance between ultrafiltration (UF) and refilling rate. Impaired reactivity of resistance and capacitance vessels in reaction to hypovolemia plays possibly a major role in the occurrence of IDH. These vessels also fulfill an important function in body temperature regulation. UF induced cutaneous vasoconstriction would result in a reduced surface heat loss and an increase in core temperature. To release body heat, skin blood flow (SBF) is increased at a later stage of the HD treatment, whereby possibly IDH can occur. Aim of the study is to develop a mathematical model which can provide insight into the impact of thermoregulatory processes on the cardiovascular system during HD treatment. The mathematical procedure has been created by coupling a thermo-physiological (TP) model with a cardiovascular (CV) model to study regulation mechanisms in the human body during HD+UF. Model simulations for isothermal vs. thermoneutral HD+UF were compared to measurement data of patients on chronic intermittent HD (n=13). Core temperature during simulated HD+UF sessions increased within the range of measurement data (0.23ºC vs. 0.32±0.41ºC). The model showed a decline in mean arterial pressure (MAP) of -7% for thermoneutral HD+UF versus -4% for isothermal HD+UF after 200 minutes during which relative blood volume (RBV) changed by -13%. In conclusion, simulation results of the combined model show possibilities for predicting circulatory and thermal responses during HD+UF

Ion-selective optical sensor for continuous on-line monitoring of dialysate sodium during dialysis

Patients with end stage renal disease are dependent on dialysis. In most outpatient centers, the dialysate is prepared with a fixed electrolyte concentration without taking into account the inter-individual differences of essential electrolytes (sodium, potassium and calcium). This one-size fits all approach can lead to acute and chronic cardiovascular complications in dialysis patients. On-line monitoring of these essential electrolytes is an important physiological step towards patient specific dialysate leading to individualized treatment. Currently, changes in electrolyte concentrations are indirectly measured by conductivity measurements, which are not ion- specific. In this paper, we present a novel optical sensor for on-line monitoring of sodium concentrations in dialysate. This sensor is ion-specific and can detect up to a single ion. The working principle is based on the selective fluorescence quenching of photo-induced electron transfer (PET) molecules. The PET molecules when complexed with sodium ions start fluorescing upon laser excitation. The emission intensity is directly correlated to the sodium concentration. To prove the working principle, a micro-optofluidic device has been fabricated in polydimethylsiloxane (PDMS) with integrated optical fibers for fluorescence light collection. The PET molecules are covalently grafted in the PDMS microchannel for continuous monitoring of the sodium dialysate concentrations. The experimental setup consists of a laser module (λ=450nm) operating at 4.5mW, a syringe pump to precisely control the sample flow and a spectrometer for fluorescence collection. The performance of the sensor has been evaluated for sodium ions ranging from 0-50mM. A clear signal and good response time was observed

Prader-Willi-like phenotype in fragile X syndrome

Prader-Willi-like phenotype in fragile X syndrome. Schrander-Stumpel C, Gerver WJ, Meyer H, Engelen J, Mulder H, Fryns JP. Department of Clinical Genetics, Maastricht University Hospital, The Netherlands. A 3-year-old boy was referred to the pediatric department because of unexplained extreme obesity. Height and occipitofrontal circumference were just above the 90th centile. Endocrine studies failed to show any significant abnormality. Motor and speech development were generally delayed. On clinical-cytogenetic-molecular grounds, Prader-Willi syndrome was excluded. Fragile X syndrome was diagnosed by the presence of the classical FMR-1 mutation and confirmed by cytogenetic studies, revealing 20% fragile X positive cells. We compare the clinical features in the present patient with the nine reported patients with fra(X) syndrome and extreme obesity. In pathogenesis, hypothalamic dysregulation is hypothesized. In differential diagnosis of Prader-Willi syndrome, fragile X has to be considered, especially when laboratory workup for Prader-Willi syndrome is negative. Clinical behavior can be of help

Tetralogy of Fallot with coronary artery to pulmonary artery fistula

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Adult monozygotic twins discordant for intra-uterine growth have indistinguishable genome-wide DNA methylation profiles

BACKGROUND: Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intra-uterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. To address this, we acquire genome-wide DNA methylation profiles from saliva DNA in a unique cohort of 17 monozygotic monochorionic female twins very discordant for birth weight. We examine if adverse prenatal growth conditions experienced by the smaller co-twins lead to long-lasting DNA methylation changes. RESULTS: Overall, co-twins show very similar genome-wide DNA methylation profiles. Since observed differences are almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3,153 are differentially methylated between the heavy and light co-twins at nominal significance, of which 45 show sensible absolute mean β-value differences. Deep bisulfite sequencing of eight such loci reveals that differences remain in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicates no significant intra-pair differences. CONCLUSIONS: Severe intra-uterine growth differences observed within these monozygotic twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies

Mathematical modeling of thermal and circulatory effects during hemodialysis.

Intradialytic hypotension (IDH) is one of the most common complications of hemodialysis (HD) treatment. The initiating factor of IDH is a decrease in blood volume, which is related to an imbalance between ultrafiltration (UF) and refilling rate. Impaired reactivity of resistance and capacitance vessels in reaction to hypovolemia plays possibly a major role in the occurrence of IDH. These vessels also fulfill an important function in body temperature regulation. UF-induced cutaneous vasoconstriction would result in a reduced surface heat loss and an increase in core temperature. To release body heat, skin blood flow is increased at a later stage of the HD treatment, whereby possibly IDH can occur. The aim of the study is to develop a mathematical model that can provide insight into the impact of thermoregulatory processes on the cardiovascular (CV) system during HD treatment. The mathematical procedure has been created by coupling a thermo-physiological model with a CV model to study regulation mechanisms in the human body during HD + UF. Model simulations for isothermal versus thermoneutral HD + UF were compared with measurement data of patients on chronic intermittent HD (n = 13). Core temperature during simulated HD + UF sessions increased within the range of measurement data (0.23 degrees C vs. 0.32 +/- 0.41 degrees C). The model showed a decline in mean arterial pressure of -7% for thermoneutral HD + UF versus -4% for isothermal HD + UF after 200 min during which relative blood volume changed by -13%. In conclusion, simulation results of the combined model show possibilities for predicting circulatory and thermal responses during HD + UF