A unique wheel-shaped exposed core LSPR-PCF sensor for dual-peak sensing: Applications in the optical communication bands, M-IR region and biosensing.

Photonic Crystal Fibers (PCF) effectiveness in practice decreases if the fabrication of the sensor becomes too complex. Keeping this in mind, we propose a one-of-a-kind wheel shaped PCF sensor with an exposed core containing only three air holes with exceptional sensing features. The sensor is equipped with dual plasmonic layers, Indium Tin Oxide (ITO, 10 % wt) and silver (Ag) with a coating of TiO2 to enhance the sensing capabilities and provide protection against oxidation. The sensor's distinctive configuration enables it to exhibit two distinct peaks within a range of refractive index from 1.32 to 1.38 for y-polarization and from 1.35 to 1.38 for x-polarization. The sensor specifications have been optimized to achieve the maximum levels of wavelength sensitivity (WS) and double peak shift sensitivity (DPSS). The sensor portrays a WS of 50,652 nm/RIU and the highest DPSS ever recorded, measuring 50,000 nm/RIU. Additionally, the sensor exhibits a significantly high scale of amplitude sensitivity (AS) of 1668.34 RIU-1 which is a very remarkable value considering silver as plasmonic material along with an outstanding figure of merit (FOM) of 1017.11 RIU-1. In addition, our sensor is able to manifest resolutions in the order of 10-6, demonstrating a resolution of 5.94 × 10-6 RIU with the deployment of amplitude interrogation method and 1.97 × 10-6 RIU with the wavelength interrogation method. The design spans an extensive spectrum, covering ultraviolet to mid-infrared wavelengths, enabling detection of biomolecules and biochemicals, along with operation in the optical communication band.

Double peak axial length measurement signal in cataract patients with epiretinal membrane.

PURPOSE: To evaluate the accuracy of axial length (AL) measurement for intraocular lens (IOL) calculation in patients with cataract and epiretinal membrane (ERM). METHODS: This prospective, cross-sectional study was performed in cataract patients with ERM. All subjects were sent for standard optical biometry, prepared for cataract surgery. Signals of AL measurement were detected as double peaks and recorded as AL1 (first peak), and AL2 (second peak). The IOL power was calculated from AL1 and AL2, and reported as IOL1 and IOL2. The IOL2 was chosen for cataract surgery in all cases. Postoperative predictive errors were compared between IOL1 and IOL2. RESULTS: Thirty-seven eyes from 37 patients were included. Mean AL1 was significantly shorter than AL2 (23.13 ± 1.28 vs. 23.60 ± 1.34 mm, p < 0.001), resulting in higher power of IOL1 than IOL2 (mean difference was 1.53 ± 0.96 diopters, p < 0.001). At 3-months post-operation, twenty-nine eyes (78.4%) (95% CI 62.8%-88.6%) showed refractive error within ± 0.5 diopter and all eyes were within ± 1.0 diopter. Postoperative predictive errors including mean arithmetic error (ME) and mean absolute error (MAE) of IOL2 were significantly lower than those of IOL1 (ME: IOL1 vs. IOL2, -0.94 ± 0.91 vs. 0.08 ± 0.51; MAE: 0.97 ± 0.88 vs. 0.39 ± 0.33 diopter, all p < 0.001). CONCLUSIONS: AL measurement in ERM can be detected as a double peak signal during biometric measurement. The IOL power calculated from the first and second peak signals is significantly different. However, the IOL power derived from the second peak signal provides better refractive outcomes. The results suggest that the second peak signal represents an accurate AL measurement.

Pharmacokinetics, Safety and Pharmacokinetics/Pharmacodynamics Analysis of Omadacycline in Chinese Healthy Subjects.

Objective: Omadacycline is a new type of aminomethylcycline antibiotic, having a broad antibacterial spectrum. But the pharmacokinetic characteristics and safety profile of the Chinese population remain unknown. It is also unclear whether the US-approved treatment regimen is applicable for the Chinese population. Methods: In a randomized, double-blinded, placebo-controlled dose-escalated trial, the pharmacokinetics of omadacycline was evaluated by a non-compartmental and compartmental model. Monte Carlo simulations were performed using the pharmacokinetic data from the Chinese population to evaluate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) of the US FDA-approved dose regimen. Results: The three-compartment model successfully described the rapid distribution and slow elimination of omadacycline after the intravenous infusion (i.v.). The double-peak concentration-time curve of the oral absorption (p.o.) was explained by the two-compartment model with two absorption compartments. The steady-state AUC of 100 mg omadacycline i.v. and 300 mg omadacycline p. o. were 12.1 and 19.4 mg h/L, respectively. Pharmacokinetics/pharmacodynamics (PK/PD) analysis showed that the omadacycline dosing regimen with a loading dose (200 mg i.v. q24 h, 100 mg i.v. q12 h, 450 mg p. o. q24 h × 2 days or 300 mg p. o. q12 h) and maintenance dose (100 mg i.v. q24 h or 300 mg p. o. q24 h) could cover the main pathogens of the indications acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP): Staphylococcus aureus and Streptococcus pneumoniae. Also, omadacycline had showed a good safety profile in the Chinese population. Conclusions: With the evidence provided, omadacycline could be a novel treatment option to Chinese patients with ABSSSI and CABP.

Effects of Accumulated Energy on Nanoparticle Formation in Pulsed-Laser Dewetting of AgCu Thin Films.

Ag50Cu50 films were deposited on glass substrates by a sputtering system. Effects of accumulated energy on nanoparticle formation in pulse-laser dewetting of AgCu films were investigated. The results showed that the properties of the dewetted films were found to be dependent on the magnitude of the energy accumulated in the film. For a low energy accumulation, the two distinct nanoparticles had rice-shaped/Ag60Cu40 and hemispherical/Ag80Cu20. Moreover, the absorption spectra contained two peaks at 700 nm and 500 nm, respectively. By contrast, for a high energy accumulation, the nanoparticles had a consistent composition of Ag60Cu40, a mean diameter of 100 nm and a peak absorption wavelength of 550 nm. Overall, the results suggest that a higher Ag content of the induced nanoparticles causes a blue shift of the absorption spectrum, while a smaller particle size induces a red shift.

Effects of control measures on the dynamics of COVID-19 and double-peak behavior in Spain.

The COVID-19 disease significantly has threatened the human lives and economy. It is a dynamic system with transmission and control as factors. Modeling the dynamics of the spread of COVID-19 based on the reported data can predict the growing trend of such a disease. In this paper, the dynamic evolution of COVID-19 in Spain is studied, and a comprehensive SEIR model is adopted to fit the obtained clinical progressive data of COVID-19 in Spain. The transmission rate between the susceptible and the self-quarantine susceptible is made to be time-variant, which is reasonable. The equilibria are found, and the stability condition is given using the basic reproduction number and eigenvalues at the points. The effect on daily confirmed cases for the transmission rate from susceptible to the exposed population due to the currently exposed and infectious is extensively investigated. The risk of the easing of the control measure is investigated. The double-peak dynamic behavior of the COVID-19 system is observed. The second wave rebound shows that the daily confirmed cases of the second peak even much higher than the first peak.

Interspecies differences on pharmacokinetics of rebamipide following oral administration to rats and dogs.

Rebamipide is used widely in East Asia for the treatment of gastric ulcers, acute gastritis, and exacerbated chronic gastritis. The objective of this study was to investigate the pharmacokinetic (PK) properties of rebamipide following single oral administration in rats and dogs. Eleven rats and dogs received single oral administrations of rebamipide (35 mg/kg and 100 mg, respectively). Blood samples were collected according to the assigned schedule, and the plasma concentration of rebamipide was determined using liquid chromatography-tandem mass spectrometry. A double-peak phenomenon was observed in the PK profile of rebamipide in rats. In contrast, rebamipide showed a conventional PK profile without double peaks in dogs. The half-life of rebamipide in rats (12.85 ± 7.86 h) was longer than that in dogs (5.62 ± 2.24 h), and the apparent total clearance (Clt /F) of rebamipide in rats (3.32 ± 1.18 L/h) was lower than that in dogs (105.01 ± 42.37 L/h). Simple allometric approaches showed that the correlation between body weight and Clt /F (R2 = 0.9287) among rats, dogs, and humans appeared satisfactory. This finding will help not only in understanding the pharmacology of rebamipide but also in establishing a strategy for in vivo evaluation of novel rebamipide formulations.

Seasonal variation in childhood mortality.

Aim: This ecological study was carried out to determine the cyclic trends in the rate of perinatal and infant mortality and among children aged under 15 years who died in traffic accidents or from drowning, respiratory disease or cancer.Methods: Monthly data on the numbers of live births, perinatal and infant deaths, and deaths from respiratory disease, cancer, traffic accidents, accidental drowning, and submersion in children aged under 15 years were obtained from the Hungarian nationwide population register. The data were aggregated over the study period and cyclic trends were investigated using the Walter-Elwood and negative binomial regression methods.Results: Significant double-peak (May and November) trends were found in mortality rates for perinatal and infant deaths, respectively. Additionally, significant (p-value < .001) seasonal variation in monthly mortality rates for deaths from respiratory diseases was observed with a peak in February, and a significant single peak was observed in mortality rates in July in both deaths from traffic accidents and drowning among children aged 0-14 years. However, there was no seasonal variation in monthly mortality rates for deaths from childhood cancer.Conclusions: Since cyclic trends in mortality suggest some effect of environmental factors in etiology, we might speculate that perinatal mortality may have been related to respiratory infections. A significant single peak was observed in mortality rates in July in both deaths from traffic accidents and drowning among children aged 0-14 years which could be related to environmental factors, such as temperature, air masses, and fronts. However, there was no seasonal variation in monthly mortality rates for deaths from childhood cancer. All of these novel findings could prove useful in preventive strategies, but further cohort studies are needed to investigate this hypothesis.What is knownSeasonality in infant mortality is known.What is newA significant cyclic trend was found in infants' mortality, with a peak in deaths in winter during the post-perinatal period and double peaks in May and November during the perinatal period, which might be associated with respiratory syncytial virus infections.Winter-peak cyclic trends were observed in both preterm and low birthweight mortality.A significant cyclic trend was observed in mortality, with a peak in deaths from traffic accidents and drowning in July for children aged 0-14 years, but seasonal variation was not found in monthly deaths from childhood cancer.

Potencial de ação duplo e alterações ecográficas do nervo mediano em doentes com síndrome do túnel cárpico / Double peak action potential and ultrasonography nerve evaluation in patients with carpal tunnel syndrome

Introdução: A síndrome do túnel cárpico (STC) é sustentada pela presença de lentificação do potencial de ação do nervo mediano no estudo ortodrómico de condução nervosa sensitiva em comparação com o nervo radial (EC-MR). Uma técnica modificada de registo simultâneo de ambos os nervos (EC-MRsimul) pode ser utilizada, detetando a lentificação do nervo mediano através da presença de potencial de ação sensitivo duplo (PAS-D). O objetivo deste estudo é correlacionar o PAS-D com os achados de EC-MR e com o edema perineural em doentes com diagnóstico de STC. Métodos: Indivíduos saudáveis e doentes com STC há menos de 12 meses foram submetidos a avaliação eletrofisiológica, incluindo o EC-MR e o EC-MRsimul. Foi também realizada ultrassonografia para registo da área seccional do nervo mediano (AS-NM) no punho e antebraço e, respetivo índice punho-antebraço (I-PA). Resultados: Foram recrutados 38 doentes com idade média de 54,8 ± 15,3 anos com STC e 18 indivíduos saudáveis. A diferença de latência distal entre o nervo mediano e radial foi superior nos doentes (0,80 ± 0,30ms vs. 0,15 ± 0,20ms; p=0,015). O EC­MRsimul demonstrou a presença de PAS-D nos indivíduos sintomáticos. A AS­NM no punho foi também superior nos doentes (8,9 ± 0,9mm2 vs. 6,6 ± 0,7mm2; p<0.003), tendo sido identificado um quisto sinovial e um neurinoma. O edema perineural traduzido pela AS-SM correlacionou-se positivamente com a diferença de latência interpico no EC-MR e com a presença de PAS-D. Conclusão: O PAS-D está associado à presença de lentificação da condução e ao edema perineural do nervo mediano no contexto de STC ou devido a lesões ocupantes de espaço. (AU)

Introduction: Carpal tunnel syndrome (CTS) is characterized by median nerve action potential slowing, which can be shown in comparative orthodromic sensory nerve conduction studies between median and radial nerve (NCS-MR). A modified technique with simultaneous recording of both nerves (NCS-MRsimul) can also be used to detect median nerve slowing through the presence of double peak action potential (DPp). The study aims to correlate the presence of DPp with NCS-MR findings and with perineural edema in patients diagnosed with STC. Methods: Healthy individuals and patients with CTS for less than 12 months underwent NCS-MR and MRsimul. An ultrasonography evaluation was also performed to record the medial nerve sectional area (SA-MN) on the wrist and forearm, and the wrist-to-forearm ratio (WFR) was calculated. Results: We recruited 38 patients with CTS whose mean age was 54.8 ± 15.3 years and 18 healthy individuals. Distal latency difference between the median and radial nerves was higher in patients with CTS (0.80 ± 0.30 ms vs. 0.15 ± 0.20 ms, p = 0.015). NCS-MRsimul showed DPp in symptomatic individuals. SA-MN in the wrist was also higher in patients with CTS (8.9 ± 0.9 mm2 vs. 6.6 ± 0.7 mm2 , p <0.003). Ultrasonography evaluation identified a synovial cyst and a neurinoma. Perineural edema traduced by higher SA-MN and WFR correlated positively with interpeak latency difference in NCS-MR and with the presence of DPp. Conclusions: DPp was associated with median nerve sensory action potential slowing and with perineural edema due to either CTS or to space-occupying lesions. (AU)

Double peak sensory nerve action potentials to single stimuli in nerve conduction studies.

INTRODUCTION: In humans, sensory nerve action potentials (SNAPs) can show 2 separate deflections, i.e., double peak potentials (DPp), which necessarily means that 1 peak is delayed with respect to the other. DPps may have various origins and be due to either physical or physiological properties. METHODS: We review the nature of commonly encountered DPps in clinical practice, provide the most likely interpretations for their physiological origin, and assess their reproducibility and clinical utility. RESULTS: We classified the DPps into 3 categories: (1) simultaneous anodal and cathodal stimulation. (2) simultaneous recording from 2 different nerves at the same site, and (3) SNAP desynchronization. CONCLUSIONS: Although the recording of DPps is not a standardized neurophysiological method, their study brings interesting cues about the physiology of nerve stimulation and paves the way for clinical application of such an observation. Muscle Nerve 55: 619-625, 2017.

A rapid and sensitive liquid chromatography-tandem mass spectrometric method for the determination of hederasaponin B in rat plasma: Application to a pharmacokinetic study.

A rapid, simple and sensitive ultra-high performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed and validated for the determination of hederasaponin B, an active triterpenoid saponin widely existed in Hedera helix L. Plasma samples were processed by protein precipitation with acetonitrile and separated on a Thermo Hypersil GOLD C18 (2.1 mm × 50 mm,1.9 µm) at flow rate of 0.3 ml/min, with a gradient elution consisting of acetonitrile and water containing 0.1% (v/v) formic acid at 30 °C and detected by electrospray ionization mass spectrometry in the positive multiple reaction monitoring (MRM) mode. The linearity was found to be within the concentration range of 0.5-5000 ng/ml with a lower limit of quantification of 0.5 ng/ml. The absolute oral bioavailability of hederasaponin B was 0.24 ± 0.49%. This indicated that the concentration-time course of the hederasaponin B existed a double-peak phenomenon. This method was further applied to the determination of hederasaponin B in rat plasma and showed good practicability, for the first time, after intragastric (25 mg/kg) and intravenous (2 mg/kg) administration in rats.

Electrically evoked compound action potentials are different depending on the site of cochlear stimulation.

One of the many parameters that can affect cochlear implant (CI) users' performance is the site of presentation of electrical stimulation, from the CI, to the auditory nerve. Evoked compound action potential (ECAP) measurements are commonly used to verify nerve function by stimulating one electrode contact in the cochlea and recording the resulting action potentials on the other contacts of the electrode array. The present study aimed to determine if the ECAP amplitude differs between the apical, middle, and basal region of the cochlea, if double peak potentials were more likely in the apex than the basal region of the cochlea, and if there were differences in the ECAP threshold and recovery function across the cochlea. ECAP measurements were performed in the apical, middle, and basal region of the cochlea at fixed sites of stimulation with varying recording electrodes. One hundred and forty one adult subjects with severe to profound sensorineural hearing loss fitted with a Standard or FLEXSOFT electrode were included in this study. ECAP responses were captured using MAESTRO System Software (MED-EL). The ECAP amplitude, threshold, and slope were determined using amplitude growth sequences. The 50% recovery rate was assessed using independent single sequences that have two stimulation pulses (a masker and a probe pulse) separated by a variable inter-pulse interval. For all recordings, ECAP peaks were annotated semi-automatically. ECAP amplitudes were greater upon stimulation of the apical region compared to the basal region of the cochlea. ECAP slopes were steeper in the apical region compared to the basal region of the cochlea and ECAP thresholds were lower in the middle region compared to the basal region of the cochlea. The incidence of double peaks was greater upon stimulation of the apical region compared to the basal region of the cochlea. This data indicates that the site and intensity of cochlear stimulation affect ECAP properties.

Stimulus waveform determines the characteristics of sensory nerve action potentials.

OBJECTIVE: In routine nerve conduction studies supramaximal electrical stimuli generate sensory nerve action potentials by depolarization of nerve fibers under the cathode. However, stimuli of submaximal intensity may give rise to action potentials generated under the anode. We tested if this phenomenon depends on the characteristics of stimulus ending. METHODS: We added a circuit to our stimulation device that allowed us to modify the end of the stimulus by increasing the time constant of the decay phase. RESULTS: Increasing the fall time caused a reduction of anode action potential (anAP) amplitude, and eventually abolished it, in all tested subjects. We subsequently examined the stimulus waveform in a series of available electromyographs stimulators and found that the anAP could only be obtained with stimulators that issued stimuli ending sharply. CONCLUSION: Our results prove that the anAP is generated at stimulus end, and depends on the sharpness of current shut down. Electromyographs produce stimuli of varying characteristics, which limits the reproducibility of anAP results by interested researchers. SIGNIFICANCE: The study of anodal action potentials might be a useful tool to have a quick appraisal of distal human sensory nerve excitability.

Double-peak elution profile of a monoclonal antibody in cation exchange chromatography is caused by histidine-protonation-based charge variants.

We have systemically investigated unusual elution behaviors of an IgG4 (mAb A) in cation exchange chromatography (CEX). This mAb A exhibited two elution peaks under certain conditions when being purified by several strong CEX columns. When either of the two peaks was isolated and re-injected on the same column, the similar pattern was observed again during elution. The protein distribution between the two peaks could be altered by NaCl concentration in the feed, or NaCl concentration in wash buffer, or elution pH, suggesting two pH-associated strong-and-weak binding configurations. The protein distributions under different pH values showed good correlation with protonated/un-protonated fractions of a histidine residue. These results suggest that the double-peak elution profile associates with histidine-protonation-based charge variants. By conducting pepsin digestion, amino-acid specific chemical modifications, peptide mapping, and measuring the effects of elution residence time, a histidine in the variable fragment (Fab) was identified to be the root cause. Besides double-peak pattern, mAb A can also exhibit peak-shouldering or single elution peak on different CEX resins, reflecting different resins' resolving capability on protonated/un-protonated forms. This work characterizes a novel cause for unusual elution behaviors in CEX and also provides alternative avenues of purification development for mAbs with similar behaviors.

Integrated pharmacokinetics and biodistribution of multiple flavonoid C-glycosides components in rat after oral administration of Abrus mollis extract and correlations with bio-effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Abrus mollis, a commonly used traditional Chinese medicine in China and other Asia countries, has been used clinically to prevent and treat hepatitis and alcoholic liver disease for decades. MATERIALS AND METHODS: A modified HPLC-MS method was developed for the determination of vicenin-2 (AM-I), isoschaftoside (AM-II), and schaftoside (AM-III) of AM extract (AME) in rat plasma and tissues (heart, liver, spleen, lungs, and kidneys). Following oral administration of AME to rat at a dose of 200mg/kg, the concentrations of AM-I, II and III in plasma and tissues were quantified. An integrated double peak pharmacokinetics model was used to fit the concentration-time curves. The effects of drug on the bile flow and toe swelling of rats induced by carrageenan were also studied. RESULTS: The limit of quantitation of this modified HPLC-MS method decreased from 25 to 5ng/mL for plasma and from 100 to 10ng/g for tissue. These concentration-time curves show two successive maximum concentrations. The results of integrated double peak pharmacokinetics in this paper indicated that the three flavonoid C-glycosides may be absorbed by two sites of intestine in vivo. These results of bile flow and toe swelling showed a significant correlation between the pharmacokinetics and pharmacodynamics. CONCLUSIONS: The novel integrated double peak pharmacokinetic approach to studying the holistic pharmacokinetic properties of traditional Chinese medicine has been successfully developed and validated using AM as a model drug. This study would be a useful guide for the holistic double peak pharmacokinetic study in consistence with the intrinsic theory and characteristics of traditional Chinese medicine.

Is effective mass in combat sports punching above its weight?

The segmental and muscular complexity of the human body can result in challenges when examining the kinetics of impacts. To better understand this complexity, combat sports literature has selected effective mass as a measure of an athlete's inertial contribution to the momentum transfer during the impact of strikes. This measure helps to clarify the analysis of striking kinetics in combat sports. This paper will review: (1) effective mass as a concept and its usage as a measure of impact intensity in combat sports, (2) the neuromuscular pattern known as "double peak muscle activation" which has been theorized to help enhance initial hand velocity upon impact and joint stiffening during impact, (3) the methods and equations used to calculate effective mass, and (4) practitioner recommendations based on the literature. We will argue in this manuscript that the act of punching presents unique challenges to the current understanding of effective mass due to additional force application during impact. This review will improve the understanding of effective mass and its roles in effective striking serving to underpin future research into performance enhancement in striking based combat sports.

Skin receptors and intradermal nerves do not generate the sensory double peak.

INTRODUCTION: The cause of the double peak observed at submaximal stimulation of sensory nerves is unknown. The first peak is generated under the cathode and the second under the anode. The double peak is thought to arise from intradermal nerves or skin receptors, and in this study we tested this assumption. METHODS: We studied the effect of different stimulus durations on anodal peak latency in volunteers. Biphasic anodal stimulation was used to investigate the latent additive effect of the trailing negative phase on the partial depolarization induced by the initial positive phase. We further tested the maximal amplitude of anode-generated potentials to estimate the number of neural structures involved in their generation. RESULTS: Increased stimulus duration caused anode-generated potential delay. Biphasic stimulation increased anode-generated amplitude 4-fold compared with monophasic stimulation. The anode-generated potential produced up to 85% of the supramaximal cathode-generated amplitude. CONCLUSIONS: The results suggest that the double peak arises from anodal break excitation and not from intradermal nerves or receptors.

Axial length estimation error caused by hidden double-peak on partial coherence interferometry in an eye with epiretinal membrane: a case report.

Here we report a patient in whom there was a myopic shift after combined cataract surgery and pars plana vitrectomy against the epiretinal membrane, related to axial measurement estimation error caused by a hidden double-peak appearance on partial coherence interferometry measurement. A 52-year-old female presented with epiretinal membrane and underwent combined cataract surgery and pars plana vitrectomy. Axial length was measured with partial coherence interferometry. Although the signal curve in the summary display showed a single peak, a 1.6 diopter myopic shift occurred. Viewed retrospectively, six of 20 individual signal curves showed a double peak. Most of them showed a higher anterior peak, with only one having a higher posterior peak. The other 14 curves showed a single peak at a similar distance to an anterior peak. The anterior peak appeared to be derived from the epiretinal membrane. The possibility of a double peak should always be considered in patients with epiretinal membrane even if the summary display of the partial coherence interferometry measurement shows a single peak. Checking all signal curves would reduce the risk of missing a hidden double peak.

Double peaked P1 visual evoked potentials in healthy ageing.

OBJECTIVES: To robustly examine the prevalence of the double peaked P1 visual evoked potential in healthy younger and older adult populations. METHODS: The evoked potentials and spectral power changes to simple visual stimuli of 26 healthy younger (M=20.0 y) and 26 healthy older adults (M=76.0 y) were examined. RESULTS: Group and individual analyses showed a clear effect of age on P1 morphology and amplitude. Older adults showed significantly lower P1 amplitude and 44% of older adults showed a double peaked P1 compared to 12% of younger adults. Double peaked P1 responses were associated with an increase in spectral power in the gamma range. CONCLUSIONS: The double peaked P1 may be more prevalent in older adults than previously demonstrated and may represent a de-synchronisation of the cortical sources of the visual P1 in healthy ageing. Increased power in post stimulus gamma in the double peak group may be indicative of compensatory neural processing. SIGNIFICANCE: Clinically the prevalence of the double peaked P1 may have been underestimated, and its reflectance of demyelinating disease overestimated. Experimentally the results suggest that any investigation of visual processing in older adults must control for early changes in P1 morphology.

The influence of pH on iron speciation in podzol extracts: iron complexes with natural organic matter, and iron mineral nanoparticles.

The quantities of natural organic matter (NOM) and associated iron (Fe) in soil extracts are known to increase with increasing extractant pH. However, it was unclear how the extraction pH affects Fe speciation for particles below 30 nm. We used flow field-flow fractionation (FlowFFF) and transmission electron microscopy (TEM) to investigate the association of Fe and trace elements with NOM and nanoparticulate iron (oxy)hydroxides in podzol extracts. For extracts prepared at the native soil pH (~4), and within a 1-30 nm size range, Fe was associated with NOM. In extracts with a pH≥7 from the E and B soil horizons, Fe was associated with NOM as well as with iron (oxy)hydroxide nanoparticles with a size of approximately 10 nm. The iron (oxy)hydroxide nanoparticles may have either formed within the soil extracts in response to the increase in pH, or they were mobilized from the soil. Additionally, pH shift experiments showed that iron (oxy)hydroxides formed when the native soil pH (~4) was increased to 9 following the extraction. The iron (oxy)hydroxide nanoparticles aggregated if the pH was decreased from 9 to 4. The speciation of Fe also influenced trace element speciation: lead was partly associated with the iron (oxy)hydroxides (when present), while copper binding to NOM remained unaffected by the presence of iron (oxy)hydroxide nanoparticles. The results of this study are important for interpreting the representativeness of soil extracts prepared at a pH other than the native soil pH, and for understanding the changes in Fe speciation that occur along a pH gradient.

Therapeutic drug monitoring and pharmacokinetic compartmental analysis of sulpiride double-peak absorption profile after oral administration to human volunteers.

BACKGROUND: The pharmacokinetics of oral drugs that exhibit double peaks cannot be described adequately by using conventional compartmental models. OBJECTIVE: The aim of this study was to describe the double-peak plasma pharmacokinetic profile of sulpiride after oral administration to healthy volunteers based on physiological and biopharmaceutical considerations. METHODS: A single 100 mg dose of sulpiride was given to 16 healthy volunteers. Blood samples were drawn at different times and analysed by a validated HPLC assay method. Plasma profiles were evaluated by non-compartmental and compartmental approaches. RESULTS: The non-compartmental parameters determined were k (0.079±0.008 h(-1)), t1/2 (9.0±2.9 h), Vd /F (330.5±87.3 L), Cl/F (38.2±9.8 L/h) and AUC0→∞ (1402.5±404.7 ng.h/mL). The compartmental analysis was described appropriately using a two-compartment body model, with first order absorption from two different sites in the gut. The parameters determined were k21 (0.68±0.2 h(-1)), ka1 (0.7±0.27 h(-1)), ka2 (2.7±1.8 h(-1)) Vc/F (45.1±15.7 L), α (33.3±1.5 h(-1)), ß (0.11±0.03 h(-1)) and time for the beginning of the absorption from the second site (4.4±2.1 h). CONCLUSION: The developed analytical method was suitable for use in pharmacokinetic studies and therapeutic drug monitoring implementation. Sulpiride was well tolerated by the patients without any serious adverse events being observed. The double peaks in the serum concentration-time profiles could be due to differential rates of absorption along the gastrointestinal tract. The discontinuous absorption model with two sites of absorption was adequate to describe the double-peak of the sulpiride plasma profile. ClinicalTrials. gov identifiers: NCT01777685.