Sampling Schedule Research Articles

FID-Net: A versatile deep neural network architecture for NMR spectral reconstruction and virtual decoupling

In recent years, the transformative potential of deep neural networks (DNNs) for analysing and interpreting NMR data has clearly been recognised. However, most applications of DNNs in NMR to date either struggle to outperform existing methodologies or are limited in scope to a narrow range of data that closely resemble the data that the network was trained on. These limitations have prevented a widescale uptake of DNNs in NMR. Addressing this, we introduce FID-Net, a deep neural network architecture inspired by WaveNet, for performing analyses on time domain NMR data. We first demonstrate the effectiveness of this architecture in reconstructing non-uniformly sampled (NUS) biomolecular NMR spectra. It is shown that a single network is able to reconstruct a diverse range of 2D NUS spectra that have been obtained with arbitrary sampling schedules, with a range of sweep widths, and a variety of other acquisition parameters. The performance of the trained FID-Net in this case exceeds or matches existing methods currently used for the reconstruction of NUS NMR spectra. Secondly, we present a network based on the FID-Net architecture that can efficiently virtually decouple 13Cα-13Cβ couplings in HNCA protein NMR spectra in a single shot analysis, while at the same time leaving glycine residues unmodulated. The ability for these DNNs to work effectively in a wide range of scenarios, without retraining, paves the way for their widespread usage in analysing NMR data.

Model-Based Estimation of Iohexol Plasma Clearance for Pragmatic Renal Function Determination in the Renal Transplantation Setting

BackgroundIohexol plasma clearance-based glomerular filtration rate (GFR) determination provides an accurate method for renal function evaluation. This technique is increasingly advocated for clinical situations that dictate highly accurate renal function assessment, as an alternative to conventional serum creatinine-based methods with limited accuracy or poor feasibility. In the renal transplantation setting, this particularly applies to living renal transplant donor eligibility screening, renal transplant function monitoring and research purposes. The dependency of current iohexol GFR estimation techniques on extensive sampling, however, has limited its clinical application. We developed a population pharmacokinetic model and limited sampling schedules, implemented in the online InsightRX precision dosing platform, to facilitate pragmatic iohexol GFR assessment.MethodsIohexol concentrations (n = 587) drawn 5 min to 4 h after administration were available from 67 renal transplant recipients and 41 living renal transplant donor candidates with measured iohexol GFRs of 27–117 mL/min/1.73 m2. These were split into a model development (n = 72) cohort and an internal validation (n = 36) cohort. External validation was performed with 1040 iohexol concentrations from 268 renal transplant recipients drawn between 5 min and 4 h after administration, and extended iohexol curves up to 24 h from 11 random patients with impaired renal function. Limited sampling schedules based on one to four blood draws within 4 h after iohexol administration were evaluated in terms of bias and imprecision, using the mean relative prediction error and mean absolute relative prediction error. The total deviation index and percentage of limited sampling schedule-based GFR predictions within ± 10% of those of the full model (P10) were assessed to aid interpretation.ResultsIohexol pharmacokinetics was best described with a two-compartmental first-order elimination model, allometrically scaled to fat-free mass, with patient type as a covariate on clearance and the central distribution volume. Model validity was confirmed during the internal and external validation. Various limited sampling schedules based on three to four blood draws within 4 h showed excellent predictive performance (mean relative prediction error < ± 0.5%, mean absolute relative prediction error < 3.5%, total deviation index < 5.5%, P10 > 97%). The best limited sampling schedules based on three to four blood draws within 3 h showed reduced predictive performance (mean relative prediction error < ± 0.75%, mean absolute relative prediction error < 5.5%, total deviation index < 9.5%, P10 ≥ 85%), but may be considered for their enhanced clinical feasibility when deemed justified.ConclusionsOur online pharmacometric tool provides an accurate, pragmatic, and ready-to-use technique for measured GFR-based renal function evaluation for clinical situations where conventional methods lack accuracy or show limited feasibility. Additional adaptation and validation of our model and limited sampling schedules for renal transplant recipients with GFRs below 30 mL/min is warranted before considering this technique in these patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-00998-z.

Observation of Conditions Preceding Peak Indoor Air Volatile Org Compound Concentrations in Vapor Intrusion Studies.

Temporal and spatial variability of indoor air volatile organic compound (VOC) concentrations can complicate vapor intrusion (VI) assessment and decision-making. Indicators and tracers (I&T) of VI, such as differential temperature, differential pressure, and indoor radon concentration, are low-cost lines of evidence to support sampling scheduling and interpretation of indoor air VOC sampling results. This study compares peak indoor air chlorinated VOC concentrations and I&T conditions before and during those peak events at five VI sites. The sites differ geographically and in their VI conceptual site models (CSM). Relative to site-specific baseline values, the results show that cold or falling outdoor temperatures, rising cross slab differential pressures, and increasing indoor radon concentrations can predict peak VOC concentrations. However, cold outdoor air temperature was not useful at one site where elevated shallow soil temperature was a better predictor. Correlations of peak VOC concentrations to elevated or rising barometric pressure and low wind speed were also observed with some exceptions. This study shows how the independent variables that control or predict peak indoor air VOC concentrations are specific to building types, climates, and VI CSMs. More I&T measurements at VI sites are needed to identify scenario-specific baseline and peak related I&T conditions to improve decision-making.

Energy-Efficient Data and Energy Integrated Management Strategy for IoT Devices Based on RF Energy Harvesting

Considering not only reducing the energy consumption based on the fixed energy source but also capturing new energy by RF energy harvesting (EH) for Internet-of-Things (IoT) devices, an integrated energy-efficient strategy for IoT devices is proposed in this article. On the one hand, a node sampling scheduling algorithm based on matrix completion is designed. All the sampling data are handled as matrix elements. The basic idea is to reduce the sampling data and then reconstruct the complete data set with the technology of matrix completion by using the spatial-temporal correlation of all the sampling data. Thus, the IoT nodes can keep dormant more instead of working on data sampling. The energy consumption can be significantly reduced with very little data loss. On the other hand, an adaptive RF energy management strategy is introduced. Based on the self-designed data and energy integrated network (DEIN) system, both data and energy are transferred between the DEIN gateway (DEING) and the DEIN Node (DEINN). With the adaptive energy management strategy, they both automatically switch between the wireless information transfer (WIT) mode and the wireless energy transfer (WET) mode. Combining energy saving with EH, the energy efficiency can be greatly enhanced. The proposed integrated solution aims to decrease the energy consumption of IoT devices and provide them with constant new energy by RF EH. Thus, their battery lives can be prolonged. Both the effectiveness and the efficiency of the proposed integrated strategy have been validated with the simulation.

Incidence, household transmission, and neutralizing antibody seroprevalence of Coronavirus Disease 2019 in Egypt: Results of a community-based cohort.

SARS-CoV-2 virus is transmitted in closed settings to people in contact with COVID-19 patients such as healthcare workers and household contacts. However, household person-to-person transmission studies are limited. Households participating in an ongoing cohort study of influenza incidence and prevalence in rural Egypt were followed. Baseline enrollment was done from August 2015 to March 2017. The study protocol was amended in April 2020 to allow COVID-19 incidence and seroprevalence studies. A total of 290 households including 1598 participants were enrolled and followed from April to October 2020 in four study sites. When a participant showed respiratory illness symptoms, a serum sample and a nasal and an oropharyngeal swab were obtained. Swabs were tested by RT-PCR for SARS-CoV-2 infection. If positive, the subject was followed and swabs collected on days three, six, nine, and 14 after the first swab day and a serum sample obtained on day 14. All subjects residing with the index case were swabbed following the same sampling schedule. Sera were collected from cohort participants in October 2020 to assess seroprevalence. Swabs were tested by RT-PCR. Sera were tested by Microneutralization Assay to measure the neutralizing antibody titer. Incidence of COVID-19, household secondary attack rate, and seroprevalence in the cohort were determined. The incidence of COVID-19 was 6.9% and the household secondary attack rate was 89.8%. Transmission within households occurred within two-days of confirming the index case. Infections were asymptomatic or mild with symptoms resolving within 10 days. The majority developed a neutralizing antibody titer by day 14 post onset. The overall seroprevalence among cohort participants was 34.8%. These results suggest that within-household transmission is high in Egypt. Asymptomatic or mild illness is common. Most infections seroconvert and have a durable neutralizing antibody titer.

Recommendations for conducting the rodent erythrocyte Pig-a assay: A report from the HESI GTTC Pig-a Workgroup.

The rodent Pig‐a assay is a flow cytometric, phenotype‐based method used to measure in vivo somatic cell mutation. An Organization for Economic Co‐operation and Development (OECD) test guideline is currently being developed to support routine use of the assay for regulatory purposes (OECD project number 4.93). This article provides advice on best practices for designing and conducting rodent Pig‐a studies in support of evaluating test substance safety, with a focus on the rat model. Various aspects of assay conduct, including laboratory proficiency, minimum number of animals per dose group, preferred treatment and blood sampling schedule, and statistical analysis are described.

Relationship between acoustic indices, length of recordings and processing time: a methodological test

Ecoacoustic approaches have the potential to provide rapid biodiversity assessments and avoid costly fieldwork. Their use in biodiversity studies for improving management and conservation of natural landscapes has grown considerably in recent years. Standardised methods for sampling acoustic information that deliver reliable and consistent results within and between ecosystems are still lacking. Sampling frequency and duration are particularly important considerations because shorter, intermittent recordings mean recorder batteries last longer and data processing is less computationally intensive, but a smaller proportion of the available soundscape is sampled. Here, we compare acoustic indices and processing time for subsamples of increasing duration clipped from 94 one-hour recordings, to test how different acoustic indices behave, in order to identify the minimum sample length required. Our results suggest that short recordings distributed across the survey period accurately represent acoustic patterns, while optimizing data collection and processing. ACI and H are the most stable indices, showing an ideal sampling schedule of ten 1-minute samples in an hour. Although ADI, AEI and NDSI well represent acoustic patterns under the same sampling schedule, these are more robust under continuous recording formats. Such targeted subsampling could greatly reduce data storage and computational power requirements in large-scale and long-term projects.

Evaluation of partial area under the curve in bioequivalence studies using destructive sampling design.

Product blood-level in vivo bioequivalence (BE) studies typically involve complete blood concentration-time profiles generated for each subject. Accordingly, each subject provides the estimates of the rate and extent of drug absorption. However, repeated blood draws are not always feasible for studies using small animals because of handling or blood volume (e.g., fish or in toxicokinetic studies when only single samples can be taken per animal). Although several proposals have been published for comparing the product extent of absorption, the issue of comparative absorption rates remains unresolved. In this paper, we propose to apply the Bailer-Satterthwaite-Fieller confidence interval for estimating the ratio of partial area under the curve in studies that use a destructive sampling design (one blood sample per subject). To characterize the behavior of this alternative approach, we examine the impact of partial area cutoff time, blood sampling schedule, and the number of subjects included at each sampling time. Using simulated situations reflective of the issues encountered with immediate-release veterinary formulations, we compare BE conclusions resulting from the use of this approach with simulated results that assuming repeated blood draws from each study subject.

Detection and impact of hysteresis when evaluating a drug's QTc effect using concentration-QTc analysis.

Early-phase studies quantifying the QTc prolongation potential for a new drug often use linear concentration-QTc (C-QTc) models, assuming no delay between plasma concentrations and QTc changes. However, that assumption is not always correct. The term "hysteresis" has been utilized to describe a time lag present between a measurable concentration and a measurable effect. To detect and quantify hysteresis and its impact on study interpretation, studies with hysteresis of 0.25-4h were simulated with different doses, half-lives, and sampling schedules in a crossover design. Hysteresis was quantified using a novel method termed exposure-normalized GRI (enGRI), a proposed modification of the Glomb-Ring Index (GRI), to account for delay and magnitude of QTc effects. With realistic sampling, the rate of false negative studies (FN) increased proportionally to the delay, even for delays shorter than 1h. Using an enGRI threshold (γ) of 2ms resulted in FN with undetected delay and FN without hysteresis at approximately the same rate. For γ = 2ms, the specificity of enGRI was > 90% throughout the investigated scenarios. We therefore propose the incorporation of enGRI when interpreting results from C-QTc analysis with the intent of characterizing QTc effects.

Model-based Dose Individualization of Sunitinib in Gastrointestinal Stromal Tumors.

Various biomarkers have been proposed for sunitinib therapy in gastrointestinal stromal tumor (GIST). However, the lack of "real-life" comparative studies hampers the selection of the most appropriate one. We, therefore, set up a pharmacometric simulation framework to compare each proposed biomarker. Models describing relations between sunitinib exposure, adverse events (hand-foot syndrome, fatigue, hypertension, and neutropenia), soluble VEGFR (sVEGFR)-3, and overall survival (OS) were connected to evaluate the differences in survival and adverse events under different dosing algorithms. Various fixed dosing regimens [4/2 (weeks on/weeks off) or 2/1 (50 mg), and continuous daily dosing (37.5 mg)] and individualization approaches [concentration-adjusted dosing (CAD), toxicity-adjusted dosing (TAD), and sVEGFR-3-adjusted dosing (VAD)] were explored following earlier suggested blood sampling schedules and dose-reduction criteria. Model-based forecasts of biomarker changes were evaluated for predictive accuracy and the advantage of a model-based dosing algorithm was evaluated for clinical implementation. The continuous daily dosing regimen was predicted to result in the longest survival. TAD (24.5 months) and VAD (25.5 months) increased median OS as compared with a fixed dose schedule (19.9 and 21.5 months, respectively) and CAD (19.7 and 21.3 months, respectively), without markedly raising the risk of intolerable toxicities. Changes in neutrophil count and sVEGFR-3 were accurately forecasted in the majority of subjects (>65%), based on biweekly blood sampling. Dose adjustments based on the pharmacodynamic biomarkers neutrophil count and sVEGFR-3 can increase OS while retaining drug safety. Future efforts could explore the possibility of incorporating a model-based dose approach in clinical practice to increase dosing accuracy for these biomarkers.

Optimised collection of non-uniformly sampled 2D-HSQC NMR spectra for use in metabolic flux analysis.

Nuclear magnetic resonance (NMR) spectroscopy is integral to metabolic studies; yet, it can suffer from the long acquisition times required to collect data of sufficient signal strength and resolution. The use of non-uniform sampling (NUS) allows faster collection of NMR spectra without loss of spectral integrity. When planning experimental methodologies to perform metabolic flux analysis (MFA) of cell metabolism, a variety of options are available for the acquisition of NUS NMR data. Before beginning data collection, decisions have to be made regarding selection of pulse sequence, number of transients and NUS specific parameters such as the sampling level and sampling schedule. Poor choices will impact data quality, which may have a negative effect on the subsequent analysis and biological interpretation. Herein, we describe factors that should be considered when setting up non-uniformly sampled 2D-1 H,13 C HSQC NMR experiments for MFA and provide a standard protocol for users to follow.

Water and Sediment Quality in the Coastal Zone Around the Mouth of Doce River After the Fundão Tailings Dam Failure.

Fundão dam (Minas Gerais, Brazil) breached on 5 November 2015, releasing 50 million m³ of Fe ore tailings and dam materials into the upper Doce River system. The tailings travelled 670 km along the river system to the ocean. Starting on 17 November 2015, 6 days before the tailings reached the Doce River mouth, a water quality monitoring program with a daily sampling schedule was implemented by Samarco Mineração S.A. (Samarco) to assess the impacts on marine water and sediment quality. Between November 2015 and August 2017 water and sediment quality were monitored at 28 locations offshore from the Doce River mouth. The sampling areas were grouped by hydrological and metocean season (i.e., rainy and dry seasons and wave and wind climates), distance from the river mouth (<5 km, >5 km and within a Marine Protected Area), and water depth. The data were compared to the Brazilian water quality standards and prebreach conditions. Statistical tests were conducted to evaluate temporal and spatial trends and patterns. For the water quality parameters of relevance (total suspended solids, turbidity, total and dissolved Fe, Al, and Mn), pulses of concentration increases were observed right after the arrival of the plume in the coastal zone and during the subsequent rainy seasons. Exceedances of prebreach conditions were more frequent closer to the Doce River mouth. During the dry season, concentrations tended to decrease, reaching prebreach levels for a number of parameters, with small short-term pulses associated with metocean factors. For sediment quality parameters of relevance (particle size, Fe, Al, and Mn), Fe was the only one that clearly resulted from the dam breach, which was mediated by river influence and oceanographic factors affecting particle size distribution. Results indicated that the Fundão dam failure did affect water and sediment quality in the Atlantic Ocean, with greater impacts closer to the river mouth and immediately after the arrival of the tailings plume, with concentrations gradually returning to preevent levels over time. Integr Environ Assess Manag 2020;16:643-654. © 2020 SETAC.

Experience with Real-Time Continuous Glucose Monitoring in Newborns with Congenital Hyperinsulinemic Hypoglycemia

Effective treatment and close monitoring of hypoglycemia in children with congenital hyperinsulinemic hypoglycemia (CHH) is vital to prevent brain damage. The current use of capillary sampling schedules does not provide a comprehensive assessment of glycemic status and fails to detect asymptomatic hypoglycemia episodes. To investigate the efficacy and accuracy of a real-time continuous glucose monitoring system (RT-CGMS) in neonates with CHH. A sensor connected to RT-CGMS was inserted into the newborn patients and maintained for at least 6 days during their stay in the hospital. We compared the readings of CGMS with capillary blood glucose values using Bland-Altman analysis. A total of 110 blood glucose values were compared to readings from the CGMS. All results were calculated and plotted for CGMS values at 0-4, 5-9, 10-14, 15-19, 20-24, and 25-29 min after capillary blood glucose sampling. CGMS readings were highly correlated with blood glucose values, especially during normoglycemia. In case of hypoglycemia, the mean difference between the CGMS and capillary glucose values was higher. Although the false positive rate for hypoglycemia was relatively high in CGMS, RT-CGMS may show some episodes of hypoglycemia earlier than blood measurement. RT-CGMS is accurate during normoglycemia, and it can reduce the number of capillary blood samples in children with CHH.

Optimal Designs for Model-Based Assessment of Insulin Sensitivity and Glucose Effectiveness.

The integrated minimal model allows assessment of clinical diagnosis indices, for example, insulin sensitivity (SI ) and glucose effectiveness (SG ), from data of the insulin-modified intravenous glucose tolerance test (IVGTT), which is laborious with an intense sampling schedule, up to 32 samples. The aim of this study was to propose a more informative, although less laborious, IVGTT design to be used for model-based assessment of SI and SG . The IVGTT design was optimized simultaneously for all design variables: glucose and insulin infusion doses, time of glucose dose and start of insulin infusion, insulin infusion duration, sampling times, and number of samples. Design efficiency was used to compare among different designs. The simultaneously optimized designs showed a profound higher efficiency than both standard rich (32 samples) and sparse (10 samples) designs. The optimized designs, after removing replicate sample times, were 1.9 and 7.1 times more efficient than the standard rich and sparse designs, respectively. After including practical aspects of the designs, for example, sufficient duration between samples and avoidance of prolonged hypoglycemia, we propose 2 practical designs with fewer sampling times and lower input of glucose and insulin than standard designs, constrained to prevent hypoglycemia. The optimized practical rich design is equally efficient in assessing SI and SG as the rich standard design, but with half the number of the samples, while the optimized practical sparse design has 1 less sample and requires 4.6 times fewer individuals for equal certainty when assessing SI and SG than the sparse standard design.

Giving Patients Choices: AstraZeneca’s Evolving Approach to Patient-Centric Sampling

This paper shares experiences and learning from introducing patient-centric sampling (PCS) into AstraZeneca trials. Through two case studies we show how modeling approaches can assist pharmacokinetic (PK) bridging studies accounting for blood partitioning and hematocritand how reduced PK sampling schedules, profiles constructed from composite data (plasma & dry blood) and combined assays (PK & pharmacodynamic) can all reduce patient sampling burden without impacting study outcomes. Following sharing some clinical operational challenges, we finally highlight some key requirements for implementing a patient-centric sampling strategy such as collaborative working across organizational silos, continuous patient engagement throughout the study lifecycle and accepting that if the aim is to give patient choice, then one solution (device, procedure and design) will not fit all.

Influence of sampling schedules on [177Lu]Lu-PSMA dosimetry

BackgroundIndividualized dosimetry is recommended for [177Lu]Lu-PSMA radioligand therapy (RLT) which is resource-intensive and protocols are often not optimized. Therefore, a simulation study was performed focusing on the determination of efficient optimal sampling schedules (OSS) for renal and tumour dosimetry by investigating different numbers of time points (TPs).MethodsSampling schedules with 1–4 TPs were investigated. Time-activity curves of the kidneys and two tumour lesions were generated based on a physiologically based pharmacokinetic (PBPK) model and biokinetic data of 13 patients who have undergone [177Lu]Lu-PSMA I&T therapy. Systematic and stochastic noise of different ratios was considered when modelling time-activity data sets. Time-integrated activity coefficients (TIACs) were estimated by simulating the hybrid planar/SPECT method for schedules comprising at least two TPs. TIACs based on one single SPECT/CT measurement were estimated using an approximation for reducing the number of fitted parameters. For each sampling schedule, the root-mean-squared error (RMSE) of the deviations of the simulated TIACs from the ground truths for 1000 replications was used as a measure for accuracy and precision.ResultsAll determined OSS included a late measurement at 192 h p.i., which was necessary for accurate and precise tumour TIACs. OSS with three TPs were identified to be 3–4, 96–100 and 192 h with an additional SPECT/CT measurement at the penultimate TP. Kidney and tumour RMSE of 6.4 to 7.7% and 6.3 to 7.8% were obtained, respectively. Shortening the total time for dosimetry to e.g. 96 h resulted in kidney and tumour RMSE of 6.8 to 8.3% and 9.1 to 11%, respectively. OSS with four TPs showed similar results as with three TPs. Planar images at 4 and 68 h and a SPECT/CT shortly after the 68 h measurement led to kidney and tumour RMSE of 8.4 to 12% and 12 to 16%, respectively. One single SPECT/CT measurement at 52 h yielded good approximations for the kidney TIACs (RMSE of 7.0%), but led to biased tumour TIACs.ConclusionOSS allow improvements in accuracy and precision of renal and tumour dosimetry for [177Lu]Lu-PSMA therapy with potentially less effort. A late TP is important regarding accurate tumour TIACs.

Validation of a Method for Estimating Vitamin A Absorption Efficiency Based on Compartmental Analysis of Post-Prandial Plasma Retinyl Ester Kinetics

Abstract Objectives Because good methods are not available to estimate vitamin A (VA) absorption, we evaluated an approach based on modeling retinyl ester response to an oral VA dose. Methods We generated data for 12 theoretical subjects, assigning values for VA absorption, stores, and kinetic parameters; we used WinSAAM (Simulation, Analysis and Modeling software) to simulate data (without and with 5% average error) for plasma chylomicron retinyl esters (RE) and retinol versus time (30 min to 8 h or 56 d, respectively) after ingestion of labeled VA; next we fit data to a previously-published 9-component model for VA metabolism to obtain “known” values for VA absorption. Then RE data only were modeled for each subject using a robust (n = 16 times) vs truncated sampling schedule (n = 10) and model-predicted absorptions were compared to known values. Areas under the plasma RE response curves (AUCs) were also calculated and compared to known absorption values. Results Known values for VA absorption based on modeling all data with error ranged from 54 – 92% (mean, 72%), VA stores from 160 – 1775 μmol, and chylomicron t1/2 from 6 – 12 min. Using the full sampling scheme for RE, the ratio of model-predicted to known absorption ranged from 0.927 – 1.06 (mean, 0.997); using the truncated scheme, the ratio was 0.814 – 1.13 (mean, 0.973). AUCs were not significantly correlated with known values for VA absorption (R2 = 0.112; P &amp;gt; 0.05), presumably because absorption and chylomicron catabolism are occurring simultaneously. Conclusions By modeling chylomicron RE tracer data after ingestion of labeled VA, absorption efficiency was estimated accurately using error-free data; using data with 5% error, estimates were within 10% of known values (full sampling) or within 20% (truncated). If subjects, after an overnight fast, consume a breakfast containing some fat and a known amount of VA, then no tracer is required to estimate VA absorption using this modeling approach. By incorporating a population-based design, the method could be used in children. Funding Sources Supported by Bill &amp; Melinda Gates Foundation (Project Number OPP1115464) and HarvestPlus (BH183438).

Contribution of Isotopic Techniques in the Hydrological Study of the Aquifers of Ica, Villacuri and Lanchas

Ica Aquifer located at the coastal zone of Ica River Valley, supplies 40% of the water to a number of farms of Ica Region which is one of the most productive valley of Peru that covers an area of 30,000 hectares of area, in which a diverse agricultural product are grown for local and external market. In the last 15 years, water-table of the aquifer was lowering at an elevated rate that concerned to farmers and authorities of the Peruvian Government, so a number of studies was carried out to increase the water supply to the agriculture areas.The main purpose of the study using isotope techniques, was to have a first insight of the hydrodynamics of Ica, Villacuri and Lanchas Aquifers and the possible interconnection between them and with Pisco River. For such purpose, 31 wells, lakes, rivers and springs of Ica and Pisco Basin where sampled during the years 2014 to 2016 both in rain and dry seasons, getting 189 samples for isotope and chemical analysis. The sampling schedule didn’t include rain sampling, instead of it, selected springs were sampled and nearby basin rain data was used.18O,2H and 13C stable isotopes and 3H, 14C radioactive isotopes of the water samples were analyzed in the laboratory of “Isotope Tracer Technologies INC”; the results of the stable isotope analysis confirm the hydraulic interconnection of the three aquifers mentioned above; it also was confirmed that the main source of recharge was provided by Ica River and evidences were found about the contribution of Pisco River in the recharge of Villacuri and Lanchas Aquifers.Analysis of 14C reveals that some wells are overexploited. All the results of 3H analysis were out of range, so it was not useful for the conclusions of the study, and a new sampling of water is required; the reason of this out of range result should be the possible contamination of the samples with no environmental Tritium.

Current Status of Magnetic Resonance on Saliva for Oral and Dental Health Early Diagnosis

Magnetic resonance spectroscopy of biomolecules has recently gained attention for clinical diagnosis. Its combination with saliva collection and analysis can promote early disease detection and monitoring, by identifying biomarkers of specific underlying pathology or disease as detected in saliva. With this novel, non-invasive technique, certain salivary biomarkers have been linked to dental and periodontal tissues pathology, as well as to specific head and neck cancer malignancies. At present, diagnostic biomarkers are still in need for further identification (e.g., diagnosis and monitoring of Sjögren’s syndrome), and nuclear magnetic resonance spectroscopy has been found to be a promising technique to compliment the current analytic methodology. Moreover, this article reports on the various data collection and analysis parameters used in the literature. Protocol standardization is yet to be established not only for the laboratory procedures, but also for the clinical sample collection. Herein, we review the current status of utilizing nuclear magnetic resonance in order to further support data on health associated biomarkers, and we also propose a saliva sampling scheduling protocol with the potential to be used in the clinical and experimental setting for standardization of the testing methodology.

Nutrition of Florida Citrus Trees, 3rd Edition: Chapter 11. Special Situations

The information provided in the 2008 2nd edition is still sound for healthy citrus trees under Florida production conditions. Much of the information provided in this document on nutrients, application methods, leaf and soil sampling and irrigation scheduling are also effective for huanglongbing (HLB) affected citrus trees. However, research conducted since HLB was detected in Florida in 2005 has established changes in many production practices, including nutrient rates, irrigation scheduling, soil pH management, and use of Citrus Under Protective Screen (CUPS). Changes to the 2nd edition of SL253 will appear in boxes similar to this one at the beginnings of chapters 2, 6, 8, 9, and 11.