Significant Degree Of Variability Research Articles

Study of Genetic Diversity and Genetic Advance in Brinjal for Morpho-Economic Traits (Solanum melongena L.)

In two distinct environments (E1 and E2), the current experiment was set up using a randomized block design with the goal of determining the extent of genetic diversity, heritability, and genetic advancement among 15 yield-related variables in brinjal. The analysis of variance results revealed that there were significant genetic variances across brinjal genotypes, indicating a significant degree of variability and boosting the opportunity for selection to improve the essential traits. There was a noticeable variance in mean values between the genotypes for several traits, from modest to wide. For most of the features under investigation, with the exception of days to 50% flowering, moderate to high genotypic coefficient of variation, moderate to high heritability, and genetic advancement as a percentage of mean were reported.

Studies on Genetic Divergence Analysis in Black Gram (Vigna mungo L. Hepper) Genotypes

In order to select superior genotypes for the creation of genetic stock for hybridization program or the introduction of a crop variety, plant breeders can assist from genetic diversity both within and between plant species. Mahalanobis D2 Statistics was used to conduct the current study on Genetic Divergence and clustering pattern utilizing twenty eight different genotypes of Black gram. The experiment was conducted in Randomized Block Design with three replications at Plant Breeding Farm, Department of Genetics and Plant Breeding, Faculty of Agriculture, Annamalai University, Chidambaram, Tamil Nadu, India. Nine different biometrical characteristics were observed and documented viz., plant height at maturity (PH), pod length (LP), number of branches per plant (NBPP), number of clusters per plant (NCPP), number of pods per cluster (NPPC), number of pods per plant (NPPP), number of seeds per pod (NSPP), 100 seed weight (SW), and seed yield per plant (SY). All of these characters have a significant degree of variability, according to an analysis of variance. Mahalanobis (D2) static revealed considerable genetic diversity among the genotypes. Genotypes were grouped into 6 clusters. Cluster VI was the largest including 11 genotypes. The intra-cluster distance for cluster IV is the maximum and the lowest intra-cluster distance was reported for cluster II. The highest inter-cluster distance was revealed between cluster I and III and then between cluster II and III. This demonstrates unambiguously that the genotypes in this cluster exhibit a wide range of genetic variation and may be useful in a black gramme hybridization scheme to increase production. Between clusters I and II, the minimal inter-cluster distance was discovered. The percentage that each character contributed to the overall divergence was as follows: the number of pods per plant (50.997), the greater seed output (50.997), and the 100 seed weight (29.456). (8.121). It is proposed that crossings between parents from the most divergent clusters should show the highest level of heterosis as well as the greatest degree of genetic architectural variability.

Prospective association of occupational and leisure-time physical activity with orthostatic blood pressure changes in older adults

Orthostatic hypotension (OH) is common in older people. We examined the influence of self-reported occupational-related physical activity (PA) and leisure-time physical exercise (PE) on orthostatic response in a sample of older people over a 2 year period. Supine and orthostatic systolic blood pressure (sBP), diastolic blood pressure (dBP), and mean blood pressure (mBP) were assessed in response to Active Stand (AS) test in 205 older subjects (> 60 years old) at baseline and 2-year follow-up. OH was found in 24 subjects (11.71%) at baseline and 20 subjects (9.76%) after 2 years, with a significant degree of variability in the occurrence of OH after 2 years. Twenty-two subjects who had OH at baseline were free of it after 2 years, two subjects had persistent OH at baseline and after 2 years. After 2 years, adults with occupational PA showed no significant decrease of blood pressure in response to AS test, while lack of undertaking an occupation-related PA was significantly related with a greater decrease in sBP and mBP in response to AS testing in the 1st min. Occupation-related PA and leisure-time-related PE were related to an increase in the response of BP on AS in change between baseline and after 2 years. High between-subjects variance in OH over 2 years was noted. Occupations that involved continuous physical activity and leisure-time physical exercise in middle age were both protective for BP decline on orthostatic stress test within 2 years.

Reproducibility and Reliability of Computing Models in Segmentation and Volumetric Measurement of Brain.

Segmentation and morphometric measurement of brain tissue and regions from non-invasive magnetic resonance images have clinical and research applications. Several software tools and models have been developed by different research groups which are increasingly used for segmentation and morphometric measurements. Variability in results has been observed in the imaging data processed with different neuroimaging pipelines which have increased the focus on standardization. The availability of several tools and models for brain morphometry poses challenges as an analysis done on the same set of data using different sets of tools and pipelines may result in different results and interpretations and there is a need for understanding the reliability and accuracy of such models. T1-weighted (T1-w) brain volumes from the publicly available OASIS3 dataset have been analysed using recent versions of FreeSurfer, FSL-FAST, CAT12, and ANTs pipelines. grey matter (GM), white matter (WM), and estimated total intracranial volume (eTIV) have been extracted and compared for inter-method variability and accuracy. All four methods are consistent and strongly reproducible in their measurement across subjects however there is a significant degree of variability between these methods. CAT12 and FreeSurfer methods have the highest degree of agreement in tissue class segmentation and are most reproducible compared to others.

An Evolution of the Surgical Management of Synpolydactyly: A Case Series of 21 Hands.

Synpolydactyly is a rare congenital anomaly characterized by syndactyly and polydactyly in the central hand. Limited treatment guidelines exist for this complex condition. A retrospective review of synpolydactyly patients was conducted at a large, tertiary pediatric referral center to describe our surgical experience and evolution of management. The Wall classification system was used to categorize cases. Eleven patients (21 hands) with synpolydactyly were identified. Most of the patients were White and had at least one first-degree relative who also had synpolydactyly. The Wall classification yielded the following results: 7 type 1A hands, 4 type 2B hands, 6 type 3 hands, and 4 uncategorizable hands. Each patient had an average of 2.6 surgeries and an average follow-up time of 5.2 years. The rates of postoperative angulation and flexion deformities were 24% and 38%, respectively, with many of these cases also demonstrating preoperative alignment abnormalities. These cases often required additional surgeries including osteotomies, capsulectomies, and/or soft tissue releases. The rate of web creep was 14% with 2 of these patients requiring revision surgery. Despite these findings, at the time of final follow-up, most patients had favorable functional outcomes, were able to engage in bimanual tasks, and were able to perform activities of daily living independently. Synpolydactyly is a rare congenital hand anomaly with a significant degree of variability in clinical presentation. The rates of angulation and flexion deformities as well as web creep are not insignificant. We have learned to prioritize correcting contractures, angulation deformities, and skin fusion, over simply trying to delete the "extra" number of bones as this may destabilize the digit(s).

Individual Case Safety Report Replication: An Analysis of Case Reporting Transmission Networks.

The basis of pharmacovigilance is provided by the exchange of Individual Case Safety Reports (ICSRs) between the recipient of the original report and other interested parties, which include Marketing Authorization Holders (MAHs) and Health Authorities (HAs). Different regulators have different reporting requirements for report transmission. This results in replication of each ICSR that will exist in multiple locations. Adding in the fact that each case will go through multiple versions, different recipients may receive different case versions at different times, potentially influencing patient safety decisions and potentially amplifying or obscuring safety signals inappropriately. The present study aimed to investigate the magnitude of replication, the variability among recipients, and the subsequent divergence across recipients of ICSRs. Seven participating TransCelerate Member Companies (MCs) queried their respective safety databases covering a 3-year period and provided aggregate ICSR submission statistics for expedited safety reports to an independent project manager. As measured in the US Food and Drug Administration (FDA)'s Adverse Event Reporting System (FAERS), ICSR volume for these seven MCs makes up approximately 20% of the total case volume. Aggregate metrics were calculated from the company data, specifically: (i) number of ICSR transmissions, (ii) average number of recipients (ANR) per case version transmitted, (iii) a submission selectivity metric, which measures the percentage of recipients not having received all sequential case version numbers, and (iv) percent of common ISCRs residing in two or more MAH databases. The analysis reflects 2,539,802 case versions, distributed through 7,602,678 submissions. The overall mean replication rate is 3.0 submissions per case version. The distribution of the ANR replication measure was observed to be very long-tailed, with a significant fraction of case versions (~12.4% of all transmissions) being sent to ten or more HA recipients. Replication is higher than average for serious, unlisted, and literature cases, ranging from 3.5 to 6.1 submissions per version. Within the subset of ICSR versions sent to three recipients, a significant degree of variability in the actual recipients (i.e., HAs) was observed, indicating that there is not one single combination of the same three HAs predominantly receiving an ICSR. Submission selectivity increases with the case version. For case version 6, the range of the submission selectivity for the MAHs ranges from ~10% to over 50%, with a median of 30.2%. Within the participating MAHs, the percentage of cases that reside within at least two safety databases is approximately 2% across five databases. Further analysis of the data from three MAHs showed percentages of 13.4%, 15.6%, and 27.9% of ICSRs originating from HAs and any other partners such as other MAHs and other institutions. Replication of ICSRs and the variation of available safety information in recipient databases were quantified and shown to be substantial. Our work shows that multiple processors and medical reviewers will likely handle the same original ICSR as a result of replication. Aside from the obvious duplicate work, this phenomenon could conceivably lead to differing clinical assessments and decisions. If replication could be reduced or even eliminated, this would enable more focus on activities with a benefit for patient safety.

Exploit computer vision inpainting approach to boost deep learning models

In today’s world, the amount of available information grows exponentially every day. Most of this data is visual data. Correspondingly, the demand for the algorithm of image rent is growing. Traditionally, the first approaches to computer vision problems were classical algorithms without the use of machine learning. Such approaches are limited by many factors. First of all, the conditions imposed on the input images are applied – the shooting angle, lighting, position of objects on the scene, etc. Other classical algorithms cannot meet the needs of modern computer vision problems. Neural network approaches and deep learning models have largely replaced classical programming algorithms. The greatest advantage of deep neural networks in computer vision tasks is not only the possibility of automatically building data processing algorithms that cannot be built in any other way, but also the comprehensiveness of such an approach – actual deep neural networks provide all stages of image processing from start to finish. But. This approach is not always optimal. Training models require a large amount of annotated data to avoid the effect of overfitting such models. In many settings, the conditions have a significant degree of variability, but are limited. In such cases, the combination of both approaches of computer vision is fruitful – pre-processing of the image is performed by classical algorithms, and prediction (classification, object search, etc.) is performed by a neural network. This article noted an example of the use of damaged images in the classification of tasks (in the extreme cases, the percentage of damage reached 60 % of the image area). We have shown in practice that the use of classic approaches for restoration of damaged areas of the image (inpainting) made it possible to increase the final accuracy of the model by up to 10 % compared to the base model trained under identical conditions on the original data.

Comparison of health-related quality of life in patients with traumatic brain injury, subarachnoid haemorrhage and cervical spine disease

Purpose The degree of disability that is acceptable to patients following traumatic brain injury (TBI) continues to be debated. While the dichotomization of outcome on the Glasgow Outcome Score (GOSE) into ‘favourable’ and ‘unfavourable’ continues to guide clinical decisions, this may not reflect an individual’s subjective experience. The aim of this study is to assess how patients’ self-reported quality of life (QoL) relates to objective outcome assessments and how it compares to other debilitating neurosurgical pathologies, including subarachnoid haemorrhage (SAH) and cervical myelopathy. Method A retrospective analysis of over 1300 patients seen in Addenbrooke’s Hospital, Cambridge, UK with TBI, SAH and patients pre- and post- cervical surgery was performed. QoL was assessed using the SF-36 questionnaire. Kruskal-Wallis test was used to analyse the difference in SF-36 domain scores between the four unpaired patient groups. To determine how the point of dichotomization of GOSE into ‘favourable’ and ‘unfavourable’ outcome affected QOL, SF-36 scores were compared between GOSE and mRS. Results There was a statistically significant difference in the median Physical Component Score (PCS) and Mental Component Score (MCS) of SF-36 between the three neurosurgical pathologies. Patients with TBI and SAH scored higher on most SF-36 domains when compared with cervical myelopathy patients in the severe category. While patients with Upper Severe Disability on GOSE showed significantly higher PC and MC scores compared to GOSE 3, there was a significant degree of variability in individual responses across the groups. Conclusion A significant number of patients following TBI and SAH have better self-reported QOL than cervical spine patients and patients’ subjective perception and expectations following injury do not always correspond to objective disability. These results can guide discussion of treatment and outcomes with patients and families.

Modeling of Cube Array Roughness: RANS, Large Eddy Simulation, and Direct Numerical Simulation

AbstractFlow over arrays of cubes is an extensively studied model problem for rough wall turbulent boundary layers. While considerable research has been performed in computationally investigating these topologies using direct numerical simulation (DNS) and large eddy simulation (LES), the ability of sublayer-resolved Reynolds-averaged Navier–Stokes (RANS) to predict the bulk flow phenomena of these systems is relatively unexplored, especially at low and high packing densities. Here, RANS simulations are conducted on six different packing densities of cubes in aligned and staggered configurations. The packing densities investigated span from what would classically be defined as isolated, up to those in the d-type roughness regime, filling in the gap in the present literature. Three different sublayer-resolved turbulence closure models were tested for each case: a low Reynolds number k–ϵ model, the Menter k–ω SST model, and a full Reynolds stress model. Comparisons of the velocity fields, secondary flow features, and drag coefficients are made between the RANS results and existing LES and DNS results. There is a significant degree of variability in the performance of the various RANS models across all comparison metrics. However, the Reynolds stress model demonstrated the best accuracy in terms of the mean velocity profile as well as drag partition across the range of packing densities.

S1002 Integration of Endoscopic Submucosal Dissection in a Hospital-Based Practice: A Financial Review

Introduction: Endoscopic submucosal dissection (ESD) is a novel, minimally invasive method for the removal of malignant and premalignant gastrointestinal lesions. Literature has been published establishing the safety and efficacy of ESD and its potential as a replacement for invasive surgery in some patients. Due to a lack of procedure-specific Current Procedural Terminology (CPT) codes many hospitals are challenged with adopting this intricate procedure in a cost-effective manner. The aim of this study was to evaluate the financial metrics from our first three years of ESD practice and gain insight into how to provide this service more cost-effectively. Methods: Financial data was reviewed from ESDs performed at our tertiary care center from 4/2018 to 3/2021 including insurance status, direct costs, charges per case, payments per case, and contribution margin. Pearson’s correlation test was utilized to assess whether charges, payments, and margins correlated within the cohort. Results: A total of 57 procedures were included, of which 7 were performed inpatient (12.2%) and 50 were outpatient (87.8%). Eleven [19.3%] had commercial insurance, 4 [7.0%] had Medicaid, 34 [59.6%] had Medicare, 4 [7.0%] had federal assistance, and 4 [7.0%] utilized a local repayment assistance program. Total charges [median, range] were $1,718,349 [$17,364, $249,687]. Total direct costs were $409,572 [$4,682, $57,446]. Total payments were $217,488 [$1,199, $50,138]. The total contribution margin was -$183,024 [-$3,334, $21,269]. Increasing charges and costs were associated with increased institutional payments while none were associated with contribution margins. Conclusion: The data depicts an overall net loss for nearly all performed ESDs. Notably, only four of the 57 ESDs yielded a positive contribution margin with three of the most recent seven ESDs netting an average of $6,538 per case. This potentially indicates increased financial viability as more experience was gained with both performing and billing ESDs. Standard deviations exceeded the mean in all fields, indicating a significant degree of variability between procedures. Until standardized CPT codes are established, ESD must be undertaken with a cost-conscious and outcomes-focused mindset to reduce institutional losses.Figure 1.: Top: Depicts relation between costs per case in relation to payments showing a strong correlation. Bottom Left: Relation between charges per case and contribution margin (CM). Bottom Right: Relation between payments per case and CM. It is notable that both bottom figures do not have statistically significant correlations. However, if outliers are not considered, there appears to be a clear negative trend in CM with increasing charges and costs per case.

Evaluating N95 Respirator Filtration, Seal, Qualitative and Quantitative Fit with Vaporous Hydrogen Peroxide Reprocessing

Background: The COVID-19 pandemic has created personal protective equipment (PPE) shortages, particularly of N95 respirators. Institutions have used decontamination strategies including vaporous hydrogen peroxide (VHP) to augment respirator supplies. VHP can be used to decontaminate nonporous surfaces without compromising material integrity. However, little is known about its impact on N95 respirator efficacy. We assessed whether repeated VHP reprocessing altered 4 key respirator efficacy qualities: quantitative fit, qualitative fit, seal check, and filtration rate. Methods: We conducted a prospective cohort study from June 15 to August 31, 2020. In total, 7 participants were fitted to a 3M 1860 small or regular N95 respirator based on qualitative and quantitative fit testing. Respirators underwent 25 disinfection cycles with the Bioquell BQ-50 VHP generator. After each cycle, participants donned and doffed respirators and performed a seal check. Participants were given 2 attempts to pass their seal check. Every 10 cycles, qualitative fit testing was done using an aerosolized Bitrex solution. Quantitative fit testing was conducted using a PortaCount Pro 8038 Fit Tester to generate a fit factor score. Appropriate fit is defined as a fit factor score of 100 or greater. Quantitative testing was done at cycles 1, 3, 5, 7, 10, 15, 20, and 25. Filtration efficiencies of particles ≥0.3 µm in diameter were measured using the TSI Optical Particle Sizer 3330 at cycles 1, 5, 10, 15, 20, and 25. The Fisher exact test was used to assess qualitative fit and seal check. The Kruskal-Wallis test was used to analyze quantitative fit and filtration rate. Results: We observed no seal-check or quantitative-fit test failures during the study window. All participants passed qualitative fit testing. Although there was a significant degree of variability in fit factor scores across disinfection cycles (mean score 163.5, p <0.05), there was no significant difference between participants (p = 0.6) (Figure 1). There was no statistically significant change in mean filtration rate from cycle 10 to 25 (P = .05), and the filtration rate remained >95% by cycle 25 (Figure 2). Conclusions: VHP reprocessing did not diminish the efficacy of N95 respirators based on the 4 metrics we assessed: filtration rate, seal check, qualitative fit, and quantitative fit. Of significance, the filtration rate remained well above the 95% standard filtration for N95 respirators—even through 25 cycles of reprocessing. VHP reprocessing is a safe, viable strategy to disinfect N95 respirators and extend their use, particularly during supply shortages.Funding: NoDisclosures: None

Insights into the production technology of the Late Bronze Age pottery identified at Topolița (Neamț County)

The aim of this paper is to identify the technological features of the Late Bronze Age ceramic assemblage discovered at Topolița (Neamț County). The archaeological site is located in the Subcarpathian area of the eastern Romania and was assigned based on the typological features of the ceramic artefacts to the Noua culture (second half of the 16th century to the 12th century BC). The dataset investigated in this study consists in 30 samples, selected to represent the stylistic and functional variability detected at the site. For assessing the various stages of the chaîne opératoire (raw materials selection, paste preparation, manufacturing procedures, surface finishing and firing conditions), the pottery samples were studied by means of an integrated analytical approach combining macroscopic observation with petrographical and mineralogical investigations performed by X-ray powder diffraction (XRPD). This study revealed various aspects of the pottery production and emphasized a rather conservative behaviour in terms of raw materials selection combined with a significant degree of variability in the processing and finishing sequences. Besides, the technological analysis of the ceramic assemblage discovered at Topolița in terms of chaîne opératoire provided qualitative data to reconstruct technological features that corresponds to networks of socially linked object-makers.

Projectile point technology: Understanding the relationship between tool design and hunting tactics

Projectile points are one of the most common items used as temporal markers in the American Southwest. This artifact type is characterized by a significant degree of variability over the last 13,000 years, which presumably reflects important changes in the prey being hunted, and the methods used to hunt this game. This paper explores the relationship between projectile point technology, tool design, and hunting tactics using a sample of over 700 points from the Tularosa Basin in southern New Mexico and west Texas. It is suggested that the design concepts of durability and penetration efficiency are productive avenues of research for explaining these long-term changes in projectile point styles.

Abstract 3441: Transcriptional profiles of CD14+ cells in situ in melanoma reveal plasticity, localization dependent function and specific T cell interactions

Abstract Mechanisms contributing to immunotherapy resistance in patients are the object of intense studies. The myeloid cells play a major role in tumors and include cells with different functions that can be grossly summarized as: (1) Antigen capture for presentation (dendritic cells, DCs) or for degradation (macrophages); (2) Tissue repair (macrophages) and (3) effector function (mast cells, monocytes, granulocytes). However, the functional status of myeloid cells in human tumors is not completely understood. To study intact tumor microenvironments, we have established a comprehensive approach for cellular and molecular analysis. Polychromatic immunofluorescence and histocytometry showed that CD14+ cells represent the majority of the total tumor immune infiltrate. Furthermore, while majority of the T cells are located outside of cancer nests, most of the T cells present in the melanoma tissue are in direct contact with CD14+ cells rather than melanoma cells. The distribution of CD14+ cells shows two distinct patterns: CD14+ cells within cancer nest (intratumoral) are in close interactions with melanoma cells and are loaded with melanoma protein; CD14+ cells in the tissue surrounding cancer nest (stromal) do not show melanoma protein cargo. Using customized immunofluorescence guided laser capture micro-dissection, we harvested CD3+ T cells based on their tissue location and CD14+ cells based on their tissue location and melanoma protein load for downstream analysis. Both stromal and intratumoral CD14+ cells display a macrophage like identity with RNA expression of so called “M2 like” macrophages markers, yet we detect a significant degree of variability in the expression levels for certain markers. Transcriptional profiling showed that CD14+ cells clustered according to their tissue localization, i.e., intratumoral vs. stromal, interestingly this localization imprint was less pronounced for T cells, where samples clustered preferentially by patient, leading to much lower number of localization specific differentially expressed genes. Computational analysis, revealed distinct gene signatures associated with different inflammatory and metabolic pathways in intratumoral and stromal CD14+ cells. Thus, transcriptome differentiates functional status of CD14+ cells related to their localization within tumor. Further the intra/stromal CD14+ signature clusters patient with significantly better long term survival across multiple cancer types in TCGA, which in metastatic melanoma was linked with dendritic cells signature in the stroma. Finally, combining our CD3+ and CD14+ LCM data we identified localization specific pairs of receptor/ligand interactions between myeloid and T cells. Citation Format: Jan Martinek, Kyung In Kim, Jianan Lin, Te-Chia Wu, Hannah Borouchov, Ananya Gulati, Lili Sun, Victor Wang, Joshy George, Philipp Henrich, Florentina Marches, Anthony Rongvaux, Michael Chiorazzi, Jeffrey H. Chuang, Paul Robson, Richard Flavell, Jacques Banchereau, Karolina Palucka. Transcriptional profiles of CD14+ cells in situ in melanoma reveal plasticity, localization dependent function and specific T cell interactions [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3441.

Characterisation of a vascular self-healing cementitious material system: Flow and curing properties

A series of characterisation studies are reported that provide new data on the behaviour of a self-healing cementitious material (SHCM) system. A ‘model’ material system is selected for study that comprises cyanoacrylate (CA) filled channels in concrete structural elements. The focus of the work is on transport and curing properties of the healing-agent, with the results of four separate studies being presented. The experimental programme encompasses the capillary flow behaviour of CA in a static natural crack, the sorption of healing-agent through a cracked surface into a concrete specimen, the development and progress of a CA curing front adjacent to a concrete substrate and the dynamic flow characteristics of CA in capillary channels. A theoretical relationship is established for each of these processes, which allows meaningful parameters to be determined that help characterise the behaviour of the material system. In all cases, the processes were shown to have a significant degree of variability but, equally, to exhibit strong behavioural trends.

Population pharmacokinetics and pharmacodynamics of the artesunate\u2013mefloquine fixed dose combination for the treatment of uncomplicated falciparum malaria in African children

BackgroundThe World Health Organization (WHO) recommends combinations of an artemisinin derivative plus an anti-malarial drug of longer half-life as treatment options for uncomplicated Plasmodium falciparum infections. In Africa, artesunate–mefloquine (ASMQ) is an infrequently used artemisinin-based combination therapy (ACT) because of perceived poor tolerance to mefloquine. However, the WHO has recommended reconsideration of the use of ASMQ in Africa. In this large clinical study, the pharmacokinetics (PK) of a fixed dose combination of ASMQ was investigated in an African paediatric population to support dosing recommendations used in Southeast Asia and South America.MethodsAmong the 472 paediatric patients aged 6–59 months from six African centres included in the large clinical trial, a subset of 50 Kenyan children underwent intensive sampling to develop AS, its metabolite dihydroartemisinin (DHA) and MQ PK models. The final MQ PK model was validated using sparse data collected in the remaining participants (NONMEM®). The doses were one or two tablets containing 25/55 mg AS/MQ administered once a day for 3 days according to patients’ age. A sensitive LC–MS/MS method was used to quantify AS, DHA and MQ concentrations in plasma. An attempt was made to investigate the relationship between the absence/presence of malaria recrudescence and MQ area under the curve (AUC) using logistic regression.ResultsAS/DHA concentration–time profiles were best described using a one-compartment model for both compounds with irreversible AS conversion into DHA. AS/DHA PK were characterized by a significant degree of variability. Body weight affected DHA PK parameters. MQ PK was characterized by a two-compartment model and a large degree of variability. Allometric scaling of MQ clearances and volumes of distribution was used to depict the relationship between MQ PK and body weight. No association was found between the model predicted AUC and appearance of recrudescence.ConclusionsThe population pharmacokinetic models developed for both AS/DHA and MQ showed a large variability in drug exposure in the investigated African paediatric population. The largest contributor to this variability was body weight, which is accommodated for by the ASMQ fixed dose combination (FDC) dosing recommendation. Besides body weight considerations, there is no indication that the dosage should be modified in children with malaria compared to adults.Trial registration Pan African Clinical Trials Registry PACTR201202000278282 registration date 2011/02/16

Clinical utility of the 6-min walk test for patients with moderate Parkinson's disease.

The aim of this study was to test the clinical utility of the 6-min walk test (6MWT) for patients with moderate Parkinson's disease (PD) through a determination of factors related to this test. This was a descriptive, observational study carried out at a General Hospital, in-patients. Twenty-four patients with moderate PD were studied. We used Hoehn and Yahr stage ratings (HY stage), Unified Parkinson Disease Rating Scales (UPDRS) motor examination score, 6MWT, Berg Balance scale, Timed 'Up & Go' test (TUG), 10-m walk test (10-m walk speed, 10-m walk steps and cadence), and the energy cost of walking (Ec). The average HY stage was 3.1±0.5 and 6MWT was 340.8±110.9 m. TUG (r=-0.68, P<0.01) and Ec (r=-0.65, P<0.01) were correlated significantly with 6MWT. Multiple regression analysis with age, HY stage, TUG, cadence, and Ec as variables indicated a significant degree of variability in the 6MWT results (R=0.77, P<0.001). The TUG (β=-0.47, P<0.01) and Ec (β=-0.4, P<0.01) were correlated independently with the 6MWT results. In contrast, age, HY stage, and cadence were not independently correlated. The 6MWT is a simple tool for assessing walking capacity for patients with PD. In this study, we confirmed the convergent validity and clinical utility of the 6MWT for patients with moderate PD. The 6MWT is useful for clinical assessment to guide the planning of rehabilitation treatment for patients with moderate PD.

Viscosity Measurements of Aviation Turbine Fuels

Kinematic viscosity has been measured for nine separate aviation turbine fuel samples. The nine samples span the range of fuel types available: conventional petroleum-derived fuels, synthetic fuels derived from the Fischer–Tropsch process, and renewable fuels derived from biomass feedstocks. Results for a tenth sample intended for use in quantifying the total sulfur in fuel oils are also included for comparison. All measurements were made at ambient pressure and over the temperature range of 293–373 K. A significant degree of variability is observed among the measured viscosities. Measurement data for the conventional fuel samples were also compared to the predictions of two existing surrogate mixture models.

Levers for Language Growth: Characteristics and Predictors of Language Trajectories between 4 and 7 Years.

BackgroundEvidence is required as to when and where to focus resources to achieve the greatest gains for children’s language development. Key to these decisions is the understanding of individual differences in children’s language trajectories and the predictors of those differences. To determine optimal timing we must understand if and when children’s relative language abilities become fixed. To determine where to focus effort we must identify mutable factors, that is those with the potential to be changed through interventions, which are associated with significant differences in children’s language scores and rate of progress.MethodsUniquely this study examined individual differences in language growth trajectories in a population sample of children between 4 and 7 years using the multilevel model for change. The influence of predictors, grouped with respect to their mutability and their proximity to the child (least-mutable, mutable-distal, mutable-proximal), were estimated.ResultsA significant degree of variability in rate of progress between 4 and 7 years was evident, much of which was systematically associated with mutable-proximal factors, that is, those factors with evidence that they are modifiable through interventions with the child or family, such as shared book reading, TV viewing and number of books in the home. Mutable-distal factors, such as family income, family literacy and neighbourhood disadvantage, hypothesised to be modifiable through social policy, were important predictors of language abilities at 4 years.ConclusionsPotential levers for language interventions lie in the child’s home learning environment from birth to age 4. However, the role of a family’s material and cultural capital must not be ignored, nor should the potential for growth into the school years. Early Years services should acknowledge the effects of multiple, cascading and cumulative risks and seek to promote child language development through the aggregation of marginal gains in the pre-school years and beyond.

Variability in Early Ahmarian lithic technology and its implications for the model of a Levantine origin of the Protoaurignacian

This paper re-examines lithic technological variability of the Early Ahmarian, one of the early Upper Palaeolithic cultural entities in the Levant, which has often been regarded as a precursor of the Protoaurignacian (the early Upper Palaeolithic in Europe) in arguments for the occurrence of a cultural spread in association with the dispersal of Homo sapiens from the Levant to Europe. Using quantitative data on several lithic techno-typological attributes, we demonstrate that there is a significant degree of variability in the Early Ahmarian between the northern and southern Levant, as previously pointed out by several researchers. In addition, we suggest that the technology similar to the southern Early Ahmarian also existed in the northern Levant, i.e., the Ksar Akil Phase 4 group (the KA 4 group), by introducing new Upper Palaeolithic assemblages from Wadi Kharar 16R, inland Syria. We then review currently available stratigraphic records and radiocarbon dates (including a new date from Wadi Kharar 16R), with special attention to their methodological background. As a result, we propose alternative chronological scenarios, including one that postulates that the southern Early Ahmarian and the KA 4 group appeared later than the northern Early Ahmarian with little or no overlap. On the basis of the alternative scenarios of chronological/geographical patterns of the Early Ahmarian variability, we propose four possible relationships between the Protoaurignacian and the Early Ahmarian, including a new scenario that the appearance of the Protoaurignacian preceded those of similar technological entities in the Levant, i.e., the southern Early Ahmarian and the KA 4 group. If the last hypothesis is substantiated, it requires us to reconsider the model of a Levantine origin of the Protoaurignacian and its palaeoanthropological implications.