Comparative Analysis of Touch and Vision

In our previous communication (1), we set forth the results of a study of intersensory transfer in children of pre-school age. Recognition of a wrong geometrical figure was taken as an index of this transfer. In other words, the test object presented visually had then to be recognized and found haptically and, contrariwise, a test object presented haptically had to be sought out and identified visually. Thus, in the process of preliminary familiarization with the test object, a mental mnemic image (for example, visual) was established, which was then compared to the haptically identified figure. When the data thus obtained were analyzed, the question arose as to whether the problem of preliminary memorization of the shape posed great difficulties among pre-school children, masking the dynamics of interrelations between the two sensory modalities in the pre-school age. Therefore, in the present investigation of intersensory interrelationships, we attempted to eliminate the reliance upon memorization of the figures, and presented them simultaneously for haptic and visual familiarization and selection.     

药物敏感试验药片法研究

药敏药片对国际三株标准菌试验,抑菌圈直径范围均符合判定标准。与进口药敏药片符合率为１００％。与药敏纸片片间差比较试验,药片抑菌圈＝１～２ｍｍ,精密度高,符合国际要求,而纸片抑菌圈＝９～１３ｍｍ,均匀度检测明显不合格。药片变异系数ＣＶ＝１．３１～２．９２,纸片ＣＶ＝１４．７８～２１．６７表明药片变量离散度小,片间差很小;而纸片变量离散度明显大,故纸片片间差很大。     

Assessment and Clinical Utility of a Non-Next-Generation Sequencing-Based Non-Invasive Prenatal Testing Technology

Background: Rolling-circle replication (RCR) is a novel technology that has not been applied to cell-free DNA (cfDNA) testing until recently. Given the cost and simplicity advantages of this technology compared to other platforms currently used in cfDNA analysis, an assessment of RCR in clinical laboratories was performed. Here, we present the first validation study from clinical laboratories utilizing RCR technology. Methods: 831 samples from spontaneously pregnant women carrying a singleton fetus, and 25 synthetic samples, were analyzed for the fetal risk of trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13), by three laboratories on three continents. All the screen-positive pregnancies were provided post-test genetic counseling and confirmatory diagnostic invasive testing (e.g., amniocentesis). The screen-negative pregnancies were routinely evaluated at birth for fetal aneuploidies, using newborn examinations, and any suspected aneuploidies would have been offered diagnostic testing or confirmed with karyotyping. Results: The study found rolling-circle replication to be a highly viable technology for the clinical assessment of fetal aneuploidies, with 100% sensitivity for T21 (95% CI: 82.35–100.00%); 100.00% sensitivity for T18 (71.51–100.00%); and 100.00% sensitivity for T13 analyses (66.37–100.00%). The specificities were >99% for each trisomy (99.7% (99.01–99.97%) for T21; 99.5% (98.62–99.85%) for T18; 99.7% (99.03–99.97%) for T13), along with a first-pass no-call rate of 0.93%. Conclusions: The study showed that using a rolling-circle replication-based cfDNA system for the evaluation of the common aneuploidies would provide greater accuracy and clinical utility compared to conventional biochemical screening, and it would provide comparable results to other reported cfDNA methodologies.     

Modern Methods for Assessment of microRNAs

Biochemistry (Moscow) - The review discusses modern methods for the quantitative and semi-quantitative analysis of miRNAs, which are small non-coding RNAs affecting numerous biological processes...     

A Standardized Obstacle Course for Assessment of Visual Function in Ultra Low Vision and Artificial Vision

We describe an indoor, portable, standardized course that can be used to evaluate obstacle avoidance in persons who have ultralow vision. Six sighted controls and 36 completely blind but otherwise healthy adult male (n=29) and female (n=13) subjects (age range 19-85 years), were enrolled in one of three studies involving testing of the BrainPort sensory substitution device. Subjects were asked to navigate the course prior to, and after, BrainPort training. They completed a total of 837 course runs in two different locations. Means and standard deviations were calculated across control types, courses, lights, and visits. We used a linear mixed effects model to compare different categories in the PPWS (percent preferred walking speed) and error percent data to show that the course iterations were properly designed. The course is relatively inexpensive, simple to administer, and has been shown to be a feasible way to test mobility function. Data analysis demonstrates that for the outcome of percent error as well as for percentage preferred walking speed, that each of the three courses is different, and that within each level, each of the three iterations are equal. This allows for randomization of the courses during administration.Abbreviations: preferred walking speed (PWS) course speed (CS) percentage preferred walking speed (PPWS)     

Differential Contributions of Vision,Touch and Muscle Proprioception to the Coding of Hand Movements

To further elucidate the mechanisms underlying multisensory integration, this study examines the controversial issue of whether congruent inputs from three different sensory sources can enhance the perception of hand movement. Illusory sensations of clockwise rotations of the right hand were induced by either separately or simultaneously stimulating visual, tactile and muscle proprioceptive channels at various intensity levels. For this purpose, mechanical vibrations were applied to the pollicis longus muscle group in the subjects’ wrists, and a textured disk was rotated under the palmar skin of the subjects’ right hands while a background visual scene was projected onto the rotating disk. The elicited kinaesthetic illusions were copied by the subjects in real time and the EMG activity in the adductor and abductor wrist muscles was recorded. The results show that the velocity of the perceived movements and the amplitude of the corresponding motor responses were modulated by the nature and intensity of the stimulation. Combining two sensory modalities resulted in faster movement illusions, except for the case of visuo-tactile co-stimulation. When a third sensory input was added to the bimodal combinations, the perceptual responses increased only when a muscle proprioceptive stimulation was added to a visuo-tactile combination. Otherwise, trisensory stimulation did not override bimodal conditions that already included a muscle proprioceptive stimulation. We confirmed that vision or touch alone can encode the kinematic parameters of hand movement, as is known for muscle proprioception. When these three sensory modalities are available, they contribute unequally to kinaesthesia. In addition to muscle proprioception, the complementary kinaesthetic content of visual or tactile inputs may optimize the velocity estimation of an on-going movement, whereas the redundant kinaesthetic content of the visual and tactile inputs may rather enhance the latency of the perception.     

Crossmodal Discrimination of 2 vs. 4 Objects across Touch and Vision in 5-Month-Old Infants

Infants are known to possess two different cognitive systems to encode numerical information. The first system encodes approximate numerosities, has no known upper limit and is functional from birth on. The second system relies on infants’ ability to track up to 3 objects in parallel, and enables them to represent exact numerosity for such small sets. It is unclear, however, whether infants may be able to represent numerosities from all ranges in a common format. In various studies, infants failed to discriminate a small vs. a large numerosity (e.g., 2 vs. 4, 3 vs. 6), although more recent studies presented evidence that infants can succeed at these discriminations in some situations. Here, we used a transfer paradigm between the tactile and visual modalities in 5-month-olds, assuming that such cross-modal paradigm may promote access to abstract representations of numerosities, continuous across the small and large ranges. Infants were first familiarized with 2 to 4 objects in the tactile modality, and subsequently tested for their preference between 2 vs. 4, or 3 vs. 6 visual objects. Results were mixed, with only partial evidence that infants may have transferred numerical information across modalities. Implications on 5-month-old infants’ ability to represent small and large numerosities in a single or in separate formats are discussed.     

温度感受器和触觉感受器的发现

2021年诺贝尔生理学或医学奖授予美国生理学家戴维·朱利叶斯(David Julius)和分子生物学家阿德姆·帕塔普蒂安(Ardem Patapoutian),以表彰他们在发现温度感受器和触觉感受器中所做出的突出贡献.机体对热、冷和机械压力等外界刺激的感知能力对于人们适应不断变化的环境至关重要,可以避免其遭受伤害.在D...     

Behavioral Testing of the Effects of Thermosensitive TRP Channel Agonists on Touch,Temperature, and Pain Sensations

It was recently found that transient receptor potential (TRP) channels play an important role in the transduction of thermal, mechanical, and chemical stimuli underlying the somatic sensation. Several types of TRP channels exhibit sensitivity to increases or decreases in temperature, as well as to the action of chemical ligands that elicit similar thermal or painful sensations. These agents include menthol, mustard oil, cinnamaldehyde (CA), gingerol, capsaicin, camphor, eugenol, and others. Cinnamaldehyde is a pungent chemical obtained from cinnamon, which acts as an agonist of the TRPA1 channels; these channels were originally reported to be activated by cold temperatures (below 18°C). TRPA1 is also implicated in cold nociception. However, its role in the formation of cold pain is more controversial, with discrepant reports that TRPA1s do or do not respond to intense cooling. Menthol derived from plants of the mint family enhances the feeling of coldness by interacting with the cold-sensitive TRPM8 channels, but its effect on pain is less well understood. Using behavioral methods, we showed that unilateral intraplantar injection of CA (5 to 20%) induced a significant concentration-dependent decrease in the latency for ipsilateral paw withdrawal from a noxious heat stimulus, i.e., heat hyperalgesia. Cinnamaldehyde also significantly reduced mechanical withdrawal thresholds for the injected paw, i.e., evoked mechanical allodynia. Bilateral intraplantar injections of CA resulted in a significant cold hyperalgesia (cold plate test) and a weak enhancement of innocuous cold avoidance (thermal preference test). In contrast to CA, menthol in a dose-dependent manner increased the latency for noxious heat-evoked withdrawal, i.e., exerted an antinociceptive effect. Menthol did not affect mechanosensation except for a weak allodynic effect when applied in the highest concentration used (40 %), indicating that it did not exert a local anesthetic effect. Menthol had a biphasic effect on cold avoidance. High concentrations of menthol reduced cold avoidance, i.e., induced cold hypoalgesia, while low menthol concentrations significantly intensified cold avoidance. The highest menthol concentration provided cold hypoalgesia (cold plate test), while lower concentrations had no effect. Taken together, our data support the idea that TRPA1 and TRPM8 channels represent promising peripheral targets for pain modulation.     

Risk Assessment and Class-Based Evaluation of Three Phosphate Esters

A category approach was used in the evaluation of a group of chemicals (triethyl phosphate, tripropyl phosphate, and tributyl phosphate) in drinking water, in support of determination of safe-harbor level for use by a standard-setting organization. Both non-cancer and cancer endpoints were considered, and risk assessment methodology developed by the U.S. Environmental Protection Agency (USEPA) was used to determine a class-based evaluation level (CBEL) and a total allowable concentration (TAC) in drinking water considered adequately protective of human health. The critical study was a chronic oncogenicity study on tributyl phosphate, with a no-observed-adverse-effect-level (NOAEL) of 9 mg/kg-day. The critical effect, combined incidence of bladder papilloma/transitional cell carcinoma, was likely non-genetic in nature, as supported by the lack of genetic toxicity observed in tributyl phosphate. The effect thus demonstrated a threshold, and this study used an oral reference dose approach and a total uncertainty factor of 100. This conservative analysis demonstrated the TAC should be twenty times greater than the default value of 0.01 mg/L.     

Limited Clinical Utility of Non-invasive Prenatal Testing for Subchromosomal Abnormalities

The use of massively parallel sequencing of maternal cfDNA for non-invasive prenatal testing (NIPT) of aneuploidy is widely available. Recently, the scope of testing has increased to include selected subchromosomal abnormalities, but the number of samples reported has been small. We developed a calling pipeline based on a segmentation algorithm for the detection of these rearrangements in maternal plasma. The same read depth used in our standard pipeline for aneuploidy NIPT detected 15/18 (83%) samples with pathogenic rearrangements > 6 Mb but only 2/10 samples with rearrangements < 6 Mb, unless they were maternally inherited. There were two false-positive calls in 534 samples with no known subchromosomal abnormalities (specificity 99.6%). Using higher read depths, we detected 29/31 fetal subchromosomal abnormalities, including the three samples with maternally inherited microduplications. We conclude that test sensitivity is a function of the fetal fraction, read depth, and size of the fetal CNV and that at least one of the two false negatives is due to a low fetal fraction. The lack of an independent method for determining fetal fraction, especially for female fetuses, leads to uncertainty in test sensitivity, which currently has implications for this technique’s future as a clinical diagnostic test. Furthermore, to be effective, NIPT must be able to detect chromosomal rearrangements across the whole genome for a very low false-positive rate. Because standard NIPT can only detect the majority of larger (>6 Mb) chromosomal rearrangements and requires knowledge of fetal fraction, we consider that it is not yet ready for routine clinical implementation.     

Results of the National External Quality Assessment for Toxoplasmosis Serological Testing in China

Background

Toxoplasmosis is typically diagnosed by serologic testing. External quality assessment (EQA) of clinical laboratories could ensure the accuracy and reliability of serological tests. We assessed the quality of toxoplasma serological assays in Chinese clinical laboratories by an EQA performed between 2004 and 2013 by the National Center for Clinical Laboratories.

Methodology and Findings

EQA panels were prepared and shipped at room temperature to participating laboratories that employed toxoplasma IgG and IgM serological detection. By 2013, 5,384 EQA test reports for toxoplasma-specific IgM and 2,666 reports for toxoplasma-specific IgG were collected. Enzyme-linked immunosorbent (ELISA) and chemical immunofluorescent assays were the most commonly used detection methods. The overall coincidence rates of negative samples were better than those of positive samples. The overall EQA score for toxoplasma-specific IgM detection ranged between 84.3% and 99.6%. The ratio of laboratories that achieved correct IgG detection ranged from 61.1% to 99.3%. However, the inter- and intra-assay variabilities were found to be considerable. The most common problem was failure to detect low titers of antibody.

Conclusion

The EQA scheme showed an improvement in toxoplasma serological testing in China. However, further optimization of assay sensitivity to detect challenging samples remains a future challenge.     

Hypothesis Testing of Inclusion of the Tolerance Interval for the Assessment of Food Safety

In the testing of food quality and safety, we contrast the contents of the newly proposed food (genetically modified food) against those of conventional foods. Because the contents vary largely between crop varieties and production environments, we propose a two-sample test of substantial equivalence that examines the inclusion of the tolerance intervals of the two populations, the population of the contents of the proposed food, which we call the target population, and the population of the contents of the conventional food, which we call the reference population. Rejection of the test hypothesis guarantees that the contents of the proposed foods essentially do not include outliers in the population of the contents of the conventional food. The existing tolerance interval (TI₀) is constructed to have at least a pre-specified level of the coverage probability. Here, we newly introduce the complementary tolerance interval (TI₁) that is guaranteed to have at most a pre-specified level of the coverage probability. By applying TI₀ and TI₁ to the samples from the target population and the reference population respectively, we construct a test statistic for testing inclusion of the two tolerance intervals. To examine the performance of the testing procedure, we conducted a simulation that reflects the effects of gene and environment, and residual from a crop experiment. As a case study, we applied the hypothesis testing to test if the distribution of the protein content of rice in Kyushu area is included in the distribution of the protein content in the other areas in Japan.     

Life Cycle Assessment of a Magazine,Part II: A Comparison of Print and Tablet Editions

The rapid development of information and communications technology (ICT) is providing new ways to access media content. Electronic media are sometimes more advantageous from an environmental perspective than paper‐based media solutions, but ICT‐based media can also bring environmental burdens. This study compared the potential environmental impacts in a life cycle perspective of a print edition of a magazine and that of its electronic edition read on a tablet device. Important objectives were to identify activities giving rise to the main environmental impacts for both the print and tablet editions, determine the key factors influencing these impacts, and address data gaps and uncertainties. A detailed assessment of the tablet edition is provided in a previous article (part 1), whereas this article compares it with the print edition. The methodology used was life cycle assessment and the environmental impacts assessed included climate change, cumulative energy/exergy demand, metal depletion, photochemical oxidant formation, particulate matter formation, terrestrial acidification, freshwater eutrophication, marine eutrophication, and fossil depletion. Use of different functional units to compare the print and tablet editions of the magazine resulted in different relative environmental impacts. In addition, emerging (low number of readers and low reading time per copy) and mature (higher number of readers and higher reading time per copy) tablet editions yielded varying results. The emerging tablet edition resulted in higher potential environmental impacts per reader than the print edition, but the mature tablet edition yielded lower impacts per reader in half the impact categories assessed. This illustrates the importance of spreading the environmental impacts over a large number of readers. The electricity mix used in product system processes did not greatly affect the results of tablet/print comparisons, but overall number of readers for the tablet edition, number of readers per copy for the print edition, file size, and degree of use of the tablet device proved crucial for the comparison results.     

Testing the Hypothesis of Fire Use for Ecosystem Management by Neanderthal and Upper Palaeolithic Modern Human Populations

Background

It has been proposed that a greater control and more extensive use of fire was one of the behavioral innovations that emerged in Africa among early Modern Humans, favouring their spread throughout the world and determining their eventual evolutionary success. We would expect, if extensive fire use for ecosystem management were a component of the modern human technical and cognitive package, as suggested for Australia, to find major disturbances in the natural biomass burning variability associated with the colonisation of Europe by Modern Humans.

Methodology/Principal Findings

Analyses of microcharcoal preserved in two deep-sea cores located off Iberia and France were used to reconstruct changes in biomass burning between 70 and 10 kyr cal BP. Results indicate that fire regime follows the Dansgaard-Oeschger climatic variability and its impacts on fuel load. No major disturbance in natural fire regime variability is observed at the time of the arrival of Modern Humans in Europe or during the remainder of the Upper Palaeolithic (40–10 kyr cal BP).

Conclusions/Significance

Results indicate that either Neanderthals and Modern humans did not influence fire regime or that, if they did, their respective influence was comparable at a regional scale, and not as pronounced as that observed in the biomass burning history of Southeast Asia.     

Life Cycle Assessment of a Magazine,Part I: Tablet Edition in Emerging and Mature States

Information and communication technology (ICT) is providing new ways to access media content. ICT has environmental benefits and burdens. The overall goal of the present study was to assess the environmental impacts of production and consumption of magazines read on tablets from a life cycle perspective. Important goals were to identify the activities giving rise to the main impacts and the key factors influencing the overall environmental impacts. Data gaps and uncertainties were also addressed. The results are compared against those for the print edition of the magazine in a separate article (part 2). The methodology used in the study was life cycle assessment. The environmental impacts assessed included climate change, cumulative energy/exergy demand, metal depletion, photochemical oxidant formation, particulate matter formation, terrestrial acidification, freshwater/marine eutrophication, fossil depletion, human toxicity, and ecotoxicity. The results indicate that content production can be the major contributor to environmental impacts if readers are few (as for the emerging version of the magazine studied). Assuming more readers (more mature version) or a larger file size for the tablet magazine, electronic storage and distribution may be the major contributor. Thus, in contrast to previous studies on electronic media, which reported a dominant impact of the use phase, this study found a higher impact for content production (emerging version) and electronic storage and distribution (mature version). However, with inefficient, low overall use of the tablet with a mature version of the tablet magazine, the greatest impact was shown to come from the reading activity (i.e., the use phase). In conclusion, the relative impacts of the tablet magazine would decrease considerably with high numbers of readers, their efficient use of the tablet (i.e., for many purposes over a long life of the device), and a smaller magazine file.     

Development and Optimisation of Spironolactone Nanoparticles for Enhanced Dissolution Rates and Stability

Stable solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) formulations to enhance the dissolution rates of poorly soluble drug spironolactone (SP) were being developed. Probe ultra-sonication method was used to prepare SLNs and NLCs. All NLCs contained stearic acid (solid lipid carrier) and oleic acid (liquid lipid content), whereas, SLNs were prepared and optimised by using the solid lipid only. The particles were characterised in terms of particle size analysis, thermal behaviour, morphology, stability and in vitro release. The zeta sizer data revealed that the increase in the concentration of oleic acid in the formulations reduced the mean particle size and the zeta potential. The increase in concentration of oleic acid from 0 to 30% (w/w) resulted in a higher entrapment efficiency. All nanoparticles were almost spherically shaped with an average particle size of about ～170 nm. The DSC traces revealed that the presence of oleic acid in the NLC formulations resulted in a shift in the melting endotherms to a higher temperature. This could be attributed to a good long-term stability of the nanoparticles. The stability results showed that the particle size remained smaller in NLC compared to that of SLN formulations after 6 months at various temperatures. The dissolution study showed about a 5.1- to 7.2-fold increase in the release of the drug in 2 h compared to the raw drug. Comparing all nanoparticle formulations indicated that the NLC composition with a ratio of 70:30 (solid:liquid lipid) is the most suitable formulation with desired drug dissolution rates, entrapment efficiency and physical stability.     

Comparison of Three Dissolution Apparatuses for Testing Calcium Phosphate Pellets used as Ibuprofen Delivery Systems

Porous calcium phosphate pellets were produced according to two granulation processes (low and high shear wet granulations) and drug loaded with five ibuprofen contents (1.75%, 7%, 12.5%, 22%, and 36%) in order to ensure both bone defect filling and local drug delivery. The drug-release kinetics from the two types of pellets was studied using three dissolution apparatuses: paddle apparatus, reciprocating cylinder, and flow-through cell. The paper compared the three dissolution methods and considered the effect of the granulation process on the ibuprofen-release kinetics. Dissolution data were analyzed using the Weibull function as well as the difference (f1) and similarity (f2) factors. Dissolution kinetics was not influenced by the granulation process, regardless of the dissolution apparatus and of the drug content. The comparison of the three dissolution devices indicated that ibuprofen was released faster from granules loaded with 36% of drug content with the reciprocating apparatus, due to the disintegration of the granules occurring during the dissolution test. For the other drug contents, dissolution profiles were not significantly different from one apparatus to another. However, the flow-through cell seemed to be more suitable for the drug-release study of implantable materials.