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The corneal epithelium (CE) is the outermost layer of the cornea with constant turnover, relative stability, remarkable plasticity, and compensatory properties to mask alterations in the underlying stroma. The advent of quantitative imaging modalities capable of producing epithelial thickness mapping (ETM) has made it possible to characterize better the different patterns of epithelial remodeling. In this comprehensive synthesis, we reviewed all available data on ETM with different methods, including very high-frequency ultrasound (VHF-US) and spectral-domain optical coherence tomography (SD-OCT) in normal individuals, corneal or systemic diseases, and corneal surgical scenarios. We excluded OCT studies that manually measured the corneal epithelial thickness (CET) (e.g., by digital calipers) or the CE (e.g., by confocal scanning or handheld pachymeters). A comparison of different CET measuring technologies and devices capable of producing thickness maps is provided. Normative data on CET and the possible effects of gender, aging, diurnal changes, refraction, and intraocular pressure are discussed. We also reviewed ETM data in several corneal disorders, including keratoconus, corneal dystrophies, recurrent epithelial erosion, herpes keratitis, keratoplasty, bullous keratopathy, carcinoma in situ, pterygium, and limbal stem cell deficiency. The available data on the potential role of ETM in indicating refractive surgeries, planning the procedure, and assessing postoperative changes are reviewed. Alterations in ETM in systemic and ocular conditions such as eyelid abnormalities and dry eye disease and the effects of contact lenses, topical medications, and cataract surgery on the ETM profile are discussed. [ABSTRACT FROM AUTHOR]

Background: Invasive recording of His bundle signals (HBS) in electrophysiological study (EPS) is important in determining HV interval, the time taken to activate the ventricles from the His bundle. Noninvasive surface measurements of HBS are attempted by averaging typically 100–200 cardiac cycles of ECG time series in body surface potential mapping (BSPM) and in magnetocardiography (MCG) which records weak cardiac magnetic fields by highly sensitive detectors. However, noninvasive beat‐by‐beat extraction of HBS is challenged by ramp‐like atrial signals and noise in PR segment of the cardiac cycle. Methods: By making use of a signal‐averaged trace showing prominent HBS as a guide trace, we developed a method combining interval‐dependent wavelet thresholding (IDWT) and signal space projection (SSP) technique to eliminate artifacts from single beats. The method was applied on MCG recorded on 21 subjects with known HV intervals based on EPS and noninvasive signal‐averaging, including five subjects with BSPM recorded subsequently. The method was also applied on stress‐MCG of a subject featuring autonomic dynamics. Results: HBS could be extracted from 19 out of 21 subjects by signal‐averaging whose timing differed from EPS between −8 and 11 ms as tested by 2 observers. HBS in single beats were seen as aligned patterns in inter‐beat contours and were appreciable in stress‐MCG and conspicuous than BSPM. The performance of the method was evaluated on simulated and measured MCG to be adequate if the signal‐to‐noise ratio was at least 20 dB. Conclusions: These results suggest the use of this method for noninvasive assessments on HBS. [ABSTRACT FROM AUTHOR]

Annual insect abundances are determined by short‐term population fluctuations and long‐term trends in community composition. Any assessment of this temporal variability needs long‐term quantitative data on abundances. Here we use museum data (1940–2017) of butterflies and burnet moths from southwestern Germany and central Austria comprising 220,758 records from 155 species, and 55,641 records from 170 species, respectively. We ask whether population fluctuations and long‐term population trends are spatially synchronized across larger spatial distances (>300 km) according to the Moran effect, and whether common trends in community composition and stability exist? Population fluctuations of 85.5% of species jointly occurring in both study regions were positively correlated (mean r = 0.30 ± 0.03). Comparing different time windows, we found different sets of species being in spatial synchrony reflecting temporal changes in butterfly community composition. Mesophilic, habitat generalist, and dispersive species were significantly more synchronized than xerothermophilic, habitat specialist, and sedentary species. Long‐distance travelers were particularly synchronized. In both study regions, species rank orders became less even with time. Stability in community composition increased with time with an ongoing trend to faunal homogenization, but not to species loss. Our study points to global and not to local drivers behind trends in butterfly population fluctuations and compositional stability, in the present case to altered land use and urbanization as major drivers toward synchrony and homogenization. Finally, our data have implications for conservation strategies as they strongly indicate that natural landscape structures are associated with higher faunal compositional variability in comparison to agricultural and urban landscapes. [ABSTRACT FROM AUTHOR]

Proton and ion beam therapy has proven to benefit tumour control with lower side-effects, mostly in paediatrics. Here we demonstrate a feasible technique for proton and ion beam spectroscopy (PIBS) capable of determining the elemental compositions of the irradiated tissues during particle therapy. This follows the developments in prompt gamma imaging for online range verification and the inheritance from prompt gamma neutron activation analysis. Samples of water solutions were prepared to emulate varying oxygen and carbon concentrations. The irradiation of those samples and other tissue surrogate inserts by protons and ion beams under clinical conditions clearly showed a logarithmic relationship between the target elemental composition and the prompt gamma production. This finding is in line with the known logarithmic dependence of the pH with the proton molar concentration. Elemental concentration changes of 1% for calcium and 2% for oxygen in adipose, brain, breast, liver, muscle and bone-related tissue surrogates were clearly identified. Real-time in vivo measurements of oxygen, carbon and calcium concentrations will be evaluated in a pre-clinical and clinical environment. This technique should have an important impact in the assessment of tumour hypoxia over the course of several treatment fractions and the tracking of calcifications in brain metastases.

Purpose. To evaluate the performance of corneal epithelial thickness mapping (ETM) and demonstrate simultaneous measurement of ETMs and corneal topography using REVO NX (Optopol Technology, Zawiercie, Poland)—an OCT device for anterior and posterior segment imaging. Methods. One hundred thirty-seven eyes of 137 normal subjects and patients with corneal diseases were recruited to the study. Each subject was scanned with REVO NX. ETMs and corneal topography maps were reconstructed from a single measurement. Corneal topography was also carried out using Pentacam (Oculus, Wetzlar, Germany). One hundred twenty-eight eyes were qualified for the final analysis. Forty healthy eyes were used to evaluate the performance of ETM, and 88 eyes were used to compare ETMs and corneal topography. The repeatability and reproducibility of ETMs in healthy subjects were assessed on the basis of 17 spatial zones derived from an 8-mm diameter corneal scan using within-subject standard deviation, test-retest repeatability, within-subject coefficient of variation (CoV), and intraclass correlation coefficient (ICC). Results. The ICC for both repeatability and reproducibility of ETMs for the central sector was 0.95. The ICC value for the other sectors was only moderately lower. However, the CoV for repeatability (≤1.55%) was slightly higher than the value reported for the RTVue device (Optovue, Inc, Fremont, California, USA), for which a CoV in the central zone of 1.07% was reported in unoperated eyes. The superior quadrants were found to be the thinnest while the inferior ones were the thickest. ETMs and topography maps created from a single OCT measurement present a complementary image of the cornea. Conclusions. ETMs obtained using REVO NX show high levels of repeatability and reproducibility in normal eyes. Because the topographic and epithelial thickness analyses are performed using the same data, which means they are based on the exact same 3D corneal model, they do not require reciprocal centration and map matching. This ensures a complete point-to-point correlation between ETMs and corneal topography maps, which paints a fuller picture of a given pathology. [ABSTRACT FROM AUTHOR]

Newly recognized polymorphonuclear neutrophil (PMNs) functions include the ability to release subcellular mediators such as neutrophil‐derived extracellular vesicles (NDEVs) involved in immune and thrombo‐inflammatory responses. Elevation of their plasmatic level has been reported in a variety of infectious and cardiovascular disorders, but the clinical use of this potential biomarker is hampered by methodological issues. Although flow cytometry (FCM) is currently used to detect NDEVs in the plasma of patients, an extensive characterization of NDEVs has never been done. Moreover, their detection remains challenging because of their small size and low antigen density. Therefore, the objective of the present study was first to establish a surface antigenic signature of NDEVs detectable by FCM and therefore to improve their detection in biological fluids by developing a strategy allowing to overcome their low fluorescent signal and reduce the background noise. By testing a large panel of 54 antibody specificities already reported to be positive on PMNs, we identified a profile of 15 membrane protein markers, including 4 (CD157, CD24, CD65 and CD66c) never described on NDEVs. Among them, CD15, CD66b and CD66c were identified as the most sensitive and specific markers to detect NDEVs by FCM. Using this antigenic signature, we developed a new strategy combining the three best antibodies in a cocktail and reducing the background noise by size exclusion chromatography (SEC). This strategy allowed a significant improvement in NDEVs enumeration in plasma from sepsis patients and made it feasible to efficiently sort NDEVs from COVID‐19 patients. Altogether, this work opens the door to a more valuable measurement of NDEVs as a potential biomarker in clinical practice. A similar strategy could also be applied to improve detection by FCM of other rare subpopulations of EVs generated by tissues with limited access, such as vascular endothelium, cancer cells or placenta. [ABSTRACT FROM AUTHOR]

This report describes the significance of the kinetic parameters (k-values) obtained from the analysis of dynamic positron emission tomography (PET) scans using the Hawkins model describing the pharmacokinetics of sodium fluoride ([18F]NaF) to understand bone physiology. Dynamic [18F]NaF PET scans may be useful as an imaging biomarker in early phase clinical trials of novel drugs in development by permitting early detection of treatment-response signals that may help avoid late-stage attrition. [ABSTRACT FROM AUTHOR]

Background: Trichotillomania (TTM) has been associated with childhood trauma and perceived stress. While it has been hypothesized that hair-pulling regulate negative emotions, the relationship between childhood trauma, perceived stress, emotion regulation, and hair-pulling has not been well-studied. Methods: Fifty-six adults with TTM and 31 healthy controls completed the Childhood Trauma Questionnaire (CTQ), Perceived Stress Scale (PSS), and Difficulties in Emotion Regulation Scale (DERS). Hair-pulling severity was measured with the Massachusetts General Hospital-Hair Pulling Scale. CTQ, PSS, and DERS total scores were compared across groups using ANCOVA and the correlation between hair-pulling severity and emotion dysregulation was determined. Regression analyses were used to estimate the association of CTQ and PSS totals with DERS, and to determine whether associations between predictors and dependent variable (DERS) differed across groups. Results: TTM patients reported higher rates of childhood trauma (p <= 0.01), perceived stress (p = 0.03), and emotion dysregulation (p <= 0.01). There was no association between emotion dysregulation and pulling severity (r = −0.02, p = 0.89). Perceived stress was associated with emotion dysregulation in both groups (p < 0.01), and no association between childhood trauma and emotion dysregulation in either group. Perceived stress was the only significant predictor of emotion dysregulation in both groups (F = 28.29, p < 0.01). Conclusion: The association between perceived stress and emotion dysregulation is not specific to TTM, and there is no association between emotion dysregulation and hair-pulling severity, suggesting that key factors other than emotion dysregulation contribute to hair-pulling. Alternative explanatory models are needed. [ABSTRACT FROM AUTHOR]

Hepatic stellate cells (HSCs) are the major profibrogenic cells that promote the pathogenesis of liver fibrosis. The crosstalk between transforming growth factor-β1 (TGF-β1) signaling and lipopolysaccharide (LPS)-induced NF-κB signaling plays a critical role in accelerating liver fibrogenesis. Until now, there have been no FDA-approved drug treatments for liver fibrosis. Barbituric acid derivatives have been used as antiasthmatic drugs in the clinic; however, the effect of barbituric acid derivatives in treating liver fibrosis remains unknown. In this study, we synthesized a series of six barbituric acid (BA) derivatives, and one of the compounds, BA-5, exhibited the best ability to ameliorate TGF-β1-induced HSC activation without overt cytotoxic effects. Then, we treated HSCs and RAW264.7 macrophages with BA-5 to analyze the cross-talk of anti-fibrotic and anti-inflammatory effects. Carbon tetrachloride (CCl4)-induced liver fibrosis mouse model was used to evaluate the therapeutic effects of BA-5. Treatment with BA-5 inhibited TGF-β1-induced α-SMA, collagen1a2, and phosphorylated smad2/3 expression in HSCs. Furthermore, BA-5 treatment reversed the LPS-induced reduction in BAMBI protein and decreased IκBα and NF-κB phosphorylation in HSCs. NF-κB nuclear translocation, MCP-1 secretion, and ICAM-1 expression were also inhibited in BA-5-treated HSCs. Conditioned medium collected from BA-5-treated HSCs showed a reduced ability to activate RAW264.7 macrophages by inhibiting the MAPK pathway. In the mouse model, BA-5 administration reduced CCl4-induced liver damage, liver fibrosis, and F4/80 expression without any adverse effects. In conclusion, our study showed that the barbituric acid derivative BA-5 inhibits HSCs activation and liver fibrosis by blocking both the TGF-β1 and LPS-induced NF-κB signaling pathways and further inhibits macrophages recruitment and activation. [ABSTRACT FROM AUTHOR]

Understanding the production, response, and genetics of signals used in mate choice can inform our understanding of the evolution of both intraspecific mate choice and reproductive isolation. Sex pheromones are important for courtship and mate choice in many insects, but we know relatively little of their role in butterflies. The butterfly Heliconius melpomene uses a complex blend of wing androconial compounds during courtship. Electroantennography in H. melpomene and its close relative Heliconius cydno showed that responses to androconial extracts were not species specific. Females of both species responded equally strongly to extracts of both species, suggesting conservation of peripheral nervous system elements across the two species. Individual blend components provoked little to no response, with the exception of octadecanal, a major component of the H. melpomene blend. Supplementing octadecanal on the wings of octadecanal‐rich H. melpomene males led to an increase in the time until mating, demonstrating the bioactivity of octadecanal in Heliconius. Using quantitative trait locus (QTL) mapping, we identified a single locus on chromosome 20 responsible for 41% of the parental species' difference in octadecanal production. This QTL does not overlap with any of the major wing color or mate choice loci, nor does it overlap with known regions of elevated or reduced FST. A set of 16 candidate fatty acid biosynthesis genes lies underneath the QTL. Pheromones in Heliconius carry information relevant for mate choice and are under simple genetic control, suggesting they could be important during speciation. [ABSTRACT FROM AUTHOR]

Background: Habit Reversal Therapy (HRT) has long been used in the treatment of Tourette Syndrome and Tic Disorders. It has more recently been used to treat Trichotillomania and skin picking behaviors, both considered as Obsessive Compulsive Related Disorders (OCRD). Objectives: This literature review sought to establish and quality assess the existing randomized controlled trial evidence supporting the use of HRT in the DSM-5 family of OCRDs. Search Methods: EMBASE, PsycINFO, PubMed, and Cochrane databases were searched for key terms relating to each OCRD (as classified in the DSM-5), and HRT. Selection Criteria: Titles and abstracts were screened, and any literature matching pre-specified criteria were then selected to be reviewed further. Of these, 8 Randomized Controlled Trials (RCT) relating to Trichotillomania, and 2 RCTs relating to Excoriation Disorder, were extracted and reviewed against the 2010 Consolidating Standards of Reporting Trials (CONSORT) statement. Results: The review identified 10 RCTs of HRT, but these were limited to patients with a primary diagnosis of Trichotillomania or "excoriation behavior," only. There were some reports of the use of HRT in Tourette Syndrome or Tic Disorder with secondary OCD, but the OCD symptoms were not reliably reported on. Conclusion: There is a gap in the current literature regarding the use of HRT in the DSM-5 OCRDs. In those RCTs that have been reported, the quality of study methodology was questionable as evaluated by CONSORT criteria. The implications of these findings are discussed, and suggestions are made for future research. [ABSTRACT FROM AUTHOR]

Rapid land loss in the Mississippi River Delta Plain has led to intensive efforts by state and federal agencies for finding solutions in coastal land restoration in the past decade. One of the proposed solutions includes diversion of the Mississippi River water into drowning wetland areas. Although a few recent studies have investigated flow-sediment relationships in the Lowermost Mississippi River (LmMR, defined as the 500 km reach from the Old River Control Structure to the river's Gulf outlet), it is unclear how individual sediment fractions behave under varying flow conditions of the river. The information can be especially pertinent because the quantity of coarse sands plays a critical role for the Mississippi-Atchafalaya River deltaic development. In this study, we utilized long-term (1973-2013) records on discharge and sediments at Tarbert Landing of the LmMR to assess sand behavior and availability under different river flow regimes, and extreme sand transport events and their recurrence. We found an average annual sand load (SL) of 27.2 megatonnes (MT) during 1973 and 2013, varying largely from 3.37 to 52.30 MT. For the entire 41-year study period, a total of approximately 1115 MT sand were discharged at Tarbert Landing, half of which occurred during the peak 20% flow events. A combination of intermediate, high and peak flow stages (i.e., river discharge was ¥18,000 cubic meter per second) produced about 71% of the total annual SL within approximately 120 days of a year. Based on the long-term sediment assessment, we predict that the LmMR has a high likelihood to transport 4 to 446 thousand tonnes of sand every day over the next 40 years, during which annual sand loads could reach a maximum of 51.68 MT. Currently, no effective plan is in place to utilize this considerably high sand quantity and we suggest that river engineering and sediment management in the LmMR consider practices of hydrograph-based approach for maximally capturing riverine sediments. [ABSTRACT FROM AUTHOR]

Despite various studies to minimize host reaction following a biomaterial implantation, an appealing strategy in regenerative medicine is to actively use such an immune response to trigger and control tissue regeneration. We have developed an in vitro model to modulate the host response by tuning biomaterials' surface properties through surface modifications techniques as a new strategy for tissue regeneration applications. Results showed tunable surface topography, roughness, wettability, and chemistry by varying treatment type and exposure, allowing for the first time to correlate the effect of these surface properties on cell attachment, morphology, strength and proliferation, as well as proinflammatory (IL-1β, IL-6) and antiflammatory cytokines (TGF-β1, IL-10) secreted in medium, and protein expression of collagen and elastin. Surface microstructuring, derived from chloroform partial etching, increased surface roughness and oxygen content. This resulted in enhanced cell adhesion, strength and proliferation as well as a balance of soluble factors for optimum collagen and elastin synthesis for tissue regeneration. By linking surface parameters to cell activity, we could determine the fate of the regenerated tissue to create successful soft tissue-engineered replacement. [ABSTRACT FROM AUTHOR]

This study focuses on 10 Gbit/s differential transimpedance amplifier. At the beginning of the work, the amplifier circuit is deeply analyzed and is optimized for the best phase linearity over the bandwidth resulted in a group delay variation less than 1 ps. The amplifier circuit is designed with 0.35 μm SiGe heterojunction bipolar transistor BICMOS process. 9 GHz bandwidth, almost 58 dBΩ transimpedance gain with less than 11.18 pA/ $$ \sqrt {\text{Hz}} $$ averaged input-referred noise current are achieved. Electrical sensitivity is 15 μA. Power consumption is 71 mW at 3.3 V single power supply. [ABSTRACT FROM AUTHOR]

Membrane vesicle cycling is orchestrated through the combined actions of proteins and lipids. At neuronal synapses, this orchestration must meet the stringent demands of speed, fidelity and sustainability of the synaptic vesicle cycle that mediates neurotransmission. Historically, the lion's share of the attention has been focused on the proteins that are involved in this cycle; but, in recent years, it has become clear that the previously unheralded plasma membrane and vesicle lipids are also key regulators of this cycle. This article reviews recent insights into the roles of lipid-modifying enzymes and lipids in the acute modulation of neurotransmission. [ABSTRACT FROM AUTHOR]

Active region is a dynamic process involving the Flexible coordination of different gaze strategies to achieve behavioral goals, although many complex behaviors rely on an ability to efficiently switch between gaze-control strategies, few studies to date have examined mechanisms of task level oculomotor control in detail. Here, we report few experiments in which subjects alternated between conflicting stimulus saccade mappings within a block of trials. The first experiment showed that there is no performance cost associated witch switching between pro and anti saccades. However, follow-up experiment demonstrate that whenever subjects alternate between arbitrary stimulus-saccade mappings, latency costs are apparent on the first trial after a task change. More detailed analysis of switch costs showed that latencies were particularly elevated for saccacdes directed toward the same location that had been the target for a saccade on the preceeding trial. This saccade "inhibition of return" effect was most marked when unexpected error feedbacks cued task switches, suggesting that saccade selection processes arc modulated by reward We conclude that there are two systems for arcade control that differ in their characteristics following a task switch. The "reflexive" control system can be enabled/disabled in advance of saccade execution without incurring any performance cost. Switch costs are only observed when two or more arbitrary stimulus-saccade mappings have to be coordinated by a "symbolic" control system. [ABSTRACT FROM AUTHOR]

Recent theory about interactions between plants and their herbivores focuses on properties of individual plants that affect their resistance to herbivores, and it extrapolates from these individual properties to those of whole communities. In this paper I question three major assumptions of this approach—costs of defenses, basic differences between classes of defenses, and step-wise coevolution—and recast the theory from a different community perspective. I propose that major differences in defenses between plants with very different life-history characteristics arise from differences in community structure, especially the numbers of herbivore species involved in the interactions. In particular, because of the diffuse pattern of herbivory on persistent plants, a new model of coevolution—diffuse coevolution—becomes appropriate when many species are involved. Complex interacting assemblages have special properties that cannot be derived just by summing up all of the simple interactions that occur. [ABSTRACT FROM PUBLISHER]

A case of vitamin D resistant hypophosphataemic osteomalacia with glycosuria and aminoaciduria is reported. The course of the disease was dramatically altered by the removal of a bone sarcoma which probably had been growing slowly since the onset of the patient's symptoms five years previously. The histology and electron microscopy of the tumour are described. Three years after the operation the patient remains free of symptoms. [ABSTRACT FROM PUBLISHER]

We characterized the structure of condensed tannins from 16 woody plant species (seven genera, six families) and determined their effects on six herbivorous insect species (four genera, two families). There were major differences in tannin structure, even between congeneric plant species. Condensed tannins differed markedly in their antiherbivore activity, averaged over these herbivores, and the herbivores differed in their sensitivity, averaged over these tannins. Furthermore, the same tannin can have different effects on different herbivores, presumably because of interactions between tannin structure and gut physiology. Results challenge the view that tannins provide an evolutionarily stable plant defense because of their uniform chemical properties. Condensed tannin can sometimes impact herbivore fitness through effects on survival and growth, but the largest effects in 45 insect-tannin combinations were less than that of many other plant metabolites at lower doses. Even at high doses, condensed tannins frequently had no strong antiherbivore activity, even against insects with no evolutionary history of encountering the tannin ( Key words: condensed tannin; detoxification; herbivory; insect growth; plant defense., INTRODUCTION Tannins were seldom mentioned in the ecological literature prior to Feeny's (1968, 1969, 1970) work with oak and winter moth caterpillars, but achieved prominence when it was hypothesized that [...]

I report on polydactyly in a Vaux's Swift (Chaetura vauxi). An extra, asymmetrically located toe was found on each foot of one swift. A check of 329 swifts from several museums produced no other examples of polydactyly in this species. A review of the literature and a query over the Internet, however, produced 10 other examples of polydactyly in wild birds., Polydactyly is a relatively common malformation phenomenon in vertebrates. It has been well documented in humans and domestic animals such as cats, dogs, mice, and chickens (Clark et al. 2000); [...]