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* Context.--The Ventana programmed death ligand-1 (PD-L1) SP142 immunohistochemical assay (IHC) is approved by the US Food and Drug Administration as the companion diagnostic assay to identify patients with locally advanced or metastatic triple-negative breast cancer for immunotherapy with atezolizumab, a monoclonal antibody targeting PD-L1. Objective.--To determine interobserver variability in PD-L1 SP142 IHC interpretation in invasive breast carcinoma. Design.--The pathology database was interrogated for all patients diagnosed with primary invasive, locally recurrent, or metastatic breast carcinoma on which PD-L1 SP142 IHC was performed from November 2018 to June 2019 at our institution. A subset of cases was selected using a computerized random-number generator. PD-L1 IHC was evaluated in stromal tumor-infiltrating immune cells using the IMpassion130 trial criteria, with positive cases defined as immunoreactivity in immune cells in 1% or more of the tumor area. IHC was interpreted on whole slide images by staff pathologists with breast pathology expertise. Interobserver variability was calculated using unweighted k. Results.--A total of 79 cases were assessed by 8 pathologists. Interobserver agreement was substantial (k = 0.727). There was complete agreement among all 8 pathologists in 62% (49 of 79) of cases, 7 pathologists or more in 84% (66 of 79) of cases, and 6 pathologists or more in 92% (73 of 79) of cases. In 4% (3 of 79) of cases, all of which were small biopsies, pathologists' interpretations were evenly split between scores of positive and negative. Conclusions.--The findings show substantial agreement in PD-L1 SP142 IHC assessment of breast carcinoma cases among 8 pathologists at a single institution. Further study is warranted to define the basis for discrepant results. (Arch Pathol Lab Med. 2021;145:1132-1137; doi: 10.5858/arpa.2020-0441-OA, Triple-negative breast carcinomas (TNBCs) lack expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) and are associated with aggressive clinical behavior. Median overall survival for [...]

Aim: Visual evoked potentials (VEP) represent an objective non-invasive and inexpensive dia­gnostic method, particularly in neuro-ophthalmology. A lot of possible dia­gnostic applications are limited because they are only examined with the use of robust equipment which is hardly transportable and immobile and handicapped patients cannot visit the specialized labs. The aim of our research work was the development of a portable inexpensive VEP device that could be used almost anywhere. Methods: All parts of the last prototype of the device (built-in visual stimulator, recording electrodes, 4-channel EEG amplifier, analog-digital converter, and control unit) with a total weight of 390 g are placed in a headset (plastic "shield" with an adjustable strap). The software for VEP recording and evaluation is used on a standard notebook (PC). The parameters of the device fulfill recommendations of the international societies for clinical electrophysiology of vision and clinical neurophysiology also enabling new applications of so far not routinely used variants of evoked potentials. Testing of the device was done so far in 91 control subjects and 135 neuroophthalmological patients. Results: Pilot studies proved comparable parameters of VEP and dia­gnostic sensitivity as in standard devices (equal results in 93% of cases). It was verified that the device is usable in various environments, at the patient's bedside, and also for basic self-examination. Conclusion: The portable device for VEP significantly increases the availability of their examination and thus enables much broader dia­gnostic applications of this method. [ABSTRACT FROM AUTHOR]

The purpose of the study is to identify promising areas of investment diplomacy in encouraging foreign investment in the economy of Azerbaijan. As a result of the study, the tasks of identifying areas of agreements with countries of the world to encourage foreign investment and identify areas belonging to attracting foreign investment have been solved. The author considers investments made in Azerbaijan; studies investments directed abroad. A limitation in the study was the lack of open information before 2000 on benefits and other measures in agreements between Azerbaijan and other countries, the lack of information on investment investments abroad by sectors of the economy, and the discrepancy in figures between the CBA and UNCTAD. The study used the methods of grouping, analysis and comparison. The legal framework, information from reports of international organizations, forums were used. The scientific novelty of the study is that the author considered new trends in the field of investment attractiveness and made proposals on the directions of Azerbaijan’s investment diplomacy. The author found that agreements, conventions and protocols have a different structure and significant differences in the content of bilateral investment treaties allow the country to retain certain leverage. In the sectoral context, the largest flows of investments were directed to the development of industry, construction and transport. Since 2006, there has been an increase in investment in the transport sector, and since 2014 in construction. Despite the growth of foreign investment in these sectors, statistics still recorded an increase in the inflow of foreign investment in the sector of crude oil and natural gas production. Also, 30% of Azerbaijan’s direct investment abroad is in the oil sector. In order to implement promising areas of Azerbaijan’s investment diplomacy in the near future, it was proposed to introduce active investment diplomacy.

Octopuses are high organized invertebrates with big brains and complex behavior. The architecture of their brain is very different than in mammals or other vertebrates. However, they have a high level of behavioral plasticity, which, obviously, has the neuronal substrate. Understanding the functioning of the octopus brain will expand our knowledge of the mechanisms of neuronal control of behavior. For this, we need the instruments, and the registration of local field potentials (LFP, or less precise term electroencephalogram) is one of the most simple, cheap, but powerful methods. Recording LFP in nonanesthetized freely-behaving octopus is challenging. Using wired devices is problematic because of the number, length, and strength of animals' arms. Wireless radio-based systems are not suitable because of the shielding properties of water which is a mandatory component of the cephalopods' environment. To solve this problem, we have developed a specialized water-resistant container for the NeuroLogger® (Newbehavior AG, Zurich, Switzerland) device. The electrodes (4 data and 1 reference) were implanted into the brain of three adult Octopus cyanea (2.5-4.2kg) under anesthesia. The capacity of the device was enough to obtain approximately 13 hours of LFP records while the animals were in the housing tank. The animals were filmed, then the video was synchronized to LFP, and behavior was manually scored by two experts. Unlike some previous reports, the LFP from octopus brains did not look like that of mammalian brains with regular oscillations during at least some behavioral states. LFP waves were mostly irregular and slow (<1Hz), with short periods of sinusoid-like activity or spikes. To reveal the possible correlation between LFP and behavioral states, we split the record into 10 s epochs and calculated the root mean square (RMS) of the signals' amplitudes. Three distinct behavioral states were selected for this analysis: sleeping (SL), non-sleeping not moving (NM), and non-sleeping actively moving (MV). Then RMS values were compared between different states for each animal. There were significant differences between at least two states in every channel and all animals. Interestingly, in some electrodes sleep activity had greater amplitudes than awake (both active and quiet). In others, the difference was the opposite. Since there is no stereotaxic atlas for the octopus brain, the positions of electrodes could be slightly different, and this results in some inconsistency across the animals. We need to collect further data to reveal the electrophysiological correlates of the octopuses' behavioral patterns. This may be real using our approach to record the brain electrical activity of these animals. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has created substantial and dynamic disruptions in society, personal behavior, and potentially chronic sound exposures, which are associated with hearing loss, cardiovascular disease, and other health impacts. Leveraging preliminary data from our unique nationwide Apple Hearing Study, we explored changes in personal sound exposures resulting from COVID-19-related social distancing. Volunteer participants opted to share environmental sound data from their Apple Watch and headphone sound data from their iPhone. Participants for this analysis were chosen from four states which exhibited diverse responses to COVID-19. Equivalent continuous average sound exposures (in A-weighted decibels, dBA) were computed per person-day and normalized to 8 hour L _EX8h exposures. Daily mean L _EX8h exposures across two time periods, a baseline period (before the first known US COVID-19 death at the time of analysis) and an intervention period (starting with each state’s first COVID-related public health social distancing announcement and ending on April 22, 2020) were defined to assess changes in sound exposure. We modeled sound levels across 5,894 participants and 516,729 monitored days using a linear mixed-effects model with random effects for participant. The overall reduction in LEX8h between baseline and intervention was 2.6 ± 0.05 dBA (mean ± SE). There was a significant day-of-week effect during the baseline period, with the lowest exposures on Monday and the highest on Saturday. This effect was not noted during the intervention period. COVID-19 social distancing measures were associated with an approximately 3 dBA reduction in personal environmental sound exposures; this represents a substantial and meaningful reduction in this harmful exposure. Our analysis demonstrates the utility of everyday use devices in detecting behavior and exposure changes associated with the COVID-19 pandemic, and the usefulness of longitudinal, large-scale characterization of personal exposures and health impacts using wearable technology.

Purpose: The aim of this neurophysiological study was to retrospectively analyze visual evoked potentials (VEPs) acquired during an examination for diagnosing optic nerve involvement in patients with Lyme neuroborreliosis (LNB). Attention was focused on LNB patients with peripheral facial palsy (PFP) and optic nerve involvement., Methods: A total of 241 Czech patients were classified as having probable/definite LNB (193/48); of these, 57 were younger than 40 years, with a median age of 26.3 years, and 184 were older than 40 years, with a median age of 58.8 years. All patients underwent pattern-reversal (PVEP) and motion-onset (MVEP) VEP examinations., Results: Abnormal VEP results were observed in 150/241 patients and were noted more often in patients over 40 years (p = 0.008). Muscle/joint problems and paresthesia were observed to be significantly more common in patients older than 40 years (p = 0.002, p = 0.030), in contrast to headache and decreased visual acuity, which were seen more often in patients younger than 40 years (p = 0.001, p = 0.033). Peripheral facial palsy was diagnosed in 26/241 LNB patients. Among patients with PFP, VEP peak times above the laboratory limit was observed in 22 (84.6%) individuals. Monitoring of patients with PFP and pathological VEP showed that the adjustment of visual system function occurred in half of the patients in one to more years, in contrast to faster recovery from peripheral facial palsy within months in most patients., Conclusion: In LNB patients, VEP helps to increase sensitivity of an early diagnostic process., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite positive prior results obtained by using event-related potentials (ERPs) in psychiatric patients, they are not routinely used in the clinical setting. This may in part be due to problems regarding a lack of transportable equipment availability. It can be difficult for these patients to repeatedly visit electrophysiological laboratories. To address this issue, we propose using a new, fully portable device for visually evoked potentials (VEP) and cognitive function assessment, that can be used for quick examinations (https://www.veppeak.com). Our device, called "VEPpeak", is built into a headset with a color LED visual stimulator. It weighs 390 g and is connected to a notebook (PC) with evaluation software via USB. In this pilot study, we verified the device's usability in 31 patients with schizophrenia. We used the oddball paradigm with the recognition of colors for the P300 wave and choice reaction time evaluation. The examination lasted only about ten minutes. The results indicated good reproducibility of large cognitive potentials (P300) with prolonged P300 latencies and reduced amplitudes in patients compared to 15 control subjects. The P300 latency and reaction time prolongation in patients correlated with their age and the sedative effect of the pharmacotherapy., Competing Interests: Declaration of Competing Interest All authors declare that their potential conflict of interest could be related only to the eventual routine use of the device in healthcare, which may be connected with a financial benefit. This will only be applicable after the device has been certified as a “medical device”., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Many modern automated vehicle sensor systems use light detection and ranging (LiDAR) sensors. The prevailing technology is scanning LiDAR, where a collimated laser beam illuminates objects sequentially point-by-point to capture 3D range data. In current systems, the point clouds from the LiDAR sensors are mainly used for object detection. To estimate the velocity of an object of interest (OoI) in the point cloud, the tracking of the object or sensor data fusion is needed. Scanning LiDAR sensors show the motion distortion effect, which occurs when objects have a relative velocity to the sensor. Often, this effect is filtered, by using sensor data fusion, to use an undistorted point cloud for object detection. In this study, we developed a method using an artificial neural network to estimate an object's velocity and direction of motion in the sensor's field of view (FoV) based on the motion distortion effect without any sensor data fusion. This network was trained and evaluated with a synthetic dataset featuring the motion distortion effect. With the method presented in this paper, one can estimate the velocity and direction of an OoI that moves independently from the sensor from a single point cloud using only one single sensor. The method achieves a root mean squared error (RMSE) of 0.1187 m s -1 and a two-sigma confidence interval of [-0.0008 m s -1 , 0.0017 m s -1 ] for the axis-wise estimation of an object's relative velocity, and an RMSE of 0.0815 m s -1 and a two-sigma confidence interval of [0.0138 m s -1 , 0.0170 m s -1 ] for the estimation of the resultant velocity. The extracted velocity information (4D-LiDAR) is available for motion prediction and object tracking and can lead to more reliable velocity data due to more redundancy for sensor data fusion.

A modified 2'-deoxycytidine triphosphate derivative (dC TO TP) bearing a thiazole orange moiety tethered via an oligoethylene glycol linker was designed and synthesized. The nucleotide was incorporated into DNA by DNA polymerases in vitro as well as in live cells. Upon incorporation of dC TO TP into DNA, the thiazole orange moiety exhibited a fluorescence lifetime that differed significantly from the non-incorporated (i.e. free and non-covalently intercalated) forms of dC TO TP. When dC TO TP was delivered into live U-2 OS cells using a synthetic nucleoside triphosphate transporter, it allowed us to distinguish and monitor cells that were actively synthesizing DNA in real time, from the very first moments after the treatment. We anticipate that this probe could be used to study chromatin organization and dynamics., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Introduction: We developed a new portable device called "VEPpeak" for the examination of visual evoked potentials (VEPs) to extend VEP examination beyond specialized electrophysiological laboratories and to simplify the use of this objective, noninvasive, and low-cost method for diagnostics of visual and central nervous system dysfunctions., Methods: VEPpeak consists of a plastic headset with a total weight of 390 g containing four EEG amplifiers, an A/D converter, a control unit, and a visual LED stimulator built in the front, vertically adjustable peak. The device is powered and controlled via USB connection from a standard PC/notebook using custom software for visual stimuli generation and for VEP recording and processing. Up to four electrodes can be placed at any scalp location or in combination with two dry electrodes incorporated into the headset. External visual stimulators, such as a tablet, can be used with synchronization. Feasibility and validation studies were conducted with 86 healthy subjects and 76 neuro-ophthalmological patients including 67 who were during the same session also tested with a conventional VEP system., Results: VEPpeak recordings to standard (pattern-reversal) and non-standard (motion-onset, red-green alternation) were robust and repeatable and obtained also in immobilized patients. Good comparability of results was achieved between VEPpeak and standard examination. Some systematic differences in peak latencies and amplitudes are consistent with differences in stimulus characteristics of the two compared systems., Discussion: VEPpeak provides an inexpensive system for clinical use requiring portability. In addition to ISCEV standard VEP protocols, free choice of stimuli and bio-signal recordings make the device universal for many electrophysiological purposes., (© 2022. The Author(s).)

Nucleosides and 2'-deoxyribonucleoside triphosphates (dNTPs) bearing 3,3'-dimethoxy-2,2'-diphenyl-6-(4-hydroxyphenyl)-bodipy fluorophore attached through a propargyl or propargyl-triethylene glycol linker to position 5 of 2'-deoxycytidine were designed and synthesized. They exerted bright red fluorescence and good sensitivity to viscosity changing their lifetime from 1.6 to 4.5 ns. The modifed dNTPs were substrates for DNA polymerases and were used in enzymatic synthesis of labeled DNA through primer extension. The modified DNA probes served as viscosity sensors responding to protein binding by changes of lifetime. The nucleotide with longer linker ( dC pegMOB TP ) was transported to live cells and incorporated into the genomic DNA, which can be useful for staining of DNA and imaging of DNA synthesis.

In the age homogenous group of 13 healthy volunteers, we examined visual evoked potentials (VEP) visually evoked cognitive potentials (event-related potentials - ERP) and choice reaction time (CRT) five times during the day (from 10.00 a.m. up to midnight) to verify whether there are significant changes of the measured parameters of the cortical evoked potentials and CRT which might reflect the level of the mental fatigue. The electrophysiological testing was done with the use of a new portable VEP device named "VEPpeak" enabling to perform the examination outside standard labs in almost any conditions. It was found that the latency of ERP (P300 peak time) and CRT displayed significant prolongation toward midnight while VEP latency and all amplitudes did not change significantly. This pilot study supports our idea that the portable VEP device possibly might be used for the objective examination of mental fatigue that is needed in many situations. This should be confirmed in a larger study also including a comparison with non-electrophysiological fatigue testing.

As part of its role in the World Health Organization's (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a total of 2,393 human influenza positive samples between 1 January 2020 and 31 December 2021 (2020: n = 2,021 samples; 2021: n = 372 samples). Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or embryonated hen's eggs for potential use in seasonal influenza virus vaccines. During 2020-2021, influenza A viruses (A(H1N1)pdm09 in 2020 and A(H3N2) in 2021) predominated over influenza B viruses. In 2020, the majority of A(H1N1)pdm09, A(H3N2) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO recommended vaccine strains for the southern hemisphere in 2020. In 2021, the majority of A(H1N1)pdm09 and A(H3N2) viruses were found to be antigenically distinct relative to the WHO recommended vaccine strains for the southern hemisphere in 2021. Of the influenza B viruses analysed at the Centre, 46.7% were found to be antigenically distinct to the respective WHO recommended vaccine strains. Of 1,538 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir (in 2020, n = 1,374; in 2021, n = 164), two A(H1N1)pdm09 viruses showed highly reduced inhibition against oseltamivir, and one A(H1N1)pdm09 virus showed highly reduced inhibition against zanamivir. All of these samples were received in 2020., (© Commonwealth of Australia CC BY-NC-ND.)