The development of the N1 and N2 components in auditory oddball paradigms: a systematic review with narrative analysis and suggested normative values.

Auditory event-related potentials (AERPs) are widely used in diverse fields of today's neuroscience, concerning auditory processing, speech perception, language acquisition, neurodevelopment, attention and cognition in normal aging, gender, developmental, neurologic and psychiatric disorders. However, its transposition to clinical practice has remained minimal. Mainly due to scarce literature on normative data across age, wide spectrum of results, variety of auditory stimuli used and to different neuropsychological meanings of AERPs components between authors. One of the most prominent AERP components studied in last decades was N1, which reflects auditory detection and discrimination. Subsequently, N2 indicates attention allocation and phonological analysis. The simultaneous analysis of N1 and N2 elicited by feasible novelty experimental paradigms, such as auditory oddball, seems an objective method to assess central auditory processing. The aim of this systematic review was to bring forward normative values for auditory oddball N1 and N2 components across age. EBSCO, PubMed, Web of Knowledge and Google Scholar were systematically searched for studies that elicited N1 and/or N2 by auditory oddball paradigm. A total of 2,764 papers were initially identified in the database, of which 19 resulted from hand search and additional references, between 1988 and 2013, last 25 years. A final total of 68 studies met the eligibility criteria with a total of 2,406 participants from control groups for N1 (age range 6.6-85 years; mean 34.42) and 1,507 for N2 (age range 9-85 years; mean 36.13). Polynomial regression analysis revealed that N1 latency decreases with aging at Fz and Cz, N1 amplitude at Cz decreases from childhood to adolescence and stabilizes after 30-40 years and at Fz the decrement finishes by 60 years and highly increases after this age. Regarding N2, latency did not covary with age but amplitude showed a significant decrement for both Cz and Fz. Results suggested reliable normative values for Cz and Fz electrode locations; however, changes in brain development and components topography over age should be considered in clinical practice.

Reporting Race and Ethnicity in Genetics Research: Do Journal Recommendations or Resources Matter?

Appeals to scrutinize the use of race and ethnicity as variables in genetics research notwithstanding, these variables continue to be inadequately explained and inconsistently used in research publications. In previous research, we found that published genetic research fails to follow suggestions offered for addressing this problem, such as explaining the basis on which these labels are assigned to populations. This study, an analysis of genetic research articles using race or ethnicity terms, explores possible features of journals that are associated with improved reporting of race and ethnicity in genetic research. A journal's expressed commitment to improving how race and ethnicity are used in genetic research, demonstrated by an editorial or in its instructions to authors, was the strongest predictor of following recommendations about reporting race and ethnicity. Journal impact factor had only a limited positive effect on attention to these issues, suggesting that editorial resources associated with higher impact factor journals are not sufficient to improve practices. Our findings reiterate that race and ethnicity variables are used inconsistently in genetic research, but also shed light on how journals might improve practices by highlighting the need for scientists to carefully scrutinize the use of these variables in their work.

Comparative Analysis of the Wear of NC11LV and Hardox 600 Steel Used in Tools for Extrusion of Clay Strands in the Process of Producing Ceramic Roof Tiles.

This article presents the results of a comparative analysis performed with respect to the wear of tools used for the extrusion of a clay strand (for ceramic roof tile) made from two materials: steel NC11LV and steel Hardox 600. The aim of the studies was to determine the causes and mechanisms of wear as well as to evaluate the possibility of choosing the optimal material, mostly in respect to its resistance to intensive wear as well as an increase in the operation time. The results of the conducted investigations included: an analysis of the technology, thermovision measurements of the forming process, a macroscopic analysis combined with 3D scanning of the worn tools, ball-on-disc tests of the sliding wear resistance and hardness measurements. The obtained results demonstrated that the tools made of steel NC11LV were much less worn than those made of steel Hardox 600, as the operation time for the NC11LV steel tools was almost three times longer. The results of the ball-on-disc tests showed a similar manner of wear for both materials (with the working temperature of about 50 °C). The higher durability of the tools made from steel NC11LV can be an effect of a slightly lower coefficient of friction in the initial period of operation as well as the presence of hard carbides, which means increased hardness and thus also higher wear resistance at working temperatures.

The impact of shift work on the well-being and subjective levels of alertness and sleepiness in firefighters and rescue service workers.

Shift work can be associated with health and sleep problems, which may lead to cognitive impairment. This study investigated the effects of shift work on sleep, health behaviours and cognitive functions of Polish rescue service workers. We tested 18 paramedics working 12-h shifts, 15 firefighters working 24-h shifts and 17 daytime workers. We measured general sleepiness, workload during shifts and the occurrence of health behaviours. Additionally, we measured attention, executive function and subjective alertness. Paramedics showed lower average sleep duration and quality, and fewer health behaviours than firefighters and the control group. However, no differences were found in performance on cognitive tests between the groups and between the measures. The results indicate that the differences in job specificity may contribute to the effects of shift work on the sleep and health of the workers.

Altered event-related potentials and theta oscillations index auditory working memory deficits in healthy aging.

Speech comprehension deficits constitute a major issue for an increasingly aged population, as they may lead older individuals to social isolation. Since conversation requires constant monitoring, updating and selecting information, auditory working memory decline, rather than impoverished hearing acuity, has been suggested a core factor. However, in stark contrast to the visual domain, the neurophysiological mechanisms underlying auditory working memory deficits in healthy aging remain poorly understood, especially those related to on-the-fly information processing under increasing load. Therefore, we investigated the behavioral costs and electrophysiological differences associated with healthy aging and working memory load during continuous auditory processing. We recorded EEG activity from 27 younger (∼25 years) and 29 older (∼70 years) participants during their performance on an auditory version of the n-back task with speech syllables and 2 workload levels (1-back; 2-back). Behavioral measures were analyzed as indices of function; event-related potentials as proxies for sensory and cognitive processes; and theta oscillatory power as a reflection of memory and central executive function. Our results show age-related differences in auditory information processing within a latency range that is consistent with a series of impaired functions, from sensory gating to cognitive resource allocation during constant information updating, especially under high load.

Cognitive functions of shift workers: paramedics and firefighters - an electroencephalography study.

Introduction. Working shifts has a negative impact on employee health and cognitive efficiency. The purpose of this study was to investigate the impact of shift work on cognitive functions - attention and working memory - using both behavioural and electrophysiological measures. Methods. The study was carried out on a group of 34 shift employees (18 paramedics, 16 firefighters) and on 17 day workers. Participants performed the attention network test and the N-back task with two conditions (1-back, 2-back) while the electroencephalography signal was recorded. Results. Observations included a higher amplitude of the P200 potential in paramedics (compared to the control group), a higher amplitude of the P300 potential after work than on a day off and the lowest increase in power in the θ band after the night shift. In firefighters, lower α desynchronization and lower synchronization in the α/ß band were observed after a 24-h shift. Paramedics and firefighters had longer reaction times (N-back task). Conclusions. The results suggest that paramedics experience problems with sustained attention. Paramedics process visual stimuli in a different way; after a night shift, performing the tasks required more engagement of cognitive resources. For firefighters, a decrease in visual attention functions and cognitive inhibition was observed.

Dosimetric Comparisons of Simulation Techniques for Left-Sided Breast Cancer in the COVID-19 Era: Techniques to Reduce Viral Transmission and Respect the Therapeutic Ratio.

Background The COVID-19 pandemic challenges our ability to safely treat breast cancer patients and requires revisiting current techniques to evaluate optimal strategies. Potential long-term sequelae of breast radiation have been addressed by deep inspiration breath-hold (DIBH), prone positioning, and four-dimensional computed tomography (4DCT) average intensity projection (AveIP)-based planning techniques. Dosimetric comparisons to determine the optimal technique to minimize the normal tissue dose for left-sided breast cancers have not been performed. Methods Ten patients with left-sided, early-stage breast cancer undergoing whole breast radiation were simulated in the prone position, supine with DIBH, and with a free-breathing 4DCT scan. The target and organs at risk (OAR) contours were delineated in all scans. Target volume coverage and OAR doses were assessed. One-way analysis of variance (ANOVA) and Kruskal-Wallis one-way ANOVA were used to detect differences in dosimetric parameters among the different treatment plans. Significance was set as p < 0.05. Results We demonstrate differences in heart and lung dose by the simulation technique. The mean heart doses in the prone, DIBH, and AveIP plans were 129 cGy, 154 cGy, and 262 cGy, respectively (p=0.02). The lung V20 in the prone, DIBH, and AveIP groups was 0.5%, 10.3% and 9.5%, respectively (p <0.001). Regardless of technique, lumpectomy planning target volume (PTV) coverage did not differ between the three plans with 95% of the lumpectomy PTV volume covered by 100.4% in prone plans, 98.5% in AveIP plans, and 99.3% in DIBH plans (p=0.7). Conclusions Prone positioning provides dosimetric advantages as compared to DIBH. When infection risks are considered as in the current coronavirus disease 2019 (COVID-19) pandemic, prone plans have advantages in reducing the risk of disease transmission. In instances where prone positioning is not feasible, obtaining an AveIP simulation may be useful in more accurately assessing heart and lung toxicity and informing a risk/benefit discussion of DIBH vs free breath-hold techniques.

Age-related differences in Voice-Onset-Time in Polish language users: An ERP study.

Using the Mismatch Negativity (MMN) paradigm we investigated for the first time cortical responses to consonant - vowel (CV) syllables differing in Voice-Onset-Time (VOT) for Polish, a member of the Slavic group of languages. The study aimed at testing age-related effects on different ERP responses in young (20-30 years of age) and elderly (60-68 years) native Polish speakers. Participants were presented with a sequence of voiced and voiceless stop CV syllables /to/ and /do/ with different VOT values (-100 ms, -70 ms, -30 ms, -20 ms, +20 ms, +50 ms). We analyzed MMN and P1, N1, N1', P2, N2 components. Our results showed an age-related decline in voicing perception in all tested ERP components. This decline could be explained in relation to a general slowing in neural processing with advancing age and may be associated with difficulties in temporal- and spectral-information processing in elderly people. Our findings revealed also that specific features of Slavic languages influence ERP morphology in a different way than reported in the literature for aspirating languages.

Training-Induced Changes in Rapid Auditory Processing in Children With Specific Language Impairment: Electrophysiological Indicators.

The brain's ability to recognize acoustic changes occurring in rapid temporal succession is important for speech and successful language development. Children with specific language impairment (SLI) are characterized by deficient dynamics of temporal information processing (TIP) in the millisecond time range accompanied by disordered language development. Furthermore, previous studies have found that intervention based on amelioration of TIP resulted in improvement of both language and other cognitive functions. This study aimed to explain the changes associated with TIP training from the perspective of event-related potentials (ERPs). Thirty-six children aged 5-8 years (26 boys, 10 girls) diagnosed with SLI underwent two types of intense audio-visual computer intervention: experimental TIP training targeted at the millisecond time range (n = 18) or control non-TIP training (n = 18). Paired 50 ms tones of 1000 Hz and 1200 Hz were presented with inter-stimulus intervals (ISIs) of either 50 ms (Short ISI Condition) or 200 ms (Long ISI Condition). Auditory ERPs were measured in a passive oddball paradigm before and after each type of training. The mismatch negativity (MMN) paradigm was applied as an electrophysiological indicator of the brain's ability to automatically detect violations of regularity in paired tones presented in rapid succession. Moreover, the P3a component was also analyzed. After 24 sessions of temporal training (in the experimental group) MMN amplitude enhancement was observed in both ISI conditions, reflecting increased efficiency in perceiving changes in rapid auditory sequences. In both experimental and control groups, P3a amplitude was enhanced in both ISIs. This may be due to the improvement of involuntary attention shifting to the auditory events involved in each training type. To conclude, temporal training, compared to non-temporal control training, improved the ability to detect changes in a rapid auditory stream in children with SLI.

Electrophysiological Indicators of the Age-Related Deterioration in the Sensitivity to Auditory Duration Deviance.

The present study investigates age-related changes in duration discrimination in millisecond time domain. We tested young (N = 20, mean age = 24.5, SD = 2.97) and elderly (N = 20, mean age = 65.2, SD = 2.94) subjects using the mismatch negativity (MMN) paradigm. White-noise bursts of two different durations (50 and 10 ms) were presented in two oddball blocks. In one block (Increment Condition), the repetitive sequence of 10 ms standards was interspersed by occasional 50 ms deviants. In the Decrement Condition, the roles of the two stimuli were reversed. We analyzed the P1-N1 complex, MMN and P3a and found the effect of age for all these components. Moreover, the impact of stimulus presentation condition (increment/decrement) was observed for MMN and P3a. Our results confirmed the previous evidence for deteriorated duration discrimination in elderly people. Additionally, we found that this effect may be influenced by procedural factors.

Temporal Information Processing and its Relation to Executive Functions in Elderly Individuals.

Normal aging triggers deterioration in cognitive functions. Evidence has shown that these age-related changes concern also executive functions (EF) as well as temporal information processing (TIP) in a millisecond range. A considerable amount of literature data has indicated that each of these two functions sets a frame for our mental activity and may be considered in terms of embodied cognition due to advanced age. The present study addresses the question whether in elderly subjects the efficiency of TIP is related to individual differences in EF. The study involved 53 normal healthy participants aged from 65 to 78. In these subjects TIP was assessed by sequencing abilities measured with temporal-order threshold (TOT). It is defined as the minimum time gap separating two auditory stimuli presented in rapid succession which is necessary for a subject to report correctly their temporal order, thus the relation 'before-after.' The EF were assessed with regard to the efficiency of the executive planning measured with the Tower of London-Drexel University (TOLDX) which has become a well-known EF task. Using Spearman's rank correlations we observed two main results. Firstly, the indices of the TOLDX indicated a coherent construct reflecting the effectiveness of executive planning in the elderly. Initiation time seemed dissociated from these coherent indices, which suggested a specific strategy of mental planning in the elderly based on on-line planning rather than on preplanning. Secondly, TOT was significantly correlated with the indices of TOLDX. Although some of these correlations were modified by subject's age, the correlation between TOT and the main index of TOLDX ('Total Move Score') was rather age resistant. These results suggest that normal aging may be characterized by an overlapping of deteriorated TIP and deteriorated EF.

ALK inhibitor PF02341066 (crizotinib) increases sensitivity to radiation in non-small cell lung cancer expressing EML4-ALK.

Crizotinib (PF02341066) is a tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) that has been shown to selectively inhibit growth of cancer cells that harbor the EML4-ALK fusion found in a subset of patients with non-small cell lung cancer (NSCLC). While in clinical trials, PF02341066 has shown a significant therapeutic benefit as a single agent; the effectiveness of combining it with other therapeutic modalities including ionizing radiation remains unknown. To further elucidate the role of PF02341066 in tumor inhibition, we examined its effects alone and in combination with radiation on downstream signaling, apoptosis, and radiosensitivity in two NSCLC cell lines in vitro: H3122, which harbors the EML4-ALK fusion, and H460, which does not. We also examined the in vivo effects of PF02341066 in H3122 mouse xenografts. In the H3122 cell line, PF02341066 inhibited phosphorylation of ALK and its downstream effectors: AKT, ERK, and STAT3. H3122 cells treated with a combination of PF02341066 and radiation showed an increase in cellular apoptosis and were sensitized to radiation therapy (dose enhancement ratio, 1.43; P < 0.0001). Moreover, in an H3122 xenograft model, the combined treatment resulted in greater tumor growth inhibition than either treatment alone (P < 0.05). None of these effects was observed in the EML4-ALK-negative H460 cells. Our findings indicate that PF02341066 acts as a radiation sensitizer in cells harboring the EML4-ALK fusion, providing a rationale for a clinical trial combining ALK inhibitor with radiation in the NSCLCs expressing ALK.

Implanted dosimeters identify radiation overdoses during IMRT for prostate cancer.

PURPOSE: Image-guided dose-escalated radiotherapy is the standard of care for the treatment of prostate cancer. Although many published methods are available that account for prostate motion during delivery, evidence demonstrating that the planned dose is actually delivered on a daily basis is lacking. We report our initial clinical experience using implantable dosimeters to quantify and adjust the dose received during intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A total of 20 patients undergoing IMRT with cone-beam computed tomography (CT) image guidance for prostate cancer had the dose verification system with radiopaque metal-oxide-semiconductor field effect transistor dosimeters implanted before treatment planning. All patients underwent planning with CT simulation in the supine position with custom immobilization, and the implanted dosimeters were located in the IMRT plans. The predicted dose for each dosimeter was defined and compared with the wireless readings before and after each treatment session. Investigations by physicians and medical physicists were initiated for two or more discrepancies >6% for any five consecutive fractions or for any discrepancy ≥10%. RESULTS: Using implanted in vivo dosimeters, dose measurements consistently >6% greater than the predicted values were observed during treatment for 3 of 20 prostate cancer patients who received IMRT with daily image guidance. A review of the daily cone-beam CT images revealed acceptable alignment of the prostate target volumes and implanted dosimeters but identified significant anatomic changes within the treated region. Repeat CT simulation and RT planning was performed, with resolution of the dose discrepancies in all 3 cases with the adoption of a new IMRT plan. CONCLUSIONS: Our report illustrates the potential effect of implanted in vivo dosimetry for prostate IMRT and emphasizes the importance of careful planning and delivery with attention to systematic shifts or anatomic changes that could alter the dose distributions.

Establishment of paternal allele-specific DNA methylation at the imprinted mouse Gtl2 locus.

The monoallelic expression of imprinted genes is controlled by epigenetic factors including DNA methylation and histone modifications. In mouse, the imprinted gene Gtl2 is associated with two differentially methylated regions: the IG-DMR, which serves as a gametic imprinting mark at which paternal allele-specific DNA methylation is inherited from sperm, and the Gtl2-DMR, which acquires DNA methylation on the paternal allele after fertilization. The timeframe during which DNA methylation is acquired at secondary DMRs during post-fertilization development and the relationship between secondary DMRs and imprinted expression have not been well established. In order to better understand the role of secondary DMRs in imprinting, we examined the methylation status of the Gtl2-DMR in pre- and post-implantation embryos. Paternal allele-specific DNA methylation of this region correlates with imprinted expression of Gtl2 during post-implantation development but is not required to implement imprinted expression during pre-implantation development, suggesting that this secondary DMR may play a role in maintaining imprinted expression. Furthermore, our developmental profile of DNA methylation patterns at the Cdkn1c- and Gtl2-DMRs illustrates that the temporal acquisition of DNA methylation at imprinted genes during post-fertilization development is not universally controlled.