Fluctuations in instantaneous frequency predict alpha amplitude during visual perception.

Rhythmic neural activity in the alpha band (8-13 Hz) is thought to have an important role in the selective processing of visual information. Typically, modulations in alpha amplitude and instantaneous frequency are thought to reflect independent mechanisms impacting dissociable aspects of visual information processing. However, in complex systems with interacting oscillators such as the brain, amplitude and frequency are mathematically dependent. Here, we record electroencephalography in human subjects and show that both alpha amplitude and instantaneous frequency predict behavioral performance in the same visual discrimination task. Consistent with a model of coupled oscillators, we show that fluctuations in instantaneous frequency predict alpha amplitude on a single trial basis, empirically demonstrating that these metrics are not independent. This interdependence suggests that changes in amplitude and instantaneous frequency reflect a common change in the excitatory and inhibitory neural activity that regulates alpha oscillations and visual information processing

Studying Behaviour Change Mechanisms under Complexity

Understanding the mechanisms underlying the effects of behaviour change interventions is vital for accumulating valid scientific evidence, and useful to informing practice and policy-making across multiple domains. Traditional approaches to such evaluations have applied study designs and statistical models, which implicitly assume that change is linear, constant and caused by independent influences on behaviour (such as behaviour change techniques). This article illustrates limitations of these standard tools, and considers the benefits of adopting a complex adaptive systems approach to behaviour change research. It (1) outlines the complexity of behaviours and behaviour change interventions; (2) introduces readers to some key features of complex systems and how these relate to human behaviour change; and (3) provides suggestions for how researchers can better account for implications of complexity in analysing change mechanisms. We focus on three common features of complex systems (i.e., interconnectedness, non-ergodicity and non-linearity), and introduce Recurrence Analysis, a method for non-linear time series analysis which is able to quantify complex dynamics. The supplemental website provides exemplifying code and data for practical analysis applications. The complex adaptive systems approach can complement traditional investigations by opening up novel avenues for understanding and theorising about the dynamics of behaviour change.Peer reviewe

Peripheral differentiation patterns of human T cells

Long-term T-cell memory is dependent on the maintenance of memory T cells in the lymphoid tissues, and at the surface interfaces that provide entry routes for pathogens. However, much of the current information on human T-cell memory is based on analyzing circulating T cells. Here, we have studied the distribution and age-related changes of memory T-cell subsets in samples from blood, mesenteric LNs, spleen, and ileum, obtained from donors ranging in age from 5 days to 67 years of age. Our data show that the main reservoir of polyclonal naive cells is found in the LNs, and the resting memory subsets capable of self-renewal are also prominent there. In contrast, nondividing but functionally active memory subsets dominate the spleen, and especially the ileum. In general, the replacement of naive cells with memory subsets continues throughout our period of observation, with no apparent plateau. In conclusion, the analysis of lymphoid and nonlymphoid tissues reveals a dynamic pattern of changes distinct to each tissue, and with substantial differences between CD4(+) and CD8(+) compartments.Peer reviewe

T cell receptor diversity in the human thymus

A diverse T cell receptor (TCR) repertoire is essential for adaptive immune responses and is generated by somatic recombination of TCR alpha and TCR beta gene segments in the thymus. Previous estimates of the total TCR diversity have studied the circulating mature repertoire, identifying 1 to 3 x 10(6) unique TCR beta and 0.5 x 10(6) TCR alpha sequences. Here we provide the first estimate of the total TCR diversity generated in the human thymus, an organ which in principle can be sampled in its entirety. High-throughput sequencing of samples from four pediatric donors detected up to 10.3 x 10(6) unique TCR beta sequences and 3.7 x 10(6) TCR alpha sequences, the highest directly observed diversity so far for either chain. To obtain an estimate of the total diversity we then used three different estimators, preseq and DivE, which measure the saturation of rarefaction curves, and Chao2, which measures the size of the overlap between samples. Our results provide an estimate of a thymic repertoire consisting of 40 to 70 x 10(6) unique TCR beta sequences and 60 to 100 x 10(6) TCR alpha sequences. The thymic repertoire is thus extremely diverse. Moreover, extrapolation of the data and comparison with earlier estimates of peripheral diversity also suggest that the thymic repertoire is transient, with different clones produced at different times. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe

Human thymic T cell repertoire is imprinted with strong convergence to shared sequences

A highly diverse repertoire of T cell antigen receptors (TCR) is created in the thymus by recombination of gene segments and the insertion or deletion of nucleotides at the junctions. Using next-generation TCR sequencing we define here the features of recombination and selection in the human TCR alpha and TCR beta locus, and show that a strikingly high proportion of the repertoire is shared by unrelated individuals. The thymic TCRa nucleotide repertoire was more diverse than TCR beta, with 4.1 x 10(6) vs. 0.81 x 10(6) unique clonotypes, and contained nonproductive clonotypes at a higher frequency (69.2% vs. 21.2%). The convergence of distinct nucleotide clonotypes to the same amino acid sequences was higher in TCRa than in TCR beta repertoire (1.45 vs. 1.06 nucleotide sequences per amino acid sequence in thymus). The gene segment usage was biased, and generally all individuals favored the same genes in both TCR alpha and TCR beta loci. Despite the high diversity, a large fraction of the repertoire was found in more than one donor. The shared fraction was bigger in TCR alpha than TCR beta repertoire, and more common in in-frame sequences than in nonproductive sequences. Thus, both biases in rearrangement and thymic selection are likely to contribute to the generation of shared repertoire in humans.Peer reviewe

Characterization of human T cell receptor repertoire data in eight thymus samples and four related blood samples

T cell receptor (TCR) is a heterodimer consisting of TCR alpha and TCR beta chains that are generated by somatic recombination of multiple gene segments. Nascent TCR repertoire undergoes thymic selections where non-functional and potentially autoreactive receptors are removed. During the last years, the development of high-throughput sequencing technology has allowed a large scale assessment of TCR repertoire and multiple analysis tools are now also available. In our recent manuscript, Human thymic T cell repertoire is imprinted with strong convergence to shared sequences [1], we show highly overlapping thymic TCR repertoires in unrelated individuals. In the current Data in Brief article, we provide a more detailed characterization of the basic features of these thymic and related peripheral blood TCR repertoires. The thymus samples were collected from eight infants undergoing corrective cardiac surgery, two of whom were monozygous twins [2]. In parallel with the surgery, a small aliquot of peripheral blood was drawn from four of the donors. Genomic DNA was extracted from mechanically released thymocytes and circulating leukocytes. The sequencing of TCR alpha and TCR beta repertoires was performed at ImmunoSEQ platform (Adaptive Biotechnologies). The obtained repertoire data were analysed applying relevant features from immunoSEQ (R) 3.0 Analyzer (Adaptive Biotechnologies) and a freely available VDJTools software package for programming language R [3]. The current data analysis displays the basic features of the sequenced repertoires including observed TCR diversity, various descriptive TCR diversity measures, and V and J gene usage. In addition, multiple methods to calculate repertoire overlap between two individuals are applied. The raw sequence data provide a large database of reference TCRs in healthy individuals at an early developmental stage. The data can be exploited to improve existing computational models on TCR repertoire behaviour as well as in the generation of new models. (C) 2021 The Authors. Published by Elsevier Inc.Peer reviewe

Randomised controlled feasibility study of a school-based multi-level intervention to increase physical activity and decrease sedentary behaviour among vocational school students

BACKGROUND: No school-based physical activity (PA) interventions among older adolescents have demonstrated long-term effectiveness, and few of them so far have addressed sedentary behaviour (SB). Based on behavioural theories and evidence, we designed a multi-level intervention to increase PA and decrease SB among vocational school students. This study investigates feasibility and acceptability of two main intervention components and research procedures. We also examine uptake of behaviour change techniques (BCTs) by the participants. METHODS: Design was an outcome assessor blinded, cluster-randomised controlled trial. Four classes of students (matched pairs) were randomised into one intervention and one control arm. The intervention consisted of (1) a 6-h group-based intervention for students, (2) two 2-h training workshops to reduce their students' sitting in class for teachers, and (3) provision of light PA equipment in classrooms. At baseline (T1), mid-intervention (T2) at 3 weeks, post-intervention (T3) and 6 months after baseline (T4) we measured hypothesised psychosocial mediators and self-reported PA and sitting. Objective assessment of PA and SB (7-day accelerometry) was conducted at T1, T3 and T4. Body composition (bioimpedance) was measured at T1 and T4. Students and teachers in the intervention arm filled in acceptability questionnaires at T3. RESULTS: Recruitment rate was 64% (students) and 88.9% (teachers), and at T3, all post-intervention measurements were completed by 33 students (retention 76.7%) and 15 teachers (retention 93.8%). Acceptability ratings of sessions were high (students M = 6.29, scale 1-7), and data collection procedures were feasible. Intervention arm students reported increased use of BCTs, but uptake of some key BCTs was suboptimal. BCT use correlated highly with objective measures of PA. Based on both self-report and student evaluation, teachers in the intervention arm increased the use of sitting reduction strategies at post-intervention and T4 follow-up (p < .05). CONCLUSIONS: We detected willingness of the target groups to participate, good response rates to questionnaires, adequate retention, as well as acceptability of the trial protocol. Investigation of BCT use among students helped further enhance intervention procedures to promote BCT use. After making necessary modifications identified, intervention effectiveness can next be tested in a definitive trial. TRIAL REGISTRATION: ISRCTN34534846 . Registered 23 May 2014. Retrospectively registered.Background: No school-based physical activity (PA) interventions among older adolescents have demonstrated long-term effectiveness, and few of them so far have addressed sedentary behaviour (SB). Based on behavioural theories and evidence, we designed a multi-level intervention to increase PA and decrease SB among vocational school students. This study investigates feasibility and acceptability of two main intervention components and research procedures. We also examine uptake of behaviour change techniques (BCTs) by the participants. Methods: Design was an outcome assessor blinded, cluster-randomised controlled trial. Four classes of students (matched pairs) were randomised into one intervention and one control arm. The intervention consisted of (1) a 6-h group-based intervention for students, (2) two 2-h training workshops to reduce their students' sitting in class for teachers, and (3) provision of light PA equipment in classrooms. At baseline (T1), mid-intervention (T2) at 3 weeks, post-intervention (T3) and 6 months after baseline (T4) we measured hypothesised psychosocial mediators and self-reported PA and sitting. Objective assessment of PA and SB (7-day accelerometry) was conducted at T1, T3 and T4. Body composition (bioimpedance) was measured at T1 and T4. Students and teachers in the intervention arm filled in acceptability questionnaires at T3. Results: Recruitment rate was 64% (students) and 88.9% (teachers), and at T3, all post-intervention measurements were completed by 33 students (retention 76.7%) and 15 teachers (retention 93.8%). Acceptability ratings of sessions were high (students M = 6.29, scale 1-7), and data collection procedures were feasible. Intervention arm students reported increased use of BCTs, but uptake of some key BCTs was suboptimal. BCT use correlated highly with objective measures of PA. Based on both self-report and student evaluation, teachers in the intervention arm increased the use of sitting reduction strategies at post-intervention and T4 follow-up (p <.05). Conclusions: We detected willingness of the target groups to participate, good response rates to questionnaires, adequate retention, as well as acceptability of the trial protocol. Investigation of BCT use among students helped further enhance intervention procedures to promote BCT use. After making necessary modifications identified, intervention effectiveness can next be tested in a definitive trial.Peer reviewe

Randomised controlled feasibility study of a school-based multi-level intervention to increase physical activity and decrease sedentary behaviour among vocational school students

BACKGROUND: No school-based physical activity (PA) interventions among older adolescents have demonstrated long-term effectiveness, and few of them so far have addressed sedentary behaviour (SB). Based on behavioural theories and evidence, we designed a multi-level intervention to increase PA and decrease SB among vocational school students. This study investigates feasibility and acceptability of two main intervention components and research procedures. We also examine uptake of behaviour change techniques (BCTs) by the participants. METHODS: Design was an outcome assessor blinded, cluster-randomised controlled trial. Four classes of students (matched pairs) were randomised into one intervention and one control arm. The intervention consisted of (1) a 6-h group-based intervention for students, (2) two 2-h training workshops to reduce their students' sitting in class for teachers, and (3) provision of light PA equipment in classrooms. At baseline (T1), mid-intervention (T2) at 3 weeks, post-intervention (T3) and 6 months after baseline (T4) we measured hypothesised psychosocial mediators and self-reported PA and sitting. Objective assessment of PA and SB (7-day accelerometry) was conducted at T1, T3 and T4. Body composition (bioimpedance) was measured at T1 and T4. Students and teachers in the intervention arm filled in acceptability questionnaires at T3. RESULTS: Recruitment rate was 64% (students) and 88.9% (teachers), and at T3, all post-intervention measurements were completed by 33 students (retention 76.7%) and 15 teachers (retention 93.8%). Acceptability ratings of sessions were high (students M = 6.29, scale 1-7), and data collection procedures were feasible. Intervention arm students reported increased use of BCTs, but uptake of some key BCTs was suboptimal. BCT use correlated highly with objective measures of PA. Based on both self-report and student evaluation, teachers in the intervention arm increased the use of sitting reduction strategies at post-intervention and T4 follow-up (p < .05). CONCLUSIONS: We detected willingness of the target groups to participate, good response rates to questionnaires, adequate retention, as well as acceptability of the trial protocol. Investigation of BCT use among students helped further enhance intervention procedures to promote BCT use. After making necessary modifications identified, intervention effectiveness can next be tested in a definitive trial. TRIAL REGISTRATION: ISRCTN34534846 . Registered 23 May 2014. Retrospectively registered.Background: No school-based physical activity (PA) interventions among older adolescents have demonstrated long-term effectiveness, and few of them so far have addressed sedentary behaviour (SB). Based on behavioural theories and evidence, we designed a multi-level intervention to increase PA and decrease SB among vocational school students. This study investigates feasibility and acceptability of two main intervention components and research procedures. We also examine uptake of behaviour change techniques (BCTs) by the participants. Methods: Design was an outcome assessor blinded, cluster-randomised controlled trial. Four classes of students (matched pairs) were randomised into one intervention and one control arm. The intervention consisted of (1) a 6-h group-based intervention for students, (2) two 2-h training workshops to reduce their students' sitting in class for teachers, and (3) provision of light PA equipment in classrooms. At baseline (T1), mid-intervention (T2) at 3 weeks, post-intervention (T3) and 6 months after baseline (T4) we measured hypothesised psychosocial mediators and self-reported PA and sitting. Objective assessment of PA and SB (7-day accelerometry) was conducted at T1, T3 and T4. Body composition (bioimpedance) was measured at T1 and T4. Students and teachers in the intervention arm filled in acceptability questionnaires at T3. Results: Recruitment rate was 64% (students) and 88.9% (teachers), and at T3, all post-intervention measurements were completed by 33 students (retention 76.7%) and 15 teachers (retention 93.8%). Acceptability ratings of sessions were high (students M = 6.29, scale 1-7), and data collection procedures were feasible. Intervention arm students reported increased use of BCTs, but uptake of some key BCTs was suboptimal. BCT use correlated highly with objective measures of PA. Based on both self-report and student evaluation, teachers in the intervention arm increased the use of sitting reduction strategies at post-intervention and T4 follow-up (p <.05). Conclusions: We detected willingness of the target groups to participate, good response rates to questionnaires, adequate retention, as well as acceptability of the trial protocol. Investigation of BCT use among students helped further enhance intervention procedures to promote BCT use. After making necessary modifications identified, intervention effectiveness can next be tested in a definitive trial.Peer reviewe

The association of HLA-G polymorphism with oral and genital HPV infection in men

The host genetic factors that influence the natural history of human papillomavirus (HPV) infection in men are not well known. Our aim was to evaluate the role of human leukocyte antigen (HLA)-G polymorphism in oral and genital HPV infection in men. Altogether, 130 men from the Finnish Family HPV Study, with a 6-year follow-up, were included in the analyses. HLA-G alleles were tested by direct sequencing. Oral, urethral, and semen samples were collected and analyzed for 24 different HPV genotypes. Unconditional logistic regression was used to determine associations between HLA-G alleles and genotypes with HPV infection and its outcomes. Overall, eight different HLA-G alleles were identified with 15 different HLA-G genotype combinations. The most common HLA-G allele among the men was G*01:01:01 (86.2%, n = 112) followed by G*01:01:02 (36.2%, n = 47). Allele G*01:01:02 showed to be protective against any- and high-risk (HR) oral HPV (OR range of 0.20-0.24, 95% CI range of 0.06-0.85). Men having allele G*01:01:01 showed a reduced risk for incident (OR 0.30, 95% CI 0.11-0.84) and persistent (OR 0.24, 95% CI 0.08-0.69) oral infections. Allele G*01:01:03 was associated with increased risk for urethral HR-HPV infections (OR 4.94, 95% CI 1.34-18.27). Among self-reported demographic data, genotype G*01:01:01/01:01:03 was associated with an increased risk for oral warts (OR 8.00, 95% CI 1.23-51.89) and allele G*01:03:01 increased the risk of pollen and/or animal allergy (OR 13.59, 95% CI 1.57-117.25). To conclude, HLA-G polymorphism in men largely impacts the outcome of an oral HPV infection and seems to associate with self-reported allergies.Peer reviewe

Identifying the inheritable component of human thymic T cell repertoire generation in monozygous twins

We have analyzed T cell receptor repertoires in a unique set of thymus samples from a pair of monozygotic twins. While genetics affect the V(D)J rearrangement and generation of junctional sequences, the thymic selections seem largely stochastic and import no detectable inheritable effect at clonal level.Non peer reviewe