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Objective: Chemotherapy-induced nausea and vomiting (CINV) are common with doxorubicin-cyclophosphamide (AC) chemotherapy. Recommended antiemetic regimens incorporate neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5HT3RA), corticosteroid, and dopamine antagonists. This post-hoc analysis compared results of 3 prospective antiemetic studies conducted among Chinese breast cancer patients who received (neo)adjuvant AC, in order to identify optimal antiemetic prophylaxis. Methods: A total of 304 patients were included: Group 1, ondansetron/dexamethasone (D1); Group 2, aprepitant/ondansetron/dexamethasone (D1); Group 3, aprepitant/ondansetron/dexamethasone (D1–3); Group 4, aprepitant/ondansetron/dexamethasone (D1–3)/olanzapine; and Group 5, netupitant/palonosetron/dexamethasone (D1–3). Antiemetic efficacies of Groups 3, 4, and 5 during cycle 1 of AC were individually compared with Group 1. In addition, emesis outcomes of patients in Groups 3 and 5, and those of Groups 2 and 3, were compared. Results: When comparing efficacies of a historical doublet (5HT3RA/dexamethasone) with triplet antiemetic regimens (NK1RA/5HT3RA/dexamethasone) with/without olanzapine, complete response (CR) percentages and quality of life (QOL) in overall phase of cycle 1 AC were compared between Group 1 and the other groups: Group 1 vs. 3, 41.9% vs. 38.3% (P = 0.6849); Group 1 vs. 4, 41.9% vs. 65.0% (P = 0.0107); and Group 1 vs. 5, 41.9% vs. 60.0% (P = 0.0460). Groups 4 and 5 achieved a better QOL. When comparing netupitant-based (Group 3) with aprepitant-based (Group 5) triplet antiemetics, CR percentages were 38.3% vs. 60.0%, respectively (P = 0.0176); Group 5 achieved a better QOL. When comparing 1 day (Group 2) vs. 3 day (Group 3) dexamethasone, CR percentages were 46.8% and 38.3%, respectively (P = 0.3459); Group 3 had a worse QOL. Conclusions: Aprepitant-containing triplets were non-superior to doublet antiemetics. Netupitant-containing triplets and adding olanzapine to aprepitant-containing triplets were superior to doublets. Netupitant/palonosetron/dexamethasone was superior to aprepitant/ondansetron/dexamethasone. Protracted administration of dexamethasone provided limited additional benefit.

Working memory deficits are prevalent in childhood epilepsy. Working memory processing is thought to be supported by the phase of hippocampal neural oscillations. Disruptions in working memory have previously been linked to the occurrence of transient epileptic activity. This study aimed to resolve the associations between oscillatory neural activity, transient epileptiform events, and working memory in children with epilepsy.Intracranial recordings were acquired from stereotactically implanted electrodes in the hippocampi, epileptogenic zones, and working memory-related networks of children with drug-resistant epilepsy during a 1-back working memory task. Interictal epileptic activity was captured using automated detectors. Hippocampal phase and interregional connectivity within working memory networks were indexed by Rayleigh Z and the phase difference derivative, respectively. Trials with and without transient epileptiform events were compared.Twelve children (mean age = 14.3 ± 2.8 years) with drug-resistant epilepsy were included in the study. In the absence of transient epileptic activity, significant delta and theta hippocampal phase resetting occurred in response to working memory stimulus presentation (Rayleigh z-score = 9, Rayleigh z-score = 8). Retrieval trials that were in phase with the preferred phase angle were associated with faster reaction times (p = .01, p = .03). Concurrently, delta and theta coordinated interactions between the hippocampi and working memory-related networks were enhanced (phase difference derivative [PDD] z-scores = 6-11). During retrieval trials with pre-encoding or pre-retrieval transient epileptic activity, phase resetting was attenuated (Rayleigh z-score = 5, Rayleigh z-score = 1), interregional connectivity was altered (PDD z-scores = 1-3), and reaction times were prolonged (p = .01, p = .03).This work highlights the role of hippocampal phase in working memory. We observe poststimulus hippocampal phase resetting coincident with enhanced interregional connectivity. The precision of hippocampal phase predicts optimal working memory processing, and transient epileptic activity prolongs working memory processing. These findings can help guide future treatments aimed at restoring memory function in this patient population.

Purpose: Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified by prior studies, there are only few studies evaluating risk factors associated with the contemporary antiemetic prophylaxis, including that of olanzapine/aprepitant- or NEPA- containing regimens. The present study aimed to identify the risk factors related to CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy.Methods: Data from 304 patients who were enrolled to 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with the occurrence of CINV. Additionally, likelihood of treatment failure in relation to number of risk factors of individual patient was evaluated.Results: Multivariate analysis of the entire study group revealed that obese status (defined as body mass index >/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA- containing antiemetic regimens were associated with high likelihood, while history of motion sickness was associated with lower likelihood, of complete response (CR) and ‘no nausea’ in the overall phase. History of vomiting in pregnancy was also associated with lower likelihood of overall CR. Patients with increasing number of risk factors had higher likelihood of treatment failure as well as shorter time to first vomiting. Those who did not achieve CR and ‘no nausea’ in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy.Conclusions: This present study confirmed the previously reported risk factors to be important for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxes are the preferred contemporary antiemetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy.

Introduction: Combat-related posttraumatic stress disorder (PTSD) is increasingly conceptualized in psychiatry as a disorder of dysfunctional neural circuits. Advances in neuroimaging have enabled the study of those networks non-invasively. PTSD is currently assessed using subjective self-reporting to inform crucial decisions, such as fitness to deploy, but objective markers would aid in diagnosis and return-to-deployment decisions. Methods: Magnetoencephalography (MEG) allows investigation of neural circuit function via imaging of brain waves (known as neural oscillations) that index information processing in the brain and would prove a reliable, objective, biomarker. These measures of brain function establish how regions communicate to form brain circuits that support thinking and behaviour. Results: Studies into intrinsic brain function, both during rest and when engaged in a task designed to tap into cognitive dysfunction, have found these neurobiological mechanisms are disrupted in PTSD and are a reliable objective marker of illness. We now know that these alterations in brain function are directly related to core symptoms of PTSD and comorbid cognitive-behavioural challenges. Discussion: Continued characterization of neural function using MEG and related methods will advance understanding of the neurobiology underlying PTSD; allow for the identification of biomarkers that, coupled with machine learning, will aid in diagnoses; provide individualized therapeutic targets for neurostimulation; predict treatment outcomes; and track disorder remission in military personnel and Veterans who are disproportionately affected by this devastating illness.

Background: Adjuvant chemotherapy improves outcomes of pts with early breast cancer, but CINV have been regarded as two of the most disturbing side effects, affecting their quality of life (QoL). In this study, the primary objective was to compare the efficacy of olanzapine in addition to the standard aprepitant-based antiemetic regimen for CINV in pts receiving the 1st cycle of adjuvant AC chemotherapy (adriamycin 60mg/m2 and cyclophosphamide 600mg/m2). The secondary objective was to compare the tolerability and efficacy of such regimen in the 4 cycles of AC. Methods: This is a prospective single center, randomized study. Eligible pts had early stage breast cancer of Chinese ethnicity; they were chemotherapy- naive and treated with adjuvant AC chemotherapy. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomly allocated to Olanzapine (with olanzapine) or Standard (without olanzapine) arms. Individual patient filled in self-reported diary and visual analogue scale for nausea from which information on nausea, vomiting and use of rescue medication were collected; outcomes were compared during acute phase (0-24 hrs), delay (24-120 hrs) and overall time-frame (0-120 hrs) from initiation of AC. QoL was assessed by Functional Living Index-Emesis (FLIE). Results: 120 pts were randomized. For CINV in Cycle 1 AC, outcomes of Olanzapine vs Standard arms were: complete response (acute phase 70.0 vs 51.7%, p=0.0397; delay phase 75.0 vs 45.0%, p=0.0008; overall time-frame 65.0 vs 38.3%, p=0.0035), complete protection (acute phase 70.0 vs 50.0%, p=0.0253; delay phase 71.7 vs 40.0%, p=0.0005; overall 61.7 vs 36.7%, p=0.0062), total control (acute phase 65.0 vs 41.7%, p=0.0104; delay phase 60.0 vs 31.7%, p=0.0018; overall 51.7 vs 26.7%, p=0.0050), ‘no vomiting’ (acute phase 73.3 vs 51.7%, p=0.0142; delay phase 76.7 vs 48.3%, p=0.0013; overall 68.3 vs 40.0%, p=0.0018), ‘no significant nausea’ (acute phase 95.0 vs 75.0%, p=0.0017; delay phase 91.7 vs 65.0%, p=0.0004; overall 91.7 vs 63.3%, p=0.0002),‘no nausea’ (acute phase 76.7 vs 53.3%, p=0.0074; delay phase 65.0 vs 35.0%, p=0.0010; overall 58.3 vs 33.3%, p=0.0060), and need of rescue medication (acute phase 3.3 vs 11.7%, p=0.0654; delay phase 6.7 vs 21.7%, p=0.0133; overall 8.3 vs 23.3%, p=0.0244). Assessment of FLIE on Day 6 after Cycle 1 AC between the Olanzapine vs Standard arms revealed better QOL mean scores for nausea domain (p Conclusions: In this prospective study of Chinese women with breast cancer, the addition of olanzapine to standard antiemetic regimen increases the control of CINV and improves the QoL of pts during AC chemotherapy. Funding: Madam Diana Hon Fun Kong Donation for Cancer Research. Citation Format: Winnie Yeo, Thomas KH Lau, Vicky TC Chan, Li Leung, Dong Lai, Elizabeth Pang, Maggie Cheung, Ashley Wong, Winnie MT Soo, Vanessa TY Yeung, Teresa Tse, Eva WM Yeung, Daisy CM Lam, Kenneth CW Wong, David R Johnson, Kim PK Ng, Herbert Loong, Joyce TY Ng, Florence Mok, Mimi KM Lee, Darren MC Poon, Yvonne SH Yau, Macy Tong, Joyce JS Suen, Frankie KF Mo. Randomized study to determine the efficacy of Olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV) in Chinese breast cancer patients (PTS) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-09.

Introduction: Magnetoencephalography (MEG) is a noninvasive technique that is used for presurgical evaluation of children with drug-resistant epilepsy (DRE).Areas covered: The contributions of MEG ...

Background There is limited work on the impact of chemotherapy‐induced nausea and vomiting (CINV) on quality of life (QoL) in adriamycin‐cyclophosphamide (AC)–treated patients with breast cancer. The objectives of the study were the following: (a) to confirm if symptoms of CINV led to lower QoL during AC; (b) to evaluate the pattern of changes in patients’ QoL during multiple cycles of AC; and (c) to assess if the QoL in an earlier cycle affected the QoL in subsequent cycles of AC. Materials and Methods This is a secondary pooled data analysis that included 303 Chinese patients with breast cancer who received 1,177 cycles of adjuvant AC in three prospective antiemetic studies. QoL data were based on Functional Living Index–emesis (FLIE) scored over three to four AC cycles. CINV symptoms assessed included “no significant nausea” (NSN), “significant nausea” (SN), “no vomiting” (NoV), “vomiting” (V), and complete response (CR). Results Across all AC cycles, the mean scores for the FLIE nausea domain for patients who experienced NSN versus SN were 10.92 versus 53.92, respectively (p, This article focuses on chemotherapy‐induced nausea and vomiting and quality of life of breast cancer patients through multiple cycles of treatment.

Chemotherapy-induced nausea and vomiting (CINV) are highly distressing symptoms for cancer patients undergoing cytotoxic chemotherapy. This dataset was obtained from a homogenous group of Chinese breast cancer patients who were uniformly planned to receive a highly emetogenic (neo)adjuvant chemotherapy regimen, consisting of doxorubicin and cyclophosphamide (commonly known as AC). Patients were being randomized to one of the two antiemetic regimens: aprepitant, ondansetron and dexamethasone with (the Olanzapine arm) or without olanzapine (the Standard arm). Patients underwent self-reported diaries and questionnaires to record their nausea and vomiting symptoms, use of rescue medication as well as their quality of life (QOL). The primary and secondary endpoints have focused on efficacy analysis during the first cycle of AC chemotherapy; the results have been reported in The Breast [1]. In this Data in Brief article, we provide outcome of the analysis of data collected during multiple cycles of chemotherapy. The data reported here include the proportion of patients with “Complete Response”, “Complete Protection” and “Total Control” of emesis in the acute (0–24 h), delayed (24–120 h) and overall periods (0–120 h), as well as QOL data during all the 4 cycles of AC.

Introductions For young premenopausal breast cancer patients, adjuvant chemotherapy may cause menstrual disruptions and premature menopause, which may in turn impair their quality of life (QoL). In this study among young breast cancer survivors who have undergone adjuvant chemotherapy, the objectives were to assess post-treatment menopausal symptoms and their associated factors, and to correlate these symptoms with breast cancer-specific QoL. Methods The study population included premenopausal young Chinese women with early-stage breast cancer who had undergone adjuvant chemotherapy between 3 and 10 years prior to enrolling into this study. At study entry, patients’ characteristics and clinical features were collected; each patient had detail menstrual history collected and each filled in MENQOL and FACT-B + 4 questionnaires. Results Two hundred eighty eligible patients were recruited. For adjuvant chemotherapy, 92% received anthracyclines and 28% received taxanes; 76% received adjuvant tamoxifen. At a median of 5.0 years from initial cancer diagnosis, 49 and 11% had become post- and peri-menopausal respectively. MENQOL at study entry revealed that physical domain score was worse in overweight/obese patients (mean scores for underweight/normal vs overweight/obese: 2.65 vs 2.97, p = 0.0162). Vasomotor domain score was worse in those who received taxanes or tamoxifen (taxane vs non-taxane: 2.91 vs. 2.35, p = 0.0140; tamoxifen vs no tamoxifen: 2.75 vs. 2.34, p = 0.0479). Sexual domain score was worse among those who had become peri/post-menopausal (peri/postmenopausal vs premenopausal: 2.82 vs. 2.29, p = 0.0229). On the other hand, patients who utilized traditional Chinese medicine had significantly worse scores for vasomotor, psychosocial and physical domains. Further, there was a significant association between MENQOL scores and FACT-B + 4 scores; less severe symptoms in the MENQOL domains were associated with better QoL scores in FACT-B + 4 physical, functional, psychosocial and emotional well-being, Breast Cancer Subscale, Arm Subscale and FACT-B total score. Conclusion Among premenopausal breast cancer women who had undergone adjuvant chemotherapy, those who had received taxanes or tamoxifen, were overweight/obese and utilized traditional Chinese medicine had more severe menopausal symptoms. Patients who experienced worse menopausal symptoms were found to have worse breast cancer-specific QoL. Interventional studies with an aim to alleviate menopausal symptoms are warranted to assess if overall QoL of these patients could be improved. Trial registration Not applicable.

Singapore’s participation in the Second International Science Study (SISS) in the 1980s marks the beginning of nearly four decades of involvement in IEA studies. International large-scale assessments (ILSAs) play an important role in complementing other information sources to inform policymakers about different aspects of the Singapore education system. The insights derived from these studies have at times served as reassurances to policymakers and program designers that progress has been made in some areas and, at other times, identified where improvements could be made. Participating in ILSAs has proved useful for Singapore. The Singapore Ministry of Education has used data from PIRLS and TIMSS for system-level monitoring and secondary analyses of the data have provided insights to inform policymaking and program development; here three actual use cases are used to illustrate the impact of ILSA in Singapore. These cases cover uses ranging from catalyzing curriculum redesign, to monitoring the implementation of a new pedagogical approach to learning science, to keeping tabs on any trade-offs from the bold, system-wide curricular and pedagogical shifts adopted. As a result of this long history of participation, the Singapore Ministry of Education has developed general principles guiding the use of data from large-scale assessments, which provide a useful framework for those interested in international efforts to improve education for all.

The Organization for Human Brain Mapping (OHBM) has been active in advocating for the instantiation of best practices in neuroimaging data acquisition, analysis, reporting and sharing of both data and analysis code to deal with issues in science related to reproducibility and replicability. Here we summarize recommendations for such practices in magnetoencephalographic (MEG) and electroencephalographic (EEG) research, recently developed by the OHBM neuroimaging community known by the abbreviated name of COBIDAS MEEG. We discuss the rationale for the guidelines and their general content, which encompass many topics under active discussion in the field. We highlight future opportunities and challenges to maximizing the sharing and exploitation of MEG and EEG data, and we also discuss how this 'living' set of guidelines will evolve to continually address new developments in neurophysiological assessment methods and multimodal integration of neurophysiological data with other data types.The Organization for Human Brain Mapping presents its best practices report for reproducible EEG and MEG research, highlighting issues and main recommendations in this Perspective.

The study reported in this paper was part of a large project that examined Singaporean children’s biliteracy development. The project was supported by a grant from the Office of Education Research of National Institute of Education, Nanyang Technological University (grant number: OER 24/10 ZDB). No views expressed in this paper represent those of the funding agency or any author’s affiliated organization.

Millions of North Americans sustain a concussion or a mild traumatic brain injury annually, and are at risk of cognitive, emotional, and physical sequelae. Although functional MRI (fMRI) studies have provided an initial framework for examining functional deficits induced by concussion, particularly working memory and attention, the temporal dynamics underlying these deficits are not well understood. We used magnetoencephalography (MEG), a modality with millisecond temporal resolution, in conjunction with a 1-back visual working memory (VWM) paradigm using scenes from everyday life to characterize spatiotemporal functional differences at specific VWM stages, in adults had had or had not had a recent concussion. MEG source-level differences between groups were determined by whole-brain analyses during encoding and recognition phases. Despite comparable behavioral performance, abnormal hypo- and hyperactivation patterns were found in brain areas involving frontoparietal, ventral occipitotemporal, temporal, and subcortical areas in concussed patients. These patterns and their timing varied as a function of VWM stagewise processing, linked to early attentional control, visuoperceptual scene processing, and VWM maintenance and retrieval processes. Parietal hypoactivation, starting at 60 ms during encoding, was correlated with symptom severity, possibly linked to impaired top-down attentional processing. Hyperactivation in the scene-selective occipitotemporal areas, the medial temporal complex, specifically the right hippocampus and orbitofrontal areas during encoding and/or recognition, lead us to posit inefficient but compensatory visuoperceptual, relational, and retrieval processing. Although injuries sustained after the concussion were considered "mild," these data suggest that they can have prolonged effects on early attentional and VWM processes.

Very preterm (VPT) birth (

Background: In this cohort study, the objectives were to determine bone mineral density (BMD) and potential associated factors for bone health among young premenopausal patients after adjuvant chemotherapy. Methods: Eligibility criteria included premenopausal Chinese aged Results: A total of 271 patients entered the study. The median time from breast cancer diagnosis to study entry was 5.0 years. The median ages at breast cancer diagnosis and at study entry were 41 and 47 years, respectively. The median BMDs for femoral neck (FN) and lumbar spine (LS) were 0.72 and 0.91 g/cm2, respectively; 40.2% had abnormal Z-scores (defined as ≤–1) and 50.2% had osteopenia/osteoporosis of either FN or LS. On multivariate analyses, factors that were identified to have a positive association with bone health (higher BMD) included higher family income (OR [95% CI] for LS = 1.573 [1.091–2.268]), taller stature (OR for LS = 2.975 [1.723–5.137]), and higher BMI (OR for FN = 2.156 [1.599–2.907]), while negatively associated factors included longer interval since last adjuvant treatment (OR for LS: 0.435 [0.250–0.757]), peri-/postmenopausal status at study entry (OR for LS = 0.443 [0.255–0.768]; OR for FN = 0.353 [0.205–0.609]), and having received adjuvant tamoxifen (OR for FN = 0.452 [0.243–0.841]). Conclusion: About 5 years after breast cancer diagnosis and adjuvant chemotherapy, >50% of premenopausal patients who had received adjuvant chemotherapy were detected to have osteopenia/osteoporosis and 40% had abnormal Z-scores for FN/LS.

Objectives Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine. Patients and methods Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored. Results 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of “Complete Response” than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of “No significant nausea” and “No nausea” during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment. Conclusion The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted., Highlights • Olanzapine is reported to reduce nausea and vomiting after highly emetogenic chemotherapy. • Reported studies are limited by heterogeneous populations receiving diverse cytotoxic regimes. • This study enrolled Chinese breast cancer patients undergoing doxorubicin/cyclophosphamide. • Adding olanzapine to aprepitant/ondansetron/dexamethasone is superior in controlling nausea and vomiting. • Baseline investigations shows a surprisingly high rate of glucose and lipids abnormalities.

OBJECTIVE Vagus nerve stimulation (VNS) is a common treatment for medically intractable epilepsy, but response rates are highly variable, with no preoperative means of identifying good candidates. This study aimed to predict VNS response using structural and functional connectomic profiling. METHODS Fifty-six children, comprising discovery (n = 38) and validation (n = 18) cohorts, were recruited from 3 separate institutions. Diffusion tensor imaging was used to identify group differences in white matter microstructure, which in turn informed beamforming of resting-state magnetoencephalography recordings. The results were used to generate a support vector machine learning classifier, which was independently validated. This algorithm was compared to a second classifier generated using 31 clinical covariates. RESULTS Treatment responders demonstrated greater fractional anisotropy in left thalamocortical, limbic, and association fibers, as well as greater connectivity in a functional network encompassing left thalamic, insular, and temporal nodes (p

Introduction: Neonatal arterial ischemic stroke (NAIS) is the most common form of childhood stroke. Unlike adults with stroke, children with left middle cerebral artery (MCA) NAIS seldom become aphasic, although adolescence often reveals the emergence of higher-order language deficits. Functional language networks may be predictive of later-emerging language outcomes, and can aid to identify at-risk children with NAIS. Methods: Five neurotypical children (2F; 5 RH; mean 12.7 ± 2.6 years), and five children with unilateral-MCA NAIS (3F; 5 RH; mean 11.3 ± 2.0 years) listened to semantically correct and incorrect sentences while magnetoencephalography (MEG) was recorded. Task-related functional connectivity was calculated using the phase lag index (PLI) across regions of interest. The relationship between the functional brain networks and language skill was examined. Results: Neurotypical children showed increased global functional connectivity for semantically correct sentences 1.8 to 2.0 seconds from stimulus onset in the theta band (4-7 Hz; p p p Conclusions: These results suggest reorganization of expected unilateral and frontal language networks towards a bilateral and temporal distribution following stroke, with less reliance on traditional language nodes. Such reorganization may underlie the language ability trajectory of children with neonatal MCA stroke. Reorganization of functional brain networks may be used as a predictive marker for language development following neonatal stroke, which can ultimately guide precision medicine and improve long-term outcomes.

Background and Purpose— Neurocognitive deficits are common among survivors of aneurysmal subarachnoid hemorrhage, even among those with good outcomes and no structural lesions. This study aims to probe the neurophysiological underpinnings of cognitive dysfunction among patients with ruptured intracranial aneurysms using magnetoencephalography (MEG). Methods— Thirteen patients who had undergone uncomplicated coiling for aneurysmal subarachnoid hemorrhage and 13 matched controls were enrolled. Neuropsychological tests were done before magnetoencephalography scans. Magnetoencephalography data were acquired in a 151-channel, whole-head magnetoencephalography system for resting state and 2 cognitive tasks (go-no-go and set-shifting). Mean time from treatment to test was 18.8 months. Results— Cognitive tasks of inhibition (go-no-go) indicated greater activation in the right anterior cingulate and inferior frontal gyrus, and cognitive set-shifting tasks (mental flexibility) indicated greater activity in the bilateral anterior cingulate cortex and right medial frontal gyrus among aneurysmal subarachnoid hemorrhage patients, with significantly different timing of activation between groups. Resting-state, beta-band connectivity of the anterior cingulate correlated negatively with Montreal Cognitive Assessment scores (left: r =−0.56; P r =−0.55; P Conclusions— We have shown increased activation in areas of the anterior cingulate gyrus and frontobasal regions during the execution of more demanding tasks in good grade. The degree of activation in the anterior cingulate gyrus has a negative correlation with cognitive (Montreal Cognitive Assessment) scores. These subtle differences may be related to the common neurocognitive and behavioral complaints seen in this patient population.

Synchronization of oscillations among brain areas is understood to mediate network communication supporting cognition, perception, and language. How task-dependent synchronization during word production develops throughout childhood and adolescence, as well as how such network coherence is related to the development of language abilities, remains poorly understood. To address this, we recorded magnetoencephalography while 73 participants aged 4–18 years performed a verb generation task. Atlas-guided source reconstruction was performed, and phase synchronization among regions was calculated. Task-dependent increases in synchronization were observed in the theta, alpha, and beta frequency ranges, and network synchronization differences were observed between age groups. Task-dependent synchronization was strongest in the theta band, as were differences between age groups. Network topologies were calculated for brain regions associated with verb generation and were significantly associated with both age and language abilities. These findings establish the maturational trajectory of network synchronization underlying expressive language abilities throughout childhood and adolescence and provide the first evidence for an association between large-scale neurophysiological network synchronization and individual differences in the development of language abilities.

Non-invasive neuroimaging methods, including magnetoencephalography and electroencephalography (MEEG), have been critical in advancing the understanding of brain function in healthy people and in individuals with neurological or psychiatric disorders. Currently, scientific practice is undergoing a tremendous change, aiming to improve both research reproducibility and transparency in data collection, documentation and analysis, and in manuscript review. To advance the practice of open science, the Organization for Human Brain Mapping created the Committee on Best Practice in Data Analysis and Sharing (COBIDAS), which produced a report for MRI-based data in 2016. This effort continues with the OHBM’s COBIDAS MEEG committee whose task was to create a similar document that describes best practice recommendations for MEEG data. The document was drafted by OHBM experts in MEEG, with input from the world-wide brain imaging community, including OHBM members who volunteered to help with this effort, as well as Executive Committee members of the International Federation for Clinical Neurophysiology. This document outlines the principles of performing open and reproducible research in MEEG. Not all MEEG data practices are described in this document. Instead, we propose principles that we believe are current best practice for most recordings and common analyses. Furthermore, we suggest reporting guidelines for Authors that will enable others in the field to fully understand and potentially replicate any study. This document should be helpful to Authors, Reviewers of manuscripts, as well as Editors of neuroscience journals.

Highlights • First MEG study of neural underpinnings of theory of mind differences in autism. • Children with autism show decreased LTPJ activity from 300 to 375 and 425 to 500 ms. • Children with autism also show increased RIFG activity from 325 to 375 ms. • Co-incident lower LTPJ and higher RIFG activity implies compensatory use of RIFG. • Executive functions may augment impaired theory of mind in autism., The social impairments observed in children with autism spectrum disorder are thought to arise in part from deficits in theory of mind, the ability to understand other people’s thoughts and feelings. To determine the temporal-spatial dynamics of brain activity underlying these atypical theory-of-mind processes, we used magnetoencephalography to characterize the sequence of functional brain patterns (i.e. when and where) related to theory-of-mind reasoning in 19 high-functioning children with autism compared to 22 age- and sex-matched typically-developing children aged 8–12 during a false-belief (theory-of-mind) task. While task performance did not differ between the two groups, children with autism showed reduced activation in the left temporoparietal junction between 300–375 and 425–500 ms, as well as increased activation in the right inferior frontal gyrus from 325 to 375 ms compared to controls. The overlap in decreased temporoparietal junction activity and increased right inferior frontal gyrus activation from 325 to 375 ms suggests that in children with autism, the right inferior frontal gyrus may compensate for deficits in the temporoparietal junction, a neural theory-of-mind network hub. As the right inferior frontal gyrus is involved in inhibitory control, this finding suggests that children with autism rely on executive functions to bolster their false-belief understanding.

Winnie Yeo,1,2 Frankie KF Mo,1,2 Elizabeth Pang,1,2 Joyce JS Suen,1 Jane Koh,1,2 Claudia HW Yip,1 Christopher CH Yip,1 Leung Li,1 Herbert HF Loong,1,2 Giok S Liem1 1Department of Clinical Oncology, Sir YK Pao Centre for Cancer, Prince of Wales Hospital, 2Hong Kong Cancer Institute, State Key Laboratory of Oncology in South China, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong Introduction: Understanding of quality of life (QoL) of young Chinese breast cancer patients after adjuvant cytotoxic chemotherapy is limited. This study aims to assess the QoL of premenopausal Chinese breast cancer women after receiving adjuvant chemotherapy.Patients and methods: Eligibility criteria included stage I–III breast cancer, premenopausal and age ≤45 years at cancer diagnosis and having received adjuvant chemotherapy within 3–10 years before entry to the present study. Patients’ background demographics at the time of breast cancer diagnosis, together with tumor characteristics and anticancer treatments, were collected. At the time of study entry, the menopausal status based on menstrual history, body mass index, and QoL (assessed using Functional Assessment of Cancer Therapy-Breast +4) were recorded.Results: Two hundred and eighty patients were recruited. Ninety-five patients (33.9%) underwent breast-conserving surgery, and nearly all (98.6%) underwent axillary dissection. For adjuvant therapies, 249 patients (88.9%) received anthracycline-containing chemotherapy and 79 (28.2%) received taxane-containing chemotherapy, while 68 (24.3%) received both. One hundred and eighty six patients (66.4%) received adjuvant radiotherapy, and 214 (76.4%) received adjuvant tamoxifen. The median time from breast cancer diagnosis to study entry was 5.01 years. QoL assessment at study entry revealed that older patients had worse social well-being (SWB; mean scores for age ≤40, 41–45, 46–50 and >50 years were 22.0, 19.3, 19.1 and 18.1, respectively, P=0.0442). Patients who underwent axillary dissection had worse scores for breast cancer subscale (BCS; mean score 22.2 vs. 28.3, P=0.0212). Patients who underwent taxane-containing chemotherapy had worse scores for arm subscale (mean score 13.8 vs. 15.3, P=0.0053).Conclusion: At a median follow-up of 5 years post-diagnosis, patients who were younger had fewer disturbances in their SWB. Patients who had axillary dissection had worse BCS scores, while those who received taxane had worse scores for arm subscale. Further studies are warranted for breast-specific QoL to address the specific issues encountered by breast cancer patients. Keywords: cytotoxic, QoL, FACT-B+4, cancer survivors breast, premenopausal

Soldiers with post-traumatic stress disorder (PTSD) exhibit elevated gamma-band synchrony in left fronto-temporal cortex, and connectivity measures in these regions correlate with comorbidities and PTSD severity, which suggests increased gamma synchrony is related to symptomology. However, little is known about the role of intrinsic, phase-synchronised networks in the disorder. Using magnetoencephalography (MEG), we characterised spectral connectivity in the default-mode, salience, visual, and attention networks during resting-state in a PTSD population and a trauma-exposed control group. Intrinsic network connectivity was examined in canonical frequency bands. We observed increased inter-network synchronisation in the PTSD group compared with controls in the gamma (30–80Hz) and high-gamma range (80–150Hz). Analyses of connectivity and symptomology revealed that PTSD severity was positively associated with beta synchrony in the ventral-attention-to-salience networks, and gamma synchrony within the salience network, but also negatively correlated with beta synchrony within the visual network. These novel results show that frequency-specific, network-level atypicalities may reflect trauma-related alterations of ongoing functional connectivity, and correlations of beta synchrony in attentional-to-salience and visual networks with PTSD severity suggest complicated network interactions mediate symptoms. These results contribute to accumulating evidence that PTSD is a complicated network-based disorder expressed as altered neural interactions.

Background Mounting evidence suggests that autism is a network disorder, characterized by atypical brain connectivity, especially in the context of high level cognitive processes such as working memory (WM). Accordingly, atypical WM processes have been related to the social and cognitive deficits observed in children with autism spectrum disorder (ASD). Methods We used magnetoencephalography (MEG) to investigate connectivity differences during a high memory load (2-back) WM task between 17 children with ASD and 20 age-, sex-, and IQ-matched controls. Results We identified reduced inter-regional alpha-band (9-15 Hz) phase synchronization in children with ASD during the WM task. Reduced WM-related brain synchronization encompassed fronto-temporal networks (ps

This pilot study investigated the benefits of adjunctive psychological intervention for smokers accessing standard smoking cessation interventions. Chronic obstructive pulmonary disease (COPD) smokers attending a smoking cessation service were offered up to 12 adjunctive clinical psychology sessions. Baseline data included demographics, smoking history, and disease severity. Outcomes included attendance and quit rate. In all, 59 patients with moderate COPD were referred. Of the 20 patients who attended training sessions, 7 (35%) were relapse prevention referrals and 13 (65%) were current smokers. Of the seven relapse prevention referrals, six (86%) maintained their quit, 2 of 13 (15%) of the current smoker group maintained a 28-day quit and 3 of 13 (23%) of current smokers reduced their tobacco intake. For COPD smokers with a heavy smoking history and multiple past quit attempts, there was insufficient evidence to show that additional psychological intervention leads to higher quit rates. Significant barriers to quitting and complex medical and psychosocial needs were identified in this group, suggesting that the current ‘one-size-fits-all’ approach to smoking cessation may not be sufficient to meet the needs of such a complex group.

BackgroundConcussion is a common form of mild traumatic brain injury (mTBI). Despite the descriptor ‘mild’, a single injury can leave long-lasting and sustained alterations to brain function, including changes to localised activity and large-scale interregional communication. Cognitive complaints are thought to arise from such functional deficits. We investigated the impact of injury on neurophysiological and functionally-specialised resting networks, known as intrinsic connectivity networks (ICNs), using MEG.MethodsWe assessed neurophysiological connectivity in 40 males, 20 with concussion, 20 without, using MEG. Regions-of-interest that comprise nodes of ICNs were defined, and their time courses derived using a beamformer approach. Pairwise fluctuations and covariations in band-limited amplitude envelopes were computed reflecting measures of functional connectivity. Intra-network connectivity was compared between groups using permutation testing, and correlated with symptoms.ResultsWe observed increased resting spectral connectivity in the default mode and motor networks in our concussion group when compared with controls, across alpha through gamma ranges. Moreover, these differences were not explained by power spectrum density (absolute changes in the spectral profiles within the ICNs). Furthermore, this increased coupling was significantly associated with symptoms in the DMN and MOT networks – but once accounting for comorbid symptoms (including, depression, anxiety, and ADHD) only the DMN continued to be associated with symptoms.ConclusionThe DMN network plays a critical role in shifting between cognitive tasks. These data suggest even a single concussion can perturb the intrinsic coupling of functionally-specialised networks in the brain and may explain persistent and wide-ranging symptomatology.

Concussion induces transient, and oftentimes chronic, lingering impairment to mental functioning, which must be driven by some underlying neurobiological perturbation - however, the physical changes related to sequelae are difficult to detect. Previous imaging studies on concussion have focused on alterations to cortical anatomy, but few have examined the cerebrum, subcortex, and cerebellum. Here, we present an analysis of these structures in a single cohort (all males, 21 patients, 22 controls) using MRI and diagnosed with a single-concussive episode in the acute and sub-acute stages of injury. Structural images were segmented into 78 cortical brain regions and 81,924 vertices using the CIVET algorithm. Subcortical volumetric analyses of the cerebellum, thalamus, globus pallidus, caudate and putamen were conducted following segmentation. Participants with concussion were found to have reduced white and grey matter volume, total cortical volume, as well as cortical thinning, primarily in left frontal areas. No differences were observed in the cerebellum or subcortical structures. In conclusion, just a single concussive episode induces measurable changes in brain structure manifesting as diffuse and local patterns of altered neuromorphometry.

Smoking cessation is the most cost-effective intervention for the prevention and treatment of smoking-related disease. Here, the authors discuss the available products for aiding smoking cessation and how to support patients wishing to quit.

It is well supported by behavioral and neuroimaging studies that typical language function is lateralized to the left hemisphere in the adult brain and this laterality is less well defined in children. The behavioral literature suggests there maybe be sex differences in language development but this has not been examined systematically using neuroimaging. In this study, magnetoencephalography (MEG) was used to investigate the spatiotemporal patterns of language lateralization as a function of age and sex. Eighty typically developing children (46 females; 4–18 years) participated in an overt visual verb generation task. An analysis method called differential beamforming was used to analyse language-related changes in oscillatory activity referred to as low-gamma event-related desynchrony (ERD). The proportion of ERD over language areas relative to total ERD was calculated. We found different patterns of laterality between boys and girls. Boys showed left hemisphere lateralization in the frontal and temporal language-related areas across age groups, whereas girls showed a more bilateral pattern, particularly in frontal, language related, areas. Differences in patterns of ERD were most striking between boys and girls in the younger age groups and these patterns became more similar with increasing age, specifically in the pre-teen years. Our findings show sex differences in language lateralization during childhood; however, these differences do not seem to persist into adulthood. We present possible explanations for these differences. We also discuss the implications of these findings for pre-surgical language mapping in children and highlight the importance of examining the question of sex-related language differences across development.

Background: Singapore needs to prepare for a rapidly ageing population in the next one to two decades. By 2030, the number of seniors aged 65 years and above will almost double in number to comprise a quarter of Singaporeans. Diseases are on the rise due to aging population, by 2030, 1 in 7 adults aged 18 to 69 years will have diabetes, 1 in 220 residents to have a heart attack, 1 in 180 residents to be diagnosed with a cancer and 1 in 230 residents to have a stroke. One big effect of this demographic clustering will be a shift in disease patterns towards chronic diseases. Objectives: This preventive health programme was designed to bring services closer to seniors to promote health and wellness in the community. Content: There are two forms of Community Health Post targeted at seniors with existing chronic diseases and those who are at risk of developing common chronic diseases. The first form of the health post provides one-to-one health coaching sessions based on a suite of health-related topics and are individualized to the needs of the individuals. This is conducted by the nurse educator. The second form of the health post comprises of group sessions which are conducted by a nurse educator, and supported by other professionals from the hospital. The group sessions aim to build on peer-motivation and support and to provide more disease-specific information focusing on self-management. Methodology: A two-week curriculum is planned for the group sessions, each lasting two hours, and conducted in the format of a workshop, with more than 30 participants per session. Health coaching topics may include: Nutrition & diet, Physical activities and falls, mental wellness, personal hygiene and chronic diseases related education talks. The group sessions are structured in a fun and interactive manner to build interest in the seniors and increase their commitment to return for all sessions and gain confidence in taking charge of their health. Conclusion: The evaluation of the Community Health Posts would provide more insights on the effectiveness of the programme as well as the areas of needs of the senior residents in preventive health.

Background Adjuvant chemotherapy improves outcome of patients with early breast cancer. However, chemotherapy may be associated with long term toxicities. In this retrospective cohort study, the objectives were to determine body weight, body mass index (BMI), blood pressure and fasting lipids levels of young premenopausal Chinese breast cancer patients after adjuvant chemotherapy. Potential factors associated with these parameters were identified. Methods Eligibility criteria include premenopausal Chinese patients who were diagnosed to have stage I-III breast cancer within 3–10 years, age 2%; 52.1% were overweight/obese; 30.7% had hypertension. Abnormal total-cholesterol and LDL-cholesterol occurred in 34.3% and 56.1% respectively. On multivariate analyses, older age was associated with reduced risk while occurrence of CRA and having received taxane-containing regimens were associated with increased risk of weight gain. Oestrogen-receptor positivity was associated with reduced risk while overweight/obese statuses were associated with increased risk of hypertension. Use of tamoxifen was associated with reduced risk of abnormal LDL-cholesterol. Weight gain, overweight/obese, older age, progression to post/peri-menopausal status at study entry, having received corticosteroid premedication before adjuvant chemotherapy and having received taxane-containing adjuvant chemotherapy were associated with increased risk of dyslipidaemias. Conclusion Among young premenopausal Chinese breast cancer patients who had received adjuvant chemotherapy, the current study has revealed that although there was only a median weight gain of 1.8 kg, there was a nearly 60% increase in abnormal BMI. Further, a significant proportion of patients were detected to have hypertension and dyslipidaemias. Interventional studies with lifestyle modifications are warranted. Electronic supplementary material The online version of this article (doi:10.1186/s12905-017-0409-8) contains supplementary material, which is available to authorized users.

Post-traumatic stress disorder (PTSD) is an anxiety disorder arising from exposure to a traumatic event. Although primarily defined in terms of behavioral symptoms, the global neurophysiological effects of traumatic stress are increasingly recognized as a critical facet of the human PTSD phenotype. Here we use magnetoencephalographic recordings to investigate two aspects of information processing: inter-regional communication (measured by functional connectivity) and the dynamic range of neural activity (measured in terms of local signal variability). We find that both measures differentiate soldiers diagnosed with PTSD from soldiers without PTSD, from healthy civilians, and from civilians with mild traumatic brain injury, which is commonly comorbid with PTSD. Specifically, soldiers with PTSD display inter-regional hypersynchrony at high frequencies (80–150 Hz), as well as a concomitant decrease in signal variability. The two patterns are spatially correlated and most pronounced in a left temporal subnetwork, including the hippocampus and amygdala. We hypothesize that the observed hypersynchrony may effectively constrain the expression of local dynamics, resulting in less variable activity and a reduced dynamic repertoire. Thus, the re-experiencing phenomena and affective sequelae in combat-related PTSD may result from functional networks becoming “stuck” in configurations reflecting memories, emotions, and thoughts originating from the traumatizing experience.SIGNIFICANCE STATEMENTThe present study investigates the effects of post-traumatic stress disorder (PTSD) in combat-exposed soldiers. We find that soldiers with PTSD exhibit hypersynchrony in a circuit of temporal lobe areas associated with learning and memory function. This rigid functional architecture is associated with a decrease in signal variability in the same areas, suggesting that the observed hypersynchrony may constrain the expression of local dynamics, resulting in a reduced dynamic range. Our findings suggest that the re-experiencing of traumatic events in PTSD may result from functional networks becoming locked in configurations that reflect memories, emotions, and thoughts associated with the traumatic experience.

Breast cancer patients regularly undergo adjuvant chemotherapies following surgery. However, these treatments are largely associated with chemotherapeutic toxicities ranging from nausea to severe myelosuppression. In this investigation, we examined the effects of four SNPs in NR1I2, CYP3A4 and CYP3A5 genes on chemotherapy-induced severe neutropenia in 311 female Chinese breast cancer patients undergoing a standard adjuvant chemotherapy regimen.Patients were monitored for adverse reactions throughout the treatment, then divided into "none or mild" (80 %) or "severe" (20 %) toxicity groups according to whether they suffered grade 4 neutropenia defined as having an absolute neutrophil counts (ANC) of less than 0.5 × 10(9)/L anytime during the treatment. DNA was extracted from patients' peripheral blood samples, then genotyped using allele-specific Tm-shift PCR and melting analysis.Logistic regression revealed that rs776746 or CYP3A5*3 strongly associated with grade 4 neutropenia (OR = 2.56, P = 0.023) after adjustment for covariates, one of which more significant factor was baseline ANC (OR = 0.68, P = 0.020). Although univariate analysis in all patients did not reveal any association at first, further analysis indicated that rs776746 is significantly associated with severe neutropenia in subgroup of breast cancer patients with normal baseline ANC (≥2.0 × 10(9)/L). These carriers of A-allele have 3.14-fold increased risk of developing severe neutropenia (P = 0.004).Our results suggested that polymorphisms in CYP3A5 might be useful pharmacogenetic markers for the prediction of severe neutropenia during chemotherapy, however, only after screening patients by their baseline ANC in the presence of gene-environmental interaction. We demonstrate an approach of pharmacogenetic analysis, in which the genetic data should be analyzed in the perspective of other clinical parameters.