Dynamic Reconfiguration of Brain Functional Network in Stroke

The brain continually reorganizes its functional network to adapt to post-stroke functional impairments. Previous studies using static modularity analysis have presented global-level behavior patterns of this network reorganization. However, it is far from understood how the brain reconfigures its functional network dynamically following a stroke. This study collected resting-state functional MRI data from 15 stroke patients, with mild (n = 6) and severe (n = 9) two subgroups based on their clinical symptoms. Additionally, 15 age-matched healthy subjects were considered as controls. By applying a multilayer network method, a dynamic modular structure was recognized based on a time-resolved function network. Then dynamic network measurements (recruitment, integration, and flexibility) were calculated to characterize the dynamic reconfiguration of post-stroke brain functional networks, hence, to reveal the neural functional rebuilding process. It was found from this investigation that severe patients tended to have reduced recruitment and increased between-network integration, while mild patients exhibited low network flexibility and less network integration. It is also noted that this severity-dependent alteration in network interaction was not able to be revealed by previous studies using static methods. Clinically, the obtained knowledge of the diverse patterns of dynamic adjustment in brain functional networks observed from the brain signal could help understand the underlying mechanism of the motor, speech, and cognitive functional impairments caused by stroke attacks. The proposed method not only could be used to evaluate patients' current brain status but also has the potential to provide insights into prognosis analysis and prediction

Dynamic Reconfiguration of Brain Functional Network in Stroke

The brain continually reorganizes its functional network to adapt to post-stroke functional impairments. Previous studies using static modularity analysis have presented global-level behavior patterns of this network reorganization. However, it is far from understood how the brain reconfigures its functional network dynamically following a stroke. This study collected resting-state functional MRI data from 15 stroke patients, with mild (n = 6) and severe (n = 9) two subgroups based on their clinical symptoms. Additionally, 15 age-matched healthy subjects were considered as controls. By applying a multilayer network method, a dynamic modular structure was recognized based on a time-resolved function network. Then dynamic network measurements (recruitment, integration, and flexibility) were calculated to characterize the dynamic reconfiguration of post-stroke brain functional networks, hence, to reveal the neural functional rebuilding process. It was found from this investigation that severe patients tended to have reduced recruitment and increased between-network integration, while mild patients exhibited low network flexibility and less network integration. It is also noted that this severity-dependent alteration in network interaction was not able to be revealed by previous studies using static methods. Clinically, the obtained knowledge of the diverse patterns of dynamic adjustment in brain functional networks observed from the brain signal could help understand the underlying mechanism of the motor, speech, and cognitive functional impairments caused by stroke attacks. The proposed method not only could be used to evaluate patients' current brain status but also has the potential to provide insights into prognosis analysis and prediction

Dynamic Reconfiguration of Brain Functional Network in Stroke

The brain continually reorganizes its functional network to adapt to post-stroke functional impairments. Previous studies using static modularity analysis have presented global-level behavior patterns of this network reorganization. However, it is far from understood how the brain reconfigures its functional network dynamically following a stroke. This study collected resting-state functional MRI data from 15 stroke patients, with mild (n = 6) and severe (n = 9) two subgroups based on their clinical symptoms. Additionally, 15 age-matched healthy subjects were considered as controls. By applying a multilayer temporal network method, a dynamic modular structure was recognized based on a time-resolved function network. The dynamic network measurements (recruitment, integration, and flexibility) were calculated to characterize the dynamic reconfiguration of post-stroke brain functional networks, hence, revealing the neural functional rebuilding process. It was found from this investigation that severe patients tended to have reduced recruitment and increased between-network integration, while mild patients exhibited low network flexibility and less network integration. It's also noted that previous studies using static methods could not reveal this severity-dependent alteration in network interaction. Clinically, the obtained knowledge of the diverse patterns of dynamic adjustment in brain functional networks observed from the brain neuronal images could help understand the underlying mechanism of the motor, speech, and cognitive functional impairments caused by stroke attacks. The present method not only could be used to evaluate patients' current brain status but also has the potential to provide insights into prognosis analysis and prediction.</p

Tracking functional network connectivity dynamics in the elderly

IntroductionFunctional magnetic resonance imaging (fMRI) has shown that aging disturbs healthy brain organization and functional connectivity. However, how this age-induced alteration impacts dynamic brain function interaction has not yet been fully investigated. Dynamic function network connectivity (DFNC) analysis can produce a brain representation based on the time-varying network connectivity changes, which can be further used to study the brain aging mechanism for people at different age stages.MethodThis presented investigation examined the dynamic functional connectivity representation and its relationship with brain age for people at an elderly stage as well as in early adulthood. Specifically, the resting-state fMRI data from the University of North Carolina cohort of 34 young adults and 28 elderly participants were fed into a DFNC analysis pipeline. This DFNC pipeline forms an integrated dynamic functional connectivity (FC) analysis framework, which consists of brain functional network parcellation, dynamic FC feature extraction, and FC dynamics examination.ResultsThe statistical analysis demonstrates that extensive dynamic connection changes in the elderly concerning the transient brain state and the method of functional interaction in the brain. In addition, various machine learning algorithms have been developed to verify the ability of dynamic FC features to distinguish the age stage. The fraction time of DFNC states has the highest performance, which can achieve a classification accuracy of over 88% by a decision tree.DiscussionThe results proved there are dynamic FC alterations in the elderly, and the alteration was found to be correlated with mnemonic discrimination ability and could have an impact on the balance of functional integration and segregation

New discrete and polymeric supramolecular architectures derived from dinuclear Co(II), Ni(II) and Cu(II) complexes of aryl-linked bis-beta-diketonato ligands and nitrogen bases: synthetic, structural and high pressure studies

New examples of nitrogen base adducts of dinuclear Co(II), Ni(II) and Cu(II) complexes of the doubly deprotonated forms of 1,3-aryl linked bis-β-diketones of type [RC([double bond, length as m-dash]O)CH2C([double bond, length as m-dash]O)C6H4C([double bond, length as m-dash]O)CH2C([double bond, length as m-dash]O)R] (L1H2) incorporating the mono- and difunctional amine bases pyridine (Py), 4-ethylpyridine (EtPy), piperidine (pipi), 1,4-piperazine (pip), N-methylmorpholine (mmorph), 1,4-dimethylpiperazine (dmpip) and N,N,N′,N′-tetramethylethylenediamine (tmen) have been synthesised by reaction of the previously reported [Cu2(L1)2]·2.5THF (R = Me), [Cu2(L1)2(THF)2] (R = t-Bu), [Ni2(L1)2(Py)4] (R = t-Bu) and [Co2(L1)2(Py)4] (R = t-Bu) complexes with individual bases of the above type. Comparative X-ray structural studies involving all ten base adduct derivatives have been obtained and reveal a range of interesting discrete and polymeric molecular architectures. The respective products have the following stoichiometries: [Cu2(L1)2(Py)2]·Py (R = Me), [Cu2(L1)2(EtPy)2]·2EtPy (R = t-Bu), [Cu2(L1)2(pipi)2]·2pipi (R = t-Bu), [Cu2(L1)2(mmorph)2] (R = t-Bu), [Cu2(L1)2(tmen)2] (R = t-Bu) and {[Cu2(L1)2(pip)]·pip·2THF}n, [Co2(L1)2(tmen)2] (R = t-Bu), [Ni2(L1)2(Py)4]·dmpip (R = t-Bu), [Ni2(L1)2(pipi)4]·pipi (R = t-Bu) and [Ni2(L1)2(tmen)2] (R = t-Bu). The effect of pressure on the X-ray structure of [Cu2(L1)2(mmorph)2] has been investigated. An increase in pressure from ambient to 9.1 kbar resulted in modest changes to the unit cell parameters as well as a corresponding decrease of 6.7 percent in the unit cell volume. While a small ‘shearing’ motion occurs between adjacent molecular units throughout the lattice, no existing bonds are broken or new bonds formed

How are Australian higher education institutions contributing to change through innovative teaching and learning in virtual worlds?

Over the past decade, teaching and learning in virtual worlds has been at the forefront of many higher education institutions around the world. The DEHub Virtual Worlds Working Group (VWWG) consisting of Australian and New Zealand higher education academics was formed in 2009. These educators are investigating the role that virtual worlds play in the future of education and actively changing the direction of their own teaching practice and curricula. 47 academics reporting on 28 Australian higher education institutions present an overview of how they have changed directions through the effective use of virtual worlds for diverse teaching and learning activities such as business scenarios and virtual excursions, role-play simulations, experimentation and language development. The case studies offer insights into the ways in which institutions are continuing to change directions in their teaching to meet changing demands for innovative teaching, learning and research in virtual worlds. This paper highlights the ways in which the authors are using virtual worlds to create opportunities for rich, immersive and authentic activities that would be difficult or not possible to achieve through more traditional approaches

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society