The Contribution of Network Organization and Integration to the Development of Cognitive Control

Cognitive control, which continues to mature throughout adolescence, is supported by the ability for well-defined organized brain networks to flexibly integrate information. However, the development of intrinsic brain network organization and its relationship to observed improvements in cognitive control are not well understood. In the present study, we used resting state functional magnetic resonance imaging (RS-fMRI), graph theory, the antisaccade task, and rigorous head motion control to characterize and relate developmental changes in network organization, connectivity strength, and integration to inhibitory control development. Subjects were 192 10–26-y-olds who were imaged during 5 min of rest. In contrast to initial studies, our results indicate that network organization is stable throughout adolescence. However, cross-network integration, predominantly of the cingulo-opercular/salience network, increased with age. Importantly, this increased integration of the cingulo-opercular/salience network significantly moderated the robust effect of age on the latency to initiate a correct inhibitory control response. These results provide compelling evidence that the transition to adult-level inhibitory control is dependent upon the refinement and strengthening of integration between specialized networks. Our findings support a novel, two-stage model of neural development, in which networks stabilize prior to adolescence and subsequently increase their integration to support the cross-domain incorporation of information processing critical for mature cognitive control

Consumption of New Zealand blackcurrant extract improves recovery from exercise-induced muscle damage in non-resistance trained men and women: A double-blind randomised trial

Background: Blackcurrant is rich in anthocyanins that may protect against exercise-induced muscle damage (EIMD) and facilitate a faster recovery of muscle function. We examined the effects of New Zealand blackcurrant (NZBC) extract on indices of muscle damage and recovery following a bout of strenuous isokinetic resistance exercise. Methods: Using a double-blind, randomised, placebo controlled, parallel design, twenty-seven healthy participants received either a 3 g·day−1 NZBC extract (n = 14) or the placebo (PLA) (n = 13) for 8 days prior to and 4 days following 60 strenuous concentric and eccentric contractions of the biceps brachii muscle on an isokinetic dynamometer. Muscle soreness (using a visual analogue scale), maximal voluntary contraction (MVC), range of motion (ROM) and blood creatine kinase (CK) were assessed before (0 h) and after (24, 48, 72 and 96 h) exercise. Results: Consumption of NZBC extract resulted in faster recovery of baseline MVC (p = 0.04), attenuated muscle soreness at 24 h (NZBC: 21 ± 10 mm vs. PLA: 40 ± 23 mm, p = 0.02) and 48 h (NZBC: 22 ± 17 vs. PLA: 44 ± 26 mm, p = 0.03) and serum CK concentration at 96 h (NZBC: 635 ± 921 UL vs. PLA: 4021 ± 4319 UL, p = 0.04) following EIMD. Conclusions: Consumption of NZBC extract prior to and following a bout of eccentric exercise attenuates muscle damage and improves functional recovery. These findings are of practical importance in recreationally active and potentially athletic populations, who may benefit from accelerated recovery following EIMD

Proteome Profiling of Breast Tumors by Gel Electrophoresis and Nanoscale Electrospray Ionization Mass Spectrometry

We have conducted proteome-wide analysis of fresh surgery specimens derived from breast cancer patients, using an approach that integrates size-based intact protein fractionation, nanoscale liquid separation of peptides, electrospray ion trap mass spectrometry, and bioinformatics. Through this approach, we have acquired a large amount of peptide fragmentation spectra from size-resolved fractions of the proteomes of several breast tumors, tissue peripheral to the tumor, and samples from patients undergoing noncancer surgery. Label-free quantitation was used to generate protein abundance maps for each proteome and perform comparative analyses. The mass spectrometry data revealed distinct qualitative and quantitative patterns distinguishing the tumors from healthy tissue as well as differences between metastatic and non-metastatic human breast cancers including many established and potential novel candidate protein biomarkers. Selected proteins were evaluated by Western blotting using tumors grouped according to histological grade, size, and receptor expression but differing in nodal status. Immunohistochemical analysis of a wide panel of breast tumors was conducted to assess expression in different types of breast cancers and the cellular distribution of the candidate proteins. These experiments provided further insights and an independent validation of the data obtained by mass spectrometry and revealed the potential of this approach for establishing multimodal markers for early metastasis, therapy outcomes, prognosis, and diagnosis in the future. © 2008 American Chemical Society

The structure of ultrathin Langmuir-Blodgett films of cadmium behenate

Grazing incidence x-ray-diffraction investigations of the structures of Langmuir-Blodgett films of cadmium behenate with 1, 2, 3, 5, and 21 monolayers are reported. The single monolayer film, deposited on a hydrophilic substrate, showed a hexagonal structure, whereas the bilayer film, deposited on a hydrophobic substrate, had a rectangular structure with herringbone orientation of the acyl chains. With multilayer films formed on a hydrophilic substrate, it was possible to detect that the hexagonal structure of the first layer was retained when additional layers were deposited and that the additional layers had the same rectangular structure as the bilayer. (c) 2005 American Institute of Physics

Opening and closing the future: climate change, adaptation, and scenario planning

The gales of climate change blow the future open and closed. In response, we are having to learn to live with a renewed notion of limits and a novel level of uncertainty. One emerging governance response is a turn to scenario planning, which generates narratives about multiple futures refracted out from the present. Like climate change itself, scenario planning, and the broader field of futures studies it is part of, is historically and socially positioned, belying its application as a mere method or tool. This paper discusses the growing turn to scenario planning within government climate change adaptation initiatives in light of parallel shifts in governance (eg, interest in efficiency and wicked problems) and adaptation efforts (eg, framed as risk management or resilience) and their shared roots in the ambiguities of sustainable development. It provides an extended introduction to a theme issue that provides, overall, a nested discussion of the role of scenario planning by government for climate change adaptation, noting how governance, climate change adaptation, and scenario planning all fold together the motifs of openness and closedness. This paper engages with the emerging field of future geographies and critical interest in future orientations to highlight the way society’s growing engagement on climate change adaptation exposes, critiques, replicates, and amplifies our existing orientations to the future and time and their politically contested and embedded character. It points to the way the motif of open futures can be both progressive and conservative, as political and economic interests seek to open up some futures while closing down others in the name of the ambivalent goals of adaptation and sustainable development

On the problem of the justification of river rights

This article aims to work out the social conditions that determine whether the communication of river rights finds success in society. Employing the context of hydropower development in the Mekong region, the article finds that an essentialist strategy which claims that river rights have unlimited ‘moral’ validity regardless of any of the decision consequences is unlikely to succeed. Instead, it is proposed that moral conflicts over river rights may ultimately only be resolvable ‘unmorally’, that is, by procedural legitimacy – and this is best captured by employing a methodological framework composed of thematic, social and temporal dimension

The pirate in the pump: children's views of objects as imaginary friends at the start of school

The main aim of this paper is to use a phenomenological approach (Merleau-Ponty, 1962. Phenomenology of Perception. Evanston: Northwestern University Press; Merleau-Ponty. 1968. The Visible and the Invisible: Followed by Working Notes. Evanston: Northern University Press) to contribute a new theoretical understanding of what imaginary friends mean for children in the context of starting school. The paper addresses the specific area of ‘object-friends’ and draws on examples from an empirical and consultative study of a small sample of five and six-year-old children’s everyday experiences of friendship in school. The paper argues that if practitioners consider embodiment approaches and listen attentively to the knowledge and information that children share about their imaginary friends, this could be used to nurture children’s early learnin

Treatment of Older Patients with Mantle-Cell Lymphoma

BACKGROUND: The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission. METHODS: We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression. RESULTS: Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005). CONCLUSIONS: R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphom

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue