Sustainability, Vol. 8, Pages 530: Implications of Reverse Innovation for Socio-Economic Sustainability: A Case Study of Philips China

The idea of reverse innovation, local innovation happening in emerging markets for the global market, has gained much academic and managerial attention in recent years. The purpose of this study is to understand how reverse innovation has successfully diffused into the product and market development strategies at Philips Inc., a prominent multinational company (MNC) of the modern era. Furthermore, the study presents the success achieved by these innovations at both the domestic and global levels, along with their implications regarding socio-economic sustainability in emerging markets. In order to investigate the research questions, a case study of Philips China was conducted involving three product innovations that were found to be suitable examples of reverse innovation. After the study of extant literature on the topic, drawing from research databases, newspaper articles, and company press releases, five semi-structuredinterviews were conducted with key managers and a market practitioner to gain sufficient understanding for this exploratory study. Subsequent case analysis concludes that these innovations are examples of reverse innovation representing a new paradigm change in innovation flow. This flow of innovation from emerging markets to developed markets as confirmed by Corsi's framework could potentially disrupt developed markets as well as contribute to ensure healthy living conditions for the population living in developing countries. If so, this represents a sustainable socio-economic change in-line with the United Nations' Sustainable Development Goal (SDG) of "ensuring healthy lives and promoting well-being for all at all ages." This is relevant as Philips aspires to be a prominent private sector player in achieving the above-stated goal by defeating non-communicable disease and strengthening local healthcare systems.

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Genomic Classification and Prognosis in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is characterized by clonal expansion of undifferentiated myeloid precursors, resulting in impaired hematopoiesis and bone marrow failure. Although many patients with AML have a response to induction chemotherapy, refractory disease is common, and relapse represents the…

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Characteristics of traditional Chinese medicine users and prescription analysis for pediatric atopic dermatitis: a population-based study

Atopic dermatitis among children is an important issue due to relapses and skin manifestations. Traditional Chinese medicine (TCM) is commonly used to treat children with atopic dermatitis. The aim of this stu...

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Anti-platelet activity of panaxatriol saponins is mediated by suppression of intracellular calcium mobilization and ERK2/p38 activation

Increased platelet aggregation is implicated in the pathogenesis of ischemic stroke and anti-platelet strategy may contribute to its therapy. Panaxatriol saponin (PTS), the main components extracted from Panax no...

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Untargeted saliva metabonomics study of breast cancer based on ultra performance liquid chromatography coupled to mass spectrometry with HILIC and RPLC separations

Publication date: 1 September 2016
Source:Talanta, Volume 158
Author(s): Liping Zhong, Fei Cheng, Xiaoyong Lu, Yixiang Duan, Xiaodong Wang
Breast cancer (BC) is not only the most frequently diagnosed cancer, but also the leading cause of cancer death among women worldwide. This study aimed to screen the potential salivary biomarkers for breast cancer diagnosis, staging, and biomarker discovery. For the first time, a UPLC-MS based method along with multivariate data analysis, was proposed for the global saliva metabonomics analysis and diagnosis of BC, which used both hydrophilic interaction chromatography (HILIC) and reversed-phase liquid chromatography (RPLC) separations and operated in both positive (ESI+) and negative (ESI−) ionization modes. On account of different polarities of endogenous metabolites, this method was established to overcome the boundedness of a single chromatographic approach. As a result, 18 potential metabolites for diagnosing BC were identified. A nonparametric Mann-Whitney U test, heat map, and the receiver operating characteristic (ROC) were exploited to analyze the data with the purpose of evaluating the predictive power of the 18 biomarkers. Significant differences (P<0.05) were disclosed in terms of the levels of the 18 potential biomarkers between BC patients and healthy controls (HC). Among the 18 biomarkers, three up-regulated metabolites, LysoPC (18:1), LysoPC (22:6) and MG (0:0/14:0/0:0) displayed the area under the curve (AUC) values of 0.920, 0.920 and 0.929, respectively, indicating the high accuracy of this method to predict BC. In this study, an integrated metabonomics analysis in human saliva for identifying potential biomarkers to diagnose and stage BC was successfully eastablished, which was non-invasive, reliable, low-cost, and simple. The HILIC was demonstrated to be essential for a comprehensive saliva metabonomics profiling as well as RPLC separation. This saliva metabonomics technique may provide new insight into the discovery and identification of diagnostic biomarkers for BC.

Graphical abstract

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Relationship Between African-American Race and Delirium in the ICU.

Objectives: Delirium is a highly prevalent syndrome of acute brain dysfunction among critically ill patients that has been linked to multiple risk factors, such as age, preexisting cognitive impairment, and use of sedatives; but to date, the relationship between race and delirium is unclear. We conducted this study to identify whether African-American race is a risk factor for developing ICU delirium. Design: A prospective cohort study. Setting: Medical and surgical ICUs of a university-affiliated, safety net hospital in Indianapolis, IN. Patients: A total of 2,087 consecutive admissions with 1,008 African Americans admitted to the ICU services from May 2009 to August 2012. Interventions: None. Measurements and Main Results: Incident delirium was defined as first positive Confusion Assessment Method for the ICU result after an initial negative Confusion Assessment Method for the ICU; and prevalent delirium was defined as positive Confusion Assessment Method for the ICU on first Confusion Assessment Method for the ICU assessment. The overall incident delirium rate in African Americans was 8.7% compared with 10.4% in Caucasians (p = 0.26). The prevalent delirium rate was 14% in both African Americans and Caucasians (p = 0.95). Significant age and race interactions were detected for incident delirium (p = 0.02) but not for prevalent delirium (p = 0.3). The hazard ratio for incident delirium for African Americans in the 18-49 years age group compared with Caucasians of similar age was 0.4 (0.1-0.9). The hazard and odds ratios for incident and prevalent delirium in other groups were not different. Conclusions: African-American race does not confer any additional risk for developing incident or prevalent delirium in the ICU. Instead, younger African Americans tend to have lower rates of incident delirium compared with Caucasians of similar age. Copyright (C) by 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Validity of Different Delirium Assessment Tools for Critically Ill Children: Covariates Matter.

Objectives: To evaluate test validity of the Pediatric Confusion Assessment Method for the ICU, the Pediatric Anesthesia Emergence Delirium scale, and the newly developed severity scale for the Pediatric Confusion Assessment Method for the ICU; to prospectively assess covariates and their influence on test validity of the scores. Design: Prospective observational cohort study. Setting: PICU of a tertiary care medical center. Patients: Critically ill patients 5 years old or older ventilated or nonventilated with an ICU length of stay of at least 24 hours. Interventions: None. Measurements and Main Results: Patients were scored with the Pediatric Confusion Assessment Method for the ICU and the Pediatric Anesthesia Emergence Delirium scale once daily for a maximum of 21 days. Validity was determined by comparing scoring results with the evaluations of the delirium experts who used the criteria of the Diagnostic and Statistical Manual, 4th Edition, Text Revision, for delirium diagnosis. Sixty-four patients were enrolled and 214 assessments were conducted and included in data analysis. The first assessments within each patient revealed sensitivities of 69.2% for the Pediatric Anesthesia Emergence Delirium scale, 76.9% for the Pediatric Confusion Assessment Method for the ICU, and 84.9% for the severity scale for the Pediatric Confusion Assessment Method for the ICU. Specificities were 98% for all scores. Considering repeated measurements, sensitivities decreased to 35.9% for the Pediatric Anesthesia Emergence Delirium scale and to 52.3% for the Pediatric Confusion Assessment Method for the ICU. The sensitivity of the severity scale for the Pediatric Confusion Assessment Method for the ICU dropped to 71.8%, which was significantly higher compared to the Pediatric Anesthesia Emergence Delirium scale (p = 0.0008). Receiver operator characteristic regression unveiled that sedation and mechanical ventilation had a significant negative effect on the validity of the Pediatric Anesthesia Emergence Delirium scale and the severity scale for the Pediatric Confusion Assessment Method for the ICU. Age and gender had a significant impact on the receiver operator characteristic curve of the severity scale for the Pediatric Confusion Assessment Method for the ICU. Conclusions: The severity scale for the Pediatric Confusion Assessment Method for the ICU showed the best test validity when used in critically ill children of 5 years old or older. Nevertheless, validity of delirium screening itself depends on patient specific factors. These factors should be taken into consideration when choosing a delirium screening instrument. Copyright (C) by 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Numerical evaluation of implantable hearing devices using a finite element model of human ear considering viscoelastic properties

Finite element method was employed in this study to analyze the change in performance of implantable hearing devices due to the consideration of soft tissues' viscoelasticity. An integrated finite element model of human ear including the external ear, middle ear and inner ear was first developed via reverse engineering and analyzed by acoustic–structure–fluid coupling. Viscoelastic properties of soft tissues in the middle ear were taken into consideration in this model. The model-derived dynamic responses including middle ear and cochlea functions showed a better agreement with experimental data at high frequencies above 3000 Hz than the Rayleigh-type damping. On this basis, a coupled finite element model consisting of the human ear and a piezoelectric actuator attached to the long process of incus was further constructed. Based on the electromechanical coupling analysis, equivalent sound pressure and power consumption of the actuator corresponding to viscoelasticity and Rayleigh damping were calculated using this model. The analytical results showed that the implant performance of the actuator evaluated using a finite element model considering viscoelastic properties gives a lower output above about 3 kHz than does Rayleigh damping model. Finite element model considering viscoelastic properties was more accurate to numerically evaluate implantable hearing devices.

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G-quadruplex RNA binding and recognition by the lysine-specific histone demethylase-1 enzyme [ARTICLE]

Lysine-specific histone demethylase 1 (LSD1) is an essential epigenetic regulator in metazoans and requires the co-repressor element-1 silencing transcription factor (CoREST) to efficiently catalyze the removal of mono- and dimethyl functional groups from histone 3 at lysine positions 4 and 9 (H3K4/9). LSD1 interacts with over 60 regulatory proteins and also associates with lncRNAs (TERRA, HOTAIR), suggesting a regulatory role for RNA in LSD1 function. We report that a stacked, intramolecular G-quadruplex (GQ) forming TERRA RNA (GG[UUAGGG]₈UUA) binds tightly to the functional LSD1–CoREST complex (K_d 96 nM), in contrast to a single GQ RNA unit ([UUAGGG]₄U), a GQ DNA ([TTAGGG]₄T), or an unstructured single-stranded RNA. Stabilization of a parallel-stranded GQ RNA structure by monovalent potassium ions (K⁺) is required for high affinity binding to the LSD1–CoREST complex. These data indicate that LSD1 can distinguish between RNA and DNA as well as structured versus unstructured nucleotide motifs. Further, cross-linking mass spectrometry identified the primary location of GQ RNA binding within the SWIRM/amine oxidase domain (AOD) of LSD1. An ssRNA binding region adjacent to this GQ binding site was also identified via X-ray crystallography. This RNA binding interface is consistent with kinetic assays, demonstrating that a GQ-forming RNA can serve as a noncompetitive inhibitor of LSD1-catalyzed demethylation. The identification of a GQ RNA binding site coupled with kinetic data suggests that structured RNAs can function as regulatory molecules in LSD1-mediated mechanisms.

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Exercise Intensity during Power Wheelchair Soccer

Publication date: Available online 8 June 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): J.P. Barfield, Laura Newsome, Laurie A. Malone
ObjectiveThe purpose of this study was to determine exercise intensity during power wheelchair soccer (PWS) among a sample of persons with mobility impairments.DesignCross-sectional descriptive.SettingOn-site training facilities of multiple PWS teams.ParticipantsThirty participants with severe mobility impairments (MAge = 29.40 ± 15.51 yrs, MBMI = 24.11 ± 6.47, MPower Soccer Experience = 7.91 ± 3.93 yrs, MDisability Sport Experience = 12.44 ± 9.73 yrs) were recruited from multiple PWS teams.InterventionsPortable metabolic carts were used to collect oxygen consumption data during resting (REST) and gameplay (GAME) conditions.Main Outcome Measure(s)Average VO2 (expressed in METs) for REST and GAME and rate of perceived exertion (RPE) for GAME.ResultsVO2 increased from 1.35 ± 0.47 METs at REST to 1.81 ± 0.65 METs during GAME. This 34% increase in exercise intensity was significant (p < .01) and supported by a mean perceived exertion score of approximately 13 (Somewhat Hard).ConclusionsAlthough not able to sustain an intensity associated with reduced secondary disease risk (i.e., 3 METs), the documented light-intensity exercise in the current study surpassed an intensity threshold associated with improved functional capacity and performance of daily living activities (i.e., 1.5 METs).



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Comparative evaluation of Health-related Quality of Life Questionnaires in patients with heart failure undergoing cardiac rehabilitation- a psychometric study

Publication date: Available online 8 June 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Fatemeh Rajati, Awat Feizi, Kamran Tavakol, Firoozeh Mostafavi, Masoumeh Sadeghi, Gholamreza Sharifirad
ObjectiveTo compare the psychometric properties of two heart failure (HF) specific quality of life questionnaires and the general health survey short-form-36 (SF-36) in heart failure patients.DesignA methodological study based on three-month follow up data for evaluating psychometric properties of health related quality of life questionnaires.SettingCardiac Rehabilitation Centre, cardiovascular research institute (Isfahan, Iran)ParticipantsEligible heart failure patientsInterventionExercise training in cardiac rehabilitationMain Outcome Measures"The SF-36", the "MacNew Heart Disease (MacNew), and the Minnesota Living with Heart Failure (MLHF) questionnaires; New York Heart Association (NYHA) functional classification.ResultsItems from MLHF and MacNew had acceptable correlations (r>0.30, p<0.05). Internal consistency and test-retest reliability were adequate and ≥ 0.7 for MLHF subscales. Correlations for MLHF and MacNew with SF-36 similar items ranged from 0.28 to 0.50 and from 0.26 to 0.60, respectively. Similar scales from MacNew and MLHF showed strong correlations at baseline as well as follow-up, supporting the convergent validity. Improvement in HRQL was significant for all MLHF subscales (p<0.001) as well as MacNew emotional (p<0.05) and social (p<0.001) subscales. The MLHF demonstrated the most responsiveness to changes and discriminated disease severity the best. The follow-up scores for all MLHF and two MacNew subscales were significantly greater in patients who improved than those who showed no change or deteriorated.ConclusionThe MLHF questionnaire was more responsive to changes of HRQL than the MacNew over time in patients with heart failure. The MacNew questionnaire was more responsive to changes than the SF-36.



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The influence of a home-based exercise intervention on human health indices in individuals with chronic spinal cord injury (HOMEX-SCI): study protocol for a randomised controlled trial

Spinal cord injury (SCI) creates a complex pathology that can lead to an increase in sedentary behaviours and deleterious changes in body composition. Consequently, individuals with SCI are at increased risk o...

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Optimising recruitment and informed consent in randomised controlled trials: the development and implementation of the Quintet Recruitment Intervention (QRI)

Pragmatic randomised controlled trials (RCTs) are considered essential to determine effective interventions for routine clinical practice, but many fail to recruit participants efficiently, and some really imp...

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First ultrastructural data on the human tapeworm Taenia asiatica eggs by scanning and transmission electron microscopy (SEM, TEM)

Abstract

Humans are definitive hosts of three species of the Taenia genus, namely Taenia solium, Taenia saginata and Taenia asiatica. The relative novelty of the latter explains the lack of knowledge concerning certain relevant aspects related to this parasite, such as its definite geographical distribution and whether its eggs can infect humans or not. So far, only the eggs of T. solium are known to be infective for humans, producing cysticercosis. Although eggs contain the infective stage, the oncosphere, there is a lack of research on the ultrastructure of eggs of human taeniids. We show, for the first time, the ultrastructure of eggs of T. asiatica by means of SEM and TEM analyses. We detected all the envelopes, namely the egg shell, vitelline layer, outer embryophoric membrane, embryophore, granular layer, basal membrane, oncospheral membrane and oncospheral tegument. Hooks surrounded by myofibrils and glycogen-like particles, the two types of secretory granules of the penetration glands, as well as several nuclei and mitochondria were also revealed in the oncospheres. In addition to the already known structures in eggs from other Taenia species, the presence of two types of small vesicles is described herein, possibly corresponding to exosomes and ectosomes because of their shape and size, which could participate in the host/parasite intercellular communication.

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DNA extraction methods and multiple sampling to improve molecular diagnosis of Sarcocystis spp. in cattle hearts

Abstract

Molecular detection of Sarcocystis spp. in tissue samples can be useful for experimental and diagnostic purposes. However, the parasite spreads unevenly through tissues, forming tissue cysts, and the cystic wall is an obstacle in DNA extraction protocols. Therefore, adequate sampling and effective disruption of the cysts are essential to improve the accuracy of DNA detection by PCR. The aims of this study were to evaluate the suitability of four protocols for DNA extraction from cysts of Sarcocystis spp. present in bovine myocardium samples or after their harvest in phosphate-buffered saline (PBS) solution as well as determine the effects of single or multiple sampling on the accuracy of molecular diagnosis of sarcocystosis in cattle hearts. Cysts and myocardium samples from nine bovine hearts were randomly distributed to four DNA extraction protocols: kit, kit with modification, DNAzol, and cetyl-trimethyl ammonium bromide (CTAB). Samples were submitted to DNA extraction and PCR as replicates of each heart (simplicate, duplicate, and triplicate), and the probability of a true positive diagnostic was calculated. Among the protocols tested, the kit with modification was determined to be the most suitable for DNA extraction from cysts in PBS solution (92.6 % of DNA detection by PCR); DNAzol resulted in higher DNA detection frequency from bovine myocardium samples (48.1 %). Multiple sampling improved the molecular diagnosis of Sarcocystis spp. infection in cattle hearts, increasing at 22.2 % the rate of true positive diagnostic.

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Demethylation of Methylated Arsenic Species during Generation of Arsanes with Tetrahydridoborate(1−) in Acidic Media

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b00735

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Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis

Psoriasis is a chronic inflammatory disease that is mediated by aberrant immune responses and driven by self-perpetuating cytokine networks. Advances in understanding the pathogenic cytokine network of psoriasis have led to the development of new treatments that provide greater efficacy in terms of…

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Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage

An acute hypertensive response in patients with intracerebral hemorrhage is common and may be associated with hematoma expansion and increased mortality. The second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) included patients with spontaneous intracerebral…

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Reliability and validity of the Khmer version of the 10-item Connor-Davidson Resilience Scale (Kh-CD-RISC10) in Cambodian adolescents

Resilience has been characterized as a defensive factor against the refinement of mental health problems. This study adapted the Connor–Davidson Resilience Scale (Kh-CD-RISC10) for use in Khmer adolescents and...

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No filters, no fridges: a method for preservation of water samples for eDNA analysis

Advancements in the detection of environmental DNA (eDNA) for detecting species of interest will likely allow for expanded use of these techniques in the field. One obstacle that continues to hinder applicatio...

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Distinguishing the C3 vs SH4 Mass Split by Comprehensive Two-Dimensional Gas Chromatography–High Resolution Time-of-Flight Mass Spectrometry

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b01137

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Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst

This article describes a process for producing polymeric self-assembled nanoparticles using visible light mediated dispersion polymerization. Using low energy visible light to control the polymerization allows for the reproducible formation of self-assembled worm-like micelles at high solids content.

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Plasminogen activator inhibitor-1 as a marker of cardiovascular response in professional mountain ultra-marathon runners

Journal Name: Clinical Chemistry and Laboratory Medicine (CCLM)
Issue: Ahead of print


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Understanding the Complexity of Porous Graphitic Carbon (PGC) Chromatography: Modulation of Mobile-Stationary Phase Interactions Overcomes Loss of Retention and Reduces Variability

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b01167

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Liquid Chromatography Chip with Low-Dispersion and Low-Pressure-Drop Turn Structure Utilizing a Distribution-Controlled Pillar Array

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b01201

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The effects of reward magnitude on reward processing: An averaged and single trial event-related potential study

Publication date: Available online 8 June 2016
Source:Biological Psychology
Author(s): Caroline C. Meadows, Philip A. Gable, Keith R. Lohse, Matthew W. Miller
From a neurobiological and motivational perspective, the feedback-related negativity (FRN) and reward positivity (RewP) event-related potential (ERP) components should increase with reward magnitude (reward associated with valence (success/failure) feedback). To test this hypothesis, we recorded participants' electroencephalograms while presenting them with potential monetary rewards ($0.00–$4.96) pre-trial for each trial of a reaction time task and presenting them with valence feedback post-trial. Averaged ERPs time-locked to valence feedback were extracted, and results revealed a valence by magnitude interaction for neural activity in the FRN/RewP time window. This interaction was driven by magnitude affecting RewP, but not FRN, amplitude. Moreover, single trial ERP analyses revealed a reliable correlation between magnitude and RewP, but not FRN, amplitude. Finally, P3b and late positive potential (LPP) amplitudes were affected by magnitude. Results partly support the neurobiological (dopamine) account of the FRN/RewP and suggest motivation affects feedback processing, as indicated by multiple ERP components.



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X-ray Powder Diffraction in Conservation Science: Towards Routine Crystal Structure Determination of Corrosion Products on Heritage Art Objects

Modern high resolution X-ray powder diffraction (XRPD) in the laboratory is used as an efficient tool to determine crystal structures of long-known corrosion products on historic objects.

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TAPE: A Biodegradable Hemostatic Glue Inspired by a Ubiquitous Compound in Plants for Surgical Application

We describe the simplest protocol to prepare biodegradable medical glue that has an effective hemostatic ability. TAPE is a water-immiscible supramolecular aggregate prepared by mixing of tannic acid, a ubiquitous compound found in plants, and poly(ethylene) glycol, yielding a 2.5 times greater water-resistant adhesion compared with commercial fibrin glue.

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A rare hepatoid adenocarcinoma from the gastric remnant

Publication date: Available online 7 June 2016
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Chih-Yin Cheng, I-Chen Wu, Yi-Ting Chen, Huang-Ming Hu




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Fractional Factorial Design of MALDI-TOF-MS Sample Preparations for the Optimized Detection of Phospholipids and Acylglycerols

Analytical Chemistry

DOI: 10.1021/acs.analchem.6b00512

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Cdk5 is a New Rapid Synaptic Homeostasis Regulator Capable of Initiating the Early Alzheimer-Like Pathology

Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase implicated in synaptic plasticity, behavior, and cognition, yet its synaptic function remains poorly understood. Here, we report that physiological Cdk5 signaling in rat hippocampal CA1 neurons regulates homeostatic synaptic transmission using an unexpectedly rapid mechanism that is different from all known slow homeostatic regulators, such as beta amyloid (Aβ) and activity-regulated cytoskeleton-associated protein (Arc, aka Arg3.1). Interestingly, overproduction of the potent Cdk5 activator p25 reduces synapse density, and dynamically regulates synaptic size by suppressing or enhancing Aβ/Arc production. Moreover, chronic overproduction of p25, seen in Alzheimer's patients, induces initially concurrent reduction in synapse density and increase in synaptic size characteristic of the early Alzheimer-like pathology, and later persistent synapse elimination in intact brains. These results identify Cdk5 as the regulator of a novel rapid form of homeostasis at central synapses and p25 as the first molecule capable of initiating the early Alzheimer's synaptic pathology.

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Neural Mechanisms of Temporal Resolution of Attention

The dynamic nature of the world requires that our visual representations are continuously updated. These representations are more precise if there is a narrow time window over which information is averaged. We assess the neural processes of visual updating by testing patients with lesions including inferior parietal cortex, control patients and healthy adults on a continuous visual monitoring task. In Experiment 1, observers kept track of the changing spatial period of a luminance grating and identified the final spatial period after the stimulus disappeared. Healthy older adults and neurological controls were able to perform better than simulated guesses, but only 3 of 11 patients with damage including parietal cortex were able to reach performance that differed from simulated guesses. The effects were unrelated to lesion size. Poor performance on this task is consistent with an inability to selectively attend to the final moment at which the stimulus was seen. To investigate the temporal limits of attention, we varied the rate of stimulus change in Experiment 2. Performance remained poor for some patients even with slow 2.5 Hz change rates. The performance of 4 patients with parietal damage displayed poor temporal precision, namely recovery of performance with slower rates of change.

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Subregional Mesiotemporal Network Topology Is Altered in Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is the most frequent drug-resistant epilepsy in adults and commonly associated with variable degrees of mesiotemporal atrophy on magnetic resonance imaging (MRI). Analyses of inter-regional connectivity have unveiled disruptions in large-scale cortico-cortical networks; little is known about the topological organization of the mesiotemporal lobe, the limbic subnetwork central to the disorder. We generated covariance networks based on high-resolution MRI surface-shape descriptors of the hippocampus, entorhinal cortex, and amygdala in 134 TLE patients and 45 age- and sex-matched controls. Graph-theoretical analysis revealed increased path length and clustering in patients, suggesting a shift toward a more regularized arrangement; findings were reproducible after split-half assessment and across 2 parcellation schemes. Analysis of inter-regional correlations and module participation showed increased within-structure covariance, but decreases between structures, particularly with regards to the hippocampus and amygdala. While higher clustering possibly reflects topological consequences of axonal sprouting, decreases in interstructure covariance may be a consequence of disconnection within limbic circuitry. Preoperative network parameters, specifically the segregation of the ipsilateral hippocampus, predicted long-term seizure freedom after surgery.

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CREB1 Genotype Modulates Adaptive Reward-Based Decisions in Humans

Cyclic AMP response element-binding protein (CREB) contributes to adaptation of mesocorticolimbic networks by modulating activity-regulated transcription and plasticity in neurons. Activity or expression changes of CREB in the nucleus accumbens (NAc) and orbital frontal cortex (OFC) interact with behavioral changes during reward-motivated learning. However, these findings from animal models have not been evaluated in humans. We tested whether CREB1 genotypes affect reward-motivated decisions and related brain activation, using BOLD fMRI in 224 young and healthy participants. More specifically, participants needed to adapt their decision to either pursue or resist immediate rewards to optimize the reward outcome. We found significant CREB1 genotype effects on choices to pursue increases of the reward outcome and on BOLD signal in the NAc, OFC, insula cortex, cingulate gyrus, hippocampus, amygdala, and precuneus during these decisions in comparison with those decisions avoiding total reward loss. Our results suggest that CREB1 genotype effects in these regions could contribute to individual differences in reward- and associative memory-based decision-making.

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Remapping, Spatial Stability, and Temporal Continuity: From the Pre-Saccadic to Postsaccadic Representation of Visual Space in LIP

As our eyes move, we have a strong percept that the world is stable in space and time; however, the signals in cortex coming from the retina change with each eye movement. It is not known how this changing input produces the visual percept we experience, although the predictive remapping of receptive fields has been described as a likely candidate. To explain how remapping accounts for perceptual stability, we examined responses of neurons in the lateral intraparietal area while animals performed a visual foraging task. When a stimulus was brought into the response field of a neuron that exhibited remapping, the onset of the postsaccadic representation occurred shortly after the saccade ends. Whenever a stimulus was taken out of the response field, the presaccadic representation abruptly ended shortly after the eyes stopped moving. In the 38% (20/52) of neurons that exhibited remapping, there was no more than 30 ms between the end of the presaccadic representation and the start of the postsaccadic representation and, in some neurons, and the population as a whole, it was continuous. We conclude by describing how this seamless shift from a presaccadic to postsaccadic representation could contribute to spatial stability and temporal continuity.

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Dissociations in Cortical Morphometry in Youth with Down Syndrome: Evidence for Reduced Surface Area but Increased Thickness

Detailed descriptions of cortical anatomy in youth with Down syndrome (DS), the most common genetic cause of intellectual disability (ID), are scant. Thus, the current study examined deviations in cortical thickness (CT) and surface area (SA), at high spatial resolution, in youth with DS, to identify focal differences relative to typically developing (TD) youth. Participants included 31 youth with DS and 45 age- and sex-matched TD controls (mean age ~16 years; range = 5–24 years). All participants completed T₁-weighted ASSET-calibrated magnetization prepared rapid gradient echo scans on a 3-T magnetic resonance imaging scanner. Replicating prior investigations, cortical volume was reduced in DS compared with controls. However, a novel dissociation for SA and CT was found—namely, SA was reduced (predominantly in frontal and temporal regions) while CT was increased (notably in several regions thought to belong to the default mode network; DMN). These findings suggest that reductions in SA rather than CT are driving the cortical volume reductions reported in prior investigations of DS. Moreover, given the link between DMN functionality and Alzheimer's symptomatology in chromosomally typical populations, future DS studies may benefit from focusing on the cortex in DMN regions, as such investigations may provide clues to the precocious onset of Alzheimer's disease in this at-risk group.

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Network-Level Structure-Function Relationships in Human Neocortex

The dynamics of spontaneous fluctuations in neural activity are shaped by underlying patterns of anatomical connectivity. While numerous studies have demonstrated edge-wise correspondence between structural and functional connections, much less is known about how large-scale coherent functional network patterns emerge from the topology of structural networks. In the present study, we deploy a multivariate statistical technique, partial least squares, to investigate the association between spatially extended structural networks and functional networks. We find multiple statistically robust patterns, reflecting reliable combinations of structural and functional subnetworks that are optimally associated with one another. Importantly, these patterns generally do not show a one-to-one correspondence between structural and functional edges, but are instead distributed and heterogeneous, with many functional relationships arising from nonoverlapping sets of anatomical connections. We also find that structural connections between high-degree hubs are disproportionately represented, suggesting that these connections are particularly important in establishing coherent functional networks. Altogether, these results demonstrate that the network organization of the cerebral cortex supports the emergence of diverse functional network configurations that often diverge from the underlying anatomical substrate.

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Probing the Cognitive Mechanism of Mental Representational Change During Chunk Decomposition: A Parametric fMRI Study

Chunk decomposition plays an important role in cognitive flexibility in particular with regards to representational change, which is critical for insight problem solving and creative thinking. In this study, we investigated the cognitive mechanism of decomposing Chinese character chunks through a parametric fMRI design. Our results from this parametric manipulation revealed widely distributed activations in frontal, parietal, and occipital cortex and negative activations in parietal and visual areas in response to chunk tightness during decomposition. To mentally manipulate the element of a given old chunk, superior parietal lobe appears to support element restructuring in a goal-directed way, whereas the negatively activated inferior parietal lobe may support preventing irrelevant objects from being attended. Moreover, determining alternative ways of restructuring requires a constellation of frontal areas in the cognitive control network, such as the right lateral prefrontal cortex in inhibiting the predominant chunk representations, the presupplementary motor area in initiating a transition of mental task set, and the inferior frontal junction in establishing task sets. In conclusion, this suggests that chunk decomposition reflects mental transformation of problem representation from an inappropriate state to a new one alongside with an evaluation of novel and insightful solutions by the caudate in the dorsal striatum.

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Distinct but Overlapping Patterns of Response to Words and Faces in the Fusiform Gyrus

Converging evidence suggests that the fusiform gyrus is involved in the processing of both faces and words. We used fMRI to investigate the extent to which the representation of words and faces in this region of the brain is based on a common neural representation. In Experiment 1, a univariate analysis revealed regions in the fusiform gyrus that were only selective for faces and other regions that were only selective for words. However, we also found regions that showed both word-selective and face-selective responses, particularly in the left hemisphere. We then used a multivariate analysis to measure the pattern of response to faces and words. Despite the overlap in regional responses, we found distinct patterns of response to both faces and words in the left and right fusiform gyrus. In Experiment 2, fMR adaptation was used to determine whether information about familiar faces and names is integrated in the fusiform gyrus. Distinct regions of the fusiform gyrus showed adaptation to either familiar faces or familiar names. However, there was no adaptation to sequences of faces and names with the same identity. Taken together, these results provide evidence for distinct, but overlapping, neural representations for words and faces in the fusiform gyrus.

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Evidence for a Specific Integrative Mechanism for Episodic Memory Mediated by AMPA/kainate Receptors in a Circuit Involving Medial Prefrontal Cortex and Hippocampal CA3 Region

We asked whether episodic-like memory requires neural mechanisms independent of those that mediate its component memories for "what," "when," and "where," and if neuronal connectivity between the medial prefrontal cortex (mPFC) and the hippocampus (HPC) CA3 subregion is essential for episodic-like memory. Unilateral lesion of the mPFC was combined with unilateral lesion of the CA3 in the ipsi- or contralateral hemispheres in rats. Episodic-like memory was tested using a task, which assesses the integration of memories for "what, where, and when" concomitantly. Tests for novel object recognition (what), object place (where), and temporal order memory (when) were also applied. Bilateral disconnection of the mPFC-CA3 circuit by N-methyl-d-aspartate (NMDA) lesions disrupted episodic-like memory, but left the component memories for object, place, and temporal order, per se, intact. Furthermore, unilateral NMDA lesion of the CA3 plus injection of (6-cyano-7-nitroquinoxaline-2,3-dione) (CNQX) (AMPA/kainate receptor antagonist), but not AP-5 (NMDA receptor antagonist), into the contralateral mPFC also disrupted episodic-like memory, indicating the mPFC AMPA/kainate receptors as critical for this circuit. These results argue for a selective neural system that specifically subserves episodic memory, as it is not critically involved in the control of its component memories for object, place, and time.

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Early Cerebellar Network Shifting in Spinocerebellar Ataxia Type 6

Spinocerebellar ataxia 6 (SCA6), an autosomal dominant degenerative disease, is characterized by diplopia, gait ataxia, and incoordination due to severe progressive degeneration of Purkinje cells in the vestibulo- and spinocerebellum. Ocular motor deficits are common, including difficulty fixating on moving objects, nystagmus and disruption of smooth pursuit movements. In presymptomatic SCA6, there are alterations in saccades and smooth-pursuit movements. We sought to assess functional and structural changes in cerebellar connectivity associated with a visual task, hypothesizing that gradual changes would parallel disease progression. We acquired functional magnetic resonance imaging and diffusion tensor imaging data during a passive smooth-pursuit task in 14 SCA6 patients, representing a range of disease duration and severity, and performed a cross-sectional comparison of cerebellar networks compared with healthy controls. We identified a shift in activation from vermis in presymptomatic individuals to lateral cerebellum in moderate-to-severe cases. Concomitantly, effective connectivity between regions of cerebral cortex and cerebellum was at its highest in moderate cases, and disappeared in severe cases. Finally, we noted structural differences in the cerebral and cerebellar peduncles. These unique results, spanning both functional and structural domains, highlight widespread changes in SCA6 and compensatory mechanisms associated with cerebellar physiology that could be utilized in developing new therapies.

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Selective Neural Synchrony Suppression as a Forward Gatekeeper to Piecemeal Conscious Perception

The emergence of conscious visual perception is assumed to ignite late (~250 ms) gamma-band oscillations shortly after an initial (~100 ms) forward sweep of neural sensory (nonconscious) information. However, this neural evidence is not utterly congruent with rich behavioral data which rather point to piecemeal (i.e., graded) perceptual processing. To address the unexplored neural mechanisms of piecemeal ignition of conscious perception, hierarchical script sensitivity of the putative visual word form area (VWFA) was exploited to signal null (i.e., sensory), partial (i.e., letter-level), and full (i.e., word-level) conscious perception. Two magnetoencephalography experiments were conducted in which healthy human participants viewed masked words (Experiment I: active task, Dutch words; Experiment II: passive task, Hebrew words) while high-frequency (broadband gamma) brain activity was measured. Findings revealed that piecemeal conscious perception did not ignite a linear piecemeal increase in oscillations. Instead, whereas late (~250 ms) gamma-band oscillations signaled full conscious perception (i.e., word-level), partial conscious perception (i.e., letter-level) was signaled via the inhibition of the early (~100 ms) forward sweep. This inhibition regulates the downstream broadcast to filter out irrelevant (i.e., masks) information. The findings thus highlight a local (VWFA) gatekeeping mechanism for conscious perception, operating by filtering out and in selective percepts.

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Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission

Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood.

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Are Developmental Trajectories of Cortical Folding Comparable Between Cross-sectional Datasets of Fetuses and Preterm Newborns?

Magnetic resonance imaging has proved to be suitable and efficient for in vivo investigation of the early process of brain gyrification in fetuses and preterm newborns but the question remains as to whether cortical-related measurements derived from both cases are comparable or not. Indeed, the developmental folding trajectories drawn up from both populations have not been compared so far, neither from cross-sectional nor from longitudinal datasets. The present study aimed to compare features of cortical folding between healthy fetuses and early imaged preterm newborns on a cross-sectional basis, over a developmental period critical for the folding process (21–36 weeks of gestational age [GA]). A particular attention was carried out to reduce the methodological biases between the 2 populations. To provide an accurate group comparison, several global parameters characterizing the cortical morphometry were derived. In both groups, those metrics provided good proxies for the dramatic brain growth and cortical folding over this developmental period. Except for the cortical volume and the rate of sulci appearance, they depicted different trajectories in both groups suggesting that the transition from into ex utero has a visible impact on cortical morphology that is at least dependent on the GA at birth in preterm newborns.

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Neural Representations of Natural and Scrambled Movies Progressively Change from Rat Striate to Temporal Cortex

In recent years, the rodent has come forward as a candidate model for investigating higher level visual abilities such as object vision. This view has been backed up substantially by evidence from behavioral studies that show rats can be trained to express visual object recognition and categorization capabilities. However, almost no studies have investigated the functional properties of rodent extrastriate visual cortex using stimuli that target object vision, leaving a gap compared with the primate literature. Therefore, we recorded single-neuron responses along a proposed ventral pathway in rat visual cortex to investigate hallmarks of primate neural object representations such as preference for intact versus scrambled stimuli and category-selectivity. We presented natural movies containing a rat or no rat as well as their phase-scrambled versions. Population analyses showed increased dissociation in representations of natural versus scrambled stimuli along the targeted stream, but without a clear preference for natural stimuli. Along the measured cortical hierarchy the neural response seemed to be driven increasingly by features that are not V1-like and destroyed by phase-scrambling. However, there was no evidence for category selectivity for the rat versus nonrat distinction. Together, these findings provide insights about differences and commonalities between rodent and primate visual cortex.

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Cortical Effects on Ipsilateral Hindlimb Muscles Revealed with Stimulus-Triggered Averaging of EMG Activity

While a large body of evidence supports the view that ipsilateral motor cortex may make an important contribution to normal movements and to recovery of function following cortical injury (Chollet et al. 1991; Fisher 1992; Caramia et al. 2000; Feydy et al. 2002), relatively little is known about the properties of output from motor cortex to ipsilateral muscles. Our aim in this study was to characterize the organization of output effects on hindlimb muscles from ipsilateral motor cortex using stimulus-triggered averaging of EMG activity. Stimulus-triggered averages of EMG activity were computed from microstimuli applied at 60–120 μA to sites in both contralateral and ipsilateral M1 of macaque monkeys during the performance of a hindlimb push–pull task. Although the poststimulus effects (PStEs) from ipsilateral M1 were fewer in number and substantially weaker, clear and consistent effects were obtained at an intensity of 120 μA. The mean onset latency of ipsilateral poststimulus facilitation was longer than contralateral effects by an average of 0.7 ms. However, the shortest latency effects in ipsilateral muscles were as short as the shortest latency effects in the corresponding contralateral muscles suggesting a minimal synaptic linkage that is equally direct in both cases.

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Expecting to See a Letter: Alpha Oscillations as Carriers of Top-Down Sensory Predictions

Predictions strongly influence perception. However, the neurophysiological processes that implement predictions remain underexplored. It has been proposed that high- and low-frequency neuronal oscillations act as carriers of sensory evidence and top-down predictions, respectively (von Stein and Sarnthein 2000; Bastos et al. 2012). However, evidence for the latter hypothesis remains scarce. In particular, it remains to be shown whether slow prestimulus alpha oscillations in task-relevant brain regions are stronger in the presence of predictions, whether they influence early categorization processes, and whether this interplay indeed boosts perception. Here, we directly address these questions by manipulating subjects' prior expectations about the identity of visually presented letters while collecting magnetoencephalographic recordings. We find that predictions lead to increased prestimulus alpha oscillations in a multisensory network representing grapheme/phoneme associations. Furthermore, alpha power interacts with stimulus degradation and top-down expectations to predict visibility ratings, and correlates with the amplitude of early sensory components (P1/N1m complex), suggesting a role in the selective amplification of predicted information. Our results thus indicate that low-frequency alpha oscillations can serve as a mechanism to carry and test sensory predictions about letters.

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