bluuebunny/crossref_metadata_2025 huggingface dataset:
Channel Characterization for 700 MHz DSRC Vehicular Communication
Authors: Sevlian Raffi , Chun Carl , Tan Ian , Bahai Ahmad , Laberteaux Ken
Published: August 2010

Adapting OFDM for vehicular communication requires extensive knowledge of anticipated multipath and Doppler environments. We present a GPS‐enabled channel sounding system built and used to conduct a channel measurement campaign. Tests conducted at the 700 MHz band in and around downtown Ann Arbor, Michigan, explored various vehicle‐to‐vehicle and vehicle‐to‐roadside channel scenarios. The measured channel metrics are used to quantify the effects on guard interval, packet duration, and subcarrier spacing for a functional OFDM system at 700 MHz. This paper is one of the first to present vehicular‐based channel‐modeling results from measured data in the 700 MHz band.
Digital Ischemia in Scleroderma Spectrum of Diseases
Authors: Schiopu Elena , Impens Ann J. , Phillips Kristine
Published: August 2010

Systemic Sclerosis (Scleroderma, SSc) is a disease of unknown etiology characterized by widespread vasculopathy and extracellular matrix deposition leading to fibrosis and autoimmune processes. Digital ischemia (digital ulcers (DUs)) is the hallmark of SSc-related vasculopathy and is characterized by endothelial dysfunction leading to intimal proliferation and thrombosis. It happens frequently (30% of the patients each year) and it is associated with significant morbidity. This paper summarizes the current information regarding pathogenesis, definitions, management, and exploratory therapies in DUs associated with SSc.
microRNA Signature and Expression of Dicer and Drosha Can Predict Prognosis and Delineate Risk Groups in Neuroblastoma
Authors: Lin Ruey-Jen , Lin You-Chin , Chen Jeremy , Kuo Huan-Hsien , Chen Yuan-Yan , Diccianni Mitchell B. , London Wendy B. , Chang Chih-Hao , Yu Alice L.
Published: August 2010

Neuroblastoma is a common childhood tumor and accounts for 15% of pediatric cancer deaths. To investigate the microRNA (miRNA) profile and role of Dicer and Drosha in neuroblastoma, we assessed the expression of 162 human miRNAs, Dicer and Drosha in 66 neuroblastoma tumors by using real-time PCR methods. We found global downregulation of miRNA expression in advanced neuroblastoma and identified 27 miRNAs that can clearly distinguish low- from high-risk patients. Furthermore, expression levels of Dicer or Drosha were low in high-risk neuroblastoma tumors, which accounted for global downregulation of miRNAs in advanced disease and correlated with poor outcome. Notably, for patients with non–MYCN-amplified tumors, low expression of Dicer can serve as a significant and independent predictor of poor outcome (hazard ratio, 9.6; P = 0.045; n = 52). Using plausible neural networks to select a combination of 15 biomarkers that consist of 12 miRNAs' signature, expression levels of Dicer and Drosha, and age at diagnosis, we were able to segregate all patients into four distinct patterns that were highly predictive of clinical outcome. In vitro studies also showed that knockdown of either Dicer or Drosha promoted the growth of neuroblastoma cell lines. Our results reveal that a combination of 15 biomarkers can delineate risk groups of neuroblastoma and serve as a powerful predictor of clinical outcome. Moreover, our findings of growth promotion by silencing Dicer/Drosha implied their potential use as therapeutic targets for neuroblastoma. Cancer Res; 70(20); 7841–50. ©2010 AACR.
Phase I Safety, Pharmacokinetics, and Inhibition of Src Activity Study of Saracatinib in Patients with Solid Tumors
Authors: Baselga José , Cervantes Andres , Martinelli Erika , Chirivella Isabel , Hoekman Klaas , Hurwitz Herbert I. , Jodrell Duncan I. , Hamberg Paul , Casado Esther , Elvin Paul , Swaisland Alan , Iacona Renee , Tabernero Josep
Published: August 2010

Purpose: This dose-escalation study evaluated the safety, tolerability, and pharmacokinetics (PK) of the oral Src inhibitor saracatinib (AZD0530) in patients with advanced solid malignancies. Tumor biopsy samples were taken to investigate the effect of saracatinib on Src activity in tumors.

Experimental Design: Part A of the study followed a multiple-ascending dose design to establish the maximum tolerated dose (MTD) of saracatinib. Part B was a randomized, parallel-group, cohort-expansion phase to further assess tolerated doses. Safety, tolerability, and Src activity (immunohistochemistry and lysate-based methodologies) were assessed after 21 days of once-daily oral dosing. PK was assessed after single and multiple dosing.

Results: In part A, 30 patients received once-daily saracatinib at doses of 60 to 250 mg; the MTD was established as 175 mg. In part B, 51 patients were randomized to receive 50 mg (n = 16), 125 mg (n = 16), or 175 mg (n = 19) of saracatinib. The most common grade ≥3 events considered to be treatment related were anemia, diarrhea, and asthenia. Tumor Src activity was reduced following saracatinib treatment. The area under the concentration-time curve and Cmax of saracatinib increased with increasing dose. Saracatinib accumulated 4- to 5-fold on once-daily dosing to reach steady-state exposure after 10 to 17 days of dosing. The half-life was ∼40 hours.

Conclusions: Saracatinib was well tolerated in patients with advanced solid malignancies. A reduction in tumor Src activity was observed. PK data show that saracatinib is suitable for once-daily oral dosing. Based on this study, the recommended dose for the phase II studies was chosen to be 175 mg/d. Clin Cancer Res; 16(19); 4876–83. ©2010 AACR.
Engineered Thio-Trastuzumab-DM1 Conjugate with an Improved Therapeutic Index to Target Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: Junutula Jagath R. , Flagella Kelly M. , Graham Richard A. , Parsons Kathryn L. , Ha Edward , Raab Helga , Bhakta Sunil , Nguyen Trung , Dugger Debra L. , Li Guangmin , Mai Elaine , Lewis Phillips Gail D. , Hiraragi Hajime , Fuji Reina N. , Tibbitts Jay , Vandlen Richard , Spencer Susan D. , Scheller Richard H. , Polakis Paul , Sliwkowski Mark X.
Published: August 2010

Purpose: Antibody drug conjugates (ADCs) combine the ideal properties of both antibodies and cytotoxic drugs by targeting potent drugs to the antigen-expressing tumor cells, thereby enhancing their antitumor activity. Successful ADC development for a given target antigen depends on optimization of antibody selection, linker stability, cytotoxic drug potency, and mode of linker-drug conjugation to the antibody. Here, we systematically examined the in vitro potency as well as in vivo preclinical efficacy and safety profiles of a heterogeneous preparation of conventional trastuzumab-mcc-DM1 (TMAb-mcc-DM1) ADC with that of a homogeneous engineered thio-trastuzumab-mpeo-DM1 (thioTMAb-mpeo-DM1) conjugate.

Experimental Design and Results: To generate thioTMAb-mpeo-DM1, one drug maytansinoid 1 (DM1) molecule was conjugated to an engineered cysteine residue at Ala114 (Kabat numbering) on each trastuzumab-heavy chain, resulting in two DM1 molecules per antibody. ThioTMAb-mpeo-DM1 retained similar in vitro anti–cell proliferation activity and human epidermal growth factor receptor 2 (HER2) binding properties to that of the conventional ADC. Furthermore, it showed improved efficacy over the conventional ADC at DM1-equivalent doses (μg/m2) and retained efficacy at equivalent antibody doses (mg/kg). An improved safety profile of >2-fold was observed in a short-term target-independent rat safety study. In cynomolgus monkey safety studies, thioTMAb-mpeo-DM1 was tolerated at higher antibody doses (up to 48 mg/kg or 6,000 μg DM1/m2) compared with the conventional ADC that had dose-limiting toxicity at 30 mg/kg (6,000 μg DM1/m2).

Conclusions: The engineered thioTMAb-mpeo-DM1 with broadened therapeutic index represents a promising antibody drug conjugate for future clinical development of HER2-positive targeted breast cancer therapies. Clin Cancer Res; 16(19); 4769–78. ©2010 AACR.
Evaluation of AR-H067637, the active metabolite of the new direct thrombin inhibitor AZD0837, in models of venous and arterial thrombosis and bleeding in anaesthetised rats
Authors: Pehrsson Susanne , Johansson Karin , Kjaer Magnus , Elg Margareta
Published: August 2010

AZD0837, currently in clinical development, is a once-daily oral anticoagulant that is bioconverted to AR-H067637, a selective, reversible direct thrombin inhibitor (DTI). When developing a new DTI, the anti-thrombotic effects are commonly investigated in in vivo animal models; this report shows the effect of AR-H067637 in venous and arterial thrombosis and bleeding models in anaesthetised rats. Thrombus formation was induced by topical application of ferric chloride to the carotid artery or to the caval vein with partial stasis. Cutaneous incision bleeding time and muscle transection blood loss were assessed, with or without acetylsalicylic acid (ASA). Activated partial thromboplastin time (APTT), ecarin coagulation time (ECT) and thrombin coagulation time (TCT) were used as plasma biomarkers of anticoagulant effect. Dalteparin was used as a reference compound. AR-H067637, given by continuous infusion, displayed a dose-dependent antithrombotic effect, with 50% inhibition (IC50) of thrombus size in venous and arterial thrombosis models obtained at plasma concentrations of 0.13 μM and 0.55 μM, respectively, without increased bleeding. Dose-dependent increased bleeding and blood loss were seen at plasma concentrations ≥1 μM AR-H067637. At the highest AR-H067637 plasma concentration tested, bleeding time and blood loss increased two and four times the vehicle group. Addition of ASA moderately potentiated bleeding time and blood loss. APTT, ECT and TCT were dose-dependently prolonged. These studies demonstrate that the DTI AR-H067637 inhibits thrombus formation in rat venous and arterial thrombosis models with no or minor increases in bleeding.
C1 inhibitor, a multi-functional serine protease inhibitor
Authors: Lu Fengxin , Mejia Pedro , Davis Alvin
Published: August 2010

C1 inhibitor (C1INH) is a serpin that regulates both complement and contact (kallikrein-kinin) system activation. It consists of a serpin domain that is highly homologous to other serpins and an amino terminal non-serpin mucin-like domain. Deficiency of C1INH results in hereditary angioedema, a disease characterised by episodes of angioedema of the skin or the mucosa of the gastrointestinal tract or the oropharynx. Although early data suggested that angioedema was mediated via complement system activation, the preponderance of the data indicate that bradykinin is the mediator. In the past few years, it has become apparent that C1INH has additional anti-inflammatory functions independent of protease inhibition. These include interactions with leukocytes that may result in enhanced phagocytosis, with endothelial cells via Eand P-selectins that interfere with leukocyte rolling and in turn results in suppression of transmigration of leukocytes across the endothelium, and interactions with extracellular matrix components that may serve to concentrate C1INH at sites of inflammation. In addition, C1INH suppresses gram negative sepsis and endotoxin shock, partly via direct interaction with endotoxin that interferes with its interaction with macrophages, thereby suppressing tumour necrosis factor-α and other inflammatory mediators. C1INH treatment improves outcome in a number of disease models, including sepsis and other bacterial infections, possibly malaria, ischaemia-reperfusion injury (intestinal, hepatic, muscle, cardiac, brain), hyper-acute transplant rejection, and other inflammatory disease models. Recent data suggest that this effectiveness is the result of mechanisms that do not require protease inhibition, in addition to both complement and contact system activation.
Incidental venous thromboembolism in ambulatory cancer patients receiving chemotherapy
Authors: Ferrante Noemi , Tursi Michele De , Iacobelli Stefano , Cuccurullo Franco , Büller Harry , Feragalli Beatrice , Porreca Ettore , Nisio Marcello Di
Published: August 2010

While the association between cancer and symptomatic venous thromboembolism (VTE) is well established, the incidence and risk factors for incidental VTE in cancer patients remain unclear. The medical records of 1,921 consecutive cancer patients starting chemotherapy from January 2003 up to March 2009 were identified. Patients with a positive history of VTE were excluded. Pre-existing signs of VTE, kind and stage of malignancy, first and subsequent lines of chemotherapy, and all follow-up computed tomography (CT) scans were analysed. The primary outcome was incidental VTE. Overall, there were 101 (5.3%) VTE, 62 (3.2%) incidental and 39 (2.0%) symptomatic during a median of eight months (range 3–72). The incidence on CT scans was 0.58% (95%CI: 0.44–0.74). Incidental VTE included 24 pulmonary embolism, 28 deep venous thrombosis of the extremities, and 10 thromboses of the cava or splanchnic veins. Half of the incidental VTE occurred in the first 3–6 months of chemotherapy with a relatively higher incidence in gyneco-logical and lung cancers. The presence of metastases, high leukocyte count, and platin-based chemotherapy increased the risk up to threefold. All patients with incidental VTE regardless the location received half to full therapeutic doses of low-molecular-weight heparin for a minimum of three months. In summary, incidental VTE is a relative common finding in patients with solid tumours, especially in the first months of chemotherapy. Further research is needed to understand the natural history of incidental thrombosis in order to develop adequate management guidelines.
Evaluation of commercial von Willebrand factor collagen binding assays to assist the discrimination of types 1 and 2 von Willebrand disease
Authors: Favaloro Emmanuel
Published: August 2010

This study reports on the evaluation of seven commercial von Wille-brand factor (VWF) collagen binding (VWF:CB) assays to potentially assist the discrimination of types 1 and 2 von Willebrand disease (VWD). Samples from 25 patients with type 1 VWD, of varying severity, were co-tested with 16 samples from patients with types 2A or 2B VWD, plus various control samples, using each commercial VWF:CB assay assessed against our standard (reference) in-house VWF:CB assay, as well as our in-house VWF antigen (VWF:Ag) and ristocetin cofactor (VWF:RCo) assays. Commercial VWF:CB assays varied in their ability to discriminate types 1 and 2A/2B VWD. The optimal VWF:CB/VWF:Ag ratio at which optimal discrimination occurred also differed between assays, with some improvements observed with some (but not all) as-says following a harmonisation process that aimed to correct for different calibrator effects. Assay variability also compromised assay utility in some test occasions. Future standardisation and improvements in some commercial VWF:CB assays are needed before the VWF:CB assay can be more fully and globally utilised for discrimination of VWD types in diagnostic laboratories.
Does Black Ethnicity Influence the Development of Stent Thrombosis in the Drug-Eluting Stent Era?
Authors: Collins Sara D. , Torguson Rebecca , Gaglia Michael A. , Lemesle Gilles , Syed Asmir I. , Ben-Dor Itsik , Li Yanlin , Maluenda Gabriel , Kaneshige Kimberly , Xue Zhenyi , Kent Kenneth M. , Pichard Augusto D. , Suddath William O. , Satler Lowell F. , Waksman Ron
Published: August 2010

Background—

It has been suggested that black race predicts stent thrombosis (ST) after drug-eluting stent implantation. Whether socioeconomic status or comorbid conditions confound the contribution of black race to the development of ST is unclear.

Methods and Results—

We compared 1594 black patients who underwent drug-eluting stent implantation with 5642 nonblack patients. Overall, 108 definite STs were reported. Multivariable Cox regression analysis was performed with adjustment for comorbidities, including median household income as a marker of socioeconomic status, to assess the impact that black race may have on the development of ST. On univariable analysis, black patients were younger (63.43±12.42 versus 65.15±12.59 years;
P
<0.001) and more likely to have a history of hypertension (89.8% versus 81.7%;
P
<0.001), diabetes mellitus (45.5% versus 30.8%;
P
<0.001), chronic renal insufficiency (19.2% versus 10.7%;
P
<0.001), and congestive heart failure (18.7% versus 13.1%;
P
<0.001). Clopidogrel compliance at the time of the ST event was higher in the black than in the nonblack population (87.5% versus 77.8%;
P
=0.068). After multivariable analysis, including adjustment for median income and clopidogrel compliance, black race emerged as a strong predictor of definite late ST.

Conclusions—

Black race is an independent predictor of definite drug-eluting stent ST. Because clopidogrel compliance was higher in black patients and socioeconomic status was not associated with ST, further investigation into the potential mechanisms of this influence of race on ST must be pursued.
Get With The Guidelines-Stroke Performance Indicators: Surveillance of Stroke Care in the Taiwan Stroke Registry
Authors: Hsieh Fang-I , Lien Li-Ming , Chen Sien-Tsong , Bai Chyi-Huey , Sun Mu-Chien , Tseng Hung-Pin , Chen Yu-Wei , Chen Chih-Hung , Jeng Jiann-Shing , Tsai Song-Yen , Lin Huey-Juan , Liu Chung-Hsiang , Lo Yuk-Keung , Chen Han-Jung , Chiu Hou-Chang , Lai Ming-Liang , Lin Ruey-Tay , Sun Ming-Hui , Yip Bak-Sau , Chiou Hung-Yi , Hsu Chung Y. ,   the Taiwan Stroke Registry Investigators
Published: August 2010

Background—

Stroke is a leading cause of death around the world. Improving the quality of stroke care is a global priority, despite the diverse healthcare economies across nations. The American Heart Association/American Stroke Association Get With the Guidelines-Stroke program (GWTG-Stroke) has improved the quality of stroke care in 790 US academic and community hospitals, with broad implications for the rest of the country. The generalizability of GWTG-Stroke across national and economic boundaries remains to be tested. The Taiwan Stroke Registry, with 30 599 stroke admissions between 2006 and 2008, was used to assess the applicability of GWTG-Stroke in Taiwan, which spends ≈1/10 of what the United States does in medical costs per new or recurrent stroke.

Methods and Results—

Taiwan Stroke Registry, sponsored by the Taiwan Department of Health, engages 39 academic and community hospitals and covers the entire country with 4 steps of quality control to ensure the reliability of entered data. Five GWTG-Stroke performance measures and 1 safety indicator are applicable to assess Taiwan Stroke Registry quality of stroke care. Demographic and outcome figures are comparable between GWTG-Stroke and Taiwan Stroke Registry. Two indicators (early and discharge antithrombotics) are close to GWTG-Stroke standards, while 3 other indicators (intravenous tissue plasminogen activator, anticoagulation for atrial fibrillation, lipid-lowering medication) and 1 safety indicator fall behind. Preliminary analysis shows that compliance with selected GWTG-Stroke guidelines is associated with better outcomes.

Conclusions—

Results suggest that GWTG-Stroke performance measures, with modification for ethnic factors, can become global standards across national and economic boundaries for assessing and improving quality of stroke care and outcomes. GWTG-Stroke can be incorporated into ongoing stroke registries across nations.
Time in Recurrent Ventricular Fibrillation and Survival After Out-of-Hospital Cardiac Arrest
Authors: Berdowski Jocelyn , ten Haaf Monique , Tijssen Jan G.P. , Chapman Fred W. , Koster Rudolph W.
Published: August 2010

Background—

Current resuscitation guidelines (2005 guidelines [G2005]) accelerate ventricular fibrillation (VF) recurrence. We investigated whether patients resuscitated under G2005 spend more time in VF and have better survival rates than patients treated under the 2000 guidelines (G2000).

Methods and Results—

We analyzed continuous ECG recordings of out-of-hospital cardiac arrests prospectively collected from January 2006 to January 2008. Patients treated according to G2000 (n=282) or G2005 (n=240) with VF as initial rhythm were included. We measured the total time a patient was in recurrent VF (the sum of all intervals from each onset of recurrent VF to each next successful shock) and the time a patient was in initial VF (time interval from rescuer arrival to first effective shock). The primary outcome measure was neurologically intact survival to discharge. The median time in recurrent VF was 2.7 minutes (quartile 1 to 3, 0.4 to 9.0 minutes) under G2000 versus 4.0 minutes (quartile 1 to 3, 0.2 to 11.6 minutes) under G2005 (
P
=0.03). Median time in initial VF was 2.7 minutes (quartile 1 to 3, 1.7 to 4.3 minutes) versus 3.9 minutes (quartile 1 to 3, 2.3 to 6.5 minutes), respectively (
P
<0.001). Increased time in recurrent VF was significantly associated with decreased neurologically intact survival in both G2000 use (odds ratio, 0.92; 95% confidence interval, 0.87 to 0.97;
P
=0.001) and G2005 use (odds ratio, 0.94; 95% confidence interval, 0.90 to 0.99;
P
=0.02). Neurologically intact survival decreased significantly with increasing time in initial VF under G2000 (odds ratio, 0.86; 95% confidence interval, 0.74 to 0.99;
P
=0.04). This observation was nonexistent in patients treated under G2005. Neurologically intact survival was 29% (82 of 282) under G2000 versus 27% (65 of 240) under G2005 (
P
=0.61).

Conclusions—

With G2005, the time in recurrent VF remains associated with worse outcome. Studies of immediate defibrillation for recurrent VF are warranted.
A Ripple-Spreading Genetic Algorithm for the Aircraft Sequencing Problem
Authors: Hu Xiao-Bing , Paolo Ezequiel A. Di
Published: August 2010

When genetic algorithms (GAs) are applied to combinatorial problems, permutation representations are usually adopted. As a result, such GAs are often confronted with feasibility and memory-efficiency problems. With the aircraft sequencing problem (ASP) as a study case, this paper reports on a novel binary-representation-based GA scheme for combinatorial problems. Unlike existing GAs for the ASP, which typically use permutation representations based on aircraft landing order, the new GA introduces a novel ripple-spreading model which transforms the original landing-order-based ASP solutions into value-based ones. In the new scheme, arriving aircraft are projected as points into an artificial space. A deterministic method inspired by the natural phenomenon of ripple-spreading on liquid surfaces is developed, which uses a few parameters as input to connect points on this space to form a landing sequence. A traditional GA, free of feasibility and memory-efficiency problems, can then be used to evolve the ripple-spreading related parameters in order to find an optimal sequence. Since the ripple-spreading model is the centerpiece of the new algorithm, it is called the ripple-spreading GA (RSGA). The advantages of the proposed RSGA are illustrated by extensive comparative studies for the case of the ASP.
A Probabilistic Analysis of a Simplified Biogeography-Based Optimization Algorithm
Authors: Simon Dan
Published: August 2010

Biogeography-based optimization (BBO) is a population-based evolutionary algorithm (EA) that is based on the mathematics of biogeography. Biogeography is the study of the geographical distribution of biological organisms. We present a simplified version of BBO and perform an approximate analysis of the BBO population using probability theory. Our analysis provides approximate values for the expected number of generations before the population's best solution improves, and the expected amount of improvement. These expected values are functions of the population size. We quantify three behaviors as the population size increases: first, we see that the best solution in the initial randomly generated population improves; second, we see that the expected number of generations before improvement increases; and third, we see that the expected amount of improvement decreases.
On the Optimal Convergence Probability of Univariate Estimation of Distribution Algorithms
Authors: Rastegar Reza
Published: August 2010

In this paper we obtain bounds on the probability of convergence to the optimal solution for the compact genetic algorithm (cGA) and the population based incremental learning (PBIL). Moreover, we give a sufficient condition for convergence of these algorithms to the optimal solution and compute a range of possible values for algorithm parameters at which there is convergence to the optimal solution with a predefined confidence level.
The First Uprising of the Cultural Revolution at Nanjing University: Dynamics, Nature, and Interpretation
Authors: Guoqiang Dong
Published: August 2010

The “2 June Incident” at Nanjing University in 1967 was a seminal event at the start of China's Cultural Revolution. By closely analyzing the origins and nature of the incident on the basis of recently released Chinese sources, the article shows that local tensions and protests had unexpectedly wide consequences. The incident was seized on by the central CCP authorities to radicalize the Cultural Revolution and plunge China into greater chaos, which also contributed to unpredictable shifts in PRC foreign policy.
Cross-modal Processing in the Occipito-temporal Cortex: A TMS Study of the Müller-Lyer Illusion
Authors: Mancini Flavia , Bolognini Nadia , Bricolo Emanuela , Vallar Giuseppe
Published: August 2010

The Müller-Lyer illusion occurs both in vision and in touch, and transfers cross-modally from vision to haptics [Mancini, F., Bricolo, E., & Vallar, G. Multisensory integration in the Müller-Lyer illusion: From vision to haptics. Quarterly Journal of Experimental Psychology, 63, 818–830, 2010]. Recent evidence suggests that the neural underpinnings of the Müller-Lyer illusion in the visual modality involve the bilateral lateral occipital complex (LOC) and right superior parietal cortex (SPC). Conversely, the neural correlates of the haptic and cross-modal illusions have never been investigated previously. Here we used repetitive TMS (rTMS) to address the causal role of the regions activated by the visual illusion in the generation of the visual, haptic, and cross-modal visuo-haptic illusory effects, investigating putative modality-specific versus cross-modal underlying processes. rTMS was administered to the right and the left hemisphere, over occipito-temporal cortex or SPC. rTMS over left and right occipito-temporal cortex impaired both unisensory (visual, haptic) and cross-modal processing of the illusion in a similar fashion. Conversely, rTMS interference over left and right SPC did not affect the illusion in any modality. These results demonstrate the causal involvement of bilateral occipito-temporal cortex in the representation of the visual, haptic, and cross-modal Müller-Lyer illusion, in favor of the hypothesis of shared underlying processes. This indicates that occipito-temporal cortex plays a cross-modal role in perception both of illusory and nonillusory shapes.
Active Ignoring in Early Visual Cortex
Authors: Payne Helen E. , Allen Harriet A.
Published: August 2010

Selective attention is critical for controlling the input to mental processes. Attentional mechanisms act not only to select relevant stimuli but also to exclude irrelevant stimuli. There is evidence that we can actively ignore irrelevant information. We measured neural activity relating to successfully ignoring distracters (using preview search) and found increases in both the precuneus and primary visual cortex during preparation to ignore distracters. We also found reductions in activity in fronto-parietal regions while previewing distracters and a reduction in activity in early visual cortex during search when a subset of items was successfully excluded from search, both associated with precuneus activity. These results are consistent with the proposal that actively excluding distractions has two components: an initial stage where distracters are encoded, and a subsequent stage where further processing of these items is inhibited. Our findings suggest that it is the precuneus that controls this process and can modulate activity in visual cortex as early as V1.
Brain Areas Consistently Linked to Individual Differences in Perceptual Decision-making in Younger as well as Older Adults before and after Training
Authors: Kühn Simone , Schmiedek Florian , Schott Björn , Ratcliff Roger , Heinze Hans-Jochen , Düzel Emrah , Lindenberger Ulman , Lövden Martin
Published: August 2010

Perceptual decision-making performance depends on several cognitive and neural processes. Here, we fit Ratcliff's diffusion model to accuracy data and reaction-time distributions from one numerical and one verbal two-choice perceptual-decision task to deconstruct these performance measures into the rate of evidence accumulation (i.e., drift rate), response criterion setting (i.e., boundary separation), and peripheral aspects of performance (i.e., nondecision time). These theoretical processes are then related to individual differences in brain activation by means of multiple regression. The sample consisted of 24 younger and 15 older adults performing the task in fMRI before and after 100 daily 1-hr behavioral training sessions in a multitude of cognitive tasks. Results showed that individual differences in boundary separation were related to striatal activity, whereas differences in drift rate were related to activity in the inferior parietal lobe. These associations were not significantly modified by adult age or perceptual expertise. We conclude that the striatum is involved in regulating response thresholds, whereas the inferior parietal lobe might represent decision-making evidence related to letters and numbers.
Sustained Preferential Processing of Social Threat Cues: Bias without Competition?
Authors: Wieser Matthias J. , McTeague Lisa M. , Keil Andreas
Published: August 2010

Stimuli of high emotional significance such as social threat cues are preferentially processed in the human brain. However, there is an ongoing debate whether or not these stimuli capture attention automatically and weaken the processing of concurrent stimuli in the visual field. This study examined continuous fluctuations of electrocortical facilitation during competition of two spatially separated facial expressions in high and low socially anxious individuals. Two facial expressions were flickered for 3000 msec at different frequencies (14 and 17.5 Hz) to separate the electrocortical signals evoked by the competing stimuli (“frequency tagging”). Angry faces compared to happy and neutral expressions were associated with greater electrocortical facilitation over visual areas only in the high socially anxious individuals. This finding was independent of the respective competing stimulus. Heightened electrocortical engagement in socially anxious participants was present in the first second of stimulus viewing and was sustained for the entire presentation period. These results, based on a continuous measure of attentional resource allocation, support the view that stimuli of high personal significance are associated with early and sustained prioritized sensory processing. These cues, however, do not interfere with the electrocortical processing of a spatially separated concurrent face, suggesting that they are effective at capturing attention, but are weak competitors for resources.
Dietary Restraint Violations Influence Reward Responses in Nucleus Accumbens and Amygdala
Authors: Demos Kathryn E. , Kelley William M. , Heatherton Todd F.
Published: August 2010

Numerous studies have demonstrated that consuming high-calorie food leads to subsequent overeating by chronic dieters. The present study investigates the neural correlates of such self-regulatory failures using fMRI. Chronic dieters (n = 50) and non-dieters (n = 50) consumed either a 15-oz glass of cold water or a 15-oz milkshake and were subsequently imaged while viewing pictures of animals, environmental scenes, people, and appetizing food items. Results revealed a functional dissociation in nucleus accumbens and amygdala activity that paralleled well-established behavioral patterns of eating observed in dieters and non-dieters. Whereas non-dieters showed the greatest nucleus accumbens activity in response to food items after water consumption, dieters showed the greatest activity after consuming the milkshake. Activity in the left amygdala demonstrated the reverse interaction. Considered together with previously reported behavioral findings, the present results offer a suggested neural substrate for diet failure.
Combating Meaninglessness: On the Automatic Defense of Meaning
Authors: Van Tongeren Daryl R. , Green Jeffrey D.
Published: August 2010

Research has found that a substantial portion of human cognition occurs beyond conscious awareness to satisfy the superordinate goal of maintaining meaning. Three experiments used a newly developed method to examine the features of meaning and how individuals automatically defend against threats to meaning. In Experiment 1, individuals who subliminally processed meaninglessness-related words, relative to those in a control group, reported being more religious and having more meaningful lives. Experiment 2 extended these results, as individuals whose meaning was threatened bolstered alternative domains of meaning (termed fluid compensation) by reporting higher self-esteem, need for closure, symbolic immortality, and a reduced need to belong. Experiment 3 ruled out an alternative explanation and clarified the effects of threatened meaning on one’s need to belong. These findings elucidate the processes of meaning maintenance in sustaining psychological equanimity. Implications for the automatic defense of meaning are discussed.
Histology Atlas of the Developing Mouse Hepatobiliary System with Emphasis on Embryonic Days 9.5-18.5
Authors: Crawford Laura Wilding , Foley Julie F. , Elmore Susan A.
Published: August 2010

Animal model phenotyping, in utero exposure toxicity studies, and investigation into causes of embryonic, fetal, or perinatal deaths have required pathologists to recognize and diagnose developmental disorders in spontaneous and engineered mouse models of disease. In mammals, the liver is the main site of hematopoiesis during fetal development, has endocrine and exocrine functions important for maintaining homeostasis in fetal and adult life; and performs other functions including waste detoxification, production and removal of glucose, glycogen storage, triglyceride and fatty acid processing, and serum protein production. Due to its role in many critical functions, alterations in the size, morphology, or function(s) of the liver often lead to embryonic lethality. Many publications and websites describe individual aspects of hepatobiliary development at defined stages. However, no single resource provides a detailed histological evaluation of H&E-stained sections of the developing murine liver and biliary systems using high-magnification and high-resolution color images. The work herein provides a histology atlas of hepatobiliary development between embryonic days 9.5-18.5. Although the focus of this work is normal hepatobiliary development, common defects in liver development are also described as a reference for pathologists who may be asked to phenotype mice with congenital, inherited, or treatment-related hepatobiliary defects.

Authors’ note: All digital images can be viewed online at https://niehsimagesepl-inc.com with the username “ToxPathLiver” and the password “embryolivers.”
Aerosol Exposure to the Angola Strain of Marburg Virus Causes Lethal Viral Hemorrhagic Fever in Cynomolgus Macaques
Authors: Alves D. A. , Glynn A. R. , Steele K. E. , Lackemeyer M. G. , Garza N. L. , Buck J. G. , Mech C. , Reed D. S.
Published: August 2010

Cynomolgus macaques were exposed to the Angola strain of Lake Victoria Marburg virus (MARV) by aerosol to examine disease course and lethality. Macaques became febrile 4 to 7 days postexposure; the peak febrile response was delayed 1 to 2 days in animals that received a lower dose; viremia coincided with the onset of fever. All 6 macaques succumbed to the infection, with the 3 macaques in the low-dose group becoming moribund on day 9, a day later than the macaques in the high-dose group. Gross pathologic lesions included maculopapular cutaneous rash; pulmonary congestion and edema; pericardial effusion; enlarged, congested, and/or hemorrhagic lymphoid tissues; enlarged friable fatty liver; and pyloric and duodenal congestion and/or hemorrhage. Fibrinous interstitial pneumonia was the most consistent pulmonary change. Lymphocytolysis and lymphoid depletion, as confirmed by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling), were observed in the mediastinal lymph nodes and spleen. MARV antigen was detected in the lungs, mediastinal lymph nodes, spleen, and liver of all animals examined. In infected macaques, nuclear expression of interleukin-33 was lost in pulmonary arteriolar and mediastinal lymph node high endothelial venule endothelial cells; interleukin-33-positive fibroblastic reticular cells in the mediastinal lymph node were consistently negative for MARV antigen. These macaques exhibited a number of features similar to those of human filovirus infections; as such, this model of aerosolized MARV-Angola might be useful in developing medical countermeasures under the Animal Rule.
Validity and Internal Consistency of the International Knee Documentation Committee Subjective Knee Evaluation Form in Children and Adolescents
Authors: Schmitt Laura C. , Paterno Mark V. , Huang Samuel
Published: August 2010

Background

The International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form (IKDC Knee Form) is a valid, reliable, and responsive measure of knee-related symptoms, function, and sports activities in adults. Despite the incidence of knee injuries in younger individuals, the measurement characteristics of the IKDC Knee Form have not been established.

Hypothesis/Purpose

The purpose of this study was to investigate the validity and internal consistency of the IKDC Knee Form in pediatric, adolescent, and young adult patients with a variety of knee conditions. The authors hypothesized that the IKDC Knee Form would be a valid and consistent measure of knee function in these age groups.

Study Design

Cohort study (diagnosis); Level of evidence, 2.

Methods

The IKDC Knee Form and Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) physical functioning component were administered to 673 individuals between 6 and 18 years of age. The internal consistency and validity of the IKDC Knee Form were determined for the entire cohort and for age group cohorts (pediatric, 6-12 years; adolescent, 13-15 years; young adult, 16-18 years) using the PedsQL physical functioning component for comparison.

Results

The results were similar across all age groups. In the original format, internal consistency was high and factor analysis showed a single, dominant component underlying the item responses for each age group. Items 2, 3, and 6 may contribute to measurement error in young individuals. Correlation between the IKDC Knee Form and PedsQL physical functioning component score was moderately high for the entire cohort (r = .83) and for all age groups (pediatric, r = .84; adolescent, r = .84; young adult, r = .79).

Conclusion

In its current form, the IKDC Knee Form is a valid and consistent knee-specific measure of symptoms, function, and sports activity in individuals between the ages of 6 and 18 years with a variety of knee problems. Further work is needed to establish the reliability and responsiveness of the IKDC Knee Form for this age group.
From psyche to soma? Changing accounts of antisocial personality disorders in the American Journal of Psychiatry
Authors: Pickersgill Martyn
Published: August 2010

The history of psychiatry is often portrayed through the metaphor of a pendulum, the profession swinging back and forth between a concern with psyche and soma. Recent work critiquing the pendulum metaphor, however, suggests that it does not account for the complexity of psychiatry.This article explores the metaphor through an analysis of the changing aetiological accounts of personality disorders associated with antisocial behaviour advanced in the American Journal of Psychiatry from 1950 onwards. It is argued that the social, scientific and economic factors which help shape overarching professional trends in psychiatry only partly structure personality disorder discourse. If the pendulum swings, therefore, not all psychiatrists move with it.
The reception of Eugen Bleuler in British psychiatry, 1892-1954
Authors: Dalzell Thomas
Published: August 2010

This article draws on over 60 years of British medical journals and psychiatry textbooks to indicate the chronological stages of the reception of Eugen Bleuler in British psychiatry. Bleuler was already well known in Britain before his schizophrenia book appeared, with the journals containing numerous references, mainly positive, to his work. The psychiatry textbooks, however, were slower to integrate his contribution. This paper argues that this was not due to Bleuler’s placing Freud on a par with Kraepelin, but because of the early negative reaction to Kraepelin’s dementia praecox concept, despite Bleuler’s wider and less ominous conception of the illness.
Burying Indigeneity: The Spatial Construction of Reality and Aboriginal Australia
Authors: Atkinson Rowland , Taylor Elizabeth , Walter Maggie
Published: August 2010

In this article we argue that spatial distance and historic socio-ethnic boundaries play a critical role in determining the relative priority given to groups that are marginally placed. These priorities are materialized through law. We utilize theories that understand ‘reality’ as something socially constructed: our impressions of the structure of everyday life are mediated in large part by our primary social group interactions. We profile the spatial distribution and relative segregation of Indigenous Australians, from urban to remote regional contexts. Our data highlights how even a predominantly urban Indigenous population remains out of the sight and mind of social and political actors due to its small numerical size and perceived social difference. We move to explain public policy formulation in terms of orientations that are influenced by the spatiality of social affiliations. We suggest that the spatially-bounded patterning of black and white lives supports the continued burial of Indigenous life. The socio-spatial construction of Indigenous life for white and other Australians has enabled both aggressive and neglectful policy instruments in which Aboriginal life appears as something that is politically, legally and spatially marginal.
Law, Boundaries and the Production of Space
Authors: Blandy Sarah , Sibley David
Published: August 2010

This special issue addresses the problematic nature of space, whether psychic, symbolic or material, from an inter-disciplinary standpoint. The diverse articles are concerned with legal, psychical, cultural, social and political boundaries. Spaces with legal meanings are the product of such boundaries, and the relation of law and space as explored by the legal geography literature underpins this collection, which investigates these issues at a range of spatial scales, from the scale of the self to the global. In considering the continuum of tension between fear and desire manifest in individuals’ internalized boundaries, we need also to make use of theories developed in psychoanalysis and social psychology. Kleinian ‘splitting’, for example, offers an explanation of law’s role in the creation and maintenance of strong boundaries which exclude ‘othered’ groups. Law’s power as a discourse is challenged by internal contradictions at the international scale, when human rights arguments confront state territorial jurisdiction; while at the other end of the scalar spectrum, regulation of conduct depends both on accepted legal notions of the self-governing individual and on assumptions of shared moral values. Other articles in this issue emphasize the nature of boundaries as liminal spaces full of attendant ambiguity, which, although legally established and enforced, prove in fact to be remarkably permeable. The interdisciplinary perspectives developed in this issue demonstrate the need to further problematize boundaries and to acknowledge the complexity of material, social and mental spaces.
Moral Entrepreneurs and Moral Geographies on the US/Mexico Border
Authors: Taylor Lawrence J.
Published: August 2010

This article explores the difference and interplay between the border as legal/political fact and the borderland as complex social/cultural reality through the development and application of the theoretical concepts of moral geography and moral entrepreneur. I argue that these concepts provide a bridge between macro, structural views of ‘the production of (borderland) space’ as used by critical geographers and the more experiential orientation suggested by geographers and anthropologists in studies of cultural landscapes and ‘place-making’. My particular concern is to apply and illustrate this argument through the ethnography of the desert borderlands straddling Arizona (USA) and Sonora (Mexico), but it is potentially useful in other contexts.
The Right to Pass Freely: Circulation, Begging, and The Bounded Self
Authors: Blomley Nicholas
Published: August 2010

Scholars of public space criticize regulation governing the behaviour of the public poor for both its illiberal effects and motivations. The arguments used to justify such regulation are frequently characterized as a smokescreen that conceal more sinister agendas, and are thus often overlooked by critics. But to fail to take such arguments seriously, I argue, is to miss their political traction. This, I suggest, has less to do with their inherent truthfulness than with their basis in a prevailing social imaginary that can be characterized as broadly liberal. As such, they reflect and help constitute a powerfully hegemonic view. At their core is a particular conception of the atomistic self-governing individual, engaged in dyadic relations, structured according to a logic of negative rights and autonomy. Begging, in particular, threatens the boundaries that lie at the core of this account: in particular, those that surround and protect the mobile subject. Rather than just damning the illiberalism of this law-talk, in other words, critics would do better to also recognize and critique its liberal nature.
Postoperative Statin Therapy Attenuates the Intensity of Systemic Inflammation and Increases Fibrinolysis After Coronary Artery Bypass Grafting
Authors: Tetik Sermin , Ak Koray , Sahin Yucel , Gulsoy Ozkan , Isbir Selim , Arsan Sinan , Yardimci Turay
Published: August 2010

A total of 25 patients undergoing coronary artery bypass grafting (CABG) were included in the study. Patients received statin (20 mg daily) postoperatively for 2 weeks. All analyses were performed at 2 different time points: preoperatively (group 1) and 2 weeks after operation (group 2). Interleukin (IL)-6, IL-8, plasminogen activator inhibitor 1 (PAI-1), tumor necrosis factor α (TNF-α), tissue plasminogen activator (t-PA) levels, and tissue factor pathway inhibitor (TFPI) were evaluated. Statin treatment caused a significant reduction in the plasma level of PAI-1 (preop: 15.04 ± 0.13 ng/mL vs postop: 13.89 ± 2.14 ng/mL; P < .05) and increased t-PA levels (preop: 109.74 ± 0.13 vs postop: 231.40 ± 1.22 ng/mL; P < .001). Plasma TNF-α and IL-6 levels did not change with treatment. Statin treatment caused a significant reduction in plasma IL-8 level (279.70 ± 3.42 ng/mL vs postop: 207.18 ± 3.63 ng/mL, P < .05), and TFPI (4.87 ± 2.05 ng/mL vs postop: 6.27 ± 1.25 ng/mL; P < .05). The results demonstrate that atorvastatin attenuates systemic inflammatory reaction after cardiac surgery.