bluuebunny/crossref_metadata_2025 huggingface dataset:
Macrophage-Induced Tumor Angiogenesis Is Regulated by the TSC2–mTOR Pathway
Authors: Chen Wei , Ma Tao , Shen Xu-ning , Xia Xue-feng , Xu Guo-dong , Bai Xue-li , Liang Ting-bo
Published: January 2012

Tumor-associated macrophages (TAM) have multifaceted roles in tumor development but they have been associated particularly closely with tumor angiogenesis. However, although the accumulation of TAM (M2 phenotype) promotes tumor angiogenesis, the mechanism through which monocytes differentiate to generate TAM is unclear. Here, we report that the mTOR pathway is a critical element in the regulation of monocyte differentiation to TAM. In human peripheral monocytes stimulated by lipopolysaccharide, mTOR was inhibited by rapamycin or activated by RNA interference–mediated knockdown of the mTOR repressor tuberous sclerosis complex 2 (TSC2). Rapamycin caused the monocytes to differentiate into M1 macrophages releasing more interleukin (IL)-12 and less IL-10, whereas TSC2 knockdown caused the monocytes to differentiate into M2 macrophages releasing less IL-12 and more IL-10. In parallel fashion, angiogenic properties were promoted or reduced in human umbilical vein endothelial cells cocultured with TSC2-deficient monocytes or rapamycin-treated monocytes, respectively. Furthermore, tumor angiogenesis and growth in murine xenografts were promoted or reduced by infusion of hosts with TSC2-deficient or TSC2-overexpressing monocytes, respectively. Finally, in vivo depletion of macrophages was sufficient to block the antiangiogenic effects of rapamycin on tumors. Our results define the TSC2–mTOR pathway as a key determinant in the differentiation of monocytes into M2 phenotype TAM that promote angiogenesis. Cancer Res; 72(6); 1363–72. ©2012 AACR.
Regulation of Cancer Progression by β-Endorphin Neuron
Authors: Sarkar Dipak K. , Murugan Sengottuvelan , Zhang Changqing , Boyadjieva Nadka
Published: January 2012

It is becoming increasingly clear that stressful life events can affect cancer growth and metastasis by modulating nervous, endocrine, and immune systems. The purpose of this review is to briefly describe the process by which stress may potentiate carcinogenesis and how reducing body stress may prevent cancer growth and progression. The opioid peptide β-endorphin plays a critical role in bringing the stress axis to a state of homeostasis. We have recently shown that enhancement of endogenous levels of β-endorphin in the hypothalamus via β-endorphin neuron transplantation suppresses stress response, promotes immune function, and reduces the incidence of cancer in rat models of prostate and breast cancers. The cancer-preventive effect of β-endorphin is mediated through the suppression of sympathetic neuronal function, which results in increased peripheral natural killer cell and macrophage activities, elevated levels of anti-inflammatory cytokines, and reduced levels of inflammatory cytokines. β-endorphin inhibition of tumor progression also involves alteration in the tumor microenvironment, possibly because of suppression of catecholamine and inflammatory cytokine production, which are known to alter DNA repair, cell-matrix attachments, angiogenic process, and epithelial–mesenchymal transition. Thus, β-endorphin cell therapy may offer some therapeutic value in cancer prevention. Cancer Res; 72(4); 836–40. ©2012 AACR.
Resampling Phase III Data to Assess Phase II Trial Designs and Endpoints
Authors: Sharma Manish R. , Karrison Theodore G. , Jin Yuyan , Bies Robert R. , Maitland Michael L. , Stadler Walter M. , Ratain Mark J.
Published: January 2012

Purpose: The best phase II design and endpoint for growth inhibitory agents is controversial. We simulated phase II trials by resampling patients from a positive (sorafenib vs. placebo; TARGET) and a negative (AE941 vs. placebo) phase III trial in metastatic renal cancer to compare the ability of various designs and endpoints to predict the known results.

Experimental Design: A total of 770 and 259 patients from TARGET and the AE 941 trial, respectively, were resampled (5,000 replicates) to simulate phase II trials with α = 0.10 (one-sided). Designs/endpoints: single arm, two-stage with response rate (RR) by Response Evaluation Criteria in Solid Tumors (RECIST; 37 patients); and randomized, two arm (20–35 patients per arm) with RR by RECIST, mean log ratio of tumor sizes (log ratio), progression-free survival (PFS) rate at 90 days (PFS-90), and overall PFS.

Results: Single-arm trials were positive with RR by RECIST in 55% and 1% of replications for sorafenib and AE 941, respectively. Randomized trials versus placebo with 20 patients per arm were positive with RR by RECIST in 55% and 7%, log ratio in 88% and 25%, PFS-90 in 64% and 15%, and overall PFS in 69% and 9% of replications for sorafenib and AE 941, respectively.

Conclusions: Compared with the single-arm design and the randomized design comparing PFS, the randomized phase II design with the log ratio endpoint has greater power to predict the positive phase III result of sorafenib in renal cancer, but a higher false positive rate for the negative phase III result of AE 941. Clin Cancer Res; 18(8); 2309–15. ©2012 AACR.
Distinct EEG Amplitude Suppression to Facial Gestures as Evidence for a Mirror Mechanism in Newborn Monkeys
Authors: Ferrari Pier Francesco , Vanderwert Ross E. , Paukner Annika , Bower Seth , Suomi Stephen J. , Fox Nathan A.
Published: January 2012

At birth, human infants and newborns of other primate species demonstrate the capacity to attend and to respond to facial stimuli provided by a caregiver. Newborn infants are also capable of exhibiting a range of facial expressions. Identification of the neural underpinnings of these capacities represents a formidable challenge in understanding social development. One possible neuronal substrate is the mirror-neuron system assumed to activate shared motor cortical representations for both observation and production of actions. We tested this hypothesis by recording scalp EEG from 1- to 7-day-old newborn rhesus macaques who were observing and producing facial gestures. We found that 5–6 Hz EEG activity was suppressed both when the infants produced facial gestures and while they were observing facial gestures of a human experimenter, but not when they were observing nonbiological stimuli. These findings demonstrate the presence of neural reactivity for biological, communicatively relevant stimuli, which may be a likely signature of neuronal mirroring. The basic elements of the mirror-neuron system appear to operate from the very first days of life and contribute to the encoding of socially relevant stimuli.
Controlling Conflict from Interfering Long-term Memory Representations
Authors: Jost Kerstin , Khader Patrick H. , Düsel Peter , Richter Franziska R. , Rohde Kristina B. , Bien Siegfried , Rösler Frank
Published: January 2012

Remembering is more than an activation of a memory trace. As retrieval cues are often not uniquely related to one specific memory, cognitive control should come into play to guide selective memory retrieval by focusing on relevant while ignoring irrelevant information. Here, we investigated, by means of EEG and fMRI, how the memory system deals with retrieval interference arising when retrieval cues are associated with two material types (faces and spatial positions), but only one is task-relevant. The topography of slow EEG potentials and the fMRI BOLD signal in posterior storage areas indicated that in such situations not only the relevant but also the irrelevant material becomes activated. This results in retrieval interference that triggers control processes mediated by the medial and lateral PFC, which are presumably involved in biasing target representations by boosting the task-relevant material. Moreover, memory-based conflict was found to be dissociable from response conflict that arises when the relevant and irrelevant materials imply different responses. The two types of conflict show different activations in the medial frontal cortex, supporting the claim of domain-specific prefrontal control systems.
The Human Ventromedial Prefrontal Cortex Is Critical for Transitive Inference
Authors: Koscik Timothy R. , Tranel Daniel
Published: January 2012

We hypothesized that the ventromedial pFC (vmPFC) is critical for making transitive inferences (e.g., the logical operation that if A > B and B > C, then A > C). To test this, participants with focal vmPFC damage, brain-damaged comparison participants, and neurologically normal participants completed a transitive inference task consisting an ordered set of arbitrary patterns. Participants first learned through trial-and-error the relationships of the patterns (e.g., Pattern A > Pattern B, Pattern B > Pattern C). After initial learning, participants were presented with novel pairings, some of which required transitive inference (e.g., Pattern A > Pattern C from the relationship above). We observed that vmPFC damage led to a specific deficit in transitive inference, suggesting that an intact vmPFC is necessary for making normal transitive inferences. Given the usefulness of transitivity in inferring social relationships, this deficit may be one of the basic features of social conduct problems associated with vmPFC damage.
Hierarchies in Action and Motor Control
Authors: Uithol Sebo , van Rooij Iris , Bekkering Harold , Haselager Pim
Published: January 2012

In analyses of the motor system, two hierarchies are often posited: The first—the action hierarchy—is a decomposition of an action into subactions and sub-subactions. The second—the control hierarchy—is a postulated hierarchy in the neural control processes that are supposed to bring about the action. A general assumption in cognitive neuroscience is that these two hierarchies are internally consistent and provide complementary descriptions of neuronal control processes. In this article, we suggest that neither offers a complete explanation and that they cannot be reconciled in a logical or conceptually coherent way. Furthermore, neither pays proper attention to the dynamics and temporal aspects of neural control processes. We will explore an alternative hierarchical organization in which causality is inherent in the dynamics over time. Specifically, high levels of the hierarchy encode more stable (goal-related) representations, whereas lower levels represent more transient (actions and motor acts) kinematics. If employed properly, a hierarchy based on this latter principle of temporal extension is not subject to the problems that plague the traditional accounts.
Quantitative Assessment of Diurnal Variation of Tropical Convection Simulated by a Global Nonhydrostatic Model without Cumulus Parameterization
Authors: Noda Akira T. , Oouchi Kazuyoshi , Satoh Masaki , Tomita Hirofumi
Published: January 2012

This study investigated the resolution dependence of diurnal variation in tropical convective systems represented by a global nonhydrostatic model without cumulus parameterization. This paper describes the detailed characteristics of diurnal variation in surface precipitation based on three-dimensional data, with the aim of explicitly clarifying the mechanism that underlies the variation. The study particularly focused on the evolution in the size of the precipitation area for deep convective systems with an analysis of the vertical structure of thermodynamic fields. This analysis compares the results of simulations with horizontal grid sizes of 14 and 7 km (R14 and R7, respectively). Over land, the phase delay of diurnal variations in R7 is about 3 h less than that in R14. R7 produces a pronounced diurnal variation in the size distributions of precipitating area(s), especially for areas with a radius of 0–100 km; this characteristic is not found for R14. Such areas actively evolve between noon and evening, leading to the smooth development of larger-scale precipitating areas having a radius of 100–150 km. The maximum surface precipitation in R7 over land occurs at around 2000 local time throughout the tropics, approximately 2 h prior to the development of nighttime deep convection. Deep convective regimes are important as agents of vertical heat transport in the tropics. The present results suggest that precipitating areas with a radius <100 km make a strong contribution to the total amount of precipitation and to mass transport.
Stability of a Double-Diffusive Interface in the Diffusive Convection Regime
Authors: Carpenter J. R. , Sommer T. , Wüest A.
Published: January 2012

In this paper, the authors explore the conditions under which a double-diffusive interface may become unstable. Focus is placed on the case of a cold, freshwater layer above a warm, salty layer [i.e., the diffusive convection (DC) regime]. The “diffusive interface” between these layers will develop gravitationally unstable boundary layers due to the more rapid diffusion of heat (the destabilizing component) relative to salt. Previous studies have assumed that a purely convective-type instability of these boundary layers is what drives convection in this system and that this may be parameterized by a boundary layer Rayleigh number. The authors test this theory by conducting both a linear stability analysis and direct numerical simulations of a diffusive interface. Their linear stability analysis reveals that the transition to instability always occurs as an oscillating diffusive convection mode and at boundary layer Rayleigh numbers much smaller than previously thought. However, these findings are based on making a quasi-steady assumption for the growth of the interfaces by molecular diffusion. When diffusing interfaces are modeled (using direct numerical simulations), the authors observe that the time dependence is significant in determining the instability of the boundary layers and that the breakdown is due to a purely convective-type instability. Their findings therefore demonstrate that the relevant instability in a DC staircase is purely convective.
Relating Lagrangian, Residual, and Isopycnal Means
Authors: Eden Carsten
Published: January 2012

Three alternative methods of averaging the general conservation equation of a fluid property in a turbulent flow in the Boussinesq approximation are compared: Lagrangian, residual, and isopycnal (or semi-Lagrangian) mean. All methods differentiate consistently but in different ways between effects of advection and irreversible changes of the average property. Because the three average properties differ, the mean transport velocities and the mean irreversible changes in the mean conservation equation differ in general.

The Lagrangian and the semi-Lagrangian (or isopycnal) mean frameworks are shown to be approximately equivalent only for weak irreversible changes, small amplitudes of the turbulent fluctuations, and particle excursion predominantly along the mean property gradient. In that case, the divergent Stokes velocity of the Lagrangian mean framework can be replaced in the Lagrangian mean conservation equation by a nondivergent, three-dimensional version of the quasi-Stokes velocity of T. J. McDougall and P. C. McIntosh, for which a closed analytical form for the streamfunction in terms of Eulerian mean quantities is given.
Ensemble Dynamics and Bred Vectors
Authors: Balci Nusret , Mazzucato Anna L. , Restrepo Juan M. , Sell George R.
Published: January 2012

The new concept of an ensemble bred vector (EBV) algorithm is introduced to assess the sensitivity of model outputs to changes in initial conditions for weather forecasting. The new algorithm is based on collective dynamics in essential ways. As such, it keeps important geometric features that are lost in the earlier bred vector (BV) algorithm. By construction, the EBV algorithm produces one or more dominant vectors and is less prone to spurious results than the BV algorithm. It retains the attractive features of the BV algorithm with regard to being able to handle legacy codes, with minimal additional coding.

The performance of the EBV algorithm is investigated by comparing it to the BV algorithm as well as the finite-time Lyapunov vectors. With the help of a continuous-time adaptation of these algorithms, a theoretical justification is given to the observed fact that the vectors produced by the BV, EBV algorithms, and the finite-time Lyapunov vectors are similar for small amplitudes. The continuum theory establishes the relationship between the two algorithms and general directional derivatives.

Numerical comparisons of BV and EBV for the three-equation Lorenz model and for a forced, dissipative partial differential equation of Cahn–Hilliard type that arises in modeling the thermohaline circulation demonstrate that the EBV yields a size-ordered description of the perturbation field and is more robust than the BV in the higher nonlinear regime. The EBV yields insight into the fractal structure of the Lorenz attractor and of the inertial manifold for the Cahn–Hilliard-type partial differential equation.
The Ghost in the Machine
Authors: Mabbett Deborah
Published: January 2012

The United States has introduced automatic enrollment into retirement savings schemes, and the United Kingdom is in the throes of doing so. The financial crisis has reminded us that returns on these schemes can be poor, even negative. Behavioral economics shows that people can be “nudged” into schemes regardless, but it also implies that the liberal account of market legitimation through informed choice cannot be applied. This article examines how risks are assigned in schemes and how enrollees might seek recourse if their expectations are disappointed. Comparing the United States and the United Kingdom, it argues that enrollees are more likely to seek recourse from the government in the United Kingdom. The explanation can be found in regulatory decisions that reflect the structure of each country’s public pension scheme. This structure is conducive to private risk bearing in the United States, but not in the United Kingdom, suggesting that regulatory market liberalism is undermined by a residual approach to public provision.
“By the Skaters, for the Skaters” The DIY Ethos of the Roller Derby Revival
Authors: Beaver Travis D.
Published: January 2012

The growth of women’s roller derby has been driven by the do-it-yourself (DIY) ethic. This means the majority of roller derby leagues are owned and operated by the participants. Drawing on an ethnographic study of three leagues, the author argues that the DIY ethos is not simply motivated by necessity; rollergirls consider it an important value of the revival. Doing it themselves ensures that skaters maintain control over their athletic activity, their organizations, and the sport as a whole. The author contends that roller derby’s DIY ethic is not about individualism. Instead, the revival is driven by rollergirls’ collective labor. The author also shows that the DIY ethic pushed women to create a sport that they control. Finally, the author discusses the barriers to participation that result from the DIY ethic.
Case Studies of Collegiate Sport Chaplains
Authors: Dzikus Lars , Hardin Robin , Waller Steven N.
Published: January 2012

The appointment of sport chaplains in public colleges or universities can be controversial and contested as in a recent case at Iowa State University. Some scholarly attention has been paid to the relationship between sport and religion, but studies on sport chaplains are just recently emerging. Through textual analysis of media coverage and promotional materials, this study examines how collegiate sport chaplains, their ministry organizations, and public universities navigate the competing interests of evangelical chaplains and state-funded institutions. The study explores the roles and responsibilities of collegiate sport chaplains at two public universities (University of Tennessee and Auburn University). It also provides a brief review of the historical context of muscular Christianity for the discussion of collegiate sport chaplaincy.
One Year after Endoscopic Sinus Surgery in Polyposis
Authors: Ehnhage Anders , Olsson Petter , Kölbeck Karl‐Gustav , Skedinger Maria , Stjärne Pär ,   NAFS Study Group
Published: January 2012

Objective

Nasal polyposis is a disease known to be associated with asthma. The long‐term effects of surgical treatment on lower airways have not been sufficiently studied.

Study Design

One‐year follow‐up of a double‐blind, randomized, placebo‐controlled study.

Setting

The study was conducted at the Karolinska University Hospital, Stockholm, Sweden.

Subjects and Methods

Fifty‐one patients, age 18 years or older, with nasal polyposis and asthma were evaluated 1 year after endoscopic sinus surgery (ESS). Outcomes included dyspnea/cough scores, mean daily peak expiratory flow rate, spirometry, butanol test, olfaction scores, peak nasal inspiratory flow, polyp scores, and health‐related quality of life (SF‐36).

Results

The short‐term postsurgery improvements in asthma symptom scores, daily peak expiratory flow rate, all nasal parameters including olfaction, and quality‐of‐life scores were generally maintained 1 year after ESS.

Conclusion

Endoscopic sinus surgery had beneficial long‐term effects on asthma, olfaction, and quality of life in patients with nasal polyposis. This is the first study to show long‐term benefits of ESS on butanol tests in patients with nasal polyposis.
Serious Health Events and Discontinuation of Routine Cancer Screening
Authors: Howard David H. , Huang Ya-Lin
Published: January 2012

Recently revised US Preventive Services Task Force screening guidelines for colorectal, breast, and prostate cancer contain separate recommendations for persons younger than 75 years and those 75 years or older. Developing an understanding of whether and how patients discontinue screening is important for evaluating the potential benefits and drawbacks of age-delimited screening recommendations as a tool for reducing overdiagnosis rates. Using Surveillance, Epidemiology, and End Results–Medicare data from 1998 to 2007, the authors identified a sample of 32,189 female and 27,669 male fee-for-service Medicare beneficiaries who received 2 consecutive breast or prostate screens, 1 year apart. They then estimated the impact of serious health events, such as heart attacks and strokes, on continuation of screening. Rescreening rates among beneficiaries who did not experience a serious health event were 78% for women and 82% for men. Rescreening rates among beneficiaries who experienced a serious health event were 55% for women and 57% for men. The rate ratios associated with a time-varying indicator for the 2-year period following a serious health event were 0.79 (95% confidence interval: 0.76 to 0.81); P < 0.001) for women and 0.87 (95% confidence interval: 0.85 to 0.89; P < 0.001) for men. Approximately one-third of patients and physicians discontinue or temporarily suspend screening for breast and prostate cancer following serious health events. Findings suggest that not all patients persist with screening until they die.
Synovial Osteochondromatosis With Malignant Transformation to Chondrosarcoma in a Dog
Authors: Aeffner F. , Weeren R. , Morrison S. , Grundmann I. N. M. , Weisbrode S. E.
Published: January 2012

A 4.5-year-old intact male Labrador Retriever dog had a 1-month history of right forelimb lameness with painful swelling of the elbow. The radiographic findings of increased synovial mass with mineralized opacities and the gross and histologic findings in the synovial biopsy specimens were consistent with a diagnosis of primary (idiopathic) synovial osteochondromatosis. Twenty months after initial presentation, based on progression of clinical signs and radiographic evidence of marked bone lysis in the distal aspect of the humerus and proximal aspects of the radius and ulna, the affected leg was amputated. The histologic diagnosis was chondrosarcoma with fibroblastic differentiation and bone lysis. The chondrosarcoma was interpreted as malignant transformation of primary synovial osteochondromatosis.
Cranial Mediastinal Liposarcoma in a Horse
Authors: Kondo H. , Wickins S. C. , Conway J. A. , Mallicote M. F. , Sanchez L. C. , Agnew D. W. , Farina L. L. , Abbott J. R.
Published: January 2012

A 23-year-old Anglo-Arabian mare was presented with tachypnea, dyspnea, and pitting edema of the ventral thoracic subcutis. On necropsy, a tan to red, friable, irregularly shaped mass (23 × 20 × 18 cm) occupied the cranial mediastinum. Histologically, the mass was classified as a liposarcoma and was composed of short interlacing bundles of spindle-shaped to irregularly rounded cells with discrete, variably sized, clear cytoplasmic vacuoles, which were stained with oil red O in frozen sections of formalin-fixed tissue.
Effects of low-dose, long-term formaldehyde exposure on the structure and functions of the ovary in rats
Authors: Wang Hai-xu , Wang Xiao-yan , Zhou Dang-xia , Zheng Lie-rui , Zhang Jing , Huo Yong-wei , Tian Hong
Published: January 2012

Formaldehyde (FA) is a ubiquitous environmental pollutant. However, the effects of FA exposure on reproduction are still a matter of scientific controversy. In this study, we assessed the ovarian toxicity of long-term, low-dose FA exposure in rats and explored the potential oxidative stress mechanisms. A total of 30 Sprague-Dawley female rats were randomly allotted to three groups, in which rats were exposed to FA at a dose of 0 mg/m3 (control), 0.5 mg/m3 and 2.46 mg/m3, respectively, by inhalation consecutively for 60 days. The results showed that the ovarian toxicity of FA is dose dependent. Ovarian structure and function in the group of rats exposed to 0.5 mg/m3 FA showed no obvious difference when compared with those in the control group. However, the activity of superoxide dismutase was significantly decreased, whereas the level of malondialdehyde was significantly increased in ovaries of rats exposed to 2.46 mg/m3 FA. Moreover, histopathological results demonstrated that the number and size of mature follicles significantly decreased, vascular congestion and interstitial edema in the ovaries of rats exposed to 2.46 mg/m3 FA. In conclusion, this study may suggest that the FA level of 0.5 mg/m3 can be considered as a safe level for FA exposure, but long-term FA exposure at a dose of 2.46 mg/m3 has a harmful effect on ovary by inducing oxidative stress.
Antinociceptive effect of Butea monosperma on vincristine-induced neuropathic pain model in rats
Authors: Thiagarajan Venkata Rathina Kumar , Shanmugam Palanichamy , Krishnan Uma Maheswari , Muthuraman Arunachalam , Singh Nirmal
Published: January 2012

Neuropathic pain is a chronic neurodegenerative disease. It is well characterized by spontaneous pain, hyperalgesia, hypothesia, dysesthesia and allodynia. The present study was designed to investigate the antinociceptive potential of Butea monosperma on vincristine-induced painful neuropathy in rats. Vincristine was administered for induction of neuropathic pain in experimental animals. Hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal hyperalgesia, cold chemical allodynia, mechanical hyperalgesia and allodynia in the hind paw and tail thermal hyperalgesia, respectively, as an index of peripheral and central pain sensation. Tissue thiobarbituric acid reactive substances (TBARSs), reduced glutathione (GSH) and total calcium levels were estimated to assess the biochemical changes in the sciatic nerve tissue. Microscopically, histopathological changes were also observed in the sciatic nerve tissue. Ethanolic extract of B. monosperma leaves and pregabalin were administered for 14 consecutive days. Vincristine administration resulted in significant reduction in behavioural (i.e. hyperalgesia and allodynic pain sensation) changes along with a rise in the levels of TBARS, total calcium and decrease in GSH levels when compared with the normal control group. Moreover, significant histological changes were also observed. Pretreatment with B. monosperma significantly attenuated vincristine-induced development of painful behavioural, biochemical and histological changes in a dose-dependent manner, which is similar to that of pregabalin-pretreated group. B. monosperma ameliorated vincristine-induced painful neuropathy. It may be due to its potential of antioxidative, neuroprotective and calcium channel inactivation.
Pneumocystis jiroveci pneumonia in patients with systemic lupus erythematosus after rituximab therapy
Authors: Tsai M-J , Chou C-W , Lin F-C , Chang S-C
Published: January 2012

Pneumocystis jiroveci pneumonia (PCP) is an uncommon but potentially life-threatening infection in immunocompromised patients with low blood T cells. Rituximab, a chimeric human/murine monoclonal antibody against the B cell-specific antigen CD20, has been increasingly used and appears to be effective in the treatment of autoimmune disorders, including systemic lupus erythematosus (SLE). PCP has been reported in some patients with autoimmune diseases or lymphoma subjected to rituximab treatment, but has not yet been reported in SLE patients. We report PCP in two patients with SLE after rituximab treatment. Fever and respiratory symptoms associated with diffuse pulmonary infiltrates developed within weeks after rituximab therapy. One patient died of respiratory failure. Another patient recovered uneventfully after treatment with clindamycin and primaquine.
WISC-IV Profiles Are Associated With Differences in Symptomatology and Outcome in Children With ADHD
Authors: Thaler Nicholas S. , Bello Danielle T. , Etcoff Lewis M.
Published: January 2012

Objective: The current study investigated the Wechsler Intelligence Scale for Children–Fourth Edition (WISC-IV) cluster profiles of children with ADHD to examine the association between IQ profiles and diagnostic frequency, symptomatology, and outcome in this population. Method: Hierarchical cluster analysis was conducted on 189 children with a diagnosis of ADHD–inattentive (ADHD-I) and ADHD–combined (ADHD-C) subtypes. Clusters were then compared across symptom rating scale factor scores, behavioral rating scales, and achievement scores. Results: A five-cluster solution was extracted. One cluster was identified to have reduced processing speed relative to other WISC-IV indexes and significantly higher ratings of inattention and incidence of ADHD-I diagnosis. A second cluster had impairments in processing speed and working memory and was associated with impaired behavioral functioning. Conclusion: Findings support a relationship between reduced processing speed and inattention and provide evidence that WISC-IV profiles may be helpful in predicting symptomatology and outcome in children with ADHD.
A Research Synthesis of the Evaluation Capacity Building Literature
Authors: Labin Susan N. , Duffy Jennifer L. , Meyers Duncan C. , Wandersman Abraham , Lesesne Catherine A.
Published: January 2012

The continuously growing demand for program results has produced an increased need for evaluation capacity building (ECB). The Integrative ECB Model was developed to integrate concepts from existing ECB theory literature and to structure a synthesis of the empirical ECB literature. The study used a broad-based research synthesis method with systematic decision rules and demonstrates the viability of the method for producing a reliable analysis of disparate data from a variety of designs. There was a high degree of consistency in what was reported in the empirical literature and the theoretical literature in terms of strategies and outcomes. Reported outcomes at the individual level included attitudes, knowledge, and behaviors and at the organizational level included practices, leadership, culture, mainstreaming, and resources. Collaborative processes and programmatic outcomes emerged as important issues for ECB models and practice. The consistency between the empirical and the theoretical literature indicates that the field is ready to develop common measures, use stronger designs, and report more systematically. This synthesis provides an overview of existing data and an empirical basis for refining strategies and common measures for enhancing the research and practice of ECB to achieve ECB and programmatic goals and outcomes.
The validity of the DSM-IV PTSD criteria in children and adolescents: A review
Authors: Blom Marloes , Oberink Riëtta
Published: January 2012

Objective:

DSM-V is on its way and doubts have been raised regarding the validity of pediatric PTSD. It is the goal of the current review to critically review the empirical literature on PTSD in youth.

Method:

A search of PsycINFO, PubMed and reference lists was conducted. Empirical information considered relevant regarding the validity of the criteria was collected.

Results/Conclusions:

The validity of the symptom criteria and clusters varies, with the Avoidance/Numbing cluster outperforming the Re-experiencing—and Arousal cluster. Factor analytic findings suggest that Arousal criterion D4 should be placed within the Re-experiencing cluster, and that the Avoidance/Numbing cluster should be split up. Some non-DSM-IV PTSD symptoms, among which guilt, have considerable validity in trauma-exposed youth and their inclusion in DSM-V PTSD should be considered. As for preschool children, alternative criteria are recommended that are more developmentally sensitive.
Assessment of the properties of poly(L-lactic acid) sheets produced with differing amounts of postconsumer recycled poly(L-lactic acid)
Authors: Chariyachotilert Chaiyatas , Joshi Satish , Selke Susan EM , Auras Rafael
Published: January 2012

The properties of sheet containing mechanically recycled postconsumer poly(L-lactic acid) bottle flakes blended with virgin poly(L-lactic acid) resin were assessed. Poly(L-lactic acid) bottles were flaked, cleaned, blended with virgin resin and then extruded and thermoformed into trays. The molecular weight, physical, optical, thermal and mechanical properties of the sheet containing 0, 20, 40, 60, 80 and 100 wt.% poly(L-lactic acid) recycled content were evaluated. The best cleaning conditions were found by using a mixed-level fractional factorial design. Cleaning conditions of 15 min, at 85°C, 1 wt.% NaOH and 0.3 wt.% surfactant were adopted for cleaning the poly(L-lactic acid) flakes. Cast-extruded virgin poly(L-lactic acid) sheet had superior mechanical and optical properties than recycled poly(L-lactic acid) sheet. Recycled poly(L-lactic acid) sheets were darker and absorbed more ultraviolet light in the 260 to 285 nm range when 20% or more recycled content was added. At 40% poly(L-lactic acid) recycled content, the sheet had increased blue and red tones and the mechanical properties in the cross-machine direction decreased. At 60% poly(L-lactic acid) recycled content or above, reduction of weight average molecular weight, tensile strength and tensile strength at yield in the machine direction were found. At 80% poly(L-lactic acid) recycled content, the melting temperature and modulus of elasticity in the machine direction decreased. All sheet samples were successfully thermoformed into trays showing the potential to use post-consumer poly(L-lactic acid) flakes in the production of poly(L-lactic acid) containers.
Traditional Peripheral Arterial Doppler Waveform Descriptors
Authors: Scissons Robert
Published: January 2012

Traditional peripheral arterial waveforms have been inconsistently defined and classified. This investigation compares waveform categorization scores from two comparable groups of sonography participants. Group 1 interpreted continuous-wave (CW) and pulsed-wave (PW) Doppler waveforms based on standard text definitions. Group 2 performed the same task following 10 minutes of detailed waveform characterization instructions with accompanying illustrations. Each group comprised 157 participants with an equal number of students, registered sonographers, and physicians. Significant differences were noted between groups 1 and 2 for 60% of CW waveforms and 33% of PW waveforms ( P < .05). In group 2, American Registry for Diagnostic Sonography (ARDMS)–registered sonographers had significantly higher CW scores than students and physicians ( P < .0001); registered vascular technologists and multispecialty ARDMS-certified sonographers had significantly higher PW scores than students, Registered Diagnostic Medical Sonographer (RDMS)–certified sonographers, and physicians ( P = .0086 and P = .0295, respectively). This study emphasizes the contribution of sonographers in arterial Doppler waveform categorization and underscores the need for standardization and education.
Acute myeloid leukemia stem cells and CD33-targeted immunotherapy
Authors: Walter Roland B. , Appelbaum Frederick R. , Estey Elihu H. , Bernstein Irwin D.
Published: January 2012

Although the identification of cancer stem cells as therapeutic targets is now actively being pursued in many human malignancies, the leukemic stem cells in acute myeloid leukemia (AML) are a paradigm of such a strategy. Heterogeneity of these cells was suggested by clonal analyses indicating the existence of both leukemias resulting from transformed multipotent CD33− stem cells as well others arising from, or predominantly involving, committed CD33+ myeloid precursors. The latter leukemias, which may be associated with an intrinsically better prognosis, offer a particularly attractive target for stem cell-directed therapies. Targeting the CD33 differentiation antigen with gemtuzumab ozogamicin was the first attempt of such an approach. Emerging clinical data indicate that gemtuzumab ozogamicin is efficacious not only for acute promyelocytic leukemia but, in combination with conventional chemotherapy, also for other favorable- and intermediate-risk AMLs, providing the first proof-of-principle evidence for the validity of this strategy. Herein, we review studies on the nature of stem cells in AML, discuss clinical data on the effectiveness of CD33-directed therapy, and consider the mechanistic basis for success and failure in various AML subsets.
Automatic categorization of diverse experimental information in the bioscience literature
Authors: Fang Ruihua , Schindelman Gary , Auken Kimberly Van , Fernandes Jolene , Chen Wen , Wang Xiaodong , Davis Paul , Tuli Mary Ann , Marygold Steven J , Millburn Gillian , Matthews Beverley , Zhang Haiyan , Brown Nick , Gelbart William M , Sternberg Paul W
Published: January 2012

Background

Curation of information from bioscience literature into biological knowledge databases is a crucial way of capturing experimental information in a computable form. During the biocuration process, a critical first step is to identify from all published literature the papers that contain results for a specific data type the curator is interested in annotating. This step normally requires curators to manually examine many papers to ascertain which few contain information of interest and thus, is usually time consuming. We developed an automatic method for identifying papers containing these curation data types among a large pool of published scientific papers based on the machine learning method Support Vector Machine (SVM). This classification system is completely automatic and can be readily applied to diverse experimental data types. It has been in use in production for automatic categorization of 10 different experimental datatypes in the biocuration process at WormBase for the past two years and it is in the process of being adopted in the biocuration process at FlyBase and theSaccharomycesGenome Database (SGD). We anticipate that this method can be readily adopted by various databases in the biocuration community and thereby greatly reducing time spent on an otherwise laborious and demanding task. We also developed a simple, readily automated procedure to utilize training papers of similar data types from different bodies of literature such asC. elegansandD. melanogasterto identify papers with any of these data types for a single database. This approach has great significance because for some data types, especially those of low occurrence, a single corpus often does not have enough training papers to achieve satisfactory performance.

Results

We successfully tested the method on ten data types from WormBase, fifteen data types from FlyBase and three data types from Mouse Genomics Informatics (MGI). It is being used in the curation work flow at WormBase for automatic association of newly published papers with ten data types including RNAi, antibody, phenotype, gene regulation, mutant allele sequence, gene expression, gene product interaction, overexpression phenotype, gene interaction, and gene structure correction.

Conclusions

Our methods are applicable to a variety of data types with training set containing several hundreds to a few thousand documents. It is completely automatic and, thus can be readily incorporated to different workflow at different literature-based databases. We believe that the work presented here can contribute greatly to the tremendous task of automating the important yet labor-intensive biocuration effort.
The cyclin-like protein Spy1/RINGO promotes mammary transformation and is elevated in human breast cancer
Authors: Al Sorkhy Mohammad , Ferraiuolo Rosa-Maria , Jalili Espanta , Malysa Agnes , Fratiloiu Andreea R , Sloane Bonnie F , Porter Lisa A
Published: January 2012

Background

Spy1 is a novel 'cyclin-like' activator of the G1/S transition capable of enhancing cell proliferation as well as inhibiting apoptosis. Spy1 protein levels are tightly regulated during normal mammary development and forced overexpression in mammary mouse models accelerates mammary tumorigenesis.

Methods

Using human tissue samples, cell culture models and in vivo analysis we study the implications of Spy1 as a mediator of mammary transformation and breast cancer proliferation.

Results

We demonstrate that this protein can facilitate transformation in a manner dependent upon the activation of the G2/M Cdk, Cdk1, and the subsequent inhibition of the anti-apoptotic regulator FOXO1. Importantly, we show for the first time that enhanced levels of Spy1 protein are found in a large number of human breast cancers and that knockdown of Spy1 impairs breast cancer cell proliferation.

Conclusions

Collectively, this work supports that Spy1 is a unique activator of Cdk1 in breast cancer cells and may represent a valuable drug target and/or a prognostic marker for subsets of breast cancers.
Expression and clinical significance of extracellular matrix protein 1 and vascular endothelial growth factor-C in lymphatic metastasis of human breast cancer
Authors: Wu Qiu-Wan , She Hong-Qiang , Liang Jing , Huang Yu-Fan , Yang Qing-Mo , Yang Qiao-Lu , Zhang Zhi-Ming
Published: January 2012

Background

Extracellular matrix protein 1 (ECM1) and vascular endothelial growth factor-C (VEGF-C) are secretory glycoproteins that are associated with lymphangiogenesis; these proteins could, therefore, play important roles in the lymphatic dissemination of tumors. However, very little is known about their potential roles in lymphangiogenesis. The aim of this study was to investigate whether correlations exist between ECM1 and VEGF-C in human breast cancer, lymphangiogenesis, and the clinicopathological characteristics of the disease.

Methods

ECM1 and VEGF-C mRNA and protein expression levels in 41 patients were investigated using real-time reverse transcriptase polymerase chain reaction (RT-PCR), or immunohistochemical (IHC) staining of breast cancer tissue, matched noncancerous breast epithelial tissues, and suspicious metastatic axillary lymph nodes. D2-40 labelled lymph vessels and lymphatic microvessel density (LMVD) were counted. Correlations between ECM1 or VEGF-C protein expression levels, LMVD, and clinicopathological parameters were statistically tested.

Results

The rate of ECM1 positive staining in breast cancer tissues was higher (31/41, 75.6%) than that in the corresponding epithelial tissues (4/41, 9.8%, P < 0.001) and lymph nodes (13/41, 31.7%, P < 0.001). Similarly, the VEGF-C expression rate in cancer specimens was higher (33/41, 80.5%) than in epithelial tissues (19/41, 46.3%, P < 0.01) or lymph nodes (15/41, 36.6%, P < 0.01). Higher ECM1 and VEGF-C mRNA expression levels were also detected in the tumor tissues, compared to the non-cancerous tissue types or lymph nodes (P < 0.05). ECM1 protein expression was positively correlated with the estrogen receptor status (P < 0.05) and LMVD (P < 0.05). LMVD in the ECM1- and VEGF-C-positive tumor specimens was higher than that in the tissue types with negative staining (P < 0.05).

Conclusions

Both ECM1 and VEGF-C were overexpressed in breast cancer tissue samples. ECM1 expression was positively correlated with estrogen responsiveness and the metastatic properties of breast cancer. We conclude, therefore, that ECM1 and VEGF-C may have a synergistic effect on lymphangiogenesis to facilitate lymphatic metastasis of breast cancer.
Socio-economic variation in CT scanning in Northern England, 1990-2002
Authors: Pearce Mark S , Salotti Jane A , McHugh Kieran , Pyo Kim Kwang , Craft Alan W , Lubin Jay , Ron Elaine , Parker Louise
Published: January 2012

Background

Socio-economic status is known to influence health throughout life. In childhood, studies have shown increased injury rates in more deprived settings. Socio-economic status may therefore be related to rates of certain medical procedures, such as computed tomography (CT) scans. This study aimed to assess socio-economic variation among young people having CT scans in Northern England between 1990 and 2002 inclusive.

Methods

Electronic data were obtained from Radiology Information Systems of all nine National Health Service hospital Trusts in the region. CT scan data, including sex, date of scan, age at scan, number and type of scans were assessed in relation to quintiles of Townsend deprivation scores, obtained from linkage of postcodes with census data, using χ2 tests and Spearman rank correlations.

Results

During the study period, 39,676 scans were recorded on 21,089 patients, with 38,007 scans and 19,485 patients (11344 male and 8132 female) linkable to Townsend scores. The overall distributions of both scans and patients by quintile of Townsend deprivation scores were significantly different to the distributions of Townsend scores from the census wards included in the study (p < 0.0001). There was a significant association between type of scan and deprivation quintile (p < 0.0001), primarily due to the higher proportions of head scans in the three most deprived quintiles, and slightly higher proportions of chest scans and abdomen and pelvis scans in the least deprived groups. There was also a significant association (p < 0.0001) between the patient's age at the time of the CT scan and Townsend deprivation quintiles, with slightly increasing proportions of younger children with increasing deprivation. A similar association with age (p < 0.0001) was seen when restricting the data to include only the first scan of each patient. The number of scans per patient was also associated with Townsend deprivation quintiles (p = 0.014).

Conclusions

Social inequalities exist in the numbers of young people undergoing CT scans with those from deprived areas more likely to do so. This may reflect the rates of injuries in these individuals and implies that certain groups within the population may receive higher radiation doses than others due to medical procedures.
Liver angiosarcoma, a rare liver malignancy, presented with intraabdominal bleeding due to rupture- a case report
Authors: Chien Chin-Ying , Hwang Cheng-cheng , Yeh Chun-nan , Chen Huang-yang , Wu Jui-Teng , Chan Siu-Cheung , Lin Chih-Lang , Yen Cho-li , Wang Wen-yen , Chiang Kun-Chun
Published: January 2012

Liver angiosarcoma is a rare disease, however it still ranks as the third of most common primary liver maligancies. The prognosis of liver angiosarcoma is very poor with almost all patients with this kind of disease die within 2 years after diagnosis. No specific symptoms and signs are closely associated with this disease. Here, we report a case presenting shock status at first due to rupture of liver angiosarcoma- induced internal bleeding. After emergent transarterial embolization (TAE), she received partial hepatectomy two weeks later. 4 months after operation, she is still with a good performance status without obvious recurrence or metastasis identified.