bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimal Control of Polymer Flooding Based on Maximum Principle
Authors: Lei Yang , Li Shurong , Zhang Xiaodong , Zhang Qiang , Guo Lanlei
Published: July 2012

Polymer flooding is one of the most important technologies for enhanced oil recovery (EOR). In this paper, an optimal control model of distributed parameter systems (DPSs) for polymer injection strategies is established, which involves the performance index as maximum of the profit, the governing equations as the fluid flow equations of polymer flooding, and the inequality constraint as the polymer concentration limitation. To cope with the optimal control problem (OCP) of this DPS, the necessary conditions for optimality are obtained through application of the calculus of variations and Pontryagin’s weak maximum principle. A gradient method is proposed for the computation of optimal injection strategies. The numerical results of an example illustrate the effectiveness of the proposed method.
RB-Pathway Disruption Is Associated with Improved Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Witkiewicz Agnieszka K. , Ertel Adam , McFalls Jeanne , Valsecchi Matias E. , Schwartz Gordon , Knudsen Erik S.
Published: July 2012

Purpose: We sought to determine whether dysregulation of the retinoblastoma (RB) tumor suppressor pathway was associated with improved response to neoadjuvant chemotherapy in breast cancer.

Experimental Design: An RB-loss signature was used to analyze the association between pathway status and pathologic complete response in gene expression datasets encompassing three different neoadjuvant regimens. Parallel immunohistochemical analysis of the RB pathway was conducted on pretreatment biopsies to determine the association with pathologic response to neoadjuvant chemotherapy.

Results: An RB-loss gene expression signature was associated with increased pathologic complete response in datasets from breast cancer patients treated with 5-fluorouracil/adriamycin/cytoxan (FAC; P < 0.001), T/FAC (P < 0.001), and Taxane/Adriaymcin (P < 0.001) neoadjuvant therapy encompassing approximately 1,000 patients. The association with improved response to neoadjuvant chemotherapy was true in both estrogen receptor (ER)–positive and ER-negative breast cancer. Elevated expression of p16ink4a is associated with the RB-loss signature (R = 0.493–0.5982), and correspondingly p16ink4a mRNA levels were strongly associated with pathologic complete response in the same datasets analyzed. In an independent cohort, immunohistochemical analyses of RB and p16ink4a revealed an association of RB loss (P = 0.0018) or elevated p16ink4a (P = 0.0253) with pathologic complete response. In addition, by Miller–Payne and clinicopathologic scoring analyses, RB-deficient tumors experienced an overall improved response to neoadjuvant chemotherapy.

Conclusion: Disruption of the RB pathway as measured by several independent methods was associated with improved response to neoadjuvant chemotherapy. The RB-pathway status was relevant for pathologic response in both ER-positive and ER-negative breast cancer with similar results observed with multiple chemotherapy regimens. Combined, these data indicate that RB status is associated with the response to neoadjuvant chemotherapy in breast cancer and could be used to inform treatment. Clin Cancer Res; 18(18); 5110–22. ©2012 AACR.
Ras-Driven Transcriptome Analysis Identifies Aurora Kinase A as a Potential Malignant Peripheral Nerve Sheath Tumor Therapeutic Target
Authors: Patel Ami V. , Eaves David , Jessen Walter J. , Rizvi Tilat A. , Ecsedy Jeffrey A. , Qian Mark G. , Aronow Bruce J. , Perentesis John P. , Serra Eduard , Cripe Timothy P. , Miller Shyra J. , Ratner Nancy
Published: July 2012

Purpose: Patients with neurofibromatosis type 1 (NF1) develop malignant peripheral nerve sheath tumors (MPNST), which are often inoperable and do not respond well to current chemotherapies or radiation. The goal of this study was to use comprehensive gene expression analysis to identify novel therapeutic targets.

Experimental Design: Nerve Schwann cells and/or their precursors are the tumorigenic cell types in MPNST because of the loss of the NF1 gene, which encodes the RasGAP protein neurofibromin. Therefore, we created a transgenic mouse model, CNP-HRas12V, expressing constitutively active HRas in Schwann cells and defined a Ras-induced gene expression signature to drive a Bayesian factor regression model analysis of differentially expressed genes in mouse and human neurofibromas and MPNSTs. We tested functional significance of Aurora kinase overexpression in MPNST in vitro and in vivo using Aurora kinase short hairpin RNAs (shRNA) and compounds that inhibit Aurora kinase.

Results: We identified 2,000 genes with probability of linkage to nerve Ras signaling of which 339 were significantly differentially expressed in mouse and human NF1-related tumor samples relative to normal nerves, including Aurora kinase A (AURKA). AURKA was dramatically overexpressed and genomically amplified in MPNSTs but not neurofibromas. Aurora kinase shRNAs and Aurora kinase inhibitors blocked MPNST cell growth in vitro. Furthermore, an AURKA selective inhibitor, MLN8237, stabilized tumor volume and significantly increased survival of mice with MPNST xenografts.

Conclusion: Integrative cross-species transcriptome analyses combined with preclinical testing has provided an effective method for identifying candidates for molecular-targeted therapeutics. Blocking Aurora kinases may be a viable treatment platform for MPNST. Clin Cancer Res; 18(18); 5020–30. ©2012 AACR.
Silent Ischemic Heart Disease in a Patient with Necrotizing Glomerulonephritis due to Wegener’s Granulomatosis
Authors: Salazar-Exaire Daniel , Ramos-Gordillo Manolo , Vela-Ojeda Jorge , Salazar-Cabrera Celia Elena , Sanchez-Uribe Magdalena , Calleja-Romero Maria Consuelo
Published: July 2012

Objective: Wegener’s granulomatosis (WG) is a necrotizing vasculitis that mainly affects the respiratory tract and kidneys, but can also affect other systems such as the eye, joints, skin, muscles, nerves, and gastrointestinal tract. Cardiac involvement is traditionally believed to be rare. We report a patient with silent myocardial infarction (MI) and review previously reported cases showing this association. Methods: A Medline database search of cases published between January 1978 and July 2008 both in English and Spanish, reporting silent MI complicating WG, was conducted. Results: We describe a typical patient with WG who had both respiratory and renal involvement and died unexpectedly following a silent MI after a period of clinical improvement induced by treatment with prednisone and cyclophosphamide. We report necropsy findings and the association with 5 additional cases of WG with silent MI reported in the literature. Conclusions: Clinicians should be aware of potential cardiac involvement due to WG. Careful evaluation of each patient, with or without cardiac symptoms, using ECG, echocardiogram, and myocardial enzymes is prudent.
The Development of a CD-ROM: An Aid to Fetal Cardiac Diagnosis and Counseling
Authors: Caldera Kalhara , Ha Derrick , Menahem Samuel
Published: July 2012

Objective: Obstetric ultrasound allows for the fetal diagnosis of complex congenital heart disease, which once diagnosed is especially stressful for the affected parents. This study aimed to develop and pilot an educational CD-ROM for parents who had a fetal diagnosis of a congenital heart defect (CHD). Material and Methods: A CD-ROM was developed which included a brief description of a normal heart in text and cartoons, followed by one of five congenital heart abnormalities (again described in text and illustrated by cartoons highlighting the anatomy), the likely interventions (surgical or by catheter), and the local outcomes. A pilot study was conducted whereby parents were provided with the CD-ROM and asked to complete a brief evaluation following the fetal diagnosis of a suspected CHD and subsequent to counseling by the pediatric cardiologist, but prior to the birth of the infant. The CD-ROM was to be viewed at the parents’ convenience. The questionnaire was returned via postal mail. Results: A CD-ROM covering five common congenital heart abnormalities was successfully developed and distributed to 20 parents. Fourteen responses were received. The feedback was favorable. The parents found the CD-ROM to be informative and easily understood and supplemented the information previously provided by the pediatric cardiologist. The diagrams were particularly helpful. Conclusion: An educational CD-ROM describing a cardiac abnormality of a fetus was successfully created and favorably received, complementing the earlier counseling given. Further development of the CD-ROM with modifications highlighting parental suggestions and to include other abnormalities will allow for a wider audience.
Decompression through Tracheobronchial Endoscopy of Bronchial Atresia Presenting as Massive Pulmonary Tumor: A New Indication for Fetoscopic Surgery
Authors: Martínez J.M. , Prat J. , Gómez O. , Crispi F. , Bennasar M. , Puerto B. , Castañón M. , Gratacós E.
Published: July 2012

This is the first report of fetoscopy to successfully treat a case of bilobar bronchial atresia presenting in the form of a massive right lung tumor causing severe thoracic compression with mediastinal shift, pulmonary hypoplasia and eventually fetal hydrops. The presence of an echolucent tubular structure in the pulmonary hilum was identified as the intrapulmonary continuation of the interrupted main bronchus, and led to the diagnosis of main bronchial atresia. After extensive discussion and counseling, a fetoscopic operation was designed and indicated. The procedure consisted of a fetal tracheoscopy and access to the right main bronchus, which was perforated with a diode laser until a communication with the dead end of the intrapulmonary main bronchus was achieved. After the operation a significant reduction in size was observed, hydrops and mediastinal shift disappeared and O/E LHR increased to 85%. The fetus was born at term and lobectomy of two dysplastic pulmonary lobes was performed. The infant is developing well at 14 months of age. This report demonstrates that fetoscopic airway decompression can achieve fetal survival in the rare event of main bronchus atresia.
Glycation and Insulin Resistance
Authors: Song Fei , Schmidt Ann Marie
Published: July 2012

Multiple biochemical, metabolic, and signal transduction pathways contribute to insulin resistance. In this review, we present evidence that the posttranslational process of protein glycation may play a role in insulin resistance. The posttranslational modifications, the advanced glycation end products (AGEs), are formed and accumulated by endogenous and exogenous mechanisms. AGEs may contribute to insulin resistance by a variety of mechanisms, including generation of tumor necrosis factor-α direct modification of the insulin molecule, thereby leading to its impaired action, generation of oxidative stress, and impairment of mitochondrial function, as examples. AGEs may stimulate signal transduction via engagement of cellular receptors, such as receptor for AGEs. AGE–receptor for AGE interaction perpetuates AGE formation and cellular stress via induction of inflammation, oxidative stress, and reduction in the expression and activity of the enzyme glyoxalase I that detoxifies the AGE precursor, methylglyoxal. Once set in motion, glycation-promoting mechanisms may stimulate ongoing AGE production and target tissue stresses that reduce insulin responsiveness. Strategies to limit AGE accumulation and action may contribute to the prevention of insulin resistance and its consequences.
Predictability of Precipitation from Continental Radar Images. Part V: Growth and Decay
Authors: Radhakrishna Basivi , Zawadzki Isztar , Fabry Frédéric
Published: July 2012

In a Lagrangian frame of reference, the accuracy of rainfall systems predicted by nowcasting algorithms can be improved by incorporating the growth and decay of the rainfall. The scale dependence of predictability of growth and decay of continental-scale precipitating systems is studied with the help of the U.S. national radar composites. The growth and decay of precipitating systems is estimated in a time interval τ by correcting the precipitation image for advection and rotation at time t + τ with respect to the precipitation image at time t and then subtracting the former from the latter. Results show that the two-dimensional correlation of growth and decay has an elliptical structure, indicating that growth and decay is nonisotropic. The probability density function of precipitation intensities and of growth and decay follows a Gaussian distribution. The scale-dependence analysis of growth and decay patterns indicates that the growth and decay of rainfall may be predictable up to about 2 h for scales larger than 250 km.
Idealized Annually Averaged Macroturbulent Hadley Circulation in a Shallow-Water Model
Authors: Adam Ori , Harnik Nili
Published: July 2012

The interaction of midlatitude eddies and the thermally driven Hadley circulation is studied using an idealized shallow-water model on the rotating sphere. The contributions of the annually averaged differential heating, vertical advection of momentum from a stationary boundary layer, and the gross effect of eddies, parameterized by Rayleigh damping, including a hemispherically asymmetric damping, are examined at steady state.

The study finds that the relative dominance of eddies, as quantified by the local Rossby number, is predicted by an effective macroturbulent Hadley circulation Prandtl number Pr. In addition, viscous solutions of the Hadley circulation width and strength, subtropical jet amplitude, and equator-to-pole temperature difference scale as deviations from the respective inviscid solutions.

Semianalytic solutions for the steady circulation are derived in the limit of weak eddy dominance (small Pr) as deviations from the respective inviscid solutions. These solutions follow a three-region paradigm: weak temperature gradient at the ascending branch of the Hadley circulation, monotonically decreasing angular momentum at the descending branch, and modified radiative–convective equilibrium at the extratropics. Using the three-region solutions, scaling relations found in the full solutions are reproduced analytically. The weak eddy-dominance solutions diverge from the full solutions as Pr increases and may become invalid for Pr > 1 due to the breakdown of the three-region global circulation structure.

The qualitative predictions of the response of the Hadley circulation to heating based on the weak eddy-dominance solutions and Pr are in agreement with the findings of more complex models and the observed atmosphere.
North Australian Sea Surface Temperatures and the El Niño–Southern Oscillation in the CMIP5 Models
Authors: Catto Jennifer L. , Nicholls Neville , Jakob Christian
Published: July 2012

Aspects of the climate of Australia are linked to interannual variability of the sea surface temperatures (SSTs) to the north of the country. SST anomalies in this region have been shown to exhibit strong, seasonally varying links to ENSO and tropical Pacific SSTs.

Previously, the models participating in phase 3 of the Coupled Model Intercomparison Project (CMIP3) have been evaluated and found to vary in their abilities to represent both the seasonal cycle of correlations between the Niño-3.4 and north Australian SSTs and the evolution of SSTs during composite El Niño and La Niña events. In this study, the new suite of models participating in the CMIP5 is evaluated using the same method. In the multimodel mean, the representation of the links is slightly improved, but generally the models do not capture the strength of the negative correlations during the second half of the year. The models also still struggle to capture the SST evolution in the north Australian region during El Niño and La Niña events.
Item Purification Does Not Always Improve DIF Detection
Authors: Magis David , Facon Bruno
Published: July 2012

Item purification is an iterative process that is often advocated as improving the identification of items affected by differential item functioning (DIF). With test-score-based DIF detection methods, item purification iteratively removes the items currently flagged as DIF from the test scores to get purified sets of items, unaffected by DIF. The purpose of this article is to highlight that item purification is not always useful and that a single run of the DIF method may return equally suitable results. Angoff’s Delta plot is considered as a counterexample DIF method, with a recent improvement to the derivation of the classification threshold. Several possible item purification processes may be defined with this method, and all of them are compared through a simulation study and a real data set analysis. It appears that none of these purification processes clearly improves the Delta plot performance. A tentative explanation is drawn from the conceptual difference between the modified Delta plot and the other traditional DIF methods.
Managing Mistrust
Authors: Ruggeri Andrea , Gizelis Theodora-Ismene , Dorussen Han
Published: July 2012

How many peacekeepers are needed to keep the peace? Under what conditions are local governments and rebel forces more willing to cooperate with an intervention force? From a theoretical perspective in which the main role of peacekeepers is to assist local actors in overcoming their commitment problems and mistrust toward each other, it follows that sufficiently robust missions should positively affect levels of cooperation. Furthermore, any effect should be conditional on the local balance of power, that is, the military leverage between government and rebel forces. Relatively weak rebel groups—facing a stronger government—should be more willing to cooperate with larger missions. In the empirical analysis, using newly collected event data on United Nation (UN) peacekeeping operations from 1989 to 2005 in African civil wars, the authors find support for conditional effect of robust peacekeeping: there is more cooperation with UN peacekeepers when the rebels are weak.
E-learning adoption in the banking workplace in Indonesia
Authors: Purnomo Sutrisno Hadi , Lee Yi-Hsuan
Published: July 2012

The main purpose of this study is to determine whether the TAM (Technology Acceptance Model) could be extended to include external variables including computer self-efficacy, prior experience, computer anxiety, management support and compatibility, to further understand the learners’ perceived usefulness and perceived ease of use of an e-learning system. The study also aims to clarify which factors are more influential in affecting the decision to use e-learning. Five factors were examined together with the TAM construct using the SEM (Structural Equation Modeling) technique. The study reveals that management support, prior experience, computer anxiety and compatibility have predictive power towards behavioral intention to use e-learning systems. The results gained from this study, which took place in the banking workplace in Indonesia, provide a conceptual framework for individuals and organizations to better understand the critical factors which influence e-learning acceptance in developing countries.
The selection of intonation contours by Chinese L2 speakers of Dutch: Orthographic closure vs. prosodic knowledge
Authors: He Xuliang , van Heuven Vincent J. , Gussenhoven Carlos
Published: July 2012

Chinese learners of Dutch and a control group of native speakers of Dutch were presented with 26 sentences in the order they come in a story, visually as well as auditorily as spoken with four intonation contours. Participants were instructed to select the most appropriate intonation contour for each sentence in a forced choice task. Chinese participants selected the most appropriate version less often than the native speakers, and their selections from the three less appropriate competitors were more chaotic than those of the control group. The performance of the more proficient Chinese participants (as established in an independent test) was closer to that of the native speakers than the performance by the less proficient participants. Chinese participants employed a policy to assign rising contours to orthographic sentences closed by a question mark and falling contours to other sentences. In addition, they avoided choosing intonation contours ending in downstepped falling pitch and falling–rising pitch, pitch contours that are uncommon in their native language. The general acquisition profile follows findings in other areas of linguistic competence in that their performance correlated with age of arrival, not with either age or length of time they had been exposed to Dutch. As far as we are aware, this is the first systematic investigation of second language (L2) learners’ competence in melody selection.
Recovery Experiences of Taiwanese Women After Terminating Abusive Relationships
Authors: Hou Wen-Li , Ko Nai-Ying , Shu Bih-Ching
Published: July 2012

This article describes the recovery experiences of women who had suffered intimate partner violence in Taiwan. A phenomenological study design using semi-structured interviews was used to obtain data from a purposive sample of eight women. Colaizzi’s approach to narrative analysis was applied. Findings indicate that “reconstructing the self” emerged as the essence of the women’s recovery experiences. Four themes were identified: Feeling shame, creating mastery, recognizing the imperfect self, and embodying the self by helping others. Understanding the recovery experience is an important step in effectively assisting women to recover from abusive relationships and to reconstruct their lives.
Violence Against Women in Delhi: A Sustainability Problematic
Authors: Narayanan Yamini
Published: July 2012

Violence against women (VAW) has traditionally been of concern to feminists and cultural sociologists, and in recent decades, has also begun to be diagnosed and understood as a development problem. However, 20 women practitioners and scholars of development in Delhi have raised this issue explicitly as a sustainability problem while referring to the high rate of gender violence in the city’s public spaces. Sustainability is one of the most problematic political notions and scholars have been justifiably concerned that it has been hijacked to legitimise a variety of agendas, including unsustainable ones that contravene principles of social justice. However, it is also a compelling and powerful political concept and therefore, it is important to reconceptualise and reclaim from a feminist perspective, and from within the theoretical and empirical framework of equity, one of the central tenets of sustainability, and social justice. Therefore in this article, employing the primary research from Delhi, I use the notion of equity to frame the VAW in the city as a sustainability problem—the lack of which has an impact on urban design, which can constrain a city’s capacity to be sustainable.
Education for Liberation: Ambedkar’s Thought and Dalit Women’s Perspectives
Authors: Velaskar Padma
Published: July 2012

Despite the phenomenal impact that it has had in transforming the lives of dalits and its continuing contemporary relevance, Ambedkar’s social and educational thought remains surprisingly neglected in Indian educational discourse. Education was assigned a revolutionary role in Ambedkar’s conception of social progress and in his vision of a just and equal society. It was identified as a key instrument of liberation from oppressive structures of Hindu caste-patriarchy as well as of reconstruction of a new social order. Women were integral to this visionary egalitarianism and were consciously mobilised as political actors in the dalit liberation movement led by Ambedkar in the early decades of the twentieth century. This article explores the interface between Ambedkar’s ideologies of liberation and education, on the one hand, and dalit women’s thoughts and perspectives, on the other hand. It seeks to incorporate gender in the understanding of the historical processes of social change. It argues that an emancipatory discourse on gender was an important component of Ambedkar’s philosophy of social democratic liberalism and permitted women an authentic identification with its underlying principles with a view to achieving a full and enlightened citizenship. The article shows how the imbibing of Ambedkar’s thought and participation in his movement constituted the bedrock of dalit women’s political education. The arena of formal education was a significant focus of women’s political involvement, and they played foundational roles as political educators and educational activists. Dalit women redefined ideals of both womanhood and educational purpose in terms of counter-hegemonic reconstructions of nation, society and community, and articulated new subject positions grounded in them.
Referral Patterns of Nonmalignant Patients to an Irish Specialist Palliative Medicine Service
Authors: Wallace Elaine M. , Tiernan Eoin
Published: July 2012

Background:

Our perception is that the proportion of referrals made to the specialist palliative medicine service (SPMS) in our institution for patients with a primary diagnosis of nonmalignant disease is high and that these patients are often referred late in their illness. We aimed to review the symptom burden and referral patterns of patients with a noncancer diagnosis to the SPMS in our centre.

Methods:

All new non-malignant referrals to the SPMS in 2009 were included. Data were collected from patients' medical records and analyzed using Excel.

Results:

Ninety-two referrals were identified: 60 (65%) female, 32 (35%) male. Mean age 76.5 years (21-92). Reasons for referral included: end-of-life care (n=55, 60%), symptom control (n=23, 25%), home care support (n=13, 14%) and psychological support (n=1, 1%). Mean time from admission to referral was 24.9 days (<1-165). Fifty-six (61%) patients were commenced on a syringe driver (CSCI), with a mean time spent on a CSCI of 2.8 days (< 1-17). Primary outcomes included: death (n=72, 78.5%), home discharge (n=9, 10%), discharge to another care institution (n=6, 6.5%), discharge from service (n=3, 3%) and hospice transfer (n=2, 2%). Mean time from referral to outcome was 4.6 days (<1-35).

Conclusion:

The proportion of noncancer patients referred to the SPMS is our institution is high. This study confirms that nonmalignant referrals are commonly sent to the SPMS when patients are actively dying or very imminently dying. Further education of colleagues is warranted in the role of the SPMS, particularly with regard to earlier referral.
Feline low-grade alimentary lymphoma: how common is it?
Authors: Russell Kieran J , Beatty Julia A , Dhand Navneet , Gunew Marcus , Lingard Amy E , Baral Randolph M , Barrs Vanessa R
Published: July 2012

Low-grade alimentary lymphoma (LGAL) requires histological assessment of biopsies for diagnosis whereas intermediate- (IGAL) and high-grade (HGAL) alimentary lymphoma (AL) can be diagnosed by cytology of intestinal or mesenteric lymph node aspirates. Assessment of the relative frequency of subtypes of AL using histology alone may be skewed towards an increased frequency of LGAL as cases of IGAL or HGAL diagnosed cytologically may not progress to biopsy. We investigated the relative prevalence of AL subtypes diagnosed by both histopathology and cytology among primary accession cases across Australia during a 5-year period. Clinicopathological features of LGAL were compared with those of IGAL/HGAL. Fifty-three cases of AL were identified, including 30 diagnosed by histology (15 LGAL, 13 HGAL, two IGAL) and 23 IGAL/HGAL diagnosed by cytology. LGAL cases comprised 50% of histological diagnoses, but only 28% of all AL. A palpable abdominal mass was more common in IGAL/HGAL (43%) than in LGAL (7%) [odds ratio (OR) 7.6, P = 0.01]. Anaemia was more common in IGAL/HGAL (41%) compared with LGAL (7%) (OR 9.6, P = 0.02). On abdominal ultrasound, a gastrointestinal mural mass was visualised in 41% of IGAL/HGAL and 0% of LGAL ( P = 0.01). Where a detailed abdominal ultrasound report was provided, gastric/intestinal wall thickening was the most commonly reported abnormality (82%). In cats with intestinal thickening, a loss of normal layering was more common ( P = 0.02) in cats with IGAL/HGAL (71%) compared with those with LGAL (20%). The relative prevalence of LGAL was lower when cases diagnosed by cytology were included in addition to those diagnosed by histology in the study population. The relative frequency with which LGAL is diagnosed has increased since initial reports from this region. A number of significant clinicopathological findings are useful to distinguish LGAL from IGAL/HGAL.
Thick recognition: Advancing theory on identity change in intractable conflicts
Authors: Strömbom Lisa
Published: July 2012

This study relates the concept of recognition to processes of conflict transformation. The recognition concept has been underdeveloped in recent International Relations literature, where the main emphasis has been on interstate relations and on recognition as cause of conflict. This article challenges that understanding through the introduction of the concept of thick recognition. Thus an understanding of recognition which is applicable also in intrastate conflicts is developed. Through a strong emphasis on intrastate relations and identity politics, I develop thoughts on how narratives of war can be reversed through the introduction of narratives of recognition. The study thus provides theoretical concepts and distinctions that can be used as a framework for the study of thick recognition and its relationship to broader processes of conflict transformation. The theoretical framework is employed in a case study on the Israeli debates about ‘New History’. Insights from the case contribute to understandings of inhibiting and facilitating circumstances for the introduction of narratives of thick recognition in conflicted societies. The study ends with a discussion on the usefulness of the theoretical concepts for further work on recognition within the field of International Relations.
Disease Modifying Drugs Targeting β-Amyloid
Authors: Ozudogru S. N. , Lippa C. F.
Published: July 2012

At this time there are no effective methods to alter the disease course in Alzheimer's disease. All FDA approved interventions are for symptomatic relief only. However, it is an exciting time as many agents in development have theorhetical potential to impact the disease course. This review discusses some of the agents that have been in clinical trials, particularly those that affect amyloid processing. Some agents have failed while others still provide hope. Since amyloid is the peptide most closely linked to disease pathogenesis, it is possible that some of the anti-amyloid agents will impact the disease progression in a meaningful way.
A method for utilizing co-primary efficacy outcome measures to screen regimens for activity in two-stage Phase II clinical trials
Authors: Sill Michael W , Rubinstein Larry , Litwin Samuel , Yothers Greg
Published: July 2012

Background

Most Phase II clinical trials utilize a single primary end point to determine the promise of a regimen for future study. However, many disorders manifest themselves in complex ways. For example, migraine headaches can cause pain, auras, photophobia, and emesis. Investigators may believe that a drug is effective at reducing migraine pain and the severity of emesis during an attack. Nevertheless, they could still be interested in proceeding with the development of the drug if it is effective against only one of these symptoms. Such a study would be a candidate for a clinical trial with co-primary end points.

Purpose

The purpose of the article is to provide a method for designing a single arm, two-stage clinical trial with dichotomous co-primary end points of efficacy that has the ability to detect activity on either response measure with high probability when the drug is active on one or both measures, while at the same time rejecting the drug with high probability when there is little activity on both dimensions. The design enables early closure for futility and is flexible with regard to attained accrual.

Methods

The design is proposed in the context of cancer clinical trials with tumor response and progression-free survival (PFS) status after a certain period. Both end points are assumed to be distributed as binomial random variables, and uninteresting probabilities of success are determined from historical controls. Given the necessity of accrual flexibility, exhaustive searching algorithms to find optimum designs do not seem feasible at this time. Instead, critical values are determined for realized sample sizes using specific procedures. Then accrual windows are found to achieve a design’s desired level of significance, probability of early termination (PET), and power.

Results

The design is illustrated with a clinical trial that examined bevacizumab in patients with recurrent endometrial cancer. This study was negative by tumor response but positive by 6-month PFS. The procedure was compared to modified procedures in the literature, indicating that the method is competitive.

Limitations

Although the procedure allows investigators to construct designs with desired levels of significance and power, the PET under the null hypothesis is smaller than for single end point studies.

Conclusions

The impact of adding an additional end point on the sample size is often minimal, but the study gains sensitivity to activity on another dimension of treatment response. The operating characteristics are fairly robust to the level of association between the two end points. Software is available online.
Optimization of de novo transcriptome assembly from high-throughput short read sequencing data improves functional annotation for non-model organisms
Authors: Haznedaroglu Berat Z , Reeves Darryl , Rismani-Yazdi Hamid , Peccia Jordan
Published: July 2012

Background

The k-mer hash length is a key factor affecting the output of de novo transcriptome assembly packages using de Bruijn graph algorithms. Assemblies constructed with varying single k-mer choices might result in the loss of unique contiguous sequences (contigs) and relevant biological information. A common solution to this problem is the clustering of single k-mer assemblies. Even though annotation is one of the primary goals of a transcriptome assembly, the success of assembly strategies does not consider the impact of k-mer selection on the annotation output. This study provides an in-depth k-mer selection analysis that is focused on the degree of functional annotation achieved for a non-model organism where no reference genome information is available. Individual k-mers and clustered assemblies (CA) were considered using three representative software packages. Pair-wise comparison analyses (between individual k-mers and CAs) were produced to reveal missing Kyoto Encyclopedia of Genes and Genomes (KEGG) ortholog identifiers (KOIs), and to determine a strategy that maximizes the recovery of biological information in a de novo transcriptome assembly.

Results

Analyses of single k-mer assemblies resulted in the generation of various quantities of contigs and functional annotations within the selection window of k-mers (k-19 to k-63). For each k-mer in this window, generated assemblies contained certain unique contigs and KOIs that were not present in the other k-mer assemblies. Producing a non-redundant CA of k-mers 19 to 63 resulted in a more complete functional annotation than any single k-mer assembly. However, a fraction of unique annotations remained (~0.19 to 0.27% of total KOIs) in the assemblies of individual k-mers (k-19 to k-63) that were not present in the non-redundant CA. A workflow to recover these unique annotations is presented.

Conclusions

This study demonstrated that different k-mer choices result in various quantities of unique contigs per single k-mer assembly which affects biological information that is retrievable from the transcriptome. This undesirable effect can be minimized, but not eliminated, with clustering of multi-k assemblies with redundancy removal. The complete extraction of biological information in de novo transcriptomics studies requires both the production of a CA and efforts to identify unique contigs that are present in individual k-mer assemblies but not in the CA.
Differential microRNA response to a high-cholesterol, high-fat diet in livers of low and high LDL-C baboons
Authors: Karere Genesio M , Glenn Jeremy P , VandeBerg John L , Cox Laura A
Published: July 2012

Background

Dysregulation of microRNA (miRNA) expression has been implicated in molecular genetic events leading to the progression and development of atherosclerosis. We hypothesized that miRNA expression profiles differ between baboons with low and high serum low-density lipoprotein cholesterol (LDL-C) concentrations in response to diet, and that a subset of these miRNAs regulate genes relevant to dyslipidemia and risk of atherosclerosis.

Results

Using Next Generation Illumina sequencing methods, we sequenced hepatic small RNA libraries from baboons differing in their LDL-C response to a high-cholesterol, high-fat (HCHF) challenge diet (low LDL-C, n = 3; high LDL-C, n = 3), resulting in 517 baboon miRNAs: 490 were identical to human miRNAs and 27 were novel. We compared miRNA expression profiles from liver biopsies collected before and after the challenge diet and observed that HCHF diet elicited expression of more miRNAs compared to baseline (chow) diet for both low and high LDL-C baboons. Eighteen miRNAs exhibited differential expression in response to HCHF diet in high LDL-C baboons compared to 10 miRNAs in low LDL-C baboons. We used TargetScan/Base tools to predict putative miRNA targets; miRNAs expressed in high LDL-C baboons had significantly more gene targets than miRNAs expressed in low LDL-C responders. Further, we identified miRNA isomers and other non-coding RNAs that were differentially expressed in response to the challenge diet in both high LDL-C and low LDL-C baboons.

Conclusions

We sequenced and annotated baboon liver miRNAs from low LDL-C and high LDL-C responders using high coverage Next Gen sequencing methods, determined expression changes in response to a HCHF diet challenge, and predicted target genes regulated by the differentially expressed miRNAs. The identified miRNAs will enrich the database for non-coding small RNAs including the extent of variation in these sequences. Further, we identified other small non-coding RNAs differentially expressed in response to diet. Our discovery of differentially expressed baboon miRNAs in response to a HCHF diet challenge that differ by LDL-C phenotype is a fundamental step in understating the role of non-coding RNAs in dyslipidemia.
Rumen microbial and fermentation characteristics are affected differently by bacterial probiotic supplementation during induced lactic and subacute acidosis in sheep
Authors: Lettat Abderzak , Nozière Pierre , Silberberg Mathieu , Morgavi Diego P , Berger Claudette , Martin Cécile
Published: July 2012

Background

Ruminal disbiosis induced by feeding is the cause of ruminal acidosis, a digestive disorder prevalent in high-producing ruminants. Because probiotic microorganisms can modulate the gastrointestinal microbiota, propionibacteria- and lactobacilli-based probiotics were tested for their effectiveness in preventing different forms of acidosis.

Results

Lactic acidosis, butyric and propionic subacute ruminal acidosis (SARA) were induced by feed chalenges in three groups of four wethers intraruminally dosed with wheat, corn or beet pulp. In each group, wethers were either not supplemented (C) or supplemented with Propionibacterium P63 alone (P) or combined with L. plantarum (Lp + P) or L. rhamnosus (Lr + P). Compared with C, all the probiotics stimulated lactobacilli proliferation, which reached up to 25% of total bacteria during wheat-induced lactic acidosis. This induced a large increase in lactate concentration, which decreased ruminal pH. During the corn-induced butyric SARA, Lp + P decreased Prevotella spp. proportion with a concomitant decrease in microbial amylase activity and total volatile fatty acids concentration, and an increase in xylanase activity and pH. Relative to the beet pulp-induced propionic SARA, P and Lr + P improved ruminal pH without affecting the microbial or fermentation characteristics. Regardless of acidosis type, denaturing gradient gel electrophoresis revealed that probiotic supplementations modified the bacterial community structure.

Conclusion

This work showed that the effectiveness of the bacterial probiotics tested depended on the acidosis type. Although these probiotics were ineffective in lactic acidosis because of a deeply disturbed rumen microbiota, some of the probiotics tested may be useful to minimize the occurrence of butyric and propionic SARA in sheep. However, their modes of action need to be further investigated.
Body mass index contributes to sympathovagal imbalance in prehypertensives
Authors: Pal Gopal Krushna , Chandrasekaran Adithan , Hariharan Ananthanarayanan Palghat , Dutta Tarun Kumar , Pal Pravati , Nanda Nivedita , Venugopal Lalitha
Published: July 2012

Background

The present study was conducted to assess the nature of sympathovagal imbalance (SVI) in prehypertensives by short-term analysis of heart rate variability (HRV) to understand the alteration in autonomic modulation and the contribution of BMI to SVI in the genesis of prehypertension.

Methods

Body mass index (BMI), basal heart rate (BHR), blood pressure (BP), rate pressure product (RPP) and HRV indices such as total power (TP), low-frequency power (LF), normalized LF (LFnu), high-frequency power (HF), normalized HF (HFnu), LF-HF ratio, mean heart rate (mean RR), square root of the mean squared differences of successive normal to normal intervals (RMSSD), standard deviation of normal to normal RR interval (SDNN), the number of interval differences of successive NN intervals greater than 50 ms (NN50) and the proportion derived by dividing NN50 by the total number of NN intervals (pNN50) were assessed in three groups of subjects: normotensives having normal BMI (Group 1), prehypertensives having normal BMI (Group 2) and prehypertensives having higher BMI (Group 3). SVI was assessed from LF-HF ratio and correlated with BMI, BHR, BP and RPP in all the groups by Pearson correlation. The contribution of BMI to SVI was assessed by multiple regression analysis.

Results

LF and LFnu were significantly increased and HF and HFnu were significantly decreased in prehypertensive subjects in comparison to normotensive subjects and the magnitude of these changes was more prominent in subjects with higher BMI compared to that of normal BMI. LF-HF ratio, the sensitive indicator of sympathovagal balance had significant correlation with BMI (P = 0.000) and diastolic blood pressure (DBP) (P = 0.002) in prehypertensives. BMI was found to be an independent contributing factor to SVI (P = 0.001) in prehypertensives.

Conclusions

It was concluded that autonomic imbalance in prehypertensives manifested in the form of increased sympathetic activity and vagal inhibition. In prehypertensives with higher BMI, vagal withdrawal was predominant than sympathetic overactivity. Magnitude of SVI (alteration in LF-HF ratio) was linked to changes in BMI and DBP. BMI had an independent influence on LF-HF ratio. It was advised that life-style modifications such as yoga and exercise would enable achieve the sympathovagal balance and blood pressure homeostasis in prehypertensives.
The diagnosis of urinary tract infections in young children (DUTY): protocol for a diagnostic and prospective observational study to derive and validate a clinical algorithm for the diagnosis of UTI in children presenting to primary care with an acute illness
Authors: Downing Harriet , Thomas-Jones Emma , Gal Micaela , Waldron Cherry-Ann , Sterne Jonathan , Hollingworth William , Hood Kerenza , Delaney Brendan , Little Paul , Howe Robin , Wootton Mandy , Macgowan Alastair , Butler Christopher C , Hay Alastair D ,   DUTY study team
Published: July 2012

Background

Urinary tract infection (UTI) is common in children, and may cause serious illness and recurrent symptoms. However, obtaining a urine sample from young children in primary care is challenging and not feasible for large numbers. Evidence regarding the predictive value of symptoms, signs and urinalysis for UTI in young children is urgently needed to help primary care clinicians better identify children who should be investigated for UTI. This paper describes the protocol for the Diagnosis of Urinary Tract infection in Young children (DUTY) study. The overall study aim is to derive and validate a cost-effective clinical algorithm for the diagnosis of UTI in children presenting to primary care acutely unwell.

Methods/design

DUTY is a multicentre, diagnostic and prospective observational study aiming to recruit at least 7,000 children aged before their fifth birthday, being assessed in primary care for any acute, non-traumatic, illness of ≤ 28 days duration. Urine samples will be obtained from eligible consented children, and data collected on medical history and presenting symptoms and signs. Urine samples will be dipstick tested in general practice and sent for microbiological analysis. All children with culture positive urines and a random sample of children with urine culture results in other, non-positive categories will be followed up to record symptom duration and healthcare resource use. A diagnostic algorithm will be constructed and validated and an economic evaluation conducted.

The primary outcome will be a validated diagnostic algorithm using a reference standard of a pure/predominant growth of at least >103, but usually >105 CFU/mL of one, but no more than two uropathogens.

We will use logistic regression to identify the clinical predictors (i.e. demographic, medical history, presenting signs and symptoms and urine dipstick analysis results) most strongly associated with a positive urine culture result. We will then use economic evaluation to compare the cost effectiveness of the candidate prediction rules.

Discussion

This study will provide novel, clinically important information on the diagnostic features of childhood UTI and the cost effectiveness of a validated prediction rule, to help primary care clinicians improve the efficiency of their diagnostic strategy for UTI in young children.
Risk factors for suicide behaviors in the observational schizophrenia outpatient health outcomes (SOHO) study
Authors: Brugnoli Roberto , Novick Diego , Haro Josep Maria , Rossi Andrea , Bortolomasi Marco , Frediani Sonia , Borgherini Giuseppe
Published: July 2012

Background

To identify risk factors for suicide using data from a large, 3-year, multinational follow-up study of schizophrenia (SOHO study).

Methods

Baseline characteristics of 8,871 adult patients with schizophrenia were included in a logistic regression post-hoc analysis comparing patients who attempted and/or committed suicide during the study with those who did not.

Results

384 (4.3%) patients attempted or committed suicide. Completed suicides were 27 (0.3%). The significant risk factors for suicide behaviors were previous suicidality, depressive symptoms, prolactin-related adverse events, male gender and history of hospitalization for schizophrenia.

Conclusions

In view of the observational design of the study and the post-hoc nature of the analysis, the identified risk factors should be confirmed by ad-hoc specifically designed studies.