bluuebunny/crossref_metadata_2025 huggingface dataset:
Threats, Inflation of National Security
Authors: Mueller John
Published: November 2011

Many political scientists argue that countries tend to balance not so much against power as against apparent threat. The next question, however, is how is it exactly that they decide what those threats are? Over the last several decades, it appears that there has been a tendency to exaggerate threats to national security and then, partly in consequence, to overreact to them.
TRANSCEND
Method
Authors: Galtung Johan
Published: November 2011

The TRANSCEND method is expressed in three word‐triples. First, there are the three phases of the method: mapping the conflict, legitimizing, and bridging incompatibilities. Second, there are the three aspects of the process: one‐on‐one, dialogue, and transcendence. Third, there are the three capacities demanded of the mediator: empathy, nonviolence, and creativity (Galtung, 2004).
Transitional Justice Systems, Psychology and
Authors: Byrne Catherine C. Jenny Escobar , Escobar Jenny
Published: November 2011

In order to understand the relationship between psychology and transitional justice mechanisms, we address what psychology is as a discipline and how it is capable of contributing to mechanisms of transitional justice. Psychology as an academic field of inquiry has taken many forms, as demarcated by divisions within the field such as cognitive, developmental, clinical, social, and political psychology, to name a few. These subfields tend to highlight the different frameworks and theories utilized to study and understand human cognition and behavior at both the individual and group level. However, peace psychology attempts to bridge the separation between these subfields by focusing on the understanding and prevention of conflict (often referred to as peacemaking) and the promotion of nonviolent initiatives seeking social justice (referred to as peacebuilding) (Christie, Wagner, & Winter, 2001). By having these specific goals in mind, peace psychology is able to draw from the different theories and methods proposed by the subfields (along with other disciplines such as philosophy, political science, and anthropology), resulting in the potential collaboration of scholars that often are bound to their specific discipline or area of expertise. In addition to examining why conflict happens and how it can be prevented or resolved, peace psychology expands the aim of psychology to be not only a field of academic and theoretical inquiry, but also a source for social change and justice. The role of psychology in transitional justice systems is to provide an understanding of particular psychological processes that can assist in the development and implementation of effective transitional justice mechanisms.
Trauma – from an Individual and a Group Perspective
Authors: Sveaass Nora
Published: November 2011

Etymologically, the word
trauma
comes from Greek and means injury or wound. In medicine, trauma means a physical injury caused by impact, force, or object penetrating the skin. In psychology, psychological trauma refers to an emotional or psychological injury, usually resulting from an extremely stressful or life‐threatening situation. It is common to differentiate between man‐made trauma or disasters and natural disasters. Man‐made is further differentiated between trauma resulting from accidents or unintended damage, loss and breakdown of systems, and trauma resulting from the ultimate betrayal as in sexual abuse and violence against children, and the intentional infliction of severe pain and systematic destruction of human mind and dignity as in torture. As will become clear, intentions, meanings, and understanding are important elements in the context of psychological trauma. (See post‐traumatic stress disorder and peace; trauma, intergenerational transmission of; traumatic stress, perpetration‐induced.)
Trauma, Intergenerational Transmission of
Authors: Tint Barbara S.
Published: November 2011

George Santayana once said: “Those who cannot remember the past are condemned to repeat it.” As we consider the generations of those who have endured communal conflict around the world, it appears possible that the opposite holds more truth: that those who do remember their past, live their past, and honor their past, are continuously replaying the cycles of struggle and conflict that are their legacy. These cycles of conflict continue in part because of the intergenerational transmission of trauma for both individuals and groups. (See intergroup violence and psychosocial interventions, cycles of.) While there has been a great deal of research dedicated to exploring the effects of psychological trauma on individuals, only recently has there been exploration surrounding the effects of collective trauma on groups in conflict and the intergenerational transmission of the psychological wounds impacting large numbers of people (Danieli, 1998; Rogers, 1990). In conflicted societies, while war and its immediate effects may be long over, the residual and lasting dimensions carry on for years and generations.
Traumatic Stress, Perpetration‐Induced
Authors: MacNair Rachel M.
Published: November 2011

In the aftermath of combat veterans returning to the United States from Vietnam, post‐trauma reactions to battle were finally officially recognized and defined as post‐traumatic stress disorder (PTSD). Because of the controversy surrounding that war, groups such as the Veterans of Foreign Wars understood PTSD to be an antiwar propaganda ploy. Nevertheless, the development from “soldier's heart” and “shell shock” and “combat fatigue” to a more clearly defined set of post‐trauma symptoms has become widespread and applied to various categories of victims ranging from concentration camps to car accidents. It also includes those who rescue others. Its use in understanding the therapeutic needs of combat veterans has become increasingly obvious and is no longer a contentious issue.
Us and Them: Moderating Dichotomous Ingroup/Outgroup Thinking
Authors: Fabick Stephen D.
Published: November 2011

Identification with one's own group and counter‐identification with other groups is motivated by our needs for identity, esteem, and safety. Group identification provides not only ingroup cohesion, but also pride through the denial of negative characteristics that are then projected onto outgroups, especially certain targeted outgroups. Such identifications create clarity and prevent fusion within a large, chaotic world.
Values, Nonviolence, and Peace Psychology
Authors: Mayton Daniel M. , Gay Chelsea K.
Published: November 2011

Milton Rokeach (1973) defines values as enduring beliefs that a specific mode of conduct or an end‐state of existence is preferred, either personally or socially, in comparison with other modes of conduct and end‐states. Values are proscriptive or prescriptive; this means they impose restraints on behavioral modes of conduct or they give directions and rules for one's behavior, respectively. Proscriptive values are inhibitory. Prescriptive values are initiatory. Because of their relevance to one's behavior, values can also be representative of a social standard for conduct. Rokeach separates values into two main divisions, instrumental and terminal. Instrumental values center on modes of conduct and can be either morally centered or competent‐centered. These types of values influence courses of action and modes of behavior. Examples of instrumental values could be behaving honestly or acting politely. Terminal values deal with end‐states of existence that are either interpersonal or intrapersonal; they are usually based on situational outcomes or a long‐term goal. Terminal values can be as broad as world peace or as narrow as personal salvation. The short‐term purpose of values is to guide behaviors and to provide a foundation for decision‐making and conflict resolution in day‐to‐day life. The function of values in the long term is to allow for the expression of basic human needs. In much the same way that Abraham Maslow believes self‐actualization is the “super‐goal,” or end‐state, Rokeach believes that terminal values are guiding us and motivating us towards that same end‐state of fulfillment and achievement as a human being. The Rokeach Values Survey (RVS) uses a ranking process to assess the priorities placed on 18 terminal and 18 instrumental values in a reliable and valid way.
Victimhood, Collective
Authors: Vollhardt Johanna Ray
Published: November 2011

In the twentieth century, an estimated 191 million people died in conflicts – over half were civilians. With the changing nature of conflict over the last decades, there has been a dramatic increase in the number of targeted civilians. Approximately three fourths of the 190 armed conflicts since World War II have not been between but within states, often targeting civilians because of their ethnic, religious, or other group memberships. Accordingly, 90% of those killed in armed conflicts today are civilians. Moreover, about 20 million people have been displaced in the last decades. Given the increasing number of civilians who become victims of conflict worldwide, we must ask ourselves how the experience of collective violence will shape attitudes and worldviews in the present and in generations to come: Will it feed into cycles of violence or promote peace?
Violent Video Games and Aggression
Authors: Byrne Mykolas , Christie Daniel J.
Published: November 2011

The presence of violent video games in mainstream culture has been controversial since
Pac Man
began chomping ghosts more than 20 years ago. While early games were simple in both graphics and game play, the last three decades have seen rapid advances in strategic complexity and visual realism, fostering an industry with production scales rivaling Hollywood and now worth more than US$25 billion (Collier, Liddell Jr., & Liddell, 2008). Video games are also now widely played by adults as well as children. The Entertainment Software Association claims that 68% of American households regularly play video games, the average gamer is 35 years old, and 40% of all players are women. Given the ubiquity of video games, it is not surprising that criticism of popular titles and attempts to regulate their content is often met with opposition both within the industry and in the broader community of gamers.
War Veterans and Family Violence
Authors: Beara Vladan
Published: November 2011

War occurs when political elites move, train, and organize a large group of people in order to kill members of other groups. War includes violence and destruction as its core elements. In every violent act, people find themselves in the role of perpetrator, victim, or witness. War represents a series of violent acts. Combatants may find themselves in all three roles at the same time. A soldier is expected to kill human beings in a controlled manner and under specific circumstances. The soldier is expected to commit or to assist and support violence against members of other groups with no regard as to whether he or she personally agrees.
War: US Children and Parental Deployment
Authors: Van Hoorn Judith L. , Levin Diane E.
Published: November 2011

The United States has been waging war in Afghanistan and Iraq for almost a decade. As of 2009, more than 700,000 children in the United States have a parent deployed in these conflicts, either currently or in the past. Mental health professionals and educators are increasingly concerned about the psychological burdens and challenges of parental combat deployment on children. “Having a primary caretaker deployed to a war zone for an indeterminate period is among the more stressful events a child can experience,” according to the report of the American Psychological Association Presidential Task Force on Military Deployment Services for Youth, Families, and Service Members (APA, 2007, p. 4).
Women and Peace Hypothesis
Authors: Maoz Ifat
Published: November 2011

The women and peace hypothesis posits that women are more oriented toward peace and compromise than are men. More specifically, women are seen as more accepting of compromise in disputes and as less likely than men to support violence and war (Caprioli & Boyer, 2001). Competition, dominance, intransigence, and territoriality are thus associated with a “male” approach to conflict, whereas cooperation, interdependence, accommodation, concern for others, tolerance, and pacifism are seen as a “female” perspective (Tessler, Nachtwey, & Grant, 1999).
Game Theory: Conflict and Cooperation
Authors: Brandstätter Eduard
Published: November 2011

Philosopher Jeremy Bentham envisioned a society in which people strive for “the greatest good for the greatest number of people.” All too often, however, striving for one's own good opposes that of others — leading to conflict rather than greatest happiness. Such conflicts are common and range from two children craving the same cake to nations negotiating thorny peace treaties. In this article I focus on conflicts and cooperation. To this end I describe a scientific school of thought, known as
game theory
, which offers a fruitful framework for classifying conflicts and for overcoming them by promoting cooperation.
Optimization of single mixed refrigerant natural gas liquefaction plant with nonlinear programming
Authors: Khan Mohd Shariq , Lee Sanggyu , Lee Moonyong
Published: November 2011

The liquefaction of natural gas (NG) in a mixed refrigerant (MR) system is an energy‐demanding process. Much energy is wasted because of its irreversibilities and its nonoptimal execution. The most important factors affecting this process's performance are the refrigerant's composition and flow rate, the suction and evaporation pressures, and the extent of refrigerant vaporization. They should be adjusted to optimize the overall operation. The adjustment of one of these variables will affect the other because of their highly nonlinear interactions. This work reports the optimization of a single MR (SMR) process of NG liquefaction. The SMR process was modeled in the UniSim Design commercial process plant simulator, and the model was optimized for compression energy with nonlinear programming (NLP) while satisfying constraints. The base case for optimization was selected by mesh searching, and case study demonstrates that NLP can reduce energy use and improve the process's efficiency. © 2011 Curtin University of Technology and John Wiley & Sons, Ltd.
New Azidotetrazoles: Structurally Interesting and Extremely Sensitive
Authors: Klapötke Thomas M. , Krumm Burkhard , Martin Franz A. , Stierstorfer Jörg
Published: November 2011

The treatment of triaminoguanidinium chloride with two equivalents of sodium nitrite under acidic conditions, followed by the cyclization with stoichiometric amounts of either sodium hydroxide solution or solid sodium carbonate yielded 1‐amino‐5‐azidotetrazole (1), 5‐azido‐1‐diazidocarbamoyltetrazole (2), and 1‐(aminoazidocarbamoyl)‐5‐azidotetrazole (3). The three novel compounds could be isolated by short‐column liquid chromatography by using chloroform in reasonable yields. The mechanism of the formation as well as the decomposition pathway of the materials was investigated and a full characterization of all three compounds is presented. Compounds 1, 2, 3 have been characterized by means of Raman and IR as well as multinuclear NMR spectroscopy, mass spectrometry, and X‐ray diffraction studies. Thermal stabilities have been evaluated by differential scanning calorimetry. Theoretical calculations have been performed to ensure the assignment of the vibrational modes obtained from Raman and IR measurements. The sensitivity values obtained from our measurements reflect the behavior of the compounds, which show an extremely high sensitivity toward mechanical as well as thermal stimuli.
Staging of multivessel percutaneous coronary interventions: An expert consensus statement from the Society for Cardiovascular Angiography and Interventions
Authors: Blankenship James C. , Moussa Issam D. , Chambers Charles C. , Brilakis Emmanouil S. , Haldis Thomas A. , Morrison Douglas A. , Dehmer Gregory J.
Published: November 2011

Percutaneous coronary interventions (PCIs) to treat multivessel coronary artery disease (MVCAD) may involve single‐vessel or multivessel interventions, performed in one or more stages. This consensus statement reviews factors that may influence choice of strategy and includes six recommendations to guide decisions regarding staging of PCI [1]. Every patient who undergoes PCI should receive optimal therapy for coronary disease, ideally before starting the procedure [2]. Multivessel PCI at the time of diagnostic catheterization should be considered only if informed consent included the risks and benefits of multivessel PCI and the risks and benefits of alternative treatments [3]. When considering multivessel PCI, the interventionist should develop a strategy regarding which stenoses to treat or evaluate, and their order, method, and timing. This strategy should maximize patient benefits, minimize patient risk, and consider the factors described in this article [4]. For planned multivessel PCI, additional vessel(s) should be treated only if the first vessel is treated successfully and if anticipated contrast and radiation doses and patient and operator conditions are favorable [5]. After the first stage of the planned multistage PCI, the need for subsequent PCI should be reviewed before it is performed [6]. Third party payers and quality auditors should recognize that multistage PCI for MVCAD is neither an indication of poor quality nor an attempt to increase reimbursement when performed according to recommendations in this article. © 2011 Wiley Periodicals, Inc.
Stable and Efficient Homogeneous Photocatalytic H2 Evolution Based on Water Soluble Pyrenetetrasulfonic Acid Functionalized Platinum Nanocomposites
Authors: Zhu Mingshan , Li Zhi , Du Yukou , Mou Zhigang , Yang Ping
Published: November 2011

Herein, 1,3,6,8‐pyrenetetrasulfonic acid (PTSA) functionalized Pt nanocomposites were synthesized and characterized by UV/vis, X‐ray photoelectron spectroscopic (XPS), FTIR, TEM, and XRD methods. Pyrenetetrasulfonic acid was not only used as the stabilizer to prevent agglomeration of Pt nanoparticles but also served as the light‐harvesting photosensitizer, absorbing irradiating light and transferring photoexited electrons to the platinum nanoparticles. The occurrence of the photoinduced electron transfer process was confirmed by the combination of time‐resolved fluorescence and photoelectrochemical spectral measurements. Photocatalytic results showed that PTSA functionalized Pt nanocomposites could be used as stable photocatalysts for photoinducing H2 evolution. At the optimal reaction conditions (nPt:nPTSA=100, pH 3), enhanced amounts of hydrogen were evolved from the system under UV/vis irradiation in the absence of an electron mediator. The corresponding amount of hydrogen evolution was 125.1 μmol for 12 h exposure to UV/vis irradiation, and the apparent quantum efficiency at a wavelength of λ=365 nm was 11.5 %.
Mononuclear–Dinuclear Equilibrium of Grafted Copper Complexes Confined in the Nanochannels of MCM‐41 Silica
Authors: Zhang Kun , Lam Koon‐Fung , Albela Belén , Xue Teng , Khrouz Lhoussain , Hou Qiong‐Wei , Yuan En‐Hui , He Ming‐Yuan , Bonneviot Laurent
Published: November 2011

Following the structural concept of copper‐containing proteins in which dinuclear copper centers are connected by hydroxide bridging ligands, a bidentate copper(II) complex has been incorporated into nano‐confined MCM‐41 silica by a multistep sequential grafting technique. Characterization by a combination of EPR spectroscopy, X‐ray photoelectron spectroscopy (XPS), UV/Vis spectroscopy, IR spectroscopy , and solid‐state 13C and 29Si cross‐polarization magic‐angle spinning (CP‐MAS) NMR suggests that dinuclear Cu complexes are bridged by hydroxide and other counterions (chloride or perchlorate ions), similar to the situation for EPR‐undetectable [CuII⋅⋅⋅CuII] dimer analogues in biological systems. More importantly, a dynamic mononuclear–dinuclear equilibrium between different coordination modes of copper is observed, which strongly depends on the nature of the counterions (Cl− or ClO4−) in the copper precursor and the pore size of the silica matrix (the so‐called confinement effect). A proton‐transfer mechanism within the hydrogen‐bonding network is suggested to explain the dynamic nature of the dinuclear copper complex supported on the MCM‐41 silica.
Which is the best foot to put forward in recurrent ovarian cancer?
Authors: Rose Peter G.
Published: November 2011

This investigation of sequential versus combination chemotherapy for platinum‐sensitive, recurrent ovarian cancer uses a study design that involves giving sequential docetaxel followed by carboplatin. On the basis of the improved progression‐free rate with the combination, use of a nonplatinum agent as the first of the sequential therapies in a platinum‐sensitive patient may not be putting the best foot forward.
Androgen deprivation for prostate cancer
Authors: Shahinian Vahakn B.
Published: November 2011

The list of adverse consequences of androgen deprivation therapy for prostate cancer continues to grow, with the latest addition being an increased risk of thromboembolism. Accordingly, use of androgen deprivation therapy should be restricted to settings where clear evidence of benefit exists.
Gene expression profiles in peripheral blood as a biomarker in cancer patients receiving peptide vaccination
Authors: Komatsu Nobukazu , Matsueda Satoko , Tashiro Kousuke , Ioji Tetsuya , Shichijo Shigeki , Noguchi Masanori , Yamada Akira , Doi Atsushi , Suekane Shigetaka , Moriya Fukuko , Matsuoka Kei , Kuhara Satoru , Itoh Kyogo , Sasada Tetsuro
Published: November 2011

BACKGROUND:

Because only a subset of patients show clinical responses to peptide‐based cancer vaccination, it is critical to identify biomarkers for selecting patients who would most likely benefit from this treatment.

METHODS:

The authors characterized the gene expression profiles in peripheral blood of vaccinated patients to identify biomarkers to predict patient prognosis. Peripheral blood was obtained from advanced castration‐resistant prostate cancer patients, who survived for >900 days (long‐term survivors, n = 20) or died within 300 days (short‐term survivors, n = 20) after treatment with personalized peptide vaccination. Gene expression profiles in prevaccination and postvaccination peripheral blood mononuclear cells (PBMCs) were assessed by DNA microarray.

RESULTS:

There were no statistically significant differences in the clinical or pathological features between the 2 groups. Microarray analysis of prevaccination PBMCs identified 19 genes that were differentially expressed between the short‐term and long‐term survivors. Among the 15 up‐regulated genes in the short‐term survivors, 13 genes, which were also differentially expressed in postvaccination PBMCs, were associated with gene signatures of granulocytes. When a set of 4 differentially expressed genes were selected as the best combination to determine patient survival, prognosis was correctly predicted in 12 of 13 patients in a validation set (accuracy, 92%).

CONCLUSIONS:

These results suggested that abnormal granulocytes present in the PBMC faction may contribute to poor prognosis in advanced prostate cancer patients receiving personalized peptide vaccination. Gene expression profiling in peripheral blood might thus be informative for devising better therapeutic strategies by predicting patient prognosis after cancer vaccines. Cancer 2012;118: 3208–21. © 2011 American Cancer Society.
Predicting the risk of chemotherapy toxicity in older patients: The Chemotherapy Risk Assessment Scale for High‐Age Patients (CRASH) score
Authors: Extermann Martine , Boler Ivette , Reich Richard R. , Lyman Gary H. , Brown Richard H. , DeFelice Joseph , Levine Richard M. , Lubiner Eric T. , Reyes Pablo , Schreiber Frederic J. , Balducci Lodovico
Published: November 2011

BACKGROUND:

Tools are lacking to assess the individual risk of severe toxicity from chemotherapy. Such tools would be especially useful for older patients, who vary considerably in terms of health status and functional reserve.

METHODS:

The authors conducted a prospective, multicentric study of patients aged ≥70 years who were starting chemotherapy. Grade 4 hematologic (H) or grade 3/4 nonhematologic (NH) toxicity according to version 3.0 of the Common Terminology Criteria for Adverse Events was defined as severe. Twenty‐four parameters were assessed. Toxicity of the regimen (Chemotox) was adjusted using an index to estimate the average per‐patient risk of chemotherapy toxicity (the MAX2 index). In total, 562 patients were accrued, and 518 patients were evaluable and were split randomly (2:1 ratio) into a derivation cohort and a validation cohort.

RESULTS:

Severe toxicity was observed in 64% of patients. The Chemotherapy Risk Assessment Scale for High‐Age Patients (CRASH) score was constructed along 2 subscores: H toxicity and NH toxicity. Predictors of H toxicity were lymphocytes, aspartate aminotransferase level, Instrumental Activities of Daily Living score, lactate dehydrogenase level, diastolic blood pressure, and Chemotox. The best model included the 4 latter predictors (risk categories: low, 7%; medium‐low, 23%; medium‐high, 54%; and high, 100%, respectively; Ptrend < .001). Predictors of NH toxicity were hemoglobin, creatinine clearance, albumin, self‐rated health, Eastern Cooperative Oncology Group performance, Mini‐Mental Status score, Mini‐Nutritional Assessment score, and Chemotox. The 4 latter predictors provided the best model (risk categories: 33%, 46%, 67%, and 93%, respectively; Ptrend < .001). The combined risk categories were 50%, 58%, 77%, and 79%, respectively; Ptrend < .001). Bootstrap internal validation and independent sample validation demonstrated stable risk categorization and Ptrend < .001.

CONCLUSIONS:

The CRASH score distinguished several risk levels of severe toxicity. The split score discriminated better than the combined score. To the authors' knowledge, this is the first score systematically integrating both chemotherapy and patient risk for older patients and has a potential for future clinical application. Cancer 2011. © 2011 American Cancer Society.
Sequential parameter estimation for fluid–structure problems: Application to hemodynamics
Authors: Bertoglio Cristóbal , Moireau Philippe , Gerbeau Jean‐Frederic
Published: November 2011

We present a robust and computationally efficient parameter estimation strategy for fluid–structure interaction problems. The method is based on a filtering algorithm restricted to the parameter space, known as the reduced‐order unscented Kalman filter. It does not require any adjoint or tangent problems. In addition, it can easily be run in parallel, which is of great interest in fluid–structure problems where the computational cost of the forward simulation is already a challenge in itself. We illustrate our methodology with the estimation of the artery wall stiffness from the wall displacement measurements – as they could be extracted from medical imaging – in a three‐dimensional idealized abdominal aortic aneurysm. We also show preliminary results about the estimation of the proximal Windkessel resistance, which is an important parameter for setting appropriate fluid boundary conditions. Copyright © 2011 John Wiley & Sons, Ltd.
A metaphoric trajectory data warehouse for Olympic athlete follow‐up
Authors: Porto Fabio , de C. Moura Ana Maria , da Silva Frederico C. , Bassini Adriana , Palazzi Daniele C. , Poltosi Maira , de Castro Luis Eduardo Viveiros , Cameron L. C.
Published: November 2011

Sport science is a research discipline that aims to understand exercise and apply scientific methods in support of increasing an athlete's performance. In this paper, we present initial results on modeling, managing and analyzing an athlete's data gathered by sport scientists. An Olympic data warehouse is designed initially to support the monitoring of an athlete's biochemical data. A trajectory data model is extended to represent the athlete's measurements along his/her training states, referred to here as metaphoric trajectories. Furthermore, a data warehouse for metaphoric trajectories is designed and two analysis approaches — a relational and a multidimensional one — are evaluated. We compare both approaches and discuss their benefits to the athlete's follow‐up analyses applied by sport scientists. Copyright © 2011 John Wiley & Sons, Ltd.
The development of fear learning and generalization in 8–13 year‐olds
Authors: Glenn Catherine R. , Klein Daniel N. , Lissek Shmuel , Britton Jennifer C. , Pine Daniel S. , Hajcak Greg
Published: November 2011

The current study examined developmental changes in fear learning and generalization in 40 healthy 8–13 year‐olds using an aversive conditioning paradigm adapted from Lau et al. [Lau et al. [2008] Journal of the American Academy of Child and Adolescent Psychiatry 47:94–102]. In this task, the conditioned stimuli (CS+/CS−) are two neutral female faces, and the unconditioned stimulus is a fearful, screaming face. The second phase of the study also included a generalization stimulus (GS): a 50% blend of the CS± faces. The eye‐blink startle reflex was utilized to measure defensive responding. Patterns of fear learning and generalization were qualified by child age. Older children demonstrated greater fear learning (i.e., larger startle during CS+ than CS−) than younger children. In addition, older children exhibited the typical pattern of generalization observed in adults, whereas younger children did not. Finally, fear learning also related to contingency awareness; only children who correctly identified the CS+ demonstrated fear‐potentiated startle to the CS+. Clinical implications and future directions are discussed. © 2011 Wiley Periodicals,Inc. Dev Psychobiol 54: 675–684, 2012.
Administration of recombinant human thioredoxin‐1 significantly delays and prevents autoimmune diabetes in nonobese diabetic mice through modulation of autoimmunity
Authors: Chernatynskaya Anna V. , Looney Benjamin , Hu Hanbo , Zhu Xiaoyan , Xia Chang‐Qing
Published: November 2011

Background

Thioredoxin as a biological antioxidant plays an important role in regulating the redox system. The administration of recombinant thioredoxin has been demonstrated to be anti‐inflammatory. In this study, the effect of recombinant human thioredoxin‐1 (rhTrx‐1) in preventing type 1 diabetes (T1D) in nonobese diabetic (NOD) mice was evaluated.

Methods

Eight‐week‐old NOD mice were treated with intravenous injection of rhTrx‐1 (5 µg/mouse/day) for 5 weeks (5 days a week), followed by every other day for additional 5 weeks. Diabetes onset was monitored twice a week. Pancreatic histology and β‐cell mass were examined by hematoxylin and eosin (H&E) and insulin immunohistochemistry staining, respectively. Adoptive transfer experiments were executed to assess autoimmune T cells modulated by rhTrx treatment.

Results

The intravenous administration of rhTrx‐1 significantly delayed and prevented T1D in NOD mice. The histology data showed that rhTrx‐1 treatment markedly reduced insulitic lesions and significantly preserved insulin‐producing β cells. Adoptive transfer of spleen cells from rhTrx‐1‐treated mice into nonobese diabetic‐severe combined immunodeficiency (NOD‐SCID) mice significantly reduced the diabetes onset than transfer of those from phosphate‐buffered saline‐treated mice. Adoptive co‐transfer experiments demonstrated that spleen cells from rhTrx‐1‐treated mice significantly delayed diabetes induced by the co‐transferred diabetogenic spleen cells from the new‐onset diabetic mice.

Conclusions

Antioxidant rhTrx‐1 effectively prevents T1D which may be attributed to its activity to modulate autoimmunity. Copyright © 2011 John Wiley & Sons, Ltd.
Analysis of the HLA and non‐HLA susceptibility loci in Japanese type 1 diabetes
Authors: Yamashita Hisakuni , Awata Takuya , Kawasaki Eiji , Ikegami Hiroshi , Tanaka Shoichiro , Maruyama Taro , Shimada Akira , Nakanishi Koji , Takahashi Kazuma , Kobayashi Tetsuro , Kawabata Yumiko , Miyashita Yumi , Kurihara Susumu , Morita‐Ohkubo Tomoko , Katayama Shigehiro ,   on behalf of The Japanese Study Group on Type 1 Diabetes Genetics
Published: November 2011

Background

We previously reported the associations of human leukocyte antigen (HLA) (DRB1 and DQB1), INS, CTLA4, IL2RA, ERBB3 and CLEC16A with Japanese type 1 diabetes (T1D). In this study, we jointly analysed these loci in addition to IFIH1 and IL7R.

Methods

A maximum of 790 T1D patients and 953 control subjects were analysed. HLA was determined by sequencing‐based typing. Seven non‐HLA single nucleotide polymorphisms were genotyped using TaqMan assay.

Results

HLA DRB1*0405, DRB1*0901 and DRB1*0802‐DQB1*0302 haplotypes were positively associated with T1D, while the DRB1*15 haplotypes were negatively associated. Non‐HLA single nucleotide polymorphisms, INS, IL2RA, ERBB3, CLEC16A and IL7R were associated with T1D. By a prediction model using the HLA loci alone (HLA model) or the non‐HLA loci alone (non‐HLA model), it was revealed that the cumulative effect of the non‐HLA model was much weaker than that of the HLA model (average increase in odds ratio: 1.17 versus 3.14). Furthermore, the area under the receiver operating characteristic curve of the non‐HLA model was also much smaller than that of the HLA model (0.65 versus 0.81, p < 10−11). Finally, a patient‐only analysis revealed the susceptible HLA haplotypes and the risk allele of INS to be negatively associated with slower onset of the disease. In addition, the DRB1*0901 haplotype and the risk alleles of ERBB3, CLEC16A and CTLA4 were positively associated with the co‐occurrence of thyroid autoimmunity.

Conclusions

Although several non‐HLA susceptibility genes in Japanese were confirmed trans‐racially and appear to contribute to the heterogeneity of the clinical phenotypes, the cumulative effect on the ability to predict the development of T1D was weak. Copyright © 2011 John Wiley & Sons, Ltd.
Delta‐cell‐specific expression of hedgehog pathway Ptch1 receptor in murine and human endocrine pancreas
Authors: Grieco F. A. , Moretti M. , Sebastiani G. , Galleri L. , Spagnuolo I. , Scafetta G. , Gulino A. , De Smaele E. , Maroder M. , Dotta F.
Published: November 2011

Background

Hedgehog pathway plays an important role during pancreas development, when its inactivation is crucial to assure expression of pancreatic marker genes involved in the organ formation and to assure an appropriate organogenesis. Patched1 (Ptch1) is a transmembrane receptor of hedgehog pathway which has a key role in this process. In fact, heterozygous Ptch1 mutant (ptc+/−) mice are affected by an impaired glucose tolerance accompanied by reduced islet function. In the light that the cell distribution of Ptch1 receptor within the endocrine pancreas has not yet been established, we aimed at identifying the pancreatic endocrine cell subset(s) expressing such molecule.

Methods

Double immunostaining for Ptch1 and pancreatic hormones insulin, glucagon and somatostatin on pancreatic paraffin sections of C57BL/6J mice and human non‐diabetic multiorgan donors was performed and analysed using confocal microscopy. In addition, diabetes was experimentally induced in mice by intraperitoneal injection of streptozotocin. Quantitative real‐time polymerase chain reaction after laser‐capture microdissection of different islets from frozen pancreatic murine tissue sections was also performed.

Results

Ptch1 receptor was detected only in somatostatin‐positive delta cells both in mice and in human pancreas; in mice its expression was not affected by streptozotocin treatment. A significant increase of Ptch1 mRNA expression levels in the islet periphery versus the islet core was observed by quantitative real‐time polymerase chain reaction, in accord with immunohistochemical observations.

Conclusion

Our data show a delta‐cell‐specific expression of Ptch1 receptor in murine and human pancreas. Copyright © 2011 John Wiley & Sons, Ltd.
Intracellular pathways of pancreatic β‐cell apoptosis in type 1 diabetes
Authors: Thomas Helen E. , Kay Thomas W.
Published: November 2011

Background

Apoptosis of β cells is a feature of type 1 diabetes. It is also increasingly recognized in type 2 diabetes and islet graft rejection.

Methods

We have studied the intracellular pathways that regulate β‐cell apoptosis in type 1 and 2 diabetes. We have examined the role of Bid, a pro‐apoptotic member of the Bcl‐2 family, using islets from mice deficient in Bid. We also studied the Bcl‐2 family molecules involved in killing by using high concentrations of reducing sugars such as glucose or ribose.

Results

We found that Bid‐deficient islets are protected from recombinant human perforin and granzyme B, as well as from Fas‐mediated killing. This makes Bid a target for protection of β cells from multiple insults relevant to type 1 diabetes. In contrast to granzyme B and death receptor signalling, we found that islets lacking Bim or Puma were protected from glucose toxicity.

Conclusions

Our data indicate that different stimuli activate different initiator molecules in the Bcl‐2‐regulated pathway in β cells. Copyright © 2011 John Wiley & Sons, Ltd.
Enteroviruses and type 1 diabetes
Authors: Tracy Steven , Drescher Kristen M. , Chapman Nora M.
Published: November 2011

Background

Human enteroviruses, which are transmitted via a faecal‐oral route, have long been associated with type 1 diabetes onset. Increased hygiene in the 20th century may now be responsible for a decreased chance of enterovirus exposure from an early age onward. Infections with enteroviruses may also be more likely to occur at a later age; the recurrent poliomyelitis epidemics in the 20th century were linked to increased hygiene, consistent with this hypothesis. The association of fewer enterovirus exposures and increased diabetes rates may seem at first non‐intuitive but may be explained using a combination of human observations and data from experimental coxsackie B virus infections in nonobese diabetic mice.

Methods

Network for Pancreatic Organ Donors with Diabetes samples were examined for the presence of detectable enteroviral RNA by RT‐PCR.

Results

Viral RNA was not detected.

Conclusions

A role for enteroviruses in the aetiology of human type 1 diabetes is hard to refute but in order to definitively link enteroviruses in general, and specific viruses in particular, with the disease, pancreas biopsy tissue must become available at the time of disease diagnosis. Copyright © 2011 John Wiley & Sons, Ltd.
Self‐reported lower respiratory tract infections and development of islet autoimmunity in children with the type 1 diabetes high‐risk HLA genotype: the MIDIA study
Authors: Rasmussen Trond , Witsø Elisabet , Tapia German , Stene Lars C. , Rønningen Kjersti S.
Published: November 2011

Aim

To test whether self‐reported lower respiratory tract infections in early infancy predicted risk for islet autoimmunity in genetically predisposed children.

Methods

The environmental triggers for type 1 diabetes (MIDIA) study recruited newborns in Norway to identify those with the human leukocyte antigen high‐risk genotype DR4‐DQ8/DR3‐DQ2. Of 46 939 newborns genotyped, 1003 (2.1%) carried the high‐risk genotype, of whom 885 children were followed longitudinally with questionnaires and blood samples for autoantibody testing at 3, 6, 9 and 12 months of age, and then annually until 4 years of age. The endpoint (autoimmunity) was defined as positivity for at least one of three autoantibodies (to insulin, glutamic acid decarboxylase (GAD) or protein tyrosine phosphatase‐like protein (IA2)) on at least two consecutive samples. The parents responded in the questionnaires, whether the child had had ‘pneumonia, bronchitis or respiratory syncytial virus’. Cox proportional hazards regression models with time‐dependent covariates were used to estimate hazard ratios for autoimmunity using STATA 10.

Results

Forty‐two children developed autoimmunity, of whom 15 later developed type 1 diabetes. For 17 of the 42 cases (40%) ‘pneumonia, bronchitis or respiratory syncytial virus’ was reported (0.5‐4 years of age) before or at the onset of autoimmunity. For 187 of the 843 non‐cases (22%) ‘pneumonia, bronchitis or respiratory syncytial virus’ was reported in the same age group. The hazard ratio was 3.4 (p = 0.001, 95% confidence interval: 1.6‐7.1) for developing autoimmunity. The estimated hazard ratio was only marginally influenced by adjustment for potential confounding factors. No association was found for other infectious self‐reported symptoms.

Conclusion

Self‐reported lower respiratory tract infections were associated with increased risk of islet autoimmunity in early infancy. Copyright © 2011 John Wiley & Sons, Ltd.
Mapping of conformational autoantibody epitopes in ZNT8
Authors: Wenzlau Janet M. , Frisch Lisa M. , Hutton John C. , Davidson Howard W.
Published: November 2011

Background

Identification of the major humoral epitopes in zinc transporter 8 (ZnT8) will expand the range of biomarkers for human type 1 diabetes and may provide clues to the mechanisms governing disease progression. Our initial studies suggested that most ZnT8‐reactive sera recognize conformational epitopes in the final 100aa region of the molecule. Subsequently we identified residue 325 as a major determinant in two epitopes linked to a genetic polymorphism with high minor allele frequency (rs13266634). The goal of the current study was to extend this analysis to identify non‐polymorphic epitopes in ZnT8.

Methods

Although the carboxy‐terminal domains of human and mouse ZnT8 are ∼80% identical, the mouse probe is not precipitated by the majority of human type 1 diabetes sera. Thus to identify key residues we systematically ‘humanized’ the mouse probe at each position that differs and evaluated the probes in radio‐immunoassays.

Results

As previously reported, only the alteration of Q > R325 by itself showed any restoration of binding to human sera. However, when clusters of structurally adjacent variant residues were also changed an additional region of antigenicity was revealed that depended on residues R332, E333, K336, and K340. Using a panel of 112 sera from recent onset subjects tested with the hC325Q and m‐R325R332E333K336K340 probes, 39.3% of the subjects were ZnT8(Q)A+, of which 38.6% (17/44) also recognized the mouse probe.

Conclusions

We conclude that the mR‐REKK probe identifies a third major epitope in ZnT8 that may add to the diagnostic utility of measuring autoantibodies to this molecule. Copyright © 2011 John Wiley & Sons, Ltd.
Development of a novel autoantibody assay for autoimmune gastritis in type 1 diabetic individuals
Authors: Wenzlau J. M. , Gardner T. J. , Frisch L. M. , Davidson H. W. , Hutton J. C.
Published: November 2011

Background

Autoimmune atrophic body gastritis (ABG) and pernicious anaemia are prototypical, organ‐specific autoimmune diseases whose prevalence in the general population is 2.0 vs 2 and 0.15–1%, respectively. The incidence of disease increases with age and is frequently associated with other autoimmune disorders such as type 1 diabetes mellitus (T1DM). Early diagnosis of ABG/pernicious anaemia is essential for the prevention and/or treatment before manifestations of chronic disease become irreversible. Parietal cell autoantibody detection via enzyme‐linked immunosorbent assay is currently the most widely used biomarker of disease with diagnosis confirmed by subsequent immunohistochemistry via biopsy.

Methods

To improve the assay we designed a specific, molecularly defined radioimmunoprecipitation assay for early detection of ABG, targeting its major antigen, the gastric H+/K+ ATPase 4A subunit ATP4A.

Results

The major antigenic domain in ATP4A was tested against a panel of sera from new onset patients with T1DM which tested positive for the gold standard T1DM autoantibodies (IAA, IA2A, GAD65A, and ZnT8A). Significant immunoreactivity to ATP4A was measured (25%) while 6% of first‐degree relatives of subjects with T1DM who were sero‐negative for T1DM autoantigens were positive for ATP4A autoantibodies. ATP4A antibody prevalence increased with age of onset of T1DM, which is atypical of other T1DM autoantibodies. Immunoreactivity to ATP4A, unlike that of T1DM antigens, demonstrates a significant gender bias in newly diagnosed individuals with T1DM.

Conclusion

Although the utility of the assay as a biomarker for T1DM is likely limited, it may serve as an improved indicator of ABG. Copyright © 2011 John Wiley & Sons, Ltd.
LIPS islet autoantibody assays in high‐throughput format for DASP 2010
Authors: Marcus Patrick , Yan Xiang , Bartley Bryan , Hagopian William
Published: November 2011

Background

For cost‐effective population‐based diabetes prediction and confirmation, islet autoantibody assays must be made more economical.

Methods

We evaluated glutamic acid decarboxylase (GAD)‐Ruc (renilla luciferase) and IA2ic (also known as ICA512ic)‐Ruc (renilla luciferase) fusion protein constructs in high‐throughput islet antibody assay formats.

Results

Antigen production via transfection onto COS cells in 100 mm culture dishes yielded sufficient antigen to assay 375 and 535 serum samples for GAD and IA2ic per dish, respectively. Antigen was usably stable after − 80 °C storage for 40–80 days after which luciferase activity decreased. The mean signal‐to‐noise ratios for luciferase‐based immunoprecitation system (LIPS) GAD and LIPS IA2ic were 88 ± 24 and 219 ± 89, respectively, comparing favourably to radio‐binding assays (RBA) in the same format. However, the coefficient of variation among triplicate wells was higher for IA2ic than for GAD in LIPS, similar to findings in RBA format. Correlation coefficients between autoantibody indices determined from the RBA and LIPS methods were only R2 = 0.79 and R2 = 0.75 for GAD and IA2ic, respectively, raising the possibility that different epitopes were favoured in the two different assay formats. Nevertheless, overall concordance for the two assay types was high, at 228/240 = 95.0% for GAD and 494/521 = 94.8% for IA2ic. Using optimal cutoffs, Diabetes Autoantibody Standardization Program (DASP) 2010 sensitivity/specificity was 80/99% for GAD RBA, 80/99% for GAD LIPS, 70/98% for IA2 RBA, and 72/99% for IA2 LIPS.

Conclusion

The LIPS assays for islet autoantibodies to GAD and IA2ic performed as well as RBA in DASP 2010. With further refinements in expression and storage, these assays may be more economical than current methods to measure islet autoantibodies in type 1 diabetes. Copyright © 2011 John Wiley & Sons, Ltd.
Zinc transporter 8 autoantibodies in fulminant, acute‐onset, and slow‐onset patients with type 1 diabetes
Authors: Kawasaki Eiji , Nakamura Kan , Kuriya Genpei , Satoh Tsuyoshi , Kobayashi Masakazu , Kuwahara Hironaga , Abiru Norio , Yamasaki Hironori , Matsuura Nobuo , Miura Junnosuke , Uchigata Yasuko , Eguchi Katsumi
Published: November 2011

Background

The aim of this study was to determine the prevalence and role of autoantibodies to zinc transporter 8 (ZnT8A) in three forms (fulminant, acute‐onset, and slow‐onset) of Japanese patients with type 1 diabetes.

Methods

One‐hundred and ninety‐six new‐onset patients with type 1 diabetes were studied: 85 were fulminant, 81 acute‐onset, and 30 slow‐onset type 1 diabetes. ZnT8A were determined by radioimmunoassay using a hybrid ZnT8 carboxy‐terminal construct (aa268‐369) carrying 325Trp and 325Arg. Furthermore, ZnT8A epitopes were analysed using ZnT8 constructs incorporating the known aa325 variants (Trp, Arg, and Gln).

Results

ZnT8A were detected in 58% patients with acute‐onset and 20% with slow‐onset type 1 diabetes (p < 0.0005). In contrast, none of sera from fulminant type 1 diabetes were reactive to ZnT8 construct. Conversion of Arg or Trp to Gln at aa325 abolished reactivity in 59% of patients with an age of onset > 10 years, which was significantly higher than that in patients ⩽10 years of age (33%, p < 0.05).

Conclusions

These results suggest that ZnT8A are an additional useful marker for acute‐onset type 1 diabetes, but not a diagnostic marker for fulminant type 1 diabetes, and ZnT8A epitope recognition is different according to the onset age. Copyright © 2011 John Wiley & Sons, Ltd.