bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Predictive Value of Interleukin-6
+
Interleukin-10
+
and Interleukin-6
−
Interleukin-10
+
Cytokine Patterns in ST-Elevation Acute Myocardial Infarction
Authors: Ammirati Enrico , Cannistraci Carlo V. , Cristell Nicole A. , Vecchio Viviana , Palini Alessio G. , Tornvall Per , Paganoni Anna M. , Miendlarzewska Ewa A. , Sangalli Laura M. , Monello Alberto , Pernow John , Björnstedt Bennermo Marie , Marenzi Giancarlo , Hu Dayi , Uren Neal G. , Cianflone Domenico , Ravasi Timothy , Manfredi Angelo A. , Maseri Attilio
Published: August 2012

Rationale:

At the onset of ST-elevation acute myocardial infarction (STEMI), patients can present with very high circulating interleukin-6 (IL-6
+
) levels or very low-IL-6
–
levels.

Objective:

We compared these 2 groups of patients to understand whether it is possible to define specific STEMI phenotypes associated with outcome based on the cytokine response.

Methods and Results:

We compared 109 patients with STEMI in the top IL-6 level (median, 15.6 pg/mL; IL-6
+
STEMI) with 96 in the bottom IL-6 level (median, 1.7 pg/mL; IL-6
−
STEMI) and 103 matched controls extracted from the multiethnic First Acute Myocardial Infarction study. We found minimal clinical differences between IL-6
+
STEMI and IL-6
−
STEMI. We assessed the inflammatory profiles of the 2 STEMI groups and the controls by measuring 18 cytokines in blood samples. We exploited clustering analysis algorithms to infer the functional modules of interacting cytokines. IL-6
+
STEMI patients were characterized by the activation of 2 modules of interacting signals comprising IL-10, IL-8, macrophage inflammatory protein-1α, and C-reactive protein, and monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, and monokine induced by interferon-γ. IL-10 was increased both in IL-6
+
STEMI and IL-6
−
STEMI patients compared with controls. IL-6
+
IL-10
+
STEMI patients had an increased risk of systolic dysfunction at discharge and an increased risk of death at 6 months in comparison with IL-6
−
IL-10
+
STEMI patients. We combined IL-10 and monokine induced by interferon-γ (derived from the 2 identified cytokine modules) with IL-6 in a formula yielding a risk index that outperformed any single cytokine in the prediction of systolic dysfunction and death.

Conclusions:

We have identified a characteristic circulating inflammatory cytokine pattern in STEMI patients, which is not related to the extent of myocardial damage. The simultaneous elevation of IL-6 and IL-10 levels distinguishes STEMI patients with worse clinical outcomes from other STEMI patients. These observations could have potential implications for risk-oriented patient stratification and immune-modulating therapies.
Carnitine Palmitoyltransferase-1b Deficiency Aggravates Pressure Overload–Induced Cardiac Hypertrophy Caused by Lipotoxicity
Authors: He Lan , Kim Teayoun , Long Qinqiang , Liu Jian , Wang Peiyong , Zhou Yiqun , Ding Yishu , Prasain Jeevan , Wood Philip A. , Yang Qinglin
Published: August 2012

Background—

Carnitine palmitoyltransferase-1 (CPT1) is a rate-limiting step of mitochondrial β-oxidation by controlling the mitochondrial uptake of long-chain acyl-CoAs. The muscle isoform, CPT1b, is the predominant isoform expressed in the heart. It has been suggested that inhibiting CPT1 activity by specific CPT1 inhibitors exerts protective effects against cardiac hypertrophy and heart failure. However, clinical and animal studies have shown mixed results, thereby creating concerns about the safety of this class of drugs. Preclinical studies using genetically modified animal models should provide a better understanding of targeting CPT1 to evaluate it as a safe and effective therapeutic approach.

Methods and Results—

Heterozygous CPT1b knockout (CPT1b
+/−
) mice were subjected to transverse aorta constriction–induced pressure overload. These mice showed overtly normal cardiac structure/function under the basal condition. Under a severe pressure-overload condition induced by 2 weeks of transverse aorta constriction, CPT1b
+/−
mice were susceptible to premature death with congestive heart failure. Under a milder pressure-overload condition, CPT1b
+/−
mice exhibited exacerbated cardiac hypertrophy and remodeling compared with wild-type littermates. There were more pronounced impairments of cardiac contraction with greater eccentric cardiac hypertrophy in CPT1b
+/−
mice than in control mice. Moreover, the CPT1b
+/−
heart exhibited exacerbated mitochondrial abnormalities and myocardial lipid accumulation with elevated triglycerides and ceramide content, leading to greater cardiomyocyte apoptosis.

Conclusions—

CPT1b deficiency can cause lipotoxicity in the heart under pathological stress, leading to exacerbation of cardiac pathology. Therefore, caution should be exercised in the clinical use of CPT1 inhibitors.
Right Ventricular Structure Is Associated With the Risk of Heart Failure and Cardiovascular Death
Authors: Kawut Steven M. , Barr R. Graham , Lima João A.C. , Praestgaard Amy , Johnson W. Craig , Chahal Harjit , Ogunyankin Kofo O. , Bristow Michael R. , Kizer Jorge R. , Tandri Harikrishna , Bluemke David A.
Published: August 2012

Background—

Changes in right ventricular (RV) morphology are associated with morbidity and mortality in heart and lung disease. We examined the association of abnormal RV structure and function with the risk of heart failure or cardiovascular death in a population-based multiethnic sample free of clinical cardiovascular disease at baseline.

Methods and Results—

The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on 5098 participants between 2000 and 2002 with follow-up for incident heart failure and cardiovascular death (“death”) until January 2008. RV volumes and mass were available for 4204 participants. The study sample (n=4144) was 61.4±10.1 years old and 47.6% male. The presence of RV hypertrophy (increased RV mass) was associated with more than twice the risk of heart failure or death after adjustment for demographics, body mass index, education, C-reactive protein level, hypertension, and smoking status (hazard ratio, 2.52; 95% confidence interval, 1.55–4.10;
P
<0.001) and a doubling (or more) of risk with left ventricular mass at the mean value or lower (
P
for interaction=0.05).

Conclusions—

RV hypertrophy was associated with the risk of heart failure or death in a multiethnic population free of clinical cardiovascular disease at baseline.
Exploring the Influence of Participation on Programme Satisfaction: Lessons from the Ahmedabad Slum Networking Project
Authors: Russ Laura W. , Takahashi Lois M.
Published: August 2012

Survey data collected from participants in the Ahmedabad Slum Networking Project (SNP) is analysed to examine the importance of community participation in explaining respondent complaints about the project overall and with the specific public services provided. Logistic regression results suggest that community involvement matters when asking about overall SNP satisfaction, but is less important in explaining negative comments concerning water, sewerage and street lighting. For these specific services, contact with NGOs and municipalities and community characteristics matter more. The paper identifies policy implications and suggests further research questions based on these findings.
Correlates of Obtaining Informed Consent to Data Linkage
Authors: Sala Emanuela , Burton Jonathan , Knies Gundi
Published: August 2012

In the United Kingdom, in order to link individual-level administrative records to survey responses, respondents need to give their consent. Using an unprecedented set of respondent, interview, and interviewer characteristics derived from the British Household Panel Survey (BHPS) matched with an interviewer survey, this research investigates which characteristics influence consent to adding health and social security records to the survey responses. We find that consent is related to respondents’ attitudes to privacy, community mindedness and data linkage salience as well as to some interview features such as the “household contagion effect” and the survey “fidelity.” Interviewer characteristics, including their personality, attitudes to persuading respondents, and job experience, are not associated with consent. Interviewers’ survey experience in the current wave and their task-specific experience, however, do influence consent. Implications of the findings are discussed and areas for future research are identified.
Maybe It’s Both of Us
Authors: Van Auken Paul
Published: August 2012

This teaching note describes my multiyear experience with interventions designed to enhance student engagement and learning through various teaching techniques, most notably active and collaborative learning through local case studies. While other aspects of this course had been successful, I was disappointed in the level of engagement—the apparent level of study and practice and the excitement and interest in the project demonstrated during class meetings and through assignments—of previous students with the semester-long research project. Intervention yielded a clear increase in student engagement but did not seem to yield increased understanding, leading to a new set of questions and additional intervention. The note provides details about the specific teaching techniques centered on active and collaborative learning in local case studies and concludes with three recommendations for instructors pursuing excellence in teaching and learning.
Bullying in the Indian workplace: A study of the ITES-BPO sector
Authors: D’Cruz Premilla , Rayner Charlotte
Published: August 2012

This article reports on an empirical enquiry undertaken in India’s ITES-BPO (offshoring-outsourcing) sector to ascertain the presence of workplace bullying, the influence of sociocultural factors, the nature of bullying categories and the availability and use of extra-organizational redressal options. Survey data, gathered through structured interviews incorporating the Work Harassment Scale, conducted with 1036 respondents located in six cities, showed that 44.3% of the sample experienced bullying, with 19.7% reporting moderate and severe levels. In keeping with India’s hierarchical society, superiors emerged as the predominant source of bullying, displaying task-focused behaviours. Yet, the presence of ‘cross-level co-bullying’ where a personal focus was emphasized points to the role of identity-based affiliations intrinsic to India’s ethos. Key informant data, gathered through unstructured interviews with lawyers/legal activists, labour commissioners and trade unionists/labour activists and thematically analysed, underscored the influence of professional self-identity, career interests and a dysfunctional judicial system in targets’ choice of extra-organizational options.
Do You Want to Convince Me or to Be Understood?
Authors: Faulmüller Nadira , Mojzisch Andreas , Kerschreiter Rudolf , Schulz-Hardt Stefan
Published: August 2012

In two experiments, we provide evidence for a fundamental discussion asymmetry, namely, preference-consistent information sharing. Despite being in a dyadic situation requiring open information exchange and being given no incentive to do so, participants communicated more information that supported their individually preferred decision alternative than information that contradicted it. Preference-consistent information sharing was not caused by biased recall and occurred in written as well as in face-to-face communication. Moreover, we tested whether preference-consistent information sharing was influenced by statements by bogus discussion partners indicating that they held a congruent versus incongruent preference to the participants’ preference and that they understood versus did not understand the participants’ preference. We found that when partners stated that they understood the participants’ preference, subsequent preference-consistent information sharing was considerably reduced. This indicates that a motivation to be understood by others might be an important driving force underlying preference-consistent information sharing.
Democratizing production through open source knowledge: from open software to open hardware
Authors: Powell Alison
Published: August 2012

The commercial success of open source software, along with a broader socio-cultural shift towards participation in media and cultural production, have inspired attempts to extend and expand open source practices. These include expansions from software into general culture through ‘Free Culture’ movements and, more recently, expansions from software into hardware and design. This article provides a critical perspective on the democratic potential of these broader ‘open’ contribution structures by examining how open source contributions to both software and hardware increase the opportunities for democratic participation in production, governance and knowledge exchange. By analysing attempts to ‘open source’ the sharing of hardware designs, it also notes the limitations of this democratization. The insights developed in the article nuance the relationship between open source cultures and commercial and market structures, identifying how the generative opportunities created by certain aspects of open source contribution structures increase the potential for democratizing production of communication tools, but also how incongruities across different open-source cultures and communities of practice limit the democratic potential of these processes.
Crowdsourcing and outsourcing: the impact of online funding and distribution on the documentary film industry in the UK
Authors: Sørensen Inge Ejbye
Published: August 2012

This article compares traditional and new ways of funding documentary film in the UK and asks what crowd financing, pay-if-you-want schemes and online distribution sites mean for documentary films and its industry today. How do online financing models impact on producers, traditional funding models and funders? And following the money, who really benefits? The first section of this article charts trends in British documentary budgets in the last decade and explores how changes in financing impact on the production of documentary films. The second focuses on new ways of funding and distributing documentary films online. Drawing on case studies of crowd investment schemes, crowdfunding and P2P distribution; interviews with documentary and multiplatform producers and commissioners, as well as on statistics and annual reports from broadcasters, lobbyists and regulators, I will argue that in real terms there has been a decline in and a polarization of documentary budgets in the UK. As a result, producers are increasingly looking to the internet to fund their documentaries. However, an online financing market suspended between ad hoc funding and long-term recuperation has consequences for the documentary industry, the kinds of documentaries made, the topics they explore and the ways in which they are produced.
A New Standardized Format for Reporting Hearing Outcome in Clinical Trials
Authors: Gurgel Richard K. , Jackler Robert K. , Dobie Robert A. , Popelka Gerald R.
Published: August 2012

The lack of an adequate standardized method for reporting level of hearing function in clinical trials has hampered the ability of investigators to draw comparisons across studies. Variability in data reported and presentation format inhibits meta‐analysis and makes it impossible to accumulate the large patient cohorts needed for statistically significant inference. Recognizing its importance to the field and after a widely inclusive discussion, the Hearing Committee of the American Academy of Otolaryngology–Head and Neck Surgery endorsed a new minimal standard for reporting hearing results in clinical trials, consisting of a scattergram relating average pure‐tone threshold to word recognition score. Investigators remain free to publish their hearing data in any format they believe is interesting and informative, as long as they include the minimal data set to facilitate interstudy comparability.
Low carbon mobility versus private car ownership: Towards a new business vision for the automotive world?
Authors: Coffey Dan , Thornley Carole
Published: August 2012

This article considers a generalized leasing model for car use as a means of better reconciling profit seeking by car makers with environmental improvements, while supporting income generation and employment in the car business sector. It locates its contribution against the ‘extended producer responsibility’ framework, proposed by some as a basis for a corporate response to environmental and resource concerns. We show that within limits a reorganization of the business model informing the volume car market offers one part of a solution to problems of economic growth and climate change. The article progresses to consider obstacles to change and options for government policy.
What price localism? The case for government investment in specialist, community-based services by and for women
Authors: Hayden Carol
Published: August 2012

This article highlights the risks for women of the Government relying on service provision through the third sector and localism, in the absence of a national strategy and infrastructure funding, using the case study of a recent evaluation of the special funds for the sexual violence third sector for the Government Equalities Office.
Physiological-based pharmacokinetic modeling of endotoxin in the rat
Authors: Hutter Joseph C , Kim Chung S
Published: August 2012

We have previously measured the distribution and pharmacokinetics of biosynthetically radiolabeled endotoxin of Salmonella typhimurium following intraperitoneal (IP) dosing (200 μg/kg) in Sprague-Dawley rats. In our experiments, the fatty acid residues were labeled with 3H and the glucosamine residues were labeled with 14C. To predict the dynamics of endotoxin exposure, we developed a physiological-based pharmacokinetic model using our measured distribution results. The model was validated with published low-dose (30 μg/kg) IP exposure results in rats. Endotoxin pharmacokinetics depended on dose and route. At high IP doses, absorption was followed by biphasic decay over 48 h in plasma. There were tissue accumulations of the fatty acid and glucosamine residues in various target organs, including the brain. We also found that the glucosamine and fatty acid components separated in vivo about 3 h after IP injection. At the lower IP dose, a smaller fraction of the dose was distributed to the tissues, with most of the dose remaining in the blood. Each component had its own dynamic behavior and target tissue distribution in the rat. The fatty acid components tended to remain in the brain stem, caudate nucleus, cerebellum, frontal cortex, hippocampus, and hypothalamus. Other organs (spleen, kidney, meninges, and choroid plexus) had similar biphasic distribution. The liver had the unique accumulation of both glucosamine and fatty acid residues.
The Role of Officer Attributes, Job Characteristics, and Arrest Activity in Explaining Police Use of Force
Authors: Brandl Steven G. , Stroshine Meghan S.
Published: August 2012

While numerous studies have examined the causes, correlates, and control of police use of force, many questions remain. This study contributes to the literature on police use of force by examining the role of officers’ background characteristics, job characteristics (patrol area and shift assignment), and arrest activity in explaining variation in the frequency with which officers use force. Analyses were conducted on 1,084 police officers employed in a large municipal police department. Use of force data were obtained from 477 official departmental reports from 2010. Results suggest that a small proportion of officers are responsible for a large proportion of force incidents, and that officers who frequently use force differ in important and significant ways from officers who use force less often (or not at all). Policy implications and directions for future research are discussed.
Homeland Security and Public Health: A Critical Integration
Authors: Carter Jeremy G. , Rip Michael
Published: August 2012

In the wake of a series of tragic events impacting public health in the United States, the Department of Health and Human Services Centers for Disease Control and Prevention and the Department of Homeland Security have attempted to facilitate information sharing across public health and homeland security organizations. Data collected as part of a national assessment of law enforcement and homeland security information sharing, funded by the National Institute of Justice, indicate such efforts to date have been helpful in establishing a foundation for information sharing, yet fall short of creating mechanisms by which tangible information sharing can occur. Recent initiatives to remedy this shortcoming are presented and recommendations for further success are discussed.
Denver’s Citizen/Police Complaint Mediation Program
Authors: Schaible Lonnie M. , Angelis Joseph De , Wolf Brian , Rosenthal Richard
Published: August 2012

Ensuring police use their authority justly is a persistent concern. Yet, there is little agreement on the most effective mechanisms for promoting accountability. The present study seeks to contribute to a growing body of research on mediation of police disputes by assessing variation in levels of satisfaction among officers and citizens. Using data collected by the Denver Office of the Independent Monitor, the study assesses the degree to which mediation produced differential levels of satisfaction. The study finds that both police and civilian participants in the mediation program were significantly more satisfied than individuals who participated in traditional complaint processing. In addition, the study finds that mediation is likely to have even stronger effects on satisfaction for Latino complainants, and female police officers. Implications and suggestions for future research are discussed.
Numerical analysis of aerodynamic characteristics for the design of a small ducted fan aircraft
Authors: Wang Zhengjie , Chen Li , Guo Shijun
Published: August 2012

This article presents a study on the flow field and aerodynamic characteristics of the propellers and rudders for the design of a small ducted fan aircraft. In the analysis, an equivalent actuation disk was created as a simplified model of the propellers. A momentum source is determined by equivalent actuation disk numerical simulation using ANSYS CFX software based on vortex theory. In addition, the momentum source distribution function for the equivalent actuation disk model is improved by using experimental data. The computational fluid dynamics method in the ANSYS CFX software is then used to simulate the flow field of the propellers slipstream and determine the key aerodynamic and design parameters for the built-up rudders of the aircraft. The improved equivalent actuation disk method is validated by using the mixing plane method and their results show a good comparison. The simulation and analysis results provide the basis for optimal design of the built-up rudder arrangement and layout for a small ducted fan aircraft.
Stepping Out of the Caveman’s Shadow
Authors: Zentner Marcel , Mitura Klaudia
Published: August 2012

An influential explanation for gender differences in mating strategies is that the sex-specific reproductive constraints faced by human ancestors shaped these differences. Other theorists have emphasized the role of societal factors, hypothesizing, for example, that gender differences in mate preferences should wane in gender-equal societies. However, findings have been ambiguous. Using recent data and a novel measure of gender equality, we revisited the role of gender parity in gender differentiation for mate preferences. In the first study, 3,177 participants from 10 nations with a gradually decreasing Global Gender Gap Index (GGI) provided online ratings of the desirability of mate attributes with reportedly evolutionary origins. In the second study, GGI scores were related to gender differences in mate preferences previously reported for 8,953 participants from 31 nations (Buss, 1989). Both studies show that gender differences in mate preferences with presumed evolutionary roots decline proportionally to increases in nations’ gender parity.
Climate, vegetation and land use as drivers of Holocene sedimentation: A case study from Lake Saint-Point (Jura Mountains, eastern France)
Authors: Magny Michel , Leroux Aurélie , Bichet Vincent , Gauthier Emilie , Richard Hervé , Walter-Simonnet Anne-Véronique
Published: August 2012

A multiproxy approach to a sediment sequence at Lake Saint-Point in the French Jura Mountains gives evidence of a strong coupling between changes in terrestrial and lacustrine ecosystems throughout the Holocene. The early Holocene (11,700–10,200 cal. BP) is characterised by the recovery of terrestrial and lake ecosystems favoured by climatic warming. During the middle Holocene (10,600–6200 cal. BP), the climatic optimum coincided with an extension of deciduous forests into the catchment area, while lake sedimentation is dominated by authigenic carbonates and low detrital inputs. After 6200 cal. BP, the Neoglacial favoured expansion of Abies-Fagus forests and increasing detrital inputs to the lake where ostracod fauna declined and changed in composition. After 1200 cal. BP, human impact was responsible for extensive forest clearings in the catchment area, while the lake basin shows contrasting pictures with increasing detrital input, resuming sedimentation of authigenic carbonates and changes in dominant ostracod species. Orbitally driven climatic variations were the dominant factor of environmental changes until c. 1200 cal. BP. Around 2600 cal. BP, human impact increased and became the major factor in the catchment area and the lake basin from 1200 cal. BP onwards. Finally, the Saint-Point record offers a clear illustration of how gradual changes in insolation or increasing human impact may provoke, even under temperate climatic conditions, abrupt responses in mid-European terrestrial and lake ecosystems, and how differences in the dates of tipping points revealed by proxies suggest specific threshold values depending on the sensitivity of indicators used and on their role in the different compartments of these ecosystems.
C6 knock-out mice are protected from thrombophilia mediated by antiphospholipid antibodies
Authors: Carrera-Marín AL , Romay-Penabad Z , Papalardo E , Reyes-Maldonado E , García-Latorre E , Vargas G , Shilagard T , Pierangeli S
Published: August 2012

Background: Complement activation plays a role in pathogenesis of the antiphospholipid syndrome (APS), but the involvement of the C5b-9 membrane attack complex (MAC) is unknown. Here we studied the effects of human polyclonal antiphospholipid (aPL) antibodies on thrombosis and tissue factor (TF) up-regulation in C6 deficient (C6−/−) mice. Methods: C6−/− mice or the wild-type C3H/HeJ (C6+/+) mice were injected twice with IgG-APS ( n = 2) or IgM-APS ( n = 1) isolated from APS patients or with the corresponding control immunoglobulins (Igs) of normal human serum, (NHS) (IgG-NHS or IgM-NHS). Then, the sizes of induced thrombi in the femoral vein were determined 72 hours after the first injection. Tissue factor was determined in homogenates of carotid arteries and in peritoneal macrophages. Results: Thrombus sizes were significantly larger in C6+/+ treated with IgG-APS1 or with IgG-APS2 or with IgM-APS when compared with C6+/+ mice treated with IgG-NHS or with IgM-NHS, respectively. The sizes of thrombi were significantly smaller in the C6−/− mice injected with IgG-APS1, IgG-APS2 or IgM-APS ( p < 0.001), compared to their C6+/+ counterparts showing an important abrogation of thrombus formation in mice lacking C6. The TF expression and activity in the C6−/− mice treated with IgG-APS or IgM-APS were diminished when compared to C3H/HeJ (C6+/+) mice treated with the same Igs. All mice injected with IgG-APS and IgM-APS had medium-high titers of anticardiolipin (aCL) and anti-β2glycoprotein I (aβ2GPI) antibodies. Conclusions: These data indicate that the C6 component of the complement system mediates aPL-thrombogenic effects, underscoring an important pathogenic mechanism and indicating the possibility of inhibiting complement to ameliorate APS-related manifestations.
Prolactin in multiple sclerosis
Authors: Zhornitsky Simon , Yong V Wee , Weiss Samuel , Metz Luanne M
Published: August 2012

Multiple sclerosis (MS) is more common among women than men. MS often goes into remission during pregnancy, when prolactin (PRL) levels are known to be high. In an animal model of demyelination, PRL promoted myelin repair, suggesting it has potential as a remyelinating therapy in MS. In this systematic review, we examined the known associations between PRL and MS, in order to elucidate its potential role in the pathophysiology and treatment of MS. A systematic search was performed in the electronic databases PubMed and EMBASE, using the keywords "prolactin" AND “multiple sclerosis.” The inclusion criteria were met by 23 studies. These studies suggested to us that elevated PRL may be more common in MS patients than in controls. Hyperprolactinemia may also be associated with clinical relapse in MS, especially among patients with hypothalamic lesions or optic neuritis; however, it is unknown if this is a cause or consequence of a relapse. Overall, most people with MS have normal PRL levels. The impact of PRL on MS outcomes remains unclear.
Ageing, Experience, Biopolitics: Life’s Unfolding
Authors: Neilson Brett
Published: August 2012

In the wake of Foucault, the debate on biopolitics has focused on the tensions of bíos and zoé, community and immunity, generation and thanatopolitics. What remains obscure in these accounts is the experiential aspect of life – its unfolding and entanglement with the ageing process. This is true both of approaches that emphasize the ethical implications of the life sciences and those that explore the biopolitical workings of wider social processes. In the contemporary capitalist formation, life’s unfolding is caught up in global flows of information, finance and labour. The organization of the human faculties, the general preconditions for knowledge and communication, becomes central to value creation. And the human body, like fixed capital for Marx, becomes a cost to be amortized as quickly as possible. Investigating these processes with regard to transformations in practices of care provides a means for reassessing current debates regarding the ageing of people and populations.
What is a Humanized Mouse? Remaking the Species and Spaces of Translational Medicine
Authors: Davies Gail
Published: August 2012

This article explores the development of a novel biomedical research organism, and its potential to remake the species and spaces of translational medicine. The humanized mouse is a complex experimental object in which mice, rendered immunodeficient through genetic alteration, are engrafted with human stem cells in the hope of reconstituting a human immune system for biomedical research and drug testing. These chimeric organisms have yet to garner the same commentary from social scientists as other human–animal hybrid forms. Yet, they are rapidly being positioned as central to translational medicine in immunological research and pharmaceutical development. This article explores the complex relations between species and spaces they seek to enact. Humanizing mice simultaneously moves these animal forms towards the intimate geographies of corporeal equivalence with humans and the expansive geographies of translational research. These multiple trajectories are achieved by the way humanized mice function as both uncertain ‘epistemic things’ and as expansive ‘collaborative things’, articulating mouse genetics with other research, notably stem cell science. In the context of post-genomics, their indeterminacy is critical to their collaborative value; their expansive potential follows as much from their biological openness as from specific expectations. Yet, these new research organisms have both accumulative and disruptive capacities, for there are patterns of interference between these trajectories, remaking boundaries between experimental practices and clinical contexts.
Animal Bodies in the Production of Scientific Knowledge: Modelling Medicine
Authors: Birke Lynda
Published: August 2012

What role do nonhuman animals play in the construction of medical knowledge? Animal researchers typically claim that their use has been essential to progress – but just how have animals fitted into the development of biomedicine? In this article, I trace how nonhuman animals, and their body parts, have become incorporated into laboratory processes and places. They have long been designed to fit into scientific procedures – now increasingly so through genetic design. Animals and procedures are closely connected – animals in science are disassembled and reassembled in various ways. Indeed, biomedical knowledge can be said to rest on a large pile of animal bodies and body parts. The process of producing animal body parts to order has implications for how we conceptualize the body (human or nonhuman), which I discuss in the final section.
Medicine as a Tactic of War
Authors: Pfingst Annie , Rosengarten Marsha
Published: August 2012

This photo-essay highlights the ways in which medicine features in the Occupied Palestinian Territories (OPT) and uses it to reflect on the nature of ethical obligation set out by Judith Butler in her work on state-achieved precarity. Although medical infrastructure of even the most basic type is tragically lacking and in some areas shockingly absent in the OPT, it is the particular way in which medicine comes to be needed that we focus on. Leaving aside the rhetoric that has claimed authority over what can or cannot be said of the Occupation, we focus on its geo-technological arrangements. By placing photos and case studies of medical obstruction within an analysis of the Occupation, we forge an encounter between reader and the Occupation to raise questions about the use of medicine in this context and the manner in which conventional ethics can give legitimacy to this use. On the basis of what we show through visual and textual documentary material, we propose ethics be understood as inherent to the geo-technological arrangements that make life possible or, as in this case, undermine, obstruct or deliberately take life. Hence the ethical obligation that Butler calls upon is reiterated in ways that encompass the everyday features of occupation including those active in the emergence of medicine as a tactic of war.
Ain’t no mountain high enough? Setting high weight loss goals predict effort and short-term weight loss
Authors: De Vet Emely , Nelissen Rob MA , Zeelenberg Marcel , De Ridder Denise TD
Published: August 2012

Although psychological theories outline that it might be beneficial to set more challenging goals, people attempting to lose weight are generally recommended to set modest weight loss goals. The present study explores whether the amount of weight loss individuals strive for is associated with more positive psychological and behavioral outcomes. Hereto, 447 overweight and obese participants trying to lose weight completed two questionnaires with a 2-month interval. Many participants set goals that could be considered unrealistically high. However, higher weight loss goals did not predict dissatisfaction but predicted more effort in the weight loss attempt, as well as more self-reported short-term weight loss when baseline commitment and motivation were controlled for.
Popular journalism and cultural change: The discourse of globalization in world music reviews
Authors: Fürsich Elfriede , Avant-Mier Roberto
Published: August 2012

This study interrogates whether popular journalism – in this case music journalism – can contribute to a productive discourse on issues of public concern. We conducted a textual analysis of the discourse on cultural globalization in the coverage on world music in the US popular press over the last 30 years. We found that music journalists developed a new cultural sensibility in several distinctive phases. The first phase was marked by a firm West/non-West dichotomy and ‘othering.’ A brief second phase denoted the confusion of prior assumptions. The third phase indicated the dissolution of traditional dichotomies and the integration of dynamic and hybrid ideas of global cultural exchange. Along with significant modifications in journalistic style and a different representation of global others, the position of music reviewers as popular journalists eventually helped their acceptance of global cultural transformations. At their best, the reviews created relevant and productive texts on the cultural dimensions of globalization.
Methodological innovation and research ethics: forces in tension or forces in harmony?
Authors: Nind Melanie , Wiles Rose , Bengry-Howell Andrew , Crow Graham
Published: August 2012

This article is an exploration of the tensions inherent in the interaction between ethics and methodological innovation. The authors focus on three cases of innovation in qualitative research methods in the social sciences: netnography, child-led research and creative research methods. Using thematic analysis of data collected through semi-structured interviews with the innovators and commentators on the innovations, they discuss issues of ethical responsibility, democratisation of research, empowerment and the relationship between research and the academy. This article highlights the ways in which innovation is about reflexivity as well as new techniques. It shows how innovation may be about managing risk rather than taking risks: the innovators are cautious as much as creative, operating within a culture in which procedural ethical regulation acts to limit methodological development and in which they (and other users of their method/approach) communicate the safe qualities alongside the innovative qualities of their approach.
Prevalence of α1-antitrypsin deficiency alleles PI*S and PI*Z worldwide and effective screening for each of the five phenotypic classes PI*MS, PI*MZ, PI*SS, PI*SZ, and PI*ZZ: a comprehensive review
Authors: de Serres Frederick J. , Blanco Ignacio
Published: August 2012

Genetic epidemiological studies on the prevalence and numbers of individuals with α1-antitrypsin deficiency in each of 97 countries worldwide were used to estimate the numbers in each of the five following phenotypic classes: PI*MS, PI*MZ, PI*SS, PI*SZ, and PI*ZZ. These 97 countries were then grouped into 10 major geographic regions to make it possible to compare the numbers in each of these five phenotypic classes in immediately adjacent countries. Such groupings also make it possible to review the spread of the PI*S and PI*Z alleles from one major geographic grouping to another in the world as well as the spread of these two deficiency alleles within a major geographic region. The data in the 10 tables on the numbers in each of the five phenotypic classes in the countries in the same geographic region as well as the prevalence of the PI*S and PI*Z alleles in countries in the same geographic region provide a novel database for the identification of large numbers of individuals in a given phenotypic class. The database also provides useful information for the identification of countries with high numbers of PI*ZZ individuals for augmentation therapy within a given geographic region.
How Quick Decisions Illuminate Moral Character
Authors: Critcher Clayton R. , Inbar Yoel , Pizarro David A.
Published: August 2012

It has been suggested that people attend to others’ actions in the service of forming impressions of their underlying dispositions. If so, it follows that in considering others’ morally relevant actions, social perceivers should be responsive to accompanying cues that help illuminate actors’ underlying moral character. This article examines one relevant cue that can characterize any decision process: the speed with which the decision is made. Two experiments show that actors who make an immoral decision quickly (vs. slowly) are evaluated more negatively. In contrast, actors who arrive at a moral decision quickly (vs. slowly) receive particularly positive moral character evaluations. Quick decisions carry this signal value because they are assumed to reflect certainty in the decision (Experiments 1 and 2), which in turn signals that more unambiguous motives drove the behavior (Experiment 2), which in turn explains the more polarized moral character evaluations. Implications for moral psychology and the law are discussed.
Conditional TRF1 knockout in the hematopoietic compartment leads to bone marrow failure and recapitulates clinical features of dyskeratosis congenita
Authors: Beier Fabian , Foronda Miguel , Martinez Paula , Blasco Maria A.
Published: August 2012

TRF1 is part of the shelterin complex, which binds telomeres and it is essential for their protection. Ablation of TRF1 induces sister telomere fusions and aberrant numbers of telomeric signals associated with telomere fragility. Dyskeratosis congenita is characterized by a mucocutaneous triad, bone marrow failure (BMF), and presence of short telomeres because of mutations in telomerase. A subset of patients, however, show mutations in the shelterin component TIN2, a TRF1-interacting protein, presenting a more severe phenotype and presence of very short telomeres despite normal telomerase activity. Allelic variations in TRF1 have been found associated with BMF. To address a possible role for TRF1 dysfunction in BMF, here we generated a mouse model with conditional TRF1 deletion in the hematopoietic system. Chronic TRF1 deletion results in increased DNA damage and cellular senescence, but not increased apoptosis, in BM progenitor cells, leading to severe aplasia. Importantly, increased compensatory proliferation of BM stem cells is associated with rapid telomere shortening and further increase in senescent cells in vivo, providing a mechanism for the very short telomeres of human patients with mutations in the shelterin TIN2. Together, these results represent proof of principle that mutations in TRF1 lead to the main clinical features of BMF.
Interphase Chromosome Flow-FISH
Authors: Keyvanfar Keyvan , Weed Jason , Swamy Prashanth , Kajigaya Sachiko , Calado Rodrigo T. , Young Neal S.
Published: August 2012

A 2-day method using flow cytometry and FISH for interphase cells was developed to detect monosomy 7 cells in myelodysplastic syndrome patients. The method, Interphase Chromosome Flow-FISH (IC Flow-FISH), involves fixation of leukocytes from blood, membrane permeabilization, hybridization of cellular DNA with peptide nucleic acid probes with cells intact, and analysis by flow cytometry. Hundreds to thousands of monosomy 7 cells were consistently detected from 10-20 mL of blood in patients with monosomy 7. Proportions of monosomy 7 cells detected in IC Flow-FISH were compared with results from conventional cytogenetics; identification of monosomy 7 populations was verified with FACS; and patient and donor cells were mixed to test for sensitivity. IC Flow-FISH allows for detecting monosomy 7 without requiring bone marrow procurement or the necessity of metaphase spreads, and wider applications to other chromosomal abnormalities are in development.
Comment on ‘Approximate ∗-derivations and approximate quadratic ∗-derivations on "Equation missing" -algebras’ [Jang, Park, J. Inequal. Appl. 2011 (2011), Article ID 55]
Authors: Park Choonkil , Shin Dong Yun , Lee Jung Rye , Lee Sung Jin
Published: August 2012

In (J. Inequal. Appl. 2011:Article ID 55, Section 4, 2011), Jang and Park proved the Hyers-Ulam stability of quadratic ∗-derivations on Banach ∗-algebras. One can easily show that all the quadratic ∗-derivations δ in Section 4 must be trivial. So the results are trivial. In this paper, we correct the statements and prove the corrected results.

MSC:39B52, 47B47, 39B72.
Urinary N-acetyl-β-D glucosaminidase as a surrogate marker for renal function in autosomal dominant polycystic kidney disease: 1 year prospective cohort study
Authors: Park Hayne Cho , Hwang Jin Ho , Kang Ah-Young , Ro Han , Kim Myung-Gyu , An Jung Nam , In Park Ji , Kim Seung Hyup , Yang Jaeseok , Oh Yun Kyu , Oh Kook-Hwan , Noh Jung Woo , Cheong Hae Il , Hwang Young-Hwan , Ahn Curie
Published: August 2012

Background

Renal failure is one of the most serious complications associated with autosomal dominant polycystic kidney disease (ADPKD). To date, early markers have failed to predict renal function deterioration at the early stages. This 1-year prospective study evaluated N-acetyl-β-D-glucosaminidase (NAG) as a new surrogate marker for renal function in ADPKD.

Methods

A total of 270 patients were enrolled in the study, and we measured urinary NAG, β2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) prospectively for 1 year to compare their predictive values for renal function.

Results

Baseline urinary NAG/Cr was negatively correlated with estimated glomerular filtration rate (GFR) (r

2
 = 0.153, P < 0.001) and positively correlated with total kidney volume (TKV) (r

2
 = 0.113, P < 0.001). Among other biomarkers, urinary NAG/Cr better discriminated patients with decreased renal function from those with conserved renal function, showing the largest area under the curve (AUC 0.794). Immunohistochemical study revealed strong staining along the cyst-lining epithelial cells as well as the nearby compressed tubular epithelial cells. However, both single and repeated measurements of urinary NAG/Cr failed to predict renal function decline in 1 year.

Conclusions

Urinary NAG/Cr may be a useful surrogate marker for renal function in ADPKD patients.
Prevalence of KRAS, BRAF, and PIK3CA somatic mutations in patients with colorectal carcinoma may vary in the same population: clues from Sardinia
Authors: Palomba Grazia , Colombino Maria , Contu Antonio , Massidda Bruno , Baldino Giovanni , Pazzola Antonio , Ionta MariaTeresa , Capelli Francesca , Trova Vittorio , Sedda Tito , Sanna Giovanni , Tanda Francesco , Budroni Mario ,   Sardinian Translational Oncology Group (STOG), Palmieri Giuseppe , Cossu Antonio
Published: August 2012

Background

Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been recently investigated worldwide. In this population-based study, we evaluated the incidence rates and distribution of such somatic mutations in genetically isolated population from Sardinia.

Methods

From April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (N = 478) were prospectively collected from Sardinian CRC patients at clinics across the entire island. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing.

Results

Overall, KRAS tumour mutation rate was 30% (145/478 positive cases). Distribution of mutation carriers was surprisingly different within the island: 87/204 (43%) in North Sardinia vs. 58/274 (21%) in Middle-South Sardinia (p<0.001). Among 384 CRC cases whose DNA was available, only one (0.3%) patient carried a mutation in BRAF gene; PIK3CA was found mutated in 67 (17%) patients. A significant inverse distribution of PIK3CA mutation rates was observed within Sardinian population: 19/183 (10%) cases from northern vs. 48/201 (24%) cases from central-southern island (p<0.001). This heterogeneity in frequencies of KRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population. Preliminary clinical evaluation of 118 KRAS wild-type patients undergoing anti-EGFR-based treatment indicated lack of role for PIK3CA in predicting response to therapy.

Conclusions

Our findings support the hypothesis that differences in patients’ origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in candidate cancer genes.