bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of Replication of Seven Pancreatic Cancer Susceptibility Loci Identified in Two Asian Populations
Authors: Campa Daniele , Rizzato Cosmeri , Bauer Andrea S. , Werner Jens , Capurso Gabriele , Costello Eithne , Talar-Wojnarowska Renata , Jamroziak Krzysztof , Pezzilli Raffaele , Gazouli Maria , Khaw Kay-Tee , Key Timothy J. , Bambi Franco , Mohelnikova-Duchonova Beatrice , Heller Anette , Landi Stefano , Vodickova Ludmila , Theodoropoulos George , Bugert Peter , Vodicka Pavel , Hoheisel Jörg D. , Delle Fave Gianfranco , Neoptolemos John P. , Soucek Pavel , Büchler Markus W. , Giese Nathalia , Canzian Federico
Published: December 2012

Background: Two recent genome-wide association studies (GWAS) of pancreatic ductal adenocarcinoma (PDAC), conducted, respectively, in a Japanese and in a Chinese population, identified eight novel loci affecting PDAC risk.

Methods: We attempted to replicate the novel loci in a series of PDACs and healthy controls of European ancestry in the context of the newly formed PANcreatic Disease ReseArch (PANDoRA) consortium. We genotyped seven single-nucleotide polymorphisms (SNP): rs12413624, rs1547374, rs372883, rs5768709, rs6464375, rs708224, rs9502893 (one SNP identified in the Chinese GWAS is not polymorphic in Caucasians) in 1,299 PDAC cases and 2,884 controls. We also attempted stratified analysis considering the different stages of the disease and addressed the possible involvement of the selected SNPs on the survival of patients.

Results: None of the SNPs were significantly associated with PDAC risk if considering the overall population of the consortium. When stratifying for country of origin, we found that in the Polish subgroup, the G allele of rs372883 was statistically significantly associated with increased risk [OR, 6.40; 95% confidence interval (CI), 2.28–17.91]. However, the sample size of the subgroups was rather small; therefore, this result can be due to chance. None of the SNPs was associated with disease progression or survival.

Conclusions: None of the SNPs associated with PDAC risk in two Asian populations were convincingly associated with PDAC risk in individuals of European descent.

Impact: This study illustrates the importance of evaluation of PDAC risk markers across ethnic groups. Cancer Epidemiol Biomarkers Prev; 22(2); 320–3. ©2012 AACR.
Resistance to BRAF Inhibition in BRAF-Mutant Colon Cancer Can Be Overcome with PI3K Inhibition or Demethylating Agents
Authors: Mao Muling , Tian Feng , Mariadason John M. , Tsao Chun C. , Lemos Robert , Dayyani Farshid , Gopal Y.N. Vashisht , Jiang Zhi-Qin , Wistuba Ignacio I. , Tang Xi M. , Bornman William G. , Bollag Gideon , Mills Gordon B. , Powis Garth , Desai Jayesh , Gallick Gary E. , Davies Michael A. , Kopetz Scott
Published: December 2012

Purpose: Vemurafenib, a selective inhibitor of BRAFV600, has shown significant activity in BRAFV600 melanoma but not in less than 10% of metastatic BRAFV600 colorectal cancers (CRC), suggesting that studies of the unique hypermethylated phenotype and concurrent oncogenic activation of BRAFmut CRC may provide combinatorial strategies.

Experimental Design: We conducted comparative proteomic analysis of BRAFV600E melanoma and CRC cell lines, followed by correlation of phosphoinositide 3-kinase (PI3K) pathway activation and sensitivity to the vemurafenib analogue PLX4720. Pharmacologic inhibitors and siRNA were used in combination with PLX4720 to inhibit PI3K and methyltransferase in cell lines and murine models.

Results: Compared with melanoma, CRC lines show higher levels of PI3K/AKT pathway activation. CRC cell lines with mutations in PTEN or PIK3CA were less sensitive to growth inhibition by PLX4720 (P = 0.03), and knockdown of PTEN expression in sensitive CRC cells reduced growth inhibition by the drug. Combined treatment of PLX4720 with PI3K inhibitors caused synergistic growth inhibition in BRAF-mutant CRC cells with both primary and secondary resistance. In addition, methyltransferase inhibition was synergistic with PLX4720 and decreased AKT activation. In vivo, PLX4720 combined with either inhibitors of AKT or methyltransferase showed greater tumor growth inhibition than PLX4720 alone. Clones with acquired resistance to PLX4720 in vitro showed PI3K/AKT activation with EGF receptor (EGFR) or KRAS amplification.

Conclusions: We show that activation of the PI3K/AKT pathway is a mechanism of both innate and acquired resistance to BRAF inhibitors in BRAFV600E CRC and suggest combinatorial approaches to improve outcomes in this poor prognosis subset of patients. Clin Cancer Res; 19(3); 657–67. ©2012 AACR.
Systemic Administration of a Novel Immune-Stimulatory Pseudovirion Suppresses Lung Metastatic Melanoma by Regionally Enhancing IFN-γ Production
Authors: Saga Kotaro , Tamai Katsuto , Yamazaki Takehiko , Kaneda Yasufumi
Published: December 2012

Purpose: Cancer immunotherapy has encountered many difficulties in the face of the expectation to eradicate cancer, and new breakthroughs are required. We have previously shown that UV-inactivated Sendai virus particles (hemagglutinating virus of Japan envelope; HVJ-E) induce immunity against multiple tumor types. In this study, a novel pseudovirion that stimulates more robust antitumor immunity was designed for cancer treatment.

Experimental Design: First, we found that culturing murine splenocytes with HVJ-E in combination with interleukin (IL)-12 resulted in a remarkable increase in IFN-γ production compared with that observed in splenocytes cultured with IL-12 alone. The synergistic effects of HVJ-E and IL-12 on IFN-γ production were caused by viral F proteins independently of HVJ-E fusion activity and not by hemagglutination from hemagglutinin-neuraminidase (HN) proteins. We next constructed HN-depleted HVJ-E expressing the Fc region of immunoglobulin G (IgG) on the envelope and single-chain IL-12 containing the ZZ domain of protein A to produce an IL-12–conjugated HVJ-E particle without hemagglutinating activity.

Results: IL-12–conjugated HVJ-E dramatically enhanced the amount of IFN-γ produced by immune cells. Intratumoral injection of IL-12–conjugated HVJ-E eradicated murine melanomas more effectively than injection of wild-type HVJ-E through increased production of melanoma-specific CTLs. IL-12–conjugated HVJ-E preferentially accumulated in the lungs after systemic administration. When small metastatic melanoma foci were formed in the lungs, systemic administration of IL-12–conjugated HVJ-E significantly reduced the number of metastatic foci by inducing local production of IFN-γ in the lungs and generating large numbers of melanoma-specific CTLs.

Conclusion: IL-12–conjugated HVJ-E is a promising tool for the treatment of cancers, including lung metastasis. Clin Cancer Res; 19(3); 668–79. ©2012 AACR.
γ-H2AX Foci Formation as a Pharmacodynamic Marker of DNA Damage Produced by DNA Cross-Linking Agents: Results from 2 Phase I Clinical Trials of SJG-136 (SG2000)
Authors: Wu Jenny , Clingen Peter H. , Spanswick Victoria J. , Mellinas-Gomez Maria , Meyer Tim , Puzanov Igor , Jodrell Duncan , Hochhauser Daniel , Hartley John A.
Published: December 2012

Purpose: To evaluate γ-H2AX foci as a pharmacodynamic marker for DNA damage induced by DNA interstrand cross-linking drugs.

Experimental Design: γ-H2AX foci formation was validated preclinically in comparison with the Comet assay, and evaluated pharmacodynamically in two phase I studies of different dosing schedules of the novel cross-linking agent SJG-136 (SG2000).

Results: The measurement of γ-H2AX foci in human fibroblasts and lymphocytes in vitro was more than 10-fold more sensitive than Comet assay measurement of cross-linking, with peak γ-H2AX response 24 hours after the peak of cross-linking. In lymphocytes from a phase I study (every three week schedule), γ-H2AX foci were detectable 1 hour following the end of administration, and in all patients, maximum response was observed at 24 hours. Significant levels of foci were still evident at days 8 and 15 consistent with the known persistence of the DNA damage produced by this agent. In two tumor biopsy samples, foci were detected 4 hours postinfusion with levels higher than in lymphocytes. Extensive foci formation was also observed before the third dose in cycle 1 in lymphocytes from a second phase I study (daily × 3 schedule). These foci also persisted with a significant level evident before the second cycle (day 21). An increased γ-H2AX response was observed during the second cycle consistent with a cumulative pharmacodynamic effect. No clear relationship between foci formation and administered drug dose was observed.

Conclusion: This is the first use of γ-H2AX as a pharmacodynamic response to a DNA cross-linking agent in a clinical trial setting. Clin Cancer Res; 19(3); 721–30. ©2012 AACR.
Breast Cancer Stem Cells: We've Got Them Surrounded
Authors: Korkaya Hasan , Wicha Max S.
Published: December 2012

Breast cancer stem cells are regulated by cell intrinsic pathways as well as by elements in the tumor microenvironment. New evidence suggests that an important interaction between the interleukin (IL)-8 receptor CXCR1/2 and HER2 is involved in this regulation. Simultaneous targeting of these pathways provides a novel therapeutic approach. Clin Cancer Res; 19(3); 511–3. ©2012 AACR.
Roles of Keap1–Nrf2 System in Upper Aerodigestive Tract Carcinogenesis
Authors: Ohkoshi Akira , Suzuki Takafumi , Ono Masao , Kobayashi Toshimitsu , Yamamoto Masayuki
Published: December 2012

Cancers in the upper aerodigestive tract, including cancers of the tongue and the esophagus, are the third leading cause of cancer-related deaths in the world, and oxidative stress is well recognized as one of the major risk factors for carcinogenesis. The Keap1–Nrf2 system plays a critical role in cellular defense against oxidative stress, but little is known about its association with upper aerodigestive tract carcinogenesis. In this study, we examined whether loss of Nrf2-function exacerbates carcinogenesis by using an experimental carcinogenesis model that is induced by 4-nitroquinoline-1-oxide (4NQO). We found that Nrf2-knockout (Nrf2-KO) mice were more susceptible to 4NQO-induced tongue and esophageal carcinogenesis than wild-type mice, which suggests that Nrf2 is important for cancer prevention. We also examined how the suppression of Keap1 function or the induction of Nrf2 activity affected 4NQO carcinogenesis. Keap1-knockdown (Keap1-KD) mice were resistant to 4NQO-induced tongue and esophageal carcinogenesis. Importantly, no growth advantage was observed in tongue tumors in the Keap1-KD mice. These results show that the Keap1–Nrf2 system regulates an important defense mechanism against upper aerodigestive tract carcinogenesis. In addition to several important functions of Nrf2 that lead to cancer chemoprevention, we hypothesize that a mechanical defense of thickened keratin layers may also be a chemopreventive factor because thickened, stratified, squamous epithelium was found on the tongue of Keap1-KD mice. Cancer Prev Res; 6(2); 149–59. ©2012 AACR.
Sympathetic Neural and Hemodynamic Responses to Upright Tilt in Patients With Pulsatile and Nonpulsatile Left Ventricular Assist Devices
Authors: Markham David W. , Fu Qi , Palmer M. Dean , Drazner Mark H. , Meyer Dan M. , Bethea Brian T. , Hastings Jeffrey L. , Fujimoto Naoki , Shibata Shigeki , Levine Benjamin D.
Published: December 2012

Background—

Left ventricular assist devices (LVADs) are now widely accepted as an option for patients with advanced heart failure. First-generation devices were pulsatile, but they had poor longevity and durability. Newer generation devices are nonpulsatile and more durable, but remain associated with an increased risk of stroke and hypertension. Moreover, little is understood about the physiological effects of the chronic absence of pulsatile flow in humans.

Methods and Results—

We evaluated patients with pulsatile (n=6) and nonpulsatile (n=11) LVADs and healthy controls (n=9) during head-up tilt while measuring hemodynamics and muscle sympathetic nerve activity. Patients with nonpulsatile devices had markedly elevated supine and upright muscle sympathetic nerve activity (mean±SD, 43±15 supine and 60±21 bursts/min at 60° head-up tilt) compared with patients with pulsatile devices (24±7 and 35±8 bursts/min;
P
<0.01) and controls (11±6 and 31±6 bursts/min;
P
<0.01); however, muscle sympathetic nerve activity was not different between patients with pulsatile flow and controls (
P
=0.34). Heart rate, mean arterial pressure, and total peripheral resistance were greater, whereas cardiac output was smaller, in LVAD patients compared with controls in both supine and upright postures. However, these hemodynamic variables were not significantly different between patients with pulsatile and nonpulsatile flow.

Conclusions—

Heart failure patients with continuous, nonpulsatile LVADs have marked sympathetic activation, which is likely due, at least in part, to baroreceptor unloading. We speculate that such chronic sympathetic activation may contribute to, or worsen end-organ diseases, and reduce the possibility of ventricular recovery. Strategies to provide some degree of arterial pulsatility, even in continuous flow LVADs may be necessary to achieve optimal outcomes in these patients.
Detecting Myocardial Ischemia at Rest With Cardiac Phase–Resolved Blood Oxygen Level–Dependent Cardiovascular Magnetic Resonance
Authors: Tsaftaris Sotirios A. , Zhou Xiangzhi , Tang Richard , Li Debiao , Dharmakumar Rohan
Published: December 2012

Background—

Fast noninvasive identification of ischemic territories at rest (before tissue-specific changes) and assessment of functional status can be valuable in the management of severe coronary artery disease. This study investigated the use of cardiac phase–resolved blood oxygen level–dependent (CP-BOLD) cardiovascular magnetic resonance in detecting myocardial ischemia at rest secondary to severe coronary artery stenosis.

Methods and Results—

CP-BOLD, standard cine, and T2-weighted images were acquired in canines (n=11) at baseline and within 20 minutes of ischemia induction (severe left anterior descending stenosis) at rest. After 3 hours of ischemia, left anterior descending stenosis was removed, and T2-weighted and late-gadolinium-enhancement images were acquired. From standard cine and CP-BOLD images, end-systolic and end-diastolic myocardium was segmented. Affected and remote sections of the myocardium were identified from postreperfusion late-gadolinium-enhancement images. Systolic-to-diastolic ratio (S/D), quotient of mean end-systolic and end-diastolic signal intensities (on CP-BOLD and standard cine), was computed for affected and remote segments at baseline and ischemia. Ejection fraction and segmental wall thickening were derived from CP-BOLD images at baseline and ischemia. On CP-BOLD images, S/D was >1 (remote and affected territories) at baseline; S/D was diminished only in affected territories during ischemia, and the findings were statistically significant (ANOVA, post hoc
P
<0.01). The dependence of S/D on ischemia was not observed in standard cine images. Computer simulations confirmed the experimental findings. Receiver-operating characteristic analysis showed that S/D identifies affected regions with performance (area under the curve, 0.87) similar to ejection fraction (area under the curve, 0.89) and segmental wall thickening (area under the curve, 0.75).

Conclusions—

Preclinical studies and computer simulations showed that CP-BOLD cardiovascular magnetic resonance could be useful in detecting myocardial ischemia at rest. Patient studies are needed for clinical translation.
Intravenous Delivery of Adeno-Associated Viral Vector Serotype 9 Mediates Effective Gene Expression in Ischemic Stroke Lesion and Brain Angiogenic Foci
Authors: Shen Fanxia , Kuo Robert , Milon-Camus Marine , Han Zhenying , Jiang Lidan , Young William L. , Su Hua
Published: December 2012

Background and Purpose—

Adeno-associated viral vector (AAV) is a powerful tool for delivering genes to treat brain diseases. Intravenous delivery of a self-complementary but not single-stranded AAV9 (ssAAV9) mediates robust gene expression in the adult brain. We tested if ssAAV9 effectively mediates gene expression in the ischemic stroke lesion and angiogenic foci.

Methods—

Focal ischemic stroke was induced by permanent occlusion of the left middle cerebral artery (MCAO) and focal angiogenesis was induced by injecting an AAV expressing vascular endothelial growth factor (AAV-VEGF) into the basal ganglia. ssAAV vectors that have cytomegalovirus (CMV) promoter driving (AAV-CMVLacZ) or hypoxia response elements controlling (AAV-H9LacZ) LacZ expression were packaged in AAV9 or AAV1 capsid and injected into mice through the jugular vein 1 hour after MCAO or 4 weeks after the induction of angiogenesis. LacZ gene expression was analyzed in the brain and other organs 5 days after LacZ vector injection.

Results—

LacZ expression was detected in the peri-infarct region of AAV9-CMVLacZ and AAV9-H9LacZ–injected MCAO mice and the brain angiogenic foci of AAV9-CMVLacZ–injected mice. Minimum LacZ expression was detected in the brain of AAV1-CMVLacZ–injected mice. Robust LacZ expression was found in the liver and heart of AAV-CMVLacZ–injected mice, but not in AAV9-H9LacZ–injected mice.

Conclusions—

ssAAV9 could be a useful tool to deliver therapeutic genes to the ischemic stroke lesion or brain angiogenic foci.
The Effects of Alteplase 3 to 6 Hours After Stroke in the EPITHET–DEFUSE Combined Dataset
Authors: Ogata Toshiyasu , Christensen Soren , Nagakane Yoshinari , Ma Henry , Campbell Bruce C.V. , Churilov Leonid , Lansberg Maarten G. , Straka Matus , De Silva Deidre A. , Mlynash Michael , Bammer Roland , Olivot Jean-Marc , Desmond Patricia M. , Albers Gregory W. , Davis Stephen M. , Donnan Geoffrey A. ,   for the EPITHET and DEFUSE Investigators
Published: December 2012

Background and Purpose—

Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE; open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled individual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques.

Methods—

The EPITHET–DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay >6 seconds), and coregistration techniques were used to define MR diffusion-weighted imaging/perfusion-weighted imaging mismatch. Neuroimaging, parameters including reperfusion, recanalization, symptomatic intracerebral hemorrhage, and clinical outcomes were assessed. Alteplase and placebo groups were compared for the primary outcome of infarct growth as well for secondary outcome measures.

Results—

From 165 patients with adequate MR scans in the EPITHET–DEFUSE pooled data, 121 patients (73.3%) were found to have mismatch. For the primary outcome analysis, 60 patients received alteplase and 41 placebo. Mismatch patients receiving alteplase had significantly attenuated infarct growth compared with placebo (
P
=0.025). The reperfusion rate was also increased (62.7% vs 31.7%;
P
=0.003). Mortality and clinical outcomes were not different between groups.

Conclusions—

The data provide further evidence that alteplase significantly attenuates infarct growth and increases reperfusion compared with placebo in the 3- to 6- hour time window in patients selected based on MR penumbral imaging.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00238537
Mediating and getting ‘burnt’ in the gap: Politics and brokerage in a Recife slum, Brazil
Authors: Koster Martijn
Published: December 2012

This article takes a fresh look at political brokerage as a complex, provisional and contested phenomenon. Although brokerage has received little recent attention, I show how it remains critical to understanding the urban poor’s involvement in electoral politics. The article focuses on how local community leaders in a Recife slum, Brazil, operate as brokers during elections. Here, they have to deal with the different interests of their patrons (politicians) and their clients (their fellow slum dwellers), and also with the latter’s contradictory views on electoral politics. Slum dwellers combine a positive image, in which electoral politics provides access to resources, with a negative image, in which it contaminates all those involved, including the brokers. Further, by showing how these slum dwellers perceive electoral politics as coming from ‘another world’, this study counters the still prevalent functionalist understandings of brokerage which depict brokers as the forgers of a shared moral universe.
Questioning success: Dispossession and the criminal entrepreneur in urban India
Authors: Sanchez Andrew
Published: December 2012

Conceptual divisions between the formal and informal sector are a marked feature of studies of Indian neoliberal dispossession, which juxtapose the experiences of an insecure informal workforce with their counterparts in an increasingly privileged and hegemonic formal sector. I suggest that dispossession be conceptually extended to areas of formal, urban India that experience economic liberalisation as a loss of job security and engage with the ideology of the enterprising individual in critical ways. Amid the casualisation of industrial labour and assumptions of endemic corruption, workers in one of India’s largest private corporations argue that the success of the neoliberal entrepreneur relies upon the use of criminality and corruption. In this environment, entrepreneurs are regarded in a politically critical manner, inviting a re-examination of the extent to which the ideology of the enterprising individual has been internalised in India’s urban centres.
Matching, Ethnicity and Identity
Authors: Wainwright John , Ridley Julie
Published: December 2012

Ethnicity and adoption have taken centre stage in the Coalition Government's focus on child care social policy in the UK. The current political perspective is one of promoting the placement of children of minority ethnic heritage with white families, in order to avoid delay in adoption where no families of a similar ethnic heritage are available. John Wainwright and Julie Ridley reflect on the contemporary debate by discussing the findings from a commissioned service evaluation of an adoption agency that specialised in recruiting families of black, Asian and dual heritage, and placing children of black and minority ethnic (BME) heritage. This service evaluation provides evidence that focusing on recruiting BME individuals and families and matching them with children of similar heritage can be effective. The evaluation utilised mixed methods, including interviews with staff in the service, prospective and current adopters, and statistical information that informed an understanding of the type of ethnic matches made. Comparison was also made with a general adoption service within the commissioning agency using the same data collection methods.
Between Colourblindness and Ethnicisation
Authors: Hübinette Tobias , Andersson Malinda
Published: December 2012

When and how are issues of race and ethnicity articulated in the everyday lives of transnational adoptees in Sweden? Which discursive and practical ambivalences and conflicts do they provoke? What happens with issues of race in a country where antiracist colourblindness is the norm, and where there has been no debate on whether whites should adopt children of colour? Based on an analysis of interviews with transnational adoptees and adoption-related documents, Tobias Hübinette and Malinda Andersson examine how discursive conditions regarding race and ethnicity are negotiated in their daily lives.
‘What the Map Cuts up the Story Cuts across’
Authors: Richards Sarah
Published: December 2012

Adoption stories, like other narratives, seek to establish a child's linear life course. As such, they attempt to encapsulate a biological beginning, a birth point. This point allows certain attributes which are assumed to be fixed and static, such as sex and ethnicity, to be ascribed to the child and these are often taken to be fundamental to the unfolding narrative. Using qualitative research with families who live in England and have adopted daughters from China, Sarah Richards explores the narratives of belonging with the girls themselves and their parents. These belonging stories are shaped by reification of biological parentage and of birth heritage that reflects the social and political context in which adoption stories are told.
New Ways of Thinking about the Influence of Cultural Identity, Place and Spirituality on Child Development within Child Placement Practice
Authors: Sharley Victoria
Published: December 2012

The policy and practice of family placement within the UK can be understood as the archetypal separation of a person from their physical environment, yet the intersection of ‘person with place’ - both past and present - has been argued to be crucial for identity formation. Indeed, intersectional analysts have called for alternative frameworks which challenge western models centering on the individual person disconnected from his or her community. An emerging body of work has drawn on Maori social work literature to explore the intersection of ‘person (identity) with place’ through an application to the concept of spirituality within western social work practice models (Zapf, 2005a, b). According to this perspective, people can have deep spiritual connections with the physical environment in which they live, creating a sense of belonging and attachment to that place. Victoria Sharley considers this Maori spiritual analysis in the context of family placement practice in the UK. In so doing, she offers a new way of thinking about the inter-relationship of cultural identity, place and spirituality as it affects the development of children separated from their birth families.
Democratizing mental health
Authors: Chettiar Teri
Published: December 2012

Shortly following the Second World War, and under the medical direction of ex-army psychiatrist T. F. Main, the Cassel Hospital for Functional Nervous Disorders emerged as a pioneering democratic ‘therapeutic community’ in the treatment of mental illness. This definitive movement away from conventional ‘custodial’ assumptions about the function of the psychiatric hospital initially grew out of a commitment to sharing therapeutic responsibility between patients and staff and to preserving patients’ pre-admission responsibilities and social identities. However, by the mid-1950s, hospital practices had come to focus pre-eminently on patients’ relationships with family members, and staff had developed a social model of mental health that focused on the family as the irreducible unit of mental treatment. By the late 1950s, this culminated in the in-patient admission of entire families for mental treatment, even when only one family member was exhibiting symptoms. At the heart of this growing post-war social-psychiatric preoccupation with the family was a new emphasis on the close relationship between mental health and individuals’ successful development toward mature responsible adulthood. The family came to be conceived as the quintessential space where both were forged. This article examines the process through which the Cassel’s social-psychiatric commitment to ‘therapeutic community’ became focused on the family as a key therapeutic site. While the family had become a central point of focus in social, political and psychological discussions of the foundation for stable democratic culture and political peace in post-war Britain, the Cassel Hospital actively experimented with these connections in therapeutic practice. This article thus illuminates the important, but frequently overlooked, role of psychiatric practices in the development of a post-war psychopolitics that established important links between the nuclear family, mental health and democratic social life.
The invention of the psychosocial: An introduction
Authors: Hayward Rhodri
Published: December 2012

Although the compound adjective ‘psychosocial’ was first used by academic psychologists in the 1890s, it was only in the interwar period that psychiatrists, psychologists and social workers began to develop detailed models of the psychosocial domain. These models marked a significant departure from earlier ideas of the relationship between society and human nature. Whereas Freudians and Darwinians had described an antagonistic relationship between biological instincts and social forces, interwar authors insisted that individual personality was made possible through collective organization. This argument was advanced by dissenting psychoanalysts such as Ian Suttie and Karen Horney; biologists including Julian Huxley and Hans Selye; philosophers (e.g. Olaf Stapledon), anthropologists (e.g. Margaret Mead) and physicians (e.g John Ryle and James Halliday).

This introduction and the essays that follow sketch out the emergence of the psycho-social by examining the methods, tools and concepts through which it was articulated. New statistical technologies and physiological theories allowed individual pathology to be read as an index of broader social problems and placed medical expertise at the centre of new political programmes. In these arguments the intangible structure of social relationships was made visible and provided a template for the development of healthy and effective forms of social organization. By examining the range of techniques deployed in the construction of the psychosocial (from surveys of civilian neurosis, techniques of family observation through to animal models of psychotic breakdown) a critical genealogy of the biopolitical basis of modern society is developed.
Hair Balls in Cats
Authors: Cannon Martha
Published: December 2012

Practical relevance:

Vomiting of hair balls is a common problem in domestic cats, to the extent that it is considered by many owners and veterinarians to be a normal feline behaviour. Whether this is ever the case remains unclear but in most shorthaired cats the frequent elimination of hair balls is an indicator of an underlying chronic disease that is causing increased ingestion of fur or altered gastrointestinal motility. Pruritic skin disease, flea infestation and/or an underlying dietary intolerance are common contributing factors that should not be overlooked.

Evidence base:

Studies concerning this common problem are lacking and there are no previously published data regarding the incidence of hair balls in pet cats or potential predisposing causes. Although a range of commercial hair ball control diets are available there is no objective information in the public domain regarding their efficacy. Similarly, no studies have evaluated the success of other commonly recommended preventive strategies.

Clinical challenges:

Despite the lack of evidence-based information, veterinarians are faced with the day-to-day challenge of helping owners to limit the extent to which their cats produce hair balls. The problem is at best an unpleasant nuisance for both cat and owner, and at worst may be a cause of significant morbidity and even, in rare cases, mortality.
Problematizing practice: MacIntyre and management
Authors: Kavanagh Donncha
Published: December 2012

Alasdair MacIntyre’s distinction between institutions and practices helps illuminate how powerful institutional forces frame and constrain the practice of organizational research as well as the output and positioning of scholarly journals like Organization. Yet his conceptual frame is limited, not least because it is unclear whether the activity of managing is, or is not, a practice. This article builds on MacIntyre’s ideas by incorporating Aristotle’s concepts of poíēsis, praxis, téchnē and phrónēsis. Rather than ask, following MacIntyre, whether management is a practice, this wider network of concepts provides a richer frame for understanding the nature of managing and the appropriate role for academia. The article outlines a phronetic paradigm for organizational inquiry, and concludes by briefly examining the implications of such a paradigm for research and learning.
Notes for anniversarifiers
Authors: Grey Christopher
Published: December 2012

A reflection on the celebration of journal anniversaries, and of anniversaries in general.
CMS: A satirical critique of three narrative histories
Authors: Mills Albert J. , Mills Jean Helms
Published: December 2012

Reflections on the 20th anniversary of Organization provide an opportunity for considerations of the role of the past and history in critical studies of management. Yet, why should we care? Arguably, the pages of Organization are replete with analyses that take into account the past and history. Indeed they are. However, as has been contended elsewhere, such accounts have been remarkably under-theorized for a field noted for its thoroughgoing critique of anything that moves. Nonetheless, it is not our intention to go over that ground so much as provide an appropriate example of the problem at hand. We do this through analysis of three selected accounts of how critical studies of management came into being as a field of study. Drawing on Hayden White’s approach to history, we analyse three histories of critical management studies through a focus on their respective narrative form, choosing to privilege our own narrative as satirical critique. Thus, the article does double duty by directly joining with the reflections on Organization and critical studies of management, while providing an argument for the need for greater theorization of the past and history. In the process we provide some clues to the development of the field of critical studies of management; problematize the associated notions of history and the past and make suggestions for future directions of what has become known as Critical Management Studies.
Multilingual scholarship and the paradox of translation and language in management and organization studies
Authors: Steyaert Chris , Janssens Maddy
Published: December 2012

This article questions the unreflexive use of English in academic practices by highlighting the paradox of multilingual scholarship and the need for practices that may help both scholars and journals to become inventive in performing multilingual scholarship. Even when academic outputs are only in English, language multiplicity exists and needs to be reflected upon. To do so, we introduce the three strategies of scandalization, scrutinization, and invention which respectively document and question the naturalization of English as lingua franca, inquire into linguistic negotiations and its effects, and make multiplicity visible. It is our belief that there is currently too little agony about and critique of the hegemony of English based on a kind of pragmatism; this situation prevents us from being more imaginative and experimental in the ways we include other languages and language differences.
The ethical difference of Organization
Authors: Rhodes Carl , Wray-Bliss Edward
Published: December 2012

Noting that from its very inception Organization laid claim to having a central interest in the ethics and politics of organization, in this article we review contributions to the Journal over the past 20 years in order to consider the ethical thinking that has developed. We suggest that there is a common thread of ethical interest that characterizes much of this work—one that clearly differentiates it from more conventional approaches to business ethics. While business ethics has as its locus of interest the ethicality of organizations themselves, central issues that have emerged in Organization concern how individuals might (or might not) maintain a valued experience of themselves as ethical subjects despite the behaviour of organizations, and how organizational arrangements might be politically contested in the name of ethics. We explore this in relation to a question that unites much of the study of ethics in Organization: how do we live (and work) together in a world beset by difference? We consider this question in terms of the issue of ethical subjectivity and the relation between an ethics of consensus and an ethics of difference. The article concludes much as the Journal started—with the proposal that ethics remains a pressing challenge for critical scholarship and practice.
Making Organization matter: looking back and looking ahead
Authors: Cheney George , Lair Daniel J. , Kendall Brenden E.
Published: December 2012

This article calls upon scholars of organizational studies to take more active roles in confronting and addressing the social, political, economic and environmental problems of today. The article begins with the observation that the birth of organizational studies was deeply concerned with changes, problems and opportunities in an increasingly ‘organized’ world and argues that our studies should not abstract organizing from the world but use our conceptual and practical tools to engage the world fully. We offer six contemporary challenges for (critical) organizational studies in a global society: abstraction and virtuality, diversity and homogeneity, distinctiveness and linkage, boundaries and limits, transformations of labour/work and trust and cynicism. The article urges readers to consider in more specific terms how their work can not only illuminate these issues but also offer something practical, at whatever location or level of analysis, to make a positive difference in pedagogy, scholarship and wider community involvement.
Memory on film
Authors: Jones Sara
Published: December 2012

This article considers the construction of authenticity in documentary films dealing with repression in the former East Germany, focusing on Stefan Weinert’s Gesicht zur Wand (2009) and Christian Klemke and Jan N. Lorenzen’s Das Ministerium für Staatssicherheit: Alltag einer Behörde (2002). Taking as its starting point the observation of two modes of authenticity in Florian Henckel von Donnersmarck’s Oscar-winning feature film, Das Leben der Anderen (2006), the article analyses the interaction between referential and emotive elements in non-fictional representations of repression. The use of eyewitness testimony is central to both documentary films, and the grouping of personal accounts can create a self-authenticating ‘mediated remembering community’. However, the observation of complementary and competing authenticities in the medium highlights how the authenticity of the witness account can be both harnessed and undermined by its (re)mediation in cultural artefacts. This adds to our understanding of how versions of contested pasts circulate and become salient.
Establishing joint decisions in a dyad
Authors: Stevanovic Melisa
Published: December 2012

This study analyses joint decisions. Drawing on video-recorded planning meetings in a workplace context as data, and on conversation analysis as a method, I investigate what is needed for a proposal to get turned into a joint decision: How do people negotiate the outcome of the decision-making processes in terms of whether they indeed comprise new decisions and whether these decisions are really joint ones? This study identifies three essential components in arriving at joint decisions (access, agreement, commitment), and discusses two other possible outcomes of decision-making processes – non-decisions and unilateral decisions – as being a direct result of the deployment of the same components. These observations help explain the exact mechanisms involved in approving and rejecting proposals in joint decision-making settings, as well as the ways in which people may negotiate their rights and obligations to participate in decision-making processes.
Recordability: Resistance and collusion in psychometric interviews with children
Authors: Iversen Clara
Published: December 2012

Different areas of child welfare work call for psychometric measurement to replace professionals’ judgements with objective numbers. Using data from a national Swedish evaluation of interventions for abused children, the present article investigates child interviewees’ resistance to constraints in psychometric questions. The article contributes to studies of how psychology operates in institutional settings; it looks into the discursive production of the interviewee’s position in the struggle between the principle of recordability and ‘sensitive’ interviewing. The findings suggest that interviewees resist questions’ structural restrictions in the service of telling the interviewer about their lives. Thus, the function of their misalignment is affiliative; it cooperates both with the institutional goal of eliciting information and with the interviewer’s interest in them. However, the interviewer’s solutions to children’s problem presentations remain focused on generating recordable answers. The article concludes that the narrow focus on recordability neglects important opportunities to talk about children’s experiences.
Ethics in praxis: Negotiating the presence and functions of a video camera in family therapy
Authors: Hutchby Ian , O’Reilly Michelle , Parker Nicola
Published: December 2012

The use of video for research purposes is something that has attracted ethical attention and debate. While the usefulness of video as a mechanism to collect data is widely agreed, the ethical sensitivity and impact of recording equipment is more contentious. In some clinical settings the presence of a camera has a dual role, as a portal to a reflecting team and as a recording device to obtain research data. Using data from one such setting, family therapy sessions, this article shows how the role played by recording equipment is negotiated in the course of talk and other activities that constitute sessions. Analysis reveals that members of the therapy interaction orient in different ways and for different purposes to the value of recordings. The article concludes that there are layers of benefit to be derived from recording of clinical interactions, including for members themselves, and this has wider implications for the ways in which qualitative research designs in health sciences are evaluated.
An Analysis of One-Star Online Reviews and Responses in the Washington, D.C., Lodging Market
Authors: Levy Stuart E. , Duan Wenjing , Boo Soyoung
Published: December 2012

The hotel industry continues to develop strategies for addressing consumer-generated online reviews, and particularly responding to poor reviews, which can have a damaging effect on a hotel’s reputation. To gain a greater understanding of the dynamics of poor reviews, this study analyzed 1,946 one-star reviews from ten popular online review websites, as well as 225 management responses from eighty-six Washington, D.C., hotels. A comprehensive complaint framework found that the most common complaints related to front desk staff, bathroom issues, room cleanliness, and guestroom noise issues. Complaints were also analyzed by hotel characteristics, including chain-scale segments, and reviewer characteristics, including purpose of travel and geographic location. Examining the reviews, highly rated hotels often respond to online complaints with appreciation, apologies, and explanations for what had gone wrong. Compensation adjustments are rarely mentioned by any hotel. The increasingly prominent role of social media necessitates that hotels use online reviews for market research and service recovery opportunities, regardless of whether they respond publicly.
Industry Trends
Authors: Houran James , Lange Rense , Kefgen Keith
Published: December 2012

We explored the idea that the timing of executives’ career moves was consistent with Bak’s notion of self-organized criticality. Consistent with predictions, time series analysis of job changes for 43 hospitality executives obeyed a power law and revealed a mixture of predictable and unpredictable patterns with a musical nature (pink noise distribution). The data showed better fit for traditional ‘organization men’ versus opportunistic ‘trailblazers.’ These differences in career patterns (rhythms) could be used to reliably distinguish between these two executive-types using neural nets. Potential implications for executive coaching and development are discussed.
Linking genome content to biofuel production yields: a meta-analysis of major catabolic pathways among select H2and ethanol-producing bacteria
Authors: Carere Carlo R , Rydzak Thomas , Verbeke Tobin J , Cicek Nazim , Levin David B , Sparling Richard
Published: December 2012

Background

Fermentative bacteria offer the potential to convert lignocellulosic waste-streams into biofuels such as hydrogen (H2) and ethanol. Current fermentative H2 and ethanol yields, however, are below theoretical maxima, vary greatly among organisms, and depend on the extent of metabolic pathways utilized. For fermentative H2 and/or ethanol production to become practical, biofuel yields must be increased. We performed a comparative meta-analysis of (i) reported end-product yields, and (ii) genes encoding pyruvate metabolism and end-product synthesis pathways to identify suitable biomarkers for screening a microorganism’s potential of H2 and/or ethanol production, and to identify targets for metabolic engineering to improve biofuel yields. Our interest in H2 and/or ethanol optimization restricted our meta-analysis to organisms with sequenced genomes and limited branched end-product pathways. These included members of the Firmicutes, Euryarchaeota, and Thermotogae.

Results

Bioinformatic analysis revealed that the absence of genes encoding acetaldehyde dehydrogenase and bifunctional acetaldehyde/alcohol dehydrogenase (AdhE) in Caldicellulosiruptor, Thermococcus, Pyrococcus, and Thermotoga species coincide with high H2 yields and low ethanol production. Organisms containing genes (or activities) for both ethanol and H2 synthesis pathways (i.e. Caldanaerobacter subterraneus subsp. tengcongensis, Ethanoligenens harbinense, and Clostridium species) had relatively uniform mixed product patterns. The absence of hydrogenases in Geobacillus and Bacillus species did not confer high ethanol production, but rather high lactate production. Only Thermoanaerobacter pseudethanolicus produced relatively high ethanol and low H2 yields. This may be attributed to the presence of genes encoding proteins that promote NADH production. Lactate dehydrogenase and pyruvate:formate lyase are not conducive for ethanol and/or H2 production. While the type(s) of encoded hydrogenases appear to have little impact on H2 production in organisms that do not encode ethanol producing pathways, they do influence reduced end-product yields in those that do.

Conclusions

Here we show that composition of genes encoding pathways involved in pyruvate catabolism and end-product synthesis pathways can be used to approximate potential end-product distribution patterns. We have identified a number of genetic biomarkers for streamlining ethanol and H2 producing capabilities. By linking genome content, reaction thermodynamics, and end-product yields, we offer potential targets for optimization of either ethanol or H2 yields through metabolic engineering.