bluuebunny/crossref_metadata_2025 huggingface dataset:
Mini‐BEAM is effective as a bridge to transplantation in patients with refractory or relapsed Hodgkin lymphoma who have failed to respond to previous lines of salvage chemotherapy but not in patients with salvage‐refractory DLBCL
Authors: Moore Sally , Kayani Irfan , Peggs Karl , Qian Wendi , Lowry Lisa , Thomson Kirsty , Linch David C. , Ardeshna Kirit
Published: March 2012

Patients with relapsed or refractory lymphoma can be cured with stem cell transplantation if they are shown to have disease that is responsive to salvage chemotherapy. Patients who fail to respond to first‐line salvage chemotherapy tend to do very poorly. Here we report on 39 such patients who received mini‐BEAM (carmustine, etoposide, cytarabine, melphalan) chemotherapy as second or subsequent‐line salvage chemotherapy. Fifty‐six percent of these patients had primary refractory disease and a further 28% had responses to first‐line therapy that lasted <12 months. Seventy‐two percent had progressive disease following the salvage chemotherapy administered immediately prior to mini‐BEAM and the remaining 28% had stable disease. Overall there was a 38% response to mini‐BEAM (complete response = 28%, partial response = 10%). Patients with Hodgkin lymphoma (HL) had a higher response rate compared to those with diffuse large B cell lymphoma (DLBCL) (63% vs. 20%). Seventy‐four percent of HL patients were able to proceed to transplantation compared with 30% of patients with DLBCL. Mini‐BEAM is a very effective bridge to transplantation in very poor risk patients with HL who have failed to respond to first‐line salvage chemotherapy. Its efficacy in non‐Hodgkin lymphoma is more modest.
The impact of erythrocyte age on eryptosis
Authors: Ghashghaeinia Mehrdad , Cluitmans Judith C. A. , Akel Ahmed , Dreischer Peter , Toulany Mahmoud , Köberle Martin , Skabytska Yuliya , Saki Mohammad , Biedermann Tilo , Duszenko Michael , Lang Florian , Wieder Thomas , Bosman Giel J. C. G. M.
Published: March 2012

Mature, circulating erythrocytes undergo senescence, which limits their life span to approximately 120 d. Upon injury, erythrocytes may undergo suicidal erythrocyte death or eryptosis, which may accelerate senescence and shorten their survival. Eryptosis is defined as cell shrinkage and exposure of phosphatidylserine at the cell surface. Triggers of eryptosis include oxidative stress. The present study addresses the impact of erythrocyte age on the relative susceptibility to eryptosis. Erythrocytes were separated into five fractions, based on age‐associated differences in density and volume. Cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, the cell volume from forward scatter, and the Ca2+ level from Fluo‐3‐dependent fluorescence. In addition, glutathione (GSH) concentrations were measured by an enzymatic/colourimetric method. After 48 h incubation in Ringer solution, Annexin V binding increased significantly with erythrocyte age. The differences were not accompanied by altered GSH concentrations, but were reversed by addition of the antioxidant N‐acetyl‐l‐cysteine in vitro. Also, N‐acetyl‐l‐cysteine significantly prolonged the half‐life of circulating mouse erythrocytes in vivo. Thus, the susceptibility to eryptosis increases with the age of the erythrocytes, and this effect is at least partially due to enhanced sensitivity to oxidative stress.
Troubled families: vulnerable families' experiences of multiple service use
Authors: Morris Kate
Published: March 2012

This paper draws on a small‐scale study examining the experiences of highly vulnerable families with complex and enduring needs. The previous UK government and the current government have sought to develop policy and service initiatives that target families who present high levels of need and require high cost services. However, to date remarkably little is known about family perspectives and experiences. In this paper, family accounts of their experiences are presented and it is suggested that from these come some difficult practice questions. The family data reveal evident gaps in existing practice and challenges social work to ‘think family’ in new ways. The paper explores how families understand they are understood at the point of engagement, the assumptions that are made about family knowledge, and how families share and withhold information about their needs and experiences. In the discussion, the argument is made for the development of nuanced practice capable of recognizing and working with the ways highly vulnerable families ‘do family’, and the processes that support and inhibit professional interventions.
Endocrine complications in primary immunodeficiency diseases in Japan
Authors: Nozaki Takafumi , Takada Hidetoshi , Ishimura Masataka , Ihara Kenji , Imai Kohsuke , Morio Tomohiro , Kobayashi Masao , Nonoyama Shigeaki , Hara Toshiro
Published: March 2012

Background

In spite of the accumulating evidence on the interaction between the immune and endocrine systems based on the recent progress in molecular genetics, there have been few epidemiological studies focused on the endocrine complications associated with primary immunodeficiency diseases (PID).

Objective

To investigate the prevalence and clinical features of endocrine complications in patients with PID in a large‐scale study.

Design and participants

This survey was conducted on patients with PID who were alive on 1 December 2008 and those who were newly diagnosed and died between 1 December 2007 and 30 November 2008 in Japan. We investigated the prevalence and the clinical data of the endocrine complications in 923 patients with PID registered in the secondary survey.

Results

Among 923 PID patients, 49 (5·3%) had endocrine disorders. The prevalence of the endocrine diseases was much higher in patients with PID than in the general population in the young age group, even after excluding patients with immune dysregulation.

Conclusions

Endocrine disorders are important complications of PID. Analysis of the endocrine manifestations in patients with PID in a large‐scale study may provide further insights into the relationship between the immune and endocrine systems.
Influences of temperature, bathymetry and fronts on spawning migration routes of Icelandic capelin (Mallotus villosus)
Authors: OLAFSDOTTIR ANNA H. , ROSE GEORGE A.
Published: March 2012

Capelin (Mallotus villosus) is the largest commercial fish stock in Icelandic waters and also an important forage fish. Capelin have adapted to the sub‐arctic environment by migrating north (67–72°N) to feed during summer in deep cold waters (>500 m; 1–3°C) before migrating south (63–65°N) to spawn in winter in warm shallow waters on the south and west coasts of Iceland (<100 m; 5–7°C). Hydroacoustic data on capelin spawning migrations from 1992 to 2007 revealed a consistent southward route along which capelin migrated actively (ground velocity >> current velocity) off the east coast (and a lesser used route off the west coast). North of 65°N, the dominant eastern route followed the bathymetry, skirting the shelf edge (>200 m bottom depth) within a funnel of near constant temperatures (approximately 2.5°C). Further south, between 65 and 64°N, as temperatures warmed to 4.5°C (reaching 7.9°C at 63.5°N), capelin abruptly moved onto the shelf and towards the coastal spawning areas. Capelin spawning migrations appear to be an innately based southward search for appropriate spawning locations, guided by bathymetry and temperature. We suggest that the extended eastern migration route minimizes exposure to cod predation and that warming conditions north of Iceland may result in a northward shift in migrations and spawning locations, as occurred in the 1920s and 1930s.
Demographic response to perturbations: the role of compensatory density dependence in a North American duck under variable harvest regulations and changing habitat
Authors: Péron Guillaume , Nicolai Christopher A. , Koons David N.
Published: March 2012

1. Most wild animal populations are subjected to many perturbations, including environmental forcing and anthropogenic mortality. How population size varies in response to these perturbations largely depends on life‐history strategy and density regulation.

2. Using the mid‐continent population of redhead Aythya americana (a North American diving duck), we investigated the population response to two major perturbations, changes in breeding habitat availability (number of ponds in the study landscape) and changes in harvest regulations directed at managing mortality patterns (bag limit). We used three types of data collected at the continental scale (capture–recovery, population surveys and age‐ and sex ratios in the harvest) and combined them into integrated population models to assess the interaction between density dependence and the effect of perturbations.

3. We observed a two‐way interaction between the effects on fecundity of pond number and population density. Hatch‐year female survival was also density dependent. Matrix modelling showed that population booms could occur after especially wet years. However, the effect of moderate variation in pond number was generally offset by density dependence the following year.

4. Mortality patterns were insensitive to changes in harvest regulations and, in males at least, insensitive to density dependence as well. We discuss potential mechanisms for compensation of hunting mortality as well as possible confounding factors.

5. Our results illustrate the interplay of density dependence and environmental variation both shaping population dynamics in a harvested species, which could be generalized to help guide the dual management of habitat and harvest regulations.
Chikungunya virus impacts the diversity of symbiotic bacteria in mosquito vector
Authors: ZOUACHE KARIMA , MICHELLAND RORY J. , FAILLOUX ANNA‐BELLA , GRUNDMANN GENEVIEVE L. , MAVINGUI PATRICK
Published: March 2012

Mosquitoes transmit numerous arboviruses including dengue and chikungunya virus (CHIKV). In recent years, mosquito species Aedes albopictus has expanded in the Indian Ocean region and was the principal vector of chikungunya outbreaks in La Reunion and neighbouring islands in 2005 and 2006. Vector‐associated bacteria have recently been found to interact with transmitted pathogens. For instance, Wolbachia modulates the replication of viruses or parasites. However, there has been no systematic evaluation of the diversity of the entire bacterial populations within mosquito individuals particularly in relation to virus invasion. Here, we investigated the effect of CHIKV infection on the whole bacterial community of Ae. albopictus. Taxonomic microarrays and quantitative PCR showed that members of Alpha‐ and Gammaproteobacteria phyla, as well as Bacteroidetes, responded to CHIKV infection. The abundance of bacteria from the Enterobacteriaceae family increased with CHIKV infection, whereas the abundance of known insect endosymbionts like Wolbachia and Blattabacterium decreased. Our results clearly link the pathogen propagation with changes in the dynamics of the bacterial community, suggesting that cooperation or competition occurs within the host, which may in turn affect the mosquito traits like vector competence.
Multiple ABC transporters are involved in the acquisition of petrobactin in Bacillus anthracis
Authors: Dixon Shandee D. , Janes Brian K. , Bourgis Alexandra , Carlson Jr Paul E. , Hanna Philip C.
Published: March 2012

In Bacillus anthracis the siderophore petrobactin is vital for iron acquisition and virulence. The petrobactin‐binding receptor FpuA is required for these processes. Here additional components of petrobactin reacquisition are described. To identify these proteins, mutants of candidate permease and ATPase genes were generated allowing for characterization of multiple petrobactin ATP‐binding cassette (ABC)‐import systems. Either of two distinct permeases, FpuB or FatCD, is required for iron acquisition and play redundant roles in petrobactin transport. A mutant strain lacking both permeases, ΔfpuBΔfatCD, was incapable of using petrobactin as an iron source and exhibited attenuated virulence in a murine model of inhalational anthrax infection. ATPase mutants were generated in either of the permease mutant backgrounds to identify the ATPase(s) interacting with each individual permease channel. Mutants lacking the FpuB permease and FatE ATPase (ΔfpuBΔfatE) and a mutant lacking the distinct ATPases FpuC and FpuD generated in the ΔfatCD background (ΔfatCDΔfpuCΔfpuD) displayed phenotypic characteristics of a mutant deficient in petrobactin import. A mutant lacking all three of the identified ATPases (ΔfatEΔfpuCΔfpuD) exhibited the same growth defect in iron‐depleted conditions. Taken together, these results provide the first description of the permease and ATPase proteins required for the import of petrobactin in B. anthracis.
‘What ever I do it’s a lost cause.’ The emotional and behavioural experiences of individuals who are ulcer free living with the threat of developing further diabetic foot ulcers: a qualitative interview study
Authors: Beattie Angela M. , Campbell Rona , Vedhara Kavita
Published: March 2012

Objective  Individuals who have had one diabetic foot ulcer (DFU) are at high risk for developing further DFUs. This study was designed to examine the emotional and behavioural consequences of living with this heightened risk of re‐ulceration.

Participants and setting  Fifteen women and men living in south‐west England were interviewed at home or at the university by an academic psychologist.

Design  Interviews were audiotaped and transcribed verbatim. Thematic analysis using the constant comparative method was employed for data analysis.

Results  Participants reported having little perceived control in preventing further DFUs. This lack of control was associated with a range of negative emotions including fears and worries about developing further foot ulcers, amputation and guilt for the past neglect. Tensions were present between participants’ beliefs and reported behaviours, that is, what they felt they ought to be doing and what they were actually doing to care for their feet; most engaged in ‘strategic adherence’, that is, conducting a trade‐off between living a normal life and following foot‐care advice.

Conclusion  A lack of perceived control appears central to the emotional and behavioural responses of individuals living with the threat of re‐ulceration. We propose that these responses may serve to increase individuals’ risk of re‐ulceration and that these ‘risk factors’ should be considered part of the management of this patient group.
Does cultural context make a difference to women’s experiences of maternity care? A qualitative study comparing the perspectives of breast‐feeding women of Bangladeshi origin and health practitioners
Authors: McFadden Alison , Renfrew Mary J , Atkin Karl
Published: March 2012

Background  Maternity services struggle to provide culturally appropriate care that meets the needs of women from diverse populations. Problems include simplistic understandings of ethnicity and the role of culture in women’s lives, and stereotypes held by health practitioners.

Objective  To explore the extent to which cultural context makes a difference to experiences of breast‐feeding support for women of Bangladeshi origin and to consider the implications for the provision of culturally appropriate care.

Methods  The study comprised individual interviews with 23 women of Bangladeshi origin and four health service managers, and focus group discussions with 28 health practitioners between February and December 2008. Participants were recruited from four localities in northern England.

Results  Women’s rich descriptions of various facets of their identities were in contrast to practitioners’ representations of women of Bangladeshi origin as homogenous. Practitioners did not recognize when the needs of women of Bangladeshi origin were similar to those of the majority white population, or where cultural context made a difference to their experiences of breast‐feeding and breast‐feeding support. Some practitioners used cultural stereotypes which, combined with organizational constraints, resulted in services not meeting many of the women’s needs.

Conclusions  Implications for education, policy and practice include the need for training of health practitioners to work with diverse populations, implementing evidence‐based practice and providing an organizational context which supports practitioners to respond to diversity without using cultural stereotypes.
Beyond rose colored glasses: the adaptive role of depressive and anxious symptoms among individuals with heart failure who were evaluated for transplantation
Authors: Madan A. , White‐Williams C. , Borckardt J.J. , Burker E.J. , Milsom V.A. , Pelic C.M. , Thurstin A.H.
Published: March 2012

The prospect of and the evaluative period for transplantation can be stressful for individuals with heart failure (HF). Little is known about the impact of psychosocial factors on service utilization and health outcomes. The current study examined the impact of depression, dysthymia, and anxiety on two‐yr hospitalization and mortality among 96 individuals with HF who were evaluated for transplantation. Results revealed that only a small percentage of individuals endorsed sufficient symptomatology to meet criteria for a psychiatric, Axis I disorder (3.1% = anxiety; 2.1% = depression; 1.0% = dysthymia) although a significant proportion of the sample was prescribed an antidepressant or an anxiolytic (37%). Multivariable regression analysis was conducted to examine the association between significant independent demographic, medical, and psychiatric predictors and total duration of hospitalizations; logistic regression analysis was used to examine the relation between predictors and mortality. An increase in anxious symptoms was associated with a decrease in total number of days hospitalized during the two‐yr period following the initial evaluation. Similarly, as depressive symptoms increased, risk of two‐yr mortality decreased. Future research should assess communication between the patient and providers to further elucidate the potential relationship between psychiatric symptoms, service utilization/hospitalization, and mortality in this patient population.
HLA‐A*31:56 and HLA‐A*31:59 were identified by polymerase chain reaction sequence‐based typing in Chinese individuals
Authors: Zhang W. , Zhu F.‐M. , He J. , Lv H.‐J. , Yan L.‐X.
Published: March 2012

Compared with HLA‐A*31:01:02, HLA‐A*31:56 shows one nucleotide difference at position 706 G>A and HLA‐A*31:59 has a single nucleotide polymorphism at position 626 C>T.
Atorvastatin protects obese mice against hepatic ischemia–reperfusion injury by Toll‐like receptor‐4 suppression and endothelial nitric oxide synthase activation
Authors: Ajamieh Hussam , Farrell Geoffrey , Wong Heng Jian , Yu Jun , Chu Eagle , Chen Jeffrey , Teoh Narci
Published: March 2012

Background and Aim:  Steatosis accentuates the severity of hepatic ischemia–reperfusion injury (IRI). 3‐Hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitors (“statins”) protect the heart and brain against post‐ischemic injury, without necessarily lowering serum cholesterol. We tested whether 10‐day or 1‐day atorvastatin administration protects livers with fatty change or non‐alcoholic steatohepatitis (NASH) against IRI.

Methods:  Mice with dietary or genetic simple steatosis (SS) or NASH were subjected to 60 min of partial hepatic ischemia/24‐h reperfusion, with/without atorvastatin administered with food (5 mg/kg body weight) for 10 days, or injected intravenously (5 mg/kg) 24 h before ischemia. Liver injury, Toll‐like receptor‐4 (TLR4), cytokines/chemokines, endothelial nitric oxide synthase (eNOS), activation and thromboxane B2 production were determined.

Results:  Atorvastatin conferred 70–90% hepatic protection against IRI in obese animals with SS or NASH, in which IRI was accentuated twofold to fivefold. IRI markedly upregulated TLR4 and activated nuclear factor‐κB (NF‐κB); atorvastatin abrogated these effects, as well as activating eNOS. Atorvastatin dampened the post‐ischemic induction of thromboxane B2, macrophage inflammatory protein‐1a, monocyte chemotactic protein‐1, tumor necrosis factor‐α, interleukin (IL)‐12 p40, γ‐interferon, IL‐6, and adhesion molecules (vascular cell adhesion molecule‐1, E‐selectin, vascular endothelial–cadherin), and reduced macrophage and neutrophil recruitment. There was no reduction in serum cholesterol that could explain these effects, and hepatic cholesterol was normal in these mice. A single 24‐h injection of atorvastatin conferred equivalent hepatoprotection.

Conclusion:  Statins exert major hepatoprotection against IRI in lean, fatty, and NASH livers that is not due to cholesterol removal. Rather, statins downregulate TLR4 to prevent NF‐κB activation, with resultant suppression of adhesion molecules, chemokines/cytokines, and thromboxane B2 production. Short‐term statin treatment is an effective, readily‐available preventive agent against hepatic IRI, irrespective of obesity and fatty liver disease.
Impact of pretransplant antinuclear antibody and antismooth muscle antibody titers on disease recurrence and graft survival following liver transplantation in autoimmune hepatitis patients
Authors: Dbouk Nader , Parekh Samir
Published: March 2012

Background and Aims:  Disease recurrence following transplantation occurs in 20–45% of patients with autoimmune hepatitis (AIH). Factors associated with an increased risk of recurrence include human leukocyte antigen (HLA) DR3 and HLA DR4 positivity, inadequate immunosuppression, and severity of inflammation in the native liver. Titers of several autoantibodies can be elevated in patients with AIH, including antinuclear antibody (ANA) and antismooth muscle antibody (SMA); however, it is unclear whether or not the degree of elevation influences the risk of disease recurrence following transplantation.

Methods:  We conducted a retrospective study to evaluate the potential impact of pretransplant titers on post‐transplant outcomes for patients with AIH. Sixty‐three patients with AIH who underwent 72 liver transplants between 1 January 1989 and 1 January 2009 were included, with a median follow up of 10 months. Patients were divided into group A (ANA or SMA ≥ 1 : 160) and group B (titers ≤ 1 : 160).

Results:  There was no significant difference in the recurrence rates or death between patients in groups A and B, respectively. Only race appeared to impact outcomes, with African American patients having a higher incidence of death and recurrent disease post‐transplant compared to other ethnicities.

Conclusions:  Based on our findings, pretransplant ANA and SMA levels do not appear to impact recurrence rates or outcomes following liver transplantation for AIH.
Assessment of inflammation and fibrosis in non‐alcoholic fatty liver disease by imaging‐based techniques
Authors: Cobbold Jeremy F L , Patel Dhupal , Taylor‐Robinson Simon D
Published: March 2012

Non‐alcoholic fatty liver disease (NALFD) is a burgeoning global health problem, and the assessment of disease severity remains a clinical challenge. Conventional imaging and clinical blood tests are frequently unable to determine disease activity (the degree of inflammatory change) and fibrotic severity, while the applicability of histological examination of liver biopsy is limited. Imaging platforms provide liver‐specific structural information, while newer applications of these technologies non‐invasively exploit the physical and chemical characteristics of liver tissue in health and disease. In this review, conventional and newer imaging‐based techniques for the assessment of inflammation and fibrosis in NAFLD are discussed in terms of diagnostic accuracy, radio‐pathological correlations, and practical considerations. In particular, recent clinical studies of ultrasound (US)‐based and magnetic resonance elastography techniques are evaluated, while the potential of contrast‐enhanced US and magnetic resonance spectroscopy techniques is discussed.

The development and application of these techniques is starting to reduce the clinical need for liver biopsy, to produce surrogate end‐points for interventional and observational clinical studies, and through this, to provide new insights into the natural history of NAFLD.
Metabolic syndrome is an independent risk factor for synchronous colorectal neoplasm in patients with gastric neoplasm
Authors: Park Wan , Lee Hyuk , Kim Eun Hye , Yoon Ji Young , Park Jun Chul , Shin Sung Kwan , Lee Sang Kil , Lee Yong Chan , Kim Won Ho , Noh Sung Hoon
Published: March 2012

Background and Aim:  There are no data on how metabolic syndrome (MetS) affects the prevalence of synchronous colorectal neoplasm (CRN) in gastric neoplasm (GN) patients. The aim of this study was to investigate a model for risk stratification for colorectal screening by evaluating the clinical characteristics of synchronous CRN in GN patients classified according to the presence of MetS.

Methods:  A cross‐sectional, case‐control study of 492 patients (368 males and 124 females) with GN, and 492 age‐matched healthy controls undergoing simultaneous upper endoscopy and colonoscopy, was conducted.

Results:  The GN group involved 446 patients without MetS, and 46 patients with MetS. In total, 177 (39.7%) and 28 (60.9%) synchronous CRN were detected in GN patients without MetS and with MetS, respectively (P = 0.006). A total of 143 (34.7%) synchronous colorectal adenomas were detected in GN patients without MetS, whereas 17 (48.6%) were detected in GN patients with MetS (P = 0.101), as well as more synchronous colorectal cancers (11.2% vs 37.9%, P < 0.001). A multivariate logistic regression analysis revealed that the presence of GN (OR = 1.54, 95% CI: 1.18–2.00, P = 0.001) and the presence of MetS (odds ratio = 1.82, 95% confidence interval: 1.19–2.78, P = 0.006) were significant independent risk factors associated with the prevalence of CRN. The frequency of synchronous CRN in GN patients with MetS was 1.96 times greater than that in the GN group without MetS.

Conclusion:  The risk of synchronous CRN is significantly increased by the presence of GN, especially in MetS patients. Screening for synchronous CRN is highly recommended for GN patients with MetS.
Interleukin‐28B single nucleotide polymorphism of donors and recipients can predict viral response to pegylated interferon/ribavirin therapy in patients with recurrent hepatitis C after living donor liver transplantation
Authors: Kawaoka Tomokazu , Takahashi Shoichi , Takaki Shintaro , Hiramatsu Akira , Waki Koji , Hiraga Nobuhiko , Miki Daiki , Tsuge Masataka , Imamura Michio , Kawakami Yoshiiku , Aikata Hiroshi , Ochi Hidenori , Onoe Takashi , Tashiro Hirotaka , Ohdan Hideki , Chayama Kazuaki
Published: March 2012

Background and Aim:  Interleukin‐28B (IL28B) single nucleotide polymorphism (SNP) influences viral response (VR) to interferon (IFN) therapy in patients with hepatitis C. We studied the relationship between VR and the IL28B polymorphism (rs8099917) in patients on long‐term pegylated IFN plus ribavirin (PEGIFN/RBV) therapy for recurrent hepatitis C after living‐donor liver transplantation (LDLT).

Methods:  Thirty‐five patients with recurrent hepatitis C after LDLT were treated with PEGIFN/RBV. We evaluated the effect of IL28B SNP on the outcome in 20 patients infected with hepatitis C virus genotype 1 who completed IFN therapy.

Results:  The sustained VR (SVR) rate was 54% (19/35) for all patients; 46% (13/28) for genotype 1. The SVR rate of donors' TT group (major genotype) was higher than that of donors' TG + GG group (minor genotype) (73% vs 20%), while that of recipients' TT group was similar to that of recipients' TG + GG group (64% vs 50%). With regard to the combined effect of donors' and recipients' IL28B SNP, the SVR rates of TT : TT (donors' : recipients'), TT : TG + GG, TG + GG : any group were 81%, 50%, and 20%, respectively. The VR rate of TT : TT, TT : TG + GG and TG + GG : any group at 12 weeks were 28%, 0%, and 0%; those at 48 weeks were 70%, 50%, 20%, and those at the end of treatment were 100%, 50%, 20%, respectively. The multivariate analysis identified IL28B of donors : recipients (TT : TT) as the only independent determinant of SVR (odds ratio 15.0, P = 0.035).

Conclusion:  Measurement of donors' and recipients' IL28B SNP can predict the response to PEGIFN/RBV therapy, and the donors' IL28B SNP might be a more significant predictor than that of the recipients.
Non‐genetic risk factors and predicting efficacy for docetaxel–drug‐induced liver injury among metastatic breast cancer patients
Authors: Wang Zheng , Liang Xu , Yu Jing , Zheng Xiaohui , Zhu Yulin , Yan Ying , Dong Ningning , Di Lijun , Song Guohong , Zhou Xinna , Wang Xiaoli , Yang Huabing , Ren Jun , Lyerly Herbert Kim
Published: March 2012

Background and Aim:  Docetaxel has been chosen as one of the most popular anticancer drugs in the treatment of breast cancer for more than a decade. There is increasingly awareness for the occurrence of docetaxel and/or docetaxel–drug‐induced liver injury (DILI), although the underlying mechanism of occurrence and its risk factors remain unclear.

Methods:  We conducted a retrospective cohort study to identify non‐genetic risk factors for docetaxel–DILI among 647 metastasis breast cancer patients treated with docetaxel‐containing regimens.

Results:  Sixty‐seven (10.36%) patients were diagnosed as docetaxel–DILI. By logistic regression analysis, premenopausal status (odds ratio [OR][95% confidence interval {CI}] = 2.24 [1.30–3.87]), past hepatitis B virus (HBV) infections (OR [95% CI] = 4.23 [1.57–11.42]), liver metastasis (OR [95% CI] = 3.70 [2.16–6.34]). The predominant occurrence of DILI was seen in groups with docetaxel combination regimens. (OR [95% CI] = 2.66 [1.59–4.55]). The potential increasing occurrence of docetaxel–DILI was associated with multiple risk factors in an exposure–response manner (P < 0.001), and patients with more than three risk factors would be exposed to a 36.61‐fold risk of DILI (95% CI = 10.18–131.62). Further analysis by the risk score and area under the receiver–operator characteristic curve (AUC) showed that those four factors contributed to an AUC of 0.7536 (95% CI = 0.70–0.81), with a predictive sensitivity of 74.63% and specificity of 65.17%.

Conclusions:  Docetaxel–DILI with a relatively higher incidence should be addressed among metastatic breast cancer patients. Four predominant risk factors, including premenopausal status, past HBV infection, liver metastasis, and docetaxel combination regimens, were potential predicators for DILI.
Clinical utility of single‐operator cholangiopancreatoscopy using a SpyGlass probe through an endoscopic retrograde cholangiopancreatography catheter
Authors: Kawakubo Kazumichi , Isayama Hiroyuki , Sasahira Naoki , Kogure Hirofumi , Takahara Naminatsu , Miyabayashi Koji , Mizuno Suguru , Yamamoto Keisuke , Mohri Dai , Sasaki Takashi , Yamamoto Natsuyo , Nakai Yousuke , Hirano Kenji , Tada Minoru , Koike Kazuhiko
Published: March 2012

Background and Aim:  A single‐operator cholangiopancreatoscopy was developed to overcome a problem in conventional peroral cholangiopancreatoscopy. The aim of this pilot study was to clarify the clinical utility of single‐operator cholangiopancreatoscopy using a SpyGlass probe through an endoscopic retrograde cholangiopancreatography (ERCP) catheter.

Methods:  Patients undergoing ERCP with a SpyGlass probe passed through a catheter were included in this study. The SpyGlass probe was inserted into the catheter following successful cannulation, and cholangiopancreatoscopy was performed by a single operator. We retrospectively analyzed the successful visualization rate of this technique.

Results:  Fifteen patients were included in this study. SpyGlass cholangiopancreatoscopy was technically successful in all patients. Successful visualization was obtained in nine patients (60%). The median SpyGlass procedure time was 10 min. Cholangiopancreatoscopic diagnoses were as follows: bile duct carcinoma in three patients; intraductal papillary mucinous adenoma in two; and intraductal pancreatic stone, benign biliary stricture, gallbladder cholesterolosis, and gallbladder carcinoma in one each. There were no cases of post‐ERCP pancreatitis.

Conclusions:  While the low rate of successful visualization must be improved, single‐operator cholangiopancreatoscopy using a SpyGlass probe through an ERCP catheter is a safe and effective procedure.
Therapeutic potential of mesenchymal stem cells overexpressing human forkhead box A2 gene in the regeneration of damaged liver tissues
Authors: Cho Jong‐Woo , Lee Chul‐Young , Ko Yong
Published: March 2012

Background and Aim:  Although a liver transplantation is considered to be the only effective long‐term treatment in many cases of liver diseases, it is limited by a lack of donor organs and immune rejection. As an autologous stem cell approach, this study was conducted to assess whether forkhead box A2 (Foxa2) gene overexpression in bone marrow‐derived mesenchymal stem cells (MSC) could protect the liver from hepatic diseases by stimulating tissue regeneration after cell transplantation.

Methods:  Rat MSC (rMSC) were isolated, characterized, and induced to hepatocytes that expressed liver‐specific markers. Four different treatments (control [phosphate‐buffered saline], rMSC alone, rMSC/pIRES–enhanced green fluorescent protein (EGFP) vector, and rMSC/pIRES–EGFP/human Foxa2) were injected into the spleen of carbon tetrachloride‐injured rats. Biochemical and histological analyses on days 30, 60, and 90 post‐transplantation were performed to evaluate the therapeutic capacities of MSC overexpressing hFoxa2.

Results:  rMSC transfected with hFoxa2 were induced into hepatogenic linage and expressed several liver‐specific genes, such as, Foxa2, α‐fetoprotein, cytokeratin‐18, hepatocyte nuclear factor‐1α, and hepatocyte growth factor. A group of animals treated with MSC/hFoxa2 showed significant recovery of liver‐specific enzyme expressions to normal levels at the end of the study (90 days). Furthermore, when compared to the fibrotic areas of the samples treated with MSC alone or MSC/vector, the fibrotic area of the samples treated with rMSC/hFoxa2 for 90 days significantly decreased, until they were completely gone.

Conclusions:  Human Foxa2 efficiently promoted the incorporation of MSC into liver grafts, suggesting that hFoxa2 genes could be used for the structural or functional recovery of damaged liver cells.
The effect of partial acclimatization to high altitude on loop gain and central sleep apnoea severity
Authors: ANDREWS GARETH , AINSLIE PHILIP N. , SHEPHERD KELLY , DAWSON ANDREW , SWART MARIANNE , LUCAS SAMUEL , BURGESS KEITH R.
Published: March 2012

Background and objective:  Loop gain is an engineering term that predicts the stability of a feedback control system, such as the control of breathing. Based on earlier studies at lower altitudes, it was hypothesized that acclimatization to high altitude would lead to a reduction in loop gain and thus central sleep apnoea (CSA) severity.

Methods:  This study used exposure to very high altitude to induce CSA in healthy subjects to investigate the effect of partial acclimatization on loop gain and CSA severity. Measurements were made on 12 subjects (age 30 ± 10 years, body mass index 22.8 ± 1.9, eight males, four females) at an altitude of 5050 m over a 2‐week period upon initial arrival (days 2–4) and following partial acclimatization (days 12–14). Sleep was studied by full polysomnography, and resting arterial blood gases were measured. Loop gain was measured by the ‘duty cycle’ method (duration of hyperpnoea/cycle length).

Results:  Partial acclimatization to high‐altitude exposure was associated with both an increase in loop gain (duty cycle fell from 0.60 ± 0.05 to 0.55 ± 0.06 (P = 0.03)) and severity of CSA (apnoea‐hypopnoea index increased from 76.8 ± 48.8 to 115.9 ± 20.2 (P = 0.01)), while partial arterial carbon dioxide concentration fell from 29 ± 3 to 26 ± 2 (P = 0.01).

Conclusions:  Contrary to the results at lower altitudes, at high‐altitude loop gain and severity of CSA increased.
Climate change impacts on tree ranges: model intercomparison facilitates understanding and quantification of uncertainty
Authors: Cheaib Alissar , Badeau Vincent , Boe Julien , Chuine Isabelle , Delire Christine , Dufrêne Eric , François Christophe , Gritti Emmanuel S. , Legay Myriam , Pagé Christian , Thuiller Wilfried , Viovy Nicolas , Leadley Paul
Published: March 2012

Ecology Letters (2012)

Model‐based projections of shifts in tree species range due to climate change are becoming an important decision support tool for forest management. However, poorly evaluated sources of uncertainty require more scrutiny before relying heavily on models for decision‐making. We evaluated uncertainty arising from differences in model formulations of tree response to climate change based on a rigorous intercomparison of projections of tree distributions in France. We compared eight models ranging from niche‐based to process‐based models. On average, models project large range contractions of temperate tree species in lowlands due to climate change. There was substantial disagreement between models for temperate broadleaf deciduous tree species, but differences in the capacity of models to account for rising CO2 impacts explained much of the disagreement. There was good quantitative agreement among models concerning the range contractions for Scots pine. For the dominant Mediterranean tree species, Holm oak, all models foresee substantial range expansion.
Phosphorus and DOC availability influence the partitioning between bacterioplankton production and respiration in tidal marsh ecosystems
Authors: del Giorgio Paul A. , Newell Roger E. I.
Published: March 2012

The organic carbon consumed by aquatic bacteria (BCC) is partitioned between bacterial production (BP) and respiration (BR), but the factors that determine BCC and its partition into BP and BR are not well understood. We explored the coupling between BR, BR and BCC, and their links to dissolved organic carbon (DOC) and nutrient availability in natural and restored tidal marshes and in the adjoining waters of Delaware Bay estuary. Labile DOC (LDOC) ranged from 3% to 22% of the DOC pool, and explained more of the variance in both BR and BCC than did bulk DOC. Bacterial growth efficiency (BGE) was highly variable (0.09–0.58), and natural Spartina alterniflora marshes had consistently higher BGE than both restoration marshes and tidal floodwaters. BGE was negatively related to the ratio of LDOC to total dissolved phosphorous, which was highest in natural marshes. The enhancement of BP observed in the marshes relative to the estuarine floodwaters had different origins: In natural marshes it was mostly due to increases in BGE, whereas in restored marshes it followed increased BCC. These results highlight the importance of P in regulating microbial metabolism in coastal areas, and the need to understand the pathways that lead to BP in these systems.
Involvement of thermophilic archaea in the biocorrosion of oil pipelines
Authors: Davidova Irene A. , Duncan Kathleen E. , Perez‐Ibarra B. Monica , Suflita Joseph M.
Published: March 2012

Two thermophilic archaea, strain PK and strain MG, were isolated from a culture enriched at 80°C from the inner surface material of a hot oil pipeline. Strain PK could ferment complex organic nitrogen sources (e.g. yeast extract, peptone, tryptone) and was able to reduce elemental sulfur (S°), Fe3+ and Mn4+. Phylogenetic analysis revealed that the organism belonged to the order Thermococcales. Incubations of this strain with elemental iron (Fe°) resulted in the abiotic formation of ferrous iron and the accumulation of volatile fatty acids during yeast extract fermentation. The other isolate, strain MG, was a H2:CO2‐utilizing methanogen, phylogenetically affiliated with the genus Methanothermobacter family. Co‐cultures of the strains grew as aggregates that produced CH4 without exogenous H2 amendment. The co‐culture produced the same suite but greater concentrations of fatty acids from yeast extract than did strain PK alone. Thus, the physiological characteristics of organisms both alone and in combination could conceivably contribute to pipeline corrosion. The Thermococcus strain PK could reduce elemental sulfur to sulfide, produce fatty acids and reduce ferric iron. The hydrogenotrophic methanogen strain MG enhanced fatty acid production by fermentative organisms but could not couple the dissolution Fe° with the consumption of water‐derived H2 like other methanogens.
BETWEEN ‘MARX AND MARKETS’? THE STATE, THE ‘LEFT TURN’ AND NATURE IN ECUADOR
Authors: ARSEL MURAT
Published: March 2012

Ecuador is a prominent example of a Latin American country that has elected a left‐wing president who aims to create a post‐neoliberal development strategy. Many of the policies pursued by President Rafael Correa have focused on changing the relationship between nature and society. The new constitution of 2008, which grants rights to nature, adapts a new development model based on indigenous cosmology and strengthens the power and regulatory remit of the state over the economy and society, is an important statement of intent in this regard. The Yasuní‐ITT (Ishpingo‐Tambococha‐Tiputini) initiative to leave oil underground in exchange for international financial contributions is the most significant manifestation of this intent in actual policy. Analysis of two emblematic changes reveals that the creation of a post‐neoliberal development strategy has so far produced partial and uneven results. While nature and natural resources have come under stricter control by the state, this has not significantly diminished their commercialisation.
UNEVEN DEVELOPMENT AND ACCUMULATION BY DISPOSSESSION IN NATURE CONSERVATION: COMPARING RECENT TRENDS IN THE AZORES AND TANZANIA
Authors: NEVES KATJA , IGOE JIM
Published: March 2012

This paper applies Harvey's concepts of uneven development and accumulation by dispossession to nature conservation, comparatively, in the contexts of whale watching in the Azores and wildlife conservation in Tanzania. In both contexts, nature conservation revolves around processes of de‐regulation, re‐regulation, and territorialisation, facilitating new forms of capitalist expansion. Adapting Bourdieu's arguments and the inter‐changeability of different forms of capital, we provide ethnographic insight on how these processes unfold. Our analysis reveals two recent trends in nature‐society relations in late capitalism: (1) these processes are less determined by ownership than the ability to render different kinds of capital commensurable with one another; and (2) they depend on specific types of ‘performances’, which are encouraged and rewarded by neoliberal forms of environmental governance.
THE FINANCIAL CRISIS AND ENVIRONMENTAL GOVERNANCE ‘AFTER’ NEOLIBERALISM
Authors: MCCARTHY JAMES
Published: March 2012

The relationships between neoliberalism and environmental governance have been the topic of much scholarly and policy debate. The recent, and ongoing, economic crisis brings new questions and urgency to these debates. This paper examines whether and how the economic crisis might be understood as a crisis of neoliberalism and what the implications might be for environmental quality and the dominance of ‘neoliberal’ approaches to environmental governance. The paper attempts to delineate some of the major potential relationships between neoliberalism and environmental governance through this crisis. It argues that although such relationships are contingent and subject to political action, in the US context at least the ongoing economic crisis has resulted in a weakening of support for environmental protections, in a manner that does not fit with current claims of the ‘post‐political’ condition. The paper concludes by outlining several positive contributions critical geographers and other analysts of nature‐society relations could make to challenging the current dominance of neoliberal policies in environmental management.
Political Legitimacy, the Egalitarian Challenge, and Democracy
Authors: MACHIN DEAN J.
Published: March 2012

abstract

This article argues against the claim that democracy is a necessary condition of political legitimacy. Instead, I propose a weaker set of conditions. First, I explain the case for the necessity of democracy. This is that only democracy can address the ‘egalitarian challenge’, i.e. ‘if we are all equal, why should only some of us wield political power?’. I show that if democracy really is a necessary condition of political legitimacy, then (what I label) the problems of domestic justice and of international legitimacy become intractable. I then argue that the egalitarian challenge is addressed where the requirements of (1) horizontal equality, (2) acceptable vertical inequality, and (3) publicity, are met and where (4) citizens have some institutionalized opportunity for a voice in decisions. I show that these conditions can be realized in non‐democratic form and conclude by explaining how the four conditions can be employed to make the problems of domestic justice and of international legitimacy more tractable. Overall, my ambitions are limited. I do not offer an all‐things‐considered case against democracy but I do show that (some) forms of non‐democratic government are permissible.
The Timing of Quarterly ‘Pro Forma’ Earnings Announcements
Authors: Brown Nerissa C. , Christensen Theodore E. , Elliott W. Brooke
Published: March 2012

Abstract:  While some prior studies suggest that the timing of earnings announcements may reflect management's attempt to better inform investors, other studies suggest that managers opportunistically time their earnings releases in an effort to alter investors’ perceptions of firm performance. However, there is limited empirical evidence on the relation between earnings announcement timing and the manipulation of reported earnings. We extend this research by examining the timing of quarterly earnings announcements that contain an adjusted (‘pro forma’) earnings measure and whether managers’ behavior is more consistent with opportunistic or information‐related motives. We find that, on average, managers accelerate the timing of earnings announcements in quarters in which they disclose an adjusted earnings metric within the earnings press release relative to quarters in which they do not. In addition, we find that the acceleration of the earnings announcement increases with the level of managers’ exclusions of recurring expenses and their use of less transparent reconciliation formats. Consistent with managerial opportunism, we find that the recurring item exclusions used to calculate pro forma earnings in accelerated earnings announcements are of relatively lower quality and are more predictive of lower future earnings. We also find that investors fail to fully unravel the low‐quality nature of the recurring item exclusions used to calculate pro forma earnings in these accelerated announcements and that this failure is attenuated by managers’ use of less transparent reconciliation formats. Taken together, our results suggest that the acceleration of pro forma earnings news is at least partially attributable to managerial opportunism.