bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Chinese ‘daodi’ ‘the hell’ in English speakers’ L2 acquisition of Chinese daodi … wh … questions? Effects and recoverability of L1 transfer at L2 interfaces
Authors: Yuan Boping
Published: April 2012

This article presents a study investigating the effects and recoverability of L1 transfer at L2 syntax–semantics and syntax–discourse interfaces in English speakers’ L2 acquisition of Chinese daodi … wh-questions, which are considered approximate counterparts of wh-the-hell questions in English. English speakers are found to be able to acquire syntactic properties of daodi … wh-questions, but the syntactic structure of the question in their L2 Chinese is influenced by their L1 semantic and discourse constraints. Removing the L1 influences is found possible in some aspects, but recovering from the L1 transfer is persistently vulnerable at the syntax–discourse interface involving appropriate answers to Chinese daodi … wh … modal questions, where the L1 and the Chinese discourse conditions are found coexistent in their L2 Chinese. The developmental data of the L2 interfaces are discussed, and it is argued that the availability of positive evidence in the input plays an important role in L2 acquisition of interfaces, as in L2 acquisition of other linguistic aspects.
State monopoly of ‘permitted violation of human rights’: The decision of the Supreme Court of Israel prohibiting the private operation and management of prisons
Authors: Harding Richard
Published: April 2012

The emergence of private sector management of state prisons over the last 30 years has been controversial. It has been strongly argued that the administration of prisons is a core state function that, morally, should not be delegated. Proponents of this view contend that the State should directly manage its prisons even if it could be demonstrated that the privately managed prisons are superior to publicly managed prisons in achieving positive correctional outcomes or having less repressive regimes or being more sensitive to human rights. Hitherto, this strongly argued moral position has not been directly tested by litigation. In the case described in this article, a challenge to the proposed privatization of an Israel prison was challenged in the Israel Supreme Court. The challenge hinged on the meaning of the Basic Law of Israel which, it was argued, created a super-legislative constitutional right for prisoners to serve their sentences under the direct management of the State. The Supreme Court upheld this argument, in effect accepting that imprisonment is a core state function. It stated that all imprisonment per se contravenes Basic Law provisions relating to life, personal liberty and human dignity. To serve a sentence in a privately managed prison would be a further contravention of the Basic Law. Accordingly, the State should have a monopoly of ‘permitted violation of human rights’.

The article discusses the implications of this decision both within the domestic context of Israel’s imprisonment standards and from the point of view of whether the decision has wider significance for the growth of private management of prisons in other jurisdictions.
A contemporary study of the decision to incarcerate white‐collar and street property offenders
Authors: Van Slyke Shanna , Bales William D.
Published: April 2012

Conventional wisdom holds that white‐collar offenders operate with relative impunity because of widespread public and governmental apathy. The present study, however, examines whether public tolerance and governmental leniency toward white‐collar offenders have endured the series of national white‐collar crime scandals emerging in 2001–2002. This study analyzes sentencing guidelines data from Florida for the period 1994 to 2004, modeling legal and extra-legal factors related to the decision to incarcerate white‐collar and street property offenders. In/out incarceration sentences imposed upon white‐collar offenders are compared with those imposed upon burglars and thieves to determine whether 21st‐century white‐collar offenders are treated more leniently than street‐level property offenders. Additional analyses consider the roles of social status and of recent corporate scandals in influencing sentencing disparities. Findings indicate that, despite operating under sentencing guidelines designed to reduce disparities, white‐collar offenders are afforded greater leniency, though this relationship varies by the type of white‐collar crime considered, the offender's social status, and whether the sentencing occurred before or after the Enron scandal. Conclusions emphasize the salience of the definition of white‐collar crime when discussing punitiveness disparities and the relationship between white‐collar crime scandals and punishment.
The governance of sexual offending across Europe: Penal policies, political economies and the institutionalization of risk
Authors: McAlinden Anne-Marie
Published: April 2012

This article examines why England and Wales have comparatively one of the most stringent systems for the governance of sexual offending within Western Europe. While England and Wales, like the USA, have adopted broadly exclusionary, managerialist penal policies based around incapacitation and targeted surveillance, many other Western European countries have opted for more inclusionary therapeutic interventions. Divergences in state approaches to sex offender risk, particularly in relation to notification and vetting schemes, are initially examined with reference to the respective theoretical frameworks of ‘policy transfer’ and differing political economies. Chiefly, however, differences in penal policies are attributed to the social and political construction of risk and its control. There may be multiple expressions of risk relating to expert, lay, moral or emotive aspects. It is argued, however, that it is the particular convergence and alignment of these dimensions on the part of the various stakeholders in the UK – government, media, public and professional – that leads to risk becoming institutionalized in the form of punitive regulatory policies for managing the dangerous.
The Leveson Inquiry: Journalism ethics and press freedom
Authors: Petley Julian
Published: April 2012

The Leveson Inquiry into the Culture, Practice and Ethics of the Press invited a number of academics to address it on the subject of how ethics are taught on journalism courses at their universities. The evidence given on this subject was generally critical of the National Council for the Training of Journalists, and this evidence is resumed here. The article then goes on to address a related, but broader, issue posed by the inquiry, namely whether press freedom brings with it any obligations or responsibilities, particularly in respect of the democratic functions which the press is supposed to fulfill. The article argues that press freedom should consist of considerably more than the freedom of press owners, managers and editors to use their papers as they wish, and that the freedom of readers to access a wide range of trustworthy news and views should also be included in any truly democratic notion of press freedom.
‘Planning ethics’ and rediscovering the idea of planning
Authors: Campbell Heather
Published: April 2012

This paper is inspired by Sue Hendler’s considerable contributions to the field of ethics and planning. There can be few more insightful vantage points from which to view planning than through exploration of the field’s engagement with ethics. A perspective derived from ethics helps to cut through the analytical noise, to expose often troubling but fundamental issues about the very nature of planning. This paper examines how ethical concerns have been, and are being, understood in planning, and the profound questions which are posed about past, present and future intellectual and professional priorities. It concludes that the planning community needs to rediscover its ethical voice and its confidence in the idea of planning.
Help for children after child sexual abuse: Using a qualitative approach to design and test therapeutic interventions that may include non-offending parents
Authors: Hill Andrew
Published: April 2012

This article is about the use of qualitative methods in the design and development of new ways of intervening to help children who have been sexually abused. Specifically, it is about ways of including non-abusing parents and carers constructively in the intervention; about the complex, triangular relationships between social workers, children and parents that result; and about the contribution of qualitative methods to the design and development of such interventions. The difficulties of defining a precise model of intervention are discussed. But despite these difficulties, this article discusses the qualitative research strategies that were used to describe causal processes leading to outcomes and to identify factors that are indicative, or counter-indicative, of constructive parental involvement in children’s therapy. Using these methods it has been possible, first, to describe the dynamics of successful helping processes, second, to identify aspects of professional expertise and, finally, to identify ways in which service users are active in shaping interventions.
The ties that bind: Using ethnographic methods to understand service engagement
Authors: Stanhope Victoria
Published: April 2012

While rates of disengagement from mental health services remain high, the Housing First program has succeeded in engaging those who are hardest-to-reach, people who have experienced long-term homelessness and co-occurring disorders. This study uses ethnographic methods to explore service engagement within Housing First, focusing on how social processes contribute to program effectiveness. Conducting participant observation and interviews, researchers followed 10 clients and 14 case managers from two treatment teams, over the course of a year. The study used symbolic interactionism as its theoretical framework. In data analysis, therefore, the researchers explored meaning-making within social exchanges. The sites and activities of the program provided a context that made it possible for case managers and residents to create shared narratives about residents’ experiences related to housing. The variation of these sites and activities led case managers to permeate many aspects of clients’ lives, playing roles similar to those of friends and family. The quality of the interaction became apparent from how case managers paid attention, listened, and communicated while engaging in these shared activities. This study illustrates that while the structural aspects of Housing First provided the context and opportunities for engagement, the quality of the interaction between the case managers and residents played a key role in engagement.
Exploring the Links Between Macro-Level Contextual Factors and Their Influence on Nursing Workforce Composition
Authors: Squires Allison , Beltrán-Sánchez Hiram
Published: April 2012

Research that links macro-level socioeconomic development variables to health care human resources workforce composition is scarce at best. The purpose of this study was to explore the links between nonnursing factors and nursing workforce composition through a secondary, descriptive analysis of year 2000, publicly available national nursing human resources data from Mexico. Building on previous research, the authors conducted multiple robust regression analysis by federal typing of nursing human resources from 31 Mexican states against macro-level socioeconomic development variables. Average education in a state was significantly associated in predicting all types of formally educated nurses in Mexico. Other results suggest that macro-level indicators have a different association with each type of nurse. Context may play a greater role in determining nursing workforce composition than previously thought. Further studies may help to explain differences both within and between countries.
How Can I Live With(out) C. Wright Mills? Breaking With the Disembodied Truth
Authors: Tröger Mandy D.
Published: April 2012

Fifty years after his death, C. Wright Mills’s efforts to deconstruct unacknowledged power structures in the United States and his comprehensive critique of academia remain absent from the general curriculum. This is partly because Mills never pretended academic work wasn’t personal; his texts pay witness to the struggles of a man who used the written word to come to terms with himself. Mills aimed to grasp it all, to make individual troubles accessible by redefining them into social issues; he failed as much as he succeeded. I make Mills a comrade on my own intellectual journey and argue that rereading Mills allows young critical scholars to rethink current social theory and their own place within it. I show how, with a critical mind nourished rather than suppressed, rereading Mills can make you realize that you are not a crazy person.
Toward the Incorporation of Forgiveness Therapy in Healing the Wounds of Eating Disorders
Authors: Lander Alvin
Published: April 2012

This article describes the utilization of forgiveness therapy with a 26-year-old female recovering anorexic. She presents for treatment highly distressed over her commission of self-injurious behaviors and ensuing harm to her person. The process model is used to facilitate self-forgiveness. Emotion provides the main analytical context for the case study. The inability to manage negative affective states is seen as a significant factor contributing to the etiology of eating disorders (EDs). In the aftermath of eating disordered behaviors, negative feelings about the self may impede full recovery. In the therapeutic process described, it is the emotional changes attempted by the client that stand out as central in her eventual attainment of self-forgiveness. The implications of the case study for practitioners considering the use of forgiveness therapy with clients recovering from EDs, as well as the gamut of self-injurious behaviors, are considered. The important role of attachment processes in the utilization of this innovative therapeutic modality is underscored.
The Systems Theory of Autistogenesis
Authors: Malone J. Patrick
Published: April 2012

The systems theory of autistogenesis accounts for genetic and environmental predisposing factors for pervasive developmental disorders. During development, regions of the brain myelinate differentially, even while neuroinflammatory events induce neurological damage. Incorrect dietary ratios of docosahexaenoic acid (DHA) to arachidonic acid (AA) promote developmental aberration characteristic of autism spectrum disorders (ASD), and commercial infant formulae possesses DHA/AA ratios unsuitable for normal brain development in those predisposed. The aromatase gene regulates DHA/AA metabolism and represents a potential biomarker for ASD. Aromatase converts testosterone to estradiol. Estradiol is neuroprotective and a modulator of oxytocin receptors deficient in autism. Neuroprotective DHA is not well synthesized in males and is regulated by estradiol. Therefore, converging evidence indicates that any disturbance to the autistogenic system linking environment to neurobiology and genetics is capable of inducing developmental disorders with gender disparity.
Uncertainty Threat Can Cause Stereotyping
Authors: Wichman Aaron L.
Published: April 2012

Uncertainty threats can cause a wide range of compensatory responses. The present research demonstrates how uncertainty threat can cause a particular response with significant social consequences: stereotyping. Participants in this study completed a measure of implicit stereotyping after being exposed to an uncertainty threat or not. They also completed an individual difference measure to tap into their needs for predictability and structure. Results showed that uncertainty threat caused increased stereotyping of an ethnic out-group when needs for predictability and structure were high. For participants who did not have a high level of these needs, uncertainty did not increase stereotyping. When uncertainty threatens important goals such as prediction and control of events, individuals who most value these goals seem to be the ones who are most likely to use stereotypes. These stereotypes, ironically, may reduce the success of accurate event prediction for the very people who place the greatest value on predictability and structure.
The transcription factor Spi-B regulates human plasmacytoid dendritic cell survival through direct induction of the antiapoptotic gene BCL2-A1
Authors: Karrich Julien J. , Balzarolo Melania , Schmidlin Heike , Libouban Marion , Nagasawa Maho , Gentek Rebecca , Kamihira Shimeru , Maeda Takahiro , Amsen Derk , Wolkers Monika C. , Blom Bianca
Published: April 2012

Plasmacytoid dendritic cells (pDCs) selectively express Toll-like receptor (TLR)–7 and TLR-9, which allow them to rapidly secrete massive amounts of type I interferons after sensing nucleic acids derived from viruses or bacteria. It is not completely understood how development and function of pDCs are controlled at the transcriptional level. One of the main factors driving pDC development is the ETS factor Spi-B, but little is known about its target genes. Here we demonstrate that Spi-B is crucial for the differentiation of hematopoietic progenitor cells into pDCs by controlling survival of pDCs and its progenitors. In search for Spi-B target genes, we identified the antiapoptotic gene Bcl2-A1 as a specific and direct target gene, thereby consolidating the critical role of Spi-B in cell survival.
An activating intragenic deletion in NOTCH1 in human T-ALL
Authors: Haydu J. Erika , De Keersmaecker Kim , Duff Mary Kaye , Paietta Elisabeth , Racevskis Janis , Wiernik Peter H. , Rowe Jacob M. , Ferrando Adolfo
Published: April 2012

Oncogenic activating mutations in NOTCH1 occur in more than 50% of T-cell acute lymphoblastic leukemias (T-ALLs). In the present study, we describe a novel mechanism of NOTCH1 activation in T-ALL in which a deletion removing the 5′ portion of NOTCH1 abolishes the negative regulatory control of the extracellular domain and leads to constitutively active NOTCH1 signaling. Polypeptides translated from truncated transcripts encoded by the NOTCH1 deletion allele retain the transmembrane domain of the receptor and are constitutively cleaved by the γ-secretase complex, resulting in high levels of NOTCH1 signaling that can be effectively blocked by γ-secretase inhibitors. Our results expand the spectrum of oncogenic lesions activating NOTCH1 signaling in human T-ALL.
Unraveling the influence of endothelial cell density on VEGF-A signaling
Authors: Napione Lucia , Pavan Simona , Veglio Andrea , Picco Andrea , Boffetta Guido , Celani Antonio , Seano Giorgio , Primo Luca , Gamba Andrea , Bussolino Federico
Published: April 2012

Vascular endothelial growth factor-A (VEGF) is the master determinant for the activation of the angiogenic program leading to the formation of new blood vessels to sustain solid tumor growth and metastasis. VEGF specific binding to VEGF receptor-2 (VEGFR-2) triggers different signaling pathways, including phospholipase C-γ (PLC-γ) and Akt cascades, crucial for endothelial proliferation, permeability, and survival. By combining biologic experiments, theoretical insights, and mathematical modeling, we found that: (1) cell density influences VEGFR-2 protein level, as receptor number is 2-fold higher in long-confluent than in sparse cells; (2) cell density affects VEGFR-2 activation by reducing its affinity for VEGF in long-confluent cells; (3) despite reduced ligand-receptor affinity, high VEGF concentrations provide long-confluent cells with a larger amount of active receptors; (4) PLC-γ and Akt are not directly sensitive to cell density but simply transduce downstream the upstream difference in VEGFR-2 protein level and activation; and (5) the mathematical model correctly predicts the existence of at least one protein tyrosine phosphatase directly targeting PLC-γ and counteracting the receptor-mediated signal. Our data-based mathematical model quantitatively describes VEGF signaling in quiescent and angiogenic endothelium and is suitable to identify new molecular determinants and therapeutic targets.
Quantitative assessment of sensing and sequestration of spherocytic erythrocytes by the human spleen
Authors: Safeukui Innocent , Buffet Pierre A. , Deplaine Guillaume , Perrot Sylvie , Brousse Valentine , Ndour Alioune , Nguyen Marie , Mercereau-Puijalon Odile , David Peter H. , Milon Geneviève , Mohandas Narla
Published: April 2012

Splenic sequestration of RBCs with reduced surface area and cellular deformability has long been recognized as contributing to pathogenesis of several RBC disorders, including hereditary spherocytosis. However, the quantitative relationship between the extent of surface area loss and splenic entrapment remains to be defined. To address this issue, in the present study, we perfused ex vivo normal human spleens with RBCs displaying various degrees of surface area loss and monitored the kinetics of their splenic retention. Treatment with increasing concentrations of lysophosphatidylcholine resulted in a dose-dependent reduction of RBC surface area at constant volume, increased osmotic fragility, and decreased deformability. The degree of splenic retention of treated RBCs increased with increasing surface area loss. RBCs with a > 18% average surface area loss (> 27% reduced surface area-to-volume ratio) were rapidly and completely entrapped in the spleen. Surface-deficient RBCs appeared to undergo volume loss after repeated passages through the spleen and escape from splenic retention. The results of the present study for the first time define the critical extent of surface area loss leading to splenic entrapment and identify an adaptive volume regulation mechanism that allows spherocytic RBCs to prolong their life span in circulation. These results have significant implications for understanding the clinical heterogeneity of RBC membrane disorders.
Relationship between body composition, inflammation and lung function in overweight and obese asthma
Authors: Scott Hayley A , Gibson Peter G , Garg Manohar L , Pretto Jeffrey J , Morgan Philip J , Callister Robin , Wood Lisa G
Published: April 2012

Background

The obese-asthma phenotype is not well defined. The aim of this study was to examine both mechanical and inflammatory influences, by comparing lung function with body composition and airway inflammation in overweight and obese asthma.

Methods

Overweight and obese (BMI 28-40 kg/m2) adults with asthma (n = 44) completed lung function assessment and underwent full-body dual energy x-ray absorptiometry. Venous blood samples and induced sputum were analysed for inflammatory markers.

Results

In females, android and thoracic fat tissue and total body lean tissue were inversely correlated with expiratory reserve volume (ERV). Conversely in males, fat tissue was not correlated with lung function, however there was a positive association between android and thoracic lean tissue and ERV. Lower body (gynoid and leg) lean tissue was positively associated with sputum %neutrophils in females, while leptin was positively associated with android and thoracic fat tissue in males.

Conclusions

This study suggests that both body composition and inflammation independently affect lung function, with distinct differences between males and females. Lean tissue exacerbates the obese-asthma phenotype in females and the mechanism responsible for this finding warrants further investigation.
A quadruple mutant of Arabidopsis reveals a β-carotene hydroxylation activity for LUT1/CYP97C1 and a regulatory role of xanthophylls on determination of the PSI/PSII ratio
Authors: Fiore Alessia , Dall'Osto Luca , Cazzaniga Stefano , Diretto Gianfranco , Giuliano Giovanni , Bassi Roberto
Published: April 2012

Background

Xanthophylls are oxygenated carotenoids playing an essential role as structural components of the photosynthetic apparatus. Xanthophylls contribute to the assembly and stability of light-harvesting complex, to light absorbance and to photoprotection. The first step in xanthophyll biosynthesis from α- and β-carotene is the hydroxylation of ε- and β-rings, performed by both non-heme iron oxygenases (CHY1, CHY2) and P450 cytochromes (LUT1/CYP97C1, LUT5/CYP97A3). The Arabidopsis triple chy1chy2lut5 mutant is almost completely depleted in β-xanthophylls.

Results

Here we report on the quadruple chy1chy2lut2lut5 mutant, additionally carrying the lut2 mutation (affecting lycopene ε-cyclase). This genotype lacks lutein and yet it shows a compensatory increase in β-xanthophylls with respect to chy1chy2lut5 mutant. Mutant plants show an even stronger photosensitivity than chy1chy2lut5, a complete lack of qE, the rapidly reversible component of non-photochemical quenching, and a peculiar organization of the pigment binding complexes into thylakoids. Biochemical analysis reveals that the chy1chy2lut2lut5 mutant is depleted in Lhcb subunits and is specifically affected in Photosystem I function, showing a deficiency in PSI-LHCI supercomplexes. Moreover, by analyzing a series of single, double, triple and quadruple Arabidopsis mutants in xanthophyll biosynthesis, we show a hitherto undescribed correlation between xanthophyll levels and the PSI-PSII ratio. The decrease in the xanthophyll/carotenoid ratio causes a proportional decrease in the LHCII and PSI core levels with respect to PSII.

Conclusions

The physiological and biochemical phenotype of the chy1chy2lut2lut5 mutant shows that (i) LUT1/CYP97C1 protein reveals a major β-carotene hydroxylase activity in vivo when depleted in its preferred substrate α-carotene; (ii) xanthophylls are needed for normal level of Photosystem I and LHCII accumulation.
A composition and size controllable approach for Au-Ag alloy nanoparticles
Authors: Sun Li , Luan Weiling , Shan Yue Jin
Published: April 2012

A capillary micro-reaction was established for the synthesis of Au-Ag alloy nanoparticles (NPs) with a flexible and controllable composition and grain size by tuning the synthesis temperature, the residence time, or the mole ratio of Au3+:Ag+. By extending the residence time from 5 to 900 s, enhancing the temperature from 120°C to 160°C, or decreasing the mole ratio of Au3+:Ag+from 1:1 to 1:20, the composition of samples was changed continuously from Au-rich to Ag-rich. The particles became large with the increase of the residence time; however, synthesis temperatures showed less effect on the particle size change. The particle size of the Au-Ag alloy NPs with various composition could be kept by adjusting the mole ratio of Au3+:Ag+. TEM observation displayed that the as-obtained NPs were sphere-like with the smallest average size of 4.0 nm, which is half of those obtained by the traditional flask method.
Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling
Authors: Basak Jacob M , Kim Jungsu , Pyatkivskyy Yuriy , Wildsmith Kristin R , Jiang Hong , Parsadanian Maia , Patterson Bruce W , Bateman Randall J , Holtzman David M
Published: April 2012

Background

Abnormal proteostasis due to alterations in protein turnover has been postulated to play a central role in several neurodegenerative diseases. Therefore, the development of techniques to quantify protein turnover in the brain is critical for understanding the pathogenic mechanisms of these diseases. We have developed a bolus stable isotope-labeling kinetics (SILK) technique coupled with multiple reaction monitoring mass spectrometry to measure the clearance of proteins in the mouse brain.

Results

Cohorts of mice were pulse labeled with 13 C6-leucine and the brains were isolated after pre-determined time points. The extent of label incorporation was measured over time using mass spectrometry to measure the ratio of labeled to unlabeled apolipoprotein E (apoE) and amyloid β (Aβ). The fractional clearance rate (FCR) was then calculated by analyzing the time course of disappearance for the labeled protein species. To validate the technique, apoE clearance was measured in mice that overexpress the low-density lipoprotein receptor (LDLR). The FCR in these mice was 2.7-fold faster than wild-type mice. To demonstrate the potential of this technique for understanding the pathogenesis of neurodegenerative disease, we applied our SILK technique to determine the effect of ATP binding cassette A1 (ABCA1) on both apoE and Aβ clearance. ABCA1 had previously been shown to regulate both the amount of apoE in the brain, along with the extent of Aβ deposition, and represents a potential molecular target for lowering brain amyloid levels in Alzheimer's disease patients. The FCR of apoE was increased by 1.9- and 1.5-fold in mice that either lacked or overexpressed ABCA1, respectively. However, ABCA1 had no effect on the FCR of Aβ, suggesting that ABCA1 does not regulate Aβ metabolism in the brain.

Conclusions

Our SILK strategy represents a straightforward, cost-effective, and efficient method to measure the clearance of proteins in the mouse brain. We expect that this technique will be applicable to the study of protein dynamics in the pathogenesis of several neurodegenerative diseases, and could aid in the evaluation of novel therapeutic agents.
Pediatric T-cell prolymphocytic leukemia with an isolated 12(p13) deletion and aberrant CD117 expression
Authors: Bellone Michael , Svensson Annika M , Zaslav Ann-Leslie , Spitzer Silvia , Golightly Marc , Celiker Mahmut , Hu Youjun , Ma Yupo , Ahmed Tahmeena
Published: April 2012

T-cell Prolymphocytic leukemia (T-PLL) is a rare post-thymic T-cell malignancy that follows an aggressive clinical course. The classical presentation includes an elevated white blood cell (WBC) count with anemia and thrombocytopenia, hepatosplenomegaly, and lymphadenopathy. T-PLL is a disease of the elderly and to our knowledge it has never been described in the pediatric age group. We report a case of T-PLL in a 9 year old male who was initially diagnosed with T-cell acute lymphoblastic lymphoma (ALL), the diagnosis was later refined to T-PLL following additional analysis of bone marrow morphology and immunophenotype. Two unusual findings in our patient included CD117 expression and an isolated chromosomal 12(p13) deletion. The patient failed to respond to standard ALL induction chemotherapy, but achieved complete remission following treatment with a fludarabine and alemtuzumab-based regimen.
Decreased plasma concentrations of apolipoprotein M in sepsis and systemic inflammatory response syndromes
Authors: Kumaraswamy Sunil B , Linder Adam , Åkesson Per , Dahlbäck Björn
Published: April 2012

Introduction

Apolipoprotein M (apoM) is present in 5% of high-density lipoprotein (HDL) particles in plasma. It is a carrier of sphingosine-1-phosphate (S1P), which is important for vascular barrier protection. The aim was to determine the plasma concentrations of apoM during sepsis and systemic inflammatory response syndrome (SIRS) and correlate them to levels of apolipoprotein A-I (apoA1), apolipoprotein B (apoB), HDL-, and low-density lipoprotein (LDL)-cholesterol.

Methods

Plasma samples from patients with (1), severe sepsis with shock (n = 26); (2), severe sepsis without shock (n = 44); (3), sepsis (n = 100); (4), infections without SIRS (n = 43); and (5) SIRS without infection (n = 20) were analyzed. The concentrations of apoM, apoA1, and apoB were measured with enzyme-linked immunosorbent assays (ELISAs). Total, HDL-, and LDL-cholesterol concentrations were measured with a commercial HDL/LDL cholesterol test.

Results

ApoM concentrations correlated negatively to acute-phase markers. Thus, apoM behaved as a negative acute-phase protein. Decreased values were observed in all patient groups (P < 0.0001), with the most drastic decreases observed in the severely sick patients. ApoM levels correlated strongly to those of apoA1, apoB, HDL, and LDL cholesterol. The HDL and LDL cholesterol levels were low in all patient groups, as compared with controls (P < 0.0001), in particular, HDL cholesterol. ApoA1 and apoB concentrations were low only in the more severely affected patients.

Conclusions

During sepsis and SIRS, the plasma concentrations of apoM decrease dramatically, the degree of decrease reflecting the severity of the disease. As a carrier for barrier-protective S1P in HDL, the decrease in apoM could contribute to the increased vascular leakage observed in sepsis and SIRS.
Air–water oxygen exchange in a large whitewater river
Authors: Hall Robert O. , Kennedy Theodore A. , Rosi‐Marshall Emma J.
Published: April 2012

Lay Abstract

Air–water gas exchange governs the rate at which atmospheric gases flow into and out of aquatic ecosystems. Knowing this rate is necessary to calculate river photosynthesis and respiration, but there are few data from large rivers, and there are no data that include whitewater rapids. We studied the Colorado River, Grand Canyon; this river has flat reaches separated by extremely large, steep, whitewater rapids. We measured gas transfer velocity (the height of the water column that can exchange all of its gas per hour) by measuring how quickly the river gained oxygen as it flowed over the first 7 major rapids. The Colorado River has low oxygen concentration as it flows out of Glen Canyon Dam, located 25 kilometers upriver from Lees Ferry. We found that gas transfer velocity increased as river slope increased. Gas transfer velocity was low in flat reaches but was up to 800 times higher in rapids, which were the highest rates ever measured in a river. Based on the rate of change of oxygen concentration per meter of river drop, we estimated gas transfer velocity for the remainder of the Colorado River in Grand Canyon. Gas exchange varied 5‐fold depending on the slope of the immediate reach. Gas transfer velocity was higher for the Colorado River than for other aquatic ecosystems because of its large rapids. Our approach of scaling gas transfer velocity to the entire river will allow comparing gas transfer velocity across rivers that have variable river slopes, such as the Colorado River, Grand Canyon.
The impact of huts on physiological stress: a refinement in post-transport housing of male guineapigs (Cavia porcellus)
Authors: Walters Sherry L , Torres-Urbano Cristobal Jose , Chichester Lee , Rose Robert E
Published: April 2012

The ideal animal model would contribute no confounding variables in experimental science. Variables affect experimental design resulting in increased animal use or repeated studies. We demonstrated a simple refinement which may reduce the number of animals used experimentally while simultaneously improving animal welfare. The objective of this study was to determine if the presence of a hut was an impact on physiological stress levels, as determined by faecal cortisol concentration, during a routine four-day acclimatization period of newly received male Hartley-Outbred guineapigs. We hypothesized that those animals provided with huts would have decreased physiological stress compared with animals not provided with huts. We examined this effect within both paired and single-housed animals. A between-subjects one-way analysis of variance revealed that pair-housed animals with a hut had significantly lower faecal cortisol concentration than pair-housed animals without a hut and the presence and absence of a hut had no significant impact on faecal cortisol concentration in single-housed animals. These findings show that presence of a hut is beneficial in reducing physiological stress when pair housing male guineapigs and does not appear to have an impact when single housing male guineapigs. In addition, we have shown that faecal cortisol, and therefore physiological stress, is still increasing on study day 4 suggesting a longer acclimatization period is necessary. A simple refinement in housing environment and acclimatization time can both reduce the number of animals used experimentally and improve animal welfare.
Psychometric Properties of the Osteoporosis-Specific Morisky Medication Adherence Scale in Postmenopausal Women with Osteoporosis Newly Treated with Bisphosphonates
Authors: Reynolds Kristi , Viswanathan Hema N , O'Malley Cynthia D , Muntner Paul , Harrison Teresa N , Cheetham T Craig , Hsu Jin-Wen Y , Gold Deborah T , Silverman Stuart , Grauer Andreas , Morisky Donald E
Published: April 2012

Background:

Poor adherence to oral osteoporosis medications is common. Strategies for improving adherence begin with identification of the problem. The 8-item Morisky Medication Adherence Scale for self-reported adherence to antihypertensive medications was modified for assessing adherence to oral osteoporosis medications. An evaluation of the measurement properties of the Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) was needed.

Objective:

To examine the psychometric properties of the OS-MMAS in women with postmenopausal osteoporosis.

Methods:

Five hundred women aged 55 years and older with osteoporosis who were newly prescribed daily or weekly oral bisphosphonates between May 15, 2010, and August 15, 2010, were randomly selected from Kaiser Permanente Southern California, a large integrated health care delivery system, and mailed a self-administered survey that included the 8-item OS-MMAS, Self-Efficacy for Appropriate Medication Use Scale (SEAMS), Beliefs about Medicines Questionnaire (BMQ), Treatment Satisfaction Questionnaire for Medication (TSQM), Gastrointestinal Symptom Rating Scale (GSRS), and 12-item Short-Form Health Survey (SF-12v2). OS-MMAS scores can range from 0 to 8, with higher scores indicating better medication adherence. Internal consistency reliability was evaluated using Cronbach α coefficient. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs) in a subset of 102 participants. Construct validity was assessed using confirmatory (actor analysis and correlations between OS-MMAS and related measures.

Results:

Of 197 participants, 150 reported that they were still taking their bisphosphonate at the time of the survey and completed the OS-MMAS. Overall, 30.7%, 32.7%, and 36.7% had tow, medium, and high OS-MMAS scores (<6, 6 to <8, and 8, respectively). Cronbach α was 0.82 and the ICC was 0.77. Convergent validity was supported by significant correlations with SEAMS, BMQ necessity, and TSQM scores. In confirmatory factor analysis, a single-factor scale was supported.

Conclusions:

The OS-MMAS showed strong psychometric properties with good reliability and construct validity and may provide a valuable assessment of self-reported medication adherence in women newly prescribed oral osteoporosis medications.
Dantrolene Sodium for the Treatment of Aldesleukin-lnduced Rigors in a Melanoma Patient
Authors: Azari Laleh M , Sheehan Vivien S , Sachdev Jasgit C , Jones Terreia S
Published: April 2012

Objective:

To report the case of a 58-year-old male with melanoma who developed aldesleukin-induced rigors and was successfully treated with intravenous dantrolene sodium 20 mg and provide a review of the literature discussing other agents that have been used to treat drug-induced rigors.

Case Summary:

A 58-year-old male was treated with 720,000 IU/kg of aldesleukin every S hours as part of his antimelanoma therapy. The patient developed rigors after aldesleukin administration and was successfully treated with 25 mg of meperidine. Later, he experienced renal dysfunction that was also linked to aldesleukin therapy and developed normeperidine-induced neurotoxicity requiring discontinuation of meperidine therapy. The rigors were treated with intravenous dantrolene sodium 20 mg every 4 hours, with complete resolution of symptoms.

Discussion:

Several antineoplastic agents can cause rigors; many of these agents can also lead to renal failure. Several agents have been investigated for their use in the management o(rigors but can cause adverse effects or are unsuitable in the setting of renal insufficiency or failure. Although meperidine remains the mainstay for the treatment and prevention of rigors, it can be associated with neurotoxicity in some patients, particularly those with impaired renal function. Given that dantrolene has been shown to be effective against rigors, it may be a useful alternative for patients who can not tolerate meperidine. Drugs with a more favorable adverse effect profile that are not eliminated through the kidneys are needed.

Conclusions:

In the oncology setting, severe rigors can result in the interruption of a patient's cancer therapy, which can increase the risk of treatment failure. Dantrolene may be a useful alternative for patients experiencing rigors who can not tolerate meperidine.
Accumulation and Growth in the Shadow of Conflicts
Authors: Stauvermann Peter J.
Published: April 2012

We introduce a simple growth model to investigate how the evolution of a society is influenced by international conflicts. We come to the result that in the long run three equilibria are possible; a war equilibrium, a peace equilibrium or cycles between war and peace. Which kind of equilibrium will be achieved depends on the effectiveness of weapons, the distribution of capital, intertemporal preferences and the production technology. In general, we conclude that the achievement of a long-lasting sustainable peace is possible, if we restrict the degree of economic inequality. The model delivers a normative reasoning for the foundation and the conservation of the European Union, even if redistribution of national incomes must take place to conserve it.
Necdin Controls Foxo1 Acetylation in Hypothalamic Arcuate Neurons to Modulate the Thyroid Axis
Authors: Hasegawa Koichi , Kawahara Tomohiro , Fujiwara Kazushiro , Shimpuku Mayumi , Sasaki Tsutomu , Kitamura Tadahiro , Yoshikawa Kazuaki
Published: April 2012

The forkhead transcription factor Foxo1 regulates energy homeostasis by modulating gene expression in the hypothalamus. Foxo1 undergoes post-translational modifications such as phosphorylation and acetylation, which modulate its functional activities. Sirtuin1 (Sirt1), a nicotinamide adenine dinucleotide-dependent protein deacetylase, regulates the acetylation status of Foxo1 in mammalian cells. Necdin, a pleiotropic protein required for neuronal development and survival, interacts with both Sirt1 and p53 to facilitate p53 deacetylation. The necdin gene (Ndn), an imprinted gene transcribed only from the paternal allele, is strongly expressed in hypothalamic neurons. Here, we demonstrate that necdin controls the acetylation status of Foxo1in vivoin hypothalamic arcuate neurons to modulate the thyroid function. Necdin forms a stable ternary complex with Sirt1 and Foxo1, diminishes Foxo1 acetylation, and suppresses the transcriptional activity of Foxo1in vitro. PaternalNdnmutant mice express high levels of acetylated Foxo1 and mRNAs encoding agouti-related protein and neuropeptide Y in the hypothalamusin vivoduring the juvenile period. The mutant mice exhibit endocrine dysfunction characteristic of hypothalamic hypothyroidism. Chemically induced hyperthyroidism and hypothyroidism lead to hypothalamic responses similar to those under necdin-deficient and excessive conditions, respectively, suggesting that thyroid hormone serves as a negative regulator of this system. These results suggest that necdin regulates Foxo1 acetylation and neuropeptide gene expression in the arcuate neurons to modulate the hypothalamic–pituitary–thyroid axis during development.
Spatial Profile of Excitatory and Inhibitory Synaptic Connectivity in Mouse Primary Auditory Cortex
Authors: Levy Robert B. , Reyes Alex D.
Published: April 2012

The role of local cortical activity in shaping neuronal responses is controversial. Among other questions, it is unknown how the diverse response patterns reportedin vivo—lateral inhibition in some cases, approximately balanced excitation and inhibition (co-tuning) in others—compare to the local spread of synaptic connectivity. Excitatory and inhibitory activity might cancel each other out, or, whether one outweighs the other, receptive field properties might be substantially affected. As a step toward addressing this question, we used multiple intracellular recording in mouse primary auditory cortical slices to map synaptic connectivity among excitatory pyramidal cells and the two broad classes of inhibitory cells, fast-spiking (FS) and non-FS cells in the principal input layer. Connection probability was distance-dependent; the spread of connectivity, parameterized by Gaussian fits to the data, was comparable for all cell types, ranging from 85 to 114 μm. With brief stimulus trains, unitary synapses formed by FS interneurons were stronger than other classes of synapses; synapse strength did not correlate with distance between cells. The physiological data were qualitatively consistent with predictions derived from anatomical reconstruction. We also analyzed the truncation of neuronal processes due to slicing; overall connectivity was reduced but the spatial pattern was unaffected. The comparable spatial patterns of connectivity and relatively strong excitatory-inhibitory interconnectivity are consistent with a theoretical model where either lateral inhibition or co-tuning can predominate, depending on the structure of the input.
Scene Construction in Amnesia: An fMRI Study
Authors: Mullally Sinéad L. , Hassabis Demis , Maguire Eleanor A.
Published: April 2012

In recent years, there has been substantial interest in how the human hippocampus not only supports recollection of past experiences, but also the construction of fictitious and future events, and the leverage this might offer for understanding the operating mechanisms of the hippocampus. Evidence that patients with bilateral hippocampal damage and amnesia cannot construct novel or future scenes/events has been influential in driving this line of research forward. There are, however, some patients with hippocampal damage and amnesia who retain the ability to construct novel scenes. This dissociation may indicate that the hippocampus is not required for scene construction, or alternatively, there could be residual function in remnant hippocampal tissue sufficient to support the basic construction of scenes. Resolving this controversy is central to current theoretical debates about the hippocampus. To investigate, we used fMRI and a scene construction task to test patient P01, who has dense amnesia, ∼50% bilateral hippocampal volume loss, and intact scene construction. We found that scene construction in P01 was associated with increased activity in a set of brain areas, including medial temporal, retrosplenial, and posterior parietal cortices, that overlapped considerably with the regions engaged in control participants performing the same task. Most notably, the remnant of P01's right hippocampus exhibited increased activity during scene construction. This suggests that the intact scene construction observed in some hippocampal-damaged amnesic patients may be supported by residual function in their lesioned hippocampus, in accordance with theoretical frameworks that ascribe a vital role to the hippocampus in scene construction.