bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary edema and blood volume after aneurysmal subarachnoid hemorrhage: a prospective observational study
Authors: Hoff Reinier G , Rinkel Gabriel JE , Verweij Bon H , Algra Ale , Kalkman Cor J
Published: April 2010

Introduction

Pulmonary edema (PED) is a severe complication after aneurysmal subarachnoid hemorrhage (SAH). PED is often treated with diuretics and a reduction in fluid intake, but this may cause intravascular volume depletion, which is associated with secondary ischemia after SAH. We prospectively studied intravascular volume in SAH patients with and without PED.

Methods

Circulating blood volume (CBV) was determined daily during the first 10 days after SAH by means of pulse dye densitometry. CBV of 60-80 ml/kg was considered normal. PED was diagnosed from clinical signs and characteristic bilateral pulmonary infiltrates on the chest radiograph. We compared CBV, cardiac index, and fluid balance between patients with and without PED with weighted linear regression, taking into account only measurements from the first day after SAH through to the day on which PED was diagnosed. Differences were adjusted for age, bodyweight, and clinical condition.

Results

In total, 102 patients were included, 17 of whom developed PED after a mean of 4 days after SAH. Patients developing PED had lower mean CBV (56.6 ml/kg) than did those without PED (66.8 ml/kg). The mean difference in CBV was -11.3 ml/kg (95% CI, -16.5 to -6.1); adjusted mean difference, -8.0 ml/kg (95% CI, -14.0 to -2.0). After adjusting, no differences were found in cardiac index or fluid balance between patients with and without PED.

Conclusions

SAH patients developing pulmonary edema have a lower blood volume than do those without PED and are hypovolemic. Measures taken to counteract pulmonary edema must be balanced against the risk of worsening hypovolemia.

Trial registration

NTR1255.
One-year mortality, quality of life and predicted life-time cost-utility in critically ill patients with acute respiratory failure
Authors: Linko Rita , Suojaranta-Ylinen Raili , Karlsson Sari , Ruokonen Esko , Varpula Tero , Pettilä Ville ,   the FINNALI study investigators
Published: April 2010

Introduction

High daily intensive care unit (ICU) costs are associated with the use of mechanical ventilation (MV) to treat acute respiratory failure (ARF), and assessment of quality of life (QOL) after critical illness and cost-effectiveness analyses are warranted.

Methods

Nationwide, prospective multicentre observational study in 25 Finnish ICUs. During an eight-week study period 958 consecutive adult ICU patients were treated with ventilatory support over 6 hours. Of those 958, 619 (64.6%) survived one year, of whom 288 (46.5%) answered the quality of life questionnaire (EQ-5D). We calculated EQ-5D index and predicted lifetime quality-adjusted life years (QALYs) gained using the age- and sex-matched life expectancy for survivors after one year. For expired patients the exact lifetime was used. We divided all hospital costs for all ARF patients by the number of hospital survivors, and by all predicted lifetime QALYs. We also adjusted for those who died before one year and for those with missing QOL to be able to estimate the total QALYs.

Results

One-year mortality was 35% (95% CI 32 to 38%). For the 288 respondents median [IQR] EQ-5D index after one year was lower than that of the age- and sex-matched general population 0.70 [0.45 to 0.89] vs. 0.84 [0.81 to 0.88]. For these 288, the mean (SD) predicted lifetime QALYs was 15.4 (13.3). After adjustment for missing QOL the mean predicted lifetime (SD) QALYs was 11.3 (13.0) for all the 958 ARF patients. The mean estimated costs were 20.739 € per hospital survivor, and mean predicted lifetime cost-utility for all ARF patients was 1391 € per QALY.

Conclusions

Despite lower health-related QOL compared to reference values, our result suggests that cost per hospital survivor and lifetime cost-utility remain reasonable regardless of age, disease severity, and type or duration of ventilation support in patients with ARF.
Standard International Prognostic Index Remains a Valid Predictor of Outcome for Patients With Aggressive CD20+B-Cell Lymphoma in the Rituximab Era
Authors: Ziepert Marita , Hasenclever Dirk , Kuhnt Evelyn , Glass Bertram , Schmitz Norbert , Pfreundschuh Michael , Loeffler Markus
Published: April 2010

Purpose

The International Prognostic Index (IPI) is widely used for risk stratification of patients with aggressive B-cell lymphoma. The introduction of rituximab has markedly improved outcome, and R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisone) has become the standard treatment for CD20+diffuse large B-cell lymphoma. To investigate whether the IPI has maintained its power for risk stratification when rituximab is combined with CHOP, we analyzed the prognostic relevance of IPI in three prospective clinical trials.

Patients and Methods

In total, 1,062 patients treated with rituximab were included (MabThera International Trial [MInT], 380 patients; dose-escalated regimen of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (MegaCHOEP) trial, 72 patients; CHOP + rituximab for patients older than age 60 years [RICOVER-60] trial, 610 patients). A multivariate proportional hazards modeling was performed for single IPI factors under rituximab on event-free, progression-free, and overall survival.

Results

IPI score was significant for all three end points. Rituximab significantly improved treatment outcome within each IPI group resulting in a quenching of the Kaplan-Meier estimators. However, IPI was a significant prognostic factor in all three end points and the ordering of the IPI groups remained valid. The relative risk estimates of single IPI factors and their order in patients treated with R-CHOP were similar to those found with CHOP.

Conclusion

The effects of rituximab were superimposed on the effects of CHOP with no interactions between chemotherapy and antibody therapy. These results demonstrate that the IPI is still valid in the R-CHOP era.
Adipocyte-Derived Microvesicles Are Associated with Multiple Angiogenic Factors and Induce Angiogenesis in Vivo and in Vitro
Authors: Aoki Naohito , Yokoyama Rumi , Asai Noriyuki , Ohki Makiko , Ohki Yuichi , Kusubata Kaori , Heissig Beate , Hattori Koichi , Nakagawa Yoshimi , Matsuda Tsukasa
Published: April 2010

We previously reported that 3T3-L1 and rat primary adipocytes secreted microvesicles, known as adipocyte-derived microvesicles (ADMs). In the present study, we further characterized the 3T3-L1 ADMs and found that they exhibited angiogenic activity in vivo. Antibody arrays and gelatin zymography analyses revealed that several angiogenic and antiangiogenic proteins, including leptin, TNFα, acidic fibroblast growth factor (FGFa), interferon-γ, and matrix metalloprotease (MMP)-2 and MMP-9, were present in the ADMs. Gene expression of most of these angiogenic factors was induced in the adipose tissue of diet-induced obese mice. Furthermore, leptin, TNFα, and MMP-2 were up-regulated at the protein level in the adipocyte fractions prepared from epididymal adipose tissues of high-fat-diet-induced obese mice. ADMs induced cell migration and tube formation of human umbilical vein endothelial cells, which were partially suppressed by neutralizing antibodies to leptin, TNFα, or FGFa but not to interferon-γ. Supporting these data, a mixture of leptin, TNFα, and FGFa induced tube formation. ADMs also promoted cell invasion of human umbilical vein endothelial cells through Matrigel, which was suppressed by the addition of the MMP inhibitor 1,10′-phenanthroline and a neutralizing antibody to MMP-2 but not to MMP-9. These results suggest that ADMs are associated with multiple angiogenic factors and play a role in angiogenesis in adipose tissue.
Prolonged Atrial Natriuretic Peptide Exposure Stimulates Guanylyl Cyclase-A Degradation
Authors: Flora Darcy R. , Potter Lincoln R.
Published: April 2010

Natriuretic peptide receptor-A (NPR-A), also known as guanylyl cyclase-A, is a transmembrane receptor guanylyl cyclase that is activated by the cardiac hormones atrial natriuretic peptide and B-type natriuretic peptide. Although ligand-dependent NPR-A degradation (also known as down-regulation) is widely acknowledged in human and animal models of volume overload, down-regulation in cultured cells is controversial. Here, we examined the effect of ANP exposure on cellular NPR-A levels as a function of time. Relative receptor concentrations were estimated using guanylyl cyclase and immunoblot assays in a wide variety of cell lines that endogenously or exogenously expressed low or high numbers of receptors. ANP exposures of 1 h markedly reduced hormone-dependent but not detergent-dependent guanylyl cyclase activities in membranes from exposed cells. However, 1-h ANP exposures did not significantly reduce NPR-A concentrations in any cell line. In contrast, exposures of greater than 1 h reduced receptor concentrations in a time-dependent manner. The time required for half of the receptors to be degraded (t1/2) in primary bovine aortic endothelial and immortalized HeLa cells was approximately 8 h. In contrast, a 24-h exposure of ANP to 293T cells stably overexpressing NPR-A caused less than half of the receptors to be degraded. To our knowledge, this is the first report to directly measure NPR-A down-regulation in endogenously expressing cells. We conclude that down-regulation is a universal property of NPR-A but is relatively slow and varies with receptor expression levels and cell type.
Humoral Autoimmunity against the Extracellular Domain of the Neuroendocrine Autoantigen IA-2 Heightens the Risk of Type 1 Diabetes
Authors: Morran Michael P. , Casu Anna , Arena Vincent C. , Pietropaolo Susan , Zhang Ying-Jian , Satin Leslie S. , Nelson Patrick , Omenn Gilbert S. , Trucco Massimo , Becker Dorothy J. , Pietropaolo Massimo
Published: April 2010

The objective of this study was to determine whether antigenic determinants localized within the extracellular domain of the neuroendocrine autoantigen tyrosine phosphatase-like protein IA-2 are targets of humoral responses in type 1 diabetes (T1DM). Previous studies indicated that the immunodominant region of IA-2 is localized within its intracellular domain (IA-2ic; amino acids 601–979). We analyzed 333 subjects from the Children’s Hospital of Pittsburgh study, 102 of whom progressed to insulin-requiring diabetes (prediabetics). Autoantibodies from these individuals were initially assayed for ICA512bdc (Barbara Davis Center amino acids 257–556; 630–979), IA-2ic (amino acids 601–979), and IA-2 full-length (amino acids 1–979) in addition to islet cell antibody (ICA), glutamic acid decarboxylase, 65-kDa isoform, and insulin autoantibodies. We identified an autoantibody response reactive with the extracellular domain of IA-2 that is associated with very high risk of T1DM progression. Relatives with no detectable autoantibodies against ICA512bdc (or IA-2ic) exhibited antibody responses against the IA-2 full-length peptide (log rank, P = 0.008). This effect was also observed in first-degree relatives who were positive for glutamic acid decarboxylase, 65–kDa isoform (log rank, P = 0.026) or at least two islet autoantibodies but were negative for ICA512bdc (log rank, P = 0.022). Competitive binding experiments and immunoprecipitation of the IA-2 extracellular domain (amino acid residues 26–577) further lend support for the presence of autoantibodies reactive with new antigenic determinants within the extracellular domain of IA-2. In summary, the addition of measurements of autoantibodies reactive with the IA-2 extracellular domain to assays geared to assess the progression of autoimmunity to clinical T1DM may more accurately characterize this risk. This has considerable implications not only for stratifying high diabetes risk but also facilitating the search for pathogenic epitopes to enable the design of peptide-based immunotherapies that may prevent the progression to overt T1DM at its preclinical stages.
The Calcemic Response to Continuous Parathyroid Hormone (PTH)(1-34) Infusion in End-Stage Kidney Disease Varies According to Bone Turnover: A Potential Role for PTH(7-84)
Authors: Wesseling-Perry Katherine , Harkins G. Chris , Wang He-jing , Elashoff Robert , Gales Barbara , Horwitz Mara J. , Stewart Andrew F. , Jüppner Harald , Salusky Isidro B.
Published: April 2010

Context: Factors contributing to PTH resistance in dialysis patients remain elusive.

Objectives: The study assessed the skeletal and biochemical response to 46 h of PTH(1-34) infusion in dialysis patients.

Design: The study was a prospective, controlled assessment of response to PTH(1-34).

Setting: The study was performed at the University of California, Los Angeles, General Clinical Research Center.

Participants: Nineteen dialysis patients and 17 healthy volunteers were studied.

Intervention: PTH(1-34) was infused at a rate of 8 pmol/kg · h for 46 h. Bone biopsy was performed in all dialysis patients.

Main Outcome Measures: Serum calcium, phosphorus, 1,25-dihydroxyvitamin D, PTH (four separate assays), and FGF-23 were determined at baseline and h 7, 23, 35, and 46 of the infusion.

Results: Serum calcium levels rose in healthy volunteers (9.2 ± 0.1 to 11.9 ± 0.3 mg/dl; P < 0.01) and in dialysis patients with adynamic/normal bone turnover (9.0 ± 0.3 to 10.7 ± 0.7 mg/dl; P < 0.05) but did not change in dialysis patients with high bone turnover. Serum phosphorus levels declined in healthy volunteers (3.9 ± 0.1 to 3.5 ± 0.1 mg/dl; P < 0.05) but increased in all dialysis patients (6.7 ± 0.4 to 8.0 ± 0.3 mg/dl; P < 0.05). Full-length PTH(1-84) declined in all subjects; however, PTH(7-84) fragments declined only in healthy subjects and in dialysis patients with normal/adynamic bone but remained unchanged in dialysis patients with high bone turnover.

Conclusions: The skeleton of dialysis patients with high bone turnover is resistant to the calcemic actions of PTH. PTH(7-84) may contribute to this phenomenon.
Assessment of Serum Apelin Levels in Girls with Anorexia Nervosa
Authors: Ziora Katarzyna , Oświęcimska Joanna , Świętochowska Elżbieta , Ziora Dariusz , Ostrowska Zofia , Stojewska Małgorzata , Klimacka-Nawrot Ewa , Dyduch Antoni , Błońska-Fajfrowska Barbara
Published: April 2010

Context: Pilot studies in rats have suggested that apelin (APE) is involved in the control of appetite and food intake. APE is secreted in the organs involved in the control of hunger and satiety: the stomach, hypothalamus, and fat tissue. Anorexia nervosa (AN) is an eating disorder that represents a good biological model of chronic fat tissue atrophy in humans. To date, there are no reports of APE expression in the fat tissue and its circulating concentrations in patients with AN.

Objective: Our objective was to assess serum APE concentrations in girls with AN.

Design, Participants, and Setting: APE-36 and APE-12 serum concentrations were evaluated in 87 Polish girls with restrictive AN, in 61 healthy (H) controls, 17 girls with no otherwise specified eating disorders (NOS), and 30 girls with simple obesity (OB).

Results: Mean serum APE-36 and APE-12 concentrations in patients with AN and NOS were significantly lower than in the H and OB groups. However, no differences between AN, H, and NOS groups were observed when APE concentrations were calculated per body mass index (BMI). In participants with normal BMI, serum APE-36 (r = 0.35) and APE-12 (r = 0.37) concentrations correlated positively with BMI.

Conclusions: We conclude that compared with H controls, serum APE-36 and APE-12 concentrations decreased as a result of fat tissue depletion in patients with AN. Conversely, obese adolescents had elevated APE-36 and APE-12 due to excessive fat mass as well as increased APE production in adipose tissue.
A New Missense Mutation in the Leptin Gene Causes Mild Obesity and Hypogonadism without Affecting T Cell Responsiveness
Authors: Fischer-Posovszky Pamela , von Schnurbein Julia , Moepps Barbara , Lahr Georgia , Strauss Gudrun , Barth Thomas F. , Kassubek Jan , Mühleder Hannes , Möller Peter , Debatin Klaus-Michael , Gierschik Peter , Wabitsch Martin
Published: April 2010

Objective: Leptin, a protein product of adipocytes, plays a critical role in the regulation of body weight, immune function, pubertal development, and fertility. So far, only three homozygous mutations in the leptin gene in a total of 13 individuals have been found leading to a phenotype of extreme obesity with marked hyperphagia and impaired immune function.

Design: Serum leptin was measured by ELISA. The leptin gene (OB) was sequenced in patient DNA. The effect of the identified novel mutation was assessed using HEK293 cells.

Results: We describe a 14-yr-old child of nonobese Austrian parents without known consanguinity. She had a body mass index of 31.5 kg/m2 (+2.46 sd score) and undetectable leptin serum levels. Sequencing of the leptin gene revealed a hitherto unknown homozygous transition (TTA to TCA) in exon 3 of the LEP gene resulting in a L72S replacement in the leptin protein. RT-PCR, Western blot, and immunohistochemical analysis indicated that the mutant leptin was expressed in the patient’s adipose tissue but retained within the cell. Using a heterologous cell system, we confirmed this finding and demonstrated that the side chain of Leu72 is crucial for intracellular leptin trafficking. Our patient showed signs of a hypogonadotropic hypogonadism. However, in contrast to the literature, she showed only mild obesity and a normal T cell responsiveness.

Conclusions: These findings shed a new light on the clinical consequences of leptin deficiency. Congenital leptin deficiency should be considered possible in pediatric patients with mild obesity even if parents are lean and unrelated.
Congenital Idiopathic Hypogonadotropic Hypogonadism: Evidence of Defects in the Hypothalamus, Pituitary, and Testes
Authors: Sykiotis Gerasimos P. , Hoang Xuan-Huong , Avbelj Magdalena , Hayes Frances J. , Thambundit Apisadaporn , Dwyer Andrew , Au Margaret , Plummer Lacey , Crowley William F. , Pitteloud Nelly
Published: April 2010

Context: Idiopathic hypogonadotropic hypogonadism (IHH) with normal smell (normosmic IHH) or anosmia (Kallmann syndrome) is associated with defects in the production or action of GnRH. Accordingly, most IHH patients respond to physiological pulsatile GnRH replacement by normalizing serum LH, FSH, and testosterone (T) levels and achieving gametogenesis; some patients, however, show atypical responses. Interestingly, several IHH-associated genes are expressed in multiple compartments of the hypothalamic-pituitary-gonadal axis.

Objective: The aim of the study was to investigate whether the clinical, biochemical, or genetic characteristics of IHH men with atypical responses to GnRH indicate alternative or additional defects in the hypothalamic-pituitary-gonadal axis.

Subjects: We studied 90 IHH men undergoing long-term pulsatile GnRH treatment over 30 yr.

Design and Setting: We conducted a retrospective study of response to GnRH at a Clinical Research Center.

Interventions: Physiological regimens of pulsatile sc GnRH were administered for at least 12 months. Dose-response studies using iv GnRH pulses assessed the pituitary LH response.

Main Outcome Measures: We measured serum T, LH, FSH, and inhibin B levels, sperm in ejaculate, and determined the sequence of IHH-associated genes.

Results: Twenty-six percent of subjects displayed atypical responses to GnRH: 1) 10 remained hypogonadotropic and hypogonadal, demonstrating pituitary and testicular defects; 2) eight achieved spermatogenesis and normal T but only with hypergonadotropism, indicating impaired testicular responsiveness to gonadotropins; and 3) five remained azoospermic despite achieving adult testicular volumes and normal hormonal profiles, suggesting primary defects in spermatogenesis. Mutations were identified only in KAL1 across groups.

Conclusion: In addition to hypothalamic GnRH deficiency, IHH men can have primary pituitary and/or testicular defects, which are unmasked by GnRH replacement.
Circulating Adiponectin Is Associated with Obesity and Serum Lipids in West Africans
Authors: Meilleur Katherine G. , Doumatey Ayo , Huang Hanxia , Charles Bashira , Chen Guanjie , Zhou Jie , Shriner Daniel , Adeyemo Adebowale , Rotimi Charles
Published: April 2010

Context: Adiponectin, a hormone secreted by adipose tissue, has both metabolic and antiinflammatory properties. Although multiple studies have described the relationship between adiponectin and obesity in several human populations, no large studies have evaluated this relationship in Africans.

Objective: We investigated the relationship between adiponectin and measures of obesity, serum lipids, and insulin resistance in a large African cohort.

Design: Participants are from the Africa America Diabetes Mellitus (AADM) Study, a case-control study of genetic and other risk factors associated with development of type 2 diabetes in Africans.

Setting: Patients were recruited from five academic medical centers in Nigeria and Ghana (Accra and Kumasi in Ghana and Enugu, Ibadan, and Lagos in Nigeria) over 10 yr.

Main Outcome Measures: Circulating adiponectin levels were measured in 690 nondiabetic controls using an ELISA. The correlation between log-transformed circulating adiponectin levels and age, gender, measures of obesity (body mass index, waist circumference, and percent fat mass), and serum lipid levels was assessed. Linear regression was used to explore the association between adiponectin levels and measures of obesity, lipids, and insulin resistance as measured by homeostasis model assessment.

Results: Significant negative associations were observed between log-adiponectin levels and measures of obesity after adjusting for age and gender. Similarly, log-adiponectin levels were significantly negatively associated with serum triglycerides and insulin resistance but positively associated with high-density lipoprotein-cholesterol and total cholesterol after adjusting for age, gender, and body mass index.

Conclusions: Circulating adiponectin is significantly associated with measures of obesity, serum lipids, and insulin resistance in this study of West African populations.
c-Myc Is Required for the ChREBP-Dependent Activation of Glucose-Responsive Genes
Authors: Zhang Pili , Metukuri Mallikarjurna R. , Bindom Sharell M. , Prochownik Edward V. , O'Doherty Robert M. , Scott Donald K.
Published: April 2010

Glucose regulates programs of gene expression that orchestrate changes in cellular phenotype in several metabolically active tissues. Carbohydrate response element-binding protein (ChREBP) and its binding partner, Mlx, mediate glucose-regulated gene expression by binding to carbohydrate response elements on target genes, such as the prototypical glucose-responsive gene, liver-type pyruvate kinase (Pklr). c-Myc is also required for the glucose response of the Pklr gene, although the relationship between c-Myc and ChREBP has not been defined. Here we describe the molecular events of the glucose-mediated activation of Pklr and determine the effects of decreasing the activity or abundance of c-Myc on this process. Time-course chromatin immunoprecipitation revealed a set of transcription factors [hepatocyte nuclear factor (HNF)1α, HNF4α, and RNA polymerase II (Pol II)] constitutively resident on the Pklr promoter, with a relative enrichment of acetylated histones 3 and 4 in the same region of the gene. Glucose did not affect HNF1α binding or the acetylation of histones H3 or H4. By contrast, glucose promoted the recruitment of ChREBP and c-Myc and increased the occupancy of HNF4α and RNA Pol II, which were coincident with the glucose-mediated increase in transcription as determined by a nuclear run-on assay. Depletion of c-Myc activity using a small molecule inhibitor (10058-F4/1RH) abolished the glucose-mediated recruitment of HNF4α, ChREBP, and RNA Pol II, without affecting basal gene expression, histone acetylation, and HNF1α or basal HNF4α occupancy. The activation and recruitment of ChREBP to several glucose-responsive genes were blocked by 1RH, indicating a general necessity for c-Myc in this process.
Mouse Oocytes Enable LH-Induced Maturation of the Cumulus-Oocyte Complex via Promoting EGF Receptor-Dependent Signaling
Authors: Su You-Qiang , Sugiura Koji , Li Qinglei , Wigglesworth Karen , Matzuk Martin M. , Eppig John J.
Published: April 2010

LH triggers the maturation of the cumulus-oocyte complex (COC), which is followed by ovulation. These ovarian follicular responses to LH are mediated by epidermal growth factor (EGF)-like growth factors produced by granulosa cells and require the participation of oocyte-derived paracrine factors. However, it is not clear how oocytes coordinate with the EGF receptor (EGFR) signaling to achieve COC maturation. The aim of the present study was to test the hypothesis that oocytes promote the expression of EGFR by cumulus cells, thus enabling them to respond to the LH-induced EGF-like peptides. Egfr mRNA and protein expression were dramatically reduced in cumulus cells of mutant mice deficient in the production of the oocyte-derived paracrine factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15). Moreover, microsurgical removal of oocytes from wild-type COCs dramatically reduced expression of Egfr mRNA and protein, and these levels were restored by either coculture with oocytes or treatment with recombinant GDF9 or GDF9 plus recombinant BMP15. Blocking Sma- and Mad-related protein (SMAD)2/3 phosphorylation in vitro inhibited Egfr expression in wild-type COCs and in GDF9-treated wild-type cumulus cells, and conditional deletion of Smad2 and Smad3 genes in granulosa cells in vivo resulted in the reduction of Egfr mRNA in cumulus cells. These results indicate that oocytes promote expression of Egfr in cumulus cells, and a SMAD2/3-dependent pathway is involved in this process. At least two oocyte-derived growth factors, GDF9 and BMP15, are required for EGFR expression by cumulus cells.
Visual Interpretations, Print, and Illustrations of Thomson's The Seasons, 1730 – 1797
Authors: Jung Sandro
Published: April 2010

In a reading of James Thomson's The Seasons that largely draws on the history of the book and the fields of print culture and illustration studies, I offer a narrative of the changing interpretation of the poem between 1730 and 1797. Not only did readers, in response to changes in zeitgeist, alter their consumption and reading practices of the text, but they also interpreted the poem by translating it into a range of different media such as furniture prints, porcelain designs, sculpture, and book illustrations. I shall examine different responses to Thomson's poem by discussing a number of illustrations that were printed in editions, published both in London and the newly emerging regional publishing centers but disseminated across Britain. Apart from documenting the representational shift from depicting the poem as theodicy to reading it as a narrative of nature and domesticity, I shall relate my discussion of the illustrations to changes in technology, the reading revolution, and the skillful marketing strategies of both cheaply produced and luxurious editions of The Seasons in the late eighteenth century. By contextualizing the production within a new midcentury book trade that catered to different classes of readers, the essay makes a contribution to understanding Thomson's text as a cultural classic of iconic significance that was being reinvented (in ever new media and interpretations) throughout the second half of the eighteenth and the first half of the ninteenth centuries.
The Prince and the Pauper
Authors: Michnik Adam
Published: April 2010

This memorial to Leszek Kołakowski by perhaps his most famous student—a cofounder of the Solidarity movement—treats Kołakowski's life story only in passing. Not a conventional eulogy, the essay runs extensively through several of the arguments Kołakowski made over the years that taught the Polish “Generation of `68” how best to undo oppression and why they should do so. Emphasis falls on the difficulty, unpredictability, and unclassifiable features of Kołakowski's writings—features that, paradoxically, did not stand in the way of his becoming not only the “prince of philosophers,” but also the best known and even the most popular thinker in Poland of the half-century following World War II.
“Decorate the Dungeon”: A Dialogue in Place of an Introduction
Authors: Perl Jeffrey M. , Richmond Colin , Sachedina Abdulaziz , Arsić Branka , Envoi Anonymous
Published: April 2010

In the place of an introduction to part 5 of the Common Knowledge symposium on forms of quietism, the journal's editor and one of its longtime columnists discuss, in dialogue format, the case of Thomas More. Could he have evaded martyrdom at the hands of Henry VIII and Thomas Cromwell? One discussant argues that More could not have done so without contemptibly abandoning his principles and surrendering fully to despotism. The other discussant disagrees, suggesting that More had to abandon some of his principles one way or the other—in resisting despotism, however quietly, More did serious harm to his wife and daughter, to the European humanist movement, and to the cause of English Catholics.
von Hippel-Lindau protein regulates transition from the fetal to the adult circulatory system in retina
Authors: Kurihara Toshihide , Kubota Yoshiaki , Ozawa Yoko , Takubo Keiyo , Noda Kousuke , Simon M. Celeste , Johnson Randall S. , Suematsu Makoto , Tsubota Kazuo , Ishida Susumu , Goda Nobuhito , Suda Toshio , Okano Hideyuki
Published: April 2010

In early neonates, the fetal circulatory system undergoes dramatic transition to the adult circulatory system. Normally, embryonic connecting vessels, such as the ductus arteriosus and the foramen ovale, close and regress. In the neonatal retina, hyaloid vessels maintaining blood flow in the embryonic retina regress, and retinal vessels take over to form the adult-type circulatory system. This process is regulated by a programmed cell death switch mediated by macrophages via Wnt and angiopoietin 2 pathways. In this study, we seek other mechanisms that regulate this process, and focus on the dramatic change in oxygen environment at the point of birth. The von Hippel-Lindau tumor suppressor protein (pVHL) is a substrate recognition component of an E3-ubiquitin ligase that rapidly destabilizes hypoxia-inducible factor αs (HIF-αs) under normoxic, but not hypoxic, conditions. To examine the role of oxygen-sensing mechanisms in retinal circulatory system transition, we generated retina-specific conditional-knockout mice for VHL (Vhlα-CreKO mice). These mice exhibit arrested transition from the fetal to the adult circulatory system, persistence of hyaloid vessels and poorly formed retinal vessels. These defects are suppressed by intraocular injection of FLT1-Fc protein [a vascular endothelial growth factor (VEGF) receptor-1 (FLT1)/Fc chimeric protein that can bind VEGF and inhibit its activity], or by inactivating the HIF-1α gene. Our results suggest that not only macrophages but also tissue oxygen-sensing mechanisms regulate the transition from the fetal to the adult circulatory system in the retina.
An interview with Steve Wilson
Authors: Senior Kathryn
Published: April 2010

Stephen Wilson is Professor of Developmental Genetics at University College, London, UK. He was recently awarded the Remedios Caro Almela Prize for Research in Developmental Neurobiology. We interviewed Steve to find out about how he started on the road to developmental biology research, how he got interested in the brain, his achievements and future challenges.
Angular Position Control of Fluid-Driven Bi-Directional Motor
Authors: Nakao Y , Ishikawa M
Published: April 2010

This paper describes the design of a rotational speed-control system and an angular position-control system for a fluid-driven bi-directional motor. The fluid-driven bi-directional motor has a driving principle similar to that of the fluid-driven spindle, which is designed for use in ultra-precision machine tools. The fluid-driven bi-directional motor was designed so that it is driven by low viscosity oil flow power. In this paper, the rotational speed controller for the motor is first discussed. In order to reduce the influence of external load torque on the rotational speed, a conventional disturbance observer is combined with the rotational speed-control system. The angular position-control system, which possesses the rotational speed feedback loop with the disturbance observer in the angular position feedback loop, is then discussed. The designed rotational speed and angular position-control systems are conventional I—P control and proportional control systems, respectively. The performance of the designed rotational speed-control system and the angular position-control system is studied via simulations and experiments. The performance of the designed control system is tested by the step response method as well as by the frequency response method, respectively. The simulation and experimental results show that the rotational speed and the angular position of the motor can be controlled by the rotational speed controller and angular position controller, respectively. In addition, the influence of the external load torque acting on the motor is successfully compensated for by means of the disturbance observer. The experimental result shows that the designed angular position-control system suppresses the steady-state positioning error to less than 0.02°, even if external constant load torque acts on the motor.
The future of surgical orthopaedics of the knee
Authors: Schlueter-Brust K , Bontemps G , Sobottke R , Röllinghoff M , Michael J W-P , Siewe J , Eysel P
Published: April 2010

Over the past two decades, orthopaedics has gone through major changes, principally in the surgical treatment options for articular defects of the knee. This paper explores the advantages and shortcomings of the current surgical treatment modalities for cartilaginous defects in the knee. Emphasis is placed on current techniques in knee arthroplasty, including a view on the future of orthopaedic knee surgery.
Quality Management and Job Quality: How the ISO 9001 Standard for Quality Management Systems Affects Employees and Employers
Authors: Levine David I. , Toffel Michael W.
Published: April 2010

Several studies have examined how the ISO 9001 quality management systems standard predicts changes in organizational outcomes such as profits. This is the first large-scale study to explore how employee outcomes such as employment, earnings, and health and safety change when employers adopt ISO 9001. We analyzed a matched sample of nearly 1,000 companies in California. ISO 9001 adopters subsequently had far lower organizational death rates than a matched control group of nonadopters. Among surviving employers, ISO adopters had higher growth rates for sales, employment, payroll, and average annual earnings. Injury rates declined slightly for ISO 9001 adopters, although total injury costs did not. These results have implications for organizational theory, managers, and public policy.
Procurement Mechanism Design in a Two-Echelon Inventory System with Price-Sensitive Demand
Authors: Zhang Fuqiang
Published: April 2010

This paper studies a buyer's procurement strategies in a two-stage supply chain with price-sensitive demand. The buyer procures a product from a supplier and then sells to the marketplace. Market demand is stochastic and depends on the buyer's selling price. The supplier's production cost is private information, and the buyer only knows the distribution of the cost. Both the buyer and the supplier can hold inventories to improve service, and a periodic-review inventory system is considered. The buyer takes two attributes into consideration when designing the procurement mechanism: quantity attribute (i.e., the total purchase quantity) and service-level attribute (i.e., the supplier's delivery performance). We first identify the optimal procurement mechanism for the buyer, which consists of a nonlinear menu of contracts for each of the two attributes. It can be shown that the optimal mechanism induces both a lower market demand and a lower service level compared to the supply chain optimum. In view of the complexity of the optimal mechanism, we proceed to search for simpler mechanisms that perform well for the buyer. We find that the above two attributes have different implications for procurement mechanism design: The value of using complex contract terms is generally negligible for the service-level attribute, whereas it can be highly valuable for the quantity attribute. In particular, we demonstrate that a fixed service-level contract, which consists of a target service level and a price-quantity menu, yields nearly optimal profit for the buyer. Additionally, the price-quantity menu is essentially a quantity discount scheme widely observed in practice.
Myopic Inventory Policies Using Individual Customer Arrival Information
Authors: Martínez-de-Albéniz Victor , Lago Alejandro
Published: April 2010

In this paper, we investigate the optimality of myopic inventory replenishment policies in a periodic-review single-echelon system, with nonstationary, correlated, stochastic demand and cost, and nonincreasing stochastic prices. Using the single-unit decomposition approach, we provide certain general conditions on the demand and cost processes under which a myopic policy is optimal. Under these conditions, the optimal policy is a myopic state-dependent base-stock policy, which can be expressed in closed form as a base-probability policy. Specifically, the order associated with a given customer should be placed if and only if its arrival probability within the leadtime is higher than a threshold. Our results generalize earlier conditions for the optimality of myopic policies. Namely, we show that myopic policies can be optimal even when the demand is correlated or stochastically decreasing.
Do Random Errors Explain Newsvendor Behavior?
Authors: Kremer Mirko , Minner Stefan , Van Wassenhove Luk N.
Published: April 2010

Previous experimental work showed that newsvendors tend to order closer to mean demand than prescribed by the normative critical fractile solution. A recently proposed explanation for this mean ordering behavior assumes that the decision maker commits random choice errors, and predicts the mean ordering pattern because there is more room to err toward mean demand than away from it. Do newsvendors exhibit mean ordering simply because they make random errors? We subject this hypothesis to an empirical test that rests on the fact that the random error explanation is insensitive to context. Our results strongly support the existence of context-sensitive decision strategies that rely directly on (biased) order-to-demand mappings, such as mean demand anchoring, demand chasing, and inventory error minimization.
On the Interaction Between Demand Substitution and Production Changeovers
Authors: Dawande Milind , Gavirneni Srinagesh , Mu Yinping , Sethi Suresh , Sriskandarajah Chelliah
Published: April 2010

This paper analyzes the trade-off between (demand) substitution costs and (production) changeover costs in a discrete-time production-inventory setting using a two-product dynamic lot-sizing model with changeover, inventory carrying, and substitution costs. We first show that the problem is polynomially solvable and then develop several insights into the behavior of such systems and identify strategies for effectively managing them. A key driver for the extent of substitution is the ratio of changeover cost to the substitution cost associated with mean demand. The interaction between changeovers and substitution is most prominent when this ratio is neither too high nor too low. Furthermore, the value of this ratio also influences the length of an appropriate rolling horizon; an increase in the value of the ratio signals an increase in the length of a near-optimal rolling horizon. We identify a complementary relationship between substitution and changeover costs: When the changeover cost is large, it is better to invest in reducing the substitution cost and vice versa. As the holding cost of the substitutable product increases, substitution is (respectively, changeovers are) utilized more when the changeover (respectively, substitution) cost is large.
Revenue Management with Partially Refundable Fares
Authors: Gallego Guillermo , Şahin Özge
Published: April 2010

We introduce and analyze an intertemporal choice model where customer valuations are uncertain and evolve over time. The model leads directly to the study of call options on capacity that are similar to partially refundable fares. We show that the capacity provider earns significantly higher revenues by selling real options on capacity than on low-to-high pricing. We also investigate the social implications and show that the use of options is both socially optimal and socially efficient.
Irregular Packing Using the Line and Arc No-Fit Polygon
Authors: Burke E. K. , Hellier R. S. R. , Kendall G. , Whitwell G.
Published: April 2010

The no-fit polygon is a geometric construct that can offer faster and more efficient handling of geometry between pairs of shapes than traditional line-by-line intersection. The detection of intersections is a critical operation within the irregular two-dimensional stock-cutting problem (also known as “nesting”), which aims to place shapes onto sheets of material so that the material is utilised as efficiently as possible and the waste (or trim loss) is reduced. The problem forms an important process within many real-world manufacturing industries such as metalworking, automotive production, aerospace, clothing and conservatory manufacture, and others. If manufacturers can reduce their costs by utilising raw materials more effectively, this can directly translate into increased profit margins or greater competitiveness within the marketplace. Moreover, there are significant environmental benefits to be gained. Several methods have been proposed to calculate no-fit polygons, but most, if not all, can only operate on geometry that consists of line segments. This paper extends the orbital sliding method of calculating no-fit polygons to enable it to handle arcs and then shows the resultant no-fit polygons being utilised successfully on the two-dimensional irregular packing problem. As far as the authors are aware, this is the first time that a no-fit polygon algorithm has been able to handle arcs robustly without decomposing to their line approximations. The modification of the authors' previously published packing algorithm to utilise the proposed no-fit polygon approach yields solutions of excellent quality (including several best-known) on well-established literature benchmark problems after only a few minutes. The authors believe that the success of the packing strategy and the line and arc no-fit polygon algorithm make this approach a serious candidate for use in real-world production environments.
Information Relaxations and Duality in Stochastic Dynamic Programs
Authors: Brown David B. , Smith James E. , Sun Peng
Published: April 2010

We describe a general technique for determining upper bounds on maximal values (or lower bounds on minimal costs) in stochastic dynamic programs. In this approach, we relax the nonanticipativity constraints that require decisions to depend only on the information available at the time a decision is made and impose a “penalty” that punishes violations of nonanticipativity. In applications, the hope is that this relaxed version of the problem will be simpler to solve than the original dynamic program. The upper bounds provided by this dual approach complement lower bounds on values that may be found by simulating with heuristic policies. We describe the theory underlying this dual approach and establish weak duality, strong duality, and complementary slackness results that are analogous to the duality results of linear programming. We also study properties of good penalties. Finally, we demonstrate the use of this dual approach in an adaptive inventory control problem with an unknown and changing demand distribution and in valuing options with stochastic volatilities and interest rates. These are complex problems of significant practical interest that are quite difficult to solve to optimality. In these examples, our dual approach requires relatively little additional computation and leads to tight bounds on the optimal values.
Technical Note—Preservation of Quasi-K-Concavity and Its Applications
Authors: Chen Xin , Zhang Yuhan , Zhou Sean X.
Published: April 2010

In this paper, we establish a new preservation property of quasi-K-concavity under certain optimization operations. One important application of the result is to analyze joint inventory-pricing models for single-product periodic-review inventory systems with concave ordering costs. At each period, an ordering quantity and a selling price of the product are determined simultaneously. Demand is random but sensitive to the price. The objective is to maximize the total expected discounted profit over a finite planning horizon. Assuming that demand is a deterministic function of the selling price plus a random perturbation with a positive Pólya or uniform distribution, we show that a generalized (s, S, p) policy is optimal.
Scientific reasoning in a real‐world context: The effect of prior belief and outcome on children's hypothesis‐testing strategies
Authors: Croker Steve , Buchanan Heather
Published: April 2010

The impact of event outcome and prior belief on scientific reasoning was investigated within a real‐world oral health context. Participants (N= 144; ranging from 3 to 11 years) were given hypothesis‐testing tasks and asked to explain their answers. Participants were presented with information that was either consistent or inconsistent with their own beliefs. Each task consisted of scenarios in which the outcome was either good or bad oral health. When the information was belief consistent and the outcome was good, or when the information was belief inconsistent and the outcome was bad, children were more likely to choose scientifically appropriate tests of the stated hypothesis (i.e. manipulate only one variable). Evidence‐based explanations were associated with scientifically appropriate choices in the good‐outcome, belief‐inconsistent scenario and the belief‐consistent, bad‐outcome scenario. Participants' performance on these tasks is explained by considering the plausibility of causal variables. A control of variables strategy was used to test hypotheses in cases in which the evidence was consistent with participants' beliefs and knowledge of causal mechanisms. In contrast, when the evidence was inconsistent with participants' beliefs, children chose to manipulate behaviours likely to lead to a positive health outcome. These findings demonstrate that context and prior knowledge interact to play an important role in children's scientific reasoning.