bluuebunny/crossref_metadata_2025 huggingface dataset:
How to quantify coughing: correlations with quality of life in chronic cough
Authors: Kelsall A. , Decalmer S. , Webster D. , Brown N. , McGuinness K. , Woodcock A. , Smith J.
Published: February 2008

Different methods are used for quantifying coughing in sound recordings, but as yet no method has been shown to be more valid than any other. In the present study, the relationships between three different units of cough were examined and their ability to predict subjective ratings of cough and cough-related quality of life were evaluated.

In total, 70 subjects (mean±sdage 55±11.7 yrs, 51 (73%) females) with chronic unexplained cough (median duration 4.8 yrs, interquartile range 2.5–10.1 yrs) performed fully ambulatory 24-h sound recordings, which were manually counted by trained observers and quantified by 1) explosive phases, 2) cough seconds and 3) cough epochs. Subjects also completed cough visual analogue scales (VAS) and the Leicester Cough Questionnaire (LCQ).

All units of cough were strongly correlated; explosive phases and cough seconds correlated slightly more strongly than cough seconds with cough epochs or explosive phases with cough epochs. LCQ scores correlated moderately with explosive phases and seconds; epochs correlated slightly less well. Cough VAS scores showed a similar pattern.

Explosive phases and seconds are interchangeable units of cough, moderately related to subjective measures and cough-related quality of life; epochs are a less satisfactory alternative.
Adenosine 5′-monophosphate in asthma: gas exchange and sputum cellular responses
Authors: Manrique H. A. , Gómez F. P. , Muñoz P. A. , Peña A. M. , Barberà J. A. , Roca J. , Rodríguez-Roisin R.
Published: February 2008

Adenosine 5′-monophosphate (AMP) bronchoprovocation reproduces the lung function abnormalities that occur spontaneously during acute asthma and detects peripheral airway inflammation better than direct bronchoconstrictive agents. Pulmonary gas exchange disturbances may reflect changes in small airways related to airway inflammation rather than bronchoconstriction alone.

The present authors investigated whether AMP induced a greater imbalance in the ventilation/perfusion ratio than methacholine (MCh), at an equivalent degree of bronchoconstriction, with and without salbutamol pre-medication. In total, 36 asthmatics were studied in three randomised, double-blind, crossover studies: 1) before and after AMP or MCh; 2) before and 30 min after salbutamol or placebo, followed by AMP; or 3) MCh challenge. Sputum was collected before and 4 h post-challenge.

Compared with MCh, AMP provoked similar pulmonary gas exchange abnormalities at an equivalent degree of intense bronchoconstriction (forced expiratory volume in one second decrease of 28–44%). While salbutamol blocked AMP- or MCh-induced bronchoconstriction, arterial oxygen tension (Pa,O2) and alveolar–arterial oxygen tension difference (PA–a,O2) disturbances induced by AMP and MCh were only partially blocked (Pa,O2by 46 and 42%, respectively;PA–a,O2by 58 and 57%, respectively). Compared with MCh, AMP increased the percentage of neutrophils (mean±seincreased from 28±4% to 38±4%), but this increase did not occur after salbutamol pre-treatment.

Both adenosine 5′-monophosphate and methacholine induced similar peripheral airway dysfunction. The fully inhibited adenosine 5′-monophosphate-induced neutrophilia with residual hypoxaemia observed after salbutamol treatment is probably related to β2-agonists acting on both bronchial and pulmonary circulation.
Genome-wide analysis of the rice and arabidopsis non-specific lipid transfer protein (nsLtp) gene families and identification of wheat nsLtp genes by EST data mining
Authors: Boutrot Freddy , Chantret Nathalie , Gautier Marie-Françoise
Published: February 2008

Background

Plant non-specific lipid transfer proteins (nsLTPs) are encoded by multigene families and possess physiological functions that remain unclear. Our objective was to characterize the complete nsLtp gene family in rice and arabidopsis and to perform wheat EST database mining for nsLtp gene discovery.

Results

In this study, we carried out a genome-wide analysis of nsLtp gene families in Oryza sativa and Arabidopsis thaliana and identified 52 rice nsLtp genes and 49 arabidopsis nsLtp genes. Here we present a complete overview of the genes and deduced protein features. Tandem duplication repeats, which represent 26 out of the 52 rice nsLtp genes and 18 out of the 49 arabidopsis nsLtp genes identified, support the complexity of the nsLtp gene families in these species. Phylogenetic analysis revealed that rice and arabidopsis nsLTPs are clustered in nine different clades. In addition, we performed comparative analysis of rice nsLtp genes and wheat (Triticum aestivum) EST sequences indexed in the UniGene database. We identified 156 putative wheat nsLtp genes, among which 91 were found in the 'Chinese Spring' cultivar. The 122 wheat non-redundant nsLTPs were organized in eight types and 33 subfamilies. Based on the observation that seven of these clades were present in arabidopsis, rice and wheat, we conclude that the major functional diversification within the nsLTP family predated the monocot/dicot divergence. In contrast, there is no type VII nsLTPs in arabidopsis and type IX nsLTPs were only identified in arabidopsis. The reason for the larger number of nsLtp genes in wheat may simply be due to the hexaploid state of wheat but may also reflect extensive duplication of gene clusters as observed on rice chromosomes 11 and 12 and arabidopsis chromosome 5.

Conclusion

Our current study provides fundamental information on the organization of the rice, arabidopsis and wheat nsLtp gene families. The multiplicity of nsLTP types provide new insights on arabidopsis, rice and wheat nsLtp gene families and will strongly support further transcript profiling or functional analyses of nsLtp genes. Until such time as specific physiological functions are defined, it seems relevant to categorize plant nsLTPs on the basis of sequence similarity and/or phylogenetic clustering.
A methodological framework to distinguish spectrum effects from spectrum biases and to assess diagnostic and screening test accuracy for patient populations: Application to the Papanicolaou cervical cancer smear test
Authors: Elie Caroline , Coste Joël ,   the French Society of Clinical Cytology Study Group
Published: February 2008

Background

A spectrum effect was defined as differences in the sensitivity or specificity of a diagnostic test according to the patient's characteristics or disease features. A spectrum effect can lead to a spectrum bias when subgroup variations in sensitivity or specificity also affect the likelihood ratios and thus post-test probabilities. We propose and illustrate a methodological framework to distinguish spectrum effects from spectrum biases.

Methods

Data were collected for 1781 women having had a cervical smear test and colposcopy followed by biopsy if abnormalities were detected (the reference standard). Logistic models were constructed to evaluate both the sensitivity and specificity, and the likelihood ratios, of the test and to identify factors independently affecting the test's characteristics.

Results

For both tests, human papillomavirus test, study setting and age affected sensitivity or specificity of the smear test (spectrum effect), but only human papillomavirus test and study setting modified the likelihood ratios (spectrum bias) for clinical reading, whereas only human papillomavirus test and age modified the likelihood ratios (spectrum bias) for "optimized" interpretation.

Conclusion

Fitting sensitivity, specificity and likelihood ratios simultaneously allows the identification of covariates that independently affect diagnostic or screening test results and distinguishes spectrum effect from spectrum bias. We recommend this approach for the development of new tests, and for reporting test accuracy for different patient populations.
Substernal oxyphil parathyroid adenoma producing PTHrP with hypercalcemia and normal PTH level
Authors: Gurrado Angela , Marzullo Andrea , Lissidini Germana , Lippolis Agostino , Rubini Domenico , Lastilla Gaetano , Testini Mario
Published: February 2008

Background

Parathyroid adenoma is the most common cause of primary hyperparathyroidism. Preoperative serum calcium and intact-parathyroid hormone levels are the most useful diagnostic parameters that allow differentiating primary hyperparathyroidism from non-parathyroid-dependent hypercalcemia. Parathyroidectomy is the definitive treatment for primary hyperparathyroidism. Approximately 5% of patients who underwent parathyroidectomy present with persistent or recurrent hyperparathyroidism due to ectopic localization of the adenoma. Functioning oxyphil parathyroid adenoma is an uncommon histological form, seldom causing primary hyperparathyroidism. Parathyroid adenoma with hypercalcemia exhibiting normal parathyroid hormone level is rare. An incidence of 5% to 33% has been documented in the literature; no etiologic explanation has been given. In 1987, parathyroid-hormone-related peptide was isolated as a causative factor of humeral hypercalcemia of malignancy. The presence of parathyroid-hormone-related peptide in parathyroid tissue under normal and pathological conditions has been described in the literature; however, its role in causing hyperparathyroidism has not yet been defined.

Case presentation

We present a case of persistent hypercalcemia with a normal level of intact-parathyroid hormone due to a substernal parathyroid adenoma, treated with radioguided parathyroidectomy. The final histological diagnosis was oxyphil adenoma, positive for parathyroid-hormone-related peptide antigens.

Conclusion

In clinical practice, this atypical biochemical presentation of primary hyperparathyroidism should be considered in the differential diagnosis of hypercalcemia. The parathyroid-hormone-related peptide should be considered not only in the presence of malignancy.
Cars, corporations, and commodities: Consequences for the social determinants of health
Authors: Woodcock James , Aldred Rachel
Published: February 2008

Social epidemiologists have drawn attention to health inequalities as avoidable and inequitable, encouraging thinking beyond proximal risk factors to the causes of the causes. However, key debates remain unresolved including the contribution of material and psychosocial pathways to health inequalities. Tools to operationalise social factors have not developed in tandem with conceptual frameworks, and research has often remained focused on the disadvantaged rather than on forces shaping population health across the distribution. Using the example of transport, we argue that closer attention to social processes (capital accumulation and motorisation) and social forms (commodity, corporation, and car) offers a way forward. Corporations tied to the car, primarily oil and vehicle manufacturers, are central to the world economy. Key drivers in establishing this hegemony are the threat of violence from motor vehicles and the creation of distance through the restructuring of place. Transport matters for epidemiology because the growth of mass car ownership is environmentally unsustainable and affects population health through a myriad of pathways. Starting from social forms and processes, rather than their embodiment as individual health outcomes and inequalities, makes visible connections between road traffic injuries, obesity, climate change, underdevelopment of oil producing countries, and the huge opportunity cost of the car economy. Methodological implications include a movement-based understanding of how place affects health and a process-orientated integration of material and psychosocial explanations that, while materially based, contests assumptions of automatic benefits from economic growth. Finally, we identify car and oil corporations as anti-health forces and suggest collaboration with them creates conflicts of interest.
Trans-visceral migration of retained surgical gauze as a cause of intestinal obstruction: a case report
Authors: Grassi Nello , Cipolla Calogero , Torcivia Adriana , Bottino Alessandro , Fiorentino Eugenio , Ficano Leonardo , Pantuso Gianni
Published: February 2008

Introduction

A retained surgical sponge in the abdomen is uncommon although it is likely that this finding is underreported in the medical literature. The intravisceral migration of retained surgical gauze is even rarer, as demonstrated by the very few cases reported.

Case presentation

Three years after undergoing anterior resection of the rectum, a 75-year-old man presented with symptoms of small bowel obstruction. Plain abdominal radiography and CT showed a radio-opaque marker; a foreign body was suspected, probably a piece of retained surgical gauze. An ileotomy of about 5 cm. was performed to confirm this diagnosis and remove the gauze.

Conclusion

Although rare, retained gauze in the abdomen is a complication of surgery. The authors consider that this event may be more frequent than it appears from reports in the literature, probably because of its medico-legal implications. If all such cases were reported, it would be possible to estimate their exact number, classify the occurrence as a possible surgical complication and thus modify its medico-forensic consequences.
Genome wide prediction of HNF4α functional binding sites by the use of local and global sequence context
Authors: Kel Alexander E , Niehof Monika , Matys Volker , Zemlin Rüdiger , Borlak Jürgen
Published: February 2008

We report an application of machine learning algorithms that enables prediction of the functional context of transcription factor binding sites in the human genome. We demonstrate that our method allowedde novoidentification of hepatic nuclear factor (HNF)4α binding sites and significantly improved an overall recognition of faithful HNF4α targets. When applied to published findings, an unprecedented high number of false positives were identified. The technique can be applied to any transcription factor.
Sequence context affects the rate of short insertions and deletions in flies and primates
Authors: Tanay Amos , Siggia Eric D
Published: February 2008

Background

Insertions and deletions (indels) are an important evolutionary force, making the evolutionary process more efficient and flexible by copying and removing genomic fragments of various lengths instead of rediscovering them by point mutations. As a mutational process, indels are known to be more active in specific sequences (like micro-satellites) but not much is known about the more general and mechanistic effect of sequence context on the insertion and deletion susceptibility of genomic loci.

Results

Here we analyze a large collection of high confidence short insertions and deletions in primates and flies, revealing extensive correlations between sequence context and indel rates and building principled models for predicting these rates from sequence. According to our results, the rate of insertion or deletion of specific lengths can vary by more than 100-fold, depending on the surrounding sequence. These mutational biases can strongly influence the composition of the genome and the rate at which particular sequences appear. We exemplify this by showing how degenerate loci in human exons are selected to reduce their frame shifting indel propensity.

Conclusion

Insertions and deletions are strongly affected by sequence context. Consequentially, genomes must adapt to significant variation in the mutational input at indel-prone and indel-immune loci.
Native-Language Literacy in Colonial Peru: The Question of Mundane Quechua Writing Revisited
Authors: Durston Alan
Published: February 2008

Scholars of indigenous societies in colonial Latin America have long noted the contrast between the abundance of indigenous-language records from Mesoamerica and their extreme scarcity in the Andes. This article evaluates the degree to which written Quechua was used in everyday communication and record keeping among the indigenous population of colonial Peru by examining a corpus of Quechua documents, mostly letters and petitions from the seventeenth century. The linguistic features and archival contexts of these documents are analyzed to determine the extent and channels of alphabetic literacy in Quechua. The article argues that a standardized written form of Quechua developed by the church was in fact widely used among the indigenous elite, but that it never became an important medium of internal administrative record keeping in indigenous communities, as did occur with Nahuatl and other Mesoamerican languages.
New Humanism
Authors: Tonglu Li
Published: February 2008

Originally proposed by Irving Babbitt and Elmer More, and inspired by Buddhist and Confucian philosophies, New Humanism opposed the moral decline fostered by relativist and determinist beliefs and by an increasingly materialistic American society during the early twentieth century. Brought back to China and transformed by Chinese scholars who had studied with Babbitt, New Humanism became a counternarrative to the May Fourth Movement, to Marxism, and to radicalism in general. This essay delineates the roles New Humanism played in China, its internal contradictions, and its intricate relationship with hegemonic discourses by examining the literary practices of three New Humanists who demonstrated, respectively, ideal/academic, political, and transcendental ways of engagement.
The Political Campaign as Genre: Ideology and Iconography during the Seventeen Years Period
Authors: Braester Yomi
Published: February 2008

The essay examines films produced during the Seventeen Years period (1949–66) and suggests that political campaigns may be akin to film genres. Insofar as generic distinctions of theme and style are produced according to the shifting interests of critics and producers, campaigns have produced a politically motivated typology. The examination of campaigns as genrelike offers an opportunity to rethink the connection not only between Maoism and its cultural manifestations but also between ideology and form in general.
Elizabeth Fox-Genovese
Authors: Higginbotham Evelyn Brooks
Published: February 2008

This memorial tribute reflects on the personal and intellectual qualities of Elizabeth Fox-Genovese (1941–2007), who was the author's teacher. Higginbotham says that her first impressions of Fox-Genovese, formed in a graduate seminar in European history at the University of Rochester in the mid-1970s, have been lasting impressions. The seminar introduced patterns of thought and behavior that proved consistent over the years, despite Fox-Genovese's several shifts in the past three decades—from Marxist to non-Marxist, historian of France to historian of antebellum Southern women, feminist to nonfeminist, and religious agnostic to devout Catholic. Higginbotham discusses political theorist C. B. McPherson's idea of “possessive individualism” and its influence on Fox-Genovese's steadfast belief that individual rights derive from society (rather than innate nature) and that the concept of individualism maintains a contradictory and fraught relationship between individual and community. Her analysis and political positions often distanced her from her colleagues. But in this meditation on a brilliant mind and complex life, Higginbotham observes that Fox-Genovese never abandoned the tendency to speak openly and candidly, and thus to present herself vulnerable to the criticism of onlookers.
Beyond Modern
Authors: Gossman Lionel
Published: February 2008

Until recently, the general judgment of the once admired and influential Nazarene painters of early-nineteenth-century Germany, among those who paid any attention to their work, was that in rejecting everything that came after the young Raphael and seeking inspiration in the Italian “primitives,” they had taken the wrong road and ended up in a cul-de-sac, in contrast to contemporaries such as Géricault and Delacroix, Constable and Turner, who had taken the road that led, without break, to modernity. To the Nazarenes, however, as to the neoclassical artists of the turn of the eighteenth and nineteenth centuries (David, Flaxman, Carstens) and their theorist Winckelmann, going back meant going forward—beyond illusionism. The obscurity into which Friedrich Overbeck, Franz Pforr, Peter Cornelius, and Julius Schnorr von Carolsfeld have fallen raises questions about the degree to which the long dominant and ideologically loaded narrative of art history as a “development” toward modernity has determined not only how viewers today respond to works of art but what art they get to see.
The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members
Authors: Farazi Thalia A. , Juranek Stefan A. , Tuschl Thomas
Published: February 2008

Several distinct classes of small RNAs, some newly identified, have been discovered to play important regulatory roles in diverse cellular processes. These classes include siRNAs, miRNAs, rasiRNAs and piRNAs. Each class binds to distinct members of the Argonaute/Piwi protein family to form ribonucleoprotein complexes that recognize partially, or nearly perfect,complementary nucleic acid targets, and that mediate a variety of regulatory processes, including transcriptional and post-transcriptional gene silencing. Based on the known relationship of Argonaute/Piwi proteins with distinct classes of small RNAs, we can now predict how many new classes of small RNAs or silencing processes remain to be discovered.
Mutation of DNA primase causes extensive apoptosis of retinal neurons through the activation of DNA damage checkpoint and tumor suppressor p53
Authors: Yamaguchi Masahiro , Fujimori-Tonou Noriko , Yoshimura Yukihiro , Kishi Tsutomu , Okamoto Hitoshi , Masai Ichiro
Published: February 2008

Apoptosis is often observed in developing tissues. However, it remains unclear how the apoptotic pathway is regulated during development. To clarify this issue, we isolated zebrafish mutants that show extensive apoptosis of retinal cells during their development. pinball eye (piy) is one such mutant, in which retinal stem cells proliferate normally but almost all retinal neurons undergo apoptosis during differentiation. We found that a missense mutation occurred in the small subunit of DNA primase (Prim1) in the piy mutant. DNA primase is essential for DNA replication; however,this mutation does not affect cell proliferation but rather induces neuronal apoptosis. RNA synthesis catalyzed by Prim1 is important for the activation of the DNA damage response, which may activate Ataxia telangiectasia mutated(ATM), Checkpoint kinase 2 (Chk2) and the tumor suppressor p53. We found that the apoptosis induced by the prim1 mutation depends on the ATM-Chk2-p53 apoptotic pathway. These data suggest that the surveillance system of genome integrity strongly influences the cell fate decision between differentiation and apoptosis during retinal neurogenesis in zebrafish.
CDC-25.1 stability is regulated by distinct domains to restrict cell division during embryogenesis inC. elegans
Authors: Hebeisen Michaël , Roy Richard
Published: February 2008

Cdc25 phosphatases are key positive cell cycle regulators that coordinate cell divisions with growth and morphogenesis in many organisms. Intriguingly in C. elegans, two cdc-25.1(gf) mutations induce tissue-specific and temporally restricted hyperplasia in the embryonic intestinal lineage, despite stabilization of the mutant CDC-25.1 protein in every blastomere. We investigated the molecular basis underlying the CDC-25.1(gf) stabilization and its associated tissue-specific phenotype. We found that both mutations affect a canonical β-TrCP phosphodegron motif, while the F-box protein LIN-23, the β-TrCP orthologue, is required for the timely degradation of CDC-25.1. Accordingly,depletion of lin-23 in wild-type embryos stabilizes CDC-25.1 and triggers intestinal hyperplasia, which is, at least in part, cdc-25.1dependent. lin-23(RNAi) causes embryonic lethality owing to cell fate transformations that convert blastomeres to an intestinal fate, sensitizing them to increased levels of CDC-25.1. Our characterization of a novel destabilizing cdc-25.1(lf) intragenic suppressor that acts independently of lin-23 indicates that additional cues impinge on different motifs of the CDC-25.1 phosphatase during early embryogenesis to control its stability and turnover, in order to ensure the timely divisions of intestinal cells and coordinate them with the formation of the developing gut.
Hammerhead redux: Does the new structure fit the old biochemical data?
Authors: Nelson Jennifer A. , Uhlenbeck Olke C.
Published: February 2008

The cleavage rates of 78 hammerhead ribozymes containing structurally conservative chemical modifications were collected from the literature and compared to the recently determined crystal structure of the Schistosoma mansoni hammerhead. With only a few exceptions, the biochemical data were consistent with the structure, indicating that the new structure closely resembles the transition state of the reaction. Since all the biochemical data were collected on minimal hammerheads that have a very different structure, the minimal hammerhead must be dynamic and occasionally adopt the quite different extended structure in order to cleave.
A New Mixed-Integer Programming Model for Harvest Scheduling Subject to Maximum Area Restrictions
Authors: Constantino Miguel , Martins Isabel , Borges José G.
Published: February 2008

Forest ecosystem management often requires spatially explicit planning because the spatial arrangement of harvests has become a critical economic and environmental concern. Recent research on exact methods has addressed both the design and the solution of forest management problems with constraints on the clearcut size, but where simultaneously harvesting two adjacent stands in the same period does not necessarily exceed the maximum opening size. Two main integer programming approaches have been proposed for this area restriction model. However, both encompass an exponential number of variables or constraints. In this work, we present a new integer programming model with a polynomial number of variables and constraints. Branch and bound is used to solve it. The model was tested with both real and hypothetical forests ranging from 45 to 1,363 polygons. Results show that the proposed model's solutions were within or slightly above 1% of the optimal solution and were obtained in a short computation time.
On the Structure of Lost-Sales Inventory Models
Authors: Zipkin Paul
Published: February 2008

We provide a new approach to the structural analysis of the standard lost-sales inventory system. This approach is, we think, easier to work with than the original one. We also derive new bounds on the optimal policy. Then, we show that more variable demand leads to higher cost. Finally, we extend the analysis to several important variations of the basic model.
Enabling Courageous Collective Action: Conversations from United Airlines Flight 93
Authors: Quinn Ryan W. , Worline Monica C.
Published: February 2008

On September 11, 2001, the passengers and crew members aboard Flight 93 responded to the hijacking of their airplane by organizing a counterattack against the hijackers. The airplane crashed into an unpopulated field, causing no damage to human lives or national landmarks beyond the lives of those aboard the airplane. We draw on this story of courageous collective action to explore the question of what makes this kind of action possible. We propose that to take courageous collective action, people need three narratives—a personal narrative that helps them understand who they are beyond the immediate situation and manage the intense emotions that accompany duress, a narrative that explains the duress that has been imposed upon them sufficiently to make moral and practical judgments about how to act, and a narrative of collective action—and the resources that make the creation of these narratives feasible. We also consider how the creation of these narratives is relevant to courageous collective action in more common organizational circumstances, and identify how this analysis suggests new insights into our understanding of the core framing tasks of social movements, ways in which social movement actors draw on social infrastructure, the role of discourse and morality in social movements, the formation of collective identity, and resource mobilization.
Vitamin D, Calcium Homeostasis, and Skeleton Accretion in Children
Authors: Weaver Connie M
Published: February 2008

Overt vitamin D deficiency early in life has classically been associated with the etiology of rickets. Recent interest has focused on vitamin D insufficiency and calcium homeostasis and bone health. A review of the literature suggests that the relationship between vitamin D status and calcium utilization has some important differences with life stage and race. In contrast to adults, serum 1,25-dihydroxyvitamin D, but not serum 25-hydroxyvitamin D, predicts calcium absorption in growing children. PTH suppression with increasing serum 25-hydroxyvitamin D varies with race in adolescents. A limitation of our understanding of vitamin D status on calcium homeostasis in children relates to the cross-sectional nature of the evidence and interventions that typically use too little vitamin D supplementation to affect status. Vitamin D status has predicted changes in BMD during growth, and higher doses have been associated with increased bone area and BMC of the hip in pubertal girls with low baseline vitamin D status. Bone accretion is related to calcium status, sexual maturity, race, and genetics. Current cross-sectional studies in children suggest that vitamin D status is less important for bone accrual than for bone health in adults. Intervention studies are needed to identify responsive groups.
Role of Vitamin D Deficiency in Chronic Kidney Disease
Authors: Gal-Moscovici Anca , Sprague Stuart M
Published: February 2008

Chronic kidney disease (CKD) has been recognized as a significant public health problem, with ∼20 million Americans, or ∼11% of the adult population, currently living with CKD. A significant source of morbidity associated with CKD is the development of disturbances of mineral metabolism, which occurs in virtually all patients during the progression of their disease, and is associated with bone loss and fractures, cardiovascular disease, immune suppression, and increased mortality. As kidney disease develops, there is decreased functional renal mass and a tendency to retain phosphorus. The reduction in functional renal mass and the retained phosphorus act to reduce renal 1α-hydroxylase activity and thus the renal production of calcitriol. Further compensation to maintain normal serum calcium and phosphorus homeostasis includes increased production and release of PTH and potentially other phosphaturic factors, such as fibroblast growth factor-23 (FGF23). This increase in FGF23 contributes to maintain normal serum phosphate independent of PTH but may worsen calcitriol deficiency by also inhibiting renal 1α-hydroxylase activity. The decrease in calcitriol also results in promoting further hyperparathyroidism and parathyroid gland hyperplasia, because calcitriol normally inhibits the production of prepro-PTH and parathyroid cell proliferation.
Targets of Vitamin D Receptor Signaling in the Mammary Gland
Authors: Welsh JoEllen
Published: February 2008

Since the discovery of the vitamin D receptor (VDR) in mammary cells, the role of the vitamin D signaling pathway in normal glandular function and in breast cancer has been extensively explored. In vitro studies have shown that the VDR ligand, 1,25-dihydroxyvitamin D (1,25D), modulates key proteins involved in signaling proliferation, differentiation, and survival of normal mammary epithelial cells. Similar anti-proliferative and pro-differentiating effects of 1,25D have been observed in VDR-positive breast cancer cells, indicating that transformation per se does not abolish vitamin D signaling. However, many transformed breast cancer lose sensitivity to 1,25D secondary to alterations in vitamin D metabolizing enzymes or downregulation of VDR function. Over the years, our laboratory has focused on three general areas: (1) defining mechanisms of vitamin D–mediated apoptosis in breast cancer cells, (2) examining changes in the vitamin D signaling pathway during transformation, including the development of vitamin D resistance, and (3) using mouse models to study the impact of the VDR on growth regulatory pathways in the context of development and tumorigenesis in vivo. Recent developments include detection of megalin-mediated uptake of vitamin D–binding protein (DBP) and identification of CYP27B1 and CYP24 metabolizing enzymes in mammary cells, demonstration of precocious mammary gland development in VDR-null mice, and identification of novel pathways triggered by 1,25D during apoptosis. Our preclinical studies have been complemented by emerging data from other groups suggesting that human breast cancer may be influenced by VDR genotype and vitamin D status. Collectively, these studies have reinforced the need to further define the regulation and function of the vitamin D pathway in cells in relation to prevention and treatment of breast cancer.
Therapy of Osteoporosis With Calcium and Vitamin D
Authors: Dawson-Hughes Bess , Bischoff-Ferrari Heike A
Published: February 2008

Inadequate intakes of vitamin D and calcium lead to reduced calcium absorption, higher bone remodeling rates, and increased bone loss. Vitamin D insufficiency has also been linked to reduced muscle function and increased risk of falling. The mechanisms for the performance and muscle effects are not well understood. Administering vitamin D to those with inadequate vitamin D status has been shown to lower fracture rates in some trials but not in others. The purpose of this presentation is (1) to examine how calcium and vitamin D work in concert, (2) to consider key evidence that increasing vitamin D intake will affect risk of falls and fractures, and (3) to estimate the 25-hydroxyvitamin D [25(OH)D] level needed to achieve maximum fracture protection.
Vitamin D–Resistant Diseases
Authors: Liberman Uri A
Published: February 2008

Hereditary vitamin D receptor defects (HVDRDs) is a more appropriate and precise title for an inborn error of metabolism commonly known as pseudo-vitamin D deficiency or vitamin D dependency, type II. It is a rare autosomal recessive disorder, ∼70 kindreds were described, but its main importance is elucidating the physiology of vitamin D and calcium homeostasis in humans. Patients usually develop the clinical and biochemical aberrations, identical to vitamin D deficiency, but with high serum levels of calcitriol, within the first year of life (i.e., muscle weakness, bone pain, deformities, and fractures). Defective calcium gut absorption leads to hypocalcemia, secondary hyperparathyroidism, hypophosphatemia, and defective mineralization of newly formed bone matrix. The disease is not cured by vitamin D replacement therapy, although some patients respond to very high doses of vitamin D or its metabolites. Cells derived from patients, mainly cultured skin fibroblasts, were used to assess steps in calcitriol action from cellular uptake to bioresponse and to elucidate the molecular aberrations in the vitamin D receptor (VDR). Point mutations in the VDR gene were identified in every patient examined, and the same defect was observed in the obligatory heterozygotes. The functional characterization of the patient's VDR reflected the localization of the mutation (18 different ones described to date), thus providing vital information about the structure–function relationship in the human VDR and the essentiality of the VDR as the mediator of vitamin D action.
Calcitriol as a Chemopreventive and Therapeutic Agent in Prostate Cancer: Role of Anti-Inflammatory Activity
Authors: Krishnan Aruna V , Moreno Jacqueline , Nonn Larisa , Swami Srilatha , Peehl Donna M , Feldman David
Published: February 2008

Calcitriol, the hormonally active form of vitamin D, inhibits the growth and development of several cancers. Inflammation has been implicated in the development and progression of many cancers, including prostate cancer (PCa). Recent research from our laboratory suggests that calcitriol exhibits anti-inflammatory actions that may contribute to its inhibitory effects in PCa. We found that calcitriol inhibits the synthesis and actions of pro-inflammatory prostaglandins (PGs) by three mechanisms: (1) inhibition of the expression of cyclooxygenase-2 (COX-2), the enzyme that synthesizes PGs, (2) induction of the expression of 15-prostaglandin dehydrogenase (15-PGDH), the enzyme that inactivates PGs, and (3) decreasing the expression of prostaglandin E and prostaglandin F PG receptors, which are the mediators of PG signaling. The combination of calcitriol and nonsteroidal anti-inflammatory drugs (NSAIDs) result in a synergistic inhibition of PCa cell growth and offers a potential therapeutic strategy. Acting on a separate anti-inflammatory pathway, calcitriol induces the expression of mitogen-activated protein kinase phosphatase 5 (MKP5), a member of a family of phosphatases that are negative regulators of MAP kinases, causing the selective dephosphorylation and inactivation of the stress-activated protein kinase p38. Because p38 activation may be both procarcinogenic and promote inflammation, this calcitriol action, especially coupled with the inhibition of the PG pathway, may contribute to the chemopreventive activity of calcitriol. We conclude that calcitriol exerts several anti-inflammatory actions in prostate cells, which contribute to its potential as a chemopreventive and therapeutic agent in PCa.
Vitamin D, Cardiovascular Disease, and Survival in Dialysis Patients
Authors: Moe Sharon M
Published: February 2008

Dialysis patients have an increased burden of cardiovascular disease, with >70% of patients dying from a cardiovascular event. Several recent retrospective cohort studies have shown an association of treatment with calcitriol or its analogs and improved survival. The similar findings of these studies increase the validity of the observations, but these studies are subject to biases inherent in this type of study design. In particular, the nonrandom choice to treat, lack of information on concomitant medications, and differences in characteristics of patients who are treated compared with those not treated can lead to significant bias. Thus, prospective studies are needed. Two, small, uncontrolled, prospective studies showed improvement in left ventricular hypertrophy in dialysis patients treated with α-calcidiol or calcitriol, and there is abundant animal and in vitro studies showing biological plausibility. Thus, given the available evidence, it seems prudent to advise that most dialysis patients receive some form of vitamin D while we await results of a prospective interventional trial. The unknown is what type and how much to give, and whether this approach is safe, especially in patients with low levels of PTH.
Contemporary Diagnosis and Treatment of Vitamin D–Related Disorders
Authors: Jones Glenville , Horst Ronald , Carter Graham , Makin Hugh LJ
Published: February 2008

Plasma 25(OH)D has emerged as a valuable biomarker for the many varied health-related effects of vitamin D in the clinic mainly because of the recognition of the importance of the enzyme, CYP27B1, or the 25(OH)D-α-hydroxylase in the extrarenal, target cell production of calcitriol. This review briefly assesses current methodology for plasma 25(OH)D assay focusing mainly on currrent controversies surrounding the definition of the normal range and performance characteristics of the assay, separate measurement of both 25(OH)D2 and 25(OH)D3, and quality assurance tesing of laboratories offering the test. Clinicians have two main types of 25(OH)D assay based on either high-performance liquid chromatography with UV or mass detection or higher throughput kits based on protein (competitive protein binding assay or radioimmunoassay) binding. Based on 30 yr of experience with measuring 25(OH)D levels, it is concluded that, in the hands of appropriately trained experts, both types of assay provide reliable and accurate results, but all laboratories providing 25(OH)D data need frequent external quality assurance service to ensure that this performance is maintained.
Women talk revisited: Personal disclosures and alignment development
Authors: DeCapua Andrea , Berkowitz Diana , Boxer Diana
Published: February 2008

This study is an analysis of small-group talk among three different groups of women in the United States. Building upon Coates' (1996) study of female talk in a British speech community, we investigate how women build close personal relationships through their discourse. The data consist of three hours of videotaped interactions among the three all-female groups in different locations in the US and among interlocutors of differing social distance. We demonstrate here how variation in speech event norms coupled with differences in social distance relationships lead to distinct communicative enactments of friendship. The participants in the three groups are as follows: four close friends from northeastern New Jersey engaging in ordinary social conversation; four members of a Jewish Sisterhood organization in Long Island, New York, having a casual get-together; and three mothers of young children in Tampa, Florida, meeting for a playgroup date. The interlocutors in the three groups are all originally from their respective geographical areas and have lived in these areas most of their lives. All are native speakers of American English.

Our analysis focuses on small group talk among women in groups in which the relationships vary according to shared history, interests, and norms for interaction in social conversation and group meeting. From an ‘etic’ perspective, the three groups represent a continuum ranging from social, interactional talk to transactional talk that ‘gets down to business.’ However, the features of disclosures through personal narratives and the structural elements of overlap are shown here to function toward ‘women talk’ (Coates 1996). It will become clear that regardless of the social distance relationship, the all women's groups share elements of relational, or rapport talk (Tannen 1990) that are pervasive even in transactional, or information sharing encounters (Brown and Yule 1983). In all three groups we find structural elements that lend themselves to personal disclosures, accomplished via narratives (the New Jersey Group), overlaps (the Long Island Group), and Relational Identity Display and Development or RID (Boxer and Cortes-Conde 1997) (the Tampa Group).
The Theta System – an overview
Authors: Reinhart Tanya
Published: February 2008

This paper presents an overview of a larger project in progress on the concepts interface. In part, it is based on the findings in Reinhart (2000), where several of the problems are discussed in greater details. However, many aspects of the system have been further developed, or changed, since that manuscript.
The Theta System – a lexico-semantic approach?
Authors: Rapp Irene
Published: February 2008

Tanya Reinhart's “The Theta System” is mainly meant to explain the linking behaviour and the particular binding properties of experiencing verbs. Following Pesetsky (1995), Reinhart argues that verbs like worry possess three arguments: a cause, an experiencer and a subject matter role. Backwards bound anaphors are enabled only if it is the subject matter which is realized externally – it originates VP-internally and its trace is c-commanded by the experiencer:

(1) Hisi health worries every patienti. (Reinhart's example (42a)) If the subject is construed as the cause, it merges directly externally, and the c-command requirement is not met. Bound anaphors are not licensed in this case:

(2) ??Hisi doctor worried every patienti. (Reinhart's example (65b))
Yet another Theta System
Authors: Vogel Ralf
Published: February 2008

Tanya Reinhart's “Theta System” (henceforth: TS) is yet another version of what we call linking theories, i.e., theories that formulate generalizations about how verbs project their semantic arguments into syntactic constituent structure. The last decades of linguistic research have seen many proposals of this kind. The TS is particularly designed to fit into a minimalist theory of syntax, but, as far as I can see, there is nothing particularly minimalist in it, apart from details of technical execution. Neither is TS the only possible linking theory within minimalism.
Comparative markedness and derived environments
Authors: Mascaró Joan
Published: February 2008

McCarthy's paper contains a simple idea with important consequences. The simple idea is that markedness constraints come in two brands, OM and NM. Whereas a “classic” markedness constraint *M bans the structure M, OM does so only if M is present in the input and NM only if M is not present in the input. The idea is simple but the array of consequences that it entails is by no means simple. It can be implemented in different ways; some of the implementation problems are discussed by the author, others are left for the future. As for the consequences, some are theoretical (relations to local constraint conjunction, sympathy, stratal OT) others empirical. The latter involve new predictions (grandfather effects) and older empirical domains, like counter-feeding opacity and derived environment effects (DEE). In this reaction to McCarthy's paper I will concentrate on the latter.
What does comparative markedness explain, what should it explain, and how?
Authors: McCarthy John J
Published: February 2008

1. Introduction

These seven commentaries treat a wide range of topics in interesting and insightful ways. It is not possible to write a coherent response that addresses all of the criticisms and suggestions, large and small, that the authors have brought up. Several main themes emerge, however, that transcend the individual commentaries, and these themes supply the structure for this reply. They include alternatives to comparative markedness, possible counterexamples, comparative markedness on other dimensions of correspondence, and questions about the authenticity of opaque phonological processes. These themes will each be addressed in turn.
Comparative markedness and containment
Authors: Oostendorp Marc Van
Published: February 2008

Introduction

‘Comparative Markedness’ (CM) tries among other things to characterize the notion ‘possible constraint’ in Optimality Theory (OT) and in this way to both extend and constrain the scope of the theory. The author is the first to admit that the theory as it stands is not perfect in my opinion, it is the best approximation to problems such as opacity and derived environment effects within OT that is currently available; but problems remain.
Counterfeeding, derived environment effects, and comparative markedness
Authors: Blumenfeld Lev
Published: February 2008

0. Introduction

One of the most interesting aspects of the Comparative Markedness (CM) theory is the unification of several phenomena traditionally thought to be unrelated. Grandfathering effects, Derived Environment Effects (DEEs), and counterfeeding opacity all turn out to be different facets of the same phenomenon, due to the presence of new and old markedness in the system.
Development of a Canadian National Standard on Design for Disassembly and Adaptability for Buildings
Authors: Clapham M. , Foo S. , Quadir J.
Published: February 2008

In recent years, both the public concern on environmental issues and the interest and demand for sustainable buildings have been growing worldwide. Architects, engineers, building developers, and buildings owners are feeling pressure to design, construct, and maintain buildings that respect sustainability and the environment. In support of sustainable development initiatives of governments and the building industry, the Canadian Standards Association (CSA) has established a Technical Committee on Sustainable Buildings, which has been tasked to develop national standards to advance the design, construction, and maintenance of buildings in a sustainable manner. This paper first discusses the standards development environment in Canada and the standards development process in CSA and goes on to describe the development of a new standard on the design for disassembly and adaptability of buildings.