bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth trajectory during early life and risk of adult schizophrenia
Authors: Perrin Megan A. , Chen Henian , Sandberg David E. , Malaspina Dolores , Brown Alan S.
Published: December 2007

Background

Growth abnormalities have been suggested as a precursor to schizophrenia, but previous studies have not assessed growth patterns using repeated measures.

Aims

To assess the association between early life/later childhood growth patterns and risk of schizophrenia.

Methods

Using prospectively collected data from a birth cohort (born 1959–1967), measurements of height, weight and body mass index (BMI) were analysed to compare growth patterns during early life and later childhood between 70 individuals with schizophrenia-spectrum disorder (SSD) and 7710 without.

Results

For women, growth in the SSD group was approximately 1 cm/year slower during early life (P<0.01); no association was observed for men. Later childhood growth was not associated with SSD. Weight patterns were not associated with SSD, whereas slower change in BMI was observed among the SSD group during later childhood.

Conclusions

The association between slower growth in early life and schizophrenia in women suggests that factors responsible for regulating growth might be important in the pathogenesis of the disorder.
Social exclusion and mental health
Authors: Morgan Craig , Burns Tom , Fitzpatrick Ray , Pinfold Vanessa , Priebe Stefan
Published: December 2007

Background

The concept of social exclusion is now widely used in discussions about the nature of disadvantage, and there are ongoing initiatives to promote social inclusion among those with mental health problems.

Aims

To conduct a conceptual and methodological review of social exclusion, focusing initially on the origins and definitions of the concept and then on approaches to its measurement, both in general and in relation to mental health.

Method

We used two main strategies. First, we utilised expertise within the study team to identify major texts and reviews on social exclusion and related topics. Second, we searched major bibliographic databases for literature on social exclusion and mental health. We adopted a non-quantitative approach to synthesising the findings.

Results

There is no single accepted definition of social exclusion. However, most emphasise lack of participation in social activities as the core characteristic. There are a number of approaches to measuring social exclusion, including use of indicator lists and dimensions. In the mental health literature, social exclusion is poorly defined and measured.

Conclusions

If social exclusion is a useful concept for understanding the social experiences of those with mental health problems, there is an urgent need for more conceptual and methodological work.
Staff and patient perspectives on unmet need and therapeutic alliance in community mental health services
Authors: Junghan Ulrich M. , Leese Morven , Priebe Stefan , Slade Mike
Published: December 2007

Background

Therapeutic alliance between clinicians and their patients is important in community mental healthcare. It is unclear whether providing effective interventions influences therapeutic alliance.

Aims

To assess the impact of meeting previously unmet mental health needs on the therapeutic alliance between patients and clinicians.

Method

Secondary analysis of data from a longitudinal study assessing 101 patients and paired staff.

Results

Patient-rated unmet need was negatively associated with patient-rated and staff-rated therapeutic alliance. Staff-rated unmet need was positively associated with patient-rated therapeutic alliance only. Reducing patient-rated unmet need increased patient-rated but not staff-rated therapeutic alliance, even when controlling for other variables. Reducing staff-rated unmet need increased staff-rated but not patient-rated therapeutic alliance, but the effect became insignificant when controlling for other variables.

Conclusions

Patient-rated therapeutic alliance will be maximised by focusing assessment and interventions on patient-rated rather than staff-rated unmet need.
Ten books
Authors: Beveridge Allan
Published: December 2007

In the novelHard Times, Charles Dickens gives his views on education. His character Mr Gradgrind believes in ‘facts’ and is suspicious of the imagination. All we need to know about the world, he maintains, can be reduced to simple facts. Dickens shows that such a philosophy leads to the impoverishment of the mind and to the weakening of ethical reasoning. Today it seems that the descendants of Mr Gradgrind are still in charge. The main psychiatric library where I work has been closed. It is argued that we can obtain all the ‘facts’ we need from the internet. The notion that books might have more to offer than prosaic detail, that they reflect the rich diversity of human experience, seems alien to the modern-day Gradgrinds.
Mental health of children and adolescents with intellectual disabilities in Britain
Authors: Emerson Eric , Hatton Chris
Published: December 2007

Background

Few studies have employed formal diagnostic criteria to determine the prevalence of psychiatric disorders in contemporaneous samples of children with and without intellectual disabilities.

Aims

To establish the prevalence of psychiatric disorders against ICD—10 criteria among children with and without intellectual disabilities, the association with social/environmental risk factors, and risk attributable to intellectual disability.

Method

Secondary analysis of the 1999 and 2004 Office for National Statistics surveys of the mental health of British children and adolescents with (n=641) and without (n = 17774) intellectual disability.

Results

Prevalence of psychiatric disorders was 36% among children with intellectual disability and 8% among children without (OR=6.5). Children with intellectual disabilities accounted for 14% of all British children with a diagnosable psychiatric disorder Increased prevalence was particularly marked for autistic-spectrum disorder (OR=33.4), hyperkinesis (OR=8.4) and conduct disorders (OR=5.7). Cumulative risk of exposure to social disadvantage was associated with increased prevalence.

Conclusions

A significant proportion of the elevated risk for psychopathology among children with intellectual disability may be due to their increased rate of exposure to psychosocial disadvantage.
Influence of childhood adversity on health among male UK military personnel
Authors: Iversen Amy C. , Fear Nicola T. , Simonoff Emily , Hull Lisa , Horn Oded , Greenberg Neil , Hotopf Matthew , Rona Roberto , Wessely Simon
Published: December 2007

Background

Exposure to childhood adversity may explain why only a minority of combatants exposed to trauma develop psychological problems.

Aims

To examine the association between self-reported childhood vulnerability and later health outcomes in a large randomly selected male military cohort.

Method

Data are derived from the first stage of a cohort study comparing Iraq veterans and non-deployed UK military personnel. We describe data collected by questionnaire from males in the regular UK armed forces (n=7937).

Results

Pre-enlistment vulnerability is associated with being single, of lower rank, having low educational attainment and serving in the Army. Pre-enlistment vulnerability is associated with a variety of negative health outcomes. Two main factors emerge as important predictors of ill health: a ‘family relationships’ factor reflecting the home environment and an ‘externalising behaviour’ factor reflecting behavioural disturbance.

Conclusions

Pre-enlistment vulnerability is an important individual risk factor for ill health in military men. Awareness of such factors is important in understanding post-combat psychiatric disorder.
Efficacy of three screening instruments in the identification of autistic-spectrum disorders
Authors: Charman Tony , Baird Gillian , Simonoff Emily , Loucas Tom , Chandler Susie , Meldrum David , Pickles Andrew
Published: December 2007

Background

Screening instruments for autistic-spectrum disorders have not been compared in the same sample.

Aims

To compare the Social Communication Questionnaire (SCQ), the Social Responsiveness Scale (SRS) and the Children's Communication Checklist (CCC).

Method

Screen and diagnostic assessments on 119 children between 9 and 13 years of age with special educational needs with and without autistic-spectrum disorders were weighted to estimate screen characteristics for a realistic target population.

Results

The SCQ performed best (area under receiver operating characteristic curve (AUC)=0.90; sensitivity 0.86; specificity 0.78). The SRS had a lower AUC (0.77) with high sensitivity (0.78) and moderate specificity (0.67). The CCC had a high sensitivity but lower specificity (AUC=0.79; sensitivity 0.93; specificity 0.46). The AUC of the SRS and CCC was lower for children with IQ < 70. Behaviour problems reduced specificity for all three instruments.

Conclusions

The SCQ, SRS and CCC showed strong to moderate ability to identify autistic-spectrum disorder in this at-risk sample of school-age children with special educational needs.
Future Developments in Therapy
Authors: ISALES CARLOS M. , McDONALD JAY M.
Published: December 2007

Abstract:  An exciting new era in bone biology is a result of our greater understanding not only of the mechanisms of action of the medications we currently use for treatment of osteoporosis but also of the molecular pathways involved in normal and abnormal bone formation. In the coming years our increased understanding of these molecular pathways will result in many new medications for osteoporosis therapy. Together with the development of new drugs it will be necessary to develop better ways of assessing bone quality. Since bone has both protein (collagen type I) and mineral (hydroxyapatite) components, both of which are essential to bone strength, measurements of bone mineral content by densitometry (DXA) will provide us with only a narrow perspective on the utility of the drug under development prior to full patient fracture studies. The information gathered from basic bone research must be used for the rational development of agents that increase bone strength within a narrow physiological window.
Synovial Fluid Fibroblasts and Lymphocytes Support the Osteoclastogenesis in Human Psoriatic Arthritis
Authors: MORI GIORGIO , CANTATORE FRANCESCO P. , BRUNETTI GIACOMINA , ORANGER ANGELA , COLAIANNI GRAZIANA , QUARTA LAURA , CORRADO ADDOLORATA , COLUCCI SILVIA , GRANO MARIA
Published: December 2007

Abstract:  Aggressive bone resorption is well recognized in psoriatic arthritis (PsA). By using in vitro osteoclastogenesis models, consisting of unstimulated mononuclear cells from peripheral blood (PBMCs) and synovial fluid (SFMCs) of PsA patients, we demonstrated the spontaneous OC formation in both culture systems. In PBMCs the osteoclastogenesis was T cell‐dependent while it was T cell‐ and fibroblast‐dependent in SFMCs. T cells isolated from PBMCs and SFMCs of PsA patients overexpressed RANKL and TNF‐α, and fibroblasts from SFMCs overexpressed RANKL. Thus, T cells and fibroblasts from synovial fluid through the production of osteoclastogenic cytokines could support the OC formation in PsA patients.
MRI and Quantification of Draining Lymph Node Function in Inflammatory Arthritis
Authors: PROULX STEVEN T. , KWOK EDMUND , YOU ZHIGANG , BECK CHRISTOPHER A. , SHEALY DAVID J. , RITCHLIN CHRISTOPHER T. , BOYCE BRENDAN F. , XING LIANPING , SCHWARZ EDWARD M.
Published: December 2007

Abstract:  While erosion and tissue necrosis are the end‐stage result of inflammatory arthritis, factors that can predict their initiation and severity are unknown. In an effort to identify these prognostic factors we developed contrast‐enhanced (CE)‐magnetic resonance imaging (MRI) for the mouse knee to assess the pathogenesis of inflammatory arthritis. Using this approach to study synovitis and draining lymph node (LN) function we first demonstrated that the LNs of TNF‐Tg mice at 5 months are significantly larger and have greater enhancement in comparison to wild‐type (WT) mice. This difference correlated with the abundance of dilated LYVE‐1+ sinuses in the draining LNs. Dynamic CE‐MRI further demonstrated differences between TNF‐Tg and WT mice in the kinetics of LN enhancement. We established an LN capacity (LNcap) measurement that is a function of both volume and CE. We demonstrated that TNF‐Tg mice have a 15‐fold increase over WT levels at 5 months age (P < 0.001). Amelioration of arthritis with anti‐TNF therapy resulted in a significant decrease in LNcap (P < 0.0001) that approached WT levels within 4 weeks. Interestingly, this functional decrease was not associated with a reduction of lymphatic vessels, which persist after therapy in both LNs and synovium. To assess the relationship between draining LN function and synovitis, a regression analysis was performed that demonstrated a significant negative correlation (R2= 0.63, P= 0.01) between LNcap and synovial volume. TNF‐Tg mice with a lower LNcap display an accelerated progression of arthritis. These results indicate a protective function of enhanced lymphatic drainage in inflammatory arthritis.
Molecular and Histological Analysis of a New Rat Model of Experimental Knee Osteoarthritis
Authors: APPLETON C. THOMAS G. , McERLAIN DAVID D. , HENRY JAMES L. , HOLDSWORTH DAVID W. , BEIER FRANK
Published: December 2007

Abstract:  Articular cartilage degeneration is the most consistently observed feature of osteoarthritis (OA). Animal and human studies have shown that various forms of exercise influence the course of the disease in different ways. In addition, early changes in articular cartilage that influence the progression of OA, such as the expression of cytokines, require further investigation. We have used a surgically induced experimental model of knee OA to address these questions. Here, we discuss our recent studies investigating the effects of an exercise paradigm in surgically induced OA, which determined that the destabilized knee joint is susceptible to enhanced degeneration when subjected to low‐intensity, low‐impact exercise. Further, we investigated early global changes in gene expression in articular chondrocytes from degenerating cartilage. Identified candidate genes including genes involved in chemokine, endothelin, and transforming growth factor‐α signaling are discussed in the context of articular cartilage degeneration in early OA.
ERK Signaling Regulates Macrophage Colony‐Stimulating Factor Expression Induced by Titanium Particles in MC3T3.E1 Murine Calvarial Preosteoblastic Cells
Authors: SEO SUNG W. , LEE DANIEL , CHO SAMUEL K , KIM ABRAHAM D. , MINEMATSU HIROSHI , CELIL AYDEMIR AYSE B. , GELLER JEFFREY A. , MACAULAY WILLIAM , YANG JAY , YOUNG‐IN LEE FRANCIS
Published: December 2007

Abstract:  Periprosthetic osteolysis poses a significant clinical problem for patients who have undergone total joint arthroplastic surgeries. It has been widely recognized that there is a strong correlation between wear particles from orthopedic implants and osteolysis. However, the molecular mechanism underlying osteolysis still remains unclear. Although wear particles interact with a mixed cellular environment, namely macrophages and immune cells, osteoblasts compose the majority of the cell population surrounding orthopedic implants. Osteoblasts are also one of the major sources of receptor activator of nuclear factor‐kappa beta (NF‐κB) ligand (RANKL), a factor necessary for osteoclastogenesis. However, macrophage colony‐stimulating factor (M‐CSF), another cytokine responsible for preosteoclast proliferation, must also be present with RANKL for osteoclastogenesis to occur. The purpose of our study is to determine the signal transduction pathway by which titanium (Ti) particles, a metallic component of many orthopedic implants, induce M‐CSF expression in MC3T3.E1 murine calvarial preosteoblastic cells. Using reverse transcriptase‐polymerase chain reaction (RT‐PCR) and enzyme‐ linked immunosorbent assay (ELISA), our study demonstrated that submicron‐sized Ti particles induce M‐CSF expression via the extracellular signal‐regulated kinase (ERK) pathway in a dose‐dependent manner. Moreover, inhibition studies showed that a specific ERK inhibitor, PD98059, significantly downregulated M‐CSF production. Our results support the hypothesis that submicron‐sized Ti particles can induce M‐CSF expression in osteoblasts and thus may have a significant role in contributing to the onset of periprosthetic osteolysis.
Lumbar Spine Bone Mineral Density Changes in Patients with Primary Hyperparathyroidism According to Age and Gender
Authors: LUMACHI FRANCO , CAMOZZI VALENTINA , ERMANI MARIO , NARDI ALFREDO , LUISETTO GIOVANNI
Published: December 2007

Abstract:  Primary hyperparathyroidism (PHPT) results from excessive secretion of parathyroid hormone (PTH), and catabolic and anabolic effects of PTH on bone may lead to overall deleterious effects on skeleton. The aim of this study was to analyze the changes in lumbar spine bone mineral density (BMD) in patients with PHPT who underwent parathyroidectomy (PTx), and to correlate the main demographics and biochemical parameters with pre‐ and postoperative BMD values. Two groups of age‐matched patients (group A = 14 postmenopausal women; group B = 13 men, overall median age 53 years, range 26–56 years) with confirmed PHPT were enrolled in the study. All patients underwent lumbar (L2‐L4 region) spine osteodensitometry using a dual‐energy X‐ray absorptiometry (DXA) prior to surgery. A significant correlation between alkaline phosphatase (ALP) and PTH (R= 0.73, P= 0.003) was found in group A patients. In group B correlations were found between calcemia and ALP (R= 0.71, P= 0.007), and between osteocalcin and both PTH (R= 0.65, P= 0.01) and ALP (R= 0.59, P= 0.03). No correlation (P= NS) was found between BMD, both basal and postoperative, and age or biochemical parameters. The 1‐year BMD were 0.937 ± 0.115 and 0.940 ± 0.201 g/cm2 (P= NS) in group A and B, respectively. A significant (P= 0.03) difference between basal and 1‐year BMD was found only in group A, while in group B the difference was not significant. In conclusion, in patients with PHPT bone turnover is increased and consequently the BMD is reduced, but unfortunately PTx does not allow for complete bone restoring. However, in premenopausal women the BMD values of the lumbar spine significantly improve after PTx, suggesting a higher bone sensitivity to serum PTH normalization due to a synergic action with estrogens.
Vitamin D in Defense of the Human Immune Response
Authors: ADAMS JOHN S. , LIU PHILIP T. , CHUN RENE , MODLIN ROBERT L. , HEWISON MARTIN
Published: December 2007

Abstract:  Defensin is a generic name reserved for an endogenously synthesized antimicrobial agent. The purpose of this review is to describe a series of discoveries that led to the proposal that 25‐hydroxylated metabolites of vitamin D are key, intracellular regulators of the synthesis and action of naturally occurring defensin molecules against bacterial antigens. The discussion will (1) highlight the basic elements of human immune response that is responsive to vitamin D, (2) recount work relevant to the extrarenal expression of the vitamin D‐1‐hydroxlase (CYP27b1) in the macrophage as an initiator of the innate immune response, and (3) describe recent work on the relevance of the vitamin D intracrine–autocrine–paracrine system in a model of a common and devastating human disease, tuberculosis.
Osteogenic Differentiation of Human Mesenchymal Bone Marrow Cells in Silk Scaffolds Is Regulated by Nitric Oxide
Authors: DAMOULIS PETROS D. , DRAKOS DIMITRIOS E. , GAGARI ELENI , KAPLAN DAVID L.
Published: December 2007

Abstract:  Bone marrow‐derived mesenchymal stem cells (BMSC) are a powerful tool for tissue engineering and can be used in the regeneration of bone and other tissues. Nitric oxide (NO) produced by the endothelial NO synthase (eNOS) plays an important role in bone development and healing. We hypothesized that NO plays a role in osteogenic differentiation of BMSC cultured in three‐dimensional silk scaffolds. eNOS protein was measured by Western Analysis and its activity was assessed by measuring nitrite in culture supernatants. Mineralization was evaluated through calcium deposition and the expression of genes associated with osteogenic differentiation (collagen I, RUNX2, and osteocalcin) was quantified using real‐time RT‐PCR. eNOS was consistently expressed with minor fluctuations, but NO production significantly increased at later time points (weeks 4 and 5). Addition of a competitive NOS inhibitor (L‐NAME) resulted in a modest decrease in calcium deposition, which became statistically significant in week 5. This was preceded by a dramatic decrease in RUNX2 and osteocalcin expression in week 4. These results support our hypothesis and implicate NO as an important player in bone tissue engineering.
Effects of Adrenal Steroids on the Bone Metabolism of Children with Congenital Adrenal Hyperplasia
Authors: LIN‐SU KAREN , NEW MARIA I.
Published: December 2007

Abstract:  The primary treatment for patients with congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase deficiency (21OHD) is glucocorticoid replacement therapy, which at supraphysiologic levels can result in diminished bone accrual and lead to osteopenia and osteoporosis. Unlike other diseases treated with chronic glucocorticoid therapy, previous studies of patients with 21OHD have not demonstrated a detrimental effect of glucocorticoid treatment on bone mineral density (BMD). It has been postulated that the elevated androgens typically found in these patients have a protective effect on bone integrity, but the precise mechanism remains unknown. We propose that the inhibitory effect of corticosteroid therapy on bone formation is counteracted by estrogen's effect on bone resorption through the RANK‐L/osteoprotegerin (OPG) system. A better understanding of the mechanism by which patients with 21OHD are protected against bone loss may lead to novel therapeutic measures to prevent or treat osteopenia and osteoporosis in other conditions, including postmenopausal women.
Selecting Patients for Osteoporosis Therapy
Authors: SILVERMAN STUART L.
Published: December 2007

Abstract: Our goal globally is to better identify individuals at risk for osteoporotic fracture so that those at high risk can be treated and unnecessary treatment for those at low risk can be avoided. Bone mineral density (BMD) information is not sufficient to identify all patients at high risk. Approximately half of patients in the community with fractures do not have osteoporosis by the 1994 World Health Organization BMD criteria. Furthermore, BMD information based on central DXA is not easily accessible worldwide. The use of clinical risk factors with or without BMD information will improve gradient of risk and help us better identify patients at high risk for fracture. The clinical risk factors identified can be integrated to predict a 10‐year absolute risk or probability of fracture. Intervention thresholds based on absolute risk will be defined regionally based on each nation's ability and willingness to pay.
The Skeletal Dysplasias
Authors: RIMOIN DAVID L. , COHN DANIEL , KRAKOW DEBORAH , WILCOX WILLIAM , LACHMAN RALPH S. , ALANAY YASEMIN
Published: December 2007

Abstract:  The skeletal dysplasias or osteochondrodysplasias are a clinically and genetically heterogeneous group of disorders of bone and/or cartilage. They are characterized by abnormalities in pattering, linear growth, differentiation, and maintenance of the human skeleton. While they have been considered to be generalized disorders of endochondral and/or membranous ossification, the extent of their clinical and molecular heterogeneity is still being elucidated. In the 2006 revision of the International Nosology and Classification of Genetic Skeletal Disorders, 372 different conditions were listed in 37 groups defined by such molecular, biochemical, and/or radiographic criteria. The evaluation of patients with chondrodysplasias mandates a multidisciplinary approach involving clinical geneticists, radiologists, molecular biologists, and biochemical geneticists for diagnosis, and a host of surgical specialists for management of their many complications. Our International Skeletal Dysplasia Registry is a worldwide referral center for the skeletal dysplasias, and we have received cases from over 3000 physicians from 50 different countries and have been involved in the identification of the molecular defect in over 40 disorders involving over 25 different genes. Instructions on accessing the Registry, using the diagnostic services provided and contributing cases for collaborative research can be found at

http://www.csmc.edu/skeletaldysplasia
.
Perspective on the Osteoclast
Authors: CACKOWSKI FRANK C. , ROODMAN G. DAVID
Published: December 2007

Abstract:  There have been reports recently that the osteoclast stimulates angiogenesis in vitro. We review the evidence suggesting that the osteoclast directly stimulates angiogenesis, and discuss the feasibility of the hypothesis that the osteoclast can be a proangiogenic cell. Reasons supporting the feasibility of this hypothesis include proangiogenic factors produced by osteoclasts, the angiogenic effects of macrophages, the antiangiogenic effects of nitrogen containing bisphosphonates, and the physical proximity of osteoclasts to endothelial cells.
Vascular Bmp–Msx2–Wnt Signaling and Oxidative Stress in Arterial Calcification
Authors: SHAO JIAN‐SU , ALY ZIYAD AL , LAI CHUNG‐FANG , CHENG SU‐LI , CAI JUN , HUANG EMILY , BEHRMANN ABE , TOWLER DWIGHT A.
Published: December 2007

Abstract:  Studies of fracture repair have revealed that paracrine endothelial–mesenchymal interactions direct bone formation that restores osseous integrity. Angiogenic growth factors and specific members of the bone morphogenetic protein (BMP) family mediate these interactions. Recently, these same signals have been shown to be critical in the vascular pathobiology of hypertension, diabetes, and atherosclerosis. In the arterial vasculature, mechanical and inflammatory redox signals, characteristic of hypertension and diabetes have emerged as a secretagogues for BMP production—with downstream activation of endothelial NADPH oxidases (Nox). Preliminary data now indicate that the paracrine signals provided by BMP and reactive oxygen species augment aortic myofibroblast Msx2–Wnt signaling and matrix turnover. The net mural response to these stimuli promotes osteogenic differentiation of calcifying vascular cells, moreover, oxidation of vascular LDL cholesterol generates oxysterols that trigger Runx2 activity via hedgehog pathways. Thus, BMP, Wnt, and hedgehog gene expression programs—osteogenic pathways highly familiar to the bone biologist—are elaborated in the arterial vasculature via redox‐regulated mechanisms. In the brief review, we recount mounting evidence that points to oxidative stress as a major contributor to the pathobiology of diabetic arterial calcification.
Fetal Growth Plate
Authors: PROVOT SYLVAIN , SCHIPANI ERNESTINA
Published: December 2007

Abstract:  Fetal growth plate chondrocyte is a unique mesenchymal tissue, as it is avascular and hypoxic. Yet, chondrocytes not only survive in this environment, but also undergo all cellular processes (proliferation, growth arrest, differentiation, etc.) required for normal endochondral bone development. A crucial mediator of the adaptive response of cells to hypoxia is a transcription factor named hypoxia‐inducible factor 1α (Hif‐1α). One target of Hif‐1α transcriptional activation is the angiogenic factor vascular endothelial growth factor (VEGF), whereas Hif‐1α accumulation is controlled by the von Hippel–Lindau (VHL) tumor suppressor, an E3‐ubiquitin ligase that induces its degradation by the proteasome. We, and others, demonstrated that each component of this pathway is a critical regulator of endochondral bone development. In particular, we previously established that Hif‐1α is a survival factor for hypoxic chondrocytes, and that it also negatively regulates cell proliferation. Interestingly, we also showed that hypoxia increases extracellular matrix accumulation in a Hif‐1α‐dependent fashion. This suggested that Hif‐1α could be critically important not only for cell survival and proliferation but also for cell differentiation. We recently demonstrated that Hif‐1α is indeed a differentiation factor since it is required in mesenchymal cells both for early chondrogenesis, and for joint development.
Historical Reflections and the Future
Authors: MacINTYRE IAIN
Published: December 2007

Abstract:  This meeting has excitingly described the modern status of skeletal biology. Many advances are described in detail but it may be of value to describe the original discovery of two iconic osteoclast regulators, calcitonin and PTH, whose development in the 1960s initiated the revolution in the field.
The Sound of Silence in Online Feedback: Estimating Trading Risks in the Presence of Reporting Bias
Authors: Dellarocas Chrysanthos , Wood Charles A.
Published: December 2007

Most online feedback mechanisms rely on voluntary reporting of privately observed outcomes. This introduces the potential for reporting bias, a situation where traders exhibit different propensities to report different outcome types to the system. Unless properly accounted for, reporting bias may severely distort the distribution of public feedback relative to the underlying distribution of private transaction outcomes and, thus, hamper the reliability of feedback mechanisms. This study offers a method that allows users of feedback mechanisms where both partners of a bilateral exchange are allowed to report their satisfaction to “see through” the distortions introduced by reporting bias and derive unbiased estimates of the underlying distribution of privately observed outcomes. A key aspect of our method lies in extracting information from the number of transactions where one or both trading partners choose to remain silent. We apply our method to a large data set of eBay feedback. Our results support the widespread belief that eBay traders are more likely to post feedback when satisfied than when dissatisfied and are consistent with the presence of positive and negative reciprocation among eBay traders. Most importantly, our analysis derives unbiased estimates of the risks that are associated with trading on eBay that, we believe, are more realistic than those suggested by a naïve interpretation of the unusually high (>99%) levels of positive feedback currently found on that system.
The Take-up Debate on the UK Family Income Supplement
Authors: Stanton David
Published: December 2007

The Family Income Supplement (FIS) is a particularly interesting aspect of UK social security provisions for families. It represents one of the few examples in the world of a social security payment designed specifically to assist low wage-earners in employment, albeit at modest levels. The introduction of FIS to help tackle the problem of family poverty represented an important departure from the philosophy behind the UK social security system as, for the first time, a cash benefit was to be paid to those in full-time employment but whose income was below a certain amount. Prior to FIS, persons in full-time employment were ineligible for any benefits aimed at reducing family poverty e.g. supplementary benefits (SB).

It was opposed by the Labour Party, the Child Poverty Action Group (CPAG) and many academics because it utilizes a means test. This opposition is most clearly stated in literature published by CPAG. For instance, Frank Field, secretary of that organization, recently wrote: ‘From the word go, the CPAG has campaigned for family allowance increases for both those in and out of work, and since 1969 every action of the poverty lobby has been aimed at underminin public confidence in means-tested benefits.’
Standard Setting and the Theory of Institutional Choice: The Case of Pollution Control
Authors: Storey D.J.
Published: December 2007

The argument presented by Majone in a recent article in Policy and Politics may be summarized thus: By all objective criteria effluent charges can be shown to be superior to other policies for controlling discharges to waterways, yet there is a reluctance among policy makers to their usage. He concludes that since it is unreasonable to assume that policy makers are stupid, or blindly prejudiced, the only possible explanation is that the self-interest of the politician or bureaucrat must be interfering with his objectivity.

It is not the purpose of this note to assert that politicians or bureaucrats are always concerned to maximize public welfare, however defined, or – to use Breton’s phrase – to ‘minimize the degree of coercion.’ Instead, it is intended to outline the pitfalls of an approach which justifies unequivocably a policy and proceeds to conclude that because of its non-introduction legislators are pursuing antisocial objectives. Specifically, the balance of the effluent charge versus the standards approach will be redressed.

Majone states that effluent charges are an efficient method of achieving a specified water quality, but that the restriction of quantities discharged in physical form (by the ‘consent’ system in the U.K. context) requires information too costly to be collected.
Women’s Aid Groups: The Economic Case for State Assistance to Battered Wives
Authors: Barr N A , Carrier J W
Published: December 2007

This paper asks two broad questions: (1) Why is that in a country with such a broadly based welfare state as ours there is so little provision for battered wives? and, (2) What resources should be devoted to assisting this group? These questions are discussed respectively in sections 2 and 3. In this section we start by describing what little assistance there has been up to now for battered wives.

The pioneer group in the field was Chiswick Women’s Aid (henceforth CWA), and it is worthwhile briefly to outline their activities. The primary function of CWA is to give assistance to battered wives and their children, as described by Pizzey The basic structure is that of a wheel, with spokes leading out from the hub to points on the rim. The hub is the so-called Crisis Refuge in Chiswick which accepts mothers and their children on a twenty-four hour, open-door basis. That is to say, mothers can arrive an any time of the day or night and will never be turned away. The Crisis Refuge, as its name implies, deals more with short-run cases than with long-run chronic situations though in this context short-run may mean several months.
Central Controls and Local Budgeting Behaviour: A Test of some Partial Models
Authors: Hansen Tore
Published: December 2007

Despite the increasing awareness among students of urban and local policy-making of the importance of central controls and regulations in shaping local policies, empirical research in this area still tends to treat local authorities as if they were more or less isolated, self-sufficient decision-making units. Attention has largely been confined to what David Easton calls the intrasocietal part of the system’s environment in searching for determinants of local decision-making behaviour, while extrasocietal forces – factors outside the geographical boundaries of the local system – have been treated only marginally or neglected altogether. The growing concern about the increased interdependencies between national and local authorities and – assumedly – the decreased autonomy of local government, has so far only led to rather general comments on the nature of these relationships in the empirical literature on urban policy-making.

This lack of concern about the wider political context within which the local government operates may be due to the fact that most empirical studies of local policy-making have been limited to local units within one country.
Local Outputs Research: Some Reflections and Proposals
Authors: Newton Kenneth , Sharpe L. J.
Published: December 2007

Research into politics is the art of the possible, and of all the possible approaches open to the political scientist in pursuit of some of the timeless questions of the discipline, the study of the fiscal and budgetary policies of government is one of the most vital. This is because it reflects such fundamental aspects of government as the setting of priorities, the allocation of resources, and the scope of the public sector itself. In other words, the fiscal approach provides one way of answering the primordial question: Why do governments vary in the policies they pursue? Until a decade or so ago, it is fair to say that most political scientists assumed that the primary determinants of public policy were political, and they therefore confined their attention to political institutions and processes, especially to legislative and pre-legislative politics. But a change has now taken place and attention has shifted to post-legislative politics; to, as it were, the object of the whole political exercise, to services, to policy, and to outputs. And instead of assuming that all can be explained by political factors, the causal nexus has been opened up to see how far underlying, non-political characteristics bear upon policy.
Towards an Economic Model of Local Government Behaviour
Authors: Grand Julian Le , Winter David
Published: December 2007

Newton and Sharpe in their contribution to this volume have drawn attention to the urgent need for developing a general theoretical framework in which future output research (in the area of British local government) can be undertaken. It is our intention in this paper to explore the possibility of rectifying this omission by the application of some theoretical constructs used by economists in the study of economic behaviour. More specifically, we examine a simple model of government behaviour incorporating the concepts of a social welfare function and production function, illustrate how it might be used in the British case to provide some insight into the determinants of local authority output decisions, and examine some of the difficulties involved. We do not present any empirical tests, and our conclusions must therefore be qualitative and highly tentative. Nonetheless it seems worth while to discuss the approach in the hope that it may be useful for subsequent empirical work.

In the first section, we examine some of the weaknesses in previous studies of UK local government expenditure.
Politics and Expenditure Models
Authors: Alt James E.
Published: December 2007

The quantitative study of local government expenditure has seen to a great extent British political scientists (as has been so often the case in urban politics) responding to an American lead. What were tested in this country were the Easton-based models of Dawson and Robinson, Dye, Sharkansky, and others, which postulated a very simple (three-variable) system. The three variables were expenditure, socio-economic context and political control, and the question raised was of the relative impact of the last two on the first. While the American studies suggested the primacy of socio-economic context, the British studies appeared to suggest that more importance should be attached to political control. However, this view of the importance of party control is disputed in a number of studies, leaving the question of the relationship of political variables to local expenditures rather a vexed one.

The American studies originated with Key’s argument that welfare policies were better provided in those areas of the American South which had competitive party systems.
Community Care: Some Research Problems and Priorities
Authors: Abrams Philip
Published: December 2007

To those with a passion for conceptual tidiness the whole field of social care must be exceptionally frustrating; within that field community care is perhaps the least tidy corner. A convenient and in some ways useful definition would see community care as a matter of the provision of help, support and protection to others by lay members of societies acting in everyday domestic and occupational settings. It could thus be distinguished from some of the other main froms of social care – institutional care, institutional treatment and community treatment – by both its typical agents and its typical milieux. The agents of community care are unspecialized and the milieux are open; both are socially given rather than administratively constructed. The distinction could be summarized figurately thus:

Any such distinction at once makes three things apparent.

1. Community care, even defined in this fairly extreme manner, is not an impossibility. We know of social systems in which effective care is provided by lay persons in socially open settings on a comprehensive and continuous basis. The most remarkable instance is possibly the Japanese tsukiai reported by Dore.
Characterization of Adult Prostatic Progenitor/Stem Cells Exhibiting Self-Renewal and Multilineage Differentiation
Authors: Barclay Wendy W. , Axanova Linara S. , Chen Wenhong , Romero Lina , Maund Sophia L. , Soker Shay , Lees Cynthia J. , Cramer Scott D.
Published: December 2007

Demonstration of the hallmarks of stem cells, self-renewal and multilineage differentiation, is a challenge that has not been met for numerous tissues postulated to possess adult stem cells, including prostate tissue. Using a defined medium, we reproducibly isolated and maintained adult mouse prostatic cells with characteristics of progenitor/stem cells. Clonal populations of cells demonstrated tissue-specific multilineage differentiation by their ability to generate organized prostatic ductal structures in vivo, with luminal and basal cell layers, when grafted under the renal capsules of mice in the presence of fetal rat urogenital mesenchyme. Complete differentiation was demonstrated by the expression and secretion of terminally differentiated prostatic secretory products into the lumens. Self-renewal was demonstrated by serial transplantation of clonal populations that generated fully differentiated ductal structures in vivo. In vitro, undifferentiated cells expressed markers associated with prostate stem cells, including Sca 1 and CD49f, as well as basal cell markers (p63 and cytokeratins 5 and 14) and, at a low level, luminal cell markers (androgen receptor and cytokeratins 8 and 18). When grafted and allowed to differentiate in the presence of fetal urogenital mesenchyme, the cells differentiated into luminal cells and basal cells with more restricted protein expression patterns. These studies are the first to report a reproducible system to assess adult prostatic progenitor/stem cells.

Disclosure of potential conflicts of interest is found at the end of this article.
Widespread Nonhematopoietic Tissue Distribution by Transplanted Human Progenitor Cells with High Aldehyde Dehydrogenase Activity
Authors: Hess David A. , Craft Timothy P. , Wirthlin Louisa , Hohm Sarah , Zhou Ping , Eades William C. , Creer Michael H. , Sands Mark S. , Nolta Jan A.
Published: December 2007

Transplanted adult progenitor cells distribute to peripheral organs and can promote endogenous cellular repair in damaged tissues. However, development of cell-based regenerative therapies has been hindered by the lack of preclinical models to efficiently assess multiple organ distribution and difficulty defining human cells with regenerative function. After transplantation into β-glucuronidase (GUSB)-deficient NOD/SCID/mucopolysaccharidosis type VII mice, we characterized the distribution of lineage-depleted human umbilical cord blood-derived cells purified by selection using high aldehyde dehydrogenase (ALDH) activity with CD133 coexpression. ALDHhi or ALDHhiCD133+ cells produced robust hematopoietic reconstitution and variable levels of tissue distribution in multiple organs. GUSB+ donor cells that coexpressed human leukocyte antigen (HLA-A,B,C) and hematopoietic (CD45+) cell surface markers were the primary cell phenotype found adjacent to the vascular beds of several tissues, including islet and ductal regions of mouse pancreata. In contrast, variable phenotypes were detected in the chimeric liver, with HLA+/CD45+ cells demonstrating robust GUSB expression adjacent to blood vessels and CD45−/HLA− cells with diluted GUSB expression predominant in the liver parenchyma. However, true nonhematopoietic human (HLA+/CD45−) cells were rarely detected in other peripheral tissues, suggesting that these GUSB+/HLA−/CD45− cells in the liver were a result of downregulated human surface marker expression in vivo, not widespread seeding of nonhematopoietic cells. However, relying solely on continued expression of cell surface markers, as used in traditional xenotransplantation models, may underestimate true tissue distribution. ALDH-expressing progenitor cells demonstrated widespread and tissue-specific distribution of variable cellular phenotypes, indicating that these adult progenitor cells should be explored in transplantation models of tissue damage.

Disclosure of potential conflicts of interest is found at the end of this article.
Constitutive Expression of the ATP-Binding Cassette Transporter ABCG2 Enhances the Growth Potential of Early Human Hematopoietic Progenitors
Authors: Ahmed Farid , Arseni Natalia , Glimm Hanno , Hiddemann Wolfgang , Buske Christian , Feuring-Buske Michaela
Published: December 2007

The ATP-binding cassette transporter, ABCG2, is a molecular determinant of the side population phenotype, which is enriched for stem and progenitor cells in various nonhematopoietic and hematopoietic tissues. ABCG2 is highly expressed in hematopoietic progenitors and silenced in differentiated hematopoietic cells, suggesting a role of ABCG2 in early hematopoiesis. To test whether ABCG2 is involved in human hematopoietic development, we retrovirally transduced umbilical cord blood-derived early hematopoietic cells and analyzed hematopoiesis in vitro and in vivo. ABCG2 increased the number of clonogenic progenitors in vitro, including the most primitive colony-forming unit-granulocyte, erythroid, macrophage, megakaryocyte, by twofold (n = 14; p < .0005). Furthermore, ABCG2 induced a threefold increase in the replating capacity of primary colonies (n = 9; p < .01). In addition, ABCG2 impaired the development of CD19+ lymphoid cells in vitro. In transplanted NOD/SCID mice, the ATP-binding cassette transporter decreased the number of human B-lymphoid cells, resulting in an inversion of the lymphoid/myeloid ratio. ABCG2 enhanced the proportion of CD34+ progenitor cells in vivo (n = 4; p < .05) and enhanced the most primitive human progenitor pool, as determined by limiting dilution competitive repopulating unit assay (p < .034). Our data characterize ABCG2 as a regulatory protein of early human hematopoietic development.

Disclosure of potential conflicts of interest is found at the end of this article.
Identification of a Novel Putative Gastrointestinal Stem Cell and Adenoma Stem Cell Marker, Doublecortin and CaM Kinase-Like-1, Following Radiation Injury and in Adenomatous Polyposis Coli/Multiple Intestinal Neoplasia Mice
Authors: May Randal , Riehl Terrence E. , Hunt Clayton , Sureban Sripathi M. , Anant Shrikant , Houchen Courtney W.
Published: December 2007

In the gut, tumorigenesis arises from intestinal or colonic crypt stem cells. Currently, no definitive markers exist that reliably identify gut stem cells. Here, we used the putative stem cell marker doublecortin and CaM kinase-like-1 (DCAMKL-1) to examine radiation-induced stem cell apoptosis and adenomatous polyposis coli (APC)/multiple intestinal neoplasia (min) mice to determine the effects of APC mutation on DCAMKL-1 expression. Immunoreactive DCAMKL-1 staining was demonstrated in the intestinal stem cell zone. Furthermore, we observed apoptosis of the cells negative for DCAMKL-1 at 6 hours. We found DNA damage in all the cells in the crypt region, including the DCAMKL-1-positive cells. We also observed stem cell apoptosis and mitotic DCAMKL-1-expressing cells 24 hours after irradiation. Moreover, in APC/min mice, DCAMKL-1-expressing cells were negative for proliferating cell nuclear antigen and nuclear β-catenin in normal-appearing intestine. However, β-catenin was nuclear in DCAMKL-1-positive cells in adenomas. Thus, nuclear translocation of β-catenin distinguishes normal and adenoma stem cells. Targeting DCAMKL-1 may represent a strategy for developing novel chemotherapeutic agents.

Disclosure of potential conflicts of interest is found at the end of this article.