bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of stellate cells in pancreatic fibrogenesis associated with acute and chronic pancreatitis
Authors: Bachem Max G , Zhou Zhengfei , Zhou Shaoxia , Siech Marco
Published: August 2006

Pancreas fibrosis is the result of a dynamic cascade of mechanisms beginning with acinar cell (AC) injury and necrosis and followed by inflammation, activation of macrophages, aggregation of platelets, release of growth factors and reactive oxygen species (ROS), activation of pancreatic stellate cells (PSC), stimulated synthesis of extracellular matrix and reduced matrix degradation. The result is a net matrix accumulation. Numerous in vivo and in vitro studies have provided strong evidence of a central role for PSC in fibrogenesis associated with acute and chronic pancreatitis. The PSC share homologies with hepatic stellate cells (HSC). In normal pancreas, the fat‐storing phenotype of PSC is found in low numbers (approx. 4% of the cells) in the periacinar and interlobular space. Similar to the stellate cell‐activating mechanisms in the liver, in pancreas injury PSC change their phenotype from the fat‐storing to a highly active matrix‐producing cell type (activated PSC). The induction of the activated phenotype of PSC has been shown to involve a number of diverse extra‐ and intracellular effector molecules, including inflammatory cytokines, growth factors, ethanol, acetaldehyde, and oxidative stress.
Early peristalsis following epidural analgesia during abdominal surgery in an extremely low birth weight infant
Authors: HOEHN THOMAS , JETZEK‐ZADER MARTIN , BLOHM MARTIN , MAYATEPEK ERTAN
Published: August 2006

The inhibiting effect of opioids on intestinal motility is a cause of particular concern in extremely low birth weight (ELBW; birth weight <1000 g) infants with decreased peristalsis. An ELBW infant (birth weight 740 g) born after 26 + 1 week of gestation had an uneventful clinical course during the first few days of life. Sudden deterioration occurred on day 8 with metabolic acidosis, hyperglycemia and frequent apnea with secondary bradycardia. A chest X ray demonstrated the presence of air beneath the diaphragm. Intestinal perforation was suspected and the infant was taken to theater for laparotomy. For pain management, a 22 G epidural catheter was inserted via the caudal approach and threaded to a mid‐thoracic level. Epidural ropivacaine was administered intraoperatively and for 48 h postoperatively. The infant was extubated on the following day. Opioids were not required or given at any stage during or after surgery. Peristalsis was present on auscultation as early as 3 h after surgery, the first stool was passed on the same day. Enteral nutrition was resumed early and tolerated well, full enteral feeding was rapidly achieved. Our case shows that the technique of caudal anesthesia is feasible in ELBW infants. We speculate that intestinal motility and establishment of full enteral feedings may be achieved earlier by epidural ropivacaine in cases of abdominal surgery in ELBW infants.
Difficult ventilation from increased abdominal pressure
Authors: GHAFFARI SINA
Published: August 2006

Airway management is one of the most important responsibilities of every anesthesiologist. A problematic situation arises when a patient is intubated correctly but not being ventilated. A case of a 4‐year‐old child who was involved in a car accident, presented for an exploratory laparotomy. Although she was successfully intubated, she could not be ventilated. The situation only improved after a large volume of fluid (urine) was drained from the abdomen.
A new method for conservation planning for the persistence of multiple species
Authors: Nicholson Emily , Westphal Michael I. , Frank Karin , Rochester Wayne A. , Pressey Robert L. , Lindenmayer David B. , Possingham Hugh P.
Published: August 2006

Although the aim of conservation planning is the persistence of biodiversity, current methods trade‐off ecological realism at a species level in favour of including multiple species and landscape features. For conservation planning to be relevant, the impact of landscape configuration on population processes and the viability of species needs to be considered. We present a novel method for selecting reserve systems that maximize persistence across multiple species, subject to a conservation budget. We use a spatially explicit metapopulation model to estimate extinction risk, a function of the ecology of the species and the amount, quality and configuration of habitat. We compare our new method with more traditional, area‐based reserve selection methods, using a ten‐species case study, and find that the expected loss of species is reduced 20‐fold. Unlike previous methods, we avoid designating arbitrary weightings between reserve size and configuration; rather, our method is based on population processes and is grounded in ecological theory.
Evaluation of denaturing gradient gel electrophoresis to differentiate Escherichia coli populations in secondary environments
Authors: Sigler Von , Pasutti Lauren
Published: August 2006

The development of methodology to differentiate mixed populations of Escherichia coli in the secondary habitat might improve monitoring of fecal pollution indicators and facilitate the development of strategies to mitigate bacterial pollution. The objective of this study was to determine the ability of denaturing gradient gel electrophoresis (DGGE) to differentiate mixed assemblages of E. coli in the natural environment. After confirming the identity of 184 environmental bacterial isolates as E. coli, each was subjected to polymerase chain reaction (PCR) of the β‐glucuronidase gene (uidA) followed by DGGE fingerprinting. The ability of DGGE to discriminate individual isolates at the strain level was determined by comparing fingerprints to those resulting from a standard, library‐dependent fingerprinting method, BOX‐PCR. Computerized analysis of fingerprints indicated that DGGE and BOX‐PCR identified 15 and 21 unique phylotypes respectively. Rank–abundance plots comparing the numerical distribution of unique E. coli phylotypes detected by both methods revealed no difference in resolution at the population level. In water and sediment samples from two beaches, DGGE effectively distinguished indigenous E. coli populations with an average rate of correct classification (site‐based) of 83%. Denaturing gradient gel electrophoresis of uidA genes isolated and PCR‐amplified from environmental samples appears to be an effective tool to differentiate unique E. coli populations and should be useful to characterize E. coli dynamics in the secondary environment.
Autotrophic CO2 fixation via the reductive tricarboxylic acid cycle in different lineages within the phylum Aquificae: evidence for two ways of citrate cleavage
Authors: Hügler Michael , Huber Harald , Molyneaux Stephen J. , Vetriani Costantino , Sievert Stefan M.
Published: August 2006

Autotrophic carbon fixation was characterized in representative members of the three lineages of the bacterial phylum Aquificae. Enzyme activity measurements and the detection of key genes demonstrated that Aquificae use the reductive tricarboxylic acid (TCA) cycle for autotrophic CO2 fixation. This is the first time that strains of the Hydrogenothermaceae and ‘Desulfurobacteriaceae’ have been investigated for enzymes of autotrophic carbon fixation. Unexpectedly, two different mechanisms of citrate cleavage could be identified within the Aquificae. Aquificaceae use citryl‐CoA synthetase and citryl‐CoA lyase, whereas Hydrogenothermaceae and ‘Desulfurobacteriaceae’ use ATP citrate lyase. The first mechanism is likely to represent the ancestral version of the reductive TCA cycle. Sequence analyses further suggest that ATP citrate lyase formed by a gene fusion of citryl‐CoA synthetase and citryl‐CoA lyase and subsequently became involved in a modified version of this pathway. However, rather than having evolved within the Aquificae, our phylogenetic analyses indicate that Aquificae obtained their ATP citrate lyase through lateral gene transfer. Aquificae play an important role in biogeochemical processes in a variety of high‐temperature habitats. Thus, these findings substantiate the hypothesis that autotrophic carbon fixation through the reductive TCA cycle is widespread and contributes significantly to biomass production particularly in hydrothermal habitats.
Abundance, distribution and potential activity of methane oxidizing bacteria in permafrost soils from the Lena Delta, Siberia
Authors: Liebner Susanne , Wagner Dirk
Published: August 2006

The methane oxidation potential of active layer profiles of permafrost soils from the Lena Delta, Siberia, was studied with regard to its respond to temperature, and abundance and distribution of type I and type II methanotrophs. Our results indicate vertical shifts within the optimal methane oxidation temperature and within the distribution of type I and type II methanotrophs. In the upper active layer, maximum methane oxidation potentials were detected at 21°C. Deep active layer zones that are constantly exposed to temperatures below 2°C showed a maximum potential to oxidize methane at 4°C. Our results indicate a dominance of psychrophilic methanotrophs close to the permafrost table. Type I methanotrophs dominated throughout the active layer profiles but their number strongly fluctuated with depth. In contrast, type II methanotrophs were constantly abundant through the whole active layer and displaced type I methanotrophs close to the permafrost table. No correlation between in situ temperatures and the distribution of type I and type II methanotrophs was found. However, the distribution of type I and type II methanotrophs correlated significantly with in situ methane concentrations. Beside vertical fluctuations, the abundance of methane oxidizers also fluctuated according to different geomorphic units. Similar methanotroph cell counts were detected in samples of a flood plain and a polygon rim, whereas cell counts in samples of a polygon centre were up to 100 times lower.
Prevention of parastomal hernia using preperitoneal mesh: a prospective observational study
Authors: Marimuthu K. , Vijayasekar C. , Ghosh D. , Mathew G.
Published: August 2006

Objective  Parastomal hernia is a common complication after stoma formation. The objective of the study was to see whether placing prophylactic preperitoneal mesh could reduce the incidence of parastomal hernia.

Method  Patients having elective bowel surgery requiring permanent stoma were included in this study. The time required for mesh insertion, day of stoma function, and early complications were recorded. Follow up was at 6 weeks, 3‐monthly for the first year and at 6‐monthly intervals thereafter.

Results  Eighteen patients fulfilled the inclusion criteria and were followed up for 6–28 months (mean 16.05). The time taken for mesh placement was 12–22 min (mean 14). One patient had to have revision surgery on day 1 for stomal necrosis – the mesh was left in situ in that instance. This patient developed superficial laparotomy wound infection. During the follow up, no patients developed parastomal hernia, stomal prolapse, stenosis, retraction, fistula or obstruction.

Conclusion  The early results, in this group of patients, show that prophylactic polypropylene mesh insertion at the time of permanent stoma formation is encouraging and long‐term results are awaited.
A single common urgent pathway for all colorectal referrals reduces time to diagnosis and treatment
Authors: Scott M. A. , Knight A. , Brown K. , Novell J. R.
Published: August 2006

Objective  Guidelines for the urgent referral of patients with suspected colorectal cancer were introduced in 2000. They aimed to facilitate the prompt diagnosis and treatment of patients with symptoms suggestive of malignant disease. Recent assessment of these guidelines has suggested that although they identify 9–14% of patients with colorectal cancer, they may be used inappropriately and may lead to delays in treatment for those patients with cancers whose symptoms do not fit the guidelines. We aimed to assess the effect of introducing a single pathway for all referrals irrespective of indicated urgency.

Method  All referral letters to a single consultant colorectal surgeon over a 6‐month period were coded ‘urgent’ irrespective of the indicated urgency on the original referral letter. Data was collected prospectively on 47 patients diagnosed with colorectal cancer identified over the trial period. Patient demographics, the mode of presentation, urgency of referral and waiting times were documented.

Results  Following the introduction of the common urgent referral pathway, no patient waited longer than 62 days from referral to treatment or 31 days from the decision to treat to first treatment, thus meeting government targets introduced in 2005.

Conclusion  The introduction of the urgent referral guidelines has accelerated the referral pathway for patients with symptoms suggestive of colorectal cancer, although this is at the expense of the majority of patients who present via conventional pathways. The introduction of a common urgent pathway allows prompt diagnosis and treatment and is of particular benefit for the majority of patients not referred via the 2‐week standard. Until a more accurate method of identifying the highest risk patients is implemented, we suggest that all patients are seen on an urgent basis.
Justification for staging of epidermoid anal carcinoma after salvage surgery: a pathological guideline
Authors: Haboubi N. Y. , Edilbe M. W. , Hill J.
Published: August 2006

The currently accepted first line treatment for epidermoid anal cancer is chemoradiotherapy (CRT). Tumour size and adjacent organ involvement are the key in the pretreatment assessment for T1–T4 tumours respectively. Residual or recurrent disease following initial CRT, is best treated by salvage anorectal excision. Pathological staging systems of resections were historically validated when surgery was the primary treatment and are therefore in need of revision. We propose a new pathological staging system for salvage anorectal excision specimens to allow improved prognostic guidelines postoperatively.
Whose Human Capital? The Challenge of Value Capture When Capital is Embedded
Authors: Bowman Cliff , Swart Juani
Published: August 2006

abstract  Current approaches that position human capital as central to value generation in knowledge‐based industries obscure the importance of the relational nature of knowledge production. That is, separable and embodied forms of capital are interdependent in value creation and capture processes. We identify a relational form of capital, embedded capital, which we argue is the critical resource in knowledge‐based industries such as professional services firms, because it allows us to include agency and interdependency in the value capture process. These dimensions have previously been overlooked by the resource‐based view of the firm. Examples of embedded capital include brand value, processes and procedures. The deployment of embedded capital is also not clearly controlled by either the firm or individual employees. A model is developed to illustrate the links between each form of capital, and the processes of value capture. This conceptual identification of the embedded form of capital is therefore of importance to future value creation and capture debates.
Effects of Firm R&D Investment and Environment on Acquisition Likelihood*
Authors: Heeley Michael B. , King David R. , Covin Jeffrey G.
Published: August 2006

abstract R&D investments contribute to the development of firm technology resources, and the possession of such resources often increases a firm's attractiveness as a potential acquisition target. However, the value ascribed to a firm's technology resources by would‐be acquirers may be moderated by its industry's environmental characteristics. Using data from 2886 firms, we find that investments in R&D predict acquisition likelihood and that R&D investments are most strongly associated with acquisition of firms under conditions of high environmental munificence and dynamism. Theoretical and managerial implications are discussed.
The Lack of Impact of Dissensus Inspired Analysis on Developments in the Field of Human Resource Management*
Authors: Keegan Anne , Boselie Paul
Published: August 2006

abstract  Mainstream HRM journals have largely ignored critical perspectives on HRM. This is the main finding from our study examining trends in publishing on HRM through an analysis of published work in the period 1995 to 2000. Using the ‘dissensus–consensus’ dimension of a framework developed by Deetz (1996) we examine the role of academic journals in constructing HRM knowledge in what turns out to be largely consensus oriented ways. We survey HRM articles in nine journals over a six year period, and conclude that HRM is primarily constituted from a consensus perspective in the mainstream HRM journals while European based general management and organization theory journals construct HRM in both dissensus and consensus oriented ways. We propose reasons why the critical debates in HRM have largely been ignored in the mainstream journals as well as what this might mean for HRM theory and practice given the lack of critical and dissenting voices so evident in leading HRM journals.
NIA0004 Unsaturated fatty acids diminish the detrimental effects of saturated fatty acids on insulin signalling in human muscle by decreasing de novo ceramide production
Authors: Sabin MA , Holly JMP , Hunt LP , Turner SJ , Grohmann MJ , Crowne EC , Stewart CEH , Shield JPH
Published: August 2006

Objective:  Fatty acids (FAs) are raised in obesity and saturated FAs have adverse effects on insulin signalling. We investigated this further using in vitro differentiated myotubes derived from 6 normal‐weight prepubertal children.

Methods:  We examined the effect of 24‐hour exposure to 750 μM palmitate, and/or 2000 μM oleate on the phosphorylation of the key insulin‐signalling molecule AKT (pAKT) in response to 100ng/mL insulin (by Western immunoblotting). We then determined whether palmitate must be metabolized to have its effect (using bromopalmitate – a non‐metabolizable form of palmitate) and whether a ceramide synthase inhibitor (Fumonisin B1) could block palmitate‐induced effects. Intracellular ceramide levels were then quantified by Thin Layer Chromatography and radiolabelling studies were utilized to assess the effects of oleate on palmitate‐induced ceramide production.

Results:  Palmitate significantly decreased insulin‐stimulated pAKT (mean (SEM) %change vs. control; −38.7% (11.7); P < 0.001), whilst oleate was without effect (−1.8% (14.0); P = 0.55). Together, oleate reversed the reduction seen with palmitate alone (+35.6% (18.4); P = 0.27). Bromopalmitate did not cause a similar decrease in pAKT (+10.7% (5.6); P = 0.23) and addition of 1 μM Fumonisin B1 prevented the palmitate‐induced effects. 750 μM palmitate led to a 2.2 fold increase in intracellular ceramide levels while only minimal increases were seen with bromopalmitate/oleate. Radiolabelling studies demonstrated that the addition of 375 μM oleate to 375 μM14C‐palmitate led to a significant decrease in de novo14C‐ceramide production compared to palmitate alone (101.6 (21.6) vs. 371.5(122.4); P < 0.001).

Conclusions:  These data suggest that saturated FAs have detrimental effects on insulin signalling in human muscle, by promoting de novo ceramide production, and that unsaturated FAs confer a degree of protection against these effects.
NIA0005 Long‐term weight maintenance: does diet composition matter? A randomized, prospective trial
Authors: Delbridge EA , Prendergast LA , Pritchard JE , Proietto J
Published: August 2006

Background:  High protein diets confer weight loss and metabolic advantages over high carbohydrate diets in the short‐to‐medium term. Little has been published on long‐term use of high protein diets, especially in the context of weight maintenance following significant weight loss.

Methods:  The study consisted of two phases. The first phase saw patients provided with a very low energy diet for 12 weeks. Patients who lost >10% of their body weight progressed to the second phase in which they were randomly allocated to a high carbohydrate (HC) (55% carbohydrate) or high protein (HP) diet (30% protein) to maintain their weight loss. Patients were followed up monthly for 12 months. Anthropometric and cardiovascular risk factors were measured.

Results:  A total of 173 overweight or obese people (88 males, 85 females) aged 43 years (SD = 10.6); weight 112.2 kg (±24.6); Body Mass Index 39.2 kg/m2 (±7.7) were enrolled. 151 patients (87.3%) completed phase I and entered phase II. There was no significant difference between the weight loss recorded during phase I for each group after randomization (mean weight loss 18.5 kg ±6.9 kg and 17.7 ± 5.0 respectively). On average, patients from both groups were reasonably successful in maintaining their weight loss at completion of phase II (HC 14.7 ± kg 12.5 vs. HP 14.8 kg ± 9.7), with no significant difference between the groups.

Conclusion:  Although a high protein diet compares favourably to a high carbohydrate diet in the short‐to‐medium term, in this study a high protein diet exhibited no advantage over a higher carbohydrate diet in achieving weight maintenance over a 12 month period.
WERTHEIMER AWARD AW0003 Ghrelin: discovery and physiological significance
Authors: Kangawa K
Published: August 2006

Energy balance is controlled by the intricate and precise interactions of substances to stimulate or suppress food intake and energy expenditure. The molecular mechanisms of energy balance are coming to light by the recent robust progresses in the molecular biology and neuroscience. In this regulation the bioactive peptides are recognized as the crucial molecules. In 1999, we discovered a novel growth hormone (GH)‐releasing peptide from rat stomach, and named it ‘ghrelin’. Ghrelin is a 28‐amino acid peptide with a marvelous structure modified by fatty acid, n‐octanoic acid. This n‐octanoyl modification at Ser‐3 is essential to its activity. Ghrelin is primarily produced in distinct endocrine cells, X/A‐like cells, in the stomach. Ghrelin‐producing neurons are also present in the hypothalamic arcuate nucleus, a region that regulates GH release and food intake. In fact, ghrelin stimulates GH release and feeding when administered centrally and peripherally. Ghrelin secretion is regulated under conditions of energy balance. Ghrelin is the first neuro‐enteric peptide that acts as a starvation‐signalling molecule in the periphery. The gastric vagal afferent is the major pathway conveying ghrelin's signals for starvation and GH secretion to the brain. Moreover, ghrelin has positive cardiovascular effects. Administration of ghrelin improves cardiac structure and function, and attenuates the development of cardiac cachexia in rats with heart failure. In humans, repeated administration of ghrelin improves left ventricular structure and function, exercise capacity, and muscle wasting in patients with chronic heart failure (CHF). These results suggest that ghrelin has cardiovascular protective effects and regulates energy metabolism through GH‐dependent and ‐independent mechanisms. Administration of ghrelin may be a new therapeutic approach for the treatment of CHF. Ghrelin also thus has multifaceted roles in the cardiovascular system and energy metabolism. Further studies of ghrelin will extend our understanding of how energy balance is controlled by the stomach.
IASO AWARD IN POPULATION SCIENCE AND PUBLIC HEALTH AW0008 Defining the risk of weight gain and limiting its impact
Authors: James WPT
Published: August 2006

Our 1976 UK obesity report based ‘normal’ weights on recalculated prewar US insurance data using BMIs despite their limited validity in females. Obesity's public health implications were then compared and distinguished from smoking in the Royal College Physicians (London) 1983 report. We established the 1985 UN's energy requirements of children and adults based on energy expenditure, not purported intakes and then developed a new classification of underweight with the lower normal BMI as 18.5 not 20. In 1986 our first WHO Europe report on diet, deficiencies and chronic diseases led to the global WHO 797 report with the first universal population dietary goals including 400g/head/d of vegetables and fruit. Our lithium tracer technique for dietary salt sources also emphasised the importance of processed food composition. We then established the IOTF 10 years ago, developed and spearheaded the WHO obesity report, highlighted the unusual needs of Asians, defined the classification of childhood obesity and produced the UN Millennium nutrition report highlighting the significance of low birth weight, maternal weight and childhood stunting in a life cycle approach to health. Our 2002 WHO global burden analyses established excess weight gain (BMI ≥ 21) as globally hazardous and our new Mexican analyses suggest the need to extend our concepts of Asian vulnerability. The new Global Prevention Alliance now demands novel socio‐economic thinking if we are to combat effectively the chronic disease epidemic.
AW0007 Histamine, a new regulator of adipogenesis?
Authors: Hegyi K , Toth S , Falus A
Published: August 2006

Background:  The key role of histamine in maintaining normal body weight is well established, just as the importance of cAMP‐responsive binding protein (CREB), a histamine mediator and a key transcription factor in adipogenesis. Our goal was to study if histamine has a role in adipocyte differentiation, too and if CREB is involved in this process.

Methods:  Primary embryonic fibroblasts of wild type and histamine‐deficient, histidine‐decarboxylase gene‐targeted mice were used. Adipogenesis was induced by a low‐potent induction cocktail of IBMX, insulin and dexamethasone applied according to the standard differentiation protocol either at stage of confluence or 2 days after it. Differentiation process was monitored by phase contrast microscope and verified by Oil Red O staining. CREB expression and activity was measured by TaqMan qRT‐PCR and Western blot, and cytoplasmic cAMP was determined by ELISA.

Results:  Histamine‐deficient embryonic fibroblasts differentiated better into adipocytes regardless the time point of induction compared to wild type ones. Enhanced constitutive CREB activity was detected in histamine‐free cells, whereas the expression did not change. Basal cytoplasmic cAMP levels were significantly higher in cells lacking histamine.

Conclusion:  These data suggest a newly recognized role for histamine in adipocyte differentiation. Histamine‐free undifferentiated embryonic fibroblasts show enhanced potential to form adipocytes indicating that histamine is involved in the induction of adipogenesis. Histamine is likely to exert its effect through controlling basal cAMP levels and thus CREB activity, a key inducer of adipocyte differentiation. Therefore histamine appears to be a newly identified regulator of adipogenesis, by helping maintain basal CREB activity.
NEW INVESTIGATOR AWARD FINALISTS NIA0001 Induction of differentiation in human preadipocytes may contribute to adipogenic effect of human adenovirus Ad‐36
Authors: Pasarica M , Loiler S , Koska J , Permana P , Ravussin E , Kilroy G , Gimble JM , Dhurandhar NV
Published: August 2006

Human adenovirus Ad‐36 causes adiposity in animal models and shows association with human obesity. The mechanism involved is unknown. We previously reported that Ad‐36 enhances differentiation of 3T3‐L1 preadipocytes and E4orf‐1 gene of the virus is responsible for the adipogenic effect in the rodent cell line. We undertook a three‐step approach to investigate the role of preadipocyte differentiation in adipogenic effect of Ad‐36. First, we showed that the viral mRNA is expressed in adipose‐derived stem cells (ASC) of animals experimentally infected with Ad‐36. Infection of rats with Ad‐36 resulted in increased epididymal fat pad weight and the expression of Ad‐36 E4orf‐1 mRNA was detected in ASC isolated from the fat pads. Next, we determined if humans naturally infected with Ad‐36 will show greater preadipocyte differentiation. Subcutaneous adipose‐tissue samples from 33 Pima Indian subjects were screened by nested‐PCR specific for Ad‐36 DNA. Nine subjects (27%) had Ad‐36 DNA. A blinded comparison of their ASC showed greater differentiation to adipocytes for the Ad‐36 DNA positive subjects (P = 0.06) compared to the Ad‐36 DNA negative group. Finally, we used a direct approach. Human‐ASC when infected with Ad‐36 showed spontaneous replication, differentiation, and lipid accumulation, which was significantly greater than the uninfected controls (P < 0.01). Ad‐36 induced lipid accumulation in human‐ASC increased in response to the viral load and the lipogenic response was observed regardless of the donor gender and over an age range of 22–57 years. These results suggest that ability of Ad‐36 to induce preadipocyte differentiation may play a role in human adiposity.
NIA0002 Novel role for adiponectin pathway in human skeletal muscle bioenergetics
Authors: Civitarese AE , Nawrocki AR , Ukropcova B , Carling S , Hulver M , DeFronzo RA , Mandarino L , Scherer P , Smith SR , Ravussin E
Published: August 2006

Insulin resistance in skeletal muscle is associated with impaired oxidative capacity and reduced size, number and function of mitochondria. Insulin‐resistant individuals have lower adiponectin concentrations, a characteristic predating the development of type‐2 diabetes (T2D). The aim of this study was to test the potential role of adiponectin in mitochondrial bioenergetics in individuals predisposed to develop T2D, in adiponectin KO mice and in primary muscle cell culture. Individuals with a family history of T2D displayed lower plasma adiponectin concentration (P = 0.03), reduced PGC1β (P = 0.04) and mtFAM (P = 0.03) mRNA, lower mitochondrial content (P = 0.006), citrate synthase (P = 0.02) and (‐HAD (P = 0.03) activity, suggesting defective mitochondrial bioenergetics in skeletal muscle. In addition, AdipoR1 was the principle correlate of mitochondrial content (r2 = 0.81), suggesting an important role in mitochondrial biogenesis. Knock out of adiponectin in mice was associated with low PGC1α and PPARδ mRNA (both, P < 0.05), reduced mitochondrial content (P < 0.05) and COX II activity (P < 0.05) and markers for type‐1 oxidative fibers in skeletal muscle. This suggests that mitochondrial function is dependent on circulating adiponectin. In primary cultures of human myotubes, treatment with adiponectin induced AMPKK/ AMPK activity, PGC1α protein, mitochondrial biogenesis (P < 0.05), palmitate oxidation (P < 0.05), citrate synthase (P < 0.05) and SOD activity (P < 0.05), and reduced mitochondrial membrane potential and the production of ROS (P < 0.05). The inhibition of adiponectin receptor expression by siRNA or of AMPK by a pharmacological agent blunted the induction in mitochondrial function. Our findings indicate a novel pathway in skeletal muscle by which adiponectin increase mitochondrial number and function and exerts an insulin sensitizing effect.
NIA0003 The role of peptide YY (PYY) in the control of appetite
Authors: Le Roux C , Batterham R , Borg C , Ghatei M , Patel A , Aylwin S , Bloom S
Published: August 2006

Peptide YY (PYY) is a 36 amino acid gut hormone produced by the distal intestinal tract that binds the Y2 receptor in the hypothalamic arcuate nucleus. We showed that increasing calorie load in normal weight humans and rodents causes a graded rise in endogenous PYY (P < 0.05). Graded doses of exogenous PYY showed a dose response curve for increased satiety (P < 0.05) and reduced calorie intake (P < 0.05). This study demonstrated two threshold levels, the lower marking the start of appetite reduction (P = 0.04) and the upper the onset of nausea (P = 0.03). We subsequently showed that obese humans and rodents have lower postprandial PYY responses (P < 0.05). Reduced plasma PYY was characterized by normal PYY mRNA levels and higher tissue PYY levels, indicating normal production, but attenuated release from the distal gut. However in obese humans and rodent exogenous PYY was still effective at increasing satiety and reducing food intake (P < 0.05). Rodents following gastric bypass showed elevated PYY, reduced food intake and gut hypertrophy (P = 0.01), while blockade of endogenous PYY increased food intake (P = 0.04). In man, gastric bypass, but not gastric banding caused increased postprandial PYY favouring enhanced satiety (P = 0.001). Our prospective human gastric bypass study showed progressively increasing PYY responses associated with enhanced satiety (P < 0.05). The sustained nature of appetite reduction after gastric bypass may partly be explained by gut adaptation and chronic elevation of PYY. Thus obesity is associated with low PYY release that reduces satiety and reinforces obesity. The maladaptive reduction in PYY release can however be overcome by gastric bypass.
Environmental correlates of physical activity in youth – a review and update
Authors: Ferreira I. , Van Der Horst K. , Wendel‐Vos W. , Kremers S. , Van Lenthe F. J. , Brug J.
Published: August 2006

Obesogenic environments are thought to underlie the increased obesity prevalence observed in youth during the past decades. Understanding the environmental factors that are associated with physical activity (PA) in youth is needed to better inform the development of effective intervention strategies attempting to halt the obesity epidemic. We conducted a systematic semi‐quantitative review of 150 studies on environmental correlates of youth PA published in the past 25 years. The ANalysis Grid for Environments Linked to Obesity (ANGELO) framework was used to classify the environmental correlates studied. Most studies retrieved used cross‐sectional designs and subjective measures of environmental factors and PA. Variables of the home and school environments were especially associated with children’s PA. Most consistent positive correlates of PA were father’s PA, time spent outdoors and school PA‐related policies (in children), and support from significant others, mother’s education level, family income, and non‐vocational school attendance (in adolescents). Low crime incidence (in adolescents) was characteristic of the neighbourhood environment associated with higher PA. Convincing evidence of an important role for many other environmental factors was, however, not found. Further research should aim at longitudinal and intervention studies, and use more objective measures of PA and its potential (environmental) determinants.
The Mobility of English School Children*
Authors: Machin Stephen , Telhaj Shqiponja , Wilson Joan
Published: August 2006

In this paper, we examine links between pupil mobility and pupil and school characteristics at all levels of compulsory schooling in England. We derive measures of mobility from two academic years of the Pupil Level Annual School Census (PLASC) data, a unique national administrative pupil‐level longitudinal data source. Our findings suggest that mobile pupils are more socially disadvantaged than non‐mobile pupils and are significantly less likely to have a good prior education record. Moreover, we find that pupils are less likely to move if the school they attend has good average performance levels. Finally, when children move school, they are more likely to end up in a school with better Key Stage performance than the one they left, but this improvement is significantly more marked for children from better‐off backgrounds.
Economic Capabilities, Choices and Outcomes at Older Ages*
Authors: Banks James
Published: August 2006

Intense policy and academic interest in the ‘economics of ageing’ has come about as a result of the demographic trends that have been experienced over the last 50 years and that are projected for the next 50 years. Key economic policy issues relate to the design of public pensions, welfare systems, healthcare and invalidity benefits, and the regulation of private pensions and other retirement saving. This paper presents an overview of the beginnings of a research agenda targeted towards increasing the empirical evidence on these issues in England and providing extensive data for subsequent research. The paper focuses on summarising some recent data on how individuals' economic circumstances, and in particular the ability and willingness to work, change from age 50 onwards. This will be a key factor in determining the ability of economic institutions to adjust to new socio‐demographic equilibria in which individuals are living for longer. Further issues for more extensive empirical research are also identified.
Financial Expectations, Consumption and Saving: A Microeconomic Analysis*
Authors: Brown Sarah , Taylor Karl
Published: August 2006

We explore the determinants of individuals' financial expectations using data from the British Household Panel Survey, 1991–2003. Our findings suggest that individuals' financial predictions are influenced by both the life cycle and the business cycle. We also investigate the extent to which the accuracy of past financial expectations affects current financial expectations. Regardless of the accuracy of the prediction, past financial optimism has a positive effect on current expectations formation whilst past financial pessimism has a negative effect. We also explore the relationship between financial realisations and expectations and we find that expectations tend to fall short of financial realisations. Finally, we investigate how financial expectations influence saving and consumption. Our findings suggest that financial optimism is inversely associated with saving and that current financial expectations serve to predict future consumption.
Effects of Family Policy Reforms in Norway: Results from a Joint Labour Supply and Childcare Choice Microsimulation Analysis*
Authors: Kornstad Tom , Thoresen Thor O.
Published: August 2006

Mothers of pre‐school children represent one part of the population that might be able to increase its labour supply. We discuss the effects of family policy changes that encourage the labour supply of these mothers, such as childcare fee reductions and increased availability of centre‐based care. The effects of policy changes are described by using a joint labour supply and childcare choice decision model. Detailed empirical results are provided with respect to mothers' labour supply, families' childcare choices, public expenditures, and distributions of income and money metric utility.
Targeted Interventions in Healthcare: The Role of Facility Placement*
Authors: Fernández Mercedes , Galiani Sebastián , Schargrodsky Ernesto
Published: August 2006

Adequate targeting is a primary concern in the design of any social programme that attempts to reach a specific group in society. This paper studies the targeting of a healthcare‐centre programme aimed at the poor that relies on household self‐selection into the programme at the local level. We find that a key variable in determining utilisation of the health centres is location. Households living near a centre are substantially more likely to use it than households living further away. This points to the importance of facility placement in targeting self‐selected health programmes to the poor.
Regression Analysis for Multistate Models Based on a Pseudo‐value Approach, with Applications to Bone Marrow Transplantation Studies
Authors: ANDERSEN PER K. , KLEIN JOHN P.
Published: August 2006

Abstract. Typically, regression analysis for multistate models has been based on regression models for the transition intensities. These models lead to highly nonlinear and very complex models for the effects of covariates on state occupation probabilities. We present a technique that models the state occupation or transition probabilities in a multistate model directly. The method is based on the pseudo‐values from a jackknife statistic constructed from non‐parametric estimators for the probability in question. These pseudo‐values are used as outcome variables in a generalized estimating equation to obtain estimates of model parameters. We examine this approach and its properties in detail for two special multistate model probabilities, the cumulative incidence function in competing risks and the current leukaemia‐free survival used in bone marrow transplants. The latter is the probability a patient is alive and in either a first or second post‐transplant remission. The techniques are illustrated on a dataset of leukaemia patients given a marrow transplant. We also discuss extensions of the model that are of current research interest.
The Typical Tools for the Job: Research Strategies in Institutional Analysis
Authors: Schneiberg Marc , Clemens Elisabeth S.
Published: August 2006

Institutional theory rests on a rejection of reductionism. Instead of reducing higher-order phenomena to aggregates of behavior, institutional theory reverses this causal imagery. It attributes the behavior of organizations and nation-states to contextual factors, notably organizational fields, national institutional systems, or the emerging global polity, Institutionalists, particularly within sociology, also emphasize specifically cultural mechanisms for these higher-order effects. This article develops the methodological foundations for these claims. It surveys and elaborates research designs for documenting higher-order effects and for differentiating the cultural mechanisms of institutional influence. It also presents new strategies for assessing multiple logics and the coherence of institutional orders, moving beyond adoption and diffusion studies to analyze the dynamic and contested processes of institutionalization and institutional change.
Trajectories of Institutional Disintegration in Late-Soviet Russia and Contemporary Iraq
Authors: Garcelon Marc
Published: August 2006

How might revolutions and other processes of institutional disintegration inform political processes preceding them? By mapping paths of agency through processes of institutional disintegration, the trajectory improvisation model of institutional breakdown overcomes “action-structure” binaries by framing political revolutions as possible outcomes of such disintegrative processes. The trajectory improvisation approach expands the trajectory adjustment model of social change developed by Gil Eyal, Iván Szelényi, and Eleanor Townsley. An overview of political revolution in Soviet Russia between 1989 and 1991 illustrates trajectory improvisation. The recent American invasion and occupation of Iraq shows alternative routes to institutional disintegration, indicating the independence of models of institutional breakdown from those of social movements. These cases illustrate both the diversity of situations the trajectory improvisation model speaks to, and the limitation of models of trajectory adjustment, improvisation, social movements, and invasions, illustrating why such models at best enable what are called “explanatory narratives” of actual historical processes.
Using Historical Data for Bayesian Sample Size Determination
Authors: De Santis Fulvio
Published: August 2006

We consider the sample size determination (SSD) problem, which is a basic yet extremely important aspect of experimental design. Specifically, we deal with the Bayesian approach to SSD, which gives researchers the possibility of taking into account pre-experimental information and uncertainty on unknown parameters. At the design stage, this fact offers the advantage of removing or mitigating typical drawbacks of classical methods, which might lead to serious miscalculation of the sample size. In this context, the leading idea is to choose the minimal sample size that guarantees a probabilistic control on the performance of quantities that are derived from the posterior distribution and used for inference on parameters of interest. We are concerned with the use of historical data—i.e. observations from previous similar studies—for SSD. We illustrate how the class of power priors can be fruitfully employed to deal with lack of homogeneity between historical data and observations of the upcoming experiment. This problem, in fact, determines the necessity of discounting prior information and of evaluating the effect of heterogeneity on the optimal sample size. Some of the most popular Bayesian SSD methods are reviewed and their use, in concert with power priors, is illustrated in several medical experimental contexts.
A Latent Markov Model for Detecting Patterns of Criminal Activity
Authors: Bartolucci Francesco , Pennoni Fulvia , Francis Brian
Published: August 2006

The paper investigates the problem of determining patterns of criminal behaviour from official criminal histories, concentrating on the variety and type of offending convictions. The analysis is carried out on the basis of a multivariate latent Markov model which allows for discrete covariates affecting the initial and the transition probabilities of the latent process. We also show some simplifications which reduce the number of parameters substantially; we include a Rasch-like parameterization of the conditional distribution of the response variables given the latent process and a constraint of partial homogeneity of the latent Markov chain. For the maximum likelihood estimation of the model we outline an EM algorithm based on recursions known in the hidden Markov literature, which make the estimation feasible also when the number of time occasions is large. Through this model, we analyse the conviction histories of a cohort of offenders who were born in England and Wales in 1953. The final model identifies five latent classes and specifies common transition probabilities for males and females between 5-year age periods, but with different initial probabilities.
Finding the Best Treatment Under Heavy Censoring and Hidden Bias
Authors: Lee Myoung-jae , Häkkinen Unto , Rosenqvist Gunnar
Published: August 2006

We analyse male survival duration after hospitalization following an acute myocardial infarction with a large (N = 11024) Finnish data set to find the best performing hospital district (and to disseminate its treatment protocol). This is a multiple-treatment problem with 21 treatments (i.e. 21 hospital districts). The task of choosing the best treatment is difficult owing to heavy right censoring (73%), which makes the usual location measures (the mean and median) unidentified; instead, only lower quantiles are identified. There is also a sample selection issue that only those who made it to a hospital alive are observed (54%); this becomes a problem if we wish to know their potential survival duration after hospitalization, if they had survived to a hospital contrary to the fact. The data set is limited in its covariates—only age is available—but includes the distance to the hospital, which plays an interesting role. Given that only age and distance are observed, it is likely that there are unobserved confounders. To account for them, a sensitivity analysis is conducted following pair matching. All estimators employed point to a clear winner and the sensitivity analysis indicates that the finding is fairly robust.
Integer‐Valued GARCH Process
Authors: Ferland René , Latour Alain , Oraichi Driss
Published: August 2006

Abstract.  An integer‐valued analogue of the classical generalized autoregressive conditional heteroskedastic (GARCH) (p,q) model with Poisson deviates is proposed and a condition for the existence of such a process is given. For the case p = 1, q = 1, it is explicitly shown that an integer‐valued GARCH process is a standard autoregressive moving average (1, 1) process. The problem of maximum likelihood estimation of parameters is treated. An application of the model to a real time series with a numerical example is given.