bluuebunny/crossref_metadata_2025 huggingface dataset:
Non‐alcoholic fatty liver disease: An expanding problem with low levels of awareness in Hong Kong
Authors: Leung Chi Man , Lai Lawrence Siu Wing , Wong Wing Hang , Chan Kam Hoi , Luk Yiu Wing , Lai Jak Yiu , Yeung Yat Wah , Hui Wai Mo
Published: August 2009

Background and Aim:  With the Westernization of the lifestyle and the rising prevalence of obesity and diabetes mellitus, non‐alcoholic fatty liver disease (NAFLD) is an emerging health problem in the Asia–Pacific region. The purpose of this study was to determine the awareness of NAFLD among the general population in Hong Kong.

Methods:  A random telephone survey was conducted from September 2007 to January 2008 using a structured multiple‐choice questionnaire. Subjects were Hong Kong residents aged 18 or above who spoke Cantonese.

Results:  In the first phase of the telephone survey, 521 subjects were interviewed and the results showed that as high as 83% of respondents had never come across the term ‘NAFLD’. Upon completion of the second phase telephone survey, a total of 508 respondents who had heard of NAFLD were successfully interviewed. Of the 508 respondents, nearly half of them (42%) expressed no idea about the prevalence of NAFLD in Hong Kong. About half of respondents (47%) knew nothing about the clinical presentation of NAFLD. The majority of them (78%) had a misconception that blood tests could provide a definite diagnosis of NAFLD. Smoking, hepatitis B carriage and a past history of hepatitis A infection were cited as risk factors of NAFLD by 52%, 57% and 42% of respondents, respectively. Of the 508 respondents who had heard of NAFLD, most of them perceived that their knowledge of NAFLD was either inadequate (46%) or highly inadequate (35%).

Conclusion:  This survey revealed an inadequate knowledge of NAFLD among the general population in Hong Kong.
Protein C and D‐dimer are related to portal vein thrombosis in patients with liver cirrhosis
Authors: Zhang Donglei , Hao Jianyu , Yang Ning
Published: August 2009

Background and Aim:  To profile changes of coagulation, anticoagulation and fibrolytic factors associated with liver function failure and portal vein thrombosis (PVT) formation in chronic liver cirrhosis patients.

Methods:  A total of 116 cirrhotic patients admitted to our hospital from June 2006 to October 2008 were included in our study. All patients were classified into two groups: PVT group (31 patients), composed of patients with PVT and a control group (85 patients), including patients without PVT. Platelet, prothrombin time (PT), activated partial prothrombin time (APTT) and fibrinogen were measured. Also, plasma samples from the patients were analyzed for the levels of antithrombin III (AT‐III), protein C (PC), protein S (PS), D‐dimer, tissue‐type plasminogen activator as well as plasminogen activator inhibitor‐1. Statistical analyses were carried out to evaluate the correlation of specific variations with the disease status.

Results:  In general, the higher Child‐Pugh scores, indicating the aggravation of hepatic impairment of the patients, correlated well with the prolonged PT/APTT and increased D‐dimer, as well as decreased platelet, fibrinogen, PC and AT‐III levels in the serum. Furthermore, we found that the PC, PS and D‐dimer levels in PVT patients were 2.32 ± 0.72 mg/L, 17.14 ± 3.62 mg/L and 0.99 ± 0.36 mg/L, respectively, both representing a significant difference compared with those in the control group without PVT. Logistic regression model shows that the odds ratio value of one unit of increase of PC and D‐dimer were 0.48 and 15.57.

Conclusions:  Cirrhotic patients displayed dysfunctions in the coagulation, anti‐coagulation and fibrolytic systems. The development of PVT in these patients may be independently associated with the decrease of PC, PS and D‐dimer. Furthermore, decreasing PC and increasing D‐dimer may be risk factors inducing PVT in cirrhotic patients.
Impact of the Tokyo guidelines on the management of patients with acute calculous cholecystitis
Authors: Lee Shou‐Wu , Yang Sheng‐Shun , Chang Chi‐Sen , Yeh Hong‐Jeh
Published: August 2009

Background and Aim:  Prompt treatments for acute calculous cholecystitis can reduce both mortality and morbidity. The aim of this retrospective study was to assess the impact of the Tokyo guidelines on management of patients with acute cholecystitis.

Methods:  The records of patients admitted due to acute calculous cholecystitis were collected between January 2007 and June 2008. Exclusion criteria included acalculous, hepatobiliary malignancy, younger than 18 years old and mortality unrelated to cholecystitis. These 235 patients were classified into three groups; grade I, grade II and grade III, according to the severity grading in the Tokyo guidelines for acute cholecystitis. They were further classified into two subgroups; those compatible with and incompatible with managements suggested in the Tokyo guidelines, for comparison.

Results:  Lower levels of platelets, lower blood pressure, higher levels of C‐reactive protein, blood urine nitrogen, prothrombin time, bilirubin, alkaline phosphatase, and more incidences of positive microorganisms cultured in bile or blood, were found in patients as the severity of disease progressed. Shorter mean length of hospital stay was compatible with the Tokyo guidelines, but no significant differences in outcomes, including incidences of survival, post‐surgery complications and mortality, were found between the two subgroups.

Conclusion:  No significant benefit of the application of the Tokyo guidelines in the management of patients was found between the two subgroups except for reduced mean length of hospital stay. The application of the Tokyo guidelines for improving the outcomes of patients with acute cholecystitis needs further investigation and evaluation.
Epidemiology of hepatitis E: Current status
Authors: Aggarwal Rakesh , Naik Sita
Published: August 2009

Hepatitis E, caused by infection with hepatitis E virus (HEV), is a common cause of acute hepatitis in areas with poor sanitation. The virus has four genotypes with one serotype: genotypes 1 and 2 exclusively infect humans, whereas genotypes 3 and 4 also infect other animals, particularly pigs. In endemic areas, both large outbreaks of acute hepatitis as well as sporadic cases occur frequently. These cases are usually due to genotype 1 or 2 HEV and are predominantly caused by fecal–oral transmission, usually through contamination of drinking water; contaminated food, materno‐fetal (vertical spread) and parenteral routes are less common modes of infection. The acute hepatitis caused by this virus has the highest attack rates in young adults and the disease is particularly severe among pregnant women. HEV superinfection can occur among persons with pre‐existing chronic liver disease. In non‐endemic regions, locally acquired disease was believed to be extremely uncommon. However, in recent years, an increasing number of cases, due mostly due to genotype 3 or 4 HEV, have been recognized. These are more often elderly men who have other coexisting illnesses, and appear to be related to zoonotic transmission from pigs, wild boars and deer, either food‐borne or otherwise. Also, chronic infection with genotype 3 HEV has been reported among immunosuppressed persons in these regions. A subunit vaccine has been shown to be effective in preventing clinical disease, but is not yet commercially available. Our understanding of hepatitis E epidemiology has undergone major changes in recent years, and the future may hold even more surprises.
Can preoperative CA19‐9 and CEA levels predict the resectability of patients with pancreatic adenocarcinoma?
Authors: Kim Young Choon , Kim Hong Joo , Park Jung Ho , Park Dong Il , Cho Yong Kyun , Sohn Chong Il , Jeon Woo Kyu , Kim Byung Ik , Shin Jun Ho
Published: August 2009

Background:  We aimed to explore the predictive ability of preoperative carbohydrate antigen 19‐9 (CA19‐9) and carcinoembryonic antigen (CEA) levels for assessing tumor resectability (R0 resection) in patients with pancreatic adenocarcinoma.

Methods:  The present study included 72 patients who had been treated surgically for potentially resectable pancreatic adenocarcinoma and 42 patients who had been treated surgically for palliation (bypass surgery) at our institution. Pancreatic adenocarcinoma was histologically confirmed by pathological examination of the resected specimen or, if unresected, by intraoperative biopsy.

Results:  For resectable disease, the mean and median values of CA19‐9 were significantly lower than for R1/2 or unresectable disease. The best cut‐off points for CEA, CA19‐9, and tumor size to predict resectability were 2.47 ng/mL, 92.77 U/mL and 11.85 cm3, respectively. A CA19‐9 ≥ 92.77 U/mL and both tumor markers no less than the cut‐off levels predicted the possibility of R1/2 or unresectability with 90.6% and 88.6% accuracy, respectively. However, either tumor marker or both tumor markers less than the cut‐off levels predicted the probability of R0 resection only with 27.1% and 40.6% accuracy, respectively. The independent contributing factors to resectability (R0 resection) by multivariate regression analysis were a CA 19‐9 < 92.77 U/mL, a tumor size < 11.85 cm3, and a less advanced AJCC stage.

Conclusion:  The present study demonstrates that preoperative serum CA19‐9 and CEA levels can be used for the prediction of resectability (R0 resection) in patients with pancreatic adenocarcinoma, which may enable a simple and cost‐effective exclusion of such patients who are unlikely to benefit from surgery.
Natural killer cells – new understanding of basic biology may lead to more effective allogeneic haematopoietic stem cell transplantation
Authors: Patil S. , Schwarer T.
Published: August 2009

The natural killer (NK) cells are part of the innate immune system and are responsible for initial defences in the surveillance against malignant cells and virally infected cells. In addition to direct cytotoxicity, cytokines produced by NK cells amplify the immune response and help control the neoplasm/pathogen. Several activating and inhibitory receptors responsible for NK cell activation are recently characterized and play a crucial role in tumour eradication. These include, but are not limited to, the killer immunoglobulin‐like receptors, C‐type lectin receptors and natural cytotoxicity receptors. The downstream signalling of some of these receptors is also characterized. The net balance in the sum of the signals generated by ligation of activating and inhibitory receptors determines the final outcome, cytotoxicity versus tolerance. NK cell‐based immunotherapy can be successfully exploited in the haematopoietic stem cell transplantation for the treatment of haematological malignancies and has a potential to separate the beneficial graft versus leukaemia effect from, often dangerous, graft versus host disease. This article reviews the NK receptors important in NK‐mediated cytotoxicity in allogeneic haematopoietic stem cell transplantation.
Testing for monogenic diabetes among children and adolescents with antibody‐negative clinically defined Type 1 diabetes
Authors: Rubio‐Cabezas O. , Edghill E. L. , Argente J. , Hattersley A. T.
Published: August 2009

Aims  Monogenic diabetes is frequently misdiagnosed as Type 1 diabetes. We aimed to screen for undiagnosed monogenic diabetes in a cohort of children who had a clinical diagnosis of Type 1 diabetes but were pancreatic autoantibody‐negative.

Methods  We studied 252 patients diagnosed clinically with Type 1 diabetes between 6 months and 17 years of age. Pancreatic autoantibodies [islet cell autoantibodies (ICA), glutamic acid decarboxylase antibodies (GADA) and/or insulinoma‐associated antigen‐2 antibodies (IA2A)] were absent in 25 cases (9.9%). The most frequent genes involved in monogenic diabetes [KCNJ11 and INS for neonatal diabetes and HNF1A and HNF4A for maturity‐onset diabetes of the young (MODY)] were directly sequenced.

Results  Two of the 25 (8%) antibody‐negative patients had de novo heterozygous mutations in INS; c.94G>A (G32S) and c.265C>T (R89C). The two patients presented with non‐ketotic hyperglycaemia at 8 and 11 months of age. In contrast, the four antibody‐positive patients who presented at a similar age (6–12 months) had a more severe metabolic derangement, manifested as ketosis in all four cases, with ketoacidosis in two. At ages 15 and 5 years, both INS mutation patients were prescribed a replacement dose of insulin with good glycaemic control [glycated haemoglobin (HbA1c) 7.0 and 7.2%]. No mutations were found in KCNJ11, HNF1A or HNF4A.

Conclusions  The identification of patients with monogenic diabetes from children with clinically defined Type 1 diabetes may be helped by clinical criteria including the absence of pancreatic autoantibodies.
Trends in yield and effects of screening intervals during 17 years of a large UK community‐based diabetic retinopathy screening programme
Authors: Misra A. , Bachmann M. O. , Greenwood R. H. , Jenkins C. , Shaw A. , Barakat O. , Flatman M. , Jones C. D.
Published: August 2009

Aims  To describe changes in risk profiles and yield in a screening programme and to investigate relationships between retinopathy prevalence, screening interval and risk factors.

Methods  We analysed a population of predominantly Type 2 diabetic patients, managed in general practice, and screened between 1990 and 2006, with up to 17 years’ follow‐up and up to 14 screening episodes each. We investigated associations between referable or sight‐threatening diabetic retinopathy (STDR), screening interval and frequency of repeated screening, whilst adjusting for age, duration and treatment of diabetes, hypertension treatment and period.

Results  Of 63 622 screening episodes among 20 788 people, 16 094 (25%) identified any retinopathy, 3136 (4.9%) identified referable retinopathy and 384 (0.60%) identified STDR. The prevalence of screening‐detected STDR decreased by 91%, from 1.7% in 1991–1993 to 0.16% in 2006. The prevalence of referable retinopathy increased from 2.0% in 1991–1993 to 6.7% in 1998–2001, then decreased to 4.7% in 2006. Compared with screening intervals of 12–18 months, screening intervals of 19–24 months were not associated with increased risk of referable retinopathy [adjusted odds ratio 0.93, 94% confidence interval (CI) 0.82–1.05], but screening intervals of more than 24 months were associated with increased risk (odds ratio 1.56, 95% CI 1.41–1.75). Screening intervals of < 12 months were associated with high risks of referable retinopathy and STDR.

Conclusions  Over time the risk of late diagnosis of STDR decreased, possibly attributable to earlier diagnosis of less severe retinopathy, decreasing risk factors and systematic screening. Screening intervals of up to 24 months should be considered for lower risk patients.
Diuretics and diabetes incidence—an appeal against the reluctance to prescribe a medication that is safe and proven
Authors: Siebenhofer A. , Jeitler K. , Rakovac I. , Horvath K.
Published: August 2009

Diabet. Med. 27, 130–135 (2010)

The publication of the scientific report of the Institute for Quality and Efficiency in Health Care (IQWiG) in Germany on the ‘Comparative evaluation of the benefits and harms of different antihypertensive drug classes [diuretics, beta‐blockers, angiotensin‐converting enzyme (ACE) inhibitors, calcium‐channel blockers and angiotensin II (AT‐II) blockers] as first‐choice therapy for patients with essential hypertension’ raised an enormous public debate, particularly as diabetes incidence was not judged to be a patient‐relevant outcome. In this assessment, the overall view of the patient‐relevant results was that diuretics can be used as first‐line antihypertensive treatment. Diabetes incidence is highest with diuretics, but minimal differences in fasting plasma glucose of ∼ 0.28 mmol/l are magnified by the transformation of continuous blood glucose values into categorical data: with the establishment of thresholds, the diagnosis of diabetes depends on being above a certain blood glucose value. The protective cardiovascular effects of diuretics do not seem to be reduced in hypertensive patients who develop new‐onset diabetes during treatment. Since blood pressure control is often worse, detection, treatment and control should be urgently improved. The debate on antihypertensive agents is mainly of scientific interest and has only minor clinical relevance for everyday patient care.
Intraepidermal nerve fibre density at wrist level in diabetic and non‐diabetic patients
Authors: Thomsen N. O. B. , Englund E. , Thrainsdottir S. , Rosén I. , Dahlin L. B.
Published: August 2009

Aims  Myelinated nerve fibre pathology has been demonstrated at wrist level in diabetic patients. We examined if quantification of intra‐epidermal nerve fibre density (IENFD) in hairy and glabrous skin at wrist level could detect signs of subclinical small nerve fibre neuropathy.

Methods  In 35 diabetic patients who were age and gender matched with 31 non‐diabetic patients, punch biopsies were obtained in conjunction with surgical carpal tunnel release. Biopsies were immunostained with anti‐protein gene product (PGP) 9.5. The IENFD was quantified using manual counting by light microscopy.

Results  We could not demonstrate significant differences in IENFD between diabetic or non‐diabetic patients. Additionally, no differences were found between patients with Type 1 and Type 2 diabetes or in diabetic patients with and without neurophysiologic signs of mild peripheral neuropathy. However, the IENFD was significantly higher in hairy skin compared with glabrous skin. Furthermore, the IENFD was significantly higher in females than in males and correlated with age, but not with duration of diabetes or glycated haemoglobin (HbA1c).

Conclusions  In mild neuropathy no difference in IENFD at the wrist level could be detected between diabetic and non‐diabetic patients. Independent of diabetes, we found IENFD to be higher in hairy skin compared with glabrous skin and higher in females than in males. These results must be taken into consideration when assessing small nerve fibre pathology in the upper extremity.
The role of fruit juice in the diet: an overview
Authors: Caswell H.
Published: August 2009

Over recent years, consumers have shown an increasing interest in health and wellbeing, with many wanting food and drink products that are healthy and nutritious, yet fit in with busy lifestyles. Fruit juice is one beverage that has seen a dramatic increase in consumer purchasing since the 1970s, and is now consumed by nearly half the UK population. While the beneficial effects of consuming diets rich in fruit and vegetables are well documented, the specific health effects of consuming fruit juice are less so. Further, the role of fruit juice in conditions such as obesity has also recently come under scrutiny, due to questions over how liquid calories affect subsequent energy intake. Limitations in the literature in this area include a lack of studies looking at different types of fruit juices and their effects on health, as well as studies that differentiate fruit juice from fruit and vegetable intake. Consuming a diet rich in fruit and vegetables (to which fruit juice can count once towards the 5 A DAY target) can help to reduce an individual's risk of suffering from a variety of chronic diseases, and should therefore be encouraged.
Policy and action for cancer prevention – highlights from a new report by the World Cancer Research Fund and the American Institute for Cancer Research
Authors: Beck K. , Thompson R. L. , Allen K.
Published: August 2009

In 2007, the World Cancer Research Fund/American Institute for Cancer Research produced food, nutrition and physical activity recommendations for personal and public health goals for reducing cancer risk. A companion publication, Policy and Action for Cancer Prevention, addresses the external influences on people's eating and physical activity habits over a lifetime and evaluates potential actions to change these behaviours. The Policy Report makes recommendations for policies and actions that will help achieve the public health goals for reducing cancer risk. The recommendations are addressed to policy‐makers and decision‐takers at international, national and local level. These recommendations, if implemented, will help influence and change the lifestyle choices that people make, thereby reducing the risk of cancer and other chronic diseases within the population. The overarching message of the Policy Report is that public health is everyone's business. The protection and improvement of public health does not happen by accident – it requires policies and actions to be implemented by all relevant sectors of society.
Can soyabean isoflavones mimic the effects of energy restriction on healthy ageing?
Authors: Ions L. , Wakeling L. , Ford D.
Published: August 2009

Energy restriction is the only known robust dietary measure effective in increasing lifespan across a wide variety of species. Our current research indicates a role for the best‐established dietary mimetic of energy restriction, the red grape polyphenol resveratrol, in altering information carried by DNA at a level superimposed on the information provided by the sequence of bases, known as epigenetic marking. These effects appear to share a common pathway with some of the effects of energy restriction that involve the protein Sirt1. Preliminary observations made in human intestinal cells reveal that isoflavones found in the soyabean may share some of these functional properties and so highlight the potential for a diet rich in these compounds to promote healthy ageing.
EuroFIR Synthesis report No 7: Food composition explained
Authors: Church S. M.
Published: August 2009

Summary

Introduction

Why food composition databases are important

How food composition databases are produced

Considerations in the use of food composition databases

Conclusions and future role of EuroFIR

Acknowledgements

References and further reading

Food composition data are fundamental to the quantitative study of nutrition and are widely used in a variety of fields, including public health. However, knowledge of both the compilation and the limitations of food composition databases, which contain information on the concentrations of nutrients in food, is beneficial to ensure that users understand how to utilise the data appropriately. This guide provides background information on the importance of food composition data, and then explains the processes involved in producing and compiling these data. It then offers guidance on some of the key issues that users should be familiar with when using andmanipulating food composition data. Suggestions for further reading are given for users who may need more detailed information on specific topics and the resources produced by the EuroFIR (European Food Information Resource) Network of Excellence are highlighted.
Capacity Development as the Model for Development Aid Organizations
Authors: Kühl Stefan
Published: August 2009

Sociological studies of organizational fashions tend to focus on commercial firms. This article looks at the Capacity Development concept that is globally applied as a model in governmentally supported development assistance organizations. The organizations themselves adopt the concept, asserting that an increase in ‘capacities’ in developing countries will contribute to a higher success rate for projects. This article argues that a primary function of concepts such as Capacity Development is to meet the legitimacy requirements of development assistance organizations. The more the effectiveness of these organizations is criticized or challenged, the more they feel the need to defend themselves by developing new — and hopefully more effective — concepts.
Developing Exclusion: The Case of the 1961 Land Reform in Colombia
Authors: Galvis Juan Pablo
Published: August 2009

The modern project of rural development has been seen as one of increasing incorporation, control and rationalization of territory by the state. Evidence from the formulation of the Colombian land reform policy of 1961 gives more nuance to this general conceptualization. Those places where the state intervened through large‐scale resettlement programmes conceived within the framework of Cold War development are the same places where war and the drug economy — the most serious threats to the state itself — took root and grew. This article examines this contradiction. It interrogates the idea of modern development as a project that necessarily brings subjects and territories into the realm of state control. It also attempts to provide a counterweight to arguments about the territorialization of the war in Colombia being the outcome of state inaction and lack of development.
World Bank‐directed Development? Negotiating Participation in the Nam Theun 2 Hydropower Project in Laos
Authors: Singh Sarinda
Published: August 2009

The omnipotence of the World Bank on a global scale means that it is often regarded as the most influential partner in bringing about transformations in developing countries. This article contributes to ongoing discussions of this issue by examining some effects of the Bank's participatory agenda in one of its flagship projects, the Nam Theun 2 (NT2) hydropower scheme in Laos. Critical accounts suggest that the Bank's promotion of participation in donor‐dependent countries like Laos is either a guise or an imposition. These propositions are considered in two settings where participation was debated around the time of the Bank's loan appraisal for NT2: first, an international stakeholders’ workshop held in Vientiane; and second, some international attempts to identify the concerns of villagers living near the NT2 dam site. In workshops and villages, participation is a negotiated performance whereby competing representations emerge through the interaction between village, state and international actors. More generally, this article shows that a grounded view of development can attend to the practices that constrain the hegemonic tendencies of the World Bank, even while maintaining awareness of the potency of its policies and interventions.
The smell of the place
Authors: Gratton Lynda
Published: August 2009

Lynda Gratton has pioneered a special field of management; her quest is to find employees and companies that “glow”, to learn about people and organizations that abound with enthusiasm, innovation, productivity and an effervescent espirit de corps. How does one identify a glowing business? It's important, she says, to first identify “the smell of the place”.
The only way is up
Authors: Sull Don
Published: August 2009

Just because the world is in a business downturn, it doesn't mean that you and your business can't be up about your future prospects. Don Sull has specialized on the upside of turbulence.
Don't let this crisis go to waste!
Authors: Jacobides Michael G.
Published: August 2009

The current downturn was a surprise to many business leaders. Some are still in a state of mental shock. It's time to think in new ways. Michael G. Jacobides says that the study of industry architectures can lead your company out of the recession.
Innovation communities: the role of networks of promotors in Open Innovation
Authors: Fichter Klaus
Published: August 2009

Research on Open Innovation has increasingly emphasised the role of communities in creating, shaping and disseminating innovations. However, the comparability of many studies has been hampered by the lack of a precise definition of the community construct, and the research on Open Innovation has to date not been well connected to insights from research on the role of transformational leaders and the networking of champions and promotors across organisational boundaries. For this reason, this paper introduces a new construct of ‘innovation communities’ based on promotor theory, which it defines as ‘networks of promotors’. It proposes a comprehensive concept of the quality of interaction in innovation communities, and presents findings of three case studies, which explore the role of promotors and networks of promotors in Open Innovation. The case studies reveal that such transformational leaders as promotors, and especially their close and informal co‐operation across functional and organisational boundaries, play a key role in Open Innovation.
Determinants and archetype users of open innovation
Authors: Keupp Marcus Matthias , Gassmann Oliver
Published: August 2009

Extant research on open innovation (OI) offers no systematic insight of how and why firms differ regarding the extent to which they conduct OI activities. Whereas past theoretical contributions have focused on explaining the externalisation of R&D activities as a result of firm‐external factors, we focus on explaining this externalisation as a result of firm‐internal weaknesses, specifically, impediments to innovation. Using the exploration–exploitation dichotomy as our theoretical framework, we develop hypotheses on how impediments to innovation influence the breadth and depth of OI. We then test these hypotheses by using an exceptionally large and detailed data set to estimate population‐averaged panel models. Our results provide support for most of the hypothesised relationships. Further, they allow to identify four ‘archetypes’ of firms that differ significantly regarding the breadth and depth of OI and the importance of impediments. Finally, we discuss the significance of these findings for both academics and managers.
Open R&D and open innovation: exploring the phenomenon
Authors: Enkel Ellen , Gassmann Oliver , Chesbrough Henry
Published: August 2009

There is currently a broad awareness of open innovation and its relevance to corporate R&D. The implications and trends that underpin open innovation are actively discussed in terms of strategic, organizational, behavioral, knowledge, legal and business perspectives, and its economic implications. This special issue aims to advance the R&D, innovation, and technology management perspective by building on past and present studies in the field and providing future directions. Recent research, including the papers in this special issue, demonstrates an increasing range of situations where the concept is regarded as applicable. Most research to date has followed the outside‐in process of open innovation, while the inside‐out process remains less explored. A third coupled process of open innovation is also attracting significant research attention. These different processes show why it is necessary to have a full understanding of how and where open innovation can add value in knowledge‐intensive processes. There may be a need for a creative interpretation and adaptation of the value propositions, or business models, in each situation. In other words, there are important implications for new and emerging methods of R&D management.
Tilting Methods for Assessing the Influence of Components in a Classifier
Authors: Hall Peter , Titterington D. M. , Xue Jing-Hao
Published: August 2009

Many contemporary classifiers are constructed to provide good performance for very high dimensional data. However, an issue that is at least as important as good classification is determining which of the many potential variables provide key information for good decisions. Responding to this issue can help us to determine which aspects of the datagenerating mechanism (e.g. which genes in a genomic study) are of greatest importance in terms of distinguishing between populations. We introduce tilting methods for addressing this problem. We apply weights to the components of data vectors, rather than to the data vectors themselves (as is commonly the case in related work). In addition we tilt in a way that is governed by L2-distance between weight vectors, rather than by the more commonly used Kullback–Leibler distance. It is shown that this approach, together with the added constraint that the weights should be non-negative, produces an algorithm which eliminates vector components that have little influence on the classification decision. In particular, use of the L2-distance in this problem produces properties that are reminiscent of those that arise when L1-penalties are employed to eliminate explanatory variables in very high dimensional prediction problems, e.g. those involving the lasso. We introduce techniques that can be implemented very rapidly, and we show how to use bootstrap methods to assess the accuracy of our variable ranking and variable elimination procedures.
Efficacy and safety of boosted and unboosted atazanavir‐containing antiretroviral regimens in real life: results from a multicentre cohort study
Authors: Giuntini R , Martinelli C , Ricci E , Vichi F , Gianelli E , Madeddu G , Abeli C , Palvarini L , Penco G , Marconi P , Grosso C , Pellicano G , Bonfanti P , Quirino T
Published: August 2009

Background

Atazanavir (ATV) has demonstrated high efficacy and safety in both treatment‐naïve and treatment‐experienced patients. Some comparative data are available on the durability of ritonavir‐boosted (ATV/r) and unboosted formulations, but there are no data on clinicians' motivations for choosing one or another in everyday practice. The aim of this study was to evaluate the long‐term efficacy of boosted and unboosted ATV in a cohort of treatment‐experienced patients.

Methods

All patients included in the study were enrolled in an observational cohort within the Surveillance Cohort Long‐Term Toxicity Antiretrovirals (SCOLTA) Project. Data on CD4 cell count, HIV viral load, metabolic parameters and adverse events of grade 3–4 are collected through an on‐line system every six months. The duration of treatment with ATV was evaluated using the Kaplan–Meier curve and boosted and unboosted regimens were compared using the log‐rank test.

Results

A total of 509 patients starting ATV as a component of their antiretroviral therapy were enrolled in the SCOLTA Project at the time of the study. Boosted ATV was received by 379 patients (74.5%) while 130 (25.5%) were treated with the unboosted formulation. The last therapeutic regimen did not influence the choice of ATV formulation. The mean observational time was 23.9 months. At the end of follow‐up, 58.5% of patients on unboosted ATV and 58.1% of patients on ATV/r continued the treatment and no statistically significant differences were observed for ATV durability between the formulations or among the single causes of therapy interruption.

Conclusions

Our results suggest that, in unselected clinical settings, ATV‐containing antiretroviral therapy is durable and safe in both its formulations.
Prevalence of drug resistance and importance of viral load measurements in Honduran HIV‐infected patients failing antiretroviral treatment
Authors: Murillo W , De Rivera IL , Parham L , Jovel E , Palou E , Karlsson AC , Albert J
Published: August 2009

Objective

The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV‐1‐infected individuals.

Methods

We collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV‐1 pol sequences were obtained using an in‐house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)‐USA list and predicted susceptibility to cART was scored using the anrs algorithm.

Results

Resistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple‐, dual‐ and single‐class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR)=1) vs. immunological failure (OR=0.11; 95% confidence interval (CI) 0.030–0.43) vs. clinical failure (OR=0.037; 95% CI 0.0063–0.22)], route of transmission (OR=42.8; 95% CI 3.73–491), and years on therapy (OR=1.81; 95% CI 1.11–2.93).

Conclusion

The prevalence of antiretroviral resistance was high in Honduran HIV‐infected patients with signs of treatment failure. A majority of study subjects showed dual‐ or triple‐class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance.
Migraine and Genetic and Acquired Vasculopathies
Authors: Stam AH , Haan J , van den Maagdenberg AMJM , Ferrari MD , Terwindt GM
Published: August 2009

It is remarkable that migraine is a prominent part of the phenotype of several genetic vasculopathies, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), retinal vasculopathy with cerebral leukodystrophy (RVCL) and hereditary infantile hemiparessis, retinal arteriolar tortuosity and leukoencephalopahty (HIHRATL). The mechanisms by which these genetic vasculopathies give rise to migraine are still unclear. Common genetic susceptibility, increased susceptibility to cortical spreading depression (CSD) and vascular endothelial dysfunction are among the possible explanations. The relation between migraine and acquired vasculopathies such as ischaemic stroke and coronary heart disease has long been established, further supporting a role of the (cerebral) blood vessels in migraine. This review focuses on genetic and acquired vasculopathies associated with migraine. We speculate how genetic and acquired vascular mechanisms might be involved in migraine.
Legal and Economic Issues in Completing the EU Internal Market for Services: An Interdisciplinary Perspective*
Authors: BADINGER HARALD , MAYDELL NIKLAS
Published: August 2009

We investigate, from an interdisciplinary perspective, the legal and economic consequences of the EU Services Directive, which was adopted in a revised version on 12 December 2006. Studies on the effect of its original version point to moderate macroeconomic effects. Compared with its initial version, the directive has undergone substantial changes, which have eliminated many core elements that would have triggered additional liberalization in services markets. As a result, the Services Directive has moved away from its economic motivation and is likely to miss its aim of completing the EU internal market for services.
The Application of Neofunctionalism to the Enlargement Process: The Case of Turkey
Authors: MACMILLAN CATHERINE
Published: August 2009

This article examines Turkey's EU accession process from a neofunctionalist viewpoint in an attempt to understand why it has proceeded so far despite considerable opposition from some of the Member States. It argues that, although neofunctionalist spillover can account for this, the eventual outcome is still far from certain.
Apatite grain boundary morphology and its response to low‐temperature fluid infiltration in crystalline basement
Authors: LAWTHER S. E. M. , DEMPSTER T. J.
Published: August 2009

Apatite grain boundaries on fractured rock surfaces have been examined in an amphibolite facies regional metamorphic granite gneiss from the central Swiss Alps. The morphology of apatite has been characterized using a scanning electron microscope and matched to surface textures in adjoining silicates. Apatites show a wide variety of different surface features ranging from planar crystal faces, to small‐scale ridges and dimples, to extensive irregular pitting. Many of these features form in response to the periodic infiltration of fluids along open grain boundaries during the cooling history of the gneiss. Apatite shows evidence of both dissolution and re‐precipitation that is controlled by the nature of the grain boundary, the structure of the adjoining silicate phase and the alteration of the host rock. Fracturing occurs in a range of retrograde conditions and is common both within the apatite and along grain boundaries. This coupled to the evidence of fluid interaction with mineral surfaces suggests that extensive permeable networks may be typical of cooling crystalline basement rocks. Grain boundary textures have the potential to reveal a unique record of fluid infiltration in the crust that would be very difficult to decipher using traditional petrographic methods.
Response of Alum Rock springs to the October 30, 2007 Alum Rock earthquake and implications for the origin of increased discharge after earthquakes
Authors: MANGA MICHAEL , ROWLAND JOEL C.
Published: August 2009

The origins of increased stream flow and spring discharge following earthquakes have been the subject of controversy, in large part because there are many models to explain observations and few measurements suitable for distinguishing between hypotheses. On October 30, 2007 a magnitude 5.5 earthquake occurred near the Alum Rock springs, California, USA. Within a day we documented a several‐fold increase in discharge. Over the following year, we have monitored a gradual return towards pre‐earthquake properties, but for the largest springs there appears to be a permanent increase in discharge. The Alum Rock springs discharge waters that are a mixture between modern (shallow) meteoric water and old (deep) connate waters expelled by regional transpression. After the earthquake, there was a small and temporary decrease in the fraction of connate water in the largest springs. Accompanying this geochemical change was a small (1–2°C) temperature decrease. Combined with the rapid response, this implies that the increased discharge has a shallow origin. Increased discharge at these springs occurs both for earthquakes that cause static volumetric expansion and for those that cause contraction, supporting models in which dynamic strains are responsible for the subsurface changes that cause flow to increase. We make a quantitative comparison between the observed changes and model predictions for three types of models: (i) a permanent increase in permeability; (ii) an increase in permeability followed by a gradual decrease to its pre‐earthquake value; and (iii) an increase of hydraulic head in the groundwater system discharging at the springs. We show that models in which the permeability of the fracture system feeding the springs increases after the earthquake are in general consistent with the changes in discharge. The postseismic decrease in discharge could either reflect the groundwater system adjusting to the new, higher permeability or a gradual return of permeability to pre‐earthquake values; the available data do not allow us to distinguish between these two scenarios. However, the response of these springs to another earthquake will provide critical constraints on the changes that occur in the subsurface and should permit a test of all three types of models.
Spring temperatures in the Sagehen Basin, Sierra Nevada, CA: implications for heat flow and groundwater circulation
Authors: BRUMM MARIA , WANG CHI‐YUEN , MANGA MICHAEL
Published: August 2009

Heat flow in the Sierra Nevada, CA, is low despite its young geologic age. We investigate the possibility that advective heat transport by groundwater flow leads to an underestimate of heat flow in the Sierras based purely on borehole measurements. Using temperature and discharge measurements at springs in Sagehen Basin, we find that groundwater removes the equivalent of approximately 20–40 mW m−2 of geothermal heat from the basin. This is comparable with other heat flow measurements in the region and indicates that, in this basin, at least, groundwater does transport a significant amount of geothermal heat within the basin. Additionally, we use estimates of the mean residence time of water discharged at the springs along with hourly temperature records in springs to provide constraints on groundwater flow depths within the basin. An analytical model based on these constraints indicates that the heat removed by groundwater may represent 20% to >90% of the total heat flow in the basin. Without better constraints on the regional hydrogeology and the depth of circulation, we cannot determine whether the heat discharged at the springs represents a change in the mode of heat transfer, i.e. from conduction to advection at shallow depths (<100 m) or whether this is a component of heat transfer that should be added to measured conductive values. If the latter is true, and Sagehen Basin is representative of the Sierras, basal heat flow in the Sierra Nevada may be higher than previously thought.
Molecular mechanisms underlying glutamatergic dysfunction in schizophrenia: therapeutic implications
Authors: Gaspar Pablo A. , Bustamante M. Leonor , Silva Hernán , Aboitiz Francisco
Published: August 2009

Early models for the etiology of schizophrenia focused on dopamine neurotransmission because of the powerful anti‐psychotic action of dopamine antagonists. Nevertheless, recent evidence increasingly supports a primarily glutamatergic dysfunction in this condition, where dopaminergic disbalance is a secondary effect. A current model for the pathophysiology of schizophrenia involves a dysfunctional mechanism by which the NMDA receptor (NMDAR) hypofunction leads to a dysregulation of GABA fast‐ spiking interneurons, consequently disinhibiting pyramidal glutamatergic output and disturbing the signal‐to‐noise ratio. This mechanism might explain better than other models some cognitive deficits observed in this disease, as well as the dopaminergic alterations and therapeutic effect of anti‐psychotics. Although the modulation of glutamate activity has, in principle, great therapeutic potential, a side effect of NMDAR overactivation is neurotoxicity, which accelerates neuropathological alterations in this illness. We propose that metabotropic glutamate receptors can have a modulatory effect over the NMDAR and regulate excitotoxity mechanisms. Therefore, in our view metabotropic glutamate receptors constitute a highly promising target for future drug treatment in this disease.
Stress‐induced responses of human skin fibroblasts in vitro reflect human longevity
Authors: Dekker Pim , Maier Andrea B. , Van Heemst Diana , De Koning‐Treurniet Corine , Blom Joke , Dirks Roeland W. , Tanke Hans J. , Westendorp Rudi G.J.
Published: August 2009

Unlike various model organisms, cellular responses to stress have not been related to human longevity. We investigated cellular responses to stress in skin fibroblasts that were isolated from young and very old subjects, and from offspring of nonagenarian siblings and their partners, representatives of the general population. Fibroblasts were exposed to rotenone and hyperglycemia and assessed for senescence‐associated β‐galactosidase (SA‐β‐gal) activity by flow cytometry. Apoptosis/cell death was measured with the Annexin‐V/PI assay and cell‐cycle analysis (Sub‐G1 content) and growth potential was determined by the colony formation assay. Compared with fibroblasts from young subjects, baseline SA‐β‐gal activity was higher in fibroblasts from old subjects (P = 0.004) as were stress‐induced increases (rotenone: P < 0.001, hyperglycemia: P = 0.027). For measures of apoptosis/cell death, fibroblasts from old subjects showed higher baseline levels (Annexin V+/PI+ cells: P = 0.040, Sub‐G1: P = 0.014) and lower stress‐induced increases (Sub‐G1: P = 0.018) than fibroblasts from young subjects. Numbers and total size of colonies under nonstressed conditions were higher for fibroblasts from young subjects (P = 0.017 and 0.006, respectively). Baseline levels of SA‐β‐gal activity and apoptosis/cell death were not different between fibroblasts from offspring and partner. Stress‐induced increases were lower for SA‐β‐gal activity (rotenone: P = 0.064, hyperglycemia: P < 0.001) and higher for apoptosis/cell death (Annexin V+/PI− cells: P = 0.041, Annexin V+/PI+ cells: P = 0.008). Numbers and total size of colonies under nonstressed conditions were higher for fibroblasts from offspring (P = 0.001 and 0.024, respectively) whereas rotenone‐induced decreases were lower (P = 0.008 and 0.004, respectively). These data provide strong support for the hypothesis that in vitro cellular responses to stress reflect the propensity for human longevity.