bluuebunny/crossref_metadata_2025 huggingface dataset:
Limits of Commercial Investor-State Arbitration: The Need for Appellate Review
Authors: Werner Jacques
Published: February 2010

This chapter explains why investor-state arbitration is often wrongfully likened to international commercial arbitration among private parties. Investor-state arbitrations involve not only private business interests but also public policies of the host state and citizen rights. Arbitral awards on investor-state disputes risk lacking credibility and democratic acceptability if they overrule, in non-transparent proceedings, democratically legitimate government decisions on grounds of investor-state contracts. Similar to the introduction of appellate review in the GATT/WTO dispute settlement system, the transparency, legitimacy, and legal coherence of investor-state arbitration could be enhanced by introduction of an appellate instance.
The Fair and Equitable Treatment Standard and Human Rights Norms
Authors: Knoll-Tudor Ioana
Published: February 2010

This chapter scrutinizes the possible interactions between human rights and investor-state arbitration focussing on the role that the fair and equitable treatment (FET) standard might play in such interaction. The FET standard is found in most of the 2,000 Bilateral Investment Treaties (BITs) signed between more than 170 countries in the world as well as in some multilateral and regional conventions, it is therefore important to first establish the sources and content of this standard. The first part of this chapter inquires into the conventional and customary sources of the FET and discusses the concrete situations in which the FET standard has already been applied. The second part focuses on the relationship between FET and HR norms. It enquires into the rationale of applying human rights norms in international investment law cases since most BITs do not contain a specific reference to HR. It then specifically focuses on the scenarios in which FET may interact with HR norms.
Human Rights Dimensions of Corporate Environmental Accountability
Authors: Morgera Elisa
Published: February 2010

This chapter focuses on the impact of environmental human rights on foreign investors' operations and the role of intergovernmental organizations in ensuring that such operations respect internationally agreed minimum standards. In the context of international practice related to corporate environmental accountability, the chapter scrutinizes the preventive role of intergovernmental organizations vis-à-vis foreign investors' actual or potential negative impacts on environmental human rights in the country in which they are operating. It explores the growing international practice spearheaded by international organizations of ‘translating’ inter-state obligations into normative benchmarks adapted to the reality of private operators, mainly foreign investors, based upon the interpretation and implementation of a combination of international soft and hard law instruments. The contribution therefore assesses the relevance for foreign investment of corporate environmental accountability.
EC Free Trade Agreements: An Alternative Model for Addressing Human Rights in Foreign Investment Regulation and Dispute Settlement?
Authors: Dimopoulos Angelos
Published: February 2010

This chapter explores whether EC Free Trade and Investment Agreements (FTAs) present a new, alternative model for addressing human rights in foreign investment regulation and dispute settlement. It provides an overview of the scope of foreign investment regulation in EC FTAs, highlighting their limited, but innovative approach to foreign investment. It then describes the dispute settlement mechanisms in the EC's FTAs and doubts their suitability for investment disputes in view of their failure to fully address the demands of investors, home and host countries. It considers the effectiveness and suitability of EC FTAs for addressing the human rights implications of foreign investment regulation, and emphasizes the importance given to human rights as an objective of EC FTAs and as an ‘essential element’ of the agreements. The chapter concludes with the future challenges and perspectives for FTAs, notably in view of the EC's willingness to deal with the challenges posed by the interaction between foreign investment and human rights.
12 The Management of Capital Flows and Financial Vulnerability in Asia1
Authors: Akyüz Yılmaz
Published: February 2010

The author deals with the management of capital flows and financial vulnerability in Asia by focusing on the crisis and developing countries. There is a growing consensus that vulnerability of emerging markets to financial contagion and shocks depends in large part on how capital inflows are managed, since options are limited during sudden stops and reversals. Vulnerabilities associated with surges in capital flows lie in four areas: (i) currency and maturity mismatches in private balance sheets, especially of financial institutions; (ii) credit, asset and investment bubbles; (iii) unsustainable currency appreciations and external deficits; and (iv) reliance on help and policy advice from the International Monetary Fund (IMF) rather than self‐insurance against sudden stops and reversals of capital flows. Crisis prevention should thus aim at preventing fragility in private balance sheets and external payments, checking financial and investment bubbles, and building adequate self‐insurance against reversal of capital inflows.
4 Sublime Marvel
Authors: Giudice Gian Francesco
Published: February 2010

The modern theory of particle physics, called the Standard Model, describes electromagnetic, weak, and strong forces and all known forms of matter in terms a single conceptual principle. This chapter gives a short overview of the events that led to the discovery of this theory. It first explains the meaning of quantum field theory, which is the language used to describe the particle world. It then presents QED, the theory which describes the electromagnetic phenomena in the domain of particle physics. Finally, the Standard Model emerges from the synthesis of three intertwined stories: the discovery of quarks, the unification of electromagnetism with the weak force, and the understanding of the strong force in terms of QCD.
11 From Extra Dimensions to New Forces
Authors: Giudice Gian Francesco
Published: February 2010

This chapter starts with a description of the intellectual investigations in worlds with extra spatial dimensions. It briefly introduces the idea of Kaluza–Klein theories and space compactification. Recent research has shown that extra dimensions may provide a solution to the naturalness problem. The most promising proposals are those of large extra dimensions and warped extra dimensions. The conceptual foundations of these theories are discussed, explaining the role of branes as a way of confining matter and forces. Finally, the chapter describes how LHC experiments can obtain empirical evidence in favour of the existence of extra spatial dimensions.
13 Epilogue
Authors: Giudice Gian Francesco
Published: February 2010

This chapter draws some conclusions, and presents speculations on the possible discoveries at the LHC.
Why some Conferences are Difficult: a Study of the Professionals' Experience of Some Initial Child Protection Conferences
Authors: Bell Margaret
Published: February 2010

The views of 261 professionals attending 36 initial child protection conferences with parental participation were collected by means of a questionnaire. Overall, the professionals found the involvement of parents beneficial to the consideration of risk and the decision‐making process, with some provisos. The data revealed that most of the negative responses arose from one third of the conferences, and that these conferences shared particular features relating to family profile and certain conference characteristics. The nature of the difficulties is identified and explored, especially with regard to the ambiguities and the uncertainties involved in risk assessments which contributed to the professionals, negative experiences, and which seemed to be heightened by the parents' presence.
The performance of junior doctors in applying clinical pharmacology knowledge and prescribing skills to standardized clinical cases
Authors: Harding Sam , Britten Nicky , Bristow David
Published: February 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Safe prescribing is a core competency in undergraduate medical education.

• A large proportion of undergraduate medical students and recently graduated doctors in the UK are not confident in their ability to prescribe effectively and safely.

• Errors are common in all healthcare settings and prescribing errors are the most common type.

WHAT THIS STUDY ADDS

• This study produced twelve valid and statistically reliable assessments of clinical pharmacology and therapeutics (CPT) knowledge and prescribing skills in areas that pose a high risk to patient safety.

• The findings show that a large proportion of foundation year 1 (FY1) doctors fail to demonstrate the level of CPT knowledge and prescribing ability judged by a subject matter expert (SME) panel to be required at this stage of their careers.

• We suggest strategies and areas where teaching can be focused to improve the safety and effectiveness of prescribing by FY1 doctors.

AIMS Recent studies suggest a worryingly high proportion of final year medical students and new doctors feel unprepared for effective and safe prescribing. Little research has been undertaken on UK junior doctors to see if these perceptions translate into unsafe prescribing practice. We aimed to measure the performance of foundation year 1 (FY1) doctors in applying clinical pharmacology and therapeutics (CPT) knowledge and prescribing skills using standardized clinical cases.

METHODS A subject matter expert (SME) panel constructed a blueprint, and from these, twelve assessments focusing on areas posing high risk to patient safety and deemed as essential for FY1 doctors to know were chosen. Assessments comprised six extended matching questions (EMQs) and six written unobserved structured clinical examinations (WUSCEs) covering seven CPT domains. Two of each assessment types were administered over three time points to 128 FY1 doctors.

RESULTS The twelve assessments were valid and statistically reliable. Across seven CPT areas tested 51–75% of FY1 doctors failed EMQs and 27–70% failed WUSCEs. The WUSCEs showed three performance trends; 30% of FY1 doctors consistently performing poorly, 50% performing around the passing score, and 20% performing consistently well. Categorical rating of the WUSCEs revealed 5% (8/161) of scripts contained errors deemed as potentially lethal.

CONCLUSIONS This study showed that a large proportion of FY1 doctors failed to demonstrate the level of CPT knowledge and prescribing ability required at this stage of their careers. We identified areas of performance weakness that posed high risk to patient safety and suggested ways to improve the prescribing by FY1 doctors.
Rupatadine does not potentiate the CNS depressant effects of lorazepam: randomized, double‐blind, crossover, repeated dose, placebo‐controlled study
Authors: García‐Gea Consuelo , Ballester Maria Rosa , Martínez Juan , Antonijoan Rosa Maria , Donado Esther , Izquierdo Iñaki , Barbanoj Manuel‐José
Published: February 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Although one defining characteristic of second generation H1‐antihistamines is their lack of CNS effects, it has been proved that some compounds of this group are not devoid of such effects.

• There is evidence that second generation H1‐antihistamine compounds without relevant CNS effects at therapeutic doses could increase the behavioural impairment produced by sedating drugs when both are taken concomitantly.

• The evaluation of possible drug interactions is crucial, especially when both compounds could have CNS effects, due to the possible consequences at the patient safety level.

WHAT THIS STUDY ADDS

• The study demonstrates the lack of CNS effects after repeated administration at therapeutic doses of the unique second generation H1‐antihistamine with anti‐PAF activity.

• The study demonstrates the lack of interaction between repeated administration of rupatadine 10 mg and a single oral dose of lorazepam 2 mg.

• The study presents a useful design to evaluate the interaction between two compounds saving time and the exposure of the volunteers to medication.

AIMThe main objective was to assess whether benzodiazepine intake when rupatadine plasma concentrations were at steady‐state would increase the CNS depressant effects. Rupatadine is a new H1‐antihistamine which also inhibits platelet activating factor (PAF) release and has been shown to be clinically effective at doses of 10 mg.

METHODSSixteen healthy young volunteers took part in a crossover, randomized, double‐blind, placebo controlled trial comprising two experimental periods (repeated administration for 7 days of rupatadine 10 mg or placebo as single oral daily doses, separated by a washout of 14 days). On days 5 and 7, according to a fully balanced design, a single oral dose of lorazepam 2 mg or placebo was added. CNS effects were evaluated on these days by seven objective tests of psychomotor performance and eight subjective visual analogue scales (VAS) at pre‐dose and several times after drug intake. Four treatment conditions were evaluated: placebo, rupatadine 10 mg, lorazepam 2 mg and rupatadine 10 mg + lorazepam 2 mg.

RESULTSSignificant CNS effects, either impairment of psychomotor performance or subjective sedation, were observed when lorazepam was administered, either alone or in combination with steady state concentrations of rupatadine. No significant differences were found between these two conditions. In addition, rupatadine was not different from placebo. All treatments were well tolerated.

CONCLUSIONRepeated doses of rupatadine (10 mg orally) did not enhance the CNS depressant effects of lorazepam (2 mg orally, single dose) either in objective psychomotor tasks or in subjective evaluations.
Omeprazole preferentially inhibits the metabolism of (+)‐(S)‐citalopram in healthy volunteers
Authors: Rocha Adriana , Coelho Eduardo B. , Sampaio Stefânia A. , Lanchote Vera L.
Published: February 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Citalopram (CITA) pharmacokinetics are enantioselective in healthy volunteers and the metabolism of (+)‐(S)‐CITA to (+)‐(S)‐DCITA is dependent on CYP2C19. Omeprazole is a potent CYP2C19 inhibitor.

WHAT THIS STUDY ADDS

• This study indicates that omeprazole induces a loss of enantioselectivity in the CITA pharmacokinetics because of the selective inhibition of (+)‐(S)‐CITA metabolism.

AIM

The study assessed the influence of omeprazole on the kinetic disposition of the (+)‐(S)‐citalopram (CITA) and (−)‐(R)‐CITA enantiomers in healthy volunteers.

METHODS

In a cross‐over study, healthy volunteers (n= 9) phenotyped as extensive metabolizers of CYP2C19 and CYP2D6 and with an oral midazolam clearance ranging from 10.9 to 149.3 ml min−1 kg−1 received a single dose of racemic CITA (20 mg orally) in combination or not with omeprazole (20 mg day−1 for 18 days). Serial blood samples were collected up to 240 h after CITA administration. CITA and demethylcitalopram (DCITA) enantiomers were analyzed by LC‐MS/MS using a Chiralcel® OD‐R column.

RESULTS

The kinetic disposition of CITA was enantioselective in the absence of treatment with omeprazole, with the observation of a greater proportion of plasma (−)‐(R)‐CITA [AUC S : R ratio of 0.53 (95% CI 0.41, 0.66) for CITA and 1.08 (95% CI 0.80, 1.76) for DCITA] than (+)‐(S)‐CITA. Racemic CITA administration to healthy volunteers in combination with omeprazole showed a loss of enantioselectivity in CITA pharmacokinetics with an increase of approximately 120% in plasma (+)‐(S)‐CITA concentrations [AUC S : R ratio of 0.95 (95% CI 0.72, 1.10) for CITA and 0.95 (95% CI 0.44, 1.72) for DCITA].

CONCLUSIONS

The administration of multiple doses of omeprazole preferentially inhibited (+)‐(S)‐CITA metabolism in healthy volunteers. Although omeprazole increased plasma concentrations of (+)‐(S)‐CITA by approximately 120%, it is difficult to evaluate the clinical outcome because the range of plasma CITA concentrations related to maximum efficacy and minimum risk of adverse effects has not been established.
Applying the light : nutrient hypothesis to stream periphyton
Authors: FANTA SHARI E. , HILL WALTER R. , SMITH TIMOTHY B. , ROBERTS BRIAN J.
Published: February 2010

1. The light : nutrient hypothesis (LNH) states that algal nutrient content is determined by the balance of light and dissolved nutrients available to algae during growth. Light and phosphorus gradients in both laboratory and natural streams were used to examine the relevance of the LNH to stream periphyton. Controlled gradients of light (12–426 μmol photons m−2 s−1) and dissolved reactive phosphorus (DRP, 3–344 μg L−1) were applied experimentally to large flow‐through laboratory streams, and natural variability in canopy cover and discharge from a wastewater treatment facility created gradients of light (0.4–35 mol photons m−2 day−1) and DRP (10–1766 μg L−1) in a natural stream.

2. Periphyton phosphorus content was strongly influenced by the light and DRP gradients, ranging from 1.8 to 10.7 μg mg AFDM−1 in the laboratory streams and from 2.3 to 36.9 μg mg AFDM−1 in the natural stream. Phosphorus content decreased with increasing light and increased with increasing water column phosphorus. The simultaneous effects of light and phosphorus were consistent with the LNH that the balance between light and nutrients determines algal nutrient content.

3. In experiments in the laboratory streams, periphyton phosphorus increased hyperbolically with increasing DRP. Uptake then began levelling off around 50 μg L−1.

4. The relationship between periphyton phosphorus and the light : phosphorus ratio was highly nonlinear in both the laboratory and natural streams, with phosphorus content declining sharply with initial increases in the light : phosphorus ratio, then leveling off at higher values of the ratio.

5. Although light and DRP both affected periphyton phosphorus content, the effects of DRP were much stronger than those of light in both the laboratory and natural streams. DRP explained substantially more of the overall variability in periphyton phosphorus than did light, and light effects were evident only at lower phosphorus concentrations (≤25 μg L−1) in the laboratory streams. These results suggest that light has a significant negative effect on the food quality of grazers in streams only under a limited set of conditions.
Responses of macroinvertebrate communities to long‐term flow variability in a Sonoran Desert stream
Authors: SPONSELLER RYAN A. , GRIMM NANCY B. , BOULTON ANDREW J. , SABO JOHN L.
Published: February 2010

Current global models predict a hotter and drier climate in the southwestern United States with anticipated increases in drought frequency and severity coupled with changes in flash flood regimes. Such changes would likely have important ecological consequences, particularly for stream and riparian ecosystems already subject to frequent hydrologic disturbance. This study assessed the potential response of aquatic macroinvertebrates to interannual variation in hydrology in a spatially intermittent desert stream (Sycamore Creek, AZ). We compiled data on the recovery of macroinvertebrate communities following spring floods, with successional sequences captured 11 times over a 16‐year period (1983–1999). This period encompassed a transition from perennial to intermittent flow in this system, and included a record drought in 1989–1990. Results show that while the size of floods initiating sequences had little explanatory power, changes in macroinvertebrate community structure during postflood succession were closely associated with antecedent flooding and drought. Year‐to‐year differences in benthic communities integrated taxon‐specific responses to antecedent disturbance, including differential resistance to channel drying, use of hyporheic refugia, and variable rates of recovery once stream flow resumed. The long‐term consequences of drying on community structure were only evident during later stages of postflood succession, illustrating an interaction between flood and drought recovery processes in this system. Our observations highlight the potential for predicted climate changes in this region to have marked and long‐lasting consequences for benthic communities in desert streams.
Carbon exchange in biological soil crust communities under differential temperatures and soil water contents: implications for global change
Authors: GROTE EDMUND E. , BELNAP JAYNE , HOUSMAN DAVID C. , SPARKS JED P.
Published: February 2010

Biological soil crusts (biocrusts) are an integral part of the soil system in arid regions worldwide, stabilizing soil surfaces, aiding vascular plant establishment, and are significant sources of ecosystem nitrogen and carbon. Hydration and temperature primarily control ecosystem CO2 flux in these systems. Using constructed mesocosms for incubations under controlled laboratory conditions, we examined the effect of temperature (5–35 °C) and water content (WC, 20–100%) on CO2 exchange in light (cyanobacterially dominated) and dark (cyanobacteria/lichen and moss dominated) biocrusts of the cool Colorado Plateau Desert in Utah and the hot Chihuahuan Desert in New Mexico. In light crusts from both Utah and New Mexico, net photosynthesis was highest at temperatures >30 °C. Net photosynthesis in light crusts from Utah was relatively insensitive to changes in soil moisture. In contrast, light crusts from New Mexico tended to exhibit higher rates of net photosynthesis at higher soil moisture. Dark crusts originating from both sites exhibited the greatest net photosynthesis at intermediate soil water content (40–60%). Declines in net photosynthesis were observed in dark crusts with crusts from Utah showing declines at temperatures >25 °C and those originating from New Mexico showing declines at temperatures >35 °C. Maximum net photosynthesis in all crust types from all locations were strongly influenced by offsets in the optimal temperature and water content for gross photosynthesis compared with dark respiration. Gross photosynthesis tended to be maximized at some intermediate value of temperature and water content and dark respiration tended to increase linearly. The results of this study suggest biocrusts are capable of CO2 exchange under a wide range of conditions. However, significant changes in the magnitude of this exchange should be expected for the temperature and precipitation changes suggested by current climate models.
Microbial 13C utilization patterns via stable isotope probing of phospholipid biomarkers in Mojave Desert soils exposed to ambient and elevated atmospheric CO2
Authors: JIN V. L. , EVANS R. D.
Published: February 2010

Changes in plant inputs under changing atmospheric CO2 can be expected to alter the size and/or functional characteristics of soil microbial communities which can determine whether soils are a C sink or source. Stable isotope probing was used to trace autotrophically fixed 13C into phospholipid fatty acid (PLFA) biomarkers in Mojave Desert soils planted with the desert shrub, Larrea tridentata. Seedlings were pulse‐labeled with 13CO2 under ambient and elevated CO2 in controlled environmental growth chambers. The label was chased into the soil by extracting soil PLFAs after labeling at Days 0, 2, 10, 24, and 49. Eighteen of 29 PLFAs identified showed 13C enrichment relative to nonlabeled control soils. Patterns of PLFA enrichment varied temporally and were similar for various PLFAs found within a microbial functional group. Enrichment of PLFA 13C generally occurred within the first 2 days in general and fungal biomarkers, followed by increasingly greater enrichment in bacterial biomarkers as the study progressed (Gram‐negative, Gram‐positive, actinobacteria). While treatment CO2 level did not affect total PLFA‐C concentrations, microbial functional group abundances and distribution responded to treatment CO2 level and these shifts persisted throughout the study. Specifically, ratios of bacterial‐to‐total PLFA‐C decreased and fungal‐to‐bacterial PLFA‐C increased under elevated CO2 compared with ambient conditions. Differences in the timing of 13C incorporation into lipid biomarkers coupled with changes in microbial functional groups indicate that microbial community characteristics in Mojave Desert soils have shifted in response to long‐term exposure to increased atmospheric CO2.
Are badgers ‘Under The Weather’? Direct and indirect impacts of climate variation on European badger (Meles meles) population dynamics
Authors: MACDONALD DAVID W. , NEWMAN CHRISTOPHER , BUESCHING CHRISTINA D. , NOUVELLET PIERRE
Published: February 2010

Weather conditions, and how they in turn define and characterize regional climatic conditions, are a primary limit on global species diversity and distribution, and increasing variability in global and regional climates have significant implications for species and habitat conservation. A Capture–Mark–Recapture study revealed that badger (Meles meles) life history parameters interact in complicated ways with annual variability in the seasonality of temperature and rainfall, both in absolute and in phenological terms. A strong predictive relationship was observed between survival and both temperature and late‐summer rainfall. This link at the population dynamics level was related to individual body‐weight increases observed between summer and autumn. In addition, fecundity was correlated with spring rainfall and temperature. We investigated and confirmed that relationships were consistent with observed variation in the intensity of a parasitic infection. Finally, fecundity during any given year correlated with conditions in the preceding autumn. Badger survival also correlated with late winter weather conditions. This period is critical for badgers insofar as it coincides with their peak involvement in road traffic accidents (RTAs). RTA rate during this period was linked strongly to temperature, underlining the intricate ways in which a changing climate might interact with anthropogenic agents to influence species' population processes. Equinoctial conditions produced significant population driver effects. That is, while summers will always be relatively warm compared with winters, spring and autumn weather can be more variable and functionally delimit the ‘productive’ vs. nonproductive period of the year in terms of badger behavioural and physiological cycles. This study highlights how appropriately informed conservation strategies, mindful of trends in climatic conditions, will become ever‐more essential to ensure the survival of many species globally.
RET gene mutations are not involved in the origin of human testicular seminoma
Authors: Chevalier N. , Barlier A. , Roche C. , Mograbi B. , Camparo P. , Devouassoux‐Shisheboran M. , Michiels J.‐F , Nebout M. , Chevallier D. , Benahmed M. , Enjalbert A. , Fénichel P.
Published: February 2010

Testicular germ cell cancers are the most common solid malignancies in young men, but their pathogenesis remains undetermined although some epidemiological data have implicated both environmental and genetic factors. Glial cell‐derived neurotrophic factor (GDNF) is secreted by Sertoli cells, and promotes germ stem cell proliferation by activating RET, a tyrosine kinase receptor. Over‐expression of GDNF in adult transgenic mice induces the development of testicular tumours that mimic human seminoma, the most frequent testicular germ cell tumour. Activating mutations of RET were previously reported in several types of cancer, including thyroid, pituitary, adrenal and melanoma cancer. Both mouse experimental model and clinical studies suggested that mutations or selective polymorphisms of RET might be associated with human seminoma. To verify this hypothesis, we conducted this study in a French University Hospital and carried out an association study using tissue samples from 66 paraffin‐embedded seminoma tumours. The most frequently mutated exons of the RET proto‐oncogene were sequenced to identify mutations or selective polymorphisms. No somatic mutations were identified. The polymorphic variants frequencies did not differ from those in a control Caucasian population. Human classical seminoma that occurs in young men does not appear to be linked with mutations or relevant polymorphisms of RET.
Relationship between cystic fibrosis respiratory tract bacterial communities and age, genotype, antibiotics and Pseudomonas aeruginosa
Authors: Klepac‐Ceraj Vanja , Lemon Katherine P. , Martin Thomas R. , Allgaier Martin , Kembel Steven W. , Knapp Alixandra A. , Lory Stephen , Brodie Eoin L. , Lynch Susan V. , Bohannan Brendan J. M. , Green Jessica L. , Maurer Brian A. , Kolter Roberto
Published: February 2010

Polymicrobial bronchopulmonary infections in cystic fibrosis (CF) cause progressive lung damage and death. Although the arrival of Pseudomonas aeruginosa often heralds a more rapid rate of pulmonary decline, there is significant inter‐individual variation in the rate of decline, the causes of which remain poorly understood. By coupling culture‐independent methods with ecological analyses, we discovered correlations between bacterial community profiles and clinical disease markers in respiratory tracts of 45 children with CF. Bacterial community complexity was inversely correlated with patient age, presence of P. aeruginosa and antibiotic exposure, and was related to CF genotype. Strikingly, bacterial communities lacking P. aeruginosa were much more similar to each other than were those containing P. aeruginosa, regardless of antibiotic exposure. This suggests that community composition might be a better predictor of disease progression than the presence of P. aeruginosa alone and deserves further study.
Knowledge arbitrage in global pharma: a synthetic view of absorptive capacity and open innovation
Authors: Hughes Benjamin , Wareham Jonathan
Published: February 2010

This case study examines a global pharmaceutical company widely using open innovation (OI). Three main research questions are addressed: (1) what OI concepts are salient in their innovation portfolio?, (2) what OI concepts are used in the strategy formulation? and (3) what other concepts are present that augment OI? Interviews with 120 managers and archival documents were analyzed using thematic analysis. Two concepts prominent in the literature, (i) value capture models and (ii) technology evaluation criteria, were not present in this portfolio. By contrast, we found a focus on OI capability building, external information sharing and uncertain knowledge arbitrage in networks. Finally, we discuss these capabilities in relation to absorptive capacity, proposing a simple, but important bi‐directional perspective to embrace OI.
You Don’t Always Get What You Pay For: Bonuses, Perceived Income and Effort
Authors: Schnedler Wendelin
Published: February 2010

Consider a principal-agent relationship in which more effort by the agent raises the likelihood of success. This paper provides conditions such that no success bonus induces the agent to exert more effort and the optimal contract is independent of success. Moreover, success bonuses may even reduce effort and thus the probability of success. The reason is that bonuses increase the perceived income of the agent and can hence reduce his willingness to exert effort. This perceived income effect has to be weighed against the incentive effect of the bonus. The tradeoff is determined by the marginal effect of effort on the success probability in relation to this probability itself (success hazard-rate of effort). The paper also discusses practical implications of the finding.
Comorbidities amongst patients with multiple sclerosis: a population‐based controlled study
Authors: Kang J.‐H. , Chen Y.‐H. , Lin H.‐C.
Published: February 2010

Background:  Data regarding the wide spectrum of comorbidity amongst patients with multiple sclerosis (MS) are still scanty, especially in Asian populations. Our goal was to analyze comorbidity prevalences and risks amongst Chinese patients with MS, compared to matched controls.

Methods:  In total, 898 patients with MS and 4490 randomly matched individuals without MS were extracted from the National Health Insurance Research Dataset in Taiwan. We selected 30 comorbid medical conditions for analysis. Conditional logistic regression analyses were used to examine the risks of comorbidity between the two groups.

Results:  The regression analyses showed that patients with MS were more likely to have systemic lupus erythematosus (OR = 26.9, 95% CI = 10.3–70.3), depression (OR = 6.9, 95% CI = 5.3–8.9), peripheral vascular disorders (OR = 6.6, 95% CI = 4.0–11.0), deficiency anemias (OR = 4.9, 95% CI = 2.8–8.7), rheumatoid arthritis (OR = 4.8, 95% CI = 2.9–8.1) and fluid and electrolyte disorders (OR = 4.8, 95% CI = 2.8–8.3) than the matched controls.

Conclusions:  Patients with MS had higher risk of multiple medical comorbidities compared to a matched control group in an ethnic Chinese population.
Hydrologic responses to earthquakes and a general metric
Authors: WANG CHI‐YUEN , MANGA MICHAEL
Published: February 2010

Geofluids(2010)10, 206–216

Hydrologic responses to earthquakes, including liquefaction, changes in stream and spring discharge, changes in the properties of groundwater such as geochemistry, temperature and turbidity, changes in the water level in wells, and the eruption of mud volcanoes, have been documented for thousands of years. Except for some water‐level changes in the near field which can be explained by poroelastic responses to static stress changes, most hydrologic responses, both within and beyond the near field, can only be explained by the dynamic responses associated with seismic waves. For these responses, the seismic energy densityemay be used as a general metric to relate and compare the various hydrologic responses. We show that liquefaction, eruption of mud volcanoes and increases in streamflow are bounded bye ∼ 10−1 J m−3; temperature changes in hot springs are bounded bye ∼ 10−2 J m−3; most sustained groundwater changes are bounded bye ∼ 10−3 J m−3; geysers and triggered seismicity may respond to seismic energy density as small as 10−3and 10−4 J m−3, respectively. Comparing the threshold energy densities with published laboratory measurements, we show that undrained consolidation induced by dynamic stresses can explain liquefaction only in the near field, but not beyond the near field. We propose that in the intermediate field and far field, most responses are triggered by changes in permeability that in turn are a response to the cyclic deformation and oscillatory fluid flow. Published laboratory measurements confirm that changes in flow and time‐varying stresses can change permeability, inducing both increases and decreases. Field measurements in wells also indicate that permeability can be changed by earthquakes in the intermediate field and far field. Further work, in particular field monitoring and measurements, are needed to assess the generality of permeability changes in explaining far‐field hydrologic responses to earthquakes.
Stereotypic movement disorder: easily missed
Authors: FREEMAN ROGER D , SOLTANIFAR ATEFEH , BAER SUSAN
Published: February 2010

Aim  To expand the understanding of stereotypic movement disorder (SMD) and its differentiation from tics and autistic stereotypies.

Method  Forty‐two children (31 males, mean age 6y 3mo, SD 2y 8mo; 11 females, mean age 6y 7mo, SD 1y 9mo) consecutively diagnosed with SMD, without‐self‐injurious behavior, intellectual disability, sensory impairment, or an autistic spectrum disorder (ASD), were assessed in a neuropsychiatry clinic. A list of probe questions on the nature of the stereotypy was administered to parents (and to children if developmentally ready). Questionnaires administered included the Stereotypy Severity Scale, Short Sensory Profile, Strengths and Difficulties Questionnaire, Repetitive Behavior Scale – Revised, and the Developmental Coordination Disorder Questionnaire. The stereotyped movement patterns were directly observed and in some cases further documented by video recordings made by parents. The probe questions were used again on follow‐up at a mean age of 10 years 7 months (SD 4y 4mo).

Results  Mean age at onset was 17 months. Males exceeded females by 3:1. Family history of a pattern of SMD was reported in 13 and neuropsychiatric comorbidity in 30 (attention‐deficit–hyperactivity disorder in 16, tics in 18, and developmental coordination disorder in 16). Obsessive–compulsive disorder occurred in only two. The Short Sensory Profile correlated with comorbidity (p<0.001), the Stereotypy Severity Scale (p=0.009), and the Repetitive Behavior Scale (p<0.001); the last correlated with the Stereotypy Severity Scale (p=0.001). Children (but not their parents) liked their movements, which were usually associated with excitement or imaginative play. Mean length of follow‐up was 4 years 8 months (SD 2y 10mo). Of the 39 children followed for longer than 6 months, the behavior stopped or was gradually shaped so as to occur primarily privately in 25. Misdiagnosis was common: 26 were initially referred as tics, 10 as ASD, five as compulsions, and one as epilepsy. Co‐occurring facial grimacing in 15 children and vocalization in 22 contributed to diagnostic confusion.

Interpretation  SMD occurs in children without ASD or intellectual disability. The generally favorable clinical course is largely due to a gradual increase in private expression of the movements. Severity of the stereotypy is associated with sensory differences and psychopathology. Differentiation of SMD from tics and ASD is important to avoid misdiagnosis and unnecessary treatment.
Early prediction of cerebral palsy by computer‐based video analysis of general movements: a feasibility study
Authors: ADDE LARS , HELBOSTAD JORUNN L , JENSENIUS ALEXANDER R , TARALDSEN GUNNAR , GRUNEWALDT KRISTINE H , STØEN RAGNHILD
Published: February 2010

Aim  The aim of this study was to investigate the predictive value of a computer‐based video analysis of the development of cerebral palsy (CP) in young infants.

Method  A prospective study of general movements used recordings from 30 high‐risk infants (13 males, 17 females; mean gestational age 31wks, SD 6wks; range 23–42wks) between 10 and 15 weeks post term when fidgety movements should be present. Recordings were analysed using computer vision software. Movement variables, derived from differences between subsequent video frames, were used for quantitative analyses. CP status was reported at 5 years.

Results  Thirteen infants developed CP (eight hemiparetic, four quadriparetic, one dyskinetic; seven ambulatory, three non‐ambulatory, and three unknown function), of whom one had fidgety movements. Variability of the centroid of motion had a sensitivity of 85% and a specificity of 71% in identifying CP. By combining this with variables reflecting the amount of motion, specificity increased to 88%. Nine out of 10 children with CP, and for whom information about functional level was available, were correctly predicted with regard to ambulatory and non‐ambulatory function.

Interpretation  Prediction of CP can be provided by computer‐based video analysis in young infants. The method may serve as an objective and feasible tool for early prediction of CP in high‐risk infants.
Superior longitudinal fasciculus and cognitive dysfunction in adolescents born preterm and at term
Authors: FRYE RICHARD E , HASAN KHADER , MALMBERG BENJAMIN , DESOUZA LAURA , SWANK PAUL , SMITH KAREN , LANDRY SUSAN
Published: February 2010

Aim  To understand the relationship between cognition and white‐matter structure in adolescents born preterm without obvious brain injury.

Methods  Thirty‐two adolescents from a longitudinal study of child development were selected according to risk of developmental disorders at birth (born at term: eight males, five females; median age 16y 1mo, interquartile range 10mo; low risk preterm: four males, five females, median age 16y, range 4mo; high risk preterm: three males, seven females, median age 16y 2mo, range 1y 2mo) and reading ability (good: three males, eight females, median age 16y, range 7mo; average: six males, three females, median age 16y 10mo, range 1y; poor: six males, six females, median age 16y, range 6mo). Preterm birth was defined as a gestational age of 36 weeks or less and a birthweight of 1600g or less. All participants had normal clinical neuroimaging findings. We examined fractional anisotropy, radial diffusivity, and volume of three major white‐matter fasciculi. The relationship between structural measures and birth risk, hemisphere, and cognitive ability (attention, lexical and sublexical decoding, auditory phonological awareness, and processing speed) were analysed using mixed‐model regression.

Results  Left‐hemisphere superior longitudinal fasciculus (SLF) fractional anisotropy and radial diffusivity were linked to reading‐related skills (fractional anisotropy vs letter–word identification, r(30)=−0.37, p<0.05; fractional anisotropy vs phoneme reversal, r(30)=−0.34, p=0.05; radial diffusivity vs letter–word identification, r(30)=0.31, p<0.10; radial diffusivity vs phoneme reversal, r(30)=0.40, p<0.05), whereas right‐hemisphere SLF fractional anisotropy was related to attention skills (fractional anisotropy vs inattentiveness, r(30)=−0.38, p<0.05). SLF volume decreased as these skills declined for adolescents born preterm (volume vs phoneme reversal, r(17)=0.58, p<0.01; volume vs inattentiveness, r(17)=−0.69, p<0.01), but not for those born at term.

Interpretation  The relationship between cognitive skills and SLF volume suggests that in adolescents born preterm, cryptic white‐matter injury may exist, possibly related to oligodendrocyte or axonal loss, despite normal clinical neuroimaging.
Narrative skills following early confirmation of permanent childhood hearing impairment
Authors: WORSFOLD SARAH , MAHON MERLE , YUEN HO MING , KENNEDY COLIN
Published: February 2010

Aim  The aim of this study was to compare spoken language production in children with permanent childhood hearing impairment (PCHI) whose PCHI was confirmed either early or late.

Method  Audio‐taped spoken narrative was assessed for syntax, phonology, morphology, and narrative in transcripts from a population‐based sample of 89 children (49 males, 40 females; age mean age 7y 7mo, SD1y 1mo, range 6y 6mo–10y 9mo) with bilateral PCHI (≥40dB hearing loss) and a comparison group of 63 children (37 males, 26 females; mean age 8y 1mo; SD 1y) with normal hearing. Of the 89 children with PCHI, 41 (21 males, 20 females) had their hearing impairment confirmed by the age of 9 months. All children with PCHI were tested with hearing aids in place, including 16 with cochlear implants. The group of children whose PCHI had been confirmed by age 9 months was compared with the group with later confirmation of PCHI using regression models on the outcome measures.

Results  Compared with those with late‐confirmed PCHI, children with early‐confirmed PCHI used significantly more sentences (mean difference 2.7; 95% confidence interval [CI] 0.49–5.24; p=0.019) and categories of high‐pitched morphological markers (mean difference 6.64; 95% CI 1.96–11.31; p=0.006). The number of categories of low‐pitched morphological markers, phonological simplifications, and sentences with multiple clauses did not differ between groups. The odds ratios (95% CI) of superior narrative structure and narrative content in children whose PCHI was confirmed early were 3.03 (1.09–8.46; p=0.034) and 4.43 (1.52–12.89; p=0.006) respectively.

Interpretation  Early confirmation compared with late confirmation of PCHI was associated with benefit to narrative skills and to certain expressive aspects of syntax and morphology, but not expressive phonology.
The anti‐protozoal drug pentamidine blocks KIR2.x‐mediated inward rectifier current by entering the cytoplasmic pore region of the channel
Authors: De Boer TP , Nalos L , Stary A , Kok B , Houtman MJC , Antoons G , Van Veen TAB , Beekman JDM , De Groot BL , Opthof T , Rook MB , Vos MA , Van Der Heyden MAG
Published: February 2010

Background and purpose: Pentamidine is a drug used in treatment of protozoal infections. Pentamidine treatment may cause sudden cardiac death by provoking cardiac arrhythmias associated with QTc prolongation and U‐wave alterations. This proarrhythmic effect was linked to inhibition of hERG trafficking, but not to acute block of ion channels contributing to the action potential. Because the U‐wave has been linked to the cardiac inward rectifier current (IK1), we examined the action and mechanism of pentamidine‐mediatedIK1block.

Experimental approach: Patch clamp measurements ofIK1were made on cultured adult canine ventricular cardiomyocytes, KIR2.1‐HEK293 cells and KIR2.x inside‐out patches. Pentamidine binding to cytoplasmic amino acid residues of KIR2.1 channels was studied by molecular modelling.

Key results: Pentamidine application (24 h) decreasedIK1in cultured canine cardiomyocytes and KIR2.1‐HEK293 cells under whole cell clamp conditions. Pentamidine inhibitedIK1in KIR2.1‐HEK293 cells 10 min after application. When applied to the cytoplasmic side under inside‐out patch clamp conditions, pentamidine block ofIK1was acute (IC50= 0.17 µM). Molecular modelling predicted pentamidine‐channel interactions in the cytoplasmic pore region of KIR2.1 at amino acids E224, D259 and E299. Mutation of these conserved residues to alanine reduced pentamidine block ofIK1. Block was independent of the presence of spermine. KIR2.2, and KIR2.3 basedIK1was also sensitive to pentamidine blockade.

Conclusions and implications: Pentamidine inhibits cardiacIK1by interacting with three negatively charged amino acids in the cytoplasmic pore region. Our findings may provide new insights for development of specificIK1blocking compounds.
How Does Preference for Natural Childbirth Relate to the Actual Mode of Delivery? A Population‐based Cohort Study from Norway
Authors: Kringeland Tone , Daltveit Anne Kjersti , Møller Anders
Published: February 2010

Abstract:  Background:  In Norway, intervention in childbirth has increased from 3 percent in 1967 to 37 percent in 2006. The objectives of this study were, first, to estimate to which extent women who expressed a preference for natural birth actually were delivered vaginally without interventions, and second, to estimate the influence that emotions and maternal background factors have on the mode of delivery.

Methods:  We used data from 39,475 pregnancies of participants in the Norwegian Mother and Child Cohort Study in which the pregnant woman had expressed a preference for natural birth, and linked these data with the pregnancy outcome as registered in the population‐based Medical Birth Registry of Norway during 2000 to 2006. The influence of maternal factors on the mode of delivery was estimated with log‐binomial regression models, stratified by parity.

Results:  Among primiparas, 29.3 percent delivered vaginally without interventions (natural birth), 56.1 percent gave birth vaginally with interventions, and 14.5 percent had a cesarean section. The strongest predictor for actually having a natural birth was age below 25 years, having more than 12 years’ education, carrying a single fetus, and having a low score for anxiety and depression. Among multiparas, 61.1 percent gave birth vaginally without interventions, 30.6 percent vaginally with interventions, and only 8.3 percent had a cesarean section. The effects of maternal age, education, and anxiety or depression on the outcome were smaller for multiparas than for primiparas.

Conclusions:  The chance of actually having a natural birth for women with a preference for a natural birth is much greater for multiparas than for primiparas. The factors that influence the chance of having a natural birth are different for primiparas and multiparas. (BIRTH 37:1 March 2010)