bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction therapy and mTOR inhibition: minimizing calcineurin inhibitor exposure in de novo renal transplant patients
Authors: Nashan Björn
Published: August 2013

Use of induction therapy with mTOR inhibitor maintenance immunosuppression to facilitate reduced calcineurin inhibitor (CNI) exposure in de novo kidney transplant patients has been explored in a series of randomized trials. These studies have typically employed interleukin‐2 receptor antagonist (IL‐2RA) induction, in low or standard immunological risk recipients. Although no study has directly compared mTOR inhibition plus reduced CNI exposure with or without induction, inclusion of IL‐2RA induction appears to permit a substantial reduction in CNI exposure without the need for high mTOR inhibitor dosing. IL‐2RA induction with an mTOR inhibitor and steroids has consistently shown similar efficacy to standard‐exposure CNI with mycophenolic acid and steroids and may improve renal function among patients who remain on the mTOR inhibitor‐based regimen. With modern mTOR inhibitor dosing, wound healing complications are of less concern and may be no more frequent than in mycophenolic acid‐based regimens. The incidence of cytomegalovirus infection appears lower in patients receiving de novo mTOR inhibition. The available evidence demonstrates that IL‐2RA induction with an mTOR inhibitor can successfully reduce CNI exposure by at least half without a penalty in terms of rejection in low‐ or moderate‐risk de novo transplant recipients and may offer renal and antiviral benefits.
Indications for intestinal transplantation: recognizing the scope and limits of total parenteral nutrition
Authors: Gotthardt Daniel N. , Gauss Annika , Zech Ulrike , Mehrabi Arianeb , Weiss Karl Heinz , Sauer Peter , Stremmel Wolfgang , Büchler Markus W. , Schemmer Peter
Published: August 2013

Total parenteral nutrition (TPN) is currently the treatment of choice for patients with intestinal failure. Intestinal failure in adults is mostly due to short bowel syndrome, which is most often caused by ischemia and Crohn's disease. However, TPN fails in a substantial number of cases. For patients with TPN failure, intestinal transplantation (ITx) may be offered as a treatment. TPN failure is considered to be present either if nutrition itself is not possible or if complications of TPN occur. These complications can, for example, originate from recurrent line infections or thrombosis. As TPN is usually a lifelong therapy and is associated with substantial impairment of the quality of life, the tolerance of each patient to this procedure is another important consideration in the decision making about whether to perform transplantation. The survival rates of intestinal transplant recipients have now reached the same level as that of recipients of other solid organ transplants. A five‐yr survival of up to 80% has been reported in specialized centers, whereas registry data show rates of <80%. Although in about one‐third of patients, isolated ITx is sufficient, patients with concurrent liver disease (mostly due to TPN) benefit from combined intestinal and liver transplantation. In some cases, multivisceral transplantation is necessary. Here, we review the current indications for ITx with a special focus on TPN.
Intestinal transplantation: review of operative techniques
Authors: Nickkholgh Arash , Contin Pietro , Abu‐Elmagd Kareem , Golriz Mohammad , Gotthardt Daniel , Morath Christian , Schemmer Peter , Mehrabi Arianeb
Published: August 2013

The improvement of outcomes in intestinal transplantation (ITx) over the last two decades has been made possible through standardization in surgical techniques, improvements in immunosuppressive and induction protocols, and post‐operative patient care. From a surgical technical point of view, all different types of small bowel containing transplants can be categorized into three main prototypes, including isolated small bowel, liver–small bowel, and multivisceral transplantations. In this review, we describe these three main prototypes and discuss the most important technical modifications of each type, as well as donor and recipient procedures, and highlight the more recent operative technical topics of discussion in the literature.
Modified body mass index and time interval between diagnosis and operation affect survival after liver transplantation for hereditary amyloidosis: a single‐center analysis
Authors: Franz Clemens , Hoffmann Katrin , Hinz Ulf , Singer Reinhard , Hund Ernst , Gotthardt Daniel N. , Ganten Tom , Kristen Arnt Volko , Hegenbart Ute , Schönland Stefan , Hinderhofer Katrin , Büchler Markus W. , Schemmer Peter
Published: August 2013

Introduction

Familial amyloid polyneuropathy (FAP) is the most common subtype of hereditary amyloidosis. The amyloid protein transthyretin deposits as rigid amyloid fibers in the extracellular matrix of various tissues including peripheral nerves, heart, and gastrointestinal tract. As the mutated amyloid protein is mainly produced in the liver, one form of treatment to halt the progression of disease is liver transplantation (LT). This study was performed to identify risk factors for decreased overall survival.

Methods

Clinical data of 21 transplant patients who underwent LT for FAP between 1996 and 2011 were analyzed retrospectively.

Results

The majority of patients had cardiac symptoms (76%), gastrointestinal symptoms (71%), or peripheral polyneuropathy (71%). A conventional operating technique was performed on 11 patients using end‐to‐end caval anastomoses, while the modified piggyback technique by Belghiti was performed on 10 patients. Overall survival analysis revealed a one‐yr survival rate of 74.3% and three‐ and five‐yr survival rates of 60.0% and 52.5%, respectively. Pre‐operative modified body mass index (mBMI) <700 kg g/L m² and time interval between diagnosis and operation before LT resulted in significantly lower overall survival (p = 0.0137; p = 0.033).

Conclusion

The pre‐operative nutritional status and time interval between diagnosis and operation before LT influence overall survival after LT for hereditary amyloidosis.
Fathom out: biogeographical subdivision across the Western Australian continental margin – a multispecies modelling approach
Authors: Woolley Skipton N. C. , McCallum Anna W. , Wilson Robin , O'Hara Timothy D. , Dunstan Piers K.
Published: August 2013

Aim

Biogeographical regions are often used as a basis for management strategies, yet a challenge for biodiversity management across broad scales is establishing biogeographical regions that are robust across taxonomic groups.

Methods

Finite mixture models were developed to predict multiple species assemblages termed archetypes. Modelled species archetypes were developed using Decapoda, Ophiuroidea and Polychaeta species, which were grouped based on their similar responses to oceanographic and geographical gradients.

Location

Outer‐shelf and slope (50–1200 m) of the continental margin of Western Australia (~11° S–36° S).

Results

Four faunal regions were defined based on cross‐taxa surrogates grouped as archetypes. These faunal regions were defined by oxygen, salinity, carbon and temperature gradients across latitude and bathymetry. Two broad latitudinal bands and two bathyal regions were described. Adjacent faunal groups were not defined by abrupt geographical breaks but rather transitions.

Main conclusions

These results suggest that faunal distributions were less finely resolved than existing marine bioregions on the Western Australian continental margin and that environmental gradients are correlated with distributions of benthic marine invertebrates. Identifying biogeographical regions based on these methods has the potential to inform management across a broad range of environments.
Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add‐on to metformin in type 2 diabetes with mild hyperglycaemia
Authors: Rosenstock J. , Seman L. J. , Jelaska A. , Hantel S. , Pinnetti S. , Hach T. , Woerle H. J.
Published: August 2013

Aims

To evaluate the effects of the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin added to metformin for 12 weeks in patients with type 2 diabetes.

Methods

This dose‐ranging, double‐blind, placebo‐controlled trial randomized 495 participants with type 2 diabetes inadequately controlled on metformin [haemoglobin A1c (HbA1c) >7 to ≤10%] to receive 1, 5, 10, 25, or 50 mg empagliflozin once daily (QD), or placebo, or open‐label sitagliptin (100 mg QD), added to metformin for 12 weeks. The primary endpoint was change in HbA1c from baseline to week 12 (empagliflozin groups versus placebo).

Results

Reductions in HbA1c of −0.09 to −0.56% were observed with empagliflozin after 12 weeks, versus an increase of 0.15% with placebo (baseline: 7.8–8.1%). Compared with placebo, empagliflozin doses from 5 to 50 mg resulted in reductions in fasting plasma glucose (−2 to −28 mg/dl vs. 5 mg/dl with placebo; p < 0.0001) and body weight (−2.3 to −2.9 kg vs. −1.2 kg; p < 0.01). Frequency of adverse events was generally similar with empagliflozin (29.6–48.6%), placebo (36.6%) and sitagliptin (35.2%). Hypoglycaemia rates were very low and balanced among groups. Most frequent adverse events with empagliflozin were urinary tract infections (4.0% vs. 2.8% with placebo) and pollakiuria (2.5% vs. 1.4% with placebo). Genital infections were reported only with empagliflozin (4.0%).

Conclusions

Once daily empagliflozin as add‐on therapy to metformin was well tolerated except for increased genital infections and resulted in reductions in HbA1c, fasting plasma glucose and body weight in patients with type 2 diabetes inadequately controlled on metformin monotherapy.
Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years
Authors: Wilding J. P. H. , Woo V. , Rohwedder K. , Sugg J. , Parikh S. ,   for the Dapagliflozin 006 Study Group
Published: August 2013

Aims

Dapagliflozin, a selective inhibitor of sodium‐glucose cotransporter 2 (SGLT2), has been shown to improve glycaemic control, stabilize insulin dosing and mitigate insulin‐associated weight gain over 48 weeks in patients whose type 2 diabetes mellitus (T2DM) was inadequately controlled despite high doses of insulin. Here the efficacy and safety of dapagliflozin therapy after a total of 104 weeks are evaluated in this population.

Methods

This was a 24‐week, randomized, placebo‐controlled, double‐blinded, multicentre trial followed by two site‐ and patient‐blinded extension periods of 24 and 56 weeks (NCT00673231), respectively. A total of 808 patients, whose T2DM was inadequately controlled on insulin ≥30 IU/day, with or without up to two oral antidiabetic drugs, were randomly assigned to receive placebo or 2.5, 5 or 10 mg/day of dapagliflozin for 104 weeks. At 48 weeks, patients on dapagliflozin 5 mg were switched to 10 mg. Outcomes over 104 weeks included change from baseline in HbA1c, insulin dose and body weight; analyses used observed cases and included data after insulin up‐titration. Adverse events (AEs) were evaluated throughout 104 weeks.

Results

Five hundred and thirteen patients (63.6%) completed the study. Mean HbA1c changes from baseline at 104 weeks were −0.4% in the placebo group and −0.6 to −0.8% in the dapagliflozin groups. In the placebo group, mean insulin dose increased by 18.3 IU/day and weight increased by 1.8 kg at 104 weeks, whereas in the dapagliflozin groups, insulin dose was stable and weight decreased by 0.9–1.4 kg. AEs, including hypoglycaemia, were balanced across groups. Proportions of patients with events suggestive of genital infection and of urinary tract infection (UTI) were higher with dapagliflozin versus placebo (genital infection 7.4–14.3% vs. 3.0%; UTI 8.4–13.8% vs. 5.6%) but most occurred in the first 24 weeks and most were single episodes that responded to routine management.

Conclusions

Dapagliflozin improved glycaemic control, stabilized insulin dosing and reduced weight without increasing major hypoglycaemic episodes over 104 weeks in patients whose T2DM was inadequately controlled on insulin. However, rates of genital infection and of UTI were elevated with dapagliflozin therapy.
Empagliflozin improves glycaemic and weight control as add‐on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24‐week, randomized, placebo‐controlled trial
Authors: Kovacs C. S. , Seshiah V. , Swallow R. , Jones R. , Rattunde H. , Woerle H. J. , Broedl U. C. ,   on behalf of the EMPA‐REG PIO™ trial investigators
Published: August 2013

Aims

This study investigated the efficacy and tolerability of empagliflozin as add‐on to pioglitazone ± metformin in patients with type 2 diabetes (T2DM).

Methods

Patients with HbA1c ≥7 and ≤10% were randomized and treated with once daily empagliflozin 10 mg (n = 165), empagliflozin 25 mg (n = 168) or placebo (n = 165) as add‐on to pioglitazone ± metformin for 24 weeks. Endpoints included changes from baseline in HbA1c (primary endpoint), fasting plasma glucose (FPG) and body weight at week 24.

Results

Adjusted mean ± standard error changes in HbA1c were −0.6 ± 0.07% and −0.7 ± 0.07% with empagliflozin 10 mg and 25 mg, respectively, vs. −0.1 ± 0.07% with placebo (both p < 0.001). More patients with HbA1c ≥7% at baseline achieved HbA1c <7% with empagliflozin 10 mg (23.8%) and 25 mg (30.0%) vs. placebo (7.7%) (both p < 0.001). FPG decreased with empagliflozin (−0.94 mmol/l for 10 mg and −1.22 mmol/l for 25 mg) and increased with placebo (+0.36 mmol/l; both p < 0.001). Adjusted mean ± standard error changes in weight were −1.62 ± 0.21 kg and −1.47 ± 0.21 kg with empagliflozin 10 mg and 25 mg, respectively, vs. +0.34 ± 0.21 kg with placebo (both p < 0.001). Similar proportions of patients reported adverse events with empagliflozin (67.3–71.4%) and placebo (72.7%). Confirmed hypoglycaemia was reported by 1.2–2.4% of patients on empagliflozin and 1.8% on placebo.

Conclusion

Empagliflozin 10 mg and 25 mg once daily for 24 weeks as add‐on to pioglitazone ± metformin reduced HbA1c, FPG and weight and were well tolerated in patients with T2DM.
Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin
Authors: Bolinder J. , Ljunggren Ö. , Johansson L. , Wilding J. , Langkilde A. M. , Sjöström C. D. , Sugg J. , Parikh S.
Published: August 2013

Aims

Dapagliflozin, a highly selective inhibitor of sodium‐glucose cotransporter 2 (SGLT2), reduces hyperglycaemia and weight in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion. Long‐term glycaemic control, body composition and bone safety were evaluated in patients with T2DM after 102 weeks of dapagliflozin treatment.

Methods

This randomized, double‐blind, placebo‐controlled study (NCT00855166) enrolled patients with T2DM [mean: age 60.7 years; HbA1c 7.2%; body mass index (BMI) 31.9 kg/m2; body weight 91.5 kg] inadequately controlled on metformin. Patients (N = 182) were randomly assigned 1 : 1 to receive dapagliflozin 10 mg/day or placebo added to open‐label metformin for a 24‐week double‐blind treatment period followed by a 78‐week site‐ and patient‐blinded extension period. At week 102, changes from baseline in HbA1c, weight, waist circumference, total body fat mass as measured by dual‐energy X‐ray absorptiometry (DXA), serum markers of bone turnover, bone mineral density (BMD) as measured by DXA, and adverse events were evaluated.

Results

A total of 140 patients (76.9%) completed the study. Over 102 weeks, dapagliflozin‐treated patients showed reductions in HbA1c by −0.3%, weight by −4.54 kg, waist circumference by −5.0 cm and fat mass by −2.80 kg without increase in rate of hypoglycaemia. Compared with placebo, no meaningful changes from baseline in markers of bone turnover or BMD were identified over 102 weeks. One fracture occurred in each treatment group. The frequency of urinary tract infection (UTI) and genital infection was similar in both treatment groups.

Conclusions

Over 102 weeks, dapagliflozin improved glycaemic control, and reduced weight and fat mass, without affecting markers of bone turnover or BMD in patients with T2DM inadequately controlled on metformin.
Efficacy and safety of initial combination treatment with sitagliptin and pioglitazone—a factorial study
Authors: Henry R. R. , Staels B. , Fonseca V. A. , Chou M. Z. , Teng R. , Golm G. T. , Langdon R. B. , Kaufman K. D. , Steinberg H. , Goldstein B. J.
Published: August 2013

Aim

To evaluate the efficacy and safety of initial combination therapy of sitagliptin 100 mg/day coadministered with all marketed doses of pioglitazone in patients with type 2 diabetes.

Methods

Patients with A1c ≥7.5 and ≤11.0% were randomized among seven arms that received, once daily, 100 mg sitagliptin alone; 15, 30 or 45 mg pioglitazone alone, or 100 mg sitagliptin plus 15, 30 or 45 mg pioglitazone for 54 weeks. The primary endpoint was change from baseline in A1c at week 24. Protocol‐specified analyses compared combination therapies with monotherapies at respective dose‐strengths and combination of sitagliptin plus pioglitazone 30 mg with pioglitazone 45 mg monotherapy. Post‐hoc analyses compared sitagliptin plus pioglitazone 15 mg with pioglitazone monotherapy at the two higher doses.

Results

Initial combination therapy with sitagliptin and pioglitazone provided significantly greater reductions in A1c (0.4–0.7% differences) and other glycaemic endpoints than either monotherapy at the same doses. Combining sitagliptin with low‐dose pioglitazone generally produced greater glycaemic improvements than higher doses of pioglitazone monotherapy (0.3–0.4% differences in A1c). Combination therapy was generally well tolerated; adverse events (AEs) of hypoglycaemia were reported with similar incidence (7.8–11.1%) in all treatment groups over the 54 weeks of study; oedema was reported in 0.5% of patients in the sitagliptin monotherapy group and 2.7–5.3% among pioglitazone‐treated groups. Significant weight gain was observed in all combination‐treated groups compared with the sitagliptin monotherapy group.

Conclusions

Initial combination therapy with sitagliptin and pioglitazone provided better glycaemic control than either monotherapy and was generally well tolerated.
The Impact of Transparency and Accountability Initiatives
Authors: Gaventa John , McGee Rosemary
Published: August 2013

This issue of Development Policy Review arises from a study of the impact and effectiveness of transparency and accountability initiatives (TAIs) in different development sectors. It analyses existing evidence, discusses how approaches to learning about TAIs might be improved, and recommends how impact and effectiveness could be enhanced.
The Impact and Effectiveness of Transparency and Accountability Initiatives: Freedom of Information
Authors: Calland Richard , Bentley Kristina
Published: August 2013

Analysis of the impact and effectiveness of Freedom of Information (FOI) legislation has been hampered by lack of systematic evidence and conceptual confusion about what kind of right it represents. This article discusses some of the main conceptual parameters of FOI theory, before reviewing the available evidence from a range of studies. It presents case studies of civil‐society activism on FOI in India and South Africa to illustrate the extent to which access to information is having an impact, in particular on socio‐economic conditions. After reviewing the range of approaches used, it concludes that the academic community and the FOI community of practice need to come together to devise robust and rigorous methodologies.
The Impact and Effectiveness of Accountability and Transparency Initiatives: The Governance of Natural Resources
Authors: Mejía Acosta Andrés
Published: August 2013

The rapid growth in the past decade in transparency and accountability initiatives (TAIs) in the extractive industries sector reflects attempts to devise institutional mechanisms to make governments accountable for the extraction, allocation and use of revenues that, if well invested, could alleviate socio‐economic inequalities among citizens. Understanding and measuring the impact and effectiveness of these initiatives is a matter of proposing and empirically validating a causal link between interventions and governance improvements. To do this requires improved data collection, reporting and analysis; a stronger focus on the allocation and use of government expenditures that come from natural‐resource wealth; and a better understanding of importance of incentives and sanctions for ensuring effective impact.
Issues related to development of antiepileptogenic therapies
Authors: Pitkänen Asla , Nehlig Astrid , Brooks‐Kayal Amy R. , Dudek F. Edward , Friedman Daniel , Galanopoulou Aristea S. , Jensen Frances E. , Kaminski Rafal M. , Kapur Jaideep , Klitgaard Henrik , Löscher Wolfgang , Mody Istvan , Schmidt Dieter
Published: August 2013

Several preclinical proof‐of‐concept studies have provided evidence for positive treatment effects on epileptogenesis. However, none of these hypothetical treatments has advanced to the clinic. The experience in other fields of neurology such as stroke, Alzheimer's disease, or amyotrophic lateral sclerosis has indicated several problems in the design of preclinical studies, which likely contribute to failures in translating the positive preclinical data to the clinic. The Working Group on “Issues related to development of antiepileptogenic therapies” of the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES) has considered the possible problems that arise when moving from proof‐of‐concept antiepileptogenesis (AEG) studies to preclinical AEG trials, and eventually to clinical AEG trials. This article summarizes the discussions and provides recommendations on how to design a preclinical AEG monotherapy trial in adult animals. We specifically address study design, animal and model selection, number of studies needed, issues related to administration of the treatment, outcome measures, statistics, and reporting. In addition, we give recommendations for future actions to advance the preclinical AEG testing.
The Role of Experts in the Elaboration of the Cape Town Convention: Between Authority and Legitimacy
Authors: Devaux Caroline
Published: August 2013

Globalisation and the development of fast transport and communications have multiplied transnational situations that States, at times, appear ill equipped to handle. Private actors, taking advantage of these new opportunities to claim their authority, are now key actors in the production of transnational law. Since their place in the production process does not have legal grounds, this paper intends to ‘transnationalise’ the legitimacy discourse by comparing its fundamental criteria to the claim to authority of a particular group of private actors—the aviation experts—during the elaboration of the Cape Town Convention. This article challenges this expertise‐based legitimation process which, despite being grounded on the ability of private actors to develop effective solutions, reveals a limited output and input legitimacy. Finally, the article suggests that the EU is well placed to carry out a legitimacy test to block the reception of undemocratic claims to authority made by influential private actors.
The effects of synthetic estrogen exposure on premating and postmating episodes of selection in sex‐role‐reversed Gulf pipefish
Authors: Rose Emily , Paczolt Kimberly A. , Jones Adam G.
Published: August 2013

Environmental estrogens have been shown to affect populations of aquatic organisms in devastating ways, including feminization of males, alterations in mating behaviors, and disruption of sexual selection. Studies have shown 17α‐ethinylestradiol (EE2) exposure to induce female‐like secondary sexual traits in male Gulf pipefish, changing how females perceive affected males. We aimed to understand the effects of EE2 exposure on the sex‐role‐reversed mating system and the strength of selection in Gulf pipefish. We used artificial Gulf pipefish breeding aggregations and microsatellite‐based parentage analysis to determine maternity. We then calculated the opportunity for selection and selection differentials on body size for both sexes during three consecutive episodes of selection. Exposure to EE2 did not affect the strength of selection, likely due to the unusual sex‐role‐reversed mating system found in this species. With respect to multiply mated females, EE2‐exposed females produced more eggs with higher embryo survivorship than nonexposed females. Thus, short‐term exposure to low concentrations (2.0 ng/L) of EE2 in Gulf pipefish enhanced female reproductive success. However, higher EE2 concentrations (5.0 ng/L) caused complete reproductive failure in Gulf pipefish males. These results call for more work on the long‐term effects of EE2 exposure in Gulf pipefish in artificial and natural populations.
Conserved systems and functional genomic assessment of nociception
Authors: Khuong Thang M. , Neely Graham Greg
Published: August 2013

Chronic pain represents a significant public health concern and current therapies do not adequately meet patient needs. With the advent of genomic technologies, pain researchers have begun to identify key loci associating with human pain diseases, and these data are instructing the development of next generation analgesics. Although human genetics efforts have been effective, complementary approaches, including functional genomics, may provide additional insight into pain genetics and help identify additional new drug targets. In the present review, we discuss the use of fruit fly systems biology combined with mammalian genetics to accelerate the discovery of novel pain genes and candidate drug targets.
Modelling transport of chokka squid (Loligo reynaudii) paralarvae off South Africa: reviewing, testing and extending the ‘Westward Transport Hypothesis’
Authors: Martins Rodrigo S. , Roberts Michael J. , Lett Christophe , Chang Nicolette , Moloney Coleen L. , Camargo Maurício G. , Vidal Erica A. G.
Published: August 2013

Annual landings of chokka squid (Loligo reynaudii), an important fishing resource for South Africa, fluctuate greatly, and are believed to be related to recruitment success. The ‘Westward Transport Hypothesis’ (WTH) attributes recruitment strength to variability in transport of newly hatched paralarvae from spawning grounds to the ‘cold ridge’ nursery region some 100–200 km to the west, where oceanographic conditions sustain high productivity. We used an individual‐based model (IBM) coupled with a 3‐D hydrodynamic model (ROMS) to test the WTH and assessed four factors that might influence successful transport – Release Area, Month, Specific Gravity (body density) and Diel Vertical Migration (DVM) – in numerical experiments that estimated successful transport of squid paralarvae to the cold ridge. A multifactor ANOVA was used to identify the primary determinants of transport success in the various experimental simulations. Among these, release area was found to be the most important, implying that adult spawning behaviour (i.e., birth site fidelity) may be more important than paralarval behaviour in determining paralarval transport variability. However, specific gravity and DVM were found to play a role by retaining paralarvae on the shelf and optimizing early transport, respectively. Upwelling events seem to facilitate transport by moving paralarvae higher in the water column and thus exposing them to faster surface currents.
The More‐than‐human Geographies of Field Science
Authors: Forsyth Isla
Published: August 2013

Geographers have increasingly begun to attend to the local environments of science, considering how these spaces shape and influence knowledge production. This paper will explore the insights a spatial analytic can contribute to the history of science by exploring one scientific performance space; the field site. Already, rich and insightful studies into the geographies of field science have figured these sites as complex, subjective and lively places. However, so far, there appears to have only been peripheral attention paid to the multiple and myriad nonhuman animals that are present in the field. The field is a site where animals have been the object of study, provided transport, companionship, sport and food, but their presence within the history of field science is conspicuously absent. This paper asks how to study the spatialities of animal lives enrolled in the diverse technologies and knowledge that encompass scientific practice, and considers what such an engagement could offer to contemporary scientific study. Therefore, this paper will review animal and hybrid geographies, and methodological tools that attend to the performativity of science, such as the actor–network theory and Pickering's ‘the mangle’. It will consider what these literatures and conceptual frameworks can add to understandings of the historical, social, cultural and political nature of more‐than‐human knowledge through a consideration of field science.
Urban China on Screen: The Sixth Generation and the Postsocialist Cinematic City
Authors: Berra John
Published: August 2013

This article will consider the relationship between the city and the cinema with regard to the films of China's ‘Sixth Generation’, a group of filmmakers who mostly graduated from the Beijing Film Academy in the late 1980s and proceeded to make films on the subject of their nation's urban fabric. These are films which utilise city narrative to comment on social–economic change, but largely observe such conditions, rather than to take apolitical stance. To explore the urban representation of the Sixth Generation, this article will provide analysis of three works that depict life in top‐tier or second‐tier mainland China cities: Biandan, guniang/So Close to Paradise (1999), Suzhou he/Suzhou River (2000) and Xiari nuanyangyang/I Love Beijing (2001). The manner in which urban space is represented will be considered, alongside the social positioning of the characters, in order to address arguments made by scholars that these films focus on the plight of the individual rather than considering the wider implications of urban planning.
Beyond the Screen: Methods for Investigating Geographies of Life ‘Online’
Authors: Kinsley Samuel
Published: August 2013

The internet and being ‘online’ is an integral part of everyday life for a substantial proportion of the population. There is an increasing impetus for researchers to engage with ‘online’ activities, not only as particular activities themselves but also as a part of the context of a wide range of geographies. The purpose of this article is to offer an overview of contemporary methodologies of researching geographies of life online. The article is structured in four sections. Beginning with a discussion of how to address a ‘field’, the article goes on to explore how geographers have addressed spatial understandings of the internet. Subsequently, themes of identity and authenticity are raised as key concerns for studies of life online, and accordingly the article moves on to discuss the ethics of such research. This article demonstrates how geographical thinking can inform and enhance social scientific research concerning the internet, particularly in relation to the articulation of spatial experience and knowledge.
The Distinction Between State and Government
Authors: Robinson Edward Heath
Published: August 2013

The terms “state” and “government” are often used interchangeably in political discourse, but they can also refer to very different entities. In political geography, a distinction between the two is often not made, or made weakly. Thus, this article reviews how these terms have been used in political geography and across allied disciplines, especially in international law. Political geographers commonly seem to draw from the anthropological and sociological uses of the terms, but the distinction between state and government is arguably most developed in international legal scholarship. This article argues that political geography would gain by adopting a distinction between state and government as it is articulated in international legal scholarship. Drawing from that literature, this article recommends that states be contrasted with governments in the following way: states are juridical entities of the international legal system; governments are the exclusive legally coercive organizations for making and enforcing certain group decisions. Arguably, ambiguity regarding the referents of these terms has hindered the development of state theory and even made it unclear what the “theory of the state” is supposed to explain. Therefore, this article concludes with a call for geographers to be just as cognizant of the distinction between state and government as they traditionally have been of the distinction between state and nation.
The Politics of Public Debt: Neoliberalism, Capitalist Development and the Restructuring of the State
Authors: Streeck Wolfgang
Published: August 2013

Rising public debt has been widespread in democratic-capitalist political economies since the 1970s, generally accompanied among other things by weak economic growth, rising unemployment, increasing inequality, growing tax resistance, and declining political participation. Following an initial period of fiscal consolidation in the 1990s, public debt took an unprecedented leap in reponse to the Great Recession. Renewed consolidation efforts, under the pressure of ‘financial markets’, point to a general decline in state expenditure, particularly discretionary and investment expenditure, and of extensive retrenchment and privatization of state functions.
Diffusion and kinetic control of weathering layer development
Authors: Reeves D. , Rothman D. H.
Published: August 2013

The formation of porous weathering rinds (layers of chemical alteration) on the exterior of rocks is a consequence of dissolution and precipitation of minerals occurring at the mineral–fluid interface within the pores. The speed at which the developed rind advances is controlled by both kinetic reaction rates and the transport of reaction products away from the pore spaces into the outside fluid. We show, using both reaction‐diffusion theory and numerics, that under diffusion limitations, the weathering rate depends on the size and curvature of the sample. This leads to a relationship between rind thickness, δ, and age,t. As the rind thickens, the result in three dimensions differs substantially from the one‐dimensional result of. We describe the conditions under which the one‐dimensional and diffusion‐limited approximations apply and how they evolve as the rock weathers. Under chemical kinetic limitations, the rind advances at a constant rate,dδ/dt = v. We defend the application of a spherical approximation to irregular non‐spherical rocks and apply our results to field observations reported in the literature to show consistency with established methods. Finally, we argue that the variability in size, as well as in mineralogy, over ensembles of grains contributes to heterogeneous weathering rates. We demonstrate that this heterogeneity can contribute to the aging, or gradual decrease with time, of weathering rates previously observed in laboratory and field measurements.
Towards generic online multicriteria decision support in patient‐centred health care
Authors: Dowie Jack , Kjer Kaltoft Mette , Salkeld Glenn , Cunich Michelle
Published: August 2013

Objective

To introduce a new online generic decision support system based on multicriteria decision analysis (MCDA), implemented in practical and user‐friendly software (Annalisa©).

Background

All parties in health care lack a simple and generic way to picture and process the decisions to be made in pursuit of improved decision making and more informed choice within an overall philosophy of person‐ and patient‐centred care.

Methods

The MCDA‐based system generates patient‐specific clinical guidance in the form of an opinion as to the merits of the alternative options in a decision, which are all scored and ranked. The scores for each option combine, in a simple expected value calculation, the best estimates available now for the performance of those options on patient‐determined criteria, with the individual patient's preferences, expressed as importance weightings for those criteria. The survey software within which the Annalisa file is embedded (Elicia©) customizes and personalizes the presentation and inputs. Principles relevant to the development of such decision‐specific MCDA‐based aids are noted and comparisons with alternative implementations presented. The necessity to trade‐off practicality (including resource constraints) with normative rigour and empirical complexity, in both their development and delivery, is emphasized.

Conclusion

The MCDA‐/Annalisa‐based decision support system represents a prescriptive addition to the portfolio of decision‐aiding tools available online to individuals and clinicians interested in pursuing shared decision making and informed choice within a commitment to transparency in relation to both the evidence and preference bases of decisions. Some empirical data establishing its usability are provided.
Monoclonal antibody differentiates chicken A system alloantigens*
Authors: FULTON J. E. , BRILES R. W. , LAMONT S. J.
Published: August 2013

Summary A monoclonal antibody (ISU‐cA) was produced that recognized certain alloantigens of the chicken A blood group locus. Antigens produced by alleles A3, A4 and A8 were positive, and those produced by A2 and A5 were negative, by haemagglutination. The specificity of ISU‐cA for chicken A blood group antigens was demonstrated by serologic analyses, genetic crosses and competitive inhibition of binding by anti‐A alloantisera. To our knowledge, this is the first reported monoclonal antibody against a chicken blood group alloantigen system other than the B complex.
Population data and a fourth allele for equine complement component 3 (C3)
Authors: BOWLING A. T. , DILEANIS S.
Published: August 2013

Summary The C3 polymorphism of equine serum or plasma revealed by agarose gel electrophoresis can be diagnosed with protein stain following acid protein fixation. In addition to the three alleles previously described (C31, C32, C33), a fourth allele (C34) was found. Population data for 25 domestic breeds and Equus przewalskii are presented.
Linkage relationships among 20 genetic markers in cattle Evidence for linkage between two pairs of blood group systems: B‐Z and S‐F/V respectively
Authors: GEORGES M. , LATHROP M. , BOUQUET Y. , HILBERT P. , MARCOTTE A. , SCHWERS A. , ROUPAIN J. , VASSART G. , HANSET R.
Published: August 2013

Summary Five bovine paternal half‐sib pedigrees for a total of 527 individuals were typed for six blood group systems: A, B, F/V, L, S, Z; for nine biochemical polymorphisms: ADA, MPI, PGM‐3(slow), NP, Gc, Pi2, Tf, Ptf1 and Ptf2; and for restriction fragment length polymorphisms at five autosomal loci: Tg, GH, LDLr, BoLA‐DQ and BoLA‐DY. Two of the pedigrees were informative for segregation at the ‘muscular hypertrophy’ locus, and one was informative at the coat colour determining ‘roan’ locus. Linkage analysis was performed between all markers. Linkage was demonstrated between the S and F/V blood group systems (z = 3·11), adding one locus to the previously identified linkage group VII (LGVII) [Pi‐2 and S], the most likely order being Pi2‐S‐F/V with maximum likelihood recombination rates of 0·208 and 0·211. Also shown to be linked were the blood group systems B and Z (z = 5·7, θ= 0·245). We confirmed the observation previously made by Andersson et al. (1988) of a high recombination rate between class II genes DQ and DY, suggesting either a larger physical distance between those genes than expected from comparative data, or the presence of a ‘recombinational hotspot’ in the bovine major histocompatibility complex. No linkage was found either with the ‘muscular hypertrophy’ locus, or with the ‘roan’ locus. However, these two loci could be excluded from respectively 1·7 and 2·5 Morgans of the bovine genome.
Restriction fragment length polymorphism analysis of the κ‐casein locus in cattle
Authors: DAMIANI G. , FERRETTI L. , ROGNONI G. , SGARAMELLA V.
Published: August 2013

Summary The two common genetic variants (A and B) of bovine κ‐casein originate from two point mutations in the codons for the aminoacids in position 136 and 148. These mutations give rise to polymorphic sites for the restriction endonucleases Hin dII, AluI, HinfI, MboII and TaqI. We have examined DNAs of several Italian Friesian cows and bulls of known and unknown genotype by Southern analyses using κ‐casein cDNA probes. Restriction fragment length polymorphisms (RFLPs) specific for the A and B alleles were identified for each of the above enzymes, except for AluI, which has a non‐polymorphic site 12bp away from the polymorphic one. We have also found two new polymorphic sites for MboII and TaqI in the non‐coding regions. These sites differentiate the A allele into two new variants, named A1 and A2. The RFLP analysis permits the characterization of κ‐casein alleles even in the absence of their expression. This should facilitate selective breeding programmes aimed at increasing the frequency of the κ‐casein B allele whose product improves the cheesemaking properties of milk.
Two new sheep haemoglobins, one of which is replaced by haemoglobin C in anaemia
Authors: KILGOUR L. , DIXON S. C. , TUCKER E. M.
Published: August 2013

Summary Two new haemoglobin variants, provisionally named Hb G and Hb H, were found during a survey of 295 Welsh Mountain cross‐bred sheep. Both haemoglobins appear to be β chain variants controlled by genes allelic to those for the common forms Hb A and Hb B. Studies on an anaemic Hb AH and an Hb AG type sheep showed that Hb G, like Hb A, is replaced by Hb C in anaemia whereas Hb H, like Hb B, is not replaced.
Genetic polymorphism of complement factor H in cattle
Authors: TABEL H. , GROAT H. J. , KRAAY G. J. , ASTON W. P.
Published: August 2013

Summary Bovine factor H was found to be polymorphic by the combined techniques of SDS‐polyacrylamide electrophoresis of bovine plasma and immunoblotting. Three phenotypes (S, SF, F) were identified in a sample population of 149 cattle. Variant S and F differed by an apparent molecular weight of 5000 daltons. Family studies demonstrated Mendelian segregation of variants S and F. The data indicate that these genetic variants of bovine factor H are encoded by two codominant alleles at a single autosomal locus.
Monoclonal antibodies to the bovine immunoglobulin G2a allotypes A1 and A2
Authors: ESTES D. M. , TEMPLETON J. W. , ADAMS L. G.
Published: August 2013

Summary Production of murine monoclonal antibodies (Mabs) to bovine IgG2a‐A1 and A2 allotypes resulted in three Mabs being selected as anti‐IgG2a‐A1 and A2 reagents. Two Mabs recognize the A1 allotype and 1 recognizes the A2 allotype. Initial epitope mapping with the Mabs indicates that one of the A1 epitopes resides in the hinge region and the other epitope resides more toward the C‐terminus of the immunoglobulin. The A2 epitope recognized by the A2 Mab does not appear to reside in the hinge region of the immunoglobulin but apparently resides more C‐terminal.
Restriction fragment length polymorphism of bovine lysozyme genes
Authors: SIGURDARDÓTTIR S. , LUNDÉN A. , ANDERSSON L.
Published: August 2013

Summary Genetic polymorphism of bovine lysozyme (LYZ) genes was investigated by analysing restriction fragment length polymorphism (RFLP). The analysis revealed three RFLP loci designated LYZ1, LYZ2 and LYZ3. Each system included two or three allelic variants. Evidence for close genetic linkage of the three loci was found. There was also a significant linkage disequilibrium among the three loci in a sample of about 200 breeding bulls from one breed. No statistically significant association was found between LYZ RFLPs and breeding values of bulls for disease or milk production traits.
Polymorphism of pig serum α‐protease inhibitor‐3 (PI3) and assignment of the locus to the Pi1, Po1A, Po1B, Pi2, Igh linkage group
Authors: STRATIL A. , CIZOVÁ D. , HOJNÝ J. , HRADECKÝ J.
Published: August 2013

Summary Polymorphism of an α‐protease inhibitor, PI3, in pig serum samples was detected using 2D agarose gel (pH 5.4) — polyacrylamide gel (pH 9.0) electrophoresis. Evidence was obtained that the five variants observed (A, B1, B2, C and D) are under genetic control by codominant alleles (Pi3A, Pi3B1, Pi3B2, Pi3C and Pi3D) at one autosomal locus. Variants A, B1, B2 and C inhibited chymotrypsin; there was no appreciable inhibition of trypsin and papain. Variant D did not inhibit chymotrypsin, and therefore its classification as a PI3 variant was put in question. PI3 typing was not possible in about 50% of the studied pigs since in those cases the PI3 variants were either too weak or absent. On the basis of backcross matings and haplotyping in complete families for protease inhibitor loci Pi1, Po1A, Pi2 and Pi3 it was proved that the Pi3 locus belongs to the protease inhibitor gene cluster, and the position of the locus in the linkage group was proposed as being Pi1‐Po1A‐(PolB)‐Pi3‐Pi2‐(Igh1, Igh2, Igh3, Igh4).
Salivary gland amylase polymorphism in pigs and cattle detected by affinity electrophoresis
Authors: ROZHKOV YU. I. , GALIMOV I. R.
Published: August 2013

Summary New allelic variants of salivary gland α‐amylase in pigs (AMY‐1C, AMY‐1D) have been detected using affinity electrophoresis. In yak, zebu and in hybrids (yak × cattle, zebu × cattle) a new AMY‐1 allelic variant (AMY‐1D) has been found using the same method.
Variation of some serum proteins in red deer, Cervus elaphus L.
Authors: STRATIL A. , GLASNÁK V. , BOBÁK P. , ČÍŽOVÁ D. , GÁBRIŠOVÁ E. , KALÁB P.
Published: August 2013

Summary Various electrophoretic techniques, immunoblotting and inhibitions of trypsin and chymotrypsin were used to study the variability of serum proteins in farmed red deer, Cervus elaphus L., of Czechoslovakian origin. Easily interpretable polymorphisms were observed in transferrin (variants A, B1, B2, C) and vitamin D binding protein, GC (variants D, F, I, S). Great variability was observed in the protease inhibitors PI2, PI3, PI4, PI5 and PI8 and in unidentified zones in the vicinity of albumin, but no genetical or physiological interpretation for this variability is yet available. Haemopexin, α1 glycoprotein, protease inhibitors PI1, PI6 and PI7 were monomorphic.
A survey of transferrins in 87 teleostean species
Authors: JAMIESON A.
Published: August 2013

Summary An electrophoretic survey of transferrin variants in 87 species of teleostean fishes showed much individual variation. The majority of the species were polymorphic at the transferrin gene locus, Tf. The clustered distribution of allelomorphs indicated some evolutionary continuity within certain taxonomic families, but this continuity was unexpectedly less apparent within genera.
Erythrocyte antigens in Norwegian goats: serological and genetic studies
Authors: NESSE L. L.
Published: August 2013

Summary Goat alloantisera and bovine blood typing reagents were used to characterize eight erythrocyte antigen specificities in Norwegian goats by cluster analysis, absorption and family studies. Most of the goat sera were produced by injecting dams once or twice with blood cells or blood from their own kids. The characterized specificities were designated N1‐N8. The two specificities N5 and N8 were recognized both by goat alloantisera and by reagents against the bovine factors E′1 and E′2 (N5) and I (N8), which are allelic factors in the bovine B‐system. In goat families, the two specificities also behaved as alleles. Consequently, the locus or gene system coding for these specificities was called the B‐system of goats. The six other erythrocyte antigens were provisionally assigned to six separate loci. In addition, a bovine anti‐sheep R factor reagent reacted with cells from 3.3% of the goats tested, whereas a monoclonal antibody against the Forssman antigen reacted with all the goats tested.