bluuebunny/crossref_metadata_2025 huggingface dataset:
A6V polymorphism of the human μ‐opioid receptor decreases signalling of morphine and endogenous opioids in vitro
Authors: Knapman Alisa , Santiago Marina , Connor Mark
Published: December 2014

Background and Purpose

Polymorphisms of the μ opioid receptor (MOPr) may contribute to the variation in responses to opioid drugs in clinical and unregulated situations. The A6V variant of MOPr (MOPr‐A6V) is present in up to 20% of individuals in some populations, and may be associated with heightened susceptibility to drug abuse. There are no functional studies examining the acute signalling of MOPr‐A6V in vitro, so we investigated potential functional differences between MOPr and MOPr‐A6V at several signalling pathways using structurally distinct opioid ligands.

Experimental Approach

CHO and AtT‐20 cells stably expressing MOPr and MOPr‐A6V were used. AC inhibition and ERK1/2 phosphorylation were assayed in CHO cells; K channel activation was assayed in AtT‐20 cells.

Key Results

Buprenorphine did not inhibit AC or stimulate ERK1/2 phosphorylation in CHO cells expressing MOPr‐A6V, but buprenorphine activation of K channels in AtT‐20 cells was preserved. [D‐Ala2, N‐MePhe4, Gly‐ol]‐enkephalin, morphine and β‐endorphin inhibition of AC was significantly reduced via MOPr‐A6V, as was signalling of all opioids to ERK1/2. However, there was little effect of the A6V variant on K channel activation.

Conclusions and Implications

Signalling to AC and ERK via the mutant MOPr‐A6V was decreased for many opioids, including the clinically significant drugs morphine, buprenorphine and fentanyl, as well endogenous opioids. The MOPr‐A6V variant is common and this compromised signalling may affect individual responses to opioid therapy, while the possible disruption of the endogenous opioid system may contribute to susceptibility to substance abuse.
Zoogeography of theSanAndreasFault system:GreatPacificFractureZones correspond with spatially concordant phylogeographic boundaries in westernNorthAmerica
Authors: Gottscho Andrew D.
Published: December 2014

The purpose of this article is to provide an ultimate tectonic explanation for several well‐studied zoogeographic boundaries along the west coast ofNorthAmerica, specifically, along the boundary of theNorthAmerican andPacific plates (theSanAndreasFault system). By reviewing 177 references from the plate tectonics and zoogeography literature,Idemonstrate that fourGreatPacificFractureZones (GPFZs) in thePacific plate correspond with distributional limits and spatially concordant phylogeographic breaks for a wide variety of marine and terrestrial animals, including invertebrates, fish, amphibians, reptiles, birds, and mammals. These boundaries are: (1)CapeMendocino and theNorthCoastDivide, (2)PointConception and theTransverseRanges, (3)PuntaEugenia and theVizcaínoDesert, and (4)CaboCorrientes and theSierraTransvolcanica. However, discussion of theGPFZsis mostly absent from the zoogeography and phylogeography literature likely due to a disconnect between biologists and geologists. I argue that the four zoogeographic boundaries reviewed here ultimately originatedviathe same geological process (triple junction evolution). Finally, I suggest how a comparative phylogeographic approach can be used to test the hypothesis presented here.
Temperature impacts on deep‐sea biodiversity
Authors: Yasuhara Moriaki , Danovaro Roberto
Published: December 2014

Temperature is considered to be a fundamental factor controlling biodiversity in marine ecosystems, but precisely what role temperature plays in modulating diversity is still not clear. The deep ocean, lacking light and in situ photosynthetic primary production, is an ideal model system to test the effects of temperature changes on biodiversity. Here we synthesize current knowledge on temperature–diversity relationships in the deep sea. Our results from both present and past deep‐sea assemblages suggest that, when a wide range of deep‐sea bottom‐water temperatures is considered, a unimodal relationship exists between temperature and diversity (that may be right skewed). It is possible that temperature is important only when at relatively high and low levels but does not play a major role in the intermediate temperature range. Possible mechanisms explaining the temperature–biodiversity relationship include the physiological‐tolerance hypothesis, the metabolic hypothesis, island biogeography theory, or some combination of these. The possible unimodal relationship discussed here may allow us to identify tipping points at which on‐going global change and deep‐water warming may increase or decrease deep‐sea biodiversity. Predicted changes in deep‐sea temperatures due to human‐induced climate change may have more adverse consequences than expected considering the sensitivity of deep‐sea ecosystems to temperature changes.
Does a Creative Designer Necessarily Translate into the Creative Design of a Product? Exploring Factors Facilitating the Creativity of a New Product
Authors: Kwon Jaehwan , Lee Moonkyu , Kim Hae‐Ryong
Published: December 2014

Product creativity is a rarely studied topic in the area of new product development; nevertheless, its importance has been recognized by many researchers in a variety of fields. In this research, two studies were conducted: the first was quantitative and the second was qualitative. These studies examined the relationships among five variables: analogical thinking ability, creative self‐efficacy, length of experience, team climate for creativity and product creativity. The results of a multiple regression indicated that analogical thinking ability is an antecedent of design creativity, and that creative self‐efficacy is a mediator between them. The results also showed that length of experience and team climate for creativity have significant moderating effects. These findings indicate that both person‐based (i.e., ability, self‐efficacy and length of experience) and situation‐based (team climate) variables are key factors in developing the creative design of a new product.
Use of Social Media in Inbound Open Innovation: Building Capabilities for Absorptive Capacity
Authors: Ooms Ward , Bell John , Kok Robert A.W.
Published: December 2014

This study investigates the effects of the use of social media in inbound open innovation on capabilities for absorptive capacity of companies. Seven explorative case studies were conducted in anR&Dand business context of two large global high‐tech companies. The results suggest that if the necessary conditions are met, social media usage increases the transparent, moderational and multi‐directional interactions that in turn influence four capabilities for absorptive capacity: connectedness, socialization tactics, cross‐functionality and receptivity, a hitherto overlooked capability. Hence, we observe that social media are boundary‐spanning tools that can be used to build and increase companies' absorptive capacity.
Laparoscopic repair of postoperative perineal hernia using a two‐mesh technique
Authors: Allen S. K. , Schwab K. , Day A. , Singh‐Ranger D. , Rockall T. A.
Published: December 2014

Aim

Perineal herniation following abdomino‐perineal excision of the rectum (APER) can be debilitating. Repair options include a transabdominal (laparoscopic or open), perineal or a combined approach, but there is no consensus on the optimal technique. We describe a novel laparoscopic two‐mesh technique and short‐ to medium‐term outcomes.

Method

Six patients underwent this operation between 2008 and 2014. Patients were positioned in a modified Lloyd−Davies position, allowing perineal access, and steep Trendelenburg to aid displacement of small bowel from the pelvis. A polypropylene mesh was shaped, placed over the hernial defect, tacked postero‐laterally and sutured antero‐laterally to reconstitute the pelvic diaphragm. A second larger mesh (composite) was placed over the first supporting mesh and secured with tacks and sutures, overlapping the hernial defect, preventing small bowel contact with the mesh.

Results

The median time from the index operation to presentation of the hernia was 5 months. One patient with dense small bowel adhesions from the primary repair had a combined laparoscopic and perineal approach. The median operating time was 141 min and median length of stay was 3 days. There were no intra‐operative complications and no recurrences over a follow‐up of 1–76 months.

Conclusion

We describe a novel laparoscopic technique for perineal hernia repair following APER with a low recurrence rate in the intermediate term.
Avifauna and urban encroachment in time and space
Authors: Rayner Laura , Ikin Karen , Evans Maldwyn J. , Gibbons Philip , Lindenmayer David B. , Manning Adrian D.
Published: December 2014

Aim

Urban expansion significantly alters fringe environments often with undesirable impacts on biodiversity. Consequently, there is a need to define clear conservation objectives for areas subject to urban encroachment. Urban fringe development is a highly dynamic process, both spatially and temporally, but few studies are equipped to examine its temporal effects on biota. We aimed to explore the impacts of urban encroachment on avifauna through space and time.

Location

The Australian Capital Territory, Australia.

Methods

We used records from an extensive 14‐year monitoring programme undertaken in temperate woodland. We fitted hierarchical generalized linear models to assess individual species responses to the distance from monitoring sites to the urban boundary, and the temporal rate of change in this distance through time. We used factorial analysis on mixed data to examine trait group responses to these predictors.

Results

Our results indicated that the occurrence of approximately half of the study region's avifauna is strongly linked to the proximity of their habitat to the urban fringe, but that the impact of urban fringe development on the occurrence of some species changed through time. We identified several species of conservation concern that respond negatively to large annual increases in urban fringe development, irrespective of its proximity to suitable habitat. Species responses to urban proximity were linked to life history traits, with small, migratory, woodland‐dependent species that rely on mid‐ and upper‐canopy structures, clearly disadvantaged by urban environments.

Main conclusions

Our findings demonstrate the breadth of species responses to urban encroachment over much larger distances than is typically investigated in urban ecological studies. We identify guilds vulnerable to the impacts of urban fringe development and therefore in need of ecologically sensitive urban design. We argue that future urban expansion towards important fringe habitats will need to be planned strategically through space and time.
Exercise‐Induced Abnormal Increase of Systolic Pulmonary Artery Pressure in Adult Patients With Sickle Cell Anemia: An Exercise Stress Echocardiography Study
Authors: de Lima‐Filho Newton Nunes , Figueiredo Maria Stella , Vicari Perla , Cançado Rodolfo , Carvalho Antonio Carlos de Camargo , Bordin José Orlando , Campos Orlando
Published: December 2014

Background

Pulmonary hypertension (PH) at rest is a risk factor for death in patients with sickle cell anemia (SCA). Exercise echocardiography (EE) can detect latent PH. We sought to investigate the occurrence of exercise‐induced abnormal response of systolic pulmonary artery pressure (SPAP) in adult patients with SCA and normal SPAP at rest, and to identify the independent predictors of this abnormal response.

Methods and Results

Forty‐four adult patients with SCA and normal SPAP at rest (tricuspid regurgitant jet flow velocity [TRV] <2.5 m/sec) were studied and divided into 2 groups: exhibiting normal SPAP after treadmill EE (TRV ≤ 2.7 m/sec) (G1), and exhibiting abnormal exercise‐induced increase of SPAP (TRV > 2.7 m/sec) (G2). TRV cutoff points at rest and during EE were based on data from healthy‐matched control subjects. Abnormal response of SPAP with exercise occurred in 57% of the sample (G2), with mean TRV level of 3.39 ± 0.41 m/sec (range 2.8–4.5 m/sec), significantly higher than those of G1 (2.29 ± 0.25 m/sec, range 2.0–2.7 m/sec; P < 0.001). Multivariate analysis identified TRV value in resting conditions ≥2.25 m/sec (P < 0.05), left atrial volume index ≥41 mL/m2 (P < 0.05), and a E/e′‐waves ratio ≥6.3 (P < 0.05) as independent predictors of exercise‐induced increase of SPAP.

Conclusion

We concluded that adult patients with SCA and normal SPAP at rest may exhibit abnormal exercise‐induced increase in SPAP, which was independently related to resting TRV levels, and indices of diastolic impairment and left ventricular filling pressure.
STRUCTURAL ESTIMATION OF SEQUENTIAL GAMES OF COMPLETE INFORMATION
Authors: Blevins Jason R.
Published: December 2014

In models of strategic interaction, there may be important order of entry effects if one player can credibly commit to an action (e.g., entry) before other players. If one estimates a simultaneous‐move model, then the move‐order effects will be confounded with the payoffs. This article considers nonparametric identification and simulation‐based estimation of sequential games of complete information. Relative to simultaneous‐move games, these models avoid the problem of multiple equilibria and require fewer payoff normalizations. We apply the estimator in several Monte Carlo experiments and to study entry‐order effects using data from the airline industry. (JEL C57, C15, L93)
Consumption conundrums unravelled
Authors: Horrell Sara , Humphries Jane , Sneath Ken
Published: December 2014

While consumption has moved to centre stage in accounts ofBritain's industrialization, evidence on the mass transformation of homes and expenditure on novelty is hard to reconcile with the poor living standards experienced by many working people. Part of the conundrum arises from the limitations of available probate evidence, but the motivational drivers behind raised consumption can also be questioned. Was it changed tastes or falling prices because of improved technology which prompted the purchase of new goods? Utilizing evidence from an alternative source, property stolen through housebreaking and burglary as reported in the Old Bailey Papers and Proceedings for 1750–1821, we identify those goods that were commonly stolen as the fashion icons of their day, trace such goods back to their original owners, thus linking ownership and status, and through analysis over time show how consumption evolved. This analysis incorporates the influence of price and real incomes on ownership, allowing the influence of price and fashion on consumption patterns to be identified separately. The findings show that, in addition to price and income effects, fashion had a strong influence, but this was not just emulation; differentiation too was evident. The evidence points to a complex interplay between desires and differentiation, aspiration and affordability, in determining the goods that people possessed.
Placebo‐induced decrease in fatigue: evidence for a central action on the preparatory phase of movement
Authors: Piedimonte Alessandro , Benedetti Fabrizio , Carlino Elisa
Published: December 2014

Placebos have been found to affect a number of pathological processes and physiological functions through expectations of clinical improvement. Recently, the study of the placebo effect has moved from the clinical to the physical performance setting, wherein placebos can boost performance by increasing muscle work and by decreasing perceived exertion. However, nothing is known about the neurobiological underpinnings of this phenomenon. Here we show for the first time that a placebo, which subjects believed to be endurance‐increasing caffeine, reduces fatigue by acting at the central level on the preparatory phase of movement. In fact, we recorded the readiness potential, which is the expression of the preparatory phase of movement at the level of the supplementary motor area, during repeated flexions of the index finger in a control group that did not receive any treatment and in a placebo group that received placebo caffeine. In the control group, as the number of flexions increased, both fatigue and readiness potential amplitude increased. By contrast, in the placebo group, as the number of flexions increased we found a decrease in perceived exertion along with no increase in readiness potential amplitude. This placebo‐induced modulation of the readiness potential suggests that placebos reduce fatigue by acting centrally during the anticipatory phase of movement, thus emphasizing the important role of the central nervous system in the generation of fatigue.
A novel KCNQ3 mutation in familial epilepsy with focal seizures and intellectual disability
Authors: Miceli Francesco , Striano Pasquale , Soldovieri Maria Virginia , Fontana Antonina , Nardello Rosaria , Robbiano Angela , Bellini Giulia , Elia Maurizio , Zara Federico , Taglialatela Maurizio , Mangano Salvatore
Published: December 2014

Mutations in the KCNQ2 gene encoding for voltage‐gated potassium channel subunits have been found in patients affected with early onset epilepsies with wide phenotypic heterogeneity, ranging from benign familial neonatal seizures (BFNS) to epileptic encephalopathy with cognitive impairment, drug resistance, and characteristic electroencephalography (EEG) and neuroradiologic features. By contrast, only few KCNQ3 mutations have been rarely described, mostly in patients with typical BFNS. We report clinical, genetic, and functional data from a family in which early onset epilepsy and neurocognitive deficits segregated with a novel mutation in KCNQ3 (c.989G>T; p.R330L). Electrophysiological studies in mammalian cells revealed that incorporation of KCNQ3 R330L mutant subunits impaired channel function, suggesting a pathogenetic role for such mutation. The degree of functional impairment of channels incorporating KCNQ3 R330L subunits was larger than that of channels carrying another KCNQ3 mutation affecting the same codon but leading to a different amino acid substitution (p.R330C), previously identified in two families with typical BFNS. These data suggest that mutations in KCNQ3, similarly to KCNQ2, can be found in patients with more severe phenotypes including intellectual disability, and that the degree of the functional impairment caused by mutations at position 330 in KCNQ3 may contribute to clinical disease severity.
Genetic background of mice strongly influences treatment resistance in the 6 Hz seizure model
Authors: Leclercq Karine , Kaminski Rafal M.
Published: December 2014

Objective

The 6 Hz model of focal seizures has been increasingly used to identify anticonvulsant compounds with potential activity against therapy‐resistant epilepsy, but the protective response to anticonvulsants in this model could be dependent on experimental conditions and selection of mouse strains.

Methods

Seizure thresholds in the 6 Hz model were compared in CF‐1, NMRI, and C57Bl/6J male mice with two different electrical stimulators (Ugo Basile 5780 and Grass S48). Dose–response curves for phenytoin and levetiracetam were generated in the three strains at 32 and 44 mA current intensities using both devices. Plasma and brain exposure to the two drugs were measured in all three strains.

Results

CF‐1 mice had the lowest seizure threshold and responded to phenytoin at 32 mA stimulation intensity, but not at 44 mA. NMRI and C57Bl/6J mice had nearly identical threshold values, but NMRI mice responded well to phenytoin at 32 mA and showed limited responsiveness to this drug at 44 mA, whereas C57Bl/6J mice were nearly completely resistant to phenytoin. Furthermore, levetiracetam showed limited efficacy and low potency in CF‐1 and C57Bl/6J mice, particularly at 44 mA, whereas in NMRI mice the drug showed much higher potency in all experimental conditions. No obvious difference in the pharmacokinetics of both phenytoin and levetiracetam was detected between the mouse strains that would have explained these unexpected variations in potency. We have also found that the protective effects of both drugs may be influenced by the device type.

Significance

Collectively these observations clearly indicate that treatment resistance of 6 Hz seizures should be interpreted with strain and experimental conditions in mind. Furthermore, it is important to note that strain differences, much like human genetic differences, may explain why some mice and patients respond to a given treatment and others do not.
Relating adaptive genetic traits to climate for Sandberg bluegrass from the intermountain western United States
Authors: Johnson Richard C. , Horning Matthew E. , Espeland Erin K. , Vance‐Borland Ken
Published: December 2014

Genetic variation for potentially adaptive traits of the key restoration species Sandberg bluegrass (Poa secunda J. Presl) was assessed over the intermountain western United States in relation to source population climate. Common gardens were established at two intermountain west sites with progeny from two maternal parents from each of 130 wild populations. Data were collected over 2 years at each site on fifteen plant traits associated with production, phenology, and morphology. Analyses of variance revealed strong population differences for all plant traits (P < 0.0001), indicating genetic variation. Both the canonical correlation and linear correlation established associations between source populations and climate variability. Populations from warmer, more arid climates had generally lower dry weight, earlier phenology, and smaller, narrower leaves than those from cooler, moister climates. The first three canonical variates were regressed with climate variables resulting in significant models (P < 0.0001) used to map 12 seed zones. Of the 700 981 km2 mapped, four seed zones represented 92% of the area in typically semi‐arid and arid regions. The association of genetic variation with source climates in the intermountain west suggested climate driven natural selection and evolution. We recommend seed transfer zones and population movement guidelines to enhance adaptation and diversity for large‐scale restoration projects.
Equine fractures: The importance of the soft tissues
Authors: Lescun T. B.
Published: December 2014

The case report byElce andGoodrich in the current issue highlights 3 aspects of fracture management related to the soft tissues. The soft tissues are not always easily and completely assessed at initial fracture evaluation, and can be a source of ongoing pain, dysfunction and treatment failure even following successful fracture healing, and will be a vital component of the structural stability of some fracture repairs. This commentary explores these 3 aspects of fracture management in the horse.
Micronotches for studying growth of small cracks
Authors: Wessel W. , Mildner J. , Pitz P. , Brueckner‐Foit A. , Wollenhaupt M. , Baumert T.
Published: December 2014

Well‐defined starter cracks at preselected sites in the microstructures are needed for systematic investigation of the characteristic features of microstructure controlled growth of small cracks. A kinked ellipsoidal micronotch with very high notch factor at the trailing kink is proposed, which triggers controlled crack initiation along the notch contour. These micronotches can be machined by femtosecond laser ablation with virtually no heat‐affected zone at the edges. Crack growth results obtained for an intermetallic γ‐TiAl alloy are presented as an illustrative example.
Reconstruction of limnology and microbialite formation conditions from carbonate clumped isotope thermometry
Authors: Petryshyn V. A. , Lim D. , Laval B. L. , Brady A. , Slater G. , Tripati A. K.
Published: December 2014

Quantitative tools for deciphering the environment of microbialite formation are relatively limited. For example, the oxygen isotope carbonate‐water geothermometer requires assumptions about the isotopic composition of the water of formation. We explored the utility of using ‘clumped’ isotope thermometry as a tool to study the temperatures of microbialite formation. We studied microbialites recovered from water depths of 10–55 m in Pavilion Lake, and 10–25 m in Kelly Lake, spanning the thermocline in both lakes. We determined the temperature of carbonate growth and the 18O/16O ratio of the waters that microbialites grew in. Results were then compared to current limnological data from the lakes to reconstruct the history of microbialite formation. Modern microbialites collected at shallow depths (11.7 m) in both lakes yield clumped isotope‐based temperatures of formation that are within error of summer water temperatures, suggesting that clumped isotope analyses may be used to reconstruct past climates and to probe the environments in which microbialites formed. The deepest microbialites (21.7–55 m) were recovered from below the present‐day thermoclines in both lakes and yield radioisotope ages indicating they primarily formed earlier in the Holocene. During this time, pollen data and our reconstructed water 18O/16O ratios indicate a period of aridity, with lower lake levels. At present, there is a close association between both photosynthetic and heterotrophic communities, and carbonate precipitation/microbialite formation, with biosignatures of photosynthetic influences on carbonate detected in microbialites from the photic zone and above the thermocline (i.e., depths of generally <20 m). Given the deeper microbialites are receiving <1% of photosynthetically active radiation (PAR), it is likely these microbialites primarily formed when lower lake levels resulted in microbialites being located higher in the photic zone, in warm surface waters.
Monitoring bypassing agent therapy – a prospective crossover study comparing thromboelastometry and thrombin generation assay
Authors: Tran H. T. T. , Sørensen B. , Bjørnsen S. , Pripp A. H. , Tjønnfjord G. E. , Andre Holme P.
Published: December 2014

The aim of this study was to evaluate the capability of thromboelastometry (ROTEM) and thrombin generation assay (TGA) to monitor the treatment response of bypassing agent (BPA) therapy and to study whether one method is superior to another. In a prospective crossover study haemophilia A patients with high titre inhibitors were included to receive a dose of 75 U kg−1 activated prothrombin complex concentrates (aPCC) intravenously. Blood sampling was performed at baseline, 15, 30 min, 1, 2, 3 and 4 h post‐infusion for TGA and ROTEM analysis. After a washout period of 14 days the subjects received recombinant FVIIa (rFVIIa) at a dose of 90 μg kg−1 and similar blood sampling was performed. Healthy subjects were used as controls. Six haemophilia A patients with inhibitors were included. We found that TGA parameters endogenous thrombin potential (ETP) and peak thrombin increased 2–3 folds from baseline 15–30 min after infusion. ROTEM parameters MaxVel and maximum clot firmness increased to a level comparable to that of healthy controls. An individual difference in response was observed for different parameters among participants. ETP and peak thrombin were almost two‐fold greater following aPCC infusion compared to rFVIIa, whereas ROTEM parameters showed no difference in response between the two products. The study showed that ROTEM and TGA have a great potential to evaluate the effect of BPA in haemophilia patients with inhibitors. TGA seemed to be more sensitive than ROTEM in reflecting the difference in treatment response between aPCC and rFVIIa. Additional prospective clinical studies are needed to clarify which assay and what parameters are clinically predictive.
Ten‐year experience of recombinant activated factor VII use in surgical patients with congenital haemophilia with inhibitors or acquired haemophilia in Japan
Authors: Takedani H. , Shima M. , Horikoshi Y. , Koyama T. , Fukutake K. , Kuwahara M. , Ishiguro N.
Published: December 2014

Patients with congenital haemophilia with inhibitors or acquired haemophilia are at risk of bleeding complications during surgery. In these patients, replacement therapy for the missing coagulation factor is ineffective, and a bypassing agent such as recombinant activated factor VII (rFVIIa) is required to manage bleeding. To evaluate the safety and haemostatic efficacy of rFVIIa treatment in Japanese patients with congenital haemophilia with inhibitors to FVIII/FIX or acquired haemophilia undergoing surgery. Postmarketing surveillance data from May 2000 to March 2010 were analysed to assess the haemostatic efficacy of 38 procedures in 22 patients with congenital haemophilia A, 13 procedures in seven patients with congenital haemophilia B, and five procedures in five patients with acquired haemophilia. Postoperative bleeding control was judged to be effective (bleeding was stopped completely or reduced considerably) for 34/38 procedures (89%) in patients with congenital haemophilia A, 10/13 procedures (77%) in patients with congenital haemophilia B, and 4/5 procedures (80%) in patients with acquired haemophilia. Tranexamic acid was used concomitantly for 36/56 procedures (64%). Safety was analysed for 66 procedures in 37 patients. Adverse effects potentially related to rFVIIa treatment included mild superficial thrombophlebitis, mild decrease in platelet count, and mild elevation of the serum alanine transaminase level in one patient each. All adverse effects resolved without treatment. Administration of rFVIIa provided adequate haemostasis without serious adverse effects in the majority of cases. The efficacy and safety data in Japanese patients were similar to previously published data from other countries.
Treatment of hepatic amyloid light‐chain amyloidosis with bortezomib and dexamethasone in a liver transplant patient
Authors: Nakano Ryosuke , Ohira Masahiro , Ide Kentaro , Ishiyama Kohei , Kobayashi Tsuyoshi , Tahara Hiroyuki , Tashiro Hirotaka , Kuroda Yoshiaki , Ichinohe Tatsuo , Arihiro Koji , Chayama Kazuaki , Ohdan Hideki
Published: December 2014

Hepatic amyloid light‐chain (AL) amyloidosis is characterized by abnormal deposition of amyloid fibrils in the liver. As this precursor protein is produced by a proliferative plasma cell clone in the bone marrow, liver transplantation (LT) does not affect the disease's progression. Here, we describe the successful treatment using bortezomib‐ and dexamethasone‐based chemotherapy, following LT, of hepatic AL amyloidosis in a 65‐year‐old woman with progressive liver failure. The patient presented with progressive hepatic dysfunction accompanied by hepatorenal syndrome requiring hemodialysis, and living donor LT was successfully performed. Histology revealed amyloid deposits in the liver and stomach, and serum immunofixation revealed AL amyloidosis (κ‐type). The patient began chemotherapy on day 45 after the LT, and remission was achieved after one course. She was subsequently discharged 83 days after the LT, with normal liver and renal function, and no clinical evidence of recurrent disease was observed at the latest follow up (22 months post‐LT).
Escherichia coli‐induced immune paralysis is not exacerbated during chronic filarial infection
Authors: Buerfent Benedikt C. , Gondorf Fabian , Wohlleber Dirk , Schumak Beatrix , Hoerauf Achim , Hübner Marc P.
Published: December 2014

Sepsis initially starts with a systemic inflammatory response (SIRS phase) and is followed by a compensatory anti‐inflammatory response syndrome (CARS) that causes impaired adaptive T‐cell immunity, immune paralysis and an increased susceptibility to secondary infections. In contrast, parasitic filariae release thousands of microfilariae into the peripheral blood without triggering inflammation, as they induce regulatory, anti‐inflammatory host responses. Hence, we investigated the impact of chronic filarial infection on adaptive T‐cell responses during the SIRS and CARS phases of a systemic bacterial infection and analysed the development of T‐cell paralysis following a subsequent adenovirus challenge in BALB/c mice. Chronic filarial infection impaired adenovirus‐specific CD8+ T‐cell cytotoxicity and interferon‐γ responses in the absence of a bacterial challenge and led to higher numbers of splenic CTLA‐4+ CD4+ T cells, whereas splenic T‐cell expression of CD69 and CD62 ligand, serum cytokine levels and regulatory T‐cell frequencies were comparable to naive controls. Irrespective of filarial infection, the SIRS phase dominated 6–24 hr after intravenous Escherichia coli challenge with increased T‐cell activation and pro‐inflammatory cytokine production, whereas the CARS phase occurred 6 days post E. coli challenge and correlated with high levels of transforming growth factor‐β and increased CD62 ligand T‐cell expression. Escherichia coli‐induced impairment of adenovirus‐specific CD8+ T‐cell cytotoxicity and interferon‐γ production was not additionally impaired by chronic filarial infection. This suggests that filarial immunoregulation does not exacerbate E. coli‐induced T‐cell paralysis.
Working with people who have killed: The experience and attitudes of forensic mental health clinicians working with forensic patients
Authors: Harris Derith M. , Happell Brenda , Manias Elizabeth
Published: December 2014

Forensic mental health (FMH) clinicians sometimes feel unsupported and unprepared for their work. This article explores their experiences of working in a FMH setting in Australia. The research examined the clinical context of clinicians working with forensic patients (FP), particularly those individuals who have killed while experiencing a mental illness. A qualitative, exploratory design was selected. Data were collected through focus groups and individual interviews with hospital and community‐based forensic clinicians from all professional groups: psychiatric medicine, social work, psychology, mental health nursing, occupational therapy, and psychiatric service officers. The main themes identified were orientation and adjustment to FMH, training in FMH, vicarious traumatization, clinical debriefing and clinical supervision, and therapeutic relationships. Participants described being frustrated and unsupported in making the transition to working with FP and felt conflicted by the emotional response that was generated when developing therapeutic relationships. Recommendations include the development of programmes that might assist clinicians and address gaps in service delivery, such as clinical governance, targeted orientation programmes, and clinical supervision.
Conservation ofKomodo dragonsVaranus komodoensisin theWaeWuul nature reserve,Flores,Indonesia: a multidisciplinary approach
Authors: Ariefiandy A. , Purwandana D. , Natali C. , Imansyah M. J. , Surahman M. , Jessop T. S. , Ciofi C.
Published: December 2014

Multidisciplinary conservation initiatives are increasingly advocated as best practice for recovering endangered species. TheKomodo dragonVaranus komodoensisis the world's largest lizard, of prominent conservation value as an umbrella species for protection of south‐east Indonesian ecosystems.Komodo dragons have faced multiple human‐related threat processes in the past 30 years and are listed on AppendixIof the Convention on International Trade in Endangered Species of Wild Fauna and Flora, and considered Vulnerable according to the International Union for Conservation of Nature Red List. We report on a protection programme conducted from 2005 to 2012 in the Wae Wuul nature reserve, on the island of Flores,Indonesia. The Wae Wuul ranger post was completely rebuilt, and community awareness and involvement of local people in habitat‐protection schemes were regularly and successfully implemented. Local rangers were trained in wildlife‐monitoring techniques. Monitoring results indicated thatKomodo dragon densities were lower in Wae Wuul than in the adjacentKomodo National Park; however, a relatively high level of genetic diversity was recorded for this population. Ungulate prey showed a relatively stable prey population density. Community‐based initiatives and regular wildlife monitoring are crucial to ensure the persistence ofKomodo dragons on Flores. The Wae Wuul protection programme is providing several sustainability indicators by which informed management plans can be designed for long‐term conservation ofKomodo dragons.
Comparison of Salt and Drought‐Stress Effects on Maize Growth and Yield Formation with Regard to Acid Invertase Activity in the Kernels
Authors: Hütsch B. W. , Jung S. , Schubert S.
Published: December 2014

The long‐term effects of salt stress (11 dS m−1) and drought stress (35 % WHC) were investigated for two maize genotypes, focusing on the relation between metabolic changes around the time of pollination and the impact on yield determinants at maturity. The relatively salt‐resistant hybrid Pioneer 3906 and the relatively drought‐resistant hybrid Fabregas were compared. The experiments were conducted in large plastic containers in a vegetation hall in two consecutive years (2011 and 2012). Plant height and leaf area were significantly reduced under both stress conditions. The transpiration rate was only slightly reduced under drought stress; but under salt stress, a significant reduction occurred 40–53 days after sowing. As a significant increase in sucrose concentrations was observed in the salt‐treated maize kernels 2 days after pollination, the availability of assimilates was not limiting and the plants could afford to save water by reduced stomatal opening. Although under both stress conditions the soluble acid invertase activity was reduced 2 days after pollination, concomitantly, an increase in hexose concentrations was observed. Thus, in these experiments, the delivery of hexoses by acid invertase activity did not limit kernel development. Differences in grain yield at maturity between salt and drought stress were most likely caused by salt‐specific effects (Na+ toxicity), Fabregas being more affected than Pioneer 3906.
Molecular evolution of candidate genes involved in post‐mating‐prezygotic reproductive isolation
Authors: Bono J. M. , Matzkin L. M. , Hoang K. , Brandsmeier L.
Published: December 2014

Traits involved in post‐copulatory interactions between the sexes may evolve rapidly as a result of sexual selection and/or sexual conflict, leading to post‐mating‐prezygotic (PMPZ) reproductive isolating barriers between diverging lineages. Although the importance of PMPZ isolation is recognized, the molecular basis of such incompatibilities is not well understood. Here, we investigate molecular evolution of a subset of Drosophila mojavensis and Drosophila arizonae reproductive tract genes. These include genes that are transcriptionally regulated by conspecific mating in females, many of which are misregulated in heterospecific crosses, and a set of male genes whose transcripts are transferred to females during mating. As a group, misregulated female genes are not more divergent and do not appear to evolve under different selection pressures than other female reproductive genes. Male transferred genes evolve at a higher rate than testis‐expressed genes, and at a similar rate compared to accessory gland protein genes, which are known to evolve rapidly. Four of the individual male transferred genes show patterns of divergent positive selection between D. mojavensis and D. arizonae. Three of the four genes belong to the sperm‐coating protein‐like family, including an ortholog of antares, which influences female fertility and receptivity in Drosophila melanogaster. Synthesis of these molecular evolutionary analyses with transcriptomics and predicted functional information makes these genes candidates for involvement in PMPZ reproductive incompatibilities between D. mojavensis and D. arizonae.
Mothers' expressed emotion towards children with autism spectrum disorder and their siblings
Authors: Griffith G. M. , Hastings R. P. , Petalas M. A. , Lloyd T. J.
Published: December 2014

Background

Expressed emotion (EE) is a construct used to measure the emotional climate within families. EE is of interest to researchers in the field of autism spectrum disorder (ASD) because of its putative implications for child development. The aim was to explore whether maternal EE differs towards a child with ASD and a non‐disabled sibling.

Methods

We adopted a within‐family design with 143 mothers of children with ASD and a non‐disabled sibling. EE was measured using the Five‐Minute Speech Sample.

Results

Wilcoxon signed‐rank tests were utilised. Mothers were coded as significantly more critical and less warm towards their child with ASD than towards the sibling. There were no significant differences in maternal emotional overinvolvement or overall EE towards the child with ASD and a sibling.

Conclusions

The data support the results of previous research suggesting that EE is linked to the relationship a mother has with individual children, rather than being evidence of the character disposition of mothers. More research is needed to understand the emotional dimensions of parent–child relationships in families with children with ASD.
Should arm span or height be used in calculating the BMI for the older people? Preliminary results
Authors: Villaverde‐Gutiérrez Carmen , Sánchez‐López Maria Jacaranda , Ramirez‐Rodrigo Jesús , Ocaña‐Peinado Francisco Manuel
Published: December 2014

Aims and objectives

To consider using arm span rather than height for calculating the body mass index, as a parameter that offers greater long‐term stability, for the nutritional assessment of persons aged over 65 years.

Background

The body mass index presents certain drawbacks for the nutritional screening of older people suffering malnutrition or at risk of malnutrition, due to the anthropometric changes that occur with increasing age, especially the progressive loss of height.

Design

Observational, cross‐sectional study, using nonprobabilistic convenience sampling, with anthropometric measurements and nutritional screening in older men and women, divided into two groups: (1) aged 65–75 years and (2) aged over 75 years.

Methodology

Height and arm span were measured to calculate two separate indices of body mass: body mass index (weight/height) and body mass index.1 (weight/arm span). Nutritional screening was conducted using the Mini Nutritional Assessment Short‐Form, which includes the body mass index as an anthropometric measure.

Results

Our results reveal statistically significant differences between the two indices, for the sample analysed. Body mass index.1 classifies a larger number of older people as suffering malnutrition and fewer as being at nutritional risk. When this new index is used, there is a displacement of the subjects at risk, thus increasing the number considered at risk of malnutrition and in need of appropriate therapeutic intervention. Therefore, the use of body mass index.1 would enable more people suffering malnutrition, who would otherwise remain untreated, to be attended.

Conclusions

As arm span, as an anthropometric measure, remains unchanged over time, it could be used instead of height, as an alternative index (body mass index.1) to the conventional body mass index. Further research is needed to determine the association between body mass index.1 and clinical status parameters to determine optimum cut‐off points.

Relevance to clinical practice

This study describes the greater stability of body mass index.1 with respect to body mass index for nutritional screening, and the resulting benefits for nutritional monitoring and intervention for older people.
Eventful Subjectivity: The Experiential Sources of Solidarity
Authors: Meyer Rachel , Kimeldorf Howard
Published: December 2014

Scholarship on events has been devoted primarily to large‐scale occurrences that transform macro structures. Here we put forward a perspective that we termeventful subjectivitywhich moves the analysis of events in two related directions. First, we shift the arena of eventful analysis from rare world historical occurrences to smaller, more frequent events. Second, we direct attention away from macro‐structural outcomes to micro‐level changes in understanding. We employ the framework of eventful subjectivity to examine a living wage campaign in Chicago, demonstrating how the multi‐faceted diversity of the campaign – in the context of collective action – engendered solidarity rather than fragmentation.
Immunohistochemical expression of fibrillin‐1 and fibrillin‐2 during tooth development
Authors: Kira‐Tatsuoka M. , Oka K. , Tsuruga E. , Ozaki M. , Sawa Y.
Published: December 2014

Background and Objective

Oxytalan fibers are categorized as a microfibril assembly without elastin deposition, and are unique components in the periodontal ligament (PDL). However, little is known about their formation during PDL development. To clarify the mechanisms of oxytalan fiber formation in developing PDL, we performed immunohistochemical analysis to detect the direct expression of fibrillin‐1 and fibrillin‐2, which are major components of microfibrils.

Material and Methods

Frozen sections of lower molars from mice at several stages of growth were prepared without chemical fixation and decalcification using the film transfer method. Immunostaining was performed with anti‐fibrillin‐1 and ‐2, and anticytokeratin antibodies.

Results

Fibrillin‐1 was not expressed in the dental follicle during the crown forming stage. At postneonatal day 9, fibrillin‐1 expression started with meshwork appearance between the epithelial cells from Hertwig's epithelial root sheath at the root dentin surface. Fibirillin‐2 was detected much earlier than fibrillin‐1 expression. Fibrillin‐2 was expressed with a liner appearance, running parallel to the root axis in PDL, and was partially co‐expressed with cytokeratin 14 expression in Hertwig's epithelial root sheath. Furthermore, we detected both fibrillin‐1 and fibrillin‐2 expression in human PDL. Fibrillin‐1 was detected in fibers with a vertically oriented root axis in PDL. Fibrillin‐2 was widely expressed in PDL, including around the epithelial cell rests of Malassez. Fibrillin‐1 and fibrillin‐2 were clearly co‐expressed in thick fiber structures in human PDL.

Conclusion

Our results suggest that both fibrillin‐1 and fibrillin‐2 expression is required to form thick oxytalan fibers in PDL. Based on the expression patterns for fibrillin‐1 and fibrillin‐2, they have different functions during tooth root and PDL development. Early expression of fibrillin‐2 may regulate dental epithelial cell behavior during root and PDL development.
TUG‐OF‐WAR, MARKET MANIPULATION, AND OPTION PRICING
Authors: Nyström Kaj , Parviainen Mikko
Published: December 2014

We develop an option pricing model based on a tug‐of‐war game. This two‐player zero‐sum stochastic differential game is formulated in the context of a multidimensional financial market. The issuer and the holder try to manipulate asset price processes in order to minimize and maximize the expected discounted reward. We prove that the game has a value and that the value function is the unique viscosity solution to a terminal value problem for a parabolic partial differential equation involving the nonlinear and completely degenerate infinity Laplace operator.
Uncovering Unobserved Economy: A General Equilibrium Characterization
Authors: Argentiero Amedeo , Bollino Carlo Andrea
Published: December 2014

This paper builds a three‐sector DSGE (Dynamic Stochastic General Equilibrium) model, considering explicitly the interactions among regular, underground and criminal sectors. We generated quarterly data for unobserved variables for Italian economy over the sample 1974:01–2011:02, through Monte Carlo simulations, and we found that underground economy is about 20 per cent of GDP, whereas criminal economy is 11 per cent. The dynamic behavior of the model shows that (1) regular production has a greater relative volatility with respect to unobserved production, (2) an efficient law enforcement activity is able to weaken unobserved activities and (3) unobserved sectors' variables exhibit a negative correlation with the corresponding ones of regular economy.