bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathologic mandibular fracture after biting crab shells following ramal bone graft
Authors: Kwon Ik Jae , Lee Byung Ho , Eo Mi Young , Kim Soung Min , Lee Jong Ho , Lee Suk Keun
Published: February 2016

The mandibular ramus is considered an appropriate choice for reconstruction of maxillofacial defects because of sufficient amounts of material and fewer donor site complications. Although bone harvesting from the mandibular ramus has many advantages, in rare cases it can result in pathologic fracture of the mandible. Here, we present a case of 59‐year‐old man who suffered a pathologic mandible fracture related to biting hard foods, such as crab shells, after a sinus bone lifting with ramal bone graft procedure performed 2 weeks prior. He underwent closed reduction by intermaxillary fixation with an arch bar over the course of 4 weeks. Three months later, the patients had a stable occlusion with normal mouth opening and sensation. To prevent this complication, the osteotomy should be performed in such a way that it is not too vertical during ramal bone harvesting. Furthermore, we wish to emphasize the importance of patients being instructed to avoid chewing hard foods for at least 4 weeks after ramal bone harvesting.
Parental anxiety in childhood epilepsy: A systematic review
Authors: Jones Chloe , Reilly Colin
Published: February 2016

The aim was to systematically review studies that have focused on symptoms of anxiety reported by parents of children (0–18 years) with epilepsy. PubMed was used to identify relevant studies. Selected studies were reviewed with respect to prevalence of above threshold scores and comparisons with controls on standardized measures of anxiety. Studies are also reported with respect to factors associated with parental anxiety, impact on child outcomes, and comparisons with studies that have included equivalent measures of symptoms of depression. Fifteen studies that met inclusion criteria were identified. None of the studies were population based. The percentage of parents scoring above cutoffs on standardized measures of anxiety was 9–58%. In comparison with parents of healthy controls, parents of children with epilepsy had higher mean scores in two of three studies where this was measured. Possible correlates of parental anxiety in childhood epilepsy that were considered varied widely across studies. Factors such as seizure frequency and use of antiepileptic drugs (AEDs) have been associated with parental anxiety in some but not all studies. With respect to child outcome, increased parental anxiety has been associated with lower quality of life and lower scores on adaptive behavior domains. Symptoms of anxiety are common among parents of children with epilepsy. There is a need for more systematic, representative studies to identify the prevalence of clinically significant anxiety and track the course of symptoms. Such studies will help to identify more clearly factors associated with parental anxiety and impact of symptoms on child and parent outcomes. Intervention studies are needed to evaluate approaches that target a reduction in symptoms and the potential impact on parental and child functioning. Furthermore, there is a need to evaluate the impact of antiepileptic therapies and interventions that focus on child neurobehavioral comorbidities on parental anxiety
Profile of retigabine‐induced neuronal apoptosis in the developing rat brain
Authors: Brown Lindsay , Gutherz Samuel , Kulick Catherine , Soper Colin , Kondratyev Alexei , Forcelli Patrick A.
Published: February 2016

Objective

Acute neonatal exposure to some, but not all, anticonvulsant drugs induces a profound increase in neuronal apoptosis in rats. Phenobarbital and phenytoin induce apoptosis at a therapeutically relevant dose range, lamotrigine and carbamazepine do so only at supratherapeutic doses or in polytherapy, and valproate does so even at subtherapeutic doses. Levetiracetam is devoid of pro‐apoptotic effects. Retigabine, a new‐generation drug, acts uniquely by enhancing the M‐type potassium current. Because its safety profile in developing animals is unstudied, we sought to determine if retigabine would induce apoptosis.

Methods

Postnatal day (P) 7 rat pups were treated with retigabine (5–30 mg/kg), vehicle (saline), or comparator drugs (phenobarbital, lamotrigine, levetiracetam, or carbamazepine). Cell death was assessed using amino‐cupric‐silver staining. A separate group of animals was treated repeatedly (three times over 24 h) with retigabine (15 mg/kg) or vehicle. To establish a pharmacokinetic profile for retigabine, we measured plasma and brain levels after drug treatment.

Results

Consistent with prior studies from our group and others, we found phenobarbital‐induced cell death throughout thalamus, nucleus accumbens, and several neocortical areas. By contrast, levetiracetam, lamotrigine, and carbamazepine were found to have no appreciable apoptotic effect on the aforementioned structures. Acute (single) exposure to retigabine, even at doses of 30 mg/kg, was also without effect on apoptosis. However, repeated (three times) exposure to retigabine triggered apoptosis in a subset of brain areas. The half‐life of retigabine in plasma was 2.5 h, with appreciable concentrations reached in the brain within 1 h of administration.

Significance

These data demonstrate that retigabine, like many other anticonvulsant drugs, is capable of triggering neuronal apoptosis in the developing rat brain. Unlike other drugs, repeated dosing of retigabine was necessary to induce this effect. This may be due to its shorter half‐life as compared to other drugs, such as phenobarbital.
Awareness of Racial Diversity in the Spanish‐Speaking World Among L2 Spanish Speakers
Authors: Abreu Laurel
Published: February 2016

For more than 30 years, foreign language instructors have considered approaches to teaching their students about Afro‐Latin cultures, yet little research appears to address students' actual awareness of these populations. Using a photo ratings survey, the present study explored the perceptions of postsecondary second language learners and their instructors concerning native Spanish speakers' physical appearance. The mean ratings assigned by the student participants to 24 photos were analyzed in conjunction with the following independent variables: first language, place of origin, race, gender, age, course level, contact with Spanish outside the classroom, having Spanish‐speaking friends or family, and travel to Spanish‐speaking countries. In addition, both students' and instructors' answers to open‐ended questions about native speaker characteristics were analyzed. Results indicated the importance for learners of having contact with Spanish outside the classroom, whether through exposure to media or encounters with Spanish speakers. Implications and suggestions are described for inclusive culture teaching.
Long‐term trends in the catch characteristics of rainbow troutOncorhynchus mykiss, in a self‐sustained recreational fishery, Tongariro River, New Zealand
Authors: Dedual M. , Rohan M.
Published: February 2016

The catch distribution of adfluvial rainbow trout,Oncorhynchus mykiss(Walbaum), amongst anglers is described from 14 868 creel surveys collected from the Tongariro River in central North Island of New Zealand between 1985 and 2013. An index of fish abundance was obtained during the period 1998–2013 from a continuous trapping programme on the Waipa Stream, an important spawning tributary of the Tongariro River. Using these two data sets, inequalities in catch distribution were quantified using the Gini coefficient and Lorenz asymmetry coefficient (LAC). Both Gini coefficient andLACshowed a slight decline over time. This occurred concurrently with reduced angling participation and a decline in fish abundance. Inequality was larger when fish were more abundant, but catch‐per‐unit‐effort was only marginally affected despite large variations in fish abundance, suggesting that some hyperstability is occurring. Several important management implications of these results are presented.
Relationships between angling effort and fish abundance in recreational marine fisheries
Authors: Camp E. V. , Ahrens R. N. M. , Allen M. S. , Lorenzen K.
Published: February 2016

Relationships between angling effort and fish abundance have critical implications for the resilience and management of recreational fisheries, but these relationships have rarely been assessed empirically. Here, angling effort was related to fish abundance in three marine recreational fisheries in Florida, USA, through a suite of regression and time series methods that accounted for socio‐economic and demographic variables. Overall, recreational angling effort was correlated with fish abundance, but further analyses provided little evidence of strong, causal relationships. Lack of strong relationships implies angling effort might increase in the future unrelated to fish abundance, a decoupling that could threaten the viability of fish populations in the absence of unpopular recreational effort limitation. The inability to establish more conclusive relationships between effort and fish abundance should motivate a future focus towards natural or manipulative experiments that may provide more powerful inferences.
Collaborative assessment of recreational fishing in a subtropical estuarine system: a case study with fishing guides from south‐eastern Brazil
Authors: Motta F. S. , Mendonça J. T. , Moro P. S.
Published: February 2016

Knowledge of recreational fisheries in Brazil is scarce and remains a critical issue to determine management actions. By adopting a collaborative approach that involved fishing guides, recreational fishing from the Iguape and Cananéia Lagoon Estuarine System (south‐eastern Brazil) was assessed. During the study period (from April 2009 to March 2010), 341 fishing operations (boat day−1) were monitored. A total of 10 051 fish specimens of 26 families and at least 51 species were examined. The fat snook, Centropomus parallelus Poey, was the most commonly caught species representing 51% of the fish caught. Annual fishing effort was estimated at 272 859 angler‐hours, and the mean catch‐per‐unit‐effort was 3.42 fish boat−1 h−1. Size structure of targeted species suggests that the populations are overexploited. The approach used in the study reinforces the importance of engaging different stakeholders in science and management and improving the communication among them.
Biological and socio‐economic aspects of recreational fisheries and their implications for the management of coastal urban areas of south‐eastern Brazil
Authors: Barrella W. , Ramires M. , Rotundo M. M. , Petrere M. , Clauzet M. , Giordano F.
Published: February 2016

A total of 442 anglers in a coastal region of SE Brazil were interviewed to obtain information about recreational fishing. The anglers were mature individuals (mean age ≈43 years) with a high level of education. However, many did not have a fishing licence. Target fishes belonged to 47 species. Mean catch (Catch per unit effort ‐ CPUE) was 4.2 fish−1 day−1 or 488 g−1 angler−1 day−1. Total estimated catch in the study period was equivalent to 2% of commercial landings, indicating that recreational fishing has little impact on fish stocks. The anglers complained that fishing conditions had worsened because of environmental degradation. Catch‐and‐release was classified as a ‘good’ attitude despite reports of practices that caused suffering to fish. However, when asked about prohibition of catch‐and‐release, which is enforced in some countries, the anglers said they would not accept such a prohibition if proposed by Brazilian fishing authorities. As a general rule, issues related to animal welfare and animal rights are not discussed widely by society or by fishing authorities in Brazil. Suggestions for integrated management of coastal resources and for monitoring recreational fishing are presented.
Host adaptation and unexpected symbiont partners enable reef‐building corals to tolerate extreme temperatures
Authors: Howells Emily J. , Abrego David , Meyer Eli , Kirk Nathan L. , Burt John A.
Published: February 2016

Understanding the potential for coral adaptation to warming seas is complicated by interactions between symbiotic partners that define stress responses and the difficulties of tracking selection in natural populations. To overcome these challenges, we characterized the contribution of both animal host and symbiotic algae to thermal tolerance in corals that have already experienced considerable warming on par with end‐of‐century projections for most coral reefs. Thermal responses in Platygyra daedalea corals from the hot Persian Gulf where summer temperatures reach 36°C were compared with conspecifics from the milder Sea of Oman. Persian Gulf corals had higher rates of survival at elevated temperatures (33 and 36°C) in both the nonsymbiotic larval stage (32–49% higher) and the symbiotic adult life stage (51% higher). Additionally, Persian Gulf hosts had fixed greater potential to mitigate oxidative stress (31–49% higher) and their Symbiodinium partners had better retention of photosynthetic performance under elevated temperature (up to 161% higher). Superior thermal tolerance of Persian Gulf vs. Sea of Oman corals was maintained after 6‐month acclimatization to a common ambient environment and was underpinned by genetic divergence in both the coral host and symbiotic algae. In P. daedalea host samples, genomewide SNP variation clustered into two discrete groups corresponding with Persian Gulf and Sea of Oman sites. Symbiodinium within host tissues predominantly belonged to ITS2 rDNA type C3 in the Persian Gulf and type D1a in the Sea of Oman contradicting patterns of Symbiodinium thermal tolerance from other regions. Our findings provide evidence that genetic adaptation of both host and Symbiodinium has enabled corals to cope with extreme temperatures in the Persian Gulf. Thus, the persistence of coral populations under continued warming will likely be determined by evolutionary rates in both, rather than single, symbiotic partners.
Dosing regimens, FVIII levels and estimated haemostatic protection with special focus on rFVIIIFc
Authors: Berntorp E. , Negrier C. , Gozzi P. , Blaas P‐M. , Lethagen S.
Published: February 2016

Introduction

Aim: To use Pharmacokinetic (PK) simulations to illustrate potential differences in clinical outcomes between prophylaxis with conventional recombinant factor VIII (rFVIII) and rFVIIIFc, an extended half‐life rFVIII covalently fused to the Fc domain of human IgG1. Methods: Population PK estimates from 180 (rFVIIIFc) and 46 (rFVIII) severe haemophilia A patients were used to simulate FVIII activity over time at various rFVIIIFc dosing regimens compared to rFVIII 30 IU kg−1 three times weekly in a typical adult patient. Results: rFVIII dosed 3x30 IU kg−1 weekly gave trough levels of 2.7, 2.8 and 0.7 IU dL−1, and time spent below 1, 3 and 5 IU dL−1 of 0.2/1.2/2.3 days week−1. rFVIIIFc 2 x 45 IU kg−1 gave higher troughs (4.4 and 1.7 IU dL−1) and shorter time spent below 1, 3 and 5 IU dL−1 (0/0.6/1.3 days week−1), with same total factor consumption. rFVIIIFc 2 x 30 IU kg−1 gave similar troughs (3.0 and 1.2 IU kg−1) and time spent below 1, 3 and 5 IU dL−1 (0/1.0/2.1 days week−1), despite total factor consumption being reduced by one‐third. The same dose and interval of rFVIIIFc (3 x 30 IU kg−1) gave substantially higher troughs (7.8, 8.5 and 3.3 IU dL−1) and markedly shorter time spent below 1, 3 and 5 IU dL−1 (0/0/0.4 days week−1). Conclusion: The lower clearance of rFVIIIFc compared to conventional rFVIII gives rFVIIIFc the potential of improved bleed prevention and reduced injection frequency at similar factor consumption. Although additional clinical data are required to confirm the conclusions, the simulations clearly show the potential of rFVIIIFc of increased flexibility to tailor treatment to the individual patient, and to advance the standard of care in haemophilia.
Efficacy of probiotics in non‐alcoholic fatty liver disease in adult and children: A meta‐analysis of randomized controlled trials
Authors: Gao Xiaolin , Zhu Yu , Wen Yang , Liu Guanjian , Wan Chaomin
Published: February 2016

Aim

To evaluate the efficacy of probiotics in the treatment of adult and childhood non‐alcoholic fatty liver disease (NAFLD).

Methods

Randomized controlled trials on the efficacy of probiotics in the treatment of adult and childhood NAFLD published before July 2015 were searched in multiple databases, including Cochrane Library, PubMed/MEDLINE, EBSCO, OVID, SCI, CNKI, and VIP. Article identification and data extraction were carried out by two reviewers based on the inclusion and exclusion criteria. RevMan 5.3 software was used for the meta‐analysis.

Results

Nine randomized controlled trials with a total of 535 cases of NAFLD were included. Statistical differences in homeostasis model assessment, total cholesterol, high density lipoprotein, triglyceride, and tumor necrosis factor‐α were detected between the probiotics and control groups with variations in different patient populations. No significant differences in body mass index (BMI), glucose, or insulin were detected between the two groups. Statistical differences in low density lipoprotein, alanine aminotransferase, aspartate transaminase, and BMI were detected between the two childhood groups (P ≤ 0.05).

Conclusion

Probiotics provided improvements in the outcomes of homeostasis model assessment, total cholesterol, high density lipoprotein, and tumor necrosis factor‐α in any NAFLD patients and triglyceride in Italian and Spanish patients, but no improvement in the outcomes of BMI, glucose, or insulin in adult NAFLD patients. The currently available data are not sufficient to compare the effects of probiotics between adult and childhood NAFLD patients.
Testing hypotheses about the function of repeated nest abandonment as a life history strategy in a passerine bird
Authors: Beckmann Christa , Martin Kathy
Published: February 2016

Nest structures are essential for successful reproduction in most bird species. Nest construction costs time and energy, and most bird species typically build one nest per breeding attempt. Some species, however, build more than one nest, and the reason for this behaviour is often unclear. In the Grey Fantail Rhipidura albiscapa, nest abandonment before egg‐laying is very common. Fantails will build up to seven nests within a breeding season, and pairs abandon up to 71% of their nests before egg‐laying. We describe multiple nest‐building behaviour in the Grey Fantail and test four hypotheses explaining nest abandonment in this species: cryptic depredation, destruction of nests during storm events, and two anti‐predatory responses (construction of decoy nests to confuse predators, and increasing concealment to ‘hide’ nests more effectively). We found support for only one hypothesis – that abandonment is related to nest concealment. Abandoned nests were significantly less concealed than nests that received eggs. Most abandoned nests were not completely built and none received eggs, thus ruling out cryptic predation. Nests were not more likely to be abandoned following storm events. The decoy nest hypothesis was refuted as abandoned nests were constructed at any point during the breeding season and some nests were dismantled and the material used to build the subsequent nest. Thus, Grey Fantails are flexible about nest‐site locations during the nest‐building phase and readily abandon nest locations if they are found to have deficient security.
Increased level of tumour necrosis factor‐alpha (TNF‐α) on the skin of Japanese obese males: measured by quantitative skin blotting
Authors: Ogai K. , Matsumoto M. , Aoki M. , Minematsu T. , Kitamura K. , Kobayashi M. , Sanada H. , Sugama J.
Published: February 2016

Objective

A state of chronic inflammation, characterized by an increased level of tumour necrosis factor‐alpha (TNF‐α), is often found in the obese population. The negative effects of elevated TNF‐α are not limited to systemic metabolism. It also reportedly affects skin integrity. Recently, the relationship between obesity and skin fragility was reported; however, there has been little insight into how the level of TNF‐α in the skin in situ is related to the severity of obesity. In this study, we aimed to measure the level of TNF‐α on the skin and to find the relationship between obesity and the level of TNF‐α detected on the skin.

Methods

We used a novel, non‐invasive method called quantitative skin blotting. Fifty‐nine healthy (but some were classified as being overweight or obese) Japanese males were enrolled as subjects. The levels of TNF‐α detected on the abdominal and thigh skin along with the body composition were measured, followed by a correlation analysis.

Results

Significant positive correlations were found between the levels of TNF‐α detected on the skin and the severity of obesity such as body mass index (BMI), body fat weight and visceral fat rating.

Conclusion

We found that high levels of TNF‐α were detected on the skin of Japanese obese males, which implied the higher TNF‐α in the skin. The elevation of skin TNF‐α may be one factor related to skin fragility that is often found in obese individuals.
Differences between diploma and baccalaureate dental hygiene education in British Columbia: a qualitative perspective
Authors: Sunell S , McFarlane RDD , Biggar HC
Published: February 2016

The British Columbia Ministry of Health in Canada approved a new registration category for dental hygienists in 2012. This category included four abilities that registrants were required to demonstrate at a 4th‐year baccalaureate degree level.

Objective

To identify the differences, if any, between diploma and bachelor's degree education with regard to the 4 legislated abilities focused on the process of care for clients with complex needs and/or disabling conditions including client safety, referrals and interprofessional collaboration.

Methods

Registrants who had entered practice with a diploma and then gained a baccalaureate degree were invited to participate in an online survey including closed‐ and open‐ended questions. The study was a mixed‐method design where the qualitative data were nested concurrently in the open‐ended questions; the data were analysed through thematic analysis using grounded theory methods.

Results and discussion

Respondents (n = 123; 51%) indicated their client care had improved with baccalaureate education due to increased knowledge, increased understanding and increased abilities to make judgements with a particular emphasis on evidence‐based decisions. These more advanced abilities provided them with increased confidence for taking action particularly in interprofessional contexts and increased the quality of their decision‐making thus leading to better care for clients.

Conclusion

Respondents described their dental hygiene services as generally being of a higher standard and specifically in the 4 legislated abilities as a direct result of baccalaureate education.
Structural analysis of HyFlex EDM instruments
Authors: Iacono F. , Pirani C. , Generali L. , Bolelli G. , Sassatelli P. , Lusvarghi L. , Gandolfi M. G. , Giorgini L. , Prati C.
Published: February 2016

Aim

To compare the phase transformation behaviour, the microstructure, the nano‐hardness and the surface chemistry of electro‐discharge machined HyFlex EDM instruments with conventionally manufactured HyFlex CM.

Methodology

New and laboratory used HyFlex EDM were examined by X‐ray diffraction (XRD) and differential scanning calorimetry (DSC). Nano‐hardness and modulus of elasticity were also investigated using a maximum load of 20 mN with a minimum of 40 significant indentations for each sample. Raman spectroscopy and field emission‐scanning electron microscope (FE‐SEM) were used to assess the surface chemistry of HyFlex EDM. HyFlex CM were subjected to the same investigations and used as a comparison. Nano‐indentation data were statistically analysed using the Student's t‐test.

Results

XRD analysis on HyFlex EDM revealed the presence of martensite and rhombohedral R‐phase, while a mixture of martensite and austenite structure was identified in HyFlex CM. DSC analysis also disclosed higher austenite finish (Af) temperatures for electro‐discharge machining (EDM) instruments. Significant differences in nano‐hardness and modulus of elasticity were found between EDM and CM files (P < 0.05). FE‐SEM and EDS analyses confirmed that both new EDM and CM files were covered by an oxide layer. Micro‐Raman spectroscopy assessed the presence of rutile‐TiO2
.

Conclusions

HyFlex EDM revealed peculiar structural properties, such as increased phase transformation temperatures and hardness. Present results corroborated previous findings and shed light on the enhanced mechanical behaviour of these instruments.
Effect of supercritical CO2 extraction process parameters on oil yield and pigment content from by‐product hemp cake
Authors: Aladić Krunoslav , Vidović Senka , Vladić Jelena , Balić Davor , Jukić Huska , Jokić Stela
Published: February 2016

This research gives an insight into the possibility of exploiting the one of the food industry's by‐products – pressed hemp cake. The complete recovery of oil from pressed hemp cake was achieved. Residual oil that remained in cake after pressing was extracted with supercritical CO2 by applying different process parameters. Optimal extraction conditions were determined using response surface methodology. Total pigment contents of the oils obtained were determined. Extraction pressure had the most significant influence on yield and pigment content of extracted hemp cake oil. Depending on the pressure, the chlorophyll a content ranged from 101.11 to 378.28 mg kg−1 and chlorophyll b from 65.14 to 189.78 mg kg−1, while total carotene content was in the range from 33.58 to 132.67 mg kg−1. The remaining oil in pressed hemp cake after supercritical CO2 extraction was determined to be 0.56 ± 0.08% and the defatted cake was rich in proteins and fibre.
Fermentation alters antioxidant capacity and polyphenol distribution in selected edible legumes
Authors: Gan Ren‐You , Shah Nagendra P. , Wang Ming‐Fu , Lui Wing‐Yee , Corke Harold
Published: February 2016

This study was designed to investigate the influences of fermentation by naturally occurring bacteria on legumes and lactic acid bacteria on antioxidant capacity and polyphenols in both soluble and bound extracts of eight common edible legumes, including black cow gram, mottled cowpea, speckled kidney bean, lentil, small rice bean, small runner bean and two soya beans. Fermentation had varying effects on the antioxidant capacity of soluble and bound extracts in different edible legumes, with fermented mottled cowpea, speckled kidney bean and small rice bean showing increased total antioxidant capacity. In addition, fermentation in general enhanced total phenolic content in all the selected legumes, which could be associated with the biotransformation between soluble phenolics and the release of bound phenolics induced by micro‐organisms involved in the fermentation process. Phenolic compounds, such as catechin, were increased in fermented mottled cowpea. Overall, fermentation could increase the bioavailability of legume polyphenols and fermented legume powders rich in antioxidant polyphenols can be used to develop novel functional foods.
Physicochemical characteristics and gelation properties of collagen superfine powder from swine skin: the effects of preheating treatment
Authors: Wang Wenhang , Zhang Yi , Ye Ran , Zhao Wenping
Published: February 2016

Following different preheating treatments (60 °C for 20 min; 80 °C for 20 min; or 120 °C for 10 min, referred as T1, T2 and T3), edible collagen superfine powder (CSP) from swine skin was prepared by superfine grinding method. The CSPs showed a preheating‐dependent decrease in the D50, with different degrees of hydrolysis (9.51–31.05%). A significant effect of preheating on rheological properties of the CSP aqueous dispersions at pH 4–9 was observed, wherein T2 had the biggest viscosity and water holding capacity. All the 5% CSP dispersions were transformed into stable cold‐set gels after heating at 50–90 °C for 20 min, with insignificant differences in strength. These attributes were consistent with microstructures of the CSP gels detected by scanning electron microscope.
A retrospective comparison of infliximab versus adalimumab as induction and maintenance therapy for Crohn disease
Authors: Varma P. , Paul E. , Huang C. , Headon B. , Sparrow M. P.
Published: February 2016

Background

In Australia, infliximab (IFX) and adalimumab (ADA) are available for the treatment of moderate–severe Crohn disease (CD) refractory to conventional therapies, with minimal local data comparing their efficacy.

Aim

The aim of this study was to compare clinical and biochemical outcomes at 3 and 12 months between patients receiving induction and maintenance therapy with IFX versus ADA.

Methods

Retrospective single‐centre audit of all patients commenced on IFX or ADA as their first anti‐tumour necrosis factor agent between July 2007 and May 2012. Clinical and biochemical parameters were compared pre‐commencement, 3 and 12 months post‐commencement.

Results

A total of 81 patients was included in the study; 63 IFX‐treated and 18 ADA‐treated. Significant Crohn disease activity index (CDAI) reductions were noted within both groups at 3 months (P < 0.001) and 12 months (P < 0.001). Similarly, significant reductions were noted in steroid doses within groups at 3 months (P < 0.05) and 12 months (P < 0.05), with notable reductions in C‐reactive protein (CRP) at 3 months within groups (P < 0.05). Adverse events occurred in 14.3% of IFX and 11.1% of ADA patients.

Comparing IFX with ADA, no difference was shown between groups in CDAI reductions at 3 months (P = 0.94) and 12 months (P = 0.95), steroid dosing at 3 months (P = 0.23) and 12 months (P = 0.81), and CRP reduction at 3 months (P = 0.33) and 12 months (P = 0.62). Fistula‐related admissions were significantly reduced in IFX patients (100% reduction post‐IFX vs 66.7% post‐ADA) (P = 0.01).

Conclusion

Clinical and biochemical outcomes were similar in patients treated with IFX or ADA as induction and maintenance therapy for CD. However, significant reductions were noted in admissions relating to fistulising disease in IFX patients.
Engineered IgG1‐Fc – one fragment to bind them all
Authors: Lobner Elisabeth , Traxlmayr Michael W. , Obinger Christian , Hasenhindl Christoph
Published: February 2016

The crystallizable fragment (Fc) of the immunoglobulin class G (IgG) is a very attractive scaffold for the design of novel therapeutics due to its quality of uniting all essential antibody functions. This article reviews the functionalization of this homodimeric glycoprotein by diversification of structural loops of CH3 domains for the design of Fcabs, i.e. antigen‐binding Fc proteins. It reports the design of libraries for the selection of nanomolar binders with wildtype‐like in vivo half‐life and correlation of Fc receptor binding and ADCC. The in vitro and preclinical biological activity of selected Fcabs is compared with that of clinically approved antibodies. Recently, the great potential of the scaffold for the development of therapeutics for clinical use has been shown when the HER2‐binding Fcab FS102 entered clinical phase I. Furthermore, methods for the engineering of biophysical properties of Fcabs applicable to proteins in general are presented as well as the different approaches in the design of heterodimeric Fc‐based scaffolds used in the generation of bispecific monoclonal antibodies. Finally, this work critically analyzes and compares the various efforts in the design of highly diverse and functional libraries that have been made in the engineering of IgG1‐Fc and structurally similar scaffolds.
Engineered hapten‐binding antibody derivatives for modulation of pharmacokinetic properties of small molecules and targeted payload delivery
Authors: Dengl Stefan , Sustmann Claudio , Brinkmann Ulrich
Published: February 2016

Hapten‐binding antibodies have for more than 50 years played a pivotal role in immunology, paving the way to antibody generation (as haptens are very important and robust immunogens), to antibody characterization (as the first structures generated more than 40 years ago were those of hapten binders), and enabled and expanded antibody engineering technologies. The latter field of engineered antibodies evolved over many years and many steps resulting in recombinant humanized or human‐derived antibody derivatives in multiple formats. Today, hapten‐binding antibodies are applied not only as reagents and tools (where they still play an important part) but evolved also to engineered targeting and pretargeting vehicles for disease diagnosis and therapy. Here we describe recent applications of hapten‐binding antibodies and of engineered mono‐ and bispecific hapten‐binding antibody derivatives. We have designed and applied these molecules for the modulation of the pharmacokinetic properties of small compounds or peptides. They are also integrated as additional binding entities into bispecific antibody formats. Here they serve as non‐covalent or covalent coupling modules to haptenylated compounds, to enable targeted payload delivery to disease tissues or cells.
Monoclonal antibodies targeting CD38 in hematological malignancies and beyond
Authors: van de Donk Niels W. C. J. , Janmaat Maarten L. , Mutis Tuna , Lammerts van Bueren Jeroen J. , Ahmadi Tahamtan , Sasser A. Kate , Lokhorst Henk M. , Parren Paul W. H. I.
Published: February 2016

CD38 is a multifunctional cell surface protein that has receptor as well as enzyme functions. The protein is generally expressed at low levels on various hematological and solid tissues, while plasma cells express particularly high levels of CD38. The protein is also expressed in a subset of hematological tumors, and shows especially broad and high expression levels in plasma cell tumors such as multiple myeloma (MM). Together, this triggered the development of various therapeutic CD38 antibodies, including daratumumab, isatuximab, and MOR202. Daratumumab binds a unique CD38 epitope and showed strong anti‐tumor activity in preclinical models. The antibody engages diverse mechanisms of action, including complement‐dependent cytotoxicity, antibody‐dependent cellular cytotoxicity, antibody‐dependent cellular phagocytosis, programmed cell death, modulation of enzymatic activity, and immunomodulatory activity. CD38‐targeting antibodies have a favorable toxicity profile in patients, and early clinical data show a marked activity in MM, while studies in other hematological malignancies are ongoing. Daratumumab has single agent activity and a limited toxicity profile, allowing favorable combination therapies with existing as well as emerging therapies, which are currently evaluated in the clinic. Finally, CD38 antibodies may have a role in the treatment of diseases beyond hematological malignancies, including solid tumors and antibody‐mediated autoimmune diseases.
Manipulation of the glycan‐specific natural antibody repertoire for immunotherapy
Authors: New J. Stewart , King R. Glenn , Kearney John F.
Published: February 2016

Natural immunoglobulin derived from innate‐like B lymphocytes plays important roles in the suppression of inflammatory responses and represents a promising therapeutic target in a growing number of allergic and autoimmune diseases. These antibodies are commonly autoreactive and incorporate evolutionarily conserved specificities, including certain glycan‐specific antibodies. Despite this conservation, exposure to bacterial polysaccharides during innate‐like B lymphocyte development, through either natural exposure or immunization, induces significant changes in clonal representation within the glycan‐reactive B cell pool. Glycan‐reactive natural antibodies (NAbs) have been reported to play protective and pathogenic roles in autoimmune and inflammatory diseases. An understanding of the composition and functions of a healthy glycan‐reactive NAb repertoire is therefore paramount. A more thorough understanding of NAb repertoire development holds promise for the design of both biological diagnostics and therapies. In this article, we review the development and functions of NAbs and examine three glycan specificities, represented in the innate‐like B cell pool, to illustrate the complex roles environmental antigens play in NAb repertoire development. We also discuss the implications of increased clonal plasticity of the innate‐like B cell repertoire during neonatal and perinatal periods, and the prospect of targeting B cell development with interventional therapies and correct defects in this important arm of the adaptive immune system.
Immigration and Democratic Principles: On Carens’ Ethics of Immigration
Authors: Song Sarah
Published: February 2016

Carens has done more than any other political theorist or philosopher to develop the normative perspective of prospective migrants from within the liberal democratic tradition, but he has not sufficiently engaged with the other side of the argument – in particular, with the value of political community and the principle of collective self‐determination. What is at stake for the immigrant‐receiving country that might justify its claim to control immigration? I first examine Carens’ theory of social membership and its connection to political community. I then discuss his method of ‘political theory from the ground up’ and his interpretation of democratic principles. I conclude with a discussion of the principle of collective self‐determination.
Haemosporidian parasites and avian host population abundance in the Lesser Antilles
Authors: Ricklefs Robert E. , Soares Leticia , Ellis Vincenzo A. , Latta Steven C.
Published: February 2016

Aim

To determine statistical relationships between the prevalence of haemosporidian (malaria) parasites and the abundance of avian host populations across islands in the Lesser Antilles.

Location

Thirteen islands in the Lesser Antilles, from Grenada in the south to St Kitts in the north.

Methods

Birds were captured by mist net and small blood samples were taken for polymerase chain reaction and DNA sequencing analysis of haemosporidian parasite infections. Similarities between islands with respect to geographical distance, avian host assemblages and haemosporidian parasite assemblages were compared by partial Mantel tests. Relative abundances of avian host populations across islands were compared to the relative abundances of common haemosporidian lineages by stepwise regression.

Results

Populations of parasite lineages were more heterogeneously distributed than were host populations across the islands; parasite lineages frequently shift between hosts on different islands and exhibit range disjunctions. Relative population sizes of two widespread and common species of bird in the Lesser Antilles, the bananaquit Coereba flaveola and the black‐faced grassquit Tiaris bicolor, were negatively related to the relative abundances of two parasite lineages, OZ01 (Plasmodium sp.) and OZ12 (Haemoproteus sp.), although the latter parasite was not recovered from either host. Positive associations between populations of Elaenia martinica and the relative abundance of three parasite lineages in populations of Vireo altiloquus additionally suggest the possibility of apparent competition between avian species mediated through haemosporidian parasites.

Main conclusions

The results of these analyses are consistent with a strong influence of some avian haemosporidian parasites on populations of their hosts, including indirect interactions through apparent competition. In addition, the heterogeneity of host–parasite associations between islands suggests an evolutionarily dynamic system that is consistent with phases of host expansion and contraction, commonly known as the taxon cycle.
Hepatitis C virus NS3‐4A inhibits the peroxisomal MAVS‐dependent antiviral signalling response
Authors: Ferreira Ana R. , Magalhães Ana C. , Camões Fátima , Gouveia Ana , Vieira Marta , Kagan Jonathan C. , Ribeiro Daniela
Published: February 2016

Hepatitis C virus (HCV) is the cause of one of the most prevalent viral infections worldwide. Upon infection, the HCV genome activates the RIG‐I‐MAVS signalling pathway leading to the production of direct antiviral effectors which prevent important steps in viral propagation.

MAVS localizes at peroxisomes and mitochondria and coordinate the activation of an effective antiviral response: peroxisomal MAVS is responsible for a rapid but short‐termed antiviral response, while the mitochondrial MAVS is associated with the activation of a stable response with delayed kinetics.

The HCV NS3‐4A protease was shown to specifically cleave the mitochondrial MAVS, inhibiting the downstream response.

In this study, we have analysed whether HCV NS3‐4A is also able to cleave the peroxisomal MAVS and whether this would have any effect on the cellular antiviral response. We show that NS3‐4A is indeed able to specifically cleave this protein and release it into the cytosol, a mechanism that seems to occur at a similar kinetic rate as the cleavage of the mitochondrial MAVS. Under these conditions, RIG‐I‐like receptor (RLR) signalling from peroxisomes is blocked and antiviral gene expression is inhibited. Our results also show that NS3‐4A is able to localize at peroxisomes in the absence of MAVS. However, mutation studies have shown that this localization pattern is preferred in the presence of a fully cleavable MAVS. These findings present evidence of a viral evasion strategy that disrupts RLR signalling on peroxisomes and provide an excellent example of how a single viral evasion strategy can block innate immune signalling from different organelles.
HDAC9 exacerbates endothelial injury in cerebral ischaemia/reperfusion injury
Authors: Shi Weichen , Wei Xinbing , Wang Ziying , Han Huirong , Fu Yi , Liu Jiang , Zhang Yan , Guo Jian , Dong Chuanqiao , Zhou Di , Zhou Quan , Chen Yuxin , Yi Fan
Published: February 2016

Histone deacetylase (HDAC) 9, a member of class II HDACs, regulates a wide variety of normal and abnormal physiological functions, which is usually expressed at high levels in the brain and skeletal muscle. Although studies have highlighted the importance of HDAC‐mediated epigenetic processes in the development of ischaemic stroke and very recent genome‐wide association studies have identified a variant in HDAC9 associated with large‐vessel ischemic stroke, the molecular events by which HDAC9 induces cerebral injury keep unclear. In this study, we found that HDAC9 was up‐regulated in the ischaemic cerebral hemisphere after cerebral ischaemia/reperfusion (I/R) injury in rats and in vivo gene silencing of HDAC9 by recombinated lentivirus infection in the brain reduced cerebral injury in experimental stroke. We further demonstrated that HDAC9 contributed to oxygen‐glucose deprivation‐induced brain microvessel endothelial cell dysfunction as demonstrated by the increased inflammatory responses, cellular apoptosis and endothelial cell permeability dysfunction accompanied by reduced expression of tight‐junction proteins. We further found that HDAC9 suppressed autophagy, which was associated with endothelial dysfunction. This study for the first time provides direct evidence that HDAC9 contributes to endothelial cell injury and demonstrates that HDAC9 is one of critical components of a signal transduction pathway that links cerebral injury to epigenetic modification in the brain.
Extreme genetic diversity in asexual grass thrips populations
Authors: Fontcuberta García‐Cuenca A. , Dumas Z. , Schwander T.
Published: February 2016

The continuous generation of genetic variation has been proposed as one of the main factors explaining the maintenance of sexual reproduction in nature. However, populations of asexual individuals may attain high levels of genetic diversity through within‐lineage diversification, replicate transitions to asexuality from sexual ancestors and migration. How these mechanisms affect genetic variation in populations of closely related sexual and asexual taxa can therefore provide insights into the role of genetic diversity for the maintenance of sexual reproduction. Here, we evaluate patterns of intra‐ and interpopulation genetic diversity in sexual and asexual populations of Aptinothrips rufus grass thrips. Asexual A. rufus populations are found throughout the world, whereas sexual populations appear to be confined to few locations in the Mediterranean region. We found that asexual A. rufus populations are characterized by extremely high levels of genetic diversity, both in comparison with their sexual relatives and in comparison with other asexual species. Migration is extensive among asexual populations over large geographic distances, whereas close sexual populations are strongly isolated from each other. The combination of extensive migration with replicate evolution of asexual lineages, and a past demographic expansion in at least one of them, generated high local clone diversities in A. rufus. These high clone diversities in asexual populations may mimic certain benefits conferred by sex via genetic diversity and could help explain the extreme success of asexual A. rufus populations.
Pollinator‐mediated assemblage processes in California wildflowers
Authors: Briscoe Runquist R. , Grossenbacher D. , Porter S. , Kay K. , Smith J.
Published: February 2016

Community assembly is the result of multiple ecological and evolutionary forces that influence species coexistence. For flowering plants, pollinators are often essential for plant reproduction and establishment, and pollinator‐mediated interactions may influence plant community composition. Here, we use null models and community phylogenetic analyses of co‐occurrence patterns to determine the role of pollinator‐mediated processes in structuring plant communities dominated by congeners. We surveyed three species‐rich genera (Limnanthes, MimulusandClarkia) with centres of diversity in the Sierra Nevada of California. Each genus contains species that co‐flower and share pollinators, and each has a robust phylogeny. Within each genus, we surveyed 44–48 communities at three spatial scales, measured floral and vegetative traits and tested for segregation or aggregation of: (i) species, (ii) floral traits (which are likely to be influenced by pollinators), and (iii) vegetative traits (which are likely affected by other environmental factors). We detected both aggregation and segregation of floral traits that were uncorrelated with vegetative trait patterns; we infer that pollinators have shaped the community assembly although the mechanisms may be varied (competition, facilitation, or filtering). We also found that mating system differences may play an important role in allowing species co‐occurrence. Together, it appears that pollinators influence community assemblage in these three clades.