bluuebunny/crossref_metadata_2025 huggingface dataset:
Does the development of chronic kidney disease and acute kidney injury affect the prognosis after living donor liver transplantation?
Authors: Inoue Yusuke , Soyama Akihiko , Takatsuki Mitsuhisa , Hidaka Masaaki , Kinoshita Ayaka , Natsuda Koji , Baimakhanov Zhassulan , Kugiyama Tota , Adachi Tomohiko , Kitasato Amane , Kuroki Tamotsu , Eguchi Susumu
Published: February 2016

Background and aims

Chronic kidney disease (CKD) and acute kidney injury (AKI) have been discussed as complications following living donor liver transplantation (LDLT). The aim of this study was to clarify the relationships among CKD, AKI, and the prognosis after LDLT.

Methods

This study included 118 patients who underwent LDLT in our department. A low eGFR (<60 mL/min/1.73 m2) was regarded to indicate CKD. AKI 1 and AKI 2 were characterized by an increase in the serum creatinine level of 0.5 and 1.0 mg/dL, respectively, within one wk after LDLT. We investigated the risk factors for and the relevance of CKD and AKI on the prognosis.

Results

AKI 1 was associated with sepsis and intra‐operative bleeding (p = 0.0032, p = 0.001). AKI 2 was associated with sepsis and hepatitis C infection (p < 0.001, p = 0.027). A pre‐operative eGFR of 60–89 and diabetes were the risk factors for the development of CKD in POY 2 (p = 0.018, p = 0.002). AKI 2, sepsis, and diabetes were the risk factors for the patient death within one yr after LDLT (p = 0.010, p = 0.002, p = 0.022). AKI 2 and sepsis were the risk factors for death within two yr after LDLT (p = 0.005, p = 0.018).

Conclusions

Recognizing the risk factors and careful management for preventing both AKI and CKD may improve the prognosis of patients following LDLT.
Characterization of dermatopathology fellowship applicants: a 5‐year single institution experience
Authors: Uhlenhake Elizabeth E. , Smoller Bruce R. , Elwood Hillary R. , Shalin Sara C. , Gardner Jerad M.
Published: February 2016

Background

Although much data have been documented on the characteristics of medical school applicants for dermatology and pathology residency programs in the United States and select medical and surgical fellowship applicants through the National Residency Matching Program, little is known about the dermatopathology applicant demographics.

Methods

We examined a 5‐year pool of dermatopathology fellowship applicants from a single institution (University of Arkansas for Medical Sciences) and compiled background profile data of the applicants to characterize an ‘average dermatopathology fellow’ applicant.

Results

A total of 229 applicants over a 5‐year period were included in the assessment. The majority were of pathology background with medical school and residency training based in the southern United States. One‐third of the applicants had original research publications, case reports or had given an oral or poster presentation in the field of dermatopathology.

Conclusions

Knowledge regarding the average applicant statistics for a dermatopathology fellowship will allow prospective applicants to evaluate their own applications for strengths and weaknesses. This will also provide institutions information regarding anticipated statistics for a competitive applicant pool.
Interference of functional monomers with polymerization efficiency of adhesives
Authors: Hanabusa Masao , Yoshihara Kumiko , Yoshida Yasuhiro , Okihara Takumi , Yamamoto Takatsugu , Momoi Yasuko , Van Meerbeek Bart
Published: February 2016

The degree of conversion (DC) of camphorquinone/amine‐based adhesives is affected by acidic functional monomers as a result of inactivation of the amine co‐initiator through an acid–base reaction. During bonding, functional monomers of self‐etch adhesives chemically interact with hydroxyapatite (HAp). Here, we tested in how far the latter interaction of functional monomers with HAp counteracts the expected reduction in DC of camphorquinone/amine‐based adhesives. The DC of three experimental adhesive formulations, containing either of the two functional monomers [10‐methacryloyloxydecyl dihydrogen phosphate (10‐MDP) or 4‐methacryloxyethyl trimellitic acid anhydride (4‐META)] or no functional monomer (no‐FM; control), was measured with and without HAp powder added to the adhesive formulations. Both the variables ‘functional monomer’ and ‘HAp’ were found to be significant, with the functional monomer reducing the DC and HAp counteracting this effect. It is concluded that the functional monomers 10‐MDP and 4‐META interfere with the polymerization efficiency of adhesives. This interference is less prominent in the presence of HAp, which would clinically correspond to when these two functional monomers of the adhesive simultaneously interact with HAp in tooth tissue.
Identification of an HV1 voltage‐gated proton channel in insects
Authors: Chaves Gustavo , Derst Christian , Franzen Arne , Mashimo Yuta , Machida Ryuichiro , Musset Boris
Published: February 2016

The voltage‐gated proton channel 1 (HV1) is an important component of the cellular proton extrusion machinery and is essential for charge compensation during the respiratory burst of phagocytes. HV1 has been identified in a wide range of eukaryotes throughout the animal kingdom, with the exception of insects. Therefore, it has been proposed that insects do not possess an HV1 channel. In the present study, we report the existence of an HV1‐type proton channel in insects. We searched insect transcriptome shotgun assembly (TSA) sequence databases and found putative HV1 orthologues in various polyneopteran insects. To confirm that these putative HV1 orthologues were functional channels, we studied the HV1 channel of Nicoletia phytophila (NpHV1), an insect of the Zygentoma order, in more detail. NpHV1 comprises 239 amino acids and is 33% identical to the human voltage‐gated proton channel 1. Patch clamp measurements in a heterologous expression system showed proton selectivity, as well as pH‐ and voltage‐dependent gating. Interestingly, NpHV1 shows slightly enhanced pH‐dependent gating compared to the human channel. Mutations in the first transmembrane segment at position 66 (Asp66), the presumed selectivity filter, lead to a loss of proton‐selective conduction, confirming the importance of this aspartate residue in voltage‐gated proton channels.

Database

Nucleotide sequence data have been deposited in the GenBank database under accession number KT780722.
Beginning Learners' Development of Interactional Competence: Alignment Activity
Authors: Tecedor Marta
Published: February 2016

This study examined the development of interactional competence (Hall, 1993; He & Young, 1998) by beginning learners of Spanish as indexed by their use of alignment moves. Discourse analysis techniques and quantitative data analysis were used to explore how 52 learners expressed alignment and changes in participation patterns in two sets of instructional peer‐to‐peer conversations. The results of the analyses show that, although subject to great individual variability and not always following native‐like standards, English native speakers in the early stages of learning Spanish are able to express varying degrees of alignment in conversations with a peer of a similar proficiency level. As they strive to create a sphere of mutual understanding, they test different options from their linguistic repertoire and learn not only from their own attempts but also from those of their interlocutor. These results suggest that repeated engagement in interactional practice does provide the linguistic, social, and pedagogical affordances learners need to develop the interactional skills that will serve them well not only to build confidence and competence in the classroom learning context, but also hopefully in the world outside the classroom.
Comparing the OPI and the OPIc: The Effect of Test Method on Oral Proficiency Scores and Student Preference
Authors: Thompson Gregory L. , Cox Troy L. , Knapp Nieves
Published: February 2016

While studies have been done to rate the validity and reliability of the Oral Proficiency Interview (OPI) and Oral Proficiency Interview–Computer (OPIc) independently, a limited amount of research has analyzed the interexam reliability of these tests, and studies have yet to be conducted comparing the results of Spanish language learners who take both exams. For this study, 154 Spanish language learners of various proficiency levels were divided into two groups and administered both the OPI and OPIc within a 2‐week period using a counterbalanced design. In addition, study participants took both a pre‐ and postsurvey that gathered data about their language learning background, familiarity with the OPI and OPIc, preparation and test‐taking strategies, and evaluations of each exam. The researchers found that 54.5% of the participants received the same rating on the OPI and OPIc, with 13.6% of examinees scoring higher on the OPI and 31.8% scoring higher on the OPIc. While the results found that students scored significantly better on the OPIc, the overall effect size was quite small. The authors also found that the overwhelming majority of the participants preferred the OPI to the OPIc. This research begins to fill important gaps and provides empirical data to examine the comparability of the Spanish OPI and OPIc.
Habitat engineering by beaver benefits aquatic biodiversity and ecosystem processes in agricultural streams
Authors: Law Alan , McLean Fiona , Willby Nigel J.
Published: February 2016

Small‐scale discontinuities, formed by accumulations of wood, are recognised as a key feature of functionally intact forested streams because they promote organic matter retention, increase habitat complexity and provide flow refugia. Re‐establishing such features in physically degraded streams is therefore a common priority for restoration schemes. Ecosystem engineering by beavers in the form of dam building might offer a natural mechanism for restoring degraded streams. Despite an increase in beaver reintroductions globally, the ecosystem engineering concept has rarely been applied to restoring biodiversity and ecosystem function, especially within degraded freshwater systems.

By comparing multiple beaver‐modified and unmodified sites on headwater streams draining 13 ha of pastureland in eastern Scotland, U.K., we investigated if hydromorphological changes caused by reintroduced beavers (Castor fiber) translate into desirable biological responses when there is a long history of physical degradation and contraction of the regional species pool due to agricultural land use.

Beaver modified in‐stream habitat by constructing 10 dams, thus creating a series of interconnected dam pools. Organic matter retention and aquatic plant biomass increased (7 and 20 fold higher respectively) in beaver ponds relative to unmodified channels, consistent with the lower fluctuation in stream stage observed below a series of dams. Growing season concentrations of extractable P and NO3 were on average 49% and 43% lower respectively below a series of dams than above, although colour and suspended solids concentrations increased.

Macroinvertebrate samples from beaver‐modified habitats were less taxon rich (alpha diversity on average 27% lower) than those from unmodified stream habitat. However, due to significant compositional differences between beaver versus unmodified habitats, a composite sample from all habitats indicated increased richness at the landscape scale; gamma diversity was 28% higher on average than in the absence of beaver‐modified habitat. Feeding guild composition shifted from grazer/scraper and filter feeder dominance in unmodified habitats to shredder and collector‐gatherer dominance in beaver‐created habitats.

Dam building by beaver in degraded environments can improve physical and biological diversity when viewed at a scale encompassing both modified and unmodified habitats. By restoring ecosystem processes locally, it may also offer wider scale benefits, including greater nutrient retention and flood attenuation. These benefits should be evaluated against evidence of any negative effects on land use or fisheries.
Nuclear magnetic resonance analysis of the conformational state of cancer mutant of fibroblast growth factor receptor 1 tyrosine kinase domain
Authors: Kobashigawa Yoshihiro , Amano Shinjiro , Yoza Kaito , Himeno Rika , Amemiya Shun , Morioka Hiroshi , Yokogawa Mariko , Kumeta Hiroyuki , Schlessinger Joseph , Inagaki Fuyuhiko
Published: February 2016

Tyrosine kinases are key enzymes that play critical roles in growth signaling, the abnormal activation of which is associated with various human cancers. Activation of tyrosine kinases is mediated by tyrosine phosphorylation in the activation‐loop, which transforms the catalytic domain to the active state conformation. Cancer mutations are supposed to transform the conformation of the catalytic domain into the active‐form independent of the phosphorylation state of the activation‐loop. Here, we report structural and biophysical analyses of cancer mutations of the tyrosine kinase domain of fibroblast growth factor receptor 1 (FGFR1). Based on the nuclear magnetic resonance analyses, phosphorylation of the activation‐loop exhibited cooperative structural transition in the activation‐loop, C‐helix and P‐loop regions, whereas cancer mutations induced structural transformation at either one or two of these regions.
Breaking Patterns? How Female Scientists Negotiate their Token Role in their Life Stories
Authors: Haas Marita , Koeszegi Sabine T. , Zedlacher Eva
Published: February 2016

Building upon token theory, this paper analyses coping behaviours of women in Science, Engineering and Technology (SET) through a professional identity perspective. It proposes that female scientists need to negotiate and balance conflicting aspects of their professional and gender identities throughout their career. A reconstructive biography analysis ofLeitmotifandGestaltof 15 life stories reveals that gender is the structuring element of the female scientists' self‐presentation. The paper presents two key cases which exemplify two alternative coping strategies: the women either use asimilarity strategy, relying on full assimilation to the masculine norms in SET, or adifference strategy, highlighting their otherness and their struggle for equality. The in‐depth analysis reveals that both strategies cannot ‘break patterns', but instead leave the dominance of masculine norms in SET unchallenged. Implications of these findings are discussed.
The Pharmacology of Indomethacin
Authors: Lucas Sylvia
Published: February 2016

Background

Over 50 years ago, indomethacin emerged as an extremely potent non‐steroidal anti‐inflammatory drug (NSAID) during a massive effort to find effective anti‐inflammatory and analgesic medications. The 1960s saw acetic acid derivatives developed into indomethacin, diclofenac, and sulindac, and propionic derivatives into ibuprofen, naproxen, and ketoprofen. Indomethacin was likely the most potent of these compounds and one of the earliest to enter clinical trials. It is not surprising that indomethacin was among the first of the NSAID medications to be used in treatment of migraine and for headaches that eventually became known as “indomethacin‐responsive” headache disorders. Potential pharmacokinetic and bio‐mechanistic differences between indomethacin and other NSAIDs are of great clinical and research interest to explain this observation.

Methods/Results

The present article summarizes pharmacologic properties of indomethacin, including pharmacokinetics with particular attention to its distribution into the central nervous system, adverse effects, drug interactions, and mechanisms of action. Data are emphasized where differences in biomechanisms are found between indomethacin and other NSAIDs. The use of indomethacin in pregnant and lactating women is reviewed.

Conclusions

NSAIDs easily enter the brain, but their high protein binding limits absolute amount of entry. All work similarly as either nonselective or selective cyclooxygenase inhibitors, but indomethacin may have more potent vasoconstrictive activity and unique direct neuronal or nitric oxide‐dependent inhibitory pathway activity.
Usual interstitial pneumonia in asbestos‐exposed cohorts – concurrent idiopathic pulmonary fibrosis or atypical asbestosis?
Authors: Attanoos Richard L , Alchami Fouad S , Pooley Frederick D , Gibbs Allen R
Published: February 2016

Aims

To determine whether usual interstitial pneumonia (UIP) pattern fibrosis is seen in asbestosis.

Methods and results

The occurrence of UIP pattern fibrosis was studied in four asbestos cohorts systematically referred following postmortem to the UK Pneumoconiosis Unit, Cardiff. The combined exposed workforce comprised >25 000 persons. Over the 17‐year period, 233 subjects were identified; 210 had degrees of interstitial fibrosis with a fibrotic non‐specific interstitial pneumonia pattern and subpleural accentuation, and three showed UIP pattern fibrosis. All three of these cases showed grade 4 fibrosis (honeycombing) with no asbestos fibre dose–response correlation. A Poisson distribution of probability analysis indicated that the observed cases of UIP in this workforce could be wholly accounted for by the prevalence of idiopathic pulmonary fibrosis (IPF) in the population.

Conclusions

UIP pattern fibrosis is rarely observed in asbestos‐exposed subjects, and shows no dose–response correlation with asbestos fibres on mineral analysis; this points to an alternative disease, such as IPF. The results indicate that UIP pattern fibrosis should not be regarded as genuine asbestosis, irrespective of the status of asbestos biomarkers, and this impacts upon the postmortem handling of asbestos‐related deaths.
Raptors as legitimate secondary dispersers of weed seeds
Authors: López‐Darias Marta , Nogales Manuel
Published: February 2016

Although raptors are not usually seen as seed dispersers, we demonstrate their important ecological role as legitimate seed dispersers of weeds. On the oceanic island of Fuerteventura in the Canary Islands, up to 11 000 weed seeds from a total of 39 and 62 different plant species, respectively, were found in 300 and 319 pellets, respectively, of two native predatory birds, the Common BuzzardButeo buteoand the Eurasian KestrelFalco tinnunculus, which consumed European RabbitsOryctolagus cuniculusand Barbary Ground SquirrelsAtlantoxerus getulus, both invasive mammals that carried these seeds in their guts. Four and seven weed species appeared with a frequency of occurrence greater than 10% in the pellets of Kestrels and Buzzards, respectively. Despite the time interval between pellet collection and germination experiments, almost 10% of planted seeds germinated, even after passing through two digestive processes, one inside the mammal and another inside the raptor. Our study encourages a change of perspective in this regard, as raptors may be involved in complex interactive dispersal processes on a wider geographical scale.
Indirect effects of mosquito control using Bti on dragonflies and damselflies (Odonata) in the Camargue
Authors: Jakob Christiane , Poulin Brigitte
Published: February 2016

Bacillus thuringiensis var. israelensis (Bti) has become the most commonly used larvicide to control mosquitoes worldwide. Bti is considered non‐toxic to most organisms, except some Diptera such as chironomids, which are a major prey in wetland food webs.

Although Odonata are important predators of mosquitoes and chironomids at the larval and adult stages, no study has ever considered the potential indirect effects of Bti on Odonata abundance through trophic interactions. We addressed this topic in the Camargue where 2500 of the 25 000 ha of mosquito larval biotopes are Bti‐sprayed (aqueous solution of VectoBac 12AS at 2.5 L ha−1) whenever mosquito larvae appear in water bodies (i.e. 30–50 aerial treatments overall annually).

Adult Odonata were surveyed along a 100‐m line transect in spring, summer and autumn at three control and three treated sites over a 5‐year period.

Mean number of species (9.9 vs. 5.2) and of individuals (100 vs. 50) detected per year were significantly higher in control areas compared to Bti‐sprayed areas. Bti treatment contributed to 87.3% of the explained variance in Odonata richness, compared to 2.9% for site, 6.8% for year and 3.0% for salinity effects.

These results are coherent with other studies carried out in the same area and time period highlighting a lower abundance of chironomids, and a lower intake of odonates by breeding birds in treated areas.

We conclude that mosquito control using Bti should be acknowledged as a potential threat to Odonata.
Physical and mechanical properties of Tunisian women hair
Authors: Sayahi E. , Harizi T. , Msahli S. , Sakli F.
Published: February 2016

Background

Mechanical analysis of human hair may provide the dermatologists with several markers of considerable diagnostic importance. The aim of this study was to analyse the physical and mechanical properties of Tunisian women's hair.

Methods

Surface characteristics were determined with scanning electron microscopy (SEM). Mechanical properties were studied using the Miniature Tensile Tester Model 675 (MTT675), and the Fibre Dimensional Analysis Unit Model 765 (FDAS765) of Dia‐Stron, UK, was used to measure the cross‐sectional area.

Results

The cross‐sectional area, stress at break, strain at break, elastic modulus and total work were 4643.21 ± 817 μm2, 201 ± 11.26 MPa, 47.3 ± 3.6%, 3.1 ± 0.16 GPa, and 9 ± 2.2 mJ, respectively. The effects of the factors ‘hair curliness’ and ‘age’ on the physical and mechanical properties were studied. The cross‐sectional area and the break load are influenced by the factors ‘age’ and ‘curl type’, whereas Young's modulus shows a significant dependency only on the age.

Conclusion

Tunisian women hair presented good mechanical properties as shown by a greater breaking stress and higher breaking strain. Both curl type and age are important factors to consider when evaluating the behaviour of hair.
Efficacy of three different pulpotomy agents in primary molars: a randomized control trial
Authors: Rajasekharan S. , Martens L. C. , Vandenbulcke J. , Jacquet W. , Bottenberg P. , Cauwels R. G. E. C.
Published: February 2016

Aim

To compare the clinical and radiographic efficacy of Biodentine™, ProRoot® White Mineral Trioxide Aggregate (WMTA) and Tempophore™ as pulpotomy medicaments in the treatment of carious primary molars.

Methodology

A parallel‐design, randomized controlled trial was developed. Patients above 3 years of age with carious primary teeth with vital pulps without spontaneous pain or history of swelling were included. Fifty‐eight patients (82 teeth) with a mean age of 4.79 ± 1.23 years were included. The teeth were randomized, blinded and allocated to one of the three groups (Biodentine™, ProRoot® WMTA or Tempophore™) for pulpotomy treatment. All teeth were followed up clinically and radiographically (after 6, 12 and 18 months) by two blinded calibrated investigators. A generalized estimating equation (GEE), Wald chi‐square test and an intention‐to‐treat analysis (ITT) with ‘last carried forward’ approach were performed using Statistical Package for Social Sciences v 21.0 (IBM Corp., Armonk, NK, USA).

Results

Forty‐six patients and 69 teeth were available for follow‐up after 18 months. Clinical success (radiographic success in parenthesis) was 95.24% (94.4%), 100% (90.9%) and 95.65% (82.4%) in the Biodentine™, ProRoot® WMTA and Tempophore™ groups, respectively, but the difference was not significant. Pulp canal obliteration was significantly different amongst the experimental groups as the Biodentine™ group exhibited significantly more pulp canal obliteration when compared to the ProRoot® WMTA group at 6 months (P = 0.008) and 18 months (P = 0.003).

Conclusions

After 18‐month follow‐up, there was no significant difference between Biodentine™ in comparison with ProRoot® WMTA or Tempophore™.
Secukinumab improves patient‐reported psoriasis symptoms of itching, pain, and scaling: results of two phase 3, randomized, placebo‐controlled clinical trials
Authors: Strober Bruce , Sigurgeirsson Bárður , Popp Georg , Sinclair Rodney , Krell James , Stonkus Sigitas , Septe Marcis , Elewski Boni E. , Gottlieb Alice B. , Zhao Yang , Tran Mary H. , Karpov Alexander , McLeod Lori D. , Mordin Margaret , Papavassilis Charis , Nyirady Judit , Lebwohl Mark
Published: February 2016

Background

Secukinumab is a human interleukin‐17A antagonist indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The objective of this analysis was to measure the treatment response on psoriasis‐related itching, pain, and scaling via the Psoriasis Symptom Diary (PSD)©.

Methods

ERASURE (n = 738) and FIXTURE (n = 1306) were double‐blind, multicenter phase 3 studies in adults randomized to secukinumab (300, 150 mg, n = 1144) or placebo (n = 574) (administered at Weeks 0, 1, 2, 3, and 4, followed by dosing every 4 weeks) or a biologic active control (FIXTURE only). Patient‐reported itching, pain, and scaling were assessed during the first 12 weeks of treatment using the PSD.

The results reported here are limited to subjects in the secukinumab and placebo treatment groups who completed the PSD. The proportions of subjects achieving prespecified responses (improvement:reduction of at least 2.2 points for itching, 2.2 points for pain, or 2.3 points for scaling) were compared for secukinumab versus placebo.

Results

Overall, 39% of subjects completed the PSD at baseline and Week 12 (n = 453 secukinumab; 225 placebo). Subjects treated with secukinumab achieved significantly greater improvements in itching, pain, and scaling at Week 12 versus placebo (all P < 0.0001) and had significantly greater proportions of itching, pain, and scaling responders at Week 12 versus placebo (all P < 0.05).

Conclusion

Secukinumab significantly improves patient‐reported itching, pain, and scaling in adults with moderate to severe psoriasis compared with placebo.
Glycosylated haemoglobin assessment in diabetic patients with acute coronary syndromes
Authors: Snir A. , Dabin B. , Hyun K. , Yamen E. , Ryan M. , Aliprandi‐Costa B. , Brieger D.
Published: February 2016

Background

Guidelines for the management of acute coronary syndromes (ACS) advocate for maintaining adequate long‐term glycaemic control in diabetic patients. Glycosylated haemoglobin (HbA1c) measurement is commonly used to monitor long‐term glycaemic control in diabetes.

Aims

To evaluate the frequency and clinical predictors of in‐hospital HbA1c measurement in diabetic patients presenting with ACS and the relationship between HbA1c assessment and mortality following discharge.

Methods

This registry‐based cohort study included 1743 diabetic patients from 33 representative hospitals across Australia with a final diagnosis of ACS. Independent predictors of HbA1c assessment were evaluated using a multivariable logistic generalised estimating equations analysis. The association between HbA1c assessment and mortality following discharge was evaluated using Cox proportional hazard analysis.

Results

Seven hundred and fourteen (41%) patients had HbA1c assessment during admission. Frequency of assessment varied markedly between hospitals (7.7–87.6%). HbA1c assessment was significantly more frequent in hospitals with catheterisation laboratories. Frequency of assessment was not associated with location of hospital (rural vs urban) or hospital capacity. Independent clinical predictors of HbA1c assessment across participating hospitals were younger age, ST‐Elevation Myocardial Infarction, cardiac catheterisation and coronary artery bypass surgery during admission. HbA1c assessment was associated with higher rates of coronary catheterisation, revascularisation and receipt of evidence‐based medicines but not with mortality during 6 months following discharge (hazard ratio, 0.48; 95% confidence interval, 0.19–1.18).

Conclusion

Frequency of HbA1c assessment varies markedly between hospitals, and most diabetic patients admitted for ACS in Australia do not receive assessment of pre‐admission glycaemic control. HbA1c assessment was associated with better evidence driven medical care.
The epidemiology of in‐hospital cardiac arrests in Australia and New Zealand
Authors: Fennessy G. , Hilton A. , Radford S. , Bellomo R. , Jones D.
Published: February 2016

Background

The epidemiology of in‐hospital cardiac arrests (IHCA) in Australia and New Zealand (ANZ) has not been systematically assessed.

Aim

To conduct a systematic review of the frequency, characteristics and outcomes of adult IHCA in ANZ.

Methods

Medline search for studies published in 1964–2014 using MeSH terms ‘arrest AND hospital AND Australia’, ‘arrest AND hospital AND New Zealand’, ‘inpatient AND arrest AND Australia’ and ‘inpatient AND arrest AND New Zealand’.

Results

We screened 934 studies, analysed 50 and included 30. Frequency of IHCA ranged from 1.31 to 6.11 per 1000 admissions in 4 population studies and 0.58 to 4.59 per 1000 in 16 cohort studies. The frequency was 4.11 versus 1.32 per 1000 admissions in hospitals with rapid response system (RRS) compared with those without (odds ratio: 0.32; 95% confidence interval 0.28‐0.37; P < 0.001). On aggregate, the initial cardiac rhythm was ventricular tachycardia/fibrillation in 31.4% (range 19.0–48.8%) in 10 studies reporting such data. On aggregate, IHCA were witnessed in 80.2% cases (three studies) and monitored patients in 53.4% cases (four studies). Details of life support were poorly documented. On aggregate, return of spontaneous circulation occurred in 46.0% of patients. Overall, 74.6% (range 59.4–77.5%) died in‐hospital but survival was higher among monitored or younger patients, in those with a shockable rhythm, or during working hours.

Conclusion

IHCA are uncommon in ANZ and three quarters die in‐hospital. However, their frequency varies markedly across institutions and may be affected by the presence of RRS. Where reported, the long‐term outcomes survivors appear to have acceptable neurological outcomes.
Fostering of advanced mutualism with gut microbiota by Immunoglobulin A
Authors: Sutherland Duncan B. , Suzuki Keiichiro , Fagarasan Sidonia
Published: February 2016

Immunoglobulin A (IgA), the most abundantly secreted antibody isotype in mammals, not only provides direct immune protection to neonates via maternal milk but also helps program the infant immune system by regulating the microbiota. IgA continues to maintain dynamic interactions with the gut microbiota throughout life and this influences immune system homeostasis as well as other physiological processes. The secretory IgA produced independently of T‐cell selection are commonly referred to as natural or innate antibodies. Our studies have shown that innate‐IgA, while effective at excluding microorganisms from the gut, does not promote mutualism with the microbiota in the same way as adaptive‐IgA that is selected in T cell‐dependent germinal center reactions. Adaptive‐IgA fosters more advanced mutualism with the microbiota than innate‐IgA by selecting and diversifying beneficial microbial communities. In this review, we suggest that the diversified microbiota resulting from adaptive‐IgA pressure was pivotal in promoting ecological adaptability and speciation potential of mammals.
Targeting plasma cells: are we any closer to a panacea for diseases of antibody‐secreting cells?
Authors: Low Michael , Infantino Simona , Grigoriadis George , Tarlinton David
Published: February 2016

Antibody‐secreting cells (ASCs) are critical for a functional and effective adaptive immune system. In a number of illnesses, however, these same cells contribute to the underlying disease state leading to significant morbidity and mortality. While therapeutic targeting of antibody‐secreting cells has progressed significantly over the last two decades, many of these conditions remain major health problems. In this review, we will discuss current and potential therapeutic targeting of ASCs in the context of the known biology of these cells.
Immunogenicity of therapeutic recombinant immunotoxins
Authors: Mazor Ronit , Onda Masanori , Pastan Ira
Published: February 2016

Recombinant immunotoxins (RITs) are chimeric proteins designed to treat cancer. They are made up of an Fv or Fab that targets an antigen on a cancer cell fused to a 38‐kDa portion of Pseudomonas exotoxin A (PE38). Because PE38 is a bacterial protein, it is highly immunogenic in patients with solid tumors that have normal immune systems, but much less immunogenic in patients with hematologic malignancies where the immune system is suppressed. RITs have shown efficacy in refractory hairy cell leukemia and in some children with acute lymphoblastic leukemia, but have been much less effective in solid tumors, because neutralizing antibodies develop and prevent additional treatment cycles. In this paper we will (i) review data from clinical trials describing the immunogenicity of PE38 in different patient populations; (ii) review results from clinical trials using different immunosuppressive drugs; and (iii) describe our efforts to make new less‐immunogenic RITs by identifying and removing T‐ and B‐cell epitopes to hide the RIT from the immune system.
Immunocytokines and bispecific antibodies: two complementary strategies for the selective activation of immune cells at the tumor site
Authors: Kiefer Jonathan D. , Neri Dario
Published: February 2016

The activation of the immune system for a selective removal of tumor cells represents an attractive strategy for the treatment of metastatic malignancies, which cannot be cured by existing methodologies. In this review, we examine the design and therapeutic potential of immunocytokines and bispecific antibodies, two classes of bifunctional products which can selectively activate the immune system at the tumor site. Certain protein engineering aspects, such as the choice of the antibody format, are common to both classes of therapeutic agents and can have a profound impact on tumor homing performance in vivo of individual products. However, immunocytokines and bispecific antibodies display different mechanisms of action. Future research activities will reveal whether an additive of even synergistic benefit can be obtained from the judicious combination of these two types of biopharmaceutical agents.
Sweeping antibody as a novel therapeutic antibody modality capable of eliminating soluble antigens from circulation
Authors: Igawa Tomoyuki , Haraya Kenta , Hattori Kunihiro
Published: February 2016

Monoclonal antibodies have become a general modality in therapeutic development, and a variety of monoclonal antibodies targeting soluble antigens have been developed. However, even with infinite binding affinity to an antigen, a conventional antibody can bind to the antigen only once and results in an increase in total plasma antigen concentration in vivo. This antibody‐mediated antigen accumulation generally occurs because the clearance from circulation of an antibody–antigen complex is much slower than that of a free antigen. This limitation has recently been overcome by sweeping antibodies, which are capable of actively eliminating soluble antigens from circulation. A sweeping antibody incorporates two antibody engineering technologies: one is variable region engineering to enable the antibody to bind to an antigen in plasma and dissociate from the antigen in endosome (after which the antigen undergoes lysosomal degradation), and the other is constant region engineering to increase the cellular uptake of the antibody–antigen complex into endosome. By enhancing the elimination of soluble antigens from circulation, sweeping antibodies can therapeutically target soluble antigens that conventional antibodies cannot. This review discusses the features, engineering technologies, advantages, and applications of sweeping antibodies that target soluble antigens.
Harnessing T cells to fight cancer with BiTE® antibody constructs – past developments and future directions
Authors: Klinger Matthias , Benjamin Jonathan , Kischel Roman , Stienen Sabine , Zugmaier Gerhard
Published: February 2016

Bispecific T‐cell engager (BiTE®) antibody constructs represent a novel immunotherapy that bridges cytotoxic T cells to tumor cells, thereby inducing target cell‐dependent polyclonal T‐cell activation and proliferation, and leading to apoptosis of bound tumor cells. Anti‐CD19 BiTE® blinatumomab has demonstrated clinical activity in Philadelphia chromosome (Ph)‐negative relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) eventually resulting in conditional approval by the U.S. Food and Drug Administration in 2014. This drug is currently further developed in pediatric and Ph+ r/r, as well as in minimal residual disease‐positive ALL, and might also offer clinical benefit for patients with non‐Hodgkin's lymphoma, especially for those with aggressive forms like diffuse large B‐cell lymphoma. Another BiTE® antibody construct in hemato‐oncology designated AMG 330 targets CD33 on acute myeloid leukemia blast cells. After showing promising ex vivo activity, this drug candidate has recently entered phase 1 clinical development, and has further indicated potential for combination with checkpoint inhibitors. In solid tumor indications, three BiTE® antibody constructs have been tested in phase 1 studies so far: anti‐EpCAM BiTE® AMG 110, anti‐CEA BiTE® MEDI‐565/AMG 211, and anti‐PSMA BiTE® BAY2010112/AMG 212. Pertinent questions comprise how to maximize BiTE® penetration and T‐cell infiltration of the tumor while simultaneously minimizing any adverse events, which is currently explored by a continuous intravenous infusion approach. Thus, BiTE® antibody constructs will hopefully provide new treatment options for patients in several indications with high unmet medical need.
Stable long‐term cultures of self‐renewing B cells and their applications
Authors: Kwakkenbos Mark J. , van Helden Pauline M. , Beaumont Tim , Spits Hergen
Published: February 2016

Monoclonal antibodies are essential therapeutics and diagnostics in a large number of diseases. Moreover, they are essential tools in all sectors of life sciences. Although the great majority of monoclonal antibodies currently in use are of mouse origin, the use of human B cells to generate monoclonal antibodies is increasing as new techniques to tap the human B cell repertoire are rapidly emerging. Cloned lines of immortalized human B cells are ideal sources of monoclonal antibodies. In this review, we summarize our studies to the regulation of the replicative life span, differentiation, and maturation of B cells that led to the development of a platform that uses immortalization of human B cells by in vitro genetic modification for antibody development. We describe a number of human antibodies that were isolated using this platform and the application of the technique in other species. We also discuss the use of immortalized B cells as antigen‐presenting cells for the discovery of tumor neoantigens.
Discovery and bio‐optimization of human antibody therapeutics using the XenoMouse® transgenic mouse platform
Authors: Foltz Ian N. , Gunasekaran Kannan , King Chadwick T.
Published: February 2016

Since the late 1990s, the use of transgenic animal platforms has transformed the discovery of fully human therapeutic monoclonal antibodies. The first approved therapy derived from a transgenic platform – the epidermal growth factor receptor antagonist panitumumab to treat advanced colorectal cancer – was developed using XenoMouse® technology. Since its approval in 2006, the science of discovering and developing therapeutic monoclonal antibodies derived from the XenoMouse® platform has advanced considerably. The emerging array of antibody therapeutics developed using transgenic technologies is expected to include antibodies and antibody fragments with novel mechanisms of action and extreme potencies. In addition to these impressive functional properties, these antibodies will be designed to have superior biophysical properties that enable highly efficient large‐scale manufacturing methods. Achieving these new heights in antibody drug discovery will ultimately bring better medicines to patients. Here, we review best practices for the discovery and bio‐optimization of monoclonal antibodies that fit functional design goals and meet high manufacturing standards.
Increased Night Temperatures During Cotton's Early Reproductive Stage Affect Leaf Physiology and Flower Bud Carbohydrate Content Decreasing Flower Bud Retention
Authors: Loka D. A. , Oosterhuis D. M.
Published: February 2016

Higher than optimum temperatures during cotton's (Gossypium hirsutum L.) growing season is a common occurrence in cotton‐growing areas around the world with negative consequences on productivity. According to climate projections, night temperatures are expected to increase more than day temperatures. The objective of this study was to monitor and record the effects of higher than optimum night temperatures during cotton's early reproductive stage on physiological (photosynthesis, respiration and membrane damage) and biochemical (leaf adenosine triphosphate (ATP) levels, as well as glutathione reductase (GR) content and soluble carbohydrate concentrations of the leaf subtending the flower buds. Number, dry weight, carbohydrate concentrations and GR levels of flower buds were also measured at the end of the experiment. Growth chamber experiments were conducted using cotton cultivar ST 5288 B2RF and treatments consisted of normal day/night temperatures (32/24 °C) and high night temperatures (32/30 °C) for 7 days at squaring (approximately 4 weeks after planting). The results indicated that high night temperatures had an immediate effect on leaf respiration rates and membrane damage by significantly increasing them compared to the control and a similar pattern was observed on leaf photosynthesis and ATP levels that were markedly decreased. Leaf GR levels were also substantially increased under conditions of high night temperatures, in contrast to flower bud GR content which remained unaffected. High night temperatures had a significant effect on leaf carbohydrate concentrations resulting in significant decreases in hexose, sucrose and starch levels. Nevertheless, flower bud sucrose content was substantially increased under conditions of high night temperatures, while hexose content was decreased and starch concentrations remained unaffected. A detrimental effect of elevated night temperatures on the number of flower buds per plant and on the dry weight of flower buds was observed, and it was concluded that high night temperatures had a negative effect on cotton flower bud production due to disruptions on flower bud carbohydrate metabolism as a result of the insufficient GR response.
Dipping in Ambulatory Blood Pressure Monitoring Correlates With Overnight Urinary Excretion of Catecholamines and Sodium
Authors: Därr Roland , Bursztyn Michael , Pamporaki Christina , Peitzsch Mirko , Siegert Gabriele , Bornstein Stefan R. , Eisenhofer Graeme
Published: February 2016

Nondipping blood pressure (BP) is associated with increased morbidity and mortality. This study examines the relationship of “dipping” in 24‐hour ambulatory BP monitoring (ABPM) with awake and sleeping urinary norepinephrine (NE) and epinephrine (EPI), and that of urinary NE and EPI with urinary sodium (UNa). Fifty nondippers and 65 dippers were included in the present study. Collected data included age, sex, body mass index, history of hypertension, current antihypertensive treatment, ABPM data, and NE, EPI, and UNa values. Hierarchical multiple regression analysis with the night‐to‐day ratio (NDR) of systolic BP as a dependent variable showed that the composite term of the NDRs of urinary NE and EPI was a significant predictor for dipping. Results also show a differential role of NE and EPI in circadian UNa excretion in dippers and nondippers. These results indicate that the sympathetic nervous system is involved in the regulation of circadian BP variations and UNa excretion.
Functional TRPV2 and TRPV4 channels in human cardiac c‐kit+ progenitor cells
Authors: Che Hui , Xiao Guo‐Sheng , Sun Hai‐Ying , Wang Yan , Li Gui‐Rong
Published: February 2016

The cellular physiology and biology of human cardiac c‐kit+ progenitor cells has not been extensively characterized and remains an area of active research. This study investigates the functional expression of transient receptor potential vanilloid (TRPV) and possible roles for this ion channel in regulating proliferation and migration of human cardiac c‐kit+ progenitor cells. We found that genes coding for TRPV2 and TRPV4 channels and their proteins are significantly expressed in human c‐kit+ cardiac stem cells. Probenecid, an activator of TRPV2, induced an increase in intracellular Ca2+ (Ca2+i), an effect that may be attenuated or abolished by the TRPV2 blocker ruthenium red. The TRPV4 channel activator 4α‐phorbol 12‐13‐dicaprinate induced Ca2+i oscillations, which can be inhibited by the TRPV4 blocker RN‐1734. The alteration of Ca2+i by probenecid or 4α‐phorbol 12‐13‐dicprinate was dramatically inhibited in cells infected with TRPV2 short hairpin RNA (shRNA) or TRPV4 shRNA. Silencing TRPV2, but not TRPV4, significantly reduced cell proliferation by arresting cells at the G0/G1 boundary of the cell cycle. Cell migration was reduced by silencing TRPV2 or TRPV4. Western blot revealed that silencing TRPV2 decreased expression of cyclin D1, cyclin E, pERK1/2 and pAkt, whereas silencing TRPV4 only reduced pAkt expression. Our results demonstrate for the first time that functional TRPV2 and TRPV4 channels are abundantly expressed in human cardiac c‐kit+ progenitor cells. TRPV2 channels, but not TRPV4 channels, participate in regulating cell cycle progression; moreover, both TRPV2 and TRPV4 are involved in migration of human cardiac c‐kit+ progenitor cells.
Effect of Instrument Lubricants on the Surface Degree of Conversion and Crosslinking Density of Nanocomposites
Authors: de Paula Felipe Costa , Valentin Regis de Souza , Borges Boniek Castillo Dutra , Medeiros Maria Cristina dos Santos , de Oliveira Raiza Freitas , da Silva Ademir Oliveira
Published: February 2016

Purpose

The surface degree of conversion and crosslink density of composites should not be affected by the use of instrument lubricants in order to provide long‐lasting tooth restorations. This study aimed to analyze the effect of instrument lubricants on the degree of conversion and crosslink density of nanocomposites.

Materials and Methods

Samples (N = 10) were fabricated according to the composites (Filtek Z350 XT, 3M ESPE, St. Paul, MN, USA; and IPS Empress Direct, Ivoclar Vivadent AG, Schaan, Liechtenstein and lubricants used (Adper Single Bond 2 and Scotchbond Multi‐Purpose bonding agent adhesive systems, 3M ESPE; 70% ethanol, absolute ethanol, and no lubricant). Single composite increments were inserted into a Teflon mold using the same dental instrument. The composite surface was then modeled using a brush wiped with each adhesive system and a spatula wiped with each ethanol. The control group was fabricated with no additional modeling. The surface degree of conversion and crosslink density were measured by Fourier transform infrared spectroscopy and the hardness decrease test, respectively. Data were analyzed using two‐way analysis of variance and the Tukey's test (p < 0.05).

Results

Filtek Z350 XT showed statistically similar degree of conversion regardless of the lubricant used, whereas the use of adhesive systems and 70% ethanol decreased the degree of conversion for IPS Empress Direct. Only Scotchbond Multi‐Purpose bonding agent decreased crosslink density for Filtek Z350 XT, whereas both adhesive systems decreased crosslink density for IPS Empress Direct.

Conclusion

Filtek Z350 XT appeared to be less sensitive to the effects of lubricants, and absolute ethanol did not affect the degree of conversion and crosslink density of the nanocomposites tested.

Clinical Significance

Although the use of lubricants may be recommended to minimize the stickiness of dental instruments and composite resin, dentists should choose materials that do not have a negative effect on the surface properties of composites. Only the use of absolute ethanol safely maintains the surface integrity of nanocomposites in comparison with adhesive system and 70% ethanol.