bluuebunny/crossref_metadata_2025 huggingface dataset:
Daylight PDT with MAL – current data and practical recommendations of an expert panel
Authors: Philipp‐Dormston Wolfgang G. , Karrer Sigrid , Petering Holger , Ulrich Claas , Dirschka Thomas , Berking Carola , Lonsdorf Anke S. , Gerber Peter Arne , Radakovic Sonja , Hunger Robert E. , Szeimies Rolf‐Markus
Published: November 2015

Photodynamic Therapy (PDT) is one of the standard treatment modalities for actinic keratoses (AKs). Daylight PDT (DL‐PDT) with MAL cream is a rather recent development, which, instead of an artificial light source, uses daylight for the activation of the photosensitizer. The present review summarizes available data based on a selective literature search, highlights practical aspects, and reflects the authors’ expert knowledge in using DL‐PDT. With respect to efficacy, study data shows that DL‐PDT is noninferior to conventional PDT (cPDT). However, given that DL‐PDT is markedly less painful, it is significantly better tolerated than cPDT. In Europe, DL‐PDT can be performed from March to October, on sunny as well as on cloudy days. UV protection of untreated areas of the body should be observed. Outside temperature should not fall below 10°C. On hot days, patients should be advised to stay in the shade if necessary. Representing a useful addition to current therapeutic options, DL‐PDT with MAL cream is, among others, suitable for patients with field cancerization and/or those who have experienced severe pain associated with cPDT.
Systemtherapie des metastasierten malignen Melanoms
Authors: Rauschenberg Ricarda , Garzarolli Marlene , Dietrich Ursula , Beissert Stefan , Meier Friedegund
Published: November 2015

Für Patienten mit metastasiertem Melanom stehen aktuell mehrere wirksame Therapieoptionen zur Verfügung. Die BRAF‐Inhibitoren Vemurafenib und Dabrafenib zeichnen sich durch eine rasche Tumorkontrolle und hohe Ansprechraten aus. In Kombination mit den MEK‐Inhibitoren Trametinib bzw. Cobimetinib erreichen sie Ansprechraten (CR + PR, komplette plus partielle Remissionen) von 70 %, wobei die Entwicklung einer Therapieresistenz verzögert wird, sowie ein medianes Gesamtüberleben von > 2 Jahren bei tolerablen Nebenwirkungen.

Der CTLA‐4‐Antikörper Ipilimumab erzielte für Patienten mit metastasiertem Melanom als erste Substanz eine signifikante Verlängerung des Gesamtüberlebens (Langzeitüberlebensrate: 20–26 %). Verzögertes Therapieansprechen und schwere immunvermittelte Nebenwirkungen können den therapeutischen Benefit einschränken. Die Monotherapie mit den PD‐1‐Antikörpern Nivolumab oder Pembrolizumab erreicht Ansprechraten (CR + PR) bis zu 45 % und 1‐Jahres‐Überlebensraten von > 70 % bei meist guter Verträglichkeit. Die Kombination Ipilimumab plus Nivolumab zeigte Ansprechraten bis zu 58 % und ein medianes progressionsfreies Überleben von > 11 Monaten. Von dieser Kombination wird ein zeitnahes und lang anhaltendes Ansprechen erwartet. Dieser potenzielle Benefit wird durch eine hohe Toxizität erkauft.

Aktuell werden in klinischen Studien Strategien für Therapiesequenz und ‐kombinationen geprüft. Insgesamt hat sich die Prognose für Patienten mit metastasiertem Melanom signifikant verbessert. In Anbetracht eines möglichen Langzeitüberlebens müssen neben akuten Nebenwirkungen auch die Langzeit‐Nebenwirkungen einer Behandlung berücksichtigt werden.
Sex differences in relationships between habitat use and reproductive performance in Soay sheep (Ovis aries)
Authors: Regan Charlotte. E. , Pilkington Jill. G. , Pemberton Josephine. M. , Crawley Michael. J.
Published: November 2015

The role of habitat use in generating individual variation in fitness has rarely been examined empirically in natural populations of long‐lived mammals, particularly for both sexes simultaneously. This is the case despite the increase in studies attempting to understand evolutionary change in such populations. Using data from the St. Kilda Soay sheep population, we quantified the association between lifetime reproductive performance (lifetime breeding and reproductive success) and the proportion of the home range covered by a key grass species, H. lanatus, for 490 females and 304 males. Increased H. lanatus cover was associated only with increased female lifetime reproductive success, but increased lifetime breeding success for both sexes, arising through increased male longevity and increased female fecundity. This work suggests that improved understanding of the causes and consequences of fitness differences will likely require us to better account for habitat‐derived individual variation, and to do so for the sexes appropriately.
Dispensability of the [4Fe‐4S] cluster in novel homologues of adenine glycosylase MutY
Authors: Trasviña‐Arenas Carlos H. , Lopez‐Castillo Laura M. , Sanchez‐Sandoval Eugenia , Brieba Luis G.
Published: November 2015

7,8‐Dihydro‐8‐deoxyguanine (8oG) is one of the most common oxidative lesions in DNA. DNA polymerases misincorporate an adenine across from this lesion. Thus, 8oG is a highly mutagenic lesion responsible for G:C→T:A transversions. MutY is an adenine glycosylase, part of the base excision repair pathway that removes adenines, when mispaired with 8oG or guanine. Its catalytic domain includes a [4Fe‐4S] cluster motif coordinated by cysteinyl ligands. When this cluster is absent, MutY activity is depleted and several studies concluded that the [4Fe‐4S] cluster motif is an indispensable component for DNA binding, substrate recognition and enzymatic activity. In the present study, we identified 46 MutY homologues that lack the canonical cysteinyl ligands, suggesting an absence of the [4Fe‐4S] cluster. A phylogenetic analysis groups these novel MutYs into two different clades. One clade is exclusive of the order Lactobacillales and another clade has a mixed composition of anaerobic and microaerophilic bacteria and species from the protozoan genus Entamoeba. Structural modeling and sequence analysis suggests that the loss of the [4Fe‐4S] cluster is compensated by a convergent solution in which bulky amino acids substitute the [4Fe‐4S] cluster. We functionally characterized MutYs from Lactobacillus brevis and Entamoeba histolytica as representative members from each clade and found that both enzymes are active adenine glycosylases. Furthermore, chimeric glycosylases, in which the [4Fe‐4S] cluster of Escherichia coli MutY is replaced by the corresponding amino acids of LbY and EhY, are also active. Our data indicates that the [4Fe‐4S] cluster plays a structural role in MutYs and evidences the existence of alternative functional solutions in nature.
Structural determinants of ligand binding in the ternary complex of human ileal bile acid binding protein with glycocholate and glycochenodeoxycholate obtained from solution NMR
Authors: Horváth Gergő , Bencsura Ákos , Simon Ágnes , Tochtrop Gregory P. , DeKoster Gregory T. , Covey Douglas F. , Cistola David P. , Toke Orsolya
Published: November 2015

Besides aiding digestion, bile salts are important signal molecules exhibiting a regulatory role in metabolic processes. Human ileal bile acid binding protein (I‐BABP) is an intracellular carrier of bile salts in the epithelial cells of the distal small intestine and has a key role in the enterohepatic circulation of bile salts. Positive binding cooperativity combined with site selectivity of glycocholate and glycochenodeoxycholate, the two most abundant bile salts in the human body, make human I‐BABP a unique member of the family of intracellular lipid binding proteins. Solution NMR structure of the ternary complex of human I‐BABP with glycocholate and glycochenodeoxycholate reveals an extensive network of hydrogen bonds and hydrophobic interactions stabilizing the bound bile salts. Conformational changes accompanying bile salt binding affects four major regions in the protein including the C/D, E/F and G/H loops as well as the helical segment. Most of these protein regions coincide with a previously described network of millisecond time scale fluctuations in the apo protein, a motion absent in the bound state. Comparison of the heterotypic doubly ligated complex with the unligated form provides further evidence of a conformation selection mechanism of ligand entry. Structural and dynamic aspects of human I‐BABP–bile salt interaction are discussed and compared with characteristics of ligand binding in other members of the intracellular lipid binding protein family.

Protein Data Bank Accession Numbers

The coordinates of the 10 lowest energy structures of the human I‐BABP : GCDA : GCA complex as well as the distance restraints used to calculate the final ensemble have been deposited in the Brookhaven Protein Data Bank with accession number 2MM3.
Improvement of renal dysfunction in a patient with hepatitis C virus‐related liver cirrhosis by daclatasvir and asunaprevir combination therapy: A case report
Authors: Tsuge Masataka , Hiramatsu Akira , Shinohara Fumi , Nakano Norihito , Nakamura Yuki , Hatooka Masahiro , Morio Kei , Morio Reona , Kan Hiromi , Fujino Hatsue , Uchida Takuro , Kobayashi Tomoki , Fukuhara Takayuki , Masaki Keiichi , Nakahara Takashi , Ono Atsushi , Nagaoki Yuko , Miki Daiki , Kawaoka Tomokazu , Hiraga Nobuhiko , Imamura Michio , Kawakami Yoshiiku , Aikata Hiroshi , Ochi Hidenori , Nelson Hayes C. , Chayama Kazuaki
Published: November 2015

Recently, treatments for chronic hepatitis C virus (HCV) infection have been drastically improved by the development of direct‐acting antiviral agents. In September 2014, dual oral therapy using daclatasvir (DCV) and asunaprevir (ASV) was approved for the treatment of chronic HCV infection in Japan. We treated a patient with HCV‐related liver cirrhosis with severe leg edema due to chronic renal dysfunction using this dual oral therapy. Although serum alanine aminotransferase increased rapidly during the first week of treatment, the antiviral therapy was able to continue, and liver function recovered spontaneously. After 1 month of treatment, serum HCV RNA became continuously undetectable, and serum albumin level gradually increased. Throughout the therapy, serum creatinine level nearly normalized, and leg edema gradually improved. These improvements continued after the combination therapy was completed. HCV RNA remained undetectable following the end of therapy, and sustained virological response at 12 weeks was achieved. It has been reported that chronic HCV infection is associated with renal dysfunction and that HCV eradication can improve it. DCV and ASV combination therapy is safe for patients who have renal dysfunction and may be a suitable therapy for chronic hepatitis C patients with renal dysfunction.
Alternative migratory locust phenotypes are associated with differences in the expression of genes encoding the methylation machinery
Authors: Robinson K. L. , Tohidi‐Esfahani D. , Ponton F. , Simpson S. J. , Sword G. A. , Lo N.
Published: November 2015

Despite the importance of locust density‐dependent polyphenism as a model system for understanding phenotypic plasticity, there is still much to be learnt about its underlying molecular control. Here we describe the first investigation into the expression of genes encoding the DNA methylation machinery in the migratory locust (Locusta migratoria). We show that the alternative solitarious and gregarious phenotypic states induced by different locust rearing densities are associated with significant differences in the expression of the target genes DNA methyltransferase 1, DNA methyltransferase 2 and methyl‐CpG‐binding domain protein 2/3. This variation was most pronounced in the embryos of solitarious vs. gregarious mothers. We mapped the embryonic methylation profiles of several intragenic regions and a Long Interspersed Nuclear Element (LINE), each of which is known to be differentially expressed between alternative locust phenotypes or has been directly implicated in phase change. LmI and three genes, adenyl cyclase‐associated binding protein 2, choline kinase alpha‐like and henna, were methylated. Our results set the stage for future studies investigating the specific role of DNA methylation in the maternal transfer of migratory locust phase polyphenism.
Does antenatal education reduce fear of childbirth?
Authors: Karabulut Ö. , Coşkuner Potur D. , Doğan Merih Y. , Cebeci Mutlu S. , Demirci N.
Published: November 2015

Aim

The aim of this study was to determine the effect of antenatal education on fear of childbirth, acceptance of pregnancy and identification with motherhood role.

Background

There is insufficient evidence pertaining to the effect of antenatal education on fear of childbirth, acceptance of pregnancy and identification with motherhood role.

Introduction

The purpose of antenatal education is to help couples make the right decisions during delivery. Through antenatal education, couples prepare themselves for delivery.

Methods

This is a quasi‐experimental and prospective study that employs a pre‐ and post‐education model. In total, 192 pregnant women (education group, n = 69 and control group, n = 123) participated in the study. Data were collected using the pregnancy identification form: the Prenatal Self‐Evaluation Questionnaire and a version of the Wijma Delivery Expectancy/Experience Questionnaire.

Results

Prior to participating in the study, the education group and control group had similar levels of acceptance of pregnancy and identification with motherhood role, whereas a significant difference was found in their fear of childbirth levels. When surveyed again after receiving education, the two groups' levels of acceptance of pregnancy and fear of childbirth were found to be significantly different. However, they had similar levels of identification with the motherhood role.

Conclusion

Antenatal education appears to increase the acceptance of pregnancy, does not affect the identification with motherhood role and reduces the fear of childbirth.

Implications for nursing and health policy

A systematic antenatal education programme, as part of routine antenatal care services, would help reduce the rate of interventional labour and facilitate pregnant women's conscious participation in the act of labour by reducing their fear of childbirth.
An Integrated Strategic and Tactical Master Surgery Scheduling Approach With Stochastic Resource Demand
Authors: Fügener Andreas
Published: November 2015

This study discusses a master surgery scheduling approach that maximizes hospital revenues while considering the impact on the downstream resources—intensive care units and general patient wards. Demand for these resources is modeled by a stochastic patient path model. I apply an integer programming model to provide the optimal allocation of how many (strategic planning problem) and what (tactical planning problem) operating room (OR) blocks to assign to each medical specialty. I demonstrate further applications of the model, such as the analysis of the value of flexible resources and the simulation of specific resource expansions. The approach is tested with real‐life data from a German university hospital and achieves significant revenue increases.
iPSC‐derived human cardiac progenitor cells improve ventricular remodelling via angiogenesis and interstitial networking of infarcted myocardium
Authors: Ja KP Myu Mia , Miao Qingfeng , Tee Nicole Gui Zhen , Lim Sze Yun , Nandihalli Manasi , Ramachandra Chrishan J.A. , Mehta Ashish , Shim Winston
Published: November 2015

We investigate the effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)‐derived progenitors and cardiomyocytes into acutely infarcted myocardium in severe combined immune deficiency mice. A total of 2 × 105 progenitors, cardiomyocytes or cell‐free saline were injected into peri‐infarcted anterior free wall. Sham‐operated animals received no injection. Myocardial function was assessed at 2‐week and 4‐week post‐infarction by using echocardiography and pressure‐volume catheterization. Early myocardial remodelling was observed at 2‐week with echocardiography derived stroke volume (SV) in saline (20.45 ± 7.36 μl, P < 0.05) and cardiomyocyte (19.52 ± 3.97 μl, P < 0.05) groups, but not in progenitor group (25.65 ± 3.61 μl), significantly deteriorated as compared to sham control group (28.41 ± 4.41 μl). Consistently, pressure–volume haemodynamic measurements showed worsening chamber dilation in saline (EDV: 23.24 ± 5.01 μl, P < 0.05; ESV: 17.08 ± 5.82 μl, P < 0.05) and cardiomyocyte (EDV: 26.45 ± 5.69 μl, P < 0.05; ESV: 18.03 ± 6.58 μl, P < 0.05) groups by 4‐week post‐infarction as compared to control (EDV: 15.26 ± 2.96 μl; ESV: 8.41 ± 2.94 μl). In contrast, cardiac progenitors (EDV: 20.09 ± 7.76 μl; ESV: 13.98 ± 6.74 μl) persistently protected chamber geometry against negative cardiac remodelling. Similarly, as compared to sham control (54.64 ± 11.37%), LV ejection fraction was preserved in progenitor group from 2‐(38.68 ± 7.34%) to 4‐week (39.56 ± 13.26%) while cardiomyocyte (36.52 ± 11.39%, P < 0.05) and saline (35.34 ± 11.86%, P < 0.05) groups deteriorated early at 2‐week. Improvements of myocardial function in the progenitor group corresponded to increased vascularization (16.12 ± 1.49/mm2 to 25.48 ± 2.08/mm2 myocardial tissue, P < 0.05) and coincided with augmented networking of cardiac telocytes in the interstitial space of infarcted zone.
P2Y12 antagonist attenuates eosinophilic inflammation and airway hyperresponsiveness in a mouse model of asthma
Authors: Suh Dong‐Hyeon , Trinh Hoang Kim Tu , Liu Jing‐Nan , Pham Le Duy , Park Sang Myun , Park Hae‐Sim , Shin Yoo Seob
Published: November 2015

Leukotriene E4 (LTE4) that plays a key role in airway inflammation is expressed on platelets and eosinophils. We investigated whether blocking of the P2Y12 receptor can suppress eosinophilic inflammation in a mouse model of asthma because platelets and eosinophils share this receptor to be activated. BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by OVA nebulization. On each challenge day, clopidogrel, a P2Y12 antagonist was administered 30 min. before each challenge. Forty‐eight hours after the last OVA challenge, mice were assessed for airway hyperresponsiveness (AHR), cell composition and cytokine levels, including chemokine ligand 5 (CCL5), in bronchoalveolar lavage (BAL) fluid. EOL cells were treated with LTE4, with or without clopidogrel treatment, and intracellular and extracellular eosinophil cationic protein (ECP) expressions were measured to find the inhibiting function of P2Y12 antagonist on eosinophilic activation. The levels of P2Y12 expression were increased markedly in the lung homogenates of OVA‐sensitized and ‐challenged mice after platelet depletion. Administration of clopidogrel decreased AHR and the number of airway inflammatory cells, including eosinophils, in BAL fluid following OVA challenge. These results were associated with decreased levels of Th2 cytokines and CCL5. Histological examination showed that inflammatory cells as well as mucus‐containing goblet cells were reduced in clopidogrel‐administered mice compared to vehicle‐treated mice. Clopidogrel inhibited extracellular ECP secretion after LTE4 stimulation in EOL‐1 cells. Clopidogrel could prevent development of AHR and airway inflammation in a mouse model of asthma. P2Y12 can be a novel therapeutic target to the suppression of eosinophils in asthma.
Methods to characterize selective sweeps using time serial samples: an ancient DNA perspective
Authors: Malaspinas Anna‐Sapfo
Published: November 2015

With hundreds of ancient genomes becoming available this year, ancient DNA research has now entered the genomics era. Utilizing the temporal aspect of these new data, we can now address fundamental evolutionary questions such as the characterization of selection processes shaping the genomes. The temporal dimension in the data has spurred the development in the last 10 years of new methods allowing the detection of loci evolving non‐neutrally but also the inference of selection coefficients across genomes capitalizing on these time serial data. To guide empirically oriented researchers towards the statistical approach most appropriate for their data, this article reviews several of those methods, discussing their underlying assumptions and the parameter ranges for which they have been developed. While I discuss some methods developed for experimental evolution, the main focus is ancient DNA.
Outcomes of dexmedetomidine treatment in pediatric patients undergoing congenital heart disease surgery: a meta‐analysis
Authors: Pan Wanying , Wang Yueting , Lin Lin , Zhou Ge , Hua Xiaoxiao , Mo Liqiu
Published: November 2015

Background

Dexmedetomidine decreases cardiac complications in adults undergoing cardiovascular surgery. This systematic review assessed whether perioperative dexmedetomidine improves congenital heart disease (CHD) surgery outcomes in children.

Methods

The PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs) or observational studies that were published until 16 April 2015 and compared dexmedetomidine with placebo or an alternative anesthetic agent during pediatric CHD surgery. The assessed outcomes included hemodynamics, ventilation length, intensive care unit (ICU) and hospital stays, blood glucose and serum cortisol levels, postoperative analgesia requirements, and postoperative delirium.

Results

Five RCTs and nine observational studies involving 2229 patients were included. In pooled analyses, dexmedetomidine was associated with shorter length of mechanical ventilation (mean difference: −93.36, 95% CI: −137.45, −49.27), lower postoperative fentanyl (mean difference: −24.11, 95% CI: −36.98, −11.24) and morphine (mean difference: −0.07, 95% CI: −0.14, 0.00) requirements, reduced stress response (i.e., lower blood glucose and serum cortisol levels), and lower risk of delirium (OR: 0.39, 95% CI: 0.21, 0.74). The hemodynamics of dexmedetomidine‐treated patients appeared more stable, but there were no significant differences in the ICU or hospital stay durations. Dexmedetomidine may increase the bradycardia and hypotension risk (OR: 3.14, 95% CI: 1.47, 6.69).

Conclusions

Current evidence indicates that dexmedetomidine improves outcomes in children undergoing CHD surgery. However, this finding largely relies on data from observational studies; high‐quality RCTs are warranted because of the potential for subject selection bias.
Vernalization response of domesticated × wild chickpea progeny is subject to strong genotype by environment interaction
Authors: Pinhasi van‐Oss Ruth , Sherman Amir , Zhang Hong‐Bin , Vandemark George , Coyne Clarice , Abbo Shahal
Published: November 2015

Vernalization insensitivity is a key feature of domesticated chickpea, and its genetic basis is not well understood. We studied vernalization response among hybrid progeny derived from two domesticated × wild crosses. The wild parents are vernalization‐sensitive, late‐flowering genotypes while both domesticated parents are vernalization insensitive. Parental lines and hybrid progeny were tested with (28 days at 4°C) and without vernalization (control). The difference in mean days to flower (∆DTF) between control and vernalization treatments was used to assess the flowering vernalization response. A wide range of ∆DTF values was observed among the hybrid progeny. Strong genotype by environment interaction effect on ∆DTF was observed for the parental accessions and hybrid progeny. We used the ∆DTF values to select vernalization responsive and non‐responsive progeny lines. However, the genotype × environment interaction strongly interfered with our selection. Chickpea breeders interested in using the wild progenitor as a donor of exotic traits should be aware of the possibility of introducing vernalization response alleles that may alter the phenology of their breeding materials in an unpredictable manner.
Pre‐infection processes of Botryosphaeriaceae spp.: adhesion of conidia to different substrata
Authors: Sammonds J. , Jaspers M. V. , Jones E. E.
Published: November 2015

Species of Botryosphaeriaceae are important wound pathogens of grapevines as causal agents of botryosphaeria dieback, but the behaviour of their conidia pre‐infection is unknown and may be important for disease development. Adhesion properties of conidia were investigated for Botryosphaeria dothidea, Neofusicoccum luteum and N. parvum on substrata with different affinities for water. Greatest adhesion on any surface was reached after 5 min for isolates N. luteum MM558, B. dothidea 007 and N. parvum G652 (53·1, 54·0 and 50·6%, respectively) and for N. luteum isolate CC445 after 20 min (61·4%). As conidia adhered well to all artificial substrata, it appeared as if the attachment process was nonspecific. Overall, surface wettability did not play a major role in the adhesion of conidia. Spore surface proteins appeared to play a role in the adhesion process because treatment of conidia of N. luteum MM558 with a protease completely prevented adhesion. Histochemical labelling of conidia and germlings with Coomassie brilliant blue (specific for proteins) was positive for all isolates, with a blue ‘halo’ often seen surrounding conidia or near the germ tube emergence point after incubation times conducive to germination. Alcian blue also stained material surrounding conidia after longer incubation times, which indicated that mucopolysaccharide and protein production may be involved in a second phase of adhesion.
A rational approach to single, dual and triple therapy in COPD
Authors: Calverley Peter , Vlies Ben
Published: November 2015

The complexity of COPD treatment has increased over the last 5 years mainly because of the proliferation of drugs and delivery devices. In this paper, we will focus on currently available therapy used for maintaining patient well‐being rather than acute relief of symptoms. We propose a series of principles for rational therapy, and following a review of how currently available treatments perform in isolation and when compared with each other, we suggest an approach to aid the rational selection of the most appropriate treatment based on current evidence.
Hematology of dugongs (Dugong dugon) in southern Queensland
Authors: Woolford Lucy , Wong Arthur , Sneath Helen L. , Long Trevor , Boyd Susan P. , Lanyon Janet M.
Published: November 2015

Background

Little is known of the hematology of the dugong (Dugong dugon), a secretive and endangered coastal marine mammal.

Objectives

This paper reports hematologic reference intervals (RI) for dugongs and characterizes morphologic, cytochemical, and ultrastructural features of dugong leukocytes.

Methods

Blood was collected from live, apparently healthy dugongs and analyzed using Cell‐Dyn 3700 or SysmexXT‐2000iV hematology analyzers. Blood films were subjected to a series of cytochemical stains, and leukocyte structure was examined using transmission electron microscopy.

Results

Reference intervals were established for 14 hematologic variables, total solids, and fibrinogen for 92 dugongs. Significant differences in some variables were found for animal size class, sex, and pregnancy status, and between analyzers. Subadults had higher leukocyte and lymphocyte counts than adults. Males had higher total solids and fibrinogen than females. Pregnant females had higherHCT,MCV, and circulating nucleatedRBC, and lower platelet counts than nonpregnant females. Lymphocytes were usually the predominant circulating leukocyte. Heterophil cytoplasmic granules were abundant, fine, round to ovoid, and intensely eosinophilic, and round to ovoid or rod‐shaped, and variably electron dense in electron microscopy. Eosinophils contained larger round eosinophilic to orange cytoplasmic granules, which ultrastructurally were bicompartmental with a round eccentric electron‐dense core. Cytochemical staining of dugong heterophils suggests biochemical similarity to those of manatees and elephants, and for eosinophils, similarity to those of elephants, ruminants, and equids.

Conclusions

Generation of hematologicRIand characterization of leukocyte morphology improves evaluation of dugong health across this population and serves as a reference for other populations outside southern Queensland.
Predictive Neuromuscular Fatigue of the Lower Extremity Utilizing Computer Modeling
Authors: Samaan Michael A. , Weinhandl Joshua T. , Hans Steven A. , Bawab Sebastian Y. , Ringleb Stacie I.
Published: November 2015

This paper studies the modeling of lower extremity muscle forces and their correlation to neuromuscular fatigue. Two analytical fatigue models were combined with a musculoskeletal model to estimate the effects of hamstrings fatigue on lower extremity muscle forces during a side step cut. One of the fatigue models (Tang) used subject-specific knee flexor muscle fatigue and recovery data while the second model (Xia) used previously established fatigue and recovery parameters. Both fatigue models were able to predict hamstrings fatigue within 20% of the experimental data, with the semimembranosus and semitendinosus muscles demonstrating the largest (11%) and smallest (1%) differences, respectively. In addition, various hamstrings fatigue levels (10–90%) on lower extremity muscle force production were assessed using one of the analytical fatigue models. As hamstrings fatigue levels increased, the quadriceps muscle forces decreased by 21% (p < 0.01), while gastrocnemius muscle forces increased by 36% (p < 0.01). The results of this study validate the use of two analytical fatigue models in determining the effects of neuromuscular fatigue during a side step cut, and therefore, this model can be used to assess fatigue effects on risk of lower extremity injury during athletic maneuvers. Understanding the effects of fatigue on muscle force production may provide insight on muscle group compensations that may lead to altered lower extremity motion patterns as seen in noncontact anterior cruciate ligament (ACL) injuries.
ANCF Continuum-Based Soil Plasticity for Wheeled Vehicle Off-Road Mobility
Authors: Recuero Antonio M. , Contreras Ulysses , Patel Mohil , Shabana Ahmed A.
Published: November 2015

This technical brief describes the procedure and demonstrates the feasibility of integrating soil/tire models using the absolute nodal coordinate formulation (ANCF). The effects of both the soil plasticity and the tire elasticity are captured using ANCF finite elements (FEs). Capturing the tire/soil dynamic interaction is necessary for the construction of higher fidelity off-road vehicle models. ANCF finite elements, as will be demonstrated in this paper, can be effectively used for the modeling of tire and soil mechanics. In this investigation, the soil model is developed using ANCF hexahedral finite elements, while the tire model can be developed using different ANCF finite elements including beam, plate, or solid elements; ANCF plate elements are used in this investigation for demonstration purposes. The Drucker–Prager plastic material, which is used to model the behavior of the soil, is appropriate for the simulation of a number of types of soils and offers a good starting point for computational plasticity in terramechanics applications. Such higher fidelity simulations can be fruitfully applied toward the investigation of complex dynamic phenomena in terramechanics. The proposed ANCF/Drucker–Prager soil model is implemented in a multibody system (MBS) algorithm which allows for using the ANCF reference node (ANCF-RN) to apply linear connectivity conditions between ANCF finite elements and the rigid components of the vehicle. This new implementation is demonstrated using a tire of an off-road wheeled vehicle. The generality of the approach allows for the simulation of general vehicle maneuvers over unprepared terrain. Unlike other approaches that implement force or superelement models into an MBS simulation environment, in the approach proposed in this paper both the soil material and vehicle parameters can be altered independently. This allows for a greater degree of flexibility in the development of computational models for the evaluation of the off-road wheeled vehicle performance.
Efficient Contact Modeling in Nonrigid Variation Simulation
Authors: Lindau Björn , Lorin Samuel , Lindkvist Lars , Söderberg Rikard
Published: November 2015

Virtual tools and methods are becoming increasingly important in order to predict the geometric outcome in early phases of the product realization process. Method of influence coefficients (MIC) in combination with Monte Carlo simulation (MCS) is a well-known technique that can be used in nonrigid variation simulation. In these simulations, contact modeling is important to ensure a correct result. Contact modeling simulates how mating surfaces are hindered from penetrating each other, giving rise to contact forces that contribute to the deformation of the parts when assembled and the final shape of the subassembly after springback. These contact forces have to be taken into consideration in each MCS-iteration. To secure reasonable response times, the calculation of the contact forces needs to be fast. In this paper, we formulate a quadratic programming (QP) problem to solve the contact problem. The case studies presented show that node-based contact modeling can be efficiently solved through QP.
A Generalized Feed-Forward Dynamic Adaptive Mesh Refinement and Derefinement Finite-Element Framework for Metal Laser Sintering—Part II: Nonlinear Thermal Simulations and Validations2
Authors: Pal Deepankar , Patil Nachiket , Kutty Khalid Haludeen , Zeng Kai , Moreland Alleyce , Hicks Adam , Beeler David , Stucker Brent
Published: November 2015

A novel multiscale thermal analysis numerical tool has been developed to address the micro–macro interactions involved in localized melting and sintering processes, such as laser sintering of metals exhibiting nonlinear thermal response. The method involves extension of a feed-forward dynamic adaptive mesh refinement and derefinement finite-element framework to incorporate nonlinear thermal phenomenon in the vicinity of the energy source and further reduce computational time and complexity when simulating spatiotemporally periodic problems posed by metal laser sintering. The thermal and microstructural predictions computed using this framework are in good agreement with the thermal contours measured using a forward-looking infrared (FLIR) imaging system and microstructures observed using an optical microscope.
Improving the Working Surface Condition of Electroplated Cubic Boron Nitride Grinding Quill in Surface Grinding of Inconel 718 by the Assistance of Ultrasonic Vibration
Authors: Li Sisi , Wu Yongbo , Fujimoto Masakazu , Nomura Mitsuyoshi
Published: November 2015

The working surface condition of abrasive tool is one of the important issues in grinding process. This article discusses the effects of the ultrasonic vibration on the working surface condition involving chips adhesion and abrasive grains wear during ultrasonic-assisted grinding (UAG) of Inconel 718 with an electroplated cBN grinding quill as the abrasive tool. In this study, scanning electron microscopic (SEM) observations were performed on the quill working surface before and after grinding at different vibration amplitudes, and the SEM images were filtered, extracted, and binarized by using image-pro plus to evaluate the quill working surface condition. The obtained results demonstrated that (1) the wear of grinding quill is dominantly attributed to chips adhesion, grains releasing, and grains fracture; (2) both the percentage of chips adhesion area and the size of chips adhered tend to decrease as the vibration amplitude increases; in contrast, the effect of ultrasonic vibration on the number of chips adhesion is not noticeable; (3) the percentage of the number of grains released/fractured decreases as the vibration amplitude rises, e.g., the percentage in UAG at vibration amplitude of Ap–p = 9.4 μm was decreased by 40% compared to that in conventional grinding (CG); and (4) higher distribution density of effective cutting edges can be achieved under larger vibration amplitude, and the mean area of effective cutting edges in UAG is smaller than that in CG, demonstrating that the ultrasonication enhances the grinding quill sharpness.
Curing-Induced Debonding and Its Influence on Strength of Adhesively Bonded Joints of Dissimilar Materials
Authors: Zhu XiaoBo , Li YongBing , Ni Jun , Lai XinMin
Published: November 2015

Adhesive bonding is thought to be a suitable method for joining dissimilar materials, such as aluminum to steel in multimaterial car-body manufacturing, but when it is combined with other joining methods, such as spot welding or self-piercing riveting, curing the adhesive at elevated temperature induces problems, such as distortion and adhesive debond. In this study, the effects of debonds were investigated by examining load–displacement curve and dissipated energy in lap-shear and peeling tests of artificially debonded joints. The results showed that the debonds caused by curing are of dog-bone type or stripe failure type, and both of them have little influence on the peel strength, but have strong influence on the shear strength and energy absorption. For the lap-shear specimens, the debonds reduce the bonding area, leading to the reduction in maximum shear force. For the double cantilever beam specimens, the debonds produce little influence on maximum peeling force but obvious variations in the peeling load curve. The energy absorption values are inversely proportional to the debonds due to the reduction in bonding area. The overall results from this research facilitate the understanding of the debonding mechanism caused by curing-induced distortion by revealing two types of debond patterns in dissimilar material bonding joints and their influences on joint performance.
Modeling and Analysis of Five-Axis Milling Configurations and Titanium Alloy Surface Topography
Authors: Prat David , Fromentin Guillaume , Poulachon Gérard , Duc Emmanuel
Published: November 2015

Five-axis milling with a ball-end cutter is commonly used to generate a good surface finish on complex parts, such as blades or impellers made of titanium alloy. The five-axis milling cutting process is not straight forward; local cutting conditions depend a lot on the geometrical configuration relating to lead and tilt angles. Furthermore, the surface quality is greatly affected by the cutting conditions that define the milling configuration. This study presents a geometrical model of five-axis milling in order to determine the effective cutting conditions, the milling mode, and the cutter location point. Subsequently, an analysis of surface topography is proposed by using the geometrical model, local criteria, and a principle component analysis of experimental data. The results show the effects of local parameters on the surface roughness, in relation to the lead and tilt angles.
Predictive Modeling of Grinding Force Considering Wheel Deformation for Toric Fewer-Axis Grinding of Large Complex Optical Mirrors
Authors: Jiang Zhenhua , Yin Yuehong , Wang Qianren , Chen Xing
Published: November 2015

Fewer-axis ultraprecision grinding has been recognized as an important means for manufacturing large complex optical mirrors. The research on grinding force is critical to obtaining a mirror with a high surface accuracy and a low subsurface damage. In this paper, a unified 3D geometric model of toric wheel–workpiece contact area and its boundaries are established based on the local geometric properties of the wheel and the workpiece at the grinding point (GP). Moreover, the discrete wheel deformation is calculated with linear superposition of force-induced deformations of single grit, resolving the difficulties of applying Hertz contact theory to irregular contact area. The new deformed wheel surface is then obtained by using the least squares method. Based on the force distribution within the contact area and the coupled relationship between grinding force and wheel deformation, the specific grinding energy and the final predicted grinding force are obtained iteratively. Finally, the proposed methods are validated through grinding experiments.
Additive Manufacturing and Performance of Functional Hydraulic Pump Impellers in Fused Deposition Modeling Technology
Authors: Fernández S. , Jiménez M. , Porras J. , Romero L. , Espinosa M. M. , Domínguez M.
Published: November 2015

Would it be possible for an additively manufactured impeller of fused deposition modeling (FDM) technology to have a functional behavior and a similar performance to that of the original impeller of a close-coupled centrifugal pump? In this research paper, different tests are conducted to answer this question and to evaluate the manufacturing process of FDM functional parts. Three performance experiments with the same centrifugal pump, using an open test rig, are carried out and compared, first using the original impeller provided by the manufacturer of the pump, second using an FDM replication of the original one without post-treatment, and third using a chemically dimethyl ketone post-treated FDM replication. The results obtained in the tests demonstrate the functional behavior of both additive FDM impellers in comparison with the one fabricated by means of conventional technology (subtractive manufacturing). Additionally, analogous head-flow curves (and also with an improved performance to the one of the original impeller) are obtained. This research paper introduces significant information concerning a low-cost and low-time manufacturing process of additive functional parts. Moreover, new results are presented regarding the performance of chemically post-treated FDM parts working in functional applications. FDM impellers of high complexity and quality, which meet performance criteria, can be achieved.
An Accurate and Efficient Approach to Undeformed Chip Geometry in Face-Hobbing and Its Application in Cutting Force Prediction
Authors: Habibi Mohsen , Chen Zezhong Chevy
Published: November 2015

Due to complexities of face-hobbing of bevel gears, such as the intricate geometry of the cutting system, multi-axis machine tool kinematic chains, and the variant cutting velocity along the cutting edge, deriving the instantaneous undeformed chip geometry, as one of the most important characteristic of material removal, is a challenging process. In the present research, all these complexities have been taken into consideration to obtain an in-process model and undeformed chip geometry, and predict cutting forces. The instantaneous undeformed chip geometry is obtained using the derived in-process model. As an application of the proposed methods, cutting forces are predicted during face-hobbing by oblique cutting theory using the derived undeformed chip geometry and converting face-hobbing into oblique cutting. The proposed methods are applied on two case studies of face-hobbing of bevel gears and the chip geometry is derived and the cutting forces are predicted.
Millennial-scale plankton regime shifts in the subtropical North Pacific Ocean
Authors: McMahon Kelton W. , McCarthy Matthew D. , Sherwood Owen A. , Larsen Thomas , Guilderson Thomas P.
Published: November 2015

Community changes centuries in the making

How might climate change affect the base of the marine food chain? Phytoplankton, the foundation of the marine ecosystem, depend on ambient oceanographic conditions such as temperature, salinity, and nutrient availability, which affect ocean chemistry and isotopic distributions. McMahon
et al.
report carbon isotopic composition changes in the North Pacific Ocean over the past 1000 years, which reflect changes in the community composition of phytoplankton in the region (see the Perspective by Vogt). An ongoing trend toward greater prevalence of nitrogen-fixing cyanobacteria that began 100 years ago might lead to a more efficient carbon pump and remove increasing amounts of CO
2
from the atmosphere.

Science
, this issue p.
1530
; see also p.
1466
The impact of diagnosis: measuring the psychological response to being diagnosed with serious or potentially lethal cardiac disease in young competitive athletes
Authors: Asif Irfan M , Price David E , Ewing Alex , Rao Ashwin L , Harmon Kimberly G , Drezner Jonathan A
Published: November 2015

Aim

To determine the psychological impact of athletes diagnosed with cardiac disease.

Methods and design

Athletes diagnosed with cardiovascular disorders were recruited to complete the Impact of Event Scale (IES), a validated tool measuring responses to a traumatic event. IES scoring =0–88 (<12= normal, 12–32=recommend monitoring, >33=significant stress reaction). Subscales include: intrusion, avoidance and hyperarousal.

Results

30 athletes (53% male, 83% Caucasian, median age 18.0, median age at diagnosis 15.7) participated. Diagnoses included: 6 hypertrophic cardiomyopathy, 9 Wolff Parkinson White, 4 Long QT syndrome, 3 atrial septal defect, 2 supraventricular tachycardia and 6 other. For the group, the mean IES-Revised (IES-R) score=16.6 (SD=12.1), subscales: intrusion 6.6 (SD=4.3), avoidance=7.4 (SD=6.5), hyperarousal=2.7 (SD=3.5). Higher risk individuals included: permanently disqualified athletes (p<0.01), athletes requiring daily medication (p<0.01), those with genetically inheritable conditions (p<0.01), and athletes undergoing medical management instead of definitive therapy (p<0.01). No differences were reported by gender (male=16.6, female=16.6). Higher IES-R scores were reported in more competitive athletes (college=17.8, high school=13.3; p=0.369) and African-American individuals (African-American=25.8, Caucasian=14.8 p=0.061), although not statistically significant. Athletes with cardiomyopathy (IES-R=24) and channelopathy (IES-R=28) reported the highest IES results. Athletes with high IES-R scores were most likely to psychologically respond through avoidance of feelings/situations/ideas.

Conclusions

Athletes diagnosed with potentially lethal cardiac disorders are at risk for significant psychological distress. These athletes tend to avoid thoughts, feelings and conversations associated with their diagnosis and should be offered consistent emotional support to mitigate psychological morbidity.

Significance

Currently, there are no recommendations to guide physicians on how to support an athlete that is newly diagnosed with a potentially career altering heart condition. Proper planning and use of appropriate support mechanisms can be useful for emotionally vulnerable athletes.
Perceived ethical acceptability of financial incentives to improve diabetic eye screening attendance
Authors: Wadge Hester , Bicknell Colin , Vlaev Ivo
Published: November 2015

Objective

To test the ethical acceptability of using financial incentives to increase diabetic retinopathy screening attendance.

Background

Financial incentives could be an effective way to increase attendance at screening for diabetic retinopathy, although there can be ethical concerns about this approach.

Design

Survey of people with diabetes in North West London. Those who were due to attend a screening appointment were invited to complete a questionnaire. Key demographic variables included age, gender, and deprivation.

Setting and participants

A questionnaire was issued to those invited to attend screening in North West London and those who run the screening service. The questionnaire captured views on aspects of the ethical problem and different incentive types.

Main variables studied

It captured views on the different dimensions of the ethical problem and different types of incentive. In order to understand how views might vary within a population, demographic variables were used to analyze the results.

Results and conclusions

Vouchers were found to be the most acceptable form of incentive, significantly more so than cash payments. Most rejected the notion of targeting those who need incentivizing, preferring equality. Age was an important factor, with those aged between 40 and 64 the most optimistic about the potential benefits. Higher levels of deprivation were linked to increased acceptability scores. While some ethical concerns are strongly held among certain groups, there is also much support for the principle of incentivizing positive behaviors. This paves the way for future research into the effectiveness of incentivizing diabetic retinopathy screening attendance.