Advanced mass spectrometry-based multi-omics technologies for exploring the pathogenesis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the primary hepatic malignancies and is the third most common cause of cancer related death worldwide. Although a wealth of knowledge has been gained concerning the initiation and progression of HCC over the last half century, efforts to improve our understanding of its pathogenesis at a molecular level are still greatly needed, to enable clinicians to enhance the standards of the current diagnosis and treatment of HCC. In the post-genome era, advanced mass spectrometry driven multi-omics technologies (e.g., profiling of DNA damage adducts, RNA modification profiling, proteomics, and metabolomics) stand at the interface between chemistry and biology, and have yielded valuable outcomes from the study of a diversity of complicated diseases. Particularly, these technologies are being broadly used to dissect various biological aspects of HCC with the purpose of biomarker discovery, interrogating pathogenesis as well as for therapeutic discovery. This proof of knowledge-based critical review aims at exploring the selected applications of those defined omics technologies in the HCC niche with an emphasis on translational applications driven by advanced mass spectrometry, toward the specific clinical use for HCC patients. This approach will enable the biomedical community, through both basic research and the clinical sciences, to enhance the applicability of mass spectrometry-based omics technologies in dissecting the pathogenesis of HCC and could lead to novel therapeutic discoveries for HCC.

Emotional climate and high quality learning experiences in science teacher education

The role of emotion during learning encounters in science teacher education is under-researched and under-theorized. In this case study we explore the emotional climates, that is, the collective states of emotional arousal, of a preservice secondary science education class to illuminate practice for producing and reproducing high quality learning experiences for preservice science teachers. Theories related to the sociology of emotions informed our analyses from data sources such as preservice teachers’ perceptions of the emotional climate of their class, emotional facial expressions, classroom conversations, and cogenerative dialogue. The major outcome from our analyses was that even though preservice teachers reported high positive emotional climate during the professor’s science demonstrations, they also valued the professor’s in the moment reflections on her teaching that were associated with low emotional climate ratings. We co-relate emotional climate data and preservice teachers’ comments during cogenerative dialogue to expand our understanding of high quality experiences and emotional climate in science teacher education. Our study also contributes refinements to research perspectives on emotional climate.

Plasma-controlled nanocrystallinity and phase composition of TiO2 : a smart way to enhance biomimetic response

This contribution sheds light on the role of crystal size and phase composition in inducing biomimetic apatite growth on the surface of nanostructured titania films synthesized by reactive magnetron sputtering of Ti targets in Ar+O2 plasmas. Unlike most existing techniques, this method enables one to deposit highly crystalline titania films with a wide range of phase composition and nanocrystal size, without any substrate heating or postannealing. Moreover, by using this dry plasma-based method one can avoid surface hydroxylation at the deposition stage, almost inevitable in wet chemical processes. Results of this work show that high phase purity and optimum crystal size appear to be the essential requirement for efficient apatite formation on magnetron plasma-fabricated bioactive titania coatings. © 2006 Wiley Periodicals, Inc.

Beliefs about infant regulation, early infant behaviors and maternal postnatal depressive symptoms

Background: Young infants may have irregular sleeping and feeding patterns. Such regulation difficulties are known correlates of maternal depressive symptoms. Parental beliefs regarding their role in regulating infant behaviours also may play a role. We investigated the association of depressive symptoms with infant feeding/sleeping behaviours, parent regulation beliefs, and the interaction of the two. Method: In 2006, 272 mothers of infants aged up to 24 weeks completed a questionnaire about infant behaviour and regulation beliefs. Participants were recruited from general medical practices and child health clinics in Brisbane, Australia. Depressive symptomology was measured using the Edinburgh Postnatal Depression Scale (EPDS). Other measures were adapted from the ALSPAC study. Results: Regression analyses were run controlling for partner support, other support, life events, and a range of demographic variables. Maternal depressive symptoms were associated with infant sleeping and feeding problems but not regulation beliefs. The most important infant predictor was sleep behaviours with feeding behaviours accounting for little additional variance. An interaction between regulation beliefs and sleep behaviours was found. Mothers with high regulation beliefs were more susceptible to postnatal depressive symptoms when infant sleep behaviours were problematic. Conclusion: Mothers of young infants who expect greater control are more susceptible to depressive symptoms when their infant presents challenging sleep behaviour.

Do children and adolescents with Down syndrome have deficits in motivation?

There appears to be a general acceptance that individuals with intellectual disability (ID) have deficits in motivation. Yet research with infants and young children has usually identified few differences in motivation for children with ID compared with those of the same mental age who are developing typically. Studies of motivation in children with ID in the middle years of childhood or adolescence are almost non-existent. However, research conducted more than 30 years ago (Harter & Zigler, 1974) continues to be cited as evidence of motivational deficits in those with ID even though the life experiences of people with ID have changed dramatically since that time.

Vision-based simultaneous localization and mapping in changing outdoor environments

For robots operating in outdoor environments, a number of factors, including weather, time of day, rough terrain, high speeds, and hardware limitations, make performing vision-based simultaneous localization and mapping with current techniques infeasible due to factors such as image blur and/or underexposure, especially on smaller platforms and low-cost hardware. In this paper, we present novel visual place-recognition and odometry techniques that address the challenges posed by low lighting, perceptual change, and low-cost cameras. Our primary contribution is a novel two-step algorithm that combines fast low-resolution whole image matching with a higher-resolution patch-verification step, as well as image saliency methods that simultaneously improve performance and decrease computing time. The algorithms are demonstrated using consumer cameras mounted on a small vehicle in a mixed urban and vegetated environment and a car traversing highway and suburban streets, at different times of day and night and in various weather conditions. The algorithms achieve reliable mapping over the course of a day, both when incrementally incorporating new visual scenes from different times of day into an existing map, and when using a static map comprising visual scenes captured at only one point in time. Using the two-step place-recognition process, we demonstrate for the first time single-image, error-free place recognition at recall rates above 50% across a day-night dataset without prior training or utilization of image sequences. This place-recognition performance enables topologically correct mapping across day-night cycles.

Learned stochastic mobility prediction for planning with control uncertainty on unstructured terrain

Motion planning for planetary rovers must consider control uncertainty in order to maintain the safety of the platform during navigation. Modelling such control uncertainty is difficult due to the complex interaction between the platform and its environment. In this paper, we propose a motion planning approach whereby the outcome of control actions is learned from experience and represented statistically using a Gaussian process regression model. This mobility prediction model is trained using sample executions of motion primitives on representative terrain, and predicts the future outcome of control actions on similar terrain. Using Gaussian process regression allows us to exploit its inherent measure of prediction uncertainty in planning. We integrate mobility prediction into a Markov decision process framework and use dynamic programming to construct a control policy for navigation to a goal region in a terrain map built using an on-board depth sensor. We consider both rigid terrain, consisting of uneven ground, small rocks, and non-traversable rocks, and also deformable terrain. We introduce two methods for training the mobility prediction model from either proprioceptive or exteroceptive observations, and report results from nearly 300 experimental trials using a planetary rover platform in a Mars-analogue environment. Our results validate the approach and demonstrate the value of planning under uncertainty for safe and reliable navigation.

Fine-needle aspiration cytology of Merkel cell carcinoma-A review of 69 cases

Background This study reviewed the clinical presentation, cytologic findings and the immunophenotype of 69 Merkel Cell Carcinoma (MCC) cases sampled by FNA. Methods Demographic and clinical data, the cytology findings and results of ancillary testing were reviewed. Results Median patient age was 78 years (37 – 104) with a 1:1.8 female to male ratio. The most common FNA sites sampled included lymph nodes in the neck, the axillary region, the inguinal region and the parotid gland. Most patients had a history of MCC (68%) &/or non-MCC malignancy (70%). The common cytologic pattern was a cellular smear with malignant cells arranged in a dispersed pattern with variable numbers of disorganised groups of cells. Cytoplasm was scant or absent and nuclei showed mild to moderate anisokaryosis, stippled chromatin, inconspicuous nucleoli and nuclear molding. Numerous apoptotic bodies were often present. Cell block samples (28 cases) were usually positive for cytokeratins in a perinuclear dot pattern, including 88% of cases with CK20 positivity. CD56 was the most sensitive (95%) neuroendocrine marker on cell blocks and was also positive with flow cytometry in 9 cases tested. Conclusions MCC is most commonly seen in FNA specimens from the head and neck of elderly patients, often with a history of previous skin lesions. Occasional cases present in younger patients and some may be mistaken for other round blue cell tumors, such as lymphoma. CD 56 may be a useful marker in cell block preparations and in flow cytometric analysis of MCC.

Flupirtine enhances the anti-hyperalgesic effects of morphine in a rat model of prostate bone metastasis

Objective Current treatments for cancer pain are often inadequate, particularly when metastasis to bone is involved. The addition to the treatment regimen of another drug that has a complementary analgesic effect may increase the overall analgesia without the necessity to increase doses, thus avoiding dose-related side effects. This project investigated the synergistic effect of the addition of the potassium channel (KCNQ2–3) modulator flupirtine to morphine treatment in a rat model of prostate cancer-induced bone pain. Design Syngeneic prostate cancer cells were injected into the right tibia of male Wistar rats under anesthesia. This led to expanding tumor within the bone in 2 weeks, together with the concurrent development of hyperalgesia to noxious heat. Paw withdrawal thresholds from noxious heat were measured before and after the maximum non-sedating doses of morphine and flupirtine given alone and in combinations. Dose-response curves for morphine (0.13–5.0 mg/kg ip) and flupirtine (1.25–10.0 mg/kg ip) given alone and in fixed-dose combinations were plotted and subjected to an isobolographic analysis. Results Both morphine (ED50 = 0.74 mg/kg) and flupirtine (ED50 = 3.32 mg/kg) caused dose-related anti-hyperalgesia at doses that did not cause sedation. Isobolographic analysis revealed that there was a synergistic interaction between flupirtine and morphine. Addition of flupirtine to morphine treatment improved morphine anti-hyperalgesia, and resulted in the reversal of cancer-induced heat hyperalgesia. Conclusions These results suggest that flupirtine in combination with morphine may be useful clinically to provide better analgesia at lower morphine doses in the management of pain caused by tumors growing in bone.

Intravenous injection of leconotide, an omega conotoxin : synergistic antihyperalgesic effects with morphine in a rat model of bone cancer pain

Objective.  Leconotide (CVID, AM336, CNSB004) is an omega conopeptide similar to ziconotide, which blocks voltage sensitive calcium channels. However, unlike ziconotide, which must be administered intrathecally, leconotide can be given intravenously because it is less toxic. This study investigated the antihyperalgesic potency of leconotide given intravenously alone and in combinations with morphine-administered intraperitoneally, in a rat model of bone cancer pain. Design.  Syngeneic rat prostate cancer cells AT3B-1 were injected into one tibia of male Wistar rats. The tumor expanded within the bone causing hyperalgesia to heat applied to the ipsilateral hind paw. Measurements were made of the maximum dose (MD) of morphine and leconotide given alone and in combinations that caused no effect in an open-field activity monitor, rotarod, and blood pressure and heart rate measurements. Paw withdrawal thresholds from noxious heat were measured. Dose response curves for morphine (0.312–5.0 mg/kg intraperitoneal) and leconotide (0.002–200 µg/kg intravenous) given alone were plotted and responses compared with those caused by morphine and leconotide in combinations. Results.  Leconotide caused minimal antihyperalgesic effects when administered alone. Morphine given alone intraperitoneally caused dose-related antihyperalgesic effects (ED50 = 2.40 ± 1.24 mg/kg), which were increased by coadministration of leconotide 20 µg/kg (morphine ED50 = 0.16 ± 1.30 mg/kg); 0.2 µg/kg (morphine ED50 = 0.39 ± 1.27 mg/kg); and 0.02 µg/kg (morphine ED50 = 1.24 ± 1.30 mg/kg). Conclusions.  Leconotide caused a significant increase in reversal by morphine of the bone cancer-induced hyperalgesia without increasing the side effect profile of either drug. Clinical Implication.  Translation into clinical practice of the method of analgesia described here will improve the quantity and quality of analgesia in patients with bone metastases. The use of an ordinary parenteral route for administration of the calcium channel blocker (leconotide) at low dose opens up the technique to large numbers of patients who could not have an intrathecal catheter for drug administration. Furthermore, the potentiating synergistic effect with morphine on hyperalgesia without increased side effects will lead to greater analgesia with improved quality of life.

Development and characterization of a novel, antimicrobial, sterile hydrogel dressing for burn wounds : single-step production with gamma irradiation creates silver nanoparticles and radical polymerization

Patients with burn wounds are susceptible to wound infection and sepsis. This research introduces a novel burn wound dressing that contains silver nanoparticles (SNPs) to treat infection in a 2-acrylamido-2-methylpropane sulfonic acid sodium salt (AMPS-Na(+) ) hydrogel. Silver nitrate was dissolved in AMPS-Na(+) solution and then exposed to gamma irradiation to form SNP-infused hydrogels. The gamma irradiation results in a cross-linked polymeric network of sterile hydrogel dressing and a reduction of silver ions to form SNPs infused in the hydrogel in a one-step process. About 80% of the total silver was released from the hydrogels after 72 h immersion in simulated body fluid solution; therefore, they could be used on wounds for up to 3 days. All the hydrogels were found to be nontoxic to normal human dermal fibroblast cells. The silver-loaded hydrogels had good inhibitory action against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Results from a pilot study on a porcine burn model showed that the 5-mM silver hydrogel was efficient at preventing bacterial colonization of wounds, and the results were comparable to the commercially available silver dressings (Acticoat(TM) , PolyMem Silver(®) ). These results support its use as a potential burn wound dressing.

The impact of work-family programs on the relationship between gender diversity and performance

Work–family programs signal an employer's perspective on gender diversity to employees, and can influence whether the effects of diversity on performance are positive or negative. This article tests the interactive effects of nonmanagement gender diversity and work–family programs on productivity, and management gender diversity and work–family programs on financial performance. The predictions were tested in 198 Australian publicly listed organizations using primary (survey) and secondary (publicly available) data based on a two-year time lag between diversity and performance. The findings indicate that nonmanagement gender diversity leads to higher productivity in organizations with many work–family programs, and management gender diversity leads to lower financial performance in organizations with few work–family programs. The results suggest different business cases at nonmanagement and management levels for the adoption of work–family programs in gender-diverse organizations.

Superstars as drivers of organizational identification : empirical findings from professional soccer

This paper examines the effect of superstars on external stakeholders’ organizational identification through the lens of sport. Drawing on social identity theory and the concept of organizational identification, as well as on role model theories and superstar economics, several hypotheses are developed regarding the influence of soccer stars on their fans’ degree of team identification. Using a proprietary data set that combines archival data on professional German soccer players and clubs with survey data on more than 1,400 soccer fans, this study finds evidence for a positive effect of superstar characteristics and role model perception. Moreover, it is found that players who qualify for the definition of a superstar are more important to fans of established teams than to fans of unsuccessful teams. The player's club tenure, however, seems to have no influence on fans’ team identification. It is further argued that the effect of soccer stars on their fans is comparable to that of executives on external stakeholders, and hence, the results are applied to the business domain. The results of this study contribute to existing research by extending the list of personnel-related determinants of organizational identification.

Sex-specific roost selection by bats in clearfell harvested plantation forest : improved knowledge advises management

To maximize energetic savings, female bats often roost communally whilst pregnant or with non-volant dependents, whereas male bats more often roost alone; however, differences in selection of roosts by sex have not often been investigated. Better understanding of female colony locations could focus management to protect the majority of bats. New Zealand's long-tailed bat (Chalinolobus tuberculatus) roost in exotic plantation forest, where sex-specific roost selection has not been investigated, and therefore such management is not possible. We investigated sex-specific roost selection by long-tailed bats for the first time. Roosts and paired nonroosts were characterized testing predictions that males and females select roosts that differ from non-roosts, and males and females select different roosts. Females and males chose Pinus radiata roosts that differed from non-roost trees. Results suggest each sex chose roosts that maximized energetic savings. Female bats used roosts closer to water sources, that warmed earlier in the day, which allowed maintenance of high temperatures. Males appeared to choose roosts that allowed torpor use for long periods of the day. Males may be less selective with their roost locations than females, as they roosted further from water sources. This could allow persistence of male bats in marginal habitat. As all female long-tailed bats chose roosts within 150 m of waterways, management to protect bats could be focused here. To protect bats least able to escape when roosts are harvested, harvest of forest stands selected by female bats as roost sites should be planned when bats are not heavily pregnant nor have non-volant dependents.

Recent surveys of bats (Mammalia: Chiroptera) from China. I. Rhinolophidae and Hipposideridae

We conducted surveys of bats in China between 1999 and 2007, resulting in the identification of at least 62 species. In this paper we present data on 19 species, comprising 12 species from the family Rhinolophidae and seven from the Hipposideridae. Rhinolophids captured were Rhinolophus affinis, R. ferrumequinum, R. lepidus, R. luctus, R. macrotis, R. siamensis, R. marshalli, R. rex, R. pearsonii, R. pusillus, R. sinicus and R. stheno. Because of extensive morphological similarities we question the species distinctiveness of R. osgoodi (may be conspecific with R. lepidus), R. paradoxolophus (which may best be treated as a subspecies of R. rex), R. huananus (probably synonymous with R. siamensis), and we are skeptical as to whether R. sinicus is distinct from R. thomasi. Hipposiderids captured were Hipposideros armiger, H. cineraceus, H. larvatus, H. pomona, H. pratti, Aselliscus stoliczkanus and Coelops frithii. Of these species, two rhinolophids (Rhinolophus marshalli and R. stheno) and one hipposiderid (Hipposideros cineraceus) represent new species records for China. We present data on species' ranges, morphology and echolocation call frequencies, as well as some notes on ecology and conservation status. China hosts a considerable diversity of rhinolophid and hipposiderid bats, yet threats to their habitats and populations are substantial.