Electron capture of tetracyanoethylene oxide in the gas phase. Rearrangement of the parent radical anion to form [(NC)(3)C](-). A joint experimental and ab initio study

Capture of an electron by tetracyanoethylene oxide can initiate a number of decomposition pathways. One of these decompositions yields [(NC)3C]− as the ionic product. Ab initio calculations (at the B3LYP/6-31+G∗ level of theory) indicate that the formation of [(NC)3C]− is initiated by capture of an electron into the LUMO of tetracyanoethylene oxide to yield the anion radical [(NC)2C–O–C(CN)2]−· that undergoes internal nucleophilic substitution to form intermediate [(NC)3C–OCCN]−·. This intermediate dissociates to form [(NC)3C]− (m/z 90) as the ionic product. The radical (NC)3C· has an electron affinity of 4.0 eV (385 kJ mol−1). Ab initio calculations show that [(NC)3C]− is trigonal planar with the negative charge mainly on the nitrogens. A pictorial representation of this structure is the resonance structure formed from three degenerate contributing structures (NC)2–CCN−. The other product of the reaction is nominally (NCCO)·, but there is no definitive experimental evidence to indicate whether this radical survives intact, or decomposes to NC· and CO. The overall process [(NC)2C–O–C(CN)2]−· → [(NC)3C]− + (NCCO)· is calculated to be endothermic by 21 kJ mol−1 with an overall barrier of 268 kJ mol−1.

A prospective model of care for breast cancer rehabilitation : bone health and arthralgias

Musculoskeletal health can be compromised by breast cancer treatment. In particular, bone loss and arthralgias are prevalent side effects experienced by women treated with chemotherapy and/or adjuvant endocrine therapy. Bone loss leads to osteoporosis and related fractures, while arthralgias threaten quality of life and compliance to treatment. Because the processes that lead to these musculoskeletal problems are initiated when treatment begins, early identification of women who may be at higher risk of developing problems, routine monitoring of bone density and pain at certain stages of treatment, and prudent application of therapeutic interventions are key to preventing and/or minimizing musculoskeletal sequelae. Exercise may be a particularly suitable intervention strategy because of its potential to address a number of impairments; it may slow bone loss, appears to reduce joint pain in noncancer conditions, and improves other breast cancer outcomes. Research efforts continue in the areas of etiology, measurement, and treatment of bone loss and arthralgias. The purpose of this review is to provide an overview of the current knowledge on the management and treatment of bone loss and arthralgias in breast cancer survivors and to present a framework for rehabilitation care to preserve musculoskeletal health in women treated for breast cancer.

The Credit Act Advisory System (CAAS) : conversion from an expert system prototype to a C++ commercial system

CAAS is a rule-based expert system, which provides advice on the Victorial Credit Act 1984. It is currently in commercial use, and has been developed in conjunction with a law firm. It uses an object-oriented hybrid reasoning approach. The system was initially prototyped using the expert system shell NExpert Object, and was then converted into the C++ language. In this paper we describe the advantages that this methodology has, for both commercial and research development.

Neutrophil gelatinase-associated lipocalin (NGAL) an early-screening biomarker for ovarian cancer : NGAL is associated with epidermal growth factor-induced epithelio-mesenchymal transition

The expression of neutrophil gelatinase-associated lipocalin (NGAL) has been shown to be upregulated in ovarian cancer cells. In this study, we report that the expression of immunoreactive NGAL (irNGAL) in ovarian tumors changes with disease grade and that this change is reflected in the concentration of NGAL in peripheral blood. A total of 59 ovarian tissues including normal, benign, borderline malignant and grades 1, 2 and 3 malignant were analyzed using immunohistochemistry. irNGAL was not present in normal ovaries and the NGAL expression was weak to moderate in benign tissues. Both borderline and grade 1 tumors displayed the highest amount of NGAL expression with moderate to strong staining, whereas in grade 2 and 3 tumors, the extent of staining was significantly less (p < 0.01) and staining intensity was weak to moderate. Staining in all cases was confined to the epithelium. NGAL expression was analyzed by ELISA in 62 serum specimens from normal and different grades of cancer patients. Compared to control samples, the NGAL concentration was 2 and 2.6-fold higher in the serum of patients with benign tumors and cancer patients with grade 1 tumors (p < 0.05) and that result was consistent with the expression of NGAL performed by Western blot. NGAL expression was evaluated by Western blot in an immortalized normal ovarian cell line (IOSE29) as well as ovarian cancer cell lines. Moderate to strong expression of NGAL was observed in epithelial ovarian cancer cell lines SKOV3 and OVCA433 while no expression of NGAL was evident in normal IOSE29 and mesenchyme-like OVHS1, PEO.36 and HEY cell lines. NGAL expression was downregulated in ovarian cancer cell lines undergoing epithelio-mesenchymal transition (EMT) induced by epidermal growth factor (EGF). Down-regulation of NGAL expression correlated with the upregulation of vimentin expression, enhanced cell dispersion and downregulation of E-cadherin expression, some of the hallmarks of EMT. EGF-induced EMT phenotypes were inhibited in the presence of AG1478, an inhibitor of EGF receptor tyrosine kinase activity. These data indicate that NGAL may be a good marker to monitor changes of benign to premalignant and malignant ovarian tumors and that the molecule may be involved in the progression of epithelial ovarian malignancies.

Invasive phenotype of MCF10A cells overexpressing c-Ha-ras and c-erbB-2 oncogenes

Infection with erbB-2 (E) of Ha-ras (H) oncogene-transfected cells has been previously shown to cooperatively induce anchorage-independent growth of the MCF10A human mammary epithelial cell line in vitro, but not to induce nude mouse tumorigenicity. Here we show that oncogene-transformed MCF10A are able to halt in the lungs of nude mice, a sign of organ colonization potential. We have therefore studied the transformants for in vitro migratory and invasive properties known to correlate with the metastatic potential of human mammary carcinoma cells in nude mice. MCF10A transfected with Ha-ras, infected with a recombinant retroviral vector containing the human c-erB-2 proto-oncogene (MCF10A-HE cells), show a higher invasive index than either the single transfectant (MCF10A-H) or MCF10A-erB-2(MCF10A-E) cells in the Boyden chamber chemotaxis and chemoinvasion assays. The MCF10A-HE cells also adopted an invasive stellate growth pattern when plated or embedded in Matrigel, in contrast to the spherical colonies formed by the single transformants MCF10A-H, MCF10A-E, and the parental cells. Dot-blot analysis of gelatinase A and TIMP-2 mRNA levels revealed increasing gelatinase A mRNA levels (HE > E > H > MCF10A) and reduced TIMP-2 expression in both single and double transformants. Furthermore, MCF10A-HE cells show more MMP-2 activity than parental MCF10A cells or the single transformants. CD44 analysis revealed differential isoform banding for the MCF10A-HE cells compared to parental cells, MCF10A-H and MCF10A-E, accompanied by increased binding of hyaluronan by the double transformants. Our results indicate that erB-2 and Ha-ras co-expression can induce a more aggressive phenotype in vitro, representative of the malignancy of mammary carcinomas.

A smoking cessation intervention for people with chronic Hepatitis C : a randomised controlled trial

Purpose The purpose of this study was to examine the validity of current practice in smoking cessation for the general population i.e., a telephone counselling and nicotine replacement therapy (NRT) intervention and its applicability to people with chronic hepatitis-C. Methods A randomised controlled trial was conducted over twelve weeks. Following consent, ninety-two smokers (outpatients) with chronic hepatitis-C were recruited by the Nurse Practitioner hepatology, randomly assigned and stratified by number of cigarettes smoked (i.e., 15 and greater; <15) into the intervention group (telephone counselling and NRT) and control group (telephone counselling). Outcomes measured included socio-demographics, nicotine dependence, depression, anxiety and stress and quality of life (QOL). All statistical data were analysed using SPSS. Results After 12 weeks, the intervention group showed a sustained reduction of smoking i.e., 5.8(CI: 2.4,9.3) cigarettes less per day, whereas the control group showed 1.6(CI:-1.9,5.2) cigarette reduction. Although not statistically significantly different (F=2.9, p=0.090) the intervention group on average smoked 4.2 fewer cigarettes compared to the control group. After twelve weeks, seven patients in the intervention group and three patients in the control group reported quitting. Whilst not statistically significant (Fisher’s Exact, p=0.311) this was a clinically significant result. No differences were found for nicotine dependence or depression, anxiety and stress. The intervention group experienced no change in QOL (-0.1,CI:-0.9, 0.6), however, the environmental score for the control group decreased by 1.8(CI:1.0, 2.6,p= 0.001). This was statistically significant. Conclusion A telephone counselling and nicotine replacement therapy intervention from the nurse practitioner, hepatology reduced smoking in patients with chronic hepatitis-C. The intervention group showed a sustained reduction over the 12 weeks. A total of 10 patients quit smoking at the end of the study. QOL deteriorated in the environmental subscale for the control group. These results informed a nurse practitioner model of care for approaches to smoking cessation.

A C-ITS based lane-changing advisory for weaving sections

Weaving sections, a common design of motorways, require extensive lane-change manoeuvres. Numerous studies have found that drivers tend to make their lane changes as soon as they enter the weaving section, as the traffic volume increases. Congestion builds up as a result of this high lane-changing concentration. Importantly, such congestion also limits the use of existing infrastructure, the weaving section downstream. This behaviour thus affects both safety and operational aspects. The potential tool for managing motorways effectively and efficiently is cooperative intelligent transport systems (C-ITS). This research investigates a lane-change distribution advisory application based on C-ITS for weaving vehicles in weaving sections. The objective of this research is to alleviate the lane-changing concentration problem by coordinating weaving vehicles to ensure that such lane-changing activities are evenly distributed over the existing weaving length. This is achieved by sending individual messages to drivers based on their location to advise them when to start their lane change. The research applied a microscopic simulation in AIMSUN to evaluate the proposed strategy’s effectiveness in a one-sided ramp weave. The proposed strategy was evaluated using different weaving advisory proportions, traffic demands and penetration rates. The evaluation revealed that the proposed lane-changing advisory has the potential to significantly improve delay.

Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis

Current models of HIV-1 morphogenesis hold that newly synthesized viral Gag polyproteins traffic to and assemble at the cell membrane into spherical protein shells. The resulting late-budding structure is thought to be released by the cellular ESCRT machinery severing the membrane tether connecting it to the producer cell. Using electron tomography and scanning transmission electron microscopy, we find that virions have a morphology and composition distinct from late-budding sites. Gag is arranged as a continuous but incomplete sphere in the released virion. In contrast, late-budding sites lacking functional ESCRT exhibited a nearly closed Gag sphere. The results lead us to propose that budding is initiated by Gag assembly, but is completed in an ESCRT-dependent manner before the Gag sphere is complete. This suggests that ESCRT functions early in HIV-1 release-akin to its role in vesicle formation-and is not restricted to severing the thin membrane tether.

Adenovirus species C is associated with chronic suppurative lung diseases in children

Background The role of human adenoviruses (HAdVs) in chronic respiratory disease pathogenesis is recognized. However, no studies have performed molecular sequencing of HAdVs from the lower airways of children with chronic endobronchial suppuration. We thus examined the major HAdV genotypes/species, and relationships to bacterial coinfection, in children with protracted bacterial bronchitis (PBB) and mild bronchiectasis (BE). Methods Bronchoalveolar lavage (BAL) samples of 245 children with PBB or mild (cylindrical) BE were included in this prospective cohort study. HAdVs were genotyped (when possible) in those whose BAL had HAdV detected (HAdV+). Presence of bacterial infection (defined as ≥104 colony-forming units/mL) was compared between BAL HAdV+ and HAdV negative (HAdV−) groups. Immune function tests were performed including blood lymphocyte subsets in a random subgroup. Results Species C HAdVs were identified in 23 of 24 (96%) HAdV+ children; 13 (57%) were HAdV-1 and 10 (43%) were HAdV-2. An HAdV+ BAL was significantly associated with bacterial coinfection with Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae (odds ratio [OR], 3.27; 95% confidence interval, 1.38–7.75; P = .007) and negatively associated with Staphylococcus aureus infection (P = .03). Young age was related to increased rates of HAdV+. Blood CD16 and CD56 natural killer cells were significantly more likely to be elevated in those with HAdV (80%) compared with those without (56.1%) (P = .027). Conclusions HAdV-C is the major HAdV species detected in the lower airways of children with PBB and BE. Younger age appears to be an important risk factor for HAdV+ of the lower airways and influences the likelihood of bacterial coinfection

The topography of multiple drug use among adolescent Australians : findings from the National Drug Strategy Household Survey

Introduction and aims: Despite evidence that many Australian adolescents have considerable experience with various drug types, little is known about the extent to which adolescents use multiple substances. The aim of this study was to examine the degree of clustering of drug types within individuals, and the extent to which demographic and psychosocial predictors are related to cluster membership. Design and method: A sample of 1402 adolescents aged 12-17. years were extracted from the Australian 2007 National Drug Strategy Household Survey. Extracted data included lifetime use of 10 substances, gender, psychological distress, physical health, perceived peer substance use, socioeconomic disadvantage, and regionality. Latent class analysis was used to determine clusters, and multinomial logistic regression employed to examine predictors of cluster membership. Result: There were 3 latent classes. The great majority (79.6%) of adolescents used alcohol only, 18.3% were limited range multidrug users (encompassing alcohol, tobacco, and marijuana), and 2% were extended range multidrug users. Perceived peer drug use and psychological distress predicted limited and extended multiple drug use. Psychological distress was a more significant predictor of extended multidrug use compared to limited multidrug use. Discussion and conclusion: In the Australian school-based prevention setting, a very strong focus on alcohol use and the linkages between alcohol, tobacco and marijuana are warranted. Psychological distress may be an important target for screening and early intervention for adolescents who use multiple drugs.

Effects of artificial shade on attack by the mahogany shoot borer, Hypsipyla robusta (Moore)

Swietenia macrophylla King (Meliaceae: Swietenioideae) provides one of the premier timbers of the world. The mahogany shoot borer Hypsipyla robusta Moore (Lepidoptera: Pyralidae) is an economically important pest of S. macrophylla throughout Asia, Africa and the Pacific. No viable method of controlling this pest is known. Previous observations have suggested that the presence of overhead shade may reduce attack by H. robusta, but this has not been investigated experimentally. This research was therefore designed to assess the influence of light availability on shoot-borer attack on S. macrophylla, by establishing seedlings under three different artificial shade regimes, then using these seedlings to test oviposition preference of adult moths, neonate larval survival and growth and development of shoot borer larvae. Oviposition preference of shoot borer moths was tested on leaves from seedlings grown under artificial shade for 63 weeks. A significant difference in choice was recorded between treatments, with 27.4 ± 1.5 eggs laid under high shade and 87.1 ± 1.8 under low shade. Neonate larval survival on early flushing leaflets of S. macrophylla did not differ significantly between shade treatments. Larval growth rate, estimated by measuring daily frass width, was significantly higher for those larvae fed on seedlings from the high and medium shade treatments (0.1 mm/day), than the low shade treatment (0.06 mm/day). In laboratory-reared larvae, the total mass of frass produced was significantly higher in the high shade treatment (0.4 g) than under the low shade treatment (0.2 g). Longer tunnel lengths were bored by larvae in plants grown under high shade (12.0 ± 2.4 cm) than under low shade (7.07 ± 1.9 cm). However, pupal mass under low shade was 48% higher than that under the high shade treatment, suggesting that plants grown under high shade were of lower nutritional quality for shoot borer larvae. These results indicate that shading of mahogany seedlings may reduce the incidence of shoot borer attack, by influencing both oviposition and larval development. The establishment of mahogany under suitable shade regimes may therefore provide a basis for controlling shoot borer attack using silvicultural approaches.

A pilot trial of mobile, patient-performed teledermoscopy

BACKGROUND Early detection by skin self-examination (SSE) could improve outcomes from melanoma. Mobile teledermoscopy may aid this process. OBJECTIVES To establish clinical accuracy of SSE plus mobile teledermoscopy compared to clinical skin examination (CSE) and test whether providing people with detailed SSE instructions improves accuracy. METHODS Men and women 50-64 years (n=58) performed SSE plus mobile teledermoscopy in their homes between May and November 2013 and were given technical instructions plus detailed SSE instructions (intervention) or technical instructions only (control). Within three months, they underwent a CSE. Outcome measures included: a) body sites examined, lesions photographed, and missed; b) sensitivityof SSE plus mobile teledermoscopy compared to in-person CSE using either patients or lesions as denominator, and; c) concordance of telediagnosis with CSE. RESULTS: 49 of 58 randomised participants completed the study, and submitted 309 lesions to the teledermatologist (156 intervention; 153 control group). Intervention group participants were more likely to submit lesions from their legs compared to control (p=0.03), no other differences between groups in number or site of missed lesions.11 participants (22%) did not photograph 14 pigmented lesions the dermatologist considered worthwhile photographing or requiring clinical monitoring. Sensitivity of SSE plus mobile teledermoscopy was 81.8% (95% confidence interval 64.5-93.0) using the patient as the denominator and 41.9 (27.6-56.2) using the lesion as denominator.-There was substantial agreement between telediagnosis and CSE (Kappa =0.90) accounting for differential diagnoses. CONCLUSIONS SSE plus mobile teledermoscopy is promising for surveillance of particular lesions even without provision of detailed SSE instructions, but in the format tested in this study, consumers may overlook lesions and send many non-pigmented lesions. This investigation demonstrates that high quality dermoscopic images can be taken by patients at home and for those sent, telediagnosis is highly accurate.