Electrical imaging and fluid modeling of convective fingering in a shallow water-table aquifer

Unstable density-driven flow can lead to enhanced solute transport in groundwater. Only recently has the complex fingering pattern associated with free convection been documented in field settings. Electrical resistivity (ER) tomography has been used to capture a snapshot of convective instabilities at a single point in time, but a thorough transient analysis is still lacking in the literature. We present the results of a 2 year experimental study at a shallow aquifer in the United Arab Emirates that was designed to specifically explore the transient nature of free convection. ER tomography data documented the presence of convective fingers following a significant rainfall event. We demonstrate that the complex fingering pattern had completely disappeared a year after the rainfall event. The observation is supported by an analysis of the aquifer halite budget and hydrodynamic modeling of the transient character of the fingering instabilities. Modeling results show that the transient dynamics of the gravitational instabilities (their initial development, infiltration into the underlying lower-density groundwater, and subsequent decay) are in agreement with the timing observed in the time-lapse ER measurements. All experimental observations and modeling results are consistent with the hypothesis that a dense brine that infiltrated into the aquifer from a surficial source was the cause of free convection at this site, and that the finite nature of the dense brine source and dispersive mixing led to the decay of instabilities with time. This study highlights the importance of the transience of free convection phenomena and suggests that these processes are more rapid than was previously understood.

Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults

BACKGROUND Asthma severity and control can be measured both subjectively and objectively. Sputum analysis for evaluation of percentage of sputum eosinophilia directly measures airway inflammation, and is one method of objectively monitoring asthma. Interventions for asthma therapies have been traditionally based on symptoms and spirometry. OBJECTIVES To evaluate the efficacy of tailoring asthma interventions based on sputum analysis in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults. SEARCH STRATEGY We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was on 31 October 2006. SELECTION CRITERIA All randomised controlled comparisons of adjustment of asthma therapy based on sputum eosinophils compared to traditional methods (primarily clinical symptoms and spirometry/peak flow). DATA COLLECTION AND ANALYSIS Results of searches were reviewed against pre-determined criteria for inclusion. Three sets of reviewers selected relevant studies.Two review authors independently assessed trial quality extracted data. Authors were contacted for further information but none were received. Data was analysed as "treatment received" and sensitivity analyses performed. MAIN RESULTS Three adult studies were included; these studies were clinically and methodologically heterogenous (use of medications, cut off for percentage of sputum eosinophils and definition of asthma exacerbation). There were no eligible paediatric studies. Of 246 participants randomised, 221 completed the trials. In the meta-analysis, a significant reduction in number of participants who had one or more asthma exacerbations occurred when treatment was based on sputum eosinophils in comparison to clinical symptoms; pooled odds ratio (OR) was 0.49 (95% CI 0.28 to 0.87); number needed to treat to benefit (NNTB) was 6 (95% CI 4 to 32).There were also differences between groups in the rate of exacerbation (any exacerbation per year) and severity of exacerbations defined by requirement for use of oral corticosteroids but the reduction in hospitalisations was not statistically significant. Data for clinical symptoms, quality of life and spirometry were not significantly different between groups. The mean dose of inhaled corticosteroids per day was similar in both groups and no adverse events were reported. However sputum induction was not always possible. AUTHORS' CONCLUSIONS Tailored asthma interventions based on sputum eosinophils is beneficial in reducing the frequency of asthma exacerbations in adults with asthma. This review supports the use of sputum eosinophils to tailor asthma therapy for adults with frequent exacerbations and severe asthma. Further studies need to be undertaken to strengthen these results and no conclusion can be drawn for children with asthma.

Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults

Background The measurement of severity and control of asthma in both children and adults can be based on subjective or objective measures. It has been advocated that fractional exhaled nitric oxide (FeNO) can be used to monitor airway inflammation as it correlates with some markers of asthma. Interventions for asthma therapies have been traditionally based on symptoms and/or spirometry. Objectives To evaluate the efficacy of tailoring asthma interventions based on exhaled nitric oxide in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was completed in February 2009. Selection criteria All randomised controlled comparisons of adjustment of asthma therapy based on exhaled nitric oxide compared to traditional methods (primarily clinical symptoms and spirometry/peak flow). Data collection and analysis Results of searches were reviewed against pre-determined criteria for inclusion. Relevant studies were independently selected in duplicate. Two authors independently assessed trial quality and extracted data. Authors were contacted for further information with response from one. Main results Two studies have been added for this update, which now includes six (2 adults and 4 children/adolescent) studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut off levels, the way in which FeNO was used to adjust therapy and duration of study. Of 1053 participants randomised, 1010 completed the trials. In the meta-analysis, there was no significant difference between groups for the primary outcome of asthma exacerbations or for other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose inhaled corticosteroid per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms, (mean difference -450 mcg; 95% CI -677 to -223 mcg budesonide equivalent/day). However, the total amount of inhaled corticosteroid used in one of the adult studies was 11% greater in the FeNO arm. In contrast, in the paediatric studies, there was a significant increase in inhaled corticosteroid dose in the FeNO strategy arm (mean difference of 140 mcg; 95% CI 29 to 251, mcg budesonide equivalent/day). Authors' conclusions Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the six studies and found only modest benefit at best and potentially higher doses of inhaled corticosteroids in children. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids cannot be routinely recommended for clinical practice at this stage and remains uncertain.

Management based on exhaled nitric oxidelevels adjusted for atopy reduces asthma exacerbations in children : A dual centre randomised controlled trial

While several randomised control trials (RCTs) have evaluated the use of fractional exhaled nitric oxide (FeNO) to improve asthma outcomes, none used FeNO cut-offs adjusted for atopy, a determinant of FeNO levels. In a dual centre RCT, we assessed whether a treatment strategy based on FeNO levels, adjusted for atopy, reduces asthma exacerbations compared with the symptoms-based management (controls). Children with asthma from hospital clinics of two hospitals were randomly allocated to receive an a-priori determined treatment hierarchy based on symptoms or FeNO levels. There was a 2-week run-in period and they were then reviewed ten times over 12-months. The primary outcome was the number of children with exacerbations over 12-months. Sixty-three children were randomised (FeNO=31, controls=32); 55 (86%) completed the study. Although we did achieve our planned sample size, significantly fewer children in the FeNO group (6 of 27) had an asthma exacerbation compared to controls (15 of 28), p=0.021; number to treat for benefit=4 (95%CI 3-24). There was no difference between groups for any secondary outcomes (quality of life, symptoms, FEV1). The final daily inhaled corticosteroids (ICS) dose was significantly (p=0.037) higher in the FeNO group (median 400µg, IQR 250-600) compared to the controls (200, IQR100-400). Taking atopy into account when using FeNO to tailor asthma medications is likely beneficial in reducing the number of children with severe exacerbations at the expense of increased ICS use. However, the strategy is unlikely beneficial for improving asthma control. A larger study is required to confirm or refute our findings.

Ethylenedione : An intrinsically short-lived molecule

Ethylenedione C2O2 is one of the elusive small molecules which have remained undetected even after numerous attempts with different experimental techniques, This is surprising, since theoretical studies predicted the triplet state of C2O2 to be stable towards spin-allowed dissociation and hence long-lived. Here we report a comprehensive study of charged and neutral ethylenedione by means of charge reversal and neutralization -reionization mass spectrometry. These experimental results, in conjunction with theoretical calculations, suggest that neutral ethylenedione is intrinsically short-lived rather than being elusive, Both the singlet and triplet states of C2O2 are predicted to dissociate rapidly into two ground-state CO molecules, and for the triplet species, this dissociation involves facile curve-crossing to the singlet surface within a few nanoseconds.

A combined neutralization-reionization mass spectrometric and theoretical study of oxyallyl and other elusive [C3,H4,O] neutrals

Five different anionic [C3′H4′O]•- isomers, i.e. the radical anions of acrolein, acetyl carbene, formyl methyl carbene, methoxy vinylidene, and oxyallyl are generated in an ion beam mass spectrometer and subjected to neutralization-reionization (NR) mass spectrometric experiments including neutral and ion decomposition difference (NIDD) mass spectrometry; the latter allows for the examination of the neutrals' unimolecular reactivity. Further, the anionic, the singlet and triplet neutral, and the cationic [C3′H4′O] •-/0/•+ potentialenergy surfaces are calculated at the B3LYP/6-311++G(d,p) level of theory. For some species, notably the singlet state of oxyallyl, the theoretical treatment is complemented by G2, CASSCF, and MR-CI calculations. Theory and experiment are in good agreement in that at the neutral stage (i) acrolein does not react within the μsec timescale, (ii) acetyl and formyl methyl carbenes isomerize to methyl ketene, (iii) methoxy vinylidene rearranges to methoxy acetylene, (iv) singlet 1A1 oxyallyl undergoes ring closure to cyclopropanone, and (v) triplet 3B2 oxyallyl may have a lifetime sufficient to survive a NR experiment.

Task-relationship-self : a framework for understanding service encounter behaviors

Research conducted over past decades has investigated selected service encounter behaviors from either a customer or service provider perspective. However, a comprehensive, dual-perspective framework is lacking. Such a framework is needed to organize knowledge of these behaviors, and thereby provide structure, clarity, and parsimony to the field. This paper describes a three-tier framework of service encounter behavior that was developed by applying grounded theory principles to interviews with customers, service employees, and other stakeholders. These informants described many ways in which they behave when executing service exchanges, dealing with service difficulties, and managing themselves in the process. Using an iterative inductive approach, a conceptual framework was developed in which specific (Tier 1) behaviors were placed within broader (Tier 2) categories, and these lower classification levels were, in turn, interpreted within a conceptual space defined by the (Tier 3) dimensions of task, relationship, and self. This framework was then elaborated and refined by reference to the psychology and marketing literature, a set of 157 audio-recorded service interactions, and an expert panel study. The paper includes comparisons between the framework and those previously proposed, propositions regarding service encounter processes and outcomes, and implications for future research and practice.

Community media production : access, institutions, and ethics

In policy terms, community media are known as the “third sector” of the media. The description reflects the historical expectation that community media can fulfill a need not met by the commercial and public service broadcasters. A defining element of this “need” has been the means to production for nonprofessionals, particularly groups not represented in the mainstream media. The historical construction of community media reveals production to be a guiding principle; both a means and an end in itself. This chapter examines the various rationales underpinning community media production, including empowerment, media diversity, and the independent producer movement. Using case studies from youth media, the chapter critiques producer-centric models of community media. In the contemporary media environment, production alone cannot meet the social needs that community media were established to address. Instead, I propose a rationale that combines both production and consumption ethics.

A mass spectrometry study of XCO+, X = Si, Ge : Is SiCO+ a main group carbonyl? Comments on the bonding in ground state SiCO and the Si,C,O (+) potential energy surface

The cation\[Si,C,O](+) has been generated by 1) the electron ionisation (EI) of tetramethoxysilane and 2) chemical ionisation (CI) of a mixture of silane and carbon monoxide. Collisional activation (CA) experiments performed for mass-selected \[Si,C,O](+), generated by using both methods, indicate that the structure is not inserted OSiC+; however, a definitive structural assignment as Si+-CO, Si+-OC or some cyclic variant is impossible based on these results alone. Neutralisation-reionisation (+NR+) experiments for EI-generated \[Si,C,O](+) reveal a small peak corresponding to SiC+, but no detectable SiO+ signal, and thus establishes the existence of the Si+-CO isomer. CCSD(T)//B3LYP calculations employing a triple-zeta basis set have been used to explore the doublet and quartet potential-energy surfaces of the cation, as well as some important neutral states The results suggest that both Si+-CO and Si+ - OC isomers are feasible; however, the global minimum is (2)Pi SiCO+. Isomeric (2)Pi SiOC+ is 12.1 kcal mol(-1) less stable than (2)Pi SiCO+, and all quartet isomers are much higher in energy. The corresponding neutrals Si-CO and Si-OC are also feasible, but the lowest energy Si - OC isomer ((3)A") is bound by only 1.5 kcal mol(-1). We attribute most, if nor all, of the recovery signal in the +NR' experiment to SiCO+ survivor ions. The nature of the bonding in the lowest energy isomers of Si+ -(CO,OC) is interpreted with the aid of natural bond order analyses, and the ground stale bonding of SiCO+ is discussed in relation to classical analogues such as metal carbonyls and ketenes.

Structural identification of hindered amine light stabilisers in coil coatings using electrospray ionisation tandem mass spectrometry

Hindered amine light stabilisers (HALS) are the most effective antioxidants currently available for polymer systems in post-production, in-service applications, yet the mechanism of their action is still not fully understood. Structural characterisation of HALS in polymer matrices, particularly the identification of structural modifications brought about by oxidative conditions, is critical to aid mechanistic understanding of the prophylactic effects of these molecules. In this work, electrospray ionisation tandem mass spectrometry (ESI-MS/MS) was applied to the analysis of a suite of commercially available 2,2,6,6-tetramethylpiperidine-based HALS. Fragmentation mechanisms for the \[M + H](+) ions are proposed, which provide a rationale for the product ions observed in the MS/MS and MS(3) mass spectra of N-H, N-CH(3), N-C(O)CH(3) and N-OR containing HALS (where R is an alkyl substituent). A common product ion at m/z 123 was identified for the group of antioxidants containing N-H, N-CH3 or N-C(0)CH3 functionality, and this product ion was employed in precursor ion scans on a triple quadrupole mass spectrometer to identify the HALS species present in a crude extract from of a polyester-based coil coating. Using MS/MS, two degradation products were unambiguously identified. This technique provides a simple and selective approach to monitoring HALS structures within complex matrices. Copyright (C) 2010 John Wiley & Sons, Ltd.

Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development

Objective To investigate the role of matrix metalloproteinase 13 (MMP-13; collagenase 3) in osteoarthritis (OA). Methods OA was surgically induced in the knees of MMP-13-knockout mice and wild-type mice, and mice were compared. Histologic scoring of femoral and tibial cartilage aggrecan loss (0-3 scale), erosion (0-7 scale), and chondrocyte hypertrophy (0-1 scale), as well as osteophyte size (0-3 scale) and maturity (0-3 scale) was performed. Serial sections were stained for type X collagen and the MMP-generated aggrecan neoepitope DIPEN. Results Following surgery, aggrecan loss and cartilage erosion were more severe in the tibia than femur (P < 0.01) and tibial cartilage erosion increased with time (P < 0.05) in wild-type mice. Cartilaginous osteophytes were present at 4 weeks and underwent ossification, with size and maturity increasing by 8 weeks (P < 0.01). There was no difference between genotypes in aggrecan loss or cartilage erosion at 4 weeks. There was less tibial cartilage erosion in knockout mice than in wild-type mice at 8 weeks (P < 0.02). Cartilaginous osteophytes were larger in knockout mice at 4 weeks (P < 0.01), but by 8 weeks osteophyte maturity and size were no different from those in wild-type mice. Articular chondrocyte hypertrophy with positive type X collagen and DIPEN staining occurred in both wild-type and knockout mouse joints. Conclusion Our findings indicate that structural cartilage damage in a mouse model of OA is dependent on MMP-13 activity. Chondrocyte hypertrophy is not regulated by MMP-13 activity in this model and does not in itself lead to cartilage erosion. MMP-13 deficiency can inhibit cartilage erosion in the presence of aggrecan depletion, supporting the potential for therapeutic intervention in established OA with MMP-13 inhibitors.

Predicting positive and negative impacts of cancer among long-term endometrial cancer survivors

OBJECTIVE Although the survival outcomes among women diagnosed with endometrial cancer are very favorable, little is known about the long-term impact of their cancer experience. This study identifies the extent of positive and negative impacts of cancer and factors associated with this, amongst long-term survivors of endometrial cancer. METHODS Australian women diagnosed with endometrial cancer (N=632) were sent questionnaires at the time of diagnosis and 3-5 years later. Hierarchical multiple regression models were used to examine whether a range of variables at diagnosis/treatment predicted subsequent scores on the Impact of Cancer Scale, which examines positive (e.g. health awareness) and negative (e.g. appearance concerns) impacts amongst cancer survivors. RESULTS Overall, women had a higher mean score for the positive than negative impact scales (M=3.5 versus M=2.5, respectively). An intermediate grade of endometrial cancer, a prior diagnosis of cancer and lower levels of education were significant, but weak, predictors of higher scores on the positive impact scale. Higher scores on the negative impact scale were predicted by a higher grade of cancer, poor physical and mental health, a younger age, being single or having lower levels of education. CONCLUSIONS The study demonstrates that factors that predict positive impact in cancer survivors differ to those that predict negative impact, suggesting that interventions to optimize cancer survivors' quality of life will need to be multi-dimensional, and this supports the need for tailored intervention.

Physical activity and physical fitness in African-American girls with and without obesity

Lack of physical activity and low levels of physical fitness are thought to be contributing factors to the high prevalence of obesity in African-American girls, To examine this hypothesis, we compared habitual physical activity and physical fitness in 54 African-American girls with obesity and 96 African-American girls without obesity residing in rural South Carolina, Participation in vigorous (greater than or equal to 6 METs) (VPA) or moderate and vigorous physical activity (greater than or equal to 4 METs) (MVPA) was assessed on three consecutive days using the Previous Day Physical Activity Recall, Cardiorespiratory fitness was assessed using the PWC 170 cycle ergometer test, Upper body strength was determined at two sites via isometric cable tensiometer tests, Relative to their counterparts without obesity, girls with obesity reported significantly fewer 30-minute blocks of VPA (0.90 +/- 0.14 vs. 1.3 +/- 0.14) and MVPA (1.2 +/- 0.18 vs. 1.7 +/- 0.16) (p<0.01), Within the entire sample, VPA and MVPA were inversely associated with body mass index (r=-0.17 and r=-0.19) and triceps skinfold thickness (r=-0.19 and r=-0.22) (p<0.05), In the PWC 170 test and isometric strength tests, girls with obesity demonstrated absolute scores that were similar to, or greater than, those of girls without obesity; however, when scores were expressed relative to bodyweight, girls with obesity demonstrated significantly lower values (p<0.05). The results support the hypothesis that lack of physical activity and low physical fitness are important contributing factors in the development and/or maintenance of obesity in African-American girls.

Association of increased basement membrane invasiveness with absence of estrogen receptor and expression of vimentin in human breast cancer cell lines

Lack of estrogen receptor (ER) and presence of vimentin (VIM) associate with poor prognosis in human breast cancer. We have explored the relationships between ER, VIM, and invasiveness in human breast cancer cell lines. In the matrigel outgrowth assay, ER+/VIM- (MCF-7, T47D, ZR-75-1), and ER-/VIM- (MDA-MB-468, SK-Br-3) cell lines were uninvasive, while ER-/VIM+ (BT549, MDA-MB-231, MDA-MB-435, MDA-MB-436, Hs578T) lines formed invasive, penetrating colonies. Similarly, ER-/VIM+ cell lines were significantly more invasive than either the ER+/VIM- or ER-/VIM- cell lines in the Boyden chamber chemoinvasion assay. Invasive activity in nude mice was only seen with ER-/ VIM+ cell lines MDA-MB-231, MDA-MB-435 and MDA-MB-436. Hs578T cells (ER-/VIM+) showed hematogenous dissemination to the lungs in one of five mice, but lacked local invasion. The ER-/VIM+ MCF-7ADR subline was significantly more active than the MCF-7 cells in vitro, but resembled the wild-type MCF-7 parent in in vivo activity. Data from these cell lines suggest that human breast cancer progression results first in the loss of ER, and subsequently in VIM acquisition, the latter being associated with increased metastatic potential through enhanced invasiveness. The MCF-7ADR data provide evidence that this transition can occur in human breast cancer cells. Vimentin expression may provide useful insights into mechanisms of invasion and/or breast cancer cell progression.

Bone sialoprotein supports breast cancer cell adhesion proliferation and migration through differential usage of the αvβ3 and αvβ5 integrins

Bone sialoprotein (BSP), a secreted glycoprotein found in bone matrix, has been implicated in the formation of mammary microcalcifications and osteotropic metastasis of human breast cancer (HBC). BSP possesses an integrin-binding RGD (Arg-Gly-Asp) domain, which may promote interactions between HBC cells and bone extracellular matrix. Purified BSP, recombinant human BSP fragments and BSP-derived RGD peptides are shown to elicit migratory, adhesive, and proliferative responses in the MDA-MB-231 HBC cell line. Recombinant BSP fragment analysis localized a significant component of these activities to the RGD domain of the protein, and synthetic RGD peptides with BSP flanking sequences (BSPRGD) also conferred these responses. The fibronectin-derived RGD counterpart, GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro), could not support these cellular responses, emphasizing specificity of the BSP configuration. Although most of the proliferative and adhesive responses could be attributed to RGD interactions, these interactions were only partly responsible for the migrational responses. Experiments with integrin-blocking antibodies demonstrated that BSP-RGD-induced migration utilizes the αvβ3 vitronectin receptor, whereas adhesion and proliferation responses were αvβ5-mediated. Using fluorescence activated cell sorting, we selected two separate subpopulations of MDA-MB-231 cells enriched for αvβ3 or αvβ5 respectively. Although some expression of the alternate αv integrin was still retained, the αvβ5-enriched MDA-MB-231 cells showed enhanced proliferative and adhesive responses, whereas the αvβ3-enriched subpopulation was suppressed for proliferation and adhesion, but showed enhanced migratory responses to BSP-RGD. In addition, similar analysis of two other HBC cell lines showed less marked, but similar RGD-dependent trends in adhesion and proliferation to the BSP fragments. Collectively, these data demonstrate BSP effects on proliferative, migratory, and adhesive functions in HBC cells and that the RGD-mediated component differentially employs αvβ3 and αvβ5 integrin receptors.