Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non-small-cell lung cancer

The epidermal growth factor receptor (EGFR) is commonly expressed in non-small-cell lung cancer (NSCLC) and promotes a host of mechanisms involved in tumorigenesis. However, EGFR expression does not reliably predict prognosis or response to EGFR-targeted therapies. The data from two previous studies of a series of 181 consecutive surgically resected stage I-IIIA NSCLC patients who had survived in excess of 60 days were explored. Of these patients, tissue was available for evaluation of EGFR in 179 patients, carbonic anhydrase (CA) IX in 177 patients and matrix metalloproteinase-9 (MMP-9) in 169 patients. We have previously reported an association between EGFR expression and MMP-9 expression. We have also reported that MMP-9 (P=0.001) and perinuclear (p)CA IX (P=0.03) but not EGFR expression were associated with a poor prognosis. Perinuclear CA IX expression was also associated with EGFR expression (P<0.001). Multivariate analysis demonstrated that coexpression of MMP-9 with EGFR conferred a worse prognosis than the expression of MMP-9 alone (P<0.001) and coexpression of EGFR and pCA IX conferred a worse prognosis than pCA IX alone (P=0.05). A model was then developed where the study population was divided into three groups: group 1 had expression of EGFR without coexpression of MMP-9 or pCA IX (number=21); group 2 had no expression of EGFR (number=75); and group 3 had coexpression of EGFR with pCA IX or MMP-9 or both (number=70). Group 3 had a worse prognosis than either groups 1 or 2 (P=0.0003 and 0.027, respectively) and group 1 had a better prognosis than group 2 (P=0.036). These data identify two cohorts of EGFR-positive patients with diametrically opposite prognoses. The group expressing either EGFR and or both MMP-9 and pCA IX may identify a group of patients with activated EGFR, which is of clinical relevance with the advent of EGFR-targeted therapies. © 2004 Cancer Research UK.

Ureaplasma parvum undergoes selection in utero resulting in genetically diverse isolates colonising the chorioamnion of fetal sheep

Ureaplasmas are the microorganisms most frequently isolated from the amniotic fluid of pregnant women and can cause chronic intrauterine infections. These tiny bacteria are thought to undergo rapid evolution and exhibit a hypermutatable phenotype; however, little is known about how ureaplasmas respond to selective pressures in utero. Using an ovine model of chronic intra-amniotic infection, we investigated if exposure of ureaplasmas to sub-inhibitory concentrations of erythromycin could induce phenotypic or genetic indicators of macrolide resistance. At 55 days gestation, 12 pregnant ewes received an intra-amniotic injection of a non-clonal, clinical U. parvum strain, followed by: (i) erythromycin treatment (IM, 30 mg/kg/day, n=6); or (ii) saline (IM, n=6) at 100 days gestation. Fetuses were then delivered surgically at 125 days gestation. Despite injecting the same inoculum into all ewes, significant differences between amniotic fluid and chorioamnion ureaplasmas were detected following chronic intra-amniotic infection. Numerous polymorphisms were observed in domain V of the 23S rRNA gene of ureaplasmas isolated from the chorioamnion (but not the amniotic fluid), resulting in a mosaic-like sequence. Chorioamnion isolates also harboured the macrolide resistance genes erm(B) and msr(D) and were associated with variable roxithromycin minimum inhibitory concentrations. Remarkably, this variability occurred independently of exposure of ureaplasmas to erythromycin, suggesting that low-level erythromycin exposure does not induce ureaplasmal macrolide resistance in utero. Rather, the significant differences observed between amniotic fluid and chorioamnion ureaplasmas suggest that different anatomical sites may select for ureaplasma sub-types within non-clonal, clinical strains. This may have implications for the treatment of intrauterine ureaplasma infections.

Continuity, Rupture, or just more of the 'Volatile and Contradictory': Glimpses of New South Wales' Penal Practice behind and through the Discursive

Throughout much of the western world more and more people are being sent to prison, one of a number of changes inspired by a 'new punitiveness' in penal and political affairs. This book seeks to understand these developments, bringing together leading authorities in the field to provide a wide-ranging analysis of new penal trends, compare the development of differing patterns of punishment across different types of societies, and to provide a range of theoretical analyses and commentaries to help understand their significance. As well as increases in imprisonment this book is also concerned to address a number of other aspects of 'the new punitiveness': firstly, the return of a number of forms of punishment previously thought extinct or inappropriate, such as the return of shaming punishments and chain gangs (in parts of the USA); and secondly, the increasing public involvement in penal affairs and penal development, for example in relation to length of sentences and the California Three Strikes Law, and a growing accreditation of the rights of victims. The book will be essential reading for students seeking to understand trends and theories of punishment on law, criminology, penology and other courses.

Does Addition of NO2 to Carbon-Centered Radicals Yield RONO or RNO2? An Investigation Using Distonic Radical Ions

Nitrogen dioxide is used as a "radical scavenger" to probe the position of carbon-centered radicals within complex radical ions in the gas phase. As with analogous neutral radical reactions, this addition results in formation of an \[M + NO2](+) adduct, but the structural identity of this species remains ambiguous. Specifically, the question remains: do such adducts have a nitro-(RNO2) or nitrosoxy-(RONO) moiety, or are both isomers present in the adduct population? In order to elucidate the products of such reactions, we have prepared and isolated three distonic phenyl radical cations and observed their reactions with nitrogen dioxide in the gas phase by ion-trap mass spectrometry. In each case, stabilized \[M + NO2](+) adduct ions are observed and isolated. The structure of these adducts is probed by collision-induced dissociation and ultraviolet photodissociation action spectroscopy and a comparison made to the analogous spectra of authentic nitro-and nitrosoxy-benzenes. We demonstrate unequivocally that for the phenyl radical cations studied here, all stabilized \[M + NO2](+) adducts are exclusively nitrobenzenes. Electronic structure calculations support these mass spectrometric observations and suggest that, under low-pressure conditions, the nitrosoxy-isomer is unlikely to be isolated from the reaction of an alkyl or aryl radical with NO2. The combined experimental and theoretical results lead to the prediction that stabilization of the nitrosoxy-isomer will only be possible for systems wherein the energy required for dissociation of the RO-NO bond (or other low energy fragmentation channels) rises close to, or above, the energy of the separated reactants.

Should I stay or should I go? The challenges and opportunities of moving between university systems

The scientific job market has evolved to a truly globalized market. This is epitomized not only by the English language being the de facto scientific language but also by the increasing share of native language journals that are being offered in multiple languages or have or will fully converted to English (such as, for example, the BISE journal in 2015). Similarly, a plethora of exchange programs exists that allow students and academic staff to visit other institutions and exchange knowledge, ideas, and learning opportunities. While student migration across scientific institutions is an established phenomenon (Gribble, 2008) with ample structures, policies, and schemes such as ERASMUS1 in place, academic staff migration between countries is still a challenge, even if exchange programs exist (Enders, 1998). One reason may be that different career paths, varying teaching loads and different evaluation schemes for what constitutes scientific excellence are notable. This also influences the decision of where to start and continue an academic career. While the university systems themselves have been examined previously (Galliers and Whitley, 2007; Lyytinen et al., 2007) and while there is knowledge about career requirements in different university systems (Dennis et al., 2006; Dean et al., 2011; Loos et al., 2013; Recker, 2013), we still do not know much about individual and contextual decisions of academics that either consider or execute a migration between university systems.

Gender stereotypes of personality : universal and accurate?

Numerous studies have documented subtle but consistent sex differences in self-reports and observer-ratings of five-factor personality traits, and such effects were found to show well-defined developmental trajectories and remarkable similarity across nations. In contrast, very little is known about perceived gender differences in five-factor traits in spite of their potential implications for gender biases at the interpersonal and societal level. In particular, it is not clear how perceived gender differences in five-factor personality vary across age groups and national contexts and to what extent they accurately reflect assessed sex differences in personality. To address these questions, we analyzed responses from 3,323 individuals across 26 nations (mean age = 22.3 years, 31% male) who were asked to rate the five-factor personality traits of typical men or women in three age groups (adolescent, adult, and older adult) in their respective nations. Raters perceived women as slightly higher in openness, agreeableness, and conscientiousness as well as some aspects of extraversion and neuroticism. Perceived gender differences were fairly consistent across nations and target age groups and mapped closely onto assessed sex differences in self- and observer-rated personality. Associations between the average size of perceived gender differences and national variations in sociodemographic characteristics, value systems, or gender equality did not reach statistical significance. Findings contribute to our understanding of the underlying mechanisms of gender stereotypes of personality and suggest that perceptions of actual sex differences may play a more important role than culturally based gender roles and socialization processes.

Cloning and tissue distribution of novel splice variants of the ovine ghrelin gene

Background The ghrelin axis is involved in the regulation of metabolism, energy balance, and the immune, cardiovascular and reproductive systems. The manipulation of this axis has potential for improving economically valuable traits in production animals, and polymorphisms in the ghrelin (GHRL) and ghrelin receptor (GHSR) genes have been associated with growth and carcass traits. Here we investigate the structure and expression of the ghrelin gene (GHRL) in sheep, Ovis aries. Results We identify two ghrelin mRNA isoforms, which we have designated Δex2 preproghrelin and Δex2,3 preproghrelin. Expression of Δex2,3 preproghrelin is likely to be restricted to ruminants, and would encode truncated ghrelin and a novel C-terminal peptide. Both Δex2 preproghrelin and canonical preproghrelin mRNA isoforms were expressed in a range of tissues. Expression of the Δex2,3 preproghrelin isoform, however, was restricted to white blood cells (WBC; where the wild-type preproghrelin isoform is not co-expressed), and gastrointestinal tissues. Expression of Δex2 preproghrelin and Δex2,3 preproghrelin mRNA was elevated in white blood cells in response to parasitic worm (helminth) infection in genetically susceptible sheep, but not in resistant sheep. Conclusions The restricted expression of the novel preproghrelin variants and their distinct WBC expression pattern during parasite infection may indicate a novel link between the ghrelin axis and metabolic and immune function in ruminants.

Including or excluding conflicts of interest among expert peer reviewers had little impact on funding success, a case study from Australia

Competition for research funding is intense and the opinions of an expert peer reviewer can mean the difference between success and failure in securing funding. The allocation of expert peer reviewers is therefore vitally important and funding agencies strive to avoid using reviewers who have real or perceived conflicts of interest. This article examines the impact of including or excluding peer reviewers based on their conflicts of interest, and the final ranking of funding proposals. Two 7-person review panels assessed a sample of National Health and Medical Research Council (NHMRC) of Australia proposals in Basic Science or Public Health. Using a pre-post comparison, the proposals were first scored after the exclusion of reviewers with a high or medium conflict, and re-scored after the return of reviewers with medium conflicts. The main outcome measures are the agreements in ranks and funding success before and after excluding the medium conflicts. Including medium conflicts of interest had little impact on the ranks or funding success. The Bland–Altman 95% limits of agreement were ± 3.3 ranks and ± 3.4 ranks in the two panels which both assessed 36 proposals. Overall there were three proposals (4%) that had a reversed funding outcome after including medium conflicts. Relaxing the conflict of interest rules would increase the number of expert reviewers included in the panel discussions which could increase the quality of peer review and make it easier to find reviewers.

Blood in our hearts or blood on our hands? The viscosity, vitality and validity of Aboriginal 'blood talk'

Blood metaphors abound in everyday social discourse among both Aboriginal and non-Aboriginal people. However, ‘Aboriginal blood talk’, more specifically, is located within a contradictory and contested space in terms of the meanings and values that can be attributed to it by Aboriginal and non-Aboriginal people. In the colonial context, blood talk operated as a tool of oppression for Aboriginal people via blood quantum discourses, yet today, Aboriginal people draw upon notions of blood, namely bloodlines, in articulating their identities. This paper juxtaposes contemporary Aboriginal blood talk as expressed by Aboriginal people against colonial blood talk and critically examines the ongoing political and intellectual governance regarding the validity of this talk in articulating Aboriginalities.

Medication Management of Adult Patients Admitted to Hospital with Epilepsy, Seizure or Convulsion

Background: An inpatient medication chart review at the Gold Coast Hospital identified shortcomings with the prescribing and monitoring of antiepileptic medications. Aim: To evaluate medication management of patients with epilepsy, seizure or convulsion; to map their transition through the health system; and to identify lifestyle behaviours that may lead to overt risks for seizure occurrence. Method: A retrospective observational audit of adult patients (16 years and over) admitted to hospital with a diagnosis of epilepsy, seizure or convulsion from 1 to 31 January 2012. Results: Majority of the 62 episodes of care investigated involved patients who were discharged directly from the ED (68%). Only 30% of all patients discharged from an inpatient unit received a discharge medication record from a pharmacist. Non-adherence with antiepileptic medications, alcohol and/ or recreational drug use and prescription medication misuse were identified as overt risks for seizure occurrence. Conclusion: Valuable insights were gained into the management of seizure patients. The role of the ED pharmacist was reviewed to focus on high-risk seizure patients. An increase in the provision of discharge medication records and patient education on the overt risks for seizure occurrence is needed.

Accolades or achievement? Addressing the unforeseen consequences of therapeutic pedagogy

Commentary "We have found little to indicate that indiscriminately promoting self-esteem in today’s children or adults, just for being themselves, offers society any compensatory benefits beyond the seductive pleasure it brings to those engaged in the exercise. (Baumeister, Campbell, Krueger, & Vohs, 2005)" In June this year, Wellesley High School became a focus of attention worldwide, following a graduation speech made by a teacher at the school. Departing from the traditional rhetoric of such ceremonies, English teacher David McCullough told the assembled graduates that they were neither special nor exceptional, but may well believe they were because they had been ‘pampered, cosseted, doted upon, helmeted, and bubble-wrapped, feted and fawned over’, an effect, he argued, of Americans’ ‘love of accolades more than genuine achievement’ (Christakis, 2012, p. 1). This assertion struck a chord not only in his home country, but more widely in the Western world, with many educators, childcare workers and parents experiencing a sense of unease about the extent to which this claim was justifiable, and if so, what sort of corrective might be needed.

To increase or decrease dosage of antimicrobials in septic patients during continuous renal replacement therapy: the eternal doubt

Critical illness, acute renal failure and continuous renal replacement therapy (CRRT) are associated with changes in pharmacokinetics. Initial antibiotic dose should be based on published volume of distribution and generally be at least the standard dose, as volume of distribution is usually unchanged or increased. Subsequent doses should be based on total clearance. Total clearance varies with the CRRT clearance which mainly depends on effluent flow rate, sieving coefficient/saturation coefficient. As antibiotic clearance by healthy kidneys is usually higher than clearance by CRRT, except for colistin, subsequent doses should generally be lower than given to patients without renal dysfunction. In the future therapeutic drug monitoring, together with sophisticated pharmacokinetic models taking into account the pharmacokinetic variability, may enable more appropriate individualized dosing.

Consistent responses of soil microbial communities to elevated nutrient inputs in grasslands across the globe

Soil microorganisms are critical to ecosystem functioning and the maintenance of soil fertility. However, despite global increases in the inputs of nitrogen (N) and phosphorus (P) to ecosystems due to human activities, we lack a predictive understanding of how microbial communities respond to elevated nutrient inputs across environmental gradients. Here we used high-throughput sequencing of marker genes to elucidate the responses of soil fungal, archaeal, and bacterial communities using an N and P addition experiment replicated at 25 globally distributed grassland sites. We also sequenced metagenomes from a subset of the sites to determine how the functional attributes of bacterial communities change in response to elevated nutrients. Despite strong compositional differences across sites, microbial communities shifted in a consistent manner with N or P additions, and the magnitude of these shifts was related to the magnitude of plant community responses to nutrient inputs. Mycorrhizal fungi and methanogenic archaea decreased in relative abundance with nutrient additions, as did the relative abundances of oligotrophic bacterial taxa. The metagenomic data provided additional evidence for this shift in bacterial life history strategies because nutrient additions decreased the average genome sizes of the bacterial community members and elicited changes in the relative abundances of representative functional genes. Our results suggest that elevated N and P inputs lead to predictable shifts in the taxonomic and functional traits of soil microbial communities, including increases in the relative abundances of faster-growing, copiotrophic bacterial taxa, with these shifts likely to impact belowground ecosystems worldwide.

Natural convection from a vertical cone in a porous medium due to the combined effects of heat and mass diffusion with non-uniform wall temperature/concentration or heat/mass flux and suction/injection

An analysis has been carried out to study the non-Darcy natural convention flow of Newtonian fluids on a vertical cone embedded in a saturated porous medium with power-law variation of the wall temperature/concentration or heat/mass flux and suction/injection with the streamwise distance x. Both non-similar and self-similar solutions have been obtained. The effects of non-Darcy parameter, ratio of the buoyancy forces due to mass and heat diffusion, variation of wall temperature/concentration or heat/mass flux and suction/injection on the Nusselt and Sherwood numbers have been studied.

Chemical Characterization of Urinary Pheromones in Brown Antechinus, Antechinus stuartii

In the small dasyurid marsupial, Antechinus stuartii, males exhibit scent-marking in the form of cloacal marking of nesting areas during the breeding season. Females of this species show no such behavior. To characterize the potential male pheromonal scent signal, urine-derived volatiles from sexually active males were analyzed by GC-MS and compared to that of females and a castrated male. More than 10 urinary compounds were identified. A series of homologous methylketones was observed in both males and females, whereas aldehydes were present only in female urine. Urine from the castrate was virtually compound-free except for minute concentrations of a compound tentatively identified as 2,4-dithiapentane. This compound was also found in one of the sexually active males. The GC profiles of the sexually active males contained high concentrations of two pyrazine derivatives and four methylketones that were not detected in the profiles of either females or the castrate. These compounds may influence social communication in the brown antechinus, Antechinus stuartii.