EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer : analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 First-Line ErbituX in lung cancer (FLEX) study showed that the addition of cetuximab to first-line chemotherapy significantly improved overall survival compared with chemotherapy alone (hazard ratio [HR] 0·871, 95% CI 0·762-0·996; p=0·044) in patients with advanced non-small-cell lung cancer (NSCLC). To define patients benefiting most from cetuximab, we studied the association of tumour EGFR expression level with clinical outcome in FLEX study patients. Methods: We used prospectively collected tumour EGFR expression data to generate an immunohistochemistry score for FLEX study patients on a continuous scale of 0-300. We used response data to select an outcome-based discriminatory threshold immunohistochemistry score for EGFR expression of 200. Treatment outcome was analysed in patients with low (immunohistochemistry score <200) and high (≥200) tumour EGFR expression. The primary endpoint in the FLEX study was overall survival. We analysed patients from the FLEX intention-to-treat (ITT) population. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: Tumour EGFR immunohistochemistry data were available for 1121 of 1125 (99·6%) patients from the FLEX study ITT population. High EGFR expression was scored for 345 (31%) evaluable patients and low for 776 (69%) patients. For patients in the high EGFR expression group, overall survival was longer in the chemotherapy plus cetuximab group than in the chemotherapy alone group (median 12·0 months [95% CI 10·2-15·2] vs 9·6 months [7·6-10·6]; HR 0·73, 0·58-0·93; p=0·011), with no meaningful increase in side-effects. We recorded no corresponding survival benefit for patients in the low EGFR expression group (median 9·8 months [8·9-12·2] vs 10·3 months [9·2-11·5]; HR 0·99, 0·84-1·16; p=0·88). A treatment interaction test assessing the difference in the HRs for overall survival between the EGFR expression groups suggested a predictive value for EGFR expression (p=0·044). Interpretation: High EGFR expression is a tumour biomarker that can predict survival benefit from the addition of cetuximab to first-line chemotherapy in patients with advanced NSCLC. Assessment of EGFR expression could offer a personalised treatment approach in this setting. Funding: Merck KGaA. © 2012 Elsevier Ltd.

Nondiscretionary residential water use : the impact of habits and water-efficient technologies

Several studies published in the last few decades have demonstrated a low price-elasticity for residential water use. In particular, it has been shown that there is a quantity of water demanded that remains constant regardless of prices and other economic factors. In this research, we characterise residential water demand based on a Stone-Geary utility function. This specification is not only theory-compatible but can also explicitly model a minimum level of consumption not dependent on prices or income. This is described as minimum threshold or nondiscretionary water use. Additionally, the Stone-Geary framework is used to model the subsistence level of water consumption that is dependent on the temporal evolution of consumer habits and stock of physical capital. The main aim of this study is to analyse the impact of water-saving habits and water-efficient technologies on residential water demand, while additionally focusing attention on nondiscretionary uses. This is informed by an empirical application using data from a survey conducted among residents of Brisbane City Council, Australia. The results will be especially useful in the design of water tariffs and other water-saving policies.

Stereotypes of age differences in personality traits : universal and accurate?

Age trajectories for personality traits are known to be similar across cultures. To address whether stereotypes of age groups reflect these age-related changes in personality, we asked participants in 26 countries (N = 3,323) to rate typical adolescents, adults, and old persons in their own country. Raters across nations tended to share similar beliefs about different age groups; adolescents were seen as impulsive, rebellious, undisciplined, preferring excitement and novelty, whereas old people were consistently considered lower on impulsivity, activity, antagonism, and Openness. These consensual age group stereotypes correlated strongly with published age differences on the five major dimensions of personality and most of 30 specific traits, using as criteria of accuracy both self-reports and observer ratings, different survey methodologies, and data from up to 50 nations. However, personal stereotypes were considerably less accurate, and consensual stereotypes tended to exaggerate differences across age groups.

The bioeconomics of nutritional poverty and child labour

This paper provides a bio-economic foundation of fertility and child labor. Drawing on the clinical and physiological literature, the model highlights the interaction between work efforts of adults and children, their subsistence consumption, and fertility. The subsistence consumption requirements are endogenous to physical efforts. Parents engaged in physically demanding occupations (e.g. non-mechanized agriculture) are likely to suffer from energy deficiency, leading to reduced future work-capacity. Consumption smoothing occurs through bearing a large number of children who provide income support as adults. Although net cost of an additional child is positive, the cost is balanced by the additional income accruing though child employment. In contrast, parents in low-physical effort occupations are less likely to su¤er from nutritional deficiency, and thus tend to have lower fertility and child labor.

New approaches to making the microenvironment of the female reproductive tract hostile to HIV

The studies presented in this review explore three distinct areas with potential for inhibiting HIV infection in women. Based on emerging information from the physiology, endocrinology and immunology of the female reproductive tract (FRT), we propose unique 'works in progress' for protecting women from HIV. Various aspects of FRT immunity are suppressed by estradiol during the menstrual cycle, making women more susceptible to HIV infection. By engineering commensal Lactobacillus to secrete the anti-HIV molecule Elafin as estradiol levels increase, women could be protected from HIV infection. Selective estrogen response modifiers enhance barrier integrity and enhance secretion of protective anti-HIV molecules. Finally, understanding the interactions and regulation of FRT endogenous antimicrobials, proteases, antiproteases, etc., all of which are under hormonal control, will open new avenues to therapeutic manipulation of the FRT mucosal microenvironment. By seeking new alternatives to preventing HIV infection in women, we may finally disrupt the HIV pandemic.

Effects of scaffold architecture on mechanical characteristics and osteoblast response to static and perfusion bioreactor cultures

Tissue engineering focuses on the repair and regeneration of tissues through the use of biodegradable scaffold systems that structurally support regions of injury whilst recruiting and/or stimulating cell populations to rebuild the target tissue. Within bone tissue engineering, the effects of scaffold architecture on cellular response have not been conclusively characterized in a controlled-density environment. We present a theoretical and practical assessment of the effects of polycaprolactone (PCL) scaffold architectural modifications on mechanical and flow characteristics as well as MC3T3-E1 preosteoblast cellular response in an in vitro static plate and custom-designed perfusion bioreactor model. Four scaffold architectures were contrasted, which varied in inter-layer lay-down angle and offset between layers, whilst maintaining a structural porosity of 60 ± 5%. We established that as layer angle was decreased (90° vs. 60°) and offset was introduced (0 vs. 0.5 between layers), structural stiffness, yield stress, strength, pore size and permeability decreased, whilst computational fluid dynamics-modeled wall shear stress was increased. Most significant effects were noted with layer offset. Seeding efficiencies in static culture were also dramatically increased due to offset (~45% to ~86%), with static culture exhibiting a much higher seeding efficiency than perfusion culture. Scaffold architecture had minimal effect on cell response in static culture. However, architecture influenced osteogenic differentiation in perfusion culture, likely by modifying the microfluidic environment.

The TFOS International Workshop on Contact Lens Discomfort: report of the contact lens interactions with the ocular surface and adnexa subcommittee

The report of this subcommittee concerns the impact of contact lenses (CLs) on the ocular surface, with a particular emphasis on CL discomfort (CLD). We define the ocular surface, its regional anatomy, and the physiological responses of each region to CL wear.

Longitudinal assessment of neuropathy in type 1 diabetes using novel ophthalmic markers (LANDMark) : study design and baseline characteristics

Aims Corneal nerve morphology and corneal sensation threshold have recently been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of the ‘Longitudinal Assessment of Neuropathy in type 1 Diabetes using novel ophthalmic Markers’(LANDMark) study. Methods The LANDMark study is a 4-year, two-site, natural history study of three participant groups: type 1 diabetes with neuropathy (T1W), type 1 diabetes without neuropathy (T1WO) and control participants without diabetes or neuropathy. All participants undergo a detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal aesthesiometry. Results 76 T1W, 166 T1WO and 154 control participants were enrolled into the study. Corneal sensation threshold (mbars) was significantly higher (i.e. sensitivity was lower) in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (p < 0.001), with no difference between T1WO and controls. Corneal nerve fibre length was lower in T1W (14.0 ± 6.4 mm/mm2) compared to T1WO (19.1 ± 5.8 mm/mm2) and controls (23.2 ± 6.3 mm/mm2) (p < 0.001). Corneal nerve fibre length was lower in T1WO compared to controls. Conclusions The LANDMark baseline findings confirm a reduction in corneal sensitivity only in Type 1 patients with neuropathy. However, corneal nerve fibre length is reduced even in Type 1 patients without neuropathy with an even greater deficit in Type 1 patients with neuropathy.

Modeling perceived influences on journalism : evidence from a cross-national survey of journalists

Surveying 1,700 journalists from seventeen countries, this study investigates perceived influences on news work. Analysis reveals a dimensional structure of six distinct domains—political, economic, organizational, professional, and procedural influences, as well as reference groups. Across countries, these six dimensions build up a hierarchical structure where organizational, professional, and procedural influences are perceived as more powerful limits to journalists' work than political and economic influences.

Mapping journalism cultures across nations : a comparative study of 18 countries

This article reports key findings from a comparative survey of the role perceptions, epistemological orientations and ethical views of 1800 journalists from 18 countries. The results show that detachment, non-involvement, providing political information and monitoring the government are considered essential journalistic functions around the globe. Impartiality, the reliability and factualness of information, as well as adherence to universal ethical principles are also valued worldwide, though their perceived importance varies across countries. Various aspects of interventionism, objectivism and the importance of separating facts from opinion, on the other hand, seem to play out differently around the globe. Western journalists are generally less supportive of any active promotion of particular values, ideas and social change, and they adhere more to universal principles in their ethical decisions. Journalists from non-western contexts, on the other hand, tend to be more interventionist in their role perceptions and more flexible in their ethical views.

Future of arthroplasty : registries and outcome measures

Since the inception of the first Joint Registry in Sweden in 1979, many countries including Finland, Norway, Denmark, Australia, New Zealand, Canada, Scotland, England and Wales now have more than 10 years experience and data, and are collecting data on more than 90% of the procedures performed nationally. There are also Joint Registries in Romania, Slovakia, Slovenia, Croatia, Hungary, France, Germany, Switzerland, Czech Republic, Italy, Austria and Portugal, and work is ongoing to develop a Joint Registry in the US...

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.

A survey of control allocation methods for underwater vehicles

A control allocation system implements a function that maps the desired control forces generated by the vehicle motion controller into the commands of the different actuators. In this article, a survey of control allocation methods for over-actuated underwater vehicles is presented. The methods are applicable for both surface vessels and underwater vehicles. The paper presents a survey of control allocation methods with focus on mathematical representation and solvability of thruster allocation problems. The paper is useful for university students and engineers who want to get an overview of state-of-the art control allocation methods as well as advance methods to solve more complex problems.

Infrared and Raman spectroscopic characterization of the Borate mineral Vonsenite

There are a large number of boron-containing minerals, of which vonsenite is one. Some discussion about the molecular structure of vonsenite exists in the literature. Whether water is involved in the structure is ill-determined. The molecular structure of vonsenite has been assessed by the combination of Raman and infrared spectroscopy. The Raman spectrum is characterized by two intense broad bands at 997 and 1059 cm−1 assigned to the BO stretching vibrational mode. A series of Raman bands in the 1200–1500 cm−1 spectral range are attributed to BO antisymmetric stretching modes and in-plane bending modes. The infrared spectrum shows complexity in this spectral range. No Raman spectrum of water in the OH stretching region could be obtained. The infrared spectrum shows a series of overlapping bands with bands identified at 3037, 3245, 3443, 3556, and 3614 cm−1. It is important to understand the structure of vonsenite in order to form nanomaterials based on its structure. Vibrational spectroscopy enables a better understanding of the structure of vonsenite.

Accessibility of pores in coal to methane and carbon dioxide

Fluid–solid interactions in natural and engineered porous solids underlie a variety of technological processes, including geological storage of anthropogenic greenhouse gases, enhanced coal bed methane recovery, membrane separation, and heterogeneous catalysis. The size, distribution and interconnectivity of pores, the chemical and physical properties of the solid and fluid phases collectively dictate how fluid molecules migrate into and through the micro- and meso-porous media, adsorb and ultimately react with the solid surfaces. Due to the high penetration power and relatively short wavelength of neutrons, smallangle neutron scattering (SANS) as well as ultra small-angle scattering (USANS) techniques are ideally suited for assessing the phase behavior of confined fluids under pressure as well as for evaluating the total porosity in engineered and natural porous systems including coal. Here we demonstrate that SANS and USANS can be also used for determining the fraction of the pore volume that is actually accessible to fluids as a function of pore sizes and study the fraction of inaccessible pores as a function of pore size in three coals from the Illinois Basin (USA) and Bowen Basin (Australia). Experiments were performed at CO2 and methane pressures up to 780 bar, including pressures corresponding to zero average contrast condition (ZAC), which is the pressure where no scattering from the accessible pores occurs. Scattering curves at the ZAC were compared with the scattering from same coals under vacuum and analysed using a newly developed approach that shows that the volume fraction of accessible pores in these coals varies between �90% in the macropore region to �30% in the mesopore region and the variation is distinctive for each of the examined coals. The developed methodology may be also applied for assessing the volume of accessible pores in other natural underground formations of interest for CO2 sequestration, such as saline aquifers as well as for estimating closed porosity in engineered porous solids of technological importance.