Cone signals and activity in myopia and emmetropia

Myopia (short-sightedness) is a common ocular disorder of children and young adults. Studies primarily using animal models have shown that the retina controls eye growth and the outer retina is likely to have a key role. One theory is that the proportion of L (long-wavelength-sensitive) and M (medium-wavelength-sensitive) cones is related to myopia development; with a high L/M cone ratio predisposing individuals to myopia. However, not all dichromats (persons with red-green colour vision deficiency) with extreme L/M cone ratios have high refractive errors. We predict that the L/M cone ratio will vary in individuals with normal trichromatic colour vision but not show a systematic difference simply due to refractive error. The aim of this study was to determine if L/M cone ratios in the central 30° are different between myopic and emmetropic young, colour normal adults. Information about L/M cone ratios was determined using the multifocal visual evoked potential (mfVEP). The mfVEP can be used to measure the response of visual cortex to different visual stimuli. The visual stimuli were generated and measurements performed using the Visual Evoked Response Imaging System (VERIS 5.1). The mfVEP was measured when the L and M cone systems were separately stimulated using the method of silent substitution. The method of silent substitution alters the output of three primary lights, each with physically different spectral distributions to control the excitation of one or more photoreceptor classes without changing the excitation of the unmodulated photoreceptor classes. The stimulus was a dartboard array subtending 30° horizontally and 30° vertically on a calibrated LCD screen. The m-sequence of the stimulus was 215-1. The N1-P1 amplitude ratio of the mfVEP was used to estimate the L/M cone ratio. Data were collected for 30 young adults (22 to 33 years of age), consisting of 10 emmetropes (+0.3±0.4 D) and 20 myopes (–3.4±1.7 D). The stimulus and analysis techniques were confirmed using responses of two dichromats. For the entire participant group, the estimated central L/M cone ratios ranged from 0.56 to 1.80 in the central 3°-13° diameter ring and from 0.94 to 1.91 in the more peripheral 13°-30° diameter ring. Within 3°-13°, the mean L/M cone ratio of the emmetropic group was 1.20±0.33 and the mean was similar, 1.20±0.26, for the myopic group. For the 13°-30° ring, the mean L/M cone ratio of the emmetropic group was 1.48±0.27 and it was slightly lower in the myopic group, 1.30±0.27. Independent-samples t-test indicated no significant difference between the L/M cone ratios of the emmetropic and myopic group for either the central 3°-13° ring (p=0.986) or the more peripheral 13°-30° ring (p=0.108). The similar distributions of estimated L/M cone ratios in the sample of emmetropes and myopes indicates that there is likely to be no association between the L/M cone ratio and refractive error in humans.

Controls on mid-Holocene fringing reef growth and termination in a high latitude, estuarine setting, Wellington Point, Southeast Queensland

Several fringing coral reefs in Moreton Bay, Southeast Queensland, some 300 km south of the Great Barrier Reef (GBR), are set in a relatively high latitude, estuarine environment that is considered marginal for coral growth. Previous work indicated that these marginal reefs, as with many fringing reefs of the inner GBR, ceased accreting in the mid-Holocene. This research presents for the first time data from the subsurface profile of the mid-Holocene fossil reef at Wellington Point comprising U/Th dates of in situ and framework corals, and trace element analysis from the age constrained carbonate fragments. Based on trace element proxies the palaeo-water quality during reef accretion was reconstructed. Results demonstrate that the reef initiated more than 7,000 yr BP during the post glacial transgression, and the initiation progressed to the west as sea level rose. In situ micro-atolls indicate that sea level was at least 1 m above present mean sea level by 6,680 years ago. The reef remained in "catch-up" mode, with a seaward sloping upper surface, until it stopped aggrading abruptly at ca 6,000 yr BP; no lateral progradation occurred. Changes in sediment composition encountered in the cores suggest that after the laterite substrate was covered by the reef, most of the sediment was produced by the carbonate factory with minimal terrigenous influence. Rare earth element, Y and Ba proxies indicate that water quality during reef accretion was similar to oceanic waters, considered suitable for coral growth. A slight decline in water quality on the basis of increased Ba in the later stages of growth may be related to increased riverine input and partial closing up of the bay due to either tidal delta progradation, climatic change and/or slight sea level fall. The age data suggest that termination of reef growth coincided with a slight lowering of sea level, activation of ENSO and consequent increase in seasonality, lowering of temperatures and the constrictions to oceanic flushing. At the cessation of reef accretion the environmental conditions in the western Moreton Bay were changing from open marine to estuarine. The living coral community appears to be similar to the fossil community, but without the branching Acropora spp. that were more common in the fossil reef. In this marginal setting coral growth periods do not always correspond to periods of reef accretion due to insufficient coral abundance. Due to several environmental constraints modern coral growth is insufficient for reef growth. Based on these findings Moreton Bay may be unsuitable as a long term coral refuge for most species currently living in the GBR.

"Ruby's Music Festival" : developing problem solving skills using online scenarios and creating opportunities to feed forward

One of the characteristics of good teaching is giving the highest quality feedback on student work but the term “feedback” is most commonly associated with summative assessment given by a teacher after work is completed. The student can often be a passive participant in the process. This article looks at the implementation of web based scenarios completed by students prior to summative assessment with the objective of improving legal problem solving skills. It examines the design process and the implementation of the problem solving activity and the approach to teaching and learning taken in the new law unit of which it is part. We argue that such activities are effective tools to feed forward and reflect on the implications for the effective teaching of law in higher education.

Production of porous metal oxides

Porous complex oxides are produced by reacting metal oxide precursors in the presence of a pore-forming material to provide pore sizes in the range of 7-250 nm, followed by removal of the pore-forming material under conditions preserving the structure and compn. of the formed oxides. The pore-forming material are carbon black particles having a particle size of 10-100 nm. The carbon particles are removed from the formed oxide by heating at 100-300°. A surfactant can be added to the reaction mixt. [on SciFinder(R)]

Overexpression of the mammalian target of rapamycin (mTOR) and angioinvasion are poor prognostic factors in early stage NSCLC: A verification study

Background: A recent study by Dhillon et al. [12], identified both angioinvasion and mTOR as prognostic biomarkers for poor survival in early stage NSCLC. The aim of this study was to verify the above study by examining the angioinvasion and mTOR expression profile in a cohort of early stage NSCLC patients and correlate the results to patient clinico-pathological data and survival. Methods: Angioinvasion was routinely recorded by the pathologist at the initial assessment of the tumor following resection. mTOR was evaluated in 141 early stage (IA-IIB) NSCLC patients (67 - squamous; 60 - adenocarcinoma; 14 - others) using immunohistochemistry (IHC) analysis with an immunohistochemical score (IHS) calculated (% positive cells × staining intensity). Intensity was scored as follows: 0 (negative); 1+ (weak); 2+ (moderate); 3+ (strong). The range of scores was 0-300. Based on the previous study a cut-off score of 30 was used to define positive versus negative patients. The impact of angioinvasion and mTOR expression on prognosis was then evaluated. Results: 101 of the 141 tumors studied expressed mTOR. There was no difference in mTOR expression between squamous cell carcinoma and adenocarcinoma. Angioinvasion (p= 0.024) and mTOR staining (p= 0.048) were significant univariate predictors of poor survival. Both remained significant after multivariate analysis (p= 0.037 and p= 0.020, respectively). Conclusions: Our findings verify angioinvasion and mTOR expression as new biomarkers for poor outcome in patients with early stage NSCLC. mTOR expressing patients may benefit from novel therapies targeting the mTOR survival pathway. © 2011 Elsevier Ireland Ltd.

Design, construction, and analysis of cell line arrays and tissue microarrays for gene expression analysis

Cell line array (CMA) and tissue microarray (TMA) technologies are high-throughput methods for analysing both the abundance and distribution of gene expression in a panel of cell lines or multiple tissue specimens in an efficient and cost-effective manner. The process is based on Kononen's method of extracting a cylindrical core of paraffin-embedded donor tissue and inserting it into a recipient paraffin block. Donor tissue from surgically resected paraffin-embedded tissue blocks, frozen needle biopsies or cell line pellets can all be arrayed in the recipient block. The representative area of interest is identified and circled on a haematoxylin and eosin (H&E)-stained section of the donor block. Using a predesigned map showing a precise spacing pattern, a high density array of up to 1,000 cores of cell pellets and/or donor tissue can be embedded into the recipient block using a tissue arrayer from Beecher Instruments. Depending on the depth of the cell line/tissue removed from the donor block 100-300 consecutive sections can be cut from each CMA/TMA block. Sections can be stained for in situ detection of protein, DNA or RNA targets using immunohistochemistry (IHC), fluorescent in situ hybridisation (FISH) or mRNA in situ hybridisation (RNA-ISH), respectively. This chapter provides detailed methods for CMA/TMA design, construction and analysis with in-depth notes on all technical aspects including tips to deal with common pitfalls the user may encounter. © Springer Science+Business Media, LLC 2011.

Phase II study of liarozole in advanced non-small cell lung cancer

The aim of this phase II study was to investigate the efficacy and tolerability of liarozole, a novel benzimidazole derivative, in non-small cell lung cancer (NSCLC). Liarozole 300 mg twice daily orally was evaluated in 14 patients with stage IIIB and IV NSCLC. 8 patients had received prior treatment with chemotherapy and/or radiotheraphy. WHO toxocity grading and response criteria were used. Liarozole was well tolerated. Grade 2 toxicities included alopecia (1 patient), dermatological toxicity (5 patients), dry mouth (2 patients) and nausea and vomiting (2 patients). Leukocytosis was seen in 5 patients, including 2 cases with an elevated white cell count pretreatment. Liarozole was discontinued in 1 patient who developed intolerable progressive pruritis associated with an erythematous rash. No objective tumour response was seen, all 14 patients developing progressive disease with 4 months of commencing treatment. Liarozole was well tolerated but was ineffective as single as single agent therapy in the management of NSCLC. The side-effect profile was compatible with inhibition of retinoic acid degradation.

A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

The aims of this phase I study were to establish the maximum tolerated dose, safety profile and activity of liposomal daunorubicin, DaunoXome (NeXstar Pharmaceuticals), in the treatment of metastatic breast cancer. DaunoXome was administered intravenously over 2 h in 21 day cycles and doses were increased from 80 to 100, 120 and 150 mg m 2. Sixteen patients were enrolled. A total of 70 cycles of DaunoXome were administered. The maximum tolerated dose was 120 mg m 2, the dose-limiting toxicity being prolonged grade 4 neutropenia or neutropenic pyrexia necessitating dose reductions at 120 and 150 mg m 2. Asymptomatic cardiotoxicity was observed in three patients: grade 1 in one treated with a cumulative dose of 800 mg m 2 and grade 2 in two, one who received a cumulative dose of 960 mg m 2 and the other a cumulative dose of 600 mg m 2 with a previous neoadjuvant doxorubicin chemotherapy of 300 mg m 2. Tumour response was evaluable in 15 patients, of whom two had objective responses, six had stable disease and seven had progressive disease. In conclusion, DaunoXome is associated with mild, manageable toxicities and has anti-tumour activity in metastatic breast cancer. The findings support further phase II evaluation of DaunoXome alone and in combination with other standard non-anthracycline cytotoxic or novel targeted agents. Although the dose-limiting toxicity for DaunoXome was febrile neutropenia at 120 mg m 2, we would recommend this dose for further evaluation, as the febrile neutropenia occurred after four or more cycles in three of the four episodes seen, was short lived and uncomplicated. © 2002 Cancer Research UK.

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.

Developing sustainable ‘liveable’ buildings, cities and communities for a sub-tropical context : residents’ perspectives

A key challenge for the 21st Century is to make our cities more liveable and foster economically sustainable, environmentally responsible, and socially inclusive communities. Design thinking, particularly a human-centred approach, offers a way to tackle this challenge. Findings from two recent Australian research projects highlight how facilitating sustainable, liveable communities in a humid sub-tropical environment requires an in-depth understanding of people’s perspectives, experiences and practices. Project 1 (‘Research House’) documents the reflections of a family who lived in a ‘test’ sustainable house for two years, outlining their experience and evaluations of universal design and sustainable technologies. The study family was very impressed with the natural lighting, natural ventilation, spaciousness and ease of access, which contributed significantly to their comfort and the liveability of their home. Project 2 (‘Inner-Urban High Density Living’) explored Brisbane residents’ opinions about high-density living, through a survey (n=636), interviews (n=24), site observations (over 300 hours) and environmental monitoring, assessing opinions on the liveability of their individual dwelling, the multi-unit host building and the surrounding neighbourhood. Nine areas, categorised into three general domains, were identified as essential for enhancing high density liveability. In terms of the dwelling, thermal comfort/ventilation, natural light, noise mitigation were important; shared space, good neighbour protocols, and support for environmentally sustainable behaviour were desired in the building/complex; and accessible/sustainable transport, amenities and services, sense of community were considered important in the surrounding neighbourhood. Combined, these findings emphasise the importance and complexity associated with designing liveable building, cities and communities, illustrating how adopting a design thinking, human-centred approach will help create sustainable communities that will meet the needs of current and future generations.

Sustainability of a successful health and nutrition program in a remote Aboriginal community

OBJECTIVE: To assess the long term effect of a nutrition program in a remote Aboriginal community (Minjilang). DESIGN: Evaluation of nutritional outcomes over the three years before and the three years after a health and nutrition program that ran from June 1989 to June 1990. Turnover of food items at the community store was used as a measure of dietary intake at Minjilang and a comparison community. SETTING: A community of about 150 Aboriginal people live at Minjilang on Croker Island, 240 km north-east of Darwin. A similar community of about 300 people on another island was used as the comparison. RESULTS: The program produced lasting improvements in dietary intake of most target foods (including fruit, vegetables and wholegrain bread) and nutrients (including folate, ascorbic acid and thiamine). Sugar intake fell in both communities before the program, but the additional decrease in sugar consumption during the program at Minjilang "rebounded" in the next year. Dietary improvements in the comparison community were delayed and smaller than at Minjilang. CONCLUSIONS: The success of the program at Minjilang was linked to an ongoing process of social change, which in turn provided a stimulus for dietary improvement in the comparison community. When Aboriginal people themselves control and maintain ownership of community-based intervention programs, nutritional improvements can be initiated and sustained.

The Tarim picrite-basalt-rhyolite suite, a Permian flood basalt from Northwest China with contrasting rhyolites produced by fractional crystallization and anatexis

We report major and trace element composition, Sr–Nd isotopic and seismological data for a picrite–basalt–rhyolite suite from the northern Tarim uplift (NTU), northwest China. The samples were recovered from 13 boreholes at depths between 5,166 and 6,333 m. The picritic samples have high MgO (14.5–16.8 wt%, volatiles included) enriched in incompatible element and have high 87Sr/86Sr and low 143Nd/144Nd isotopic ratios (εNd (t) = −5.3; Sri = 0.707), resembling the Karoo high-Ti picrites. All the basaltic samples are enriched in TiO2 (2.1–3.2 wt%, volatiles free), have high FeOt abundances (11.27–15.75 wt%, volatiles free), are enriched in incompatible elements and have high Sr and low Nd isotopic ratios (Sri = 0.7049–0.7065; εNd (t) = −4.1 to −0.4). High Nb/La ratios (0.91–1.34) of basalts attest that they are mantle-derived magma with negligible crustal contamination. The rhyolite samples can be subdivided into two coeval groups with overlapping U–Pb zircon ages between 291 ± 4 and 272 ± 2 Ma. Group 1 rhyolites are enriched in Nb and Ta, have similar Nb/La, Nb/U, and Sr–Nd isotopic compositions to the associated basalts, implying that they are formed by fractional crystallization of the basalts. Group 2 rhyolites are depleted in Nb and Ta, have low Nb/La ratios, and have very high Sr and low Nd isotopic ratios, implying that crustal materials have been extensively, if not exclusively, involved in their source. The picrite–basalt–rhyolite suite from the NTU, together with Permian volcanic rocks from elsewhere Tarim basin, constitute a Large Igneous Province (LIP) that is characterized by large areal extent, rapid eruption, OIB-type chemical composition, and eruption of high temperature picritic magma. The Early Permian magmatism, which covered an area >300,000 km2, is therefore named the Tarim Flood Basalt.

Toward understanding social engineering

There is no doubt that social engineering plays a vital role in compromising most security defenses, and in attacks on people, organizations, companies, or even governments. It is the art of deceiving and tricking people to reveal critical information or to perform an action that benefits the attacker in some way. Fraudulent and deceptive people have been using social engineering traps and tactics using information technology such as e-mails, social networks, web sites, and applications to trick victims into obeying them, accepting threats, and falling victim to various crimes and attacks such as phishing, sexual abuse, financial abuse, identity theft, impersonation, physical crime, and many other forms of attack. Although organizations, researchers, practitioners, and lawyers recognize the severe risk of social engineering-based threats, there is a severe lack of understanding and controlling of such threats. One side of the problem is perhaps the unclear concept of social engineering as well as the complexity of understand human behaviors in behaving toward, approaching, accepting, and failing to recognize threats or the deception behind them. The aim of this paper is to explain the definition of social engineering based on the related theories of the many related disciplines such as psychology, sociology, information technology, marketing, and behaviourism. We hope, by this work, to help researchers, practitioners, lawyers, and other decision makers to get a fuller picture of social engineering and, therefore, to open new directions of collaboration toward detecting and controlling it.

Reconstruction of the ancestral marsupial karyotype from comparative gene maps

BACKGROUND: The increasing number of assembled mammalian genomes makes it possible to compare genome organisation across mammalian lineages and reconstruct chromosomes of the ancestral marsupial and therian (marsupial and eutherian) mammals. However, the reconstruction of ancestral genomes requires genome assemblies to be anchored to chromosomes. The recently sequenced tammar wallaby (Macropus eugenii) genome was assembled into over 300,000 contigs. We previously devised an efficient strategy for mapping large evolutionarily conserved blocks in non-model mammals, and applied this to determine the arrangement of conserved blocks on all wallaby chromosomes, thereby permitting comparative maps to be constructed and resolve the long debated issue between a 2n=14 and 2n=22 ancestral marsupial karyotype. RESULTS: We identified large blocks of genes conserved between human and opossum, and mapped genes corresponding to the ends of these blocks by fluorescence in situ hybridization (FISH). A total of 242 genes was assigned to wallaby chromosomes in the present study, bringing the total number of genes mapped to 554 and making it the most densely cytogenetically mapped marsupial genome. We used these gene assignments to construct comparative maps between wallaby and opossum, which uncovered many intrachromosomal rearrangements, particularly for genes found on wallaby chromosomes X and 3. Expanding comparisons to include chicken and human permitted the putative ancestral marsupial (2n=14) and therian mammal (2n=19) karyotypes to be reconstructed. CONCLUSIONS: Our physical mapping data for the tammar wallaby has uncovered the events shaping marsupial genomes and enabled us to predict the ancestral marsupial karyotype, supporting a 2n=14 ancestor. Futhermore, our predicted therian ancestral karyotype has helped to understand the evolution of the ancestral eutherian genome.

Photodissociation of TEMPO-modified peptides: New approaches to radical-directed dissociation of biomolecules

Radical-directed dissociation of gas phase ions is emerging as a powerful and complementary alternative to traditional tandem mass spectrometric techniques for biomolecular structural analysis. Previous studies have identified that coupling of 2-[(2,2,6,6-tetramethylpiperidin-1-oxyl)methyl] benzoic acid (TEMPO-Bz) to the N-terminus of a peptide introduces a labile oxygen-carbon bond that can be selectively activated upon collisional activation to produce a radical ion. Here we demonstrate that structurally-defined peptide radical ions can also be generated upon UV laser photodissociation of the same TEMPO-Bz derivatives in a linear ion-trap mass spectrometer. When subjected to further mass spectrometric analyses, the radical ions formed by a single laser pulse undergo identical dissociations as those formed by collisional activation of the same precursor ion, and can thus be used to derive molecular structure. Mapping the initial radical formation process as a function of photon energy by photodissociation action spectroscopy reveals that photoproduct formation is selective but occurs only in modest yield across the wavelength range (300-220 nm), with the photoproduct yield maximised between 235 and 225 nm. Based on the analysis of a set of model compounds, structural modifications to the TEMPO-Bz derivative are suggested to optimise radical photoproduct yield. Future development of such probes offers the advantage of increased sensitivity and selectivity for radical-directed dissociation. © 2014 the Owner Societies.