Conspicuity of staircase configuration: Effects of markings and contrast.

PURPOSE: To be able to walk safely up or down a staircase, we must be able to judge the configuration and slope of the staircase and our viewing position. Adding markings to the stairs might help form correct perceptions of the staircase geometry. In this study, we examined how visual judgements about staircase configuration are affected by different marking patterns. METHODS: Fifteen normally sighted young participants viewed computer-generated images of staircases as seen from the top landing of the stairs. Marking patterns included contrasting baseboard, transverse edge-stripes, longitudinal side-stripes, longitudinal stripes, diamond patterns, longitudinal stripes extended to landing and diamond patterns extended to landing. For comparison, we included the no-marking condition as a control. We tested several contrast levels of marking patterns (3.2%-50%), pitch lines of the staircases (shallow/medium/steep) and viewing positions (left/centre/right). The effect of the overall shape cue of the staircase on participants' performance was also evaluated. We measured participants' accuracies in judging whether the staircase was shallow, medium or steep, and whether the viewing position was located to the left, centre or right. RESULTS: Transverse edge-stripes markings yielded fewer underestimations of slope (9% [transverse] vs. 18% [others]) when compared with other markers. The presence of an overall shape cue helped both slope (67% [presence] vs. 51% [absence]) and viewing position judgements (79% [presence] vs. 62% [absence]). When the overall shape cue was present, only the transverse edge-stripes markings yielded a significant improvement in performance (compared with no-marking condition). When the cue was absent, performance was significantly better with markings with high and moderate contrasts. CONCLUSIONS: Adding marking patterns such as high-contrast transverse stripes to stairs may help enhance the visibility of the stairs and judgements of staircase geometry. This might be particularly useful for people with visual impairment or normally sighted individuals under compromised environmental conditions.

Ancient marine sediment DNA reveals diatom transition in Antarctica.

Antarctica is one of the most vulnerable regions to climate change on Earth and studying the past and present responses of this polar marine ecosystem to environmental change is a matter of urgency. Sedimentary ancient DNA (sedaDNA) analysis can provide such insights into past ecosystem-wide changes. Here we present authenticated (through extensive contamination control and sedaDNA damage analysis) metagenomic marine eukaryote sedaDNA from the Scotia Sea region acquired during IODP Expedition 382. We also provide a marine eukaryote sedaDNA record of ~1 Mio. years and diatom and chlorophyte sedaDNA dating back to ~540 ka (using taxonomic marker genes SSU, LSU, psbO). We find evidence of warm phases being associated with high relative diatom abundance, and a marked transition from diatoms comprising <10% of all eukaryotes prior to ~14.5 ka, to ~50% after this time, i.e., following Meltwater Pulse 1A, alongside a composition change from sea-ice to open-ocean species. Our study demonstrates that sedaDNA tools can be expanded to hundreds of thousands of years, opening the pathway to the study of ecosystem-wide marine shifts and paleo-productivity phases throughout multiple glacial-interglacial cycles.

Episodes of Early Pleistocene West Antarctic Ice Sheet Retreat Recorded by Iceberg Alley Sediments.

Ice loss in the Southern Hemisphere has been greatest over the past 30 years in West Antarctica. The high sensitivity of this region to climate change has motivated geologists to examine marine sedimentary records for evidence of past episodes of West Antarctic Ice Sheet (WAIS) instability. Sediments accumulating in the Scotia Sea are useful to examine for this purpose because they receive iceberg-rafted debris (IBRD) sourced from the Pacific- and Atlantic-facing sectors of West Antarctica. Here we report on the sedimentology and provenance of the oldest of three cm-scale coarse-grained layers recovered from this sea at International Ocean Discovery Program Site U1538. These layers are preserved in opal-rich sediments deposited ∼1.2 Ma during a relatively warm regional climate. Our microCT-based analysis of the layer's in-situ fabric confirms its ice-rafted origin. We further infer that it is the product of an intense but short-lived episode of IBRD deposition. Based on the petrography of its sand fraction and the Phanerozoic 40Ar/39Ar ages of hornblende and mica it contains, we conclude that the IBRD it contains was likely sourced from the Weddell Sea and/or Amundsen Sea embayment(s) of West Antarctica. We attribute the high concentrations of IBRD in these layers to "dirty" icebergs calved from the WAIS following its retreat inland from its modern grounding line. These layers also sit at the top of a ∼366-m thick Pliocene and early Pleistocene sequence that is much more dropstone-rich than its overlying sediments. We speculate this fact may reflect that WAIS mass-balance was highly dynamic during the ∼41-kyr (inter)glacial world.

Antiphased dust deposition and productivity in the Antarctic Zone over 1.5 million years.

The Southern Ocean paleoceanography provides key insights into how iron fertilization and oceanic productivity developed through Pleistocene ice-ages and their role in influencing the carbon cycle. We report a high-resolution record of dust deposition and ocean productivity for the Antarctic Zone, close to the main dust source, Patagonia. Our deep-ocean records cover the last 1.5 Ma, thus doubling that from Antarctic ice-cores. We find a 5 to 15-fold increase in dust deposition during glacials and a 2 to 5-fold increase in biogenic silica deposition, reflecting higher ocean productivity during interglacials. This antiphasing persisted throughout the last 25 glacial cycles. Dust deposition became more pronounced across the Mid-Pleistocene Transition (MPT) in the Southern Hemisphere, with an abrupt shift suggesting more severe glaciations since ~0.9 Ma. Productivity was intermediate pre-MPT, lowest during the MPT and highest since 0.4 Ma. Generally, glacials experienced extended sea-ice cover, reduced bottom-water export and Weddell Gyre dynamics, which helped lower atmospheric CO2 levels.

Students' perceptions on their use of an EHR: pilot questionnaire study.

INTRODUCTION: Many clinical education programmes have not incorporated the use of the electronic health record (EHR) into their curriculum. It is important to incorporate technologies that will be used in real-world settings to better prepare students for clinical practice. OBJECTIVES: To undertake a review of literature to identify a training evaluation framework; to conduct a self-completion survey, pretraining and post-training, to determine students' perceptions on the benefit of using EHR training system. SETTING: Nursing School, University, North West England, UK; University Ethic Committee Approval Received. PARTICIPANTS: Registered nurses undertaking a validated return to practice course; 24 participants for the first cohort who completed pretraining questionnaire and 23 for the second post-training cohort. RESULTS: The statistical results show that the students perceived that the training improved their capability in employing digital systems with statistically significant difference in the assessed preproficiency and post proficiency in the use of digital clinical systems (premedians and post medians are 2 and 5 on 10-point Likert scale, p=0.041). There was also an indication of an improvement in the knowledge of EHR systems although not statistically significant. Most students perceived it increased their knowledge on digital systems. CONCLUSION: Students perceived an increase in proficiency with the EHR. There was evidence of improvement in confidence in the use of the EHR, but this confidence would be enhanced by additional use of the system. Some desire to increase confidence further and to develop knowledge of digital systems was expressed.

Harmonization of Outcomes and Vision Endpoints in Vision Restoration Trials: Recommendations from the International HOVER Taskforce.

Translational research in vision prosthetics, gene therapy, optogenetics, stem cell and other forms of transplantation, and sensory substitution is creating new therapeutic options for patients with neural forms of blindness. The technical challenges faced by each of these disciplines differ considerably, but they all face the same challenge of how to assess vision in patients with ultra-low vision (ULV), who will be the earliest subjects to receive new therapies. Historically, there were few tests to assess vision in ULV patients. In the 1990s, the field of visual prosthetics expanded rapidly, and this activity led to a heightened need to develop better tests to quantify end points for clinical studies. Each group tended to develop novel tests, which made it difficult to compare outcomes across groups. The common lack of validation of the tests and the variable use of controls added to the challenge of interpreting the outcomes of these clinical studies. In 2014, at the bi-annual International "Eye and the Chip" meeting of experts in the field of visual prosthetics, a group of interested leaders agreed to work cooperatively to develop the International Harmonization of Outcomes and Vision Endpoints in Vision Restoration Trials (HOVER) Taskforce. Under this banner, more than 80 specialists across seven topic areas joined an effort to formulate guidelines for performing and reporting psychophysical tests in humans who participate in clinical trials for visual restoration. This document provides the complete version of the consensus opinions from the HOVER taskforce, which, together with its rules of governance, will be posted on the website of the Henry Ford Department of Ophthalmology (www.artificialvision.org). Research groups or companies that choose to follow these guidelines are encouraged to include a specific statement to that effect in their communications to the public. The Executive Committee of the HOVER Taskforce will maintain a list of all human psychophysical research in the relevant fields of research on the same website to provide an overview of methods and outcomes of all clinical work being performed in an attempt to restore vision to the blind. This website will also specify which scientific publications contain the statement of certification. The website will be updated every 2 years and continue to exist as a living document of worldwide efforts to restore vision to the blind. The HOVER consensus document has been written by over 80 of the world's experts in vision restoration and low vision and provides recommendations on the measurement and reporting of patient outcomes in vision restoration trials.

The Biochemical Literacy Framework: Inviting pedagogical innovation in higher education.

When developing meaningful curricula, institutions must engage with the desired disciplinary attributes of their graduates. Successfully employed in several areas, including psychology and chemistry, disciplinary literacies provide structure for the development of core competencies-pursuing progressive education. To this end, we have sought to develop a comprehensive blueprint of a graduate biochemist, providing detailed insight into the development of skills in the context of disciplinary knowledge. The Biochemical Literacy Framework (BCLF) aspires to encourage innovative course design in both the biochemical field and beyond through stimulating discussion among individuals developing undergraduate biochemistry degree courses based on pedagogical best practice. Here, we examine the concept of biochemical literacy aiming to start answering the question: What must individuals do and know to approach and transform ideas in the context of the biochemical sciences? The BCLF began with the guidance published by relevant learned societies - including the Royal Society of Biology, the Biochemical Society, the American Society for Biochemistry and Molecular Biology and the Quality Assurance Agency, before considering relevant pedagogical literature. We propose that biochemical literacy is comprised of seven key skills: critical thinking, self-management, communication, information literacy, visual literacy, practical skills and content knowledge. Together, these form a dynamic, highly interconnected and interrelated meta-literacy supporting the use of evidence-based, robust learning techniques. The BCLF is intended to form the foundation for discussion between colleagues, in addition to forming the groundwork for both pragmatic and exploratory future studies into facilitating and further defining biochemical literacy.

Temperature is a poor proxy for synergistic climate forcing of plankton evolution.

Changes in biodiversity at all levels from molecules to ecosystems are often linked to climate change, which is widely represented univariately by temperature. A global environmental driving mechanism of biodiversity dynamics is thus implied by the strong correlation between temperature proxies and diversity patterns in a wide variety of fauna and flora. Yet climate consists of many interacting variables. Species probably respond to the entire climate system as opposed to its individual facets. Here, we examine ecological and morphological traits of 12 633 individuals of two species of planktonic foraminifera with similar ecologies but contrasting evolutionary outcomes. Our results show that morphological and ecological changes are correlated to the interactions between multiple environmental factors. Models including interactions between climate variables explain at least twice as much variation in size, shape and abundance changes as models assuming that climate parameters operate independently. No dominant climatic driver can be identified: temperature alone explains remarkably little variation through our highly resolved temporal sequences, implying that a multivariate approach is required to understand evolutionary response to abiotic forcing. Our results caution against the use of a 'silver bullet' environmental parameter to represent global climate while studying evolutionary responses to abiotic change, and show that more comprehensive reconstruction of palaeobiological dynamics requires multiple biotic and abiotic dimensions.

The Breakdown of Static and Evolutionary Allometries during Climatic Upheaval.

The influence of within-species variation and covariation on evolutionary patterns is well established for generational and macroevolutionary processes, most prominently through genetic lines of least resistance. However, it is not known whether intraspecific phenotypic variation also directs microevolutionary trajectories into the long term when a species is subject to varying environmental conditions. Here we present a continuous, high-resolution bivariate record of size and shape changes among 12,633 individual planktonic foraminifera of a surviving and an extinct-going species over 500,000 years. Our study interval spans the late Pliocene to earliest Pleistocene intensification of northern hemisphere glaciation, an interval of profound climate upheaval that can be divided into three phases of increasing glacial intensity. Within each of these three Plio-Pleistocene climate phases, the within-population allometries predict evolutionary change from one time step to the next and that the within-phase among-population (i.e., evolutionary) allometries match their corresponding static (within-population) allometries. However, the evolutionary allometry across the three climate phases deviates significantly from the static and phase-specific evolutionary allometries in the extinct-going species. Although intraspecific variation leaves a clear signature on mean evolutionary change from one time step to the next, our study suggests that the link between intraspecific variation and longer-term micro- and macroevolutionary phenomena is prone to environmental perturbation that can overcome constraints induced by within-species trait covariation.

Slope of psychometric functions and termination rule analysis for low contrast acuity charts.

PURPOSE: To assess whether the slopes of psychometric functions for measuring low contrast letter acuity were different from those for measuring high contrast letter acuity. METHODS: Ten participants, wearing their best spectacle correction, were assessed monocularly. Stimuli were logarithmic progression charts, generated on a computer monitor, with nine rows of five randomised Sloan letters generated in either high contrast format (Weber contrast 99.2%) or low contrast format (Weber contrast 18.7%). For each participant, psychometric functions were generated by probit analysis of the data on each of 16 attempts at a low contrast chart and 16 attempts at a high contrast chart. Each of these probit fits yielded an estimate of Probit Size which provided information about how steep or flat the psychometric function was, along with an estimate of Probit Acuity Threshold. RESULTS: Probit Size was significantly larger (p < 0.001) for low contrast charts than for high contrast charts, indicating that psychometric functions were flatter for low contrast charts. Mean Probit Sizes in logMAR were 0.099 (SEM 0.022) for low contrast charts and 0.071 (SEM 0.009) for high contrast charts if a guess rate of 1/26 was assumed, or were 0.086 (SEM 0.019) for low contrast charts and 0.064 for high contrast charts if a guess rate of 1/10 was assumed. Monte Carlo analysis showed that these means were likely to be biased estimates, with true Probit Size probably being larger (i.e. slightly flatter fits) by 0.016-0.019 logMAR. As expected, Probit Acuity Thresholds were poorer for low contrast charts than for high contrast charts (p < 0.001). CONCLUSION: Our Monte Carlo modelling showed that such differences in acuity psychometric functions would be expected to give greater intra-subject variability in low contrast letter-by-letter acuity thresholds than for high contrast letter-by-letter acuity thresholds, and that this difference would depend on the termination rule used when measuring acuity. Likewise the variation in letter-by- letter acuity thresholds with termination rule will be different for high and low contrast charts. For low contrast and high contrast Sloan letter charts in a standard logarithmic format, a termination rule of four mistakes on a row, will give close to optimum sensitivity-to-change.

Lens Opacity and Hydrogen Sulfide in a New Zealand Geothermal Area.

PURPOSE: Hydrogen sulfide (H2S) is a highly toxic gas with well-established, acute irritation effects on the eye. The population of Rotorua, New Zealand, sited on an active geothermal field, has some of the highest ambient H2S exposures in the world. Evidence from ecological studies in Rotorua has suggested that H2S is associated with cataract. The purpose of the present study was, using more detailed exposure characterization, clinical examinations, and anterior eye photography, to more directly investigate this previously reported association. METHODS: Enrolled were 1637 adults, ages 18 to 65, from a comprehensive Rotorua primary care medical register. Patients underwent a comprehensive ophthalmic examination, including pupillary dilation and lens photography to capture evidence of any nuclear opacity, nuclear color, and cortical and posterior subcapsular opacity. Photographs were scored for all four outcomes on the LOCS III scale with decimalized interpolation between the exemplars. H2S exposure for up to the last 30 years was estimated based on networks of passive samplers set out across Rotorua and knowledge of residential, workplace, and school locations over the 30 years. Data analysis using linear and logistic regression examined associations between the degree of opacification and nuclear color or cataract (defined as a LOCS III score ≥2.0) in relation to H2S exposure. RESULTS: No associations were found between estimated H2S exposures and any of the four ophthalmic outcome measures. CONCLUSIONS: Overall, results were generally reassuring. They provided no evidence that H2S exposure at the levels found in Rotorua is associated with cataract. The previously found association between cataract and H2S exposure in the Rotorua population seems likely to be attributable to the limitations of the ecological study design. These results cannot rule out the possibility of an association with cataract at higher levels of H2S exposure.

Emergency Abdominal Surgery in the Elderly: Can We Predict Mortality?

BACKGROUND: The United Kingdom population is ageing. Half of patients requiring an emergency laparotomy are aged over 70, 20 % die within 30 days, and less than half receive good care. Frailty and delay in management are associated with poor surgical outcomes. P-POSSUM risk scoring is widely accepted, but its validity in patients aged over 70 undergoing emergency laparotomy is unclear. AIMS: To assess if P-POSSUM risk stratification reliably predicts inpatient mortality in this group and establish whether those who died within 30 days received delayed care. METHODS: Observational study of consecutive patients aged 70 and over fulfilling the National Emergency Laparotomy Audit criteria from a tertiary hospital. The predictive value of pre-operative P-POSSUM, ASA, lactate and other routine variables was assessed. Surgical review, decision to operate, consultant surgical review, antibiotic prescription, laparotomy and discharge or death time points were assessed by 30-day survival. RESULTS: One hundred and ninety-three patients were included. This represented 46.28 % of those undergoing an emergency laparotomy in our centre. Pre-operative P-POSSUM scoring, ASA grade and lactate were moderate predictors of mortality (AUC 0.784 and 0.771, respectively, lactate AUC 0.705, all p ≤ 0.001). No correlation existed between pre-operative P-POSSUM and days to death (p = 0.209), nor were there delays in key management timings in those who died in 30 days. CONCLUSIONS: P-POSSUM scoring may predict inpatient mortality with moderate discrimination. Addition of frailty scoring in this high-risk group might better identify those with a high risk of mortality after emergency laparotomy and would be a fertile area for further research.

Tumour infiltrating lymphocytes correlate with improved survival in patients with oesophageal adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma (OAC) is increasingly common in the west, and survival remains poor at 10-15 % at 5 years. Immune responses are increasingly implicated as a determining factor of tumour progression. The ability of lymphocytes to recognise tumour antigens provides a mechanism for a host immune attack against cancer providing a potential treatment strategy. MATERIALS AND METHODS: Tumour infiltrating lymphocytes (TILs: CD3+, CD4+, CD8+ and FOXp3+) were assessed by immunohistochemistry using tissue microarrays in a contemporary and homogeneous cohort of OAC patients (n = 128) undergoing curative treatment. RESULTS: Multivariate analysis identified three independent prognostic factors for improved cancer-specific survival (CSS): increased CD8+ TILs (p = 0.003), completeness of resection (p < 0.0001) and lower pathological N stage (p < 0.0001). Independent prognostic factors for favourable disease-free survival included surgery-only treatment (p = 0.015), completeness of resection (p = 0.001), increased CD8+ TILs (p < 0.0001) and reduced pathological N stage (p < 0.0001). Higher levels of TILs in the pathological specimen were associated with significant pathological response to neoadjuvant chemotherapy (NAC). On multivariate analysis increased levels of CD4+ (p = 0.017) and CD8+ TILs (p = 0.005) were associated with significant local tumour regression and lymph node downstaging, respectively. DISCUSSION: Our results establish an association of TILs and survival in OAC, as seen in other solid tumours, and identify particular TIL subsets that are present at higher levels in patients who responded to NAC compared to non-responders. These findings highlight potential therapeutic strategies in EAC based on utilising the host immunological response and highlight the immune responses biomarker potential.

Mid-Pleistocene climate transition drives net mass loss from rapidly uplifting St. Elias Mountains, Alaska.

Erosion, sediment production, and routing on a tectonically active continental margin reflect both tectonic and climatic processes; partitioning the relative importance of these processes remains controversial. Gulf of Alaska contains a preserved sedimentary record of the Yakutat Terrane collision with North America. Because tectonic convergence in the coastal St. Elias orogen has been roughly constant for 6 My, variations in its eroded sediments preserved in the offshore Surveyor Fan constrain a budget of tectonic material influx, erosion, and sediment output. Seismically imaged sediment volumes calibrated with chronologies derived from Integrated Ocean Drilling Program boreholes show that erosion accelerated in response to Northern Hemisphere glacial intensification (∼ 2.7 Ma) and that the 900-km-long Surveyor Channel inception appears to correlate with this event. However, tectonic influx exceeded integrated sediment efflux over the interval 2.8-1.2 Ma. Volumetric erosion accelerated following the onset of quasi-periodic (∼ 100-ky) glacial cycles in the mid-Pleistocene climate transition (1.2-0.7 Ma). Since then, erosion and transport of material out of the orogen has outpaced tectonic influx by 50-80%. Such a rapid net mass loss explains apparent increases in exhumation rates inferred onshore from exposure dates and mapped out-of-sequence fault patterns. The 1.2-My mass budget imbalance must relax back toward equilibrium in balance with tectonic influx over the timescale of orogenic wedge response (millions of years). The St. Elias Range provides a key example of how active orogenic systems respond to transient mass fluxes, and of the possible influence of climate-driven erosive processes that diverge from equilibrium on the million-year scale.

Effect of font size and glare on computer tasks in young and older adults.

PURPOSE: At a fixed viewing distance (VD), reading speed increases with print size. It is not known if this holds for computer tasks when postures are not constrained. Reflective glare on a monitor may reduce productivity. The effects of both may be modified by age. We evaluated effects of age, font size, and glare on performance for visually demanding text-based tasks on a computer. METHODS: Nineteen young (18 to 35 years old) and eight older (55 to 65 years old wearing progressive lenses that correct for presbyopia) subjects participated in a study with two trial factors: font size (1.78, 2.23, and 3.56 mm) and glare (produced by bright light-emitting diode task light reflective off a matte liquid crystal display monitor). The monitor location was fixed but subjects were allowed to change their posture and move the chair. Subjects performed visual tasks that required similar visual skills to common tasks such as Internet use, data entry, or word processing. RESULTS: Productivity, accuracy, and VD increased as font size increased. For each 1-mm increase in font size, there was a mean productivity gain of 3 correct clicks/min and an improvement in accuracy of 2%. Font size increase also led to lowered perceived task difficulty. Adding reflective glare on the monitor surface led to a reduced VD but had no effect on productivity or accuracy. With visual corrections for presbyopia, age had no effect on these relationships. CONCLUSIONS: Productivity is improved when the font is increased from 1.78 or 2.23 to 3.56 mm for text-based computer tasks. The largest font size corresponds to a visual angle of font of 23.4 arcmin. This visual angle of font is above the high end of ISO recommendations (International Organization for Standardization, 1992, 2011). The findings may be useful for setting the font sizes for computers and for training office workers.

The relevance of the Siewert classification in the era of multimodal therapy for adenocarcinoma of the gastro-oesophageal junction.

INTRODUCTION: The Siewert classification has been used to plan treatment for tumours of the gastro-oesophageal junction since its proposal in the 1980s. The purpose of this study was to assess its continued relevance by evaluating whether there were differences in the biology and clinical characteristics of adenocarcinomas by Siewert type, in a contemporary cohort of patients, in whom the majority had received neoadjuvant chemotherapy. METHODS: A prospective database was reviewed for all patients who underwent resection from 2005 to 2011 and analysed with regard to Siewert classification determined from the pathological specimen, treatment and clinicopathological outcomes. RESULTS: Two hundred and sixteen patients underwent oesophagogastric resection: 133 for type I, 51 for type II and 33 for type III tumours. 135 Patients (62.5%) received neoadjuvant chemotherapy with no difference between groups. There were no significant differences in age, sex, pT stage, pN stage, pM stage, ASA, or inpatient complications between patients with adenocarcinoma based on their Siewert classification. There was a significant increase in maximum tumour diameter (P = 0.023), perineural invasion (P = 0.021) and vascular invasion (P = 0.020), associated with more distal tumours (Type III > Type II > Type I). Median overall survival was significantly shorter for more distal tumours (Type I: 4.96 years vs. Type II: 3.3 years vs. Type III: 2.64 years; P = 0.04). The surgical approach did not influence survival. CONCLUSION: In the era of multi-modal treatment pathological Siewert tumour type is of prognostic value, as patients with Type III disease are likely to have larger and more aggressive tumours that lead to worse outcomes.

The Robustness of Pathway Analysis in Identifying Potential Drug Targets in Non-Small Cell Lung Carcinoma.

The identification of genes responsible for causing cancers from gene expression data has had varied success. Often the genes identified depend on the methods used for detecting expression patterns, or on the ways that the data had been normalized and filtered. The use of gene set enrichment analysis is one way to introduce biological information in order to improve the detection of differentially expressed genes and pathways. In this paper we show that the use of network models while still subject to the problems of normalization is a more robust method for detecting pathways that are differentially overrepresented in lung cancer data. Such differences may provide opportunities for novel therapeutics. In addition, we present evidence that non-small cell lung carcinoma is not a series of homogeneous diseases; rather that there is a heterogeny within the genotype which defies phenotype classification. This diversity helps to explain the lack of progress in developing therapies against non-small cell carcinoma and suggests that drug development may consider multiple pathways as treatment targets.

The role of systemic inflammatory and nutritional blood-borne markers in predicting response to neoadjuvant chemotherapy and survival in oesophagogastric cancer.

The aim of this study was to interrogate whether blood-borne inflammatory and nutritional markers predict long-term survival and response to neoadjuvant chemotherapy in radically treated oesophagogastric cancer patients. This retrospective study included 246 patients who underwent oesophageal resection for high-grade dysplasia or carcinoma between 2005 and 2010. The predictive value of routine preoperative immunonutritional blood tests was assessed for their association with survival and response to chemotherapy. On multivariate analysis, higher neutrophil-lymphocyte ratio (NLR) (p < 0.0001), N stage (p < 0.0001) and perineural invasion (p < 0.0001) were associated with poor overall survival. Regarding disease-free survival, multivariate analysis showed reduced serum albumin (p = 0.034), N stage (p < 0.0001), M stage (p = 0.037), vascular invasion (p < 0.0001) and presence of R1 resection (p = 0.003) to correlate with earlier recurrence. In those who received neoadjuvant chemotherapy, analysis of prechemotherapy characteristics showed only serum albumin (p = 0.037) to predict pathological response to chemotherapy. Preoperative immunonutritional markers, NLR and albumin, were independent prognostic markers for overall survival and disease-free survival, respectively, after oesophageal cancer resection. Prospective studies evaluating the role of immunonutritional modulation to improve response to chemotherapy and long-term outcome are required.

Visual acuity testing. From the laboratory to the clinic.

The need for precision in visual acuity assessment for low vision research led to the design of the Bailey-Lovie letter chart. This paper describes the decisions behind the design principles used and how the logarithmic progression of sizes led to the development of the logMAR designation of visual acuity and the improved sensitivity gained from letter-by-letter scoring. While the principles have since been adopted by most major clinical research studies and for use in most low vision clinics, use of charts of this design and application of letter-by-letter scoring are also important for the accurate assessment of visual acuity in any clinical setting. We discuss the test protocols that should be applied to visual acuity testing and the use of other tests for assessing profound low vision when the limits of visual acuity measurement by letter charts are reached.