Flat Γ Moiré Bands in Twisted Bilayer WSe_{2}.

The recent observation of correlated phases in transition metal dichalcogenide moiré systems at integer and fractional filling promises new insight into metal-insulator transitions and the unusual states of matter that can emerge near such transitions. Here, we combine real- and momentum-space mapping techniques to study moiré superlattice effects in 57.4° twisted WSe_{2} (tWSe_{2}). Our data reveal a split-off flat band that derives from the monolayer Γ states. Using advanced data analysis, we directly quantify the moiré potential from our data. We further demonstrate that the global valence band maximum in tWSe_{2} is close in energy to this flat band but derives from the monolayer K states which show weaker superlattice effects. These results constrain theoretical models and open the perspective that Γ-valley flat bands might be involved in the correlated physics of twisted WSe_{2}.

Chemical and Cellular Formation of Reactive Oxygen Species from Secondary Organic Aerosols in Epithelial Lining Fluid.

INTRODUCTION: Oxidative stress mediated by reactive oxygen species (ROS) is a key process for adverse aerosol health effects. Secondary organic aerosols (SOA) account for a major fraction of particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5). PM2.5 inhalation and deposition into the respiratory tract causes the formation of ROS by chemical reactions and phagocytosis of macrophages in the epithelial lining fluid (ELF), but their relative contributions are not well quantified and their link to oxidative stress remains uncertain. The specific aims of this project were (1) elucidating the chemical mechanism and quantifying the formation kinetics of ROS in the ELF by SOA; (2) quantifying the relative importance of ROS formation by chemical reactions and macrophages in the ELF. METHODS: SOA particles were generated using reaction chambers from oxidation of various precursors including isoprene, terpenes, and aromatic compounds with or without nitrogen oxides (NOx). We collected size-segregated PM at two highway sites in Anaheim, CA, and Long Beach, CA, and at an urban site in Irvine, CA, during two wildfire events. The collected particles were extracted into water or surrogate ELF that contained lung antioxidants. ROS generation was quantified using electron paramagnetic resonance (EPR) spectroscopy with a spin-trapping technique. PM oxidative potential (OP) was also quantified using the dithiothreitol assay. In addition, kinetic modeling was applied for analysis and interpretation of experimental data. Finally, we quantified cellular superoxide release by RAW264.7 macrophage cells upon exposure to quinones and isoprene SOA using a chemiluminescence assay as calibrated with an EPR spin-probing technique. We also applied cellular imaging techniques to study the cellular mechanism of superoxide release and oxidative damage on cell membranes. RESULTS: Superoxide radicals (·O2-) were formed from aqueous reactions of biogenic SOA generated by hydroxy radical (·OH) photooxidation of isoprene, ß-pinene, α-terpineol, and d-limonene. The temporal evolution of ·OH and ·O2- formation was elucidated by kinetic modeling with a cascade of aqueous reactions, including the decomposition of organic hydroperoxides (ROOH), ·OH oxidation of primary or secondary alcohols, and unimolecular decomposition of α-hydroxyperoxyl radicals. Relative yields of various types of ROS reflected the relative abundance of ROOH and alcohols contained in SOA, which generated under high NOx conditions, exhibited lower ROS yields. ROS formation by SOA was also affected by pH. Isoprene SOA had higher ·OH and organic radical yields at neutral than at acidic pH. At low pH ·O2- was the dominant species generated by all types of SOA. At neutral pH, α-terpineol SOA exhibited a substantial yield of carbon-centered organic radicals (R·), while no radical formation was observed by aromatic SOA.Organic radicals in the ELF were formed by mixtures of Fe2+ and SOA generated from photooxidation of isoprene, α-terpineol, and toluene. The molar yields of organic radicals by SOA were 5-10 times higher in ELF than in water. Fe2+ enhanced organic radical yields by a factor of 20-80. Ascorbate mediated redox cycling of iron ions and sustained organic peroxide decomposition, as supported by kinetic modeling reproducing time- and concentration-dependence of organic radical formation, as well as by additional experiments observing the formation of Fe2+ and ascorbate radicals in mixtures of ascorbate and Fe3+. ·OH and superoxide were found to be efficiently scavenged by antioxidants.Wildfire PM mainly generated ·OH and R· with minor contributions from superoxide and oxygen-centered organic radicals (RO·). PM OP was high in wildfire PM, exhibiting very weak correlation with radical forms of ROS. These results were in stark contrast with PM collected at highway and urban sites, which generated much higher amounts of radicals dominated by ·OH radicals that correlated well with OP. By combining field measurements of size-segregated chemical composition, a human respiratory tract model, and kinetic modeling, we quantified production rates and concentrations of different types of ROS in different regions of the ELF by considering particle-size-dependent respiratory deposition. While hydrogen peroxide (H2O2) and ·O2- production were governed by Fe and Cu ions, ·OH radicals were mainly generated by organic compounds and Fenton-like reactions of metal ions. We obtained mixed results for correlations between PM OP and ROS formation, providing rationale and limitations of the use of oxidative potential as an indicator for PM toxicity in epidemiological and toxicological studies.Quinones and isoprene SOA activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in macrophages, releasing massive amounts of superoxide via respiratory burst and overwhelming the superoxide formation by aqueous chemical reactions in the ELF. The threshold dose for macrophage activation was much smaller for quinones compared with isoprene SOA. The released ROS caused lipid peroxidation to increase cell membrane fluidity, inducing oxidative damage and stress. Further increases of doses led to the activation of antioxidant response elements, reducing the net cellular superoxide production. At very high doses and long exposure times, chemical production became comparably important or dominant if the escalation of oxidative stress led to cell death. CONCLUSIONS: The mechanistic understandings and quantitative information on ROS generation by SOA particles provided a basis for further elucidation of adverse aerosol health effects and oxidative stress by PM2.5. For a comprehensive assessment of PM toxicity and health effects via oxidative stress, it is important to consider both chemical reactions and cellular processes for the formation of ROS in the ELF. Chemical composition of PM strongly influences ROS formation; further investigations are required to study ROS formation from various PM sources. Such research will provide critical information to environmental agencies and policymakers for the development of air quality policy and regulation.

Influences on the dietary intakes of preschool children: a systematic scoping review.

BACKGROUND: Better diet quality of preschool children is associated with many important health outcomes, but there is significant room for improvement in many children's dietary intakes. The determinants of children's dietary intakes are complex and whole systems approaches may be effective tools for changing dietary intake. Collation of all the evidence available on determinants of preschool children's dietary intake is necessary to 'map' the whole system of influence. Therefore, this systematic scoping review of available literature on determinants of dietary intakes in preschool children was undertaken. METHODS: The Joanna Briggs Institute methods for conducting a systematic scoping review were followed. Articles published since 2000 which assessed influences on the dietary intakes of preschool children were identified, yielding a total of 246 papers. Studies of children with clinical conditions (excluding obesity), or those conducted in middle and low-income countries were excluded, due to the different systems of influence in these populations. Data were extracted and information synthesised based on ecological level (child, parent, household, childcare, or wider determinants). RESULTS: Most articles focused on influences at the parental level (n = 118, 48%), followed by those at the child level (n = 73, 30%). Most of the studies were of cross-sectional design (n = 109, 44%). Whilst many studies considered influences at multiple ecological levels (n = 63, 26%) few analyses determined interactions between factors in their relationship with children's dietary intakes, which is needed going forward using systems methods. CONCLUSION: A wealth of evidence exists examining influences on the dietary intakes of preschool children and this information would benefit from analysis using a systems thinking approach in order to assess effective levers for intervention and what works, for whom, under what circumstances.

Letter to the Editor on: "The Effects of Physical Exercise on Tumor Vasculature: Systematic Review and Meta-Analysis."

Dear Editor,We read with interest the recent article "The Effects of Physical Exercise on Tumor Vasculature: Systematic Review and Meta-analysis" 1 and after careful appraisal and consideration we feel that some aspects of the data and analysis warrant further review. The study reported some promising results, namely that both chronic and acute exercise appear to improve intratumoral vascularisation in animal models. This is an important finding given increased vascularisation through tumor modulation may have the potential to improve chemotherapy delivery and efficacy 2. However, after conducting further investigations, we query several details in the data extraction and analysis decision-making that we believe impact the conclusions of this article.

Differences between race and sex in measures of hip morphology: a population-based comparative study.

OBJECTIVE: This paper aims to (i) identify differences in measures of hip morphology between four racial groups using anteroposterior (AP) hip x-rays, and (ii) examine whether these differences vary by sex. METHODS: 912 hip x-rays (456 individuals) from four racial groups (European Caucasians, American Caucasians, African Americans and Chinese) were obtained. Males and females (45-75 years) with no radiographic hip OA (Kellgren and Lawrence < Grade 2 or Croft < Grade 1) were included. Eleven features of hip joint morphology were analysed. Linear regression with generalised estimating equations (GEE) was used to determine race and sex differences in hip morphology. Post-hoc Bonferroni procedure was used to adjust for multiple comparisons. RESULTS: The final analysis included 875 hips. Chinese hips showed significant differences for the majority of measures to other racial groups. Chinese were characterised by more shallow and narrow acetabular sockets, reduced femoral head coverage, smaller femoral head diameter, and a lesser angle of alignment between the femoral neck and shaft. Variation was found between other racial groups, but with few statistically significant differences. The average of lateral centre edge angle, minimum neck width and neck length differed between race and sex (p-value for interaction < 0.05). CONCLUSIONS: Significant differences were found in measures of morphology between Chinese hips compared to African Americans or Caucasian groups; these may explain variation in hip OA prevalence rates between these groups and the lower rate of hip OA in Chinese. Sex differences were also identified, which may further explain male-female prevalence differences for OA.

Sex and psychiatric comorbidity correlates of the premonitory urge for tic scale in youth with persistent tic disorders.

The premonitory urge for tics scale (PUTS) is a common self-report measure of premonitory sensations preceding tics. The present study aimed to examine the internal consistency and concurrent validity of the PUTS by sex and psychiatric comorbidity status; and explored interactions between sex and psychiatric comorbidity in predicting premonitory urge and tic symptom severity. Seventy-four youth and young adults with persistent tic disorders completed the PUTS, while their parents completed the parent tic questionnaire (PTQ) and a demographic measure. Independent samples t-tests revealed no significant sex differences in PUTS items or total score. The PUTS total score also did not significantly differ between participants with and without attention-deficit hyperactivity disorder (ADHD) and/or obsessive-compulsive disorder (OCD) comorbidity. Internal consistency did not significantly differ between females (α = 0.85) and males (α = 0.75), and those with comorbid ADHD and/or OCD (α = 0.83) relative to those without (α = 0.69). With respect to concurrent validity, the PUTS total was significantly correlated with PTQ tic frequency, intensity, number, and severity for males but not for females. Among those with ADHD and/or OCD, the PUTS total score was correlated significantly and strongly with tic number and moderately with tic intensity. Interactions between sex and psychiatric comorbidity performed using 2 × 2 analysis of variance did not significantly predict the PUTS total or PTQ subscale scores. Findings suggest sex and comorbidity status may influence premonitory urge expression. Results have implications for understanding and measurement of the premonitory urge.

Prospective analysis of health-related quality of life after surgery for spinal metastases.

PURPOSE: Most spinal metastases are detected late, and thus, the impact of treatment on the health-related quality of life (HRQOL) is an important consideration. This study investigated the HRQOL following surgery for spinal metastases. METHODS: A prospective study of patients operated for symptomatic spinal metastases, at a single tertiary referral spine centre (2011-2013). Data were collected pre-operatively and up to 2 years following surgery (if alive). The HRQOL assessment was performed using recognised systems including the Frankel score (neurological status), EQ-5D, and the Oswestry Disability Index. RESULTS: A total of 199 patients were studied (median age 65 years, 43% (86) F; 57% (113) M). The Frankel score improved significantly after surgery in 69 patients (35%), worsened in 17 (8%), with 20/39 patients regaining the ability to walk (51%). All the HRQOL scores improved significantly following surgery. The complication rate was 27% and median survival 270 days, and 44 patients (22%) survived at 2 years. CONCLUSIONS: This large prospective study showed that surgical treatment for spinal metastases significantly improved the HRQOL.

Latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy.

AIM: To assess if latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy. METHODS: Participants with LADA (n=31), Type 2 diabetes (n=31) and healthy control participants without diabetes (n=31) underwent a detailed assessment of neurologic deficits, quantitative sensory testing, electrophysiology, skin biopsy and corneal confocal microscopy. RESULTS: The groups were matched for age (healthy control without diabetes: 53.5±9.1 vs. Type 2 diabetes: 58.0±6.5 vs. LADA: 53.2±11.6 years), duration of diabetes (Type 2 diabetes: 10.0±8.3 vs. LADA: 11.0±9.1 years) and blood pressure. However, BMI (P=0.01) and triglycerides (P=0.0008) were lower and HbA1c (P=0.0005), total cholesterol (P=0.01) and HDL (P=0.002) were higher in participants with LADA compared with Type 2 diabetes. Peroneal motor nerve conduction velocity (P=0.04) and sural sensory nerve conduction velocity (P=0.008) were lower in participants with latent autoimmune diabetes in adults compared with Type 2 diabetes. Intra-epidermal nerve fibre density (P=0.008), corneal nerve fibre density (P=0.003) and corneal nerve branch density (P=0.006) were significantly lower in participants with LADA compared with Type 2 diabetes. There were no significant differences in the other neuropathy parameters. CONCLUSIONS: Despite comparable age and duration of diabetes, participants with LADA demonstrate more severe neuropathy and particularly small fibre neuropathy, compared with participants with Type 2 diabetes.

Does surgical site infection influence neurological outcome and survival in patients undergoing surgery for metastatic spinal cord compression?

PURPOSE: Most of the literature on infection after surgery for spinal metastases focuses on incidence and risk factors for surgical site infection (SSI). To the best of our knowledge, there is no report on the influence of infection on neurological outcome and survival in patients undergoing emergent surgery for metastatic spinal cord compression (MSCC). METHODS: Our aim was to establish if SSIs adversely affected the neurological outcome and survival in patients with MSCC. We reviewed 318 consecutive patients admitted for surgical intervention for MSCC from October 2005 to October 2012. Morbidity (neurological outcome, length of hospital stay and additional procedures) and survival rates were analysed. RESULTS: During this study period, the incidence of infection was 29/318 (9.1%). The median length of stay in hospital in the infected group was 25 days compared to 13 days in the non-infected group (p = 0.001). Twenty out of the 29 (69%) infected patients underwent an additional procedure (29 procedures in total) compared to 9/289 (3%) non-infected patients (p = 0.001). There was no statistical difference between the two groups with regard to neurological outcome (p = 0.37) but the survival rate was statistically different between the two groups [infected group: median survival 131 days (19-1558) vs. non-infected group: 258 days (5-2696; p = 0.03)]. CONCLUSION: Surgical site infection increased the morbidity with considerably longer hospital stay and requirement for additional procedures. Although there was no difference in neurological outcome, the infected group of patients had a significantly shorter survival. These slides can be retrieved under Electronic Supplementary Material.

Effects of personal air pollution exposure on asthma symptoms, lung function and airway inflammation.

BACKGROUND: There is evidence that air pollution increases the risk of asthma hospitalizations and healthcare utilization, but the effects on day-to-day asthma control are not fully understood. OBJECTIVE: We undertook a prospective single-centre panel study to test the hypothesis that personal air pollution exposure is associated with asthma symptoms, lung function and airway inflammation. METHODS: Thirty-two patients with a clinical diagnosis of asthma were provided with a personal air pollution monitor (Cairclip NO2 /O3 ) which was kept on or around their person throughout the 12-week follow-up period. Ambient levels of NO2 and particulate matter were modelled based upon satellite imaging data. Directly measured ozone, NO2 and particulate matter levels were obtained from a monitoring station in central Leicester. Participants made daily electronic records of asthma symptoms, peak expiratory flow and exhaled nitric oxide. Spirometry and asthma symptom questionnaires were completed at fortnightly study visits. Data were analysed using linear mixed effects models and cross-correlation. RESULTS: Cairclip exposure data were of good quality with clear evidence of diurnal variability and a missing data rate of approximately 20%. We were unable to detect consistent relationships between personal air pollution exposure and clinical outcomes in the group as a whole. In an exploratory subgroup analysis, total oxidant exposure was associated with increased daytime symptoms in women but not men. CONCLUSIONS AND CLINICAL RELEVANCE: We did not find compelling evidence that air pollution exposure impacts on day-to-day clinical control in an unselected asthma population, but further studies are required in larger populations with higher exposure levels. Women may be more susceptible than men to the effects of air pollution, an observation which requires confirmation in future studies.

Milk-fat globule epidermal growth factor 8 (MFGE8) is expressed at the embryo- and fetal-maternal interface in equine pregnancy.

Milk-fat globule epidermal growth factor (EGF) 8 protein (MFGE8), also known as lactadherin, promotes cell adhesion in an Arg-Gly-Asp (RGD)-dependent modus via integrins. In the present study, the expression of MFGE8 was examined in equine endometrium during oestrus and at Days 12 and 16 after ovulation in pregnant and non-pregnant mares and in mares during the 5th month of gestation. Results demonstrated that MFGE8 is expressed at the embryo- and fetal-maternal interface in equine pregnancy. In non-pregnant endometrium its expression was upregulated by oestrogen, a finding that was confirmed using endometrial explant culture. MFGE8 was expressed at similar levels by conceptuses collected 13 and 14 days after ovulation and by allantochorion sampled during the 5th month of gestation. Pericytes of endometrial blood vessels displayed strong MFGE8 expression upon in situ hybridisation. During the 5th month of gestation, the fetal side of the allantochorionic villi in particular displayed pronounced staining upon in situ hybridisation, confirming that MFGE8 expression is not restricted to early pregnancy but persists and is present at the fetal-maternal interface. Potential roles of MFGE8 in equine pregnancy include mediating cell-cell adhesion, promotion of angiogenesis and placental transfer of fatty acids.

A reference genome for Nicotiana tabacum enables map-based cloning of homeologous loci implicated in nitrogen utilization efficiency.

BACKGROUND: Tobacco (Nicotiana tabacum) is an important plant model system that has played a key role in the early development of molecular plant biology. The tobacco genome is large and its characterisation challenging because it is an allotetraploid, likely arising from hybridisation between diploid N. sylvestris and N. tomentosiformis ancestors. A draft assembly was recently published for N. tabacum, but because of the aforementioned genome complexities it was of limited utility due to a high level of fragmentation. RESULTS: Here we report an improved tobacco genome assembly, which, aided by the application of optical mapping, achieves an N50 size of 2.17 Mb and enables anchoring of 64% of the genome to pseudomolecules; a significant increase from the previous value of 19%. We use this assembly to identify two homeologous genes that explain the differentiation of the burley tobacco market class, with potential for greater understanding of Nitrogen Utilization Efficiency and Nitrogen Use Efficiency in plants; an important trait for future sustainability of agricultural production. CONCLUSIONS: Development of an improved genome assembly for N. tabacum enables what we believe to be the first successful map-based gene discovery for the species, and demonstrates the value of an improved assembly for future research in this model and commercially-important species.

Myeloid-derived suppressor cell-like fibrocytes are increased and associated with preserved lung function in chronic obstructive pulmonary disease.

BACKGROUND: The role of fibrocytes in chronic obstructive pulmonary disease (COPD) is unknown. We sought to enumerate blood and tissue fibrocytes in COPD and determine the association of blood fibrocytes with clinical features of disease. METHODS: Utilizing flow cytometry to identify circulating, collagen type 1+ cells, we found two populations: (i) CD45+ CD34+ (fibrocytes) and (ii) CD45+ CD34- [myeloid-derived suppressor cell (MDSC)-like fibrocytes] cells in stable COPD (n = 41) and control (n = 29) subjects. Lung resection material from a separate group of subjects with (n = 11) or without (n = 11) COPD was collected for tissue fibrocyte detection. We examined circulating fibrocyte populations for correlations with clinical parameters including quantitative computed tomography (qCT) and determined pathways of association between correlated variables using a path analysis model. RESULTS: Blood and tissue fibrocytes were not increased compared to control subjects nor were blood fibrocytes associated with lung function or qCT, but were increased in eosinophilic COPD. Myeloid-derived suppressor cell-like fibrocytes were increased in COPD compared to controls [2.3 (1.1-4.9), P = 0.038]. Our path analysis model showed that collagen type 1 intensity for MDSC-like fibrocytes was positively associated with lung function through associations with air trapping, predominately in the upper lobes. CONCLUSION: We have demonstrated that two circulating populations of fibrocyte exist in COPD, with distinct clinical associations, but are not prevalent in proximal or small airway tissue. Blood MDSC-like fibrocytes, however, are increased and associated with preserved lung function through a small airway-dependent mechanism in COPD.

Investigating non-specific binding to chemically engineered sensor surfaces using liposomes as models.

Nanoparticles are ubiquitously used for signal enhancement in (bio)sensors, but their true possible performance is typically hampered by non-specific binding. A better understanding of the nature and the prevention of non-specific binding through surface engineering of the particles and sensor surfaces is needed to intelligently design (bio)sensors and potentially avoid bulk blocking methods. Hence, two types of liposomes were used as model for signal-enhancing nanoparticles. Their surface was engineered to bear negative surface charge. One type was synthesized with additional 6 mol% -COOH groups. Their interaction with four typical chemically modified sensor surfaces was then mechanistically characterized by surface plasmon resonance (SPR) spectroscopy. It was shown that the non-specific binding can be described with Langmuir isotherms providing quantitative information of dissociation constants and surface loading with especially high correlation coefficients (>0.97) for all the studied sensor surfaces modified with hydrophilic alkane thiols. By tailoring the sensor surface chemistry, non-specific binding was significantly minimized. Here, carboxyl- or methyl-terminated surfaces performed best. In fact, the pairing of -COOH groups on the sensor surface with -COOH groups on the liposomes almost completely eliminated non-specific binding, resulting in a SPR signal change of only 1 mRIU (refractive index unit) at 100 µM phospholipid concentration. Surprisingly though, -OH groups on the surface, which are also commonly used in sensing applications, did not lead to decreased adsorption, but caused significant signal changes (4 mRIU at 100 µM phospholipid) due to non-specific binding. Overall, the mechanistic studies presented here demonstrate that by careful design of the nanoparticle surface and by choosing sensor surfaces with terminal -CH3 or -COOH groups, improved sensing (micro)systems with very low non-specific adsorption can be obtained.

Factors affecting school physical education provision in England: a cross-sectional analysis.

BACKGROUND: Attitudes towards physical activity are largely developed during childhood meaning that school physical education classes can have a strong influence. METHODS: National level data of school pupils (n = 21 515) in England were analysed to examine the association between school provision of physical education with sex, age, geographic and socioeconomic factors. RESULTS: Children attending independent schools had more scheduled physical education time (P < 0.001; 95% confidence interval (CI) 18 to 30 extra min per week). This association was true for males (P = 0.024); schools located in the South (P < 0.001; 95% CI 2 to 3) and rural areas (P < 0.001; 95% CI 3 to 5); or with a higher percentage of pupils eligible for free school meals (P < 0.001; 95% CI 3 to 4). Schools in more affluent areas (P < 0.001; 95% CI -1 to -2) and those with lower percentages of pupils from ethnic minorities (P < 0.001; 95% CI -1 to -2) also had higher minutes of physical education provision per week. Regarding age, 93% of schools met the guidelines in Years 1-9; only 45% did in Years 10-13. CONCLUSION: Differences in physical education were found in relation to school type, socioeconomic status and geographical factors. Age-related differences in compliance with guidelines are of concern; ways to increase provision for older children should be investigated.

Cooperative adsorption behavior of phosphopeptides on TiO2 leads to biased enrichment, detection and quantification.

The adsorption behavior of phosphopeptides onto TiO2 surfaces was studied using the quartz crystal microbalance with dissipation monitoring (QCM-D) as the main experimental technique. The main focus is the characterization of the emergence of positive cooperativity under conditions where the peptides have a positively charged C-term. It is shown that when carrying no net charge, small water-soluble peptides as a rule develop positive cooperativity. The impact of the adsorption mechanism on the outcome of TiO2 based enrichment methods was investigated with the help of matrix assisted laser desorption-ionization mass spectrometry (MALDI-MS). The data presented illustrate how the phosphopeptide profile in the enriched material may deviate from that in the native sample, as cooperative phosphopeptides are overrepresented in the former. Furthermore, commonly employed washing and elution solutions may facilitate preferential release of certain peptides, leading to further bias in the recovered sample. Taken together, the results of the present study demonstrate that thorough understanding of the mechanisms behind the adsorption of phosphopeptides on the enrichment material is necessary in order to develop reliable qualitative and quantitative methods for phosphoproteomics.

Characterizing dilute combustion instabilities in a multi-cylinder spark-ignited engine using symbolic analysis.

Spark-ignited internal combustion engines have evolved considerably in recent years in response to increasingly stringent regulations for emissions and fuel economy. One new advanced engine strategy ustilizes high levels of exhaust gas recirculation (EGR) to reduce combustion temperatures, thereby increasing thermodynamic efficiency and reducing nitrogen oxide emissions. While this strategy can be highly effective, it also poses major control and design challenges due to the large combustion oscillations that develop at sufficiently high EGR levels. Previous research has documented that combustion instabilities can propagate between successive engine cycles in individual cylinders via self-generated feedback of reactive species and thermal energy in the retained residual exhaust gases. In this work, we use symbolic analysis to characterize multi-cylinder combustion oscillations in an experimental engine operating with external EGR. At low levels of EGR, intra-cylinder oscillations are clearly visible and appear to be associated with brief, intermittent coupling among cylinders. As EGR is increased further, a point is reached where all four cylinders lock almost completely in phase and alternate simultaneously between two distinct bi-stable combustion states. From a practical perspective, it is important to understand the causes of this phenomenon and develop diagnostics that might be applied to ameliorate its effects. We demonstrate here that two approaches for symbolizing the engine combustion measurements can provide useful probes for characterizing these instabilities.

The Silver Surfer: Trends of Internet Usage in the Over 65 and the Potential Health Benefits.

The Internet provides medical information and interventions with promising benefits. This cross-sectional study explores trends in Internet use among the elderly in Ireland from 2002 to 2010 and considers possible implications for health benefit. Data were analysed on 1606 Irish individuals. Internet use in Ireland is increasing at similar rates to the rest of Europe; the percentage of over-65s using the Internet in Ireland nearly trebled from 2002 to 2010, from 26(8.3%) to 92 (24. 1%) (p < 0.001). Subgroups of this population displayed significantly higher rates of Internet usage; namely those with a better education, living with a partner, males and urban dwellers. Of those with good subjective general health, 230 (21%) had internet access, versus 36 (7.1%) with poor health. Web-based interventions targeting the elderly should become more available. These could be particularly useful in populations with limited access to transport and mobility.

Standardizing corneal nerve fibre length for nerve tortuosity increases its association with measures of diabetic neuropathy.

AIMS: Recent studies on corneal markers have advocated corneal nerve fibre length as the most important measure of diabetic peripheral neuropathy. The aim of this study was to determine if standardizing corneal nerve fibre length for tortuosity increases its association with other measures of diabetic peripheral neuropathy. METHODS: Two hundred and thirty-one individuals with diabetes with either predominantly mild or absent neuropathic changes and 61 control subjects underwent evaluation of diabetic neuropathy symptom score, neuropathy disability score, testing with 10-g monofilament, quantitative sensory testing (warm, cold, vibration detection) and nerve conduction studies. Corneal nerve fibre length and corneal nerve fibre tortuosity were measured using corneal confocal microscopy. A tortuosity-standardised corneal nerve fibre length variable was generated by dividing corneal nerve fibre length by corneal nerve fibre tortuosity. Differences in corneal nerve morphology between individuals with and without diabetic peripheral neuropathy and control subjects were determined and associations were estimated between corneal morphology and established tests of, and risk factors for, diabetic peripheral neuropathy. RESULTS: The tortuosity-standardised corneal nerve fibre length variable was better than corneal nerve fibre length in demonstrating differences between individuals with diabetes, with and without neuropathy (tortuosity-standardised corneal nerve fibre length variable: 70.5 ± 27.3 vs. 84.9 ± 28.7, P < 0.001, receiver operating characteristic area under the curve = 0.67; corneal nerve fibre length: 15.9 ± 6.9 vs. 18.4 ± 6.2 mm/mm², P = 0.004, receiver operating characteristic area under the curve = 0.64). Furthermore, the tortuosity-standardised corneal nerve fibre length variable demonstrated a significant difference between the control subjects and individuals with diabetes, without neuropathy, while corneal nerve fibre length did not (tortuosity-standardised corneal nerve fibre length variable: 94.3 ± 27.1 vs. 84.9 ± 28.7, P = 0.028; corneal nerve fibre length: 20.1 ± 6.3 vs. 18.4 ± 6.2 mm/mm², P = 0.084). Correlations between corneal nerve fibre length and established measures of neuropathy and risk factors for neuropathy were higher when a correction was made for the nerve tortuosity. CONCLUSIONS: Standardizing corneal nerve fibre length for tortuosity enhances the ability to differentiate individuals with diabetes, with and without neuropathy.

Metastatic spinal cord compression as a result of the unknown primary tumour.

PURPOSE: Patients presenting with metastatic spinal cord compression (MSCC) due to an unknown primary tumour (UPT) present an interesting problem with limited literature available to provide guidance on management. Our aim was twofold-first, to analyse all our patients with MSCC due to a UPT pre-operatively, to review their treatment and outcome; second, make comparisons with those patients who presented with MSCC due to a known primary tumour (KPT) during the same period. METHODS: All data was collected retrospectively from October 2004 to October 2009, then prospectively from October 2009 to October 2012 (8 years). We reviewed all patient records held on the database, including patient demographics, primary tumour, neurological outcome (Frankel grade), complications and survival. RESULTS: During the 8-year study period, out of the 382 patients who underwent emergency surgery for MSCC, 285 patients were included in whom complete information was available. Of these, 17 patients presented with MSCC due to a UPT (6 %; mean age 61 years, 5 M, 12 F). When compared to those with a known primary, the UPT group trended to a longer duration of symptoms prior to surgery (200 vs. 156 days, p = 0.86). They had a similar neurological outcome (88 % remained the same or improved post-operatively vs. 90 % in KPT group; p = 0.42), similar complication rate (23.5 vs. 33.6 %; p = 0.32) and survival (222 vs. 251 days, p = 0.42). The primary site in the UPT group was confirmed in 10/17 (58.8 %)-all 10 were adenocarcinoma [lung (6) and GI (4)]. DISCUSSION: In our series, the incidence of MSCC due to an unknown primary was 6 %. They had similar overall outcome (neurology post-operatively, complications and survival) to those patients with MSCC from a known primary. Our experience would suggest that we need to treat these patients expeditiously with thorough evaluation and urgent treatment.