Centennial-scale climate change in Ireland during the Holocene

We examine mid- to late Holocene centennial-scale climate variability in Ireland using proxy data from peatlands, lakes and a speleothem. A high degree of between-record variability is apparent in the proxy data and significant chronological uncertainties are present. However, tephra layers provide a robust tool for correlation and improve the chronological precision of the records. Although we can find no statistically significant coherence in the dataset as a whole, a selection of high-quality peatland water table reconstructions co-vary more than would be expected by chance alone. A locally weighted regression model with bootstrapping can be used to construct a ‘best-estimate’ palaeoclimatic reconstruction from these datasets. Visual comparison and cross-wavelet analysis of peatland water table compilations from Ireland and Northern Britain show that there are some periods of coherence between these records. Some terrestrial palaeoclimatic changes in Ireland appear to coincide with changes in the North Atlantic thermohaline circulation and solar activity. However, these relationships are inconsistent and may be obscured by chronological uncertainties. We conclude by suggesting an agenda for future Holocene climate research in Ireland. ©2013 Elsevier B.V. All rights reserved.

Proximity to a tobacco store and smoking cessation:A cohort study

Background
It is not clear whether the availability of tobacco affects the likelihood of smoking cessation. We examined whether the proximity to a tobacco store and
the number of stores were associated with smoking cessation, and compared results for proximity variables based on walking and straight-line (as the crow flies) distance.

Methods
The study population consisted of 8751 baseline smokers from the Finnish Public Sector study in 1997–2005. Smoking intensity (cigarettes/day) was
determined at baseline and smoking cessation was determined from a follow-up survey in 2008–2009. Proximity was measured using straight-line and walking
distance from home to the nearest tobacco store, and another exposure variable was the number of stores within 0.50 km from home. We calculated associations
with log-binomial regression models, adjusting for individual-level and area-level confounders.

Results
Of the participants, 3482 (39.8%) quit smoking during the follow-up (mean follow-up 5.5 years, SD 2.3 years). Among men who were moderate/heavy smokers at baseline and lived <0.50 km walking distance from the nearest tobacco store, the likelihood of smoking cessation was 27% (95% CI 12% to 40%) lower compared with those living ≥0.50 km from a store. Having even one store within 0.50 km walking distance from home decreased cessation in men who were moderate/heavy smokers by 37% (95% CI 19% to 51%). No decrease was found for men who were light smokers at baseline or for women.

Conclusions
Living within walking distance of a tobacco store reduced the likelihood of smoking cessation among men who were moderate/heavy smokers.

Prediction of surface roughness during hard turning of AISI 4340 steel (69 HRC)

In this study, 39 sets of hard turning (HT) experimental trials were performed on a Mori-Seiki SL-25Y (4-axis) computer numerical controlled (CNC) lathe to study the effect of cutting parameters in influencing the machined surface roughness. In all the trials, AISI 4340 steel workpiece (hardened up to 69 HRC) was machined with a commercially available CBN insert (Warren Tooling Limited, UK) under dry conditions. The surface topography of the machined samples was examined by using a white light interferometer and a reconfirmation of measurement was done using a Form Talysurf. The machining outcome was used as an input to develop various regression models to predict the average machined surface roughness on this material. Three regression models - Multiple regression, Random Forest, and Quantile regression were applied to the experimental outcomes. To the best of the authors’ knowledge, this paper is the first to apply Random Forest or Quantile regression techniques to the machining domain. The performance of these models was compared to each other to ascertain how feed, depth of cut, and spindle speed affect surface roughness and finally to obtain a mathematical equation correlating these variables. It was concluded that the random forest regression model is a superior choice over multiple regression models for prediction of surface roughness during machining of AISI 4340 steel (69 HRC).

Root Cause Analysis by a Combined Sparse Classification and Monte Carlo Approach

Classification methods with embedded feature selection capability are very appealing for the analysis of complex processes since they allow the analysis of root causes even when the number of input variables is high. In this work, we investigate the performance of three techniques for classification within a Monte Carlo strategy with the aim of root cause analysis. We consider the naive bayes classifier and the logistic regression model with two different implementations for controlling model complexity, namely, a LASSO-like implementation with a L1 norm regularization and a fully Bayesian implementation of the logistic model, the so called relevance vector machine. Several challenges can arise when estimating such models mainly linked to the characteristics of the data: a large number of input variables, high correlation among subsets of variables, the situation where the number of variables is higher than the number of available data points and the case of unbalanced datasets. Using an ecological and a semiconductor manufacturing dataset, we show advantages and drawbacks of each method, highlighting the superior performance in term of classification accuracy for the relevance vector machine with respect to the other classifiers. Moreover, we show how the combination of the proposed techniques and the Monte Carlo approach can be used to get more robust insights into the problem under analysis when faced with challenging modelling conditions.

Characterisation of the frequent exacerbator phenotype in COPD patients in a large UK primary care population

BACKGROUND: The 'frequent exacerbator' is recognised as an important phenotype in COPD. Current understanding about this phenotype comes from prospective longitudinal clinical trials in secondary/tertiary care with little information reported in primary care populations.

AIMS: To characterize the frequent-exacerbator phenotype and identify associated risk factors in a large UK primary care COPD population.

METHODS: Using a large database of primary care patients from 80 UK general practices, patients were categorised using GOLD 2014 criteria into high and low risk groups based on exacerbation history. A multivariate logistic regression model was used to investigate covariates associated with the frequent-exacerbator phenotype and risk of experiencing a severe exacerbation (leading to hospitalisation).

RESULTS: Of the total study population (n = 9219), 2612 (28%) fulfilled the criteria for high risk frequent-exacerbators. Independent risk factors (adjusted odds ratio [95% CI]) for ≥2 exacerbations were: most severely impaired modified Medical Research Council (mMRC) dyspnoea score (mMRC grade 4: 4.37 [2.64-7.23]), lower FEV1 percent predicted (FEV1 <30%: 2.42 [1.61-3.65]), co-morbid cardiovascular disease (1.42 [1.19-1.68]), depression (1.56 [1.22-1.99]) or osteoporosis (1.54 [1.19-2.01]), and female gender (1.20 [1.01-1.43]). Older patients (≥75 years), those with most severe lung impairment (FEV1 <30%), those with highest mMRC score and those with co-morbid osteoporosis were identified as most at risk of experiencing exacerbations requiring hospitalisation.

CONCLUSIONS: Although COPD exacerbations occur across all grades of disease severity, female patients with high dyspnoea scores, more severely impaired lung function and co-morbidities are at greatest risk. Elderly patients, with severely impaired lung function, high mMRC scores and osteoporosis are associated with experience of severe exacerbations requiring hospitalisation.

Metastatic non-small cell lung cancer: a benchmark for quality end-of-life cancer care?

Objectives: To investigate the quality of end-of-life care for patients with metastatic non-small cell lung cancer (NSCLC). Design and participants: Retrospective cohort study of patients from first hospitalisation for metastatic disease until death, using hospital, emergency department and death registration data from Victoria, Australia, between 1 July 2003 and 30 June 2010. Main outcome measures: Emergency department and hospital use; aggressiveness of care including intensive care and chemotherapy in last 30 days; palliative and supportive care provision; and place of death. Results: Metastatic NSCLC patients underwent limited aggressive treatment such as intensive care (5%) and chemotherapy (< 1%) at the end of life; however, high numbers died in acute hospitals (42%) and 61% had a length of stay of greater than 14 days in the last month of life. Although 62% were referred to palliative care services, this occurred late in the illness. In a logistic regression model adjusted for year of metastasis, age, sex, metastatic site and survival, the odds ratio (OR) of dying in an acute hospital bed compared with death at home or in a hospice unit decreased with receipt of palliative care (OR, 0.25; 95% CI, 0.21–0.30) and multimodality supportive care (OR, 0.65; 95% CI, 0.56–0.75). Conclusion: Because early palliative care for patients with metastatic NSCLC is recommended, we propose that this group be considered a benchmark of quality end-of-life care. Future work is required to determine appropriate quality-of-care targets in this and other cancer patient cohorts, with particular focus on the timeliness of palliative care engagement.

Bird diversity and environmental gradients in Britain:a test of the species-energy hypothesis

1. We tested the species diversity-energy hypothesis using the British bird fauna. This predicts that temperature patterns should match diversity patterns. We also tested the hypothesis that the mechanism operates directly through effects of temperature on thermoregulatory loads; this further predicts that seasonal changes in temperature cause matching changes in patterns of diversity, and that species' body mass is influential.

2. We defined four assemblages using migration status (residents or visitors) and season (summer or winter distribution). Records of species' presence/absence in a total of 2362, 10 x 10-km, quadrats covering most of Britain were used, together with a wide selection of habitat, topographic and seasonal climatic data.

3. We fitted a logistic regression model to each species' distribution using the environmental data. We then combined these individual species models mathematically to form a diversity model. Analysis of this composite model revealed that summer temperature was the factor most strongly associated with diversity.

4. Although the species-energy hypothesis was supported, the direct mechanism, predicting an important role for body mass and matching seasonal patterns of change between diversity and temperature, was not supported.

5. However, summer temperature is the best overall explanation for bird diversity patterns in Britain. It is a better predictor of winter diversity than winter temperature. Winter diversity is predicted more precisely from environmental factors than summer diversity.

6. Climate change is likely to influence the diversity of different areas to different extents; for resident species, low diversity areas may respond more strongly as climate change progresses. For winter visitors, higher diversity areas may respond more strongly, while summer visitors are approximately neutral.

PREDICTING THE SPATIAL-DISTRIBUTION OF CLIMATE - TEMPERATURE IN GREAT-BRITAIN

1. The prediction and mapping of climate in areas between climate stations is of increasing importance in ecology.

2. Four categories of model, simple interpolation, thin plate splines, multiple linear regression and mixed spline-regression, were tested for their ability to predict the spatial distribution of temperature on the British mainland. The models were tested by external cross-verification.

3. The British distribution of mean daily temperature was predicted with the greatest accuracy by using a mixed model: a thin plate spline fitted to the surface of the country, after correction of the data by a selection from 16 independent topographical variables (such as altitude, distance from the sea, slope and topographic roughness), chosen by multiple regression from a digital terrain model (DTM) of the country.

4. The next most accurate method was a pure multiple regression model using the DTM. Both regression and thin plate spline models based on a few variables (latitude, longitude and altitude) only were comparatively unsatisfactory, but some rather simple methods of surface interpolation (such as bilinear interpolation after correction to sea level) gave moderately satisfactory results. Differences between the methods seemed to be dependent largely on their ability to model the effect of the sea on land temperatures.

5. Prediction of temperature by the best methods was greater than 95% accurate in all months of the year, as shown by the correlation between the predicted and actual values. The predicted temperatures were calculated at real altitudes, not subject to sea-level correction.

6. A minimum of just over 30 temperature recording stations would generate a satisfactory surface, provided the stations were well spaced.

7. Maps of mean daily temperature, using the best overall methods are provided; further important variables, such as continentality and length of growing season, were also mapped. Many of these are believed to be the first detailed representations at real altitude.

8. The interpolated monthly temperature surfaces are available on disk.

The Cyclin D1 (CCND1) A870G polymorphism predicts clinical outcome to lapatinib and capecitabine in HER2-positive metastatic breast cancer

BACKGROUND: Lapatinib plus capecitabine emerged as an efficacious therapy in metastatic breast cancer (mBC). We aimed to identify germline single-nucleotide polymorphisms (SNPs) in genes involved in capecitabine catabolism and human epidermal receptor signaling that were associated with clinical outcome to assist in selecting patients likely to benefit from this combination.

PATIENTS AND METHODS: DNA was extracted from 240 of 399 patients enrolled in EGF100151 clinical trial (NCT00078572; clinicaltrials.gov) and SNPs were successfully evaluated in 234 patients. The associations between SNPs and clinical outcome were analyzed using Fisher's exact test, Kaplan-Meier curves, log-rank tests, likelihood ratio test within logistic or Cox regression model, as appropriate.

RESULTS: There were significant interactions between CCND1 A870G and clinical outcome. Patients carrying the A-allele were more likely to benefit from lapatinib plus capecitabine versus capecitabine when compared with patients harboring G/G (P = 0.022, 0.024 and 0.04, respectively). In patients with the A-allele, the response rate (RR) was significantly higher with lapatinib plus capecitabine (35%) compared with capecitabine (11%; P = 0.001) but not between treatments in patients with G/G (RR = 24% and 32%, respectively; P = 0.85). Time to tumor progression (TTP) was longer in patients with the A-allele treated with lapatinib plus capecitabine compared with capecitabine (median TTP = 7.9 and 3.4 months; P < 0.001), but not in patients with G/G (median TTP = 6.1 and 6.6 months; P = 0.92).

CONCLUSION: Our findings suggest that CCND1A870G may be useful in predicting clinical outcome in HER2-positive mBC patients treated with lapatinib plus capecitabine.

Heller's myotomy and pneumatic dilatation in the treatment of achalasia: a population-based case–control study assessing long-term quality of life

Long-term health-related quality-of-life (HRQL) outcomes have not been widely reported in the
treatment of achalasia. The aims of this study were to examine long-term disease-specific and general HRQL in
achalasia patients using a population-based case–control method, and to assess HRQL between treatment interventions.
Manometrically diagnosed achalasia cases (n = 120) were identified and matched with controls (n = 115)
using a population-based approach. Participants completed general (SF-12) and disease-specific (Achalasia Severity
Questionnaire [ASQ]) HRQL questionnaires, as appropriate, in a structured interview. Mean composite scores
for SF-12 (Mental Component Summary score [MCS-12] and Physical Component Summary score [PCS-12]) and
ASQ were compared between cases and controls, or between intervention groups, using an independent t-test.
Adjusted mean differences in HRQL scores were evaluated using a linear regression model. Achalasia cases were
treated with a Heller’s myotomy (n = 43), pneumatic dilatation (n = 44), or both modalities (n = 33). The median
time from last treatment to HRQL assessment was 5.7 years (interquartile range 2.4–11.5). Comparing achalasia
patients with controls, PCS-12 was significantly worse (40.9 vs. 44.2, P = 0.01), but MCS-12 was similar. However,
both PCS-12 (39.9 vs. 44.2, P = 0.03) and MCS-12 (46.7 vs. 53.5, P = 0.004) were significantly impaired in those
requiring dual treatment compared with controls. Overall however, there was no difference in adjusted HRQL
between patients treated with Heller’s myotomy, pneumatic dilatation or both treatment modalities. In summary,
despite treatment achalasia patients have significantly worse long-term physical HRQL compared with population
controls. No HRQL differences were observed between the treatment modalities to suggest a benefit of one
treatment over another.

Age-Related Macular Degeneration-Associated Genes in Alzheimer Disease

Objectives: Given the clinical and pathological similarities between age-relatedmacular degeneration (AMD) and Alzheimer disease (AD), to assess whether AMDassociatedsingle nucleotide polymorphisms (SNPs), including those from complementrelatedgenes, are associated with AD. 
Design: A case-control association study-typedesign. 
Setting: A UK tertiary care dementia clinic. 
Participants: 322 cognitivelynormal participants and 258 cases with a clinical diagnosis of AD.
Measurements:Polymorphisms in the following genes were studied: CFH, ARMS2, C2/CFB, C3, CFI/PLA2G12a, SERPING1, TLR3, TLR4, CRP, APOE, and TOMM40. Haplotypes were analysedfor CFH, TOMM40, and APOE. Univariate analysis was performed for each geneticchange and case-comparator status, and then correction for multiple testing performed. 
Results: The presence of an ε4 APOE allele was significantly associated with AD. Noassociation was evident between CFH SNPs or haplotypes, or other AMD-associated SNPstested, and AD. The exceptions were TOMM40 SNPs, which were associated with AD evenafter correction for multiple comparisons. The associations disappeared, however, whenentered into a regression model including APOE genotypes. 
Conclusions: The resultsfor most SNPs tested, as well as CFH haplotypes, are novel. The functional effects ofabnormal complement activity in AD’s pathogenesis may be contradictory, butmethodological reasons may underlie the lack of association—for example, geneticchanges other than SNPs being involved.

Influence of corneal structure, corneal responsiveness, and other ocular parameters on tonometric measurement of intraocular pressure.

PURPOSE: To estimate the relationships between ocular parameters and tonometrically measured intraocular pressure (IOP), to determine the influence of ocular parameters on different instrument measurements of IOP, and to evaluate the association of ocular parameters with a parameter called hysteresis. METHODS: Patients presenting at a glaucoma clinic were recruited for this study. Subjects underwent IOP measurement with the Goldmann applanation tonometer (GAT), the TonoPen, and the Reichert Ocular Response Analyzer (ORA), and also measurements of central corneal thickness (CCT), axial length, corneal curvature, corneal astigmatism, central visual acuity, and refractive error. Chart information was reviewed to determine glaucoma treatment history. The ORA instrument provided a measurement called corneal hysteresis. The association between measured IOP and the other ocular characteristics was estimated using generalized estimating equations. RESULTS: Among 230 patients, IOP measurements from the TonoPen read lowest, and ORA read highest, and GAT measurements were closest to the mean IOP of the 3 instruments. In a multiple regression model adjusting for age, sex, race, and other ocular characteristics, a 10 microm increase in CCT was associated with an increase of 0.79 mm Hg measured IOP in untreated eyes (P<0.0001). Of the 3 tonometers, GAT was the least affected by CCT (0.66 mm Hg/10 mum, P<0.0001). Hysteresis was significantly correlated with CCT with a modest correlation coefficient (r=0.20, P<0.0007). CONCLUSIONS: Among parameters related to measured IOP, features in addition to CCT, such as hysteresis and corneal curvature, may also be important. Tonometric instruments seem to be affected differently by various physiologic characteristics.

HOTVal Toolkit

**************************************************************************** Scroll down to "Additional Files" to access the HOTVal Toolkit. **************************************************************************** HOTVal is a hotel valuation spreadsheet based on a regression model discussed in the Center for Real Estate and Finance at Cornell called Cornell Hotel Indices: Second Quarter 2012: The Trend is Our Friend by Crocker H. Liu, Adam D. Nowak, and Robert M. White, Jr. The model which will be continually updated, provides a rough estimation of the value of a hotel property once the user inputs information on whether the hotel is a large or small hotel, the year and quarter of the valuation, the state where the property is located, the number of rooms, the number of floors, the land area of the hotel property, the actual age of the hotel and whether the hotel is located in a Gateway city. For the first three inputs as well as the last input, if the user clicks on a cell highlighted in yellow, a pull down menu will appear to expedite inputting. The model is provided as a free public service by The Center for Real Estate and Finance at the School of Hotel Administration at Cornell University to academics and practitioners on an as-is, best-effort basis with no warranties or claims regarding its usefulness or implications. The estimates should be considered preliminary and subject to revision. *This October 2016 version updates the previous Hotel Valuation model, published in 2012 , provides valuation estimates up to and including the third quarter of 2016.

Maternal breastfeeding in Portugal: factors associated with the duration and premature cessation

Tese de mestrado em Bioestatística, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2013