Predictive value of heidelberg retina tomograph parameters for the development of glaucoma in the European glaucoma prevention study

PURPOSE: To determine whether baseline Heidelberg Retina Tomograph (HRT) measurements of the optic disc are associated with the development of open-angle glaucoma (OAG) in individuals with ocular hypertension in the European Glaucoma Prevention Study (EGPS). DESIGN: Retrospective analysis of a prospective, randomized, multicenter, double-masked, controlled clinical trial. METHODS: There were 489 participants in the HRT Ancillary Study to the EGPS. Each baseline HRT parameter was assessed in univariate and multivariate proportional hazards models to determine its association with the development of OAG. Proportional hazards models were used to identify HRT variables that predicted which participants in the EGPS had developed OAG. Development of OAG was based on visual field and/or optic disc changes. RESULTS: At a median follow-up time of about 5 years, 61 participants developed OAG. In multivariate analyses, adjusting for randomization arm, age, baseline IOP, central corneal thickness, pattern standard deviation, and HRT disc area, the following HRT parameters were associated with the development of OAG: the "outside normal limits" classification of the Frederick Mikelberg (FSM) discriminant function (hazard ratio [HR] 2.51, 95% confidence interval [CI]: 1.45-4.35), larger mean cup depth (HR 1.64, 95% CI: 1.21-2.23), cup-to-disc area ratio (HR 1.43, 95% CI: 1.14-1.80), linear cup-to-disc ratio (HR 1.43, 95% CI: 1.13-1.80), cup area (HR 1.33, 95% CI: 1.08-1.64), smaller rim area (HR 1.33, 95% CI: 1.07-1.64), larger cup volume (HR 1.30, 95% CI: 1.05-1.61), smaller rim volume (HR 1.25, 95% CI: 1.01-1.54), larger maximum cup depth (HR 1.18, 95% CI: 1.01-1.36), and cup shape measure (HR 1.18, 95% CI: 1.01-1.36). CONCLUSIONS: Several baseline HRT parameters, alone or in combination with baseline clinical and demographic factors, were significantly associated with the development of OAG among the EGPS participants

Anomalous diffusion as a signature of collapsing phase in two dimensional self-gravitating systems

A two dimensional self-gravitating Hamiltonian model made by $N$ fully-coupled classical particles exhibits a transition from a collapsing phase (CP) at low energy to a homogeneous phase (HP) at high energy. From a dynamical point of view, the two phases are characterized by two distinct single-particle motions : namely, superdiffusive in the CP and ballistic in the HP. Anomalous diffusion is observed up to a time $\tau$ that increases linearly with $N$. Therefore, the finite particle number acts like a white noise source for the system, inhibiting anomalous transport at longer times.Comment: 10 pages, Revtex - 3 Figs - Submitted to Physical Review

Diffusion entropy and waiting time statistics of hard x-ray solar flares

We analyze the waiting time distribution of time distances $\tau$ between two nearest-neighbor flares. This analysis is based on the joint use of two distinct techniques. The first is the direct evaluation of the distribution function $\psi(\tau)$, or of the probability, $\Psi(tau)$, that no time distance smaller than a given $\tau$ is found. We adopt the paradigm of the inverse power law behavior, and we focus on the determination of the inverse power index $\mu$, without ruling out different asymptotic properties that might be revealed, at larger scales, with the help of richer statistics. The second technique, called Diffusion Entropy (DE) method, rests on the evaluation of the entropy of the diffusion process generated by the time series. The details of the diffusion process depend on three different walking rules, which determine the form and the time duration of the transition to the scaling regime, as well as the scaling parameter $\delta$. With the first two rules the information contained in the time series is transmitted, to a great extent, to the transition, as well as to the scaling regime. The same information is essentially conveyed, by using the third rules, into the scaling regime, which, in fact, emerges very quickly after a fast transition process. We show that the significant information hidden within the time series concerns memory induced by the solar cycle, as well as the power index $\mu$. The scaling parameter $\delta$ becomes a simple function of $\mu$, when memory is annihilated. Thus, the three walking rules yield a unique and precise value of $\mu$ if the memory is wisely taken under control, or cancelled by shuffling the data. All this makes compelling the conclusion that $\mu = 2.138 \pm 0.01$.Comment: 23 pages, 13 figure

High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice.

Purpose. Several studies have suggested that KRAS somatic mutations may predict resistance to cetuximab- and panitumumab-based treatments in metastatic colorectal cancer (CRC) patients. Nevertheless, most experiences were conducted on samples from primaries. The aim of this study was to evaluate the grade of concordance in terms of KRAS status between primaries and related metastases. Patients and Methods. We analyzed KRAS codon 12 and 13 mutations from formalin-fixed sections of 107 CRC primaries and related metastases. Eight pairs were excluded from the analysis because of the low amount of tumor tissue in the available samples. The main characteristics were: 50 men, 49 women; median age at diagnosis, 71 years (range, 41-84). The metastatic sites analyzed were the liver in 80 patients (80.8%), lung in seven patients (7.1%), and other sites in 12 patients (12.1%). Results. A KRAS mutation was found in 38 (38.4%) primary tumors and in 36 (36.4%) related metastases. The rate of concordance was 96.0% (95% confidence interval, 90.0%-98.9%). Discordance was observed in only four (4%) patients. Conclusions. Our results indicate that the detection of KRAS mutations in either primary or metastatic tumors from patients with CRC is concordant and this assessment could be used to predict response to targeted therapies such as cetuximab and panitumumab

A Path Toward the Use of Trail Users’ Tweets to Assess Effectiveness of the Environmental Stewardship Scheme: An Exploratory Analysis of the Pennine Way National Trail

Large and unofficial data sets, for instance those gathered from social media, are increasingly being used in geographical research and explored as decision support tools for policy development. Social media data have the potential to provide new insight into phenomena about which there is little information from conventional sources. Within this context, this paper explores the potential of social media data to evaluate the aesthetic management of landscape. Specifically, this project utilises the perceptions of visitors to the Pennine Way National Trail, which passes through land managed under the Environmental Stewardship Scheme (ESS). The method analyses sentiment in trail users’ public Twitter messages (tweets) with the aim of assessing the extent to which the ESS maintains landscape character within the trail corridor. The method demonstrates the importance of filtering social media data to convert it into useful information. After filtering, the results are based on 161 messages directly related to the trail. Although small, this sample illustrates the potential for social media to be used as a cheap and increasingly abundant source of information. We suggest that social media data in this context should be seen as a resource that can complement, rather than replace, conventional data sources such as questionnaires and interviews. Furthermore, we provide guidance on how social media could be effectively used by conservation bodies, such as Natural England, which are charged with the management of areas of environmental value worldwide

Equilibrium and dynamical properties of two dimensional self-gravitating systems

A system of N classical particles in a 2D periodic cell interacting via long-range attractive potential is studied. For low energy density $U$ a collapsed phase is identified, while in the high energy limit the particles are homogeneously distributed. A phase transition from the collapsed to the homogeneous state occurs at critical energy U_c. A theoretical analysis within the canonical ensemble identifies such a transition as first order. But microcanonical simulations reveal a negative specific heat regime near $U_c$. The dynamical behaviour of the system is affected by this transition : below U_c anomalous diffusion is observed, while for U > U_c the motion of the particles is almost ballistic. In the collapsed phase, finite $N$-effects act like a noise source of variance O(1/N), that restores normal diffusion on a time scale diverging with N. As a consequence, the asymptotic diffusion coefficient will also diverge algebraically with N and superdiffusion will be observable at any time in the limit N \to \infty. A Lyapunov analysis reveals that for U > U_c the maximal exponent \lambda decreases proportionally to N^{-1/3} and vanishes in the mean-field limit. For sufficiently small energy, in spite of a clear non ergodicity of the system, a common scaling law \lambda \propto U^{1/2} is observed for any initial conditions.Comment: 17 pages, Revtex - 15 PS Figs - Subimitted to Physical Review E - Two column version with included figures : less paper waste

Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer

Some trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer. Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m(2) day 1, LV 100 mg/m(2) as 2 h infusion and 5-FU 400 mg/m(2) as bolus, days 1 and 2 followed by 600 mg/m(2)/day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm). From February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85-1.17; P = 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82-1.18; P = 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively. A more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy

Systematic aortic and pelvic lymphadenectomy versus resection of bulky nodes only in optimally debulked advanced ovarian cancer: A randomized clinical trial

The role of systematic aortic and pelvic lymphadenectomy in patients with optimally debulked advanced ovarian cancer is unclear and has not been addressed by randomized studies. We conducted a randomized clinical trial to determine whether systematic aortic and pelvic lymphadenectomy improves progression-free and overall survival compared with resection of bulky nodes only. Methods: From January 1991 through May 2003, 427 eligible patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIB-C and IV epithelial ovarian carcinoma were randomly assigned to undergo systematic pelvic and para-aortic lymphadenectomy (n = 216) or resection of bulky nodes only (n = 211). Progression-free survival and overall survival were analyzed using a logrank statistic and a Cox multivariable regression analysis. All statistical tests were two-sided. Results: After a median followup of 68.4 months, 292 events (i.e., recurrences or deaths) were observed, and 202 patients had died. Sites of first recurrences were similar in both arms. The adjusted risk for first event was statistically significantly lower in the systematic lymphadenectomy arm (hazard ratio [HR] =.75, 95% confidence interval [CI] = 0.59 to 0.94; P =.01) than in the no-lymphadenectomy arm, corresponding to 5-year progression-free survival rates of 31.2 and 21.6% in the systematic lymphadenectomy and control arms, respectively (difference = 9.6%, 95% CI = 1.5% to 21.6%), and to median progression-free survival of 29.4 and 22.4 months, respectively (difference = 7 months, 95% CI = 1.0 to 14.4 months). The risk of death was similar in both arms (HR = 0.97, 95% CI = 0.74 to 1.29; P =.85), corresponding to 5-year overall survival rates of 48.5 and 47%, respectively (difference = 1.5%, 95% CI = -8.4% to 10.6%), and to median overall survival of 58.7 and 56.3 months, respectively (difference = 2.4 months, 95% CI = -11.8 to 21.0 months). Median operating time was longer, and the percentage of patients requiring blood transfusions was higher in the systematic lymphadenectomy arm than in the no-lymphadenectomy arm (300 versus 210 minutes, P <.001, and 72% versus 59%; P =.006, respectively). Conclusion: Systematic lymphadenectomy improves progression-free but not overall survival in women with optimally debulked advanced ovarian carcinoma

KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer

BACKGROUND: KRAS codons 12 and 13 mutations predict resistance to anti-EGFR monoclonal antibodies (moAbs) in metastatic colorectal cancer. Also, BRAF V600E mutation has been associated with resistance. Additional KRAS mutations are described in CRC. METHODS: We investigated the role of KRAS codons 61 and 146 and BRAF V600E mutations in predicting resistance to cetuximab plus irinotecan in a cohort of KRAS codons 12 and 13 wild-type patients. RESULTS: Among 87 KRAS codons 12 and 13 wild-type patients, KRAS codons 61 and 146 were mutated in 7 and 1 case, respectively. None of mutated patients responded vs 22 of 68 wild type (P = 0.096). Eleven patients were not evaluable. KRAS mutations were associated with shorter progression-free survival (PFS, HR: 0.46, P = 0.028). None of 13 BRAF-mutated patients responded vs 24 of 74 BRAF wild type (P = 0.016). BRAF mutation was associated with a trend towards shorter PFS (HR: 0.59, P = 0.073). In the subgroup of BRAF wild-type patients, KRAS codons 61/146 mutations determined a lower response rate (0 vs 37%, P = 0.047) and worse PFS (HR: 0.45, P = 0.023). Patients bearing KRAS or BRAF mutations had poorer response rate (0 vs 37%, P = 0.0005) and PFS (HR: 0.51, P = 0.006) compared with KRAS and BRAF wild-type patients. CONCLUSION: Assessing KRAS codons 61/146 and BRAF V600E mutations might help optimising the selection of the candidate patients to receive anti-EGFR moAbs. British Journal of Cancer (2009) 101, 715-721. doi: 10.1038/sj.bjc.6605177 www.bjcancer.com Published online 14 July 2009 (C) 2009 Cancer Research U