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1.  Macroscopic Equations Governing Noisy Spiking Neuronal Populations with Linear Synapses 
PLoS ONE  2013;8(11):e78917.
Deriving tractable reduced equations of biological neural networks capturing the macroscopic dynamics of sub-populations of neurons has been a longstanding problem in computational neuroscience. In this paper, we propose a reduction of large-scale multi-population stochastic networks based on the mean-field theory. We derive, for a wide class of spiking neuron models, a system of differential equations of the type of the usual Wilson-Cowan systems describing the macroscopic activity of populations, under the assumption that synaptic integration is linear with random coefficients. Our reduction involves one unknown function, the effective non-linearity of the network of populations, which can be analytically determined in simple cases, and numerically computed in general. This function depends on the underlying properties of the cells, and in particular the noise level. Appropriate parameters and functions involved in the reduction are given for different models of neurons: McKean, Fitzhugh-Nagumo and Hodgkin-Huxley models. Simulations of the reduced model show a precise agreement with the macroscopic dynamics of the networks for the first two models.
PMCID: PMC3827287  PMID: 24236067
2.  All-oral combination of oral vinorelbine and capecitabine as first-line chemotherapy in HER2-negative metastatic breast cancer: an International Phase II Trial 
British Journal of Cancer  2009;101(2):232-237.
This multicentre, international phase II trial evaluated the efficacy and safety profile of a first-line combination of oral vinorelbine plus capecitabine for women with metastatic breast cancer (MBC).
Patients with measurable, HER2-negative disease received, as a first line in metastatic setting, 3-weekly cycles of oral vinorelbine 80 mg m−2 (after a first cycle at 60) on day 1 and day 8, plus capecitabine 1000 mg m−2 (750 if ⩾65 years of age) twice daily, on days 1–14. Treatment was continued until progression or unacceptable toxicity.
A total of 55 patients were enrolled and 54 were treated (median age: 58.5 years). Most (78%) had visceral involvement and 63% had received earlier (neo)adjuvant chemotherapy. The objective response rate (RECIST) in 49 evaluable patients was 51% (95% confidence interval (CI), 36–66), including complete response in 4%. The clinical benefit rate (response or stable disease for ⩾6 months) was 63% (95% CI, 48–77). The median duration of response was 7.2 months (95% CI, 6.4–10.2). After a median follow-up of 41 months, median progression-free survival was 8.4 months (95% CI, 5.8–9.7) and median overall survival was 29.2 months (95% CI, 18.2–40.1). Treatment-related adverse events were manageable, the main grade 3–4 toxicity was neutropaenia (49%); two patients experienced febrile neutropaenia and three patients had a neutropaenic infection (including one septic death). A particularly low rate of alopaecia was observed.
These results show that the all-oral combination of oral vinorelbine and capecitabine is an effective and well-tolerated first-line regimen for MBC.
PMCID: PMC2720198  PMID: 19584872
oral therapy; first-line chemotherapy; metastatic breast cancer; HER2 negative
3.  Long-Term Survival in Adult Neuroblastoma with Multiple Recurrences 
Case Reports in Oncology  2010;3(1):45-48.
Neuroblastoma (NB) rarely occurs in adults, and less than 10% of the cases occur in patients older than 10 years. Currently, there are no standard treatment guidelines for adult NB patients. We report the case of a young man suffering from NB in adulthood with multiple recurrences. Treatment included multiple resections, chemotherapy, and radiotherapy. This patient remains free of clinical disease more than 7 years after diagnosis.
PMCID: PMC2918842  PMID: 20740158
Adults; Long-term survival; Neuroblastoma
4.  A second locus for Aicardi‐Goutières syndrome at chromosome 13q14–21 
Journal of Medical Genetics  2005;43(5):444-450.
Aicardi‐Goutières syndrome (AGS) is an autosomal recessive, early onset encephalopathy characterised by calcification of the basal ganglia, chronic cerebrospinal fluid lymphocytosis, and negative serological investigations for common prenatal infections. AGS may result from a perturbation of interferon α metabolism. The disorder is genetically heterogeneous with approximately 50% of families mapping to the first known locus at 3p21 (AGS1).
A genome‐wide scan was performed in 10 families with a clinical diagnosis of AGS in whom linkage to AGS1 had been excluded. Higher density genotyping in regions of interest was also undertaken using the 10 mapping pedigrees and seven additional AGS families.
Our results demonstrate significant linkage to a second AGS locus (AGS2) at chromosome 13q14–21 with a maximum multipoint heterogeneity logarithm of the odds (LOD) score of 5.75 at D13S768. The AGS2 locus lies within a 4.7 cM region as defined by a 1 LOD‐unit support interval.
We have identified a second AGS disease locus and at least one further locus. As in a number of other conditions, genetic heterogeneity represents a significant obstacle to gene identification in AGS. The localisation of AGS2 represents an important step in this process.
PMCID: PMC2649012  PMID: 15908569
AGS2; Aicardi‐Goutières syndrome; interferon α; intracranial calcification; 13q14–21
5.  Concomitant intensive chemoradiotherapy induction in non-metastatic inflammatory breast cancer: long-term follow-up 
British Journal of Cancer  2007;97(7):883-887.
The aim of this study was to evaluate with a long follow-up the efficacy of concomitant chemoradiotherapy in non-metastatic inflammatory breast cancer (IBC) and to evaluate the breast conservation rate. Between 1990 and 2000, 66 non-metastatic patients with IBC were treated with chemotherapy and concomitant irradiation. The induction chemotherapy consisted of epirubicine, cyclophosphamide and vindesine, in association with split-course bi-fractionated irradiation to a total dose of 65 Gy with concomitant cisplatin and 5-fluorouracil. Maintenance chemotherapy consisted of high-dose methotrexate and six cycles of epirubicine, cyclophosphamide and fluorouracil. Hormonal treatment was given if indicated. Mastectomy was not systemic. Among 65 evaluable patients, 57 (87.6%) achieved a complete clinical response and had a breast conservation. Only six loco regional relapses were noted in six patients with a delay of 20 months and with concomitant metastatic dissemination in four cases. Median disease-free survival (DFS) was 28 months. Median overall survival (OS) was 63 months and median follow-up was 55.5 months. Induction chemotherapy and concomitant irradiation is feasible in patients with IBC, permitting a breast conservation with a high rate of local control with an OS comparable to that of the best recent series.
PMCID: PMC2360400  PMID: 17876327
inflammatory breast cancer; chemoradiotherapy; breast conservation
6.  Expression Levels of Thymidylate Synthase, Thymidylate Phosphorylase and Dihydropyrimidine Dehydrogenase in Head and Neck Squamous Cell Carcinoma: Preliminary Study 
Pharyngo-laryngeal tumors classified as T3-4, N0-3, M0, are conventionally treated by mutilating surgery (total (pharyngo)-laryngectomy). Neo-adjuvant chemotherapy with 5-FU/platinum salt can be proposed in an attempt to preserve the larynx. The level of the response to chemotherapy ranges from 36 to 54% of cases. Thus, a large number of patients receive chemotherapy that is ineffective and not free from adverse effects. Three main enzymes are involved in the metabolism of 5-FU: thymidylate synthase (TS), thymidylate phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). Several studies suggest that a high level of expression of these three genes correlates with a poor clinical response to 5-FU. The main purpose of our study was to look for a correlation between the levels of expression of the genes for sensitivity to 5-FU (TS, TP, DPD) within the tumor and the clinical response observed after three courses of chemotherapy combining 5-FU/platinum salt in patients presenting with advanced cancer of the pharyngo-larynx.
This was a prospective genetic study that had required approval from the Ethics Committee. The main assessment criterion was based on the assessment of the clinical response by an ENT panendoscopy and a cervical CT scan, after three courses of chemotherapy. The expression of the genes was determined by quantitative RT-PCR, using total RNA extracted from tumor biopsies taken during the initial panendoscopy.
The means calculated, in our study, for the three genes of interest (TS, TP, DPD) were lower in the responder group than those in the non-responder group.
Our preliminary findings reveal trends that confirm the hypothesis that the lower the level of expression of the sensitivity genes, the better the clinical response to chemotherapy. They now form part of a larger study that is currently in progress.
PMCID: PMC3161652  PMID: 21892263
5-FU; genes of sensitivity; chemotherapy; squamous cell carcinoma; pharyngolarynx
7.  Phase II multicentre study of docetaxel plus 5-fluorouracil in patients with anthracycline-pretreated metastatic breast cancer 
British Journal of Cancer  2003;88(11):1669-1674.
PMCID: PMC2377146  PMID: 12771978
metastatic breast cancer; docetaxel; 5-FU
8.  Sequential or alternating administration of docetaxel (Taxotere®) combined with FEC in metastatic breast cancer: a randomised phase II trial 
British Journal of Cancer  2002;86(5):692-697.
The aim of this study, using a Fleming single-stage design, was to explore the efficacy and safety of Taxotere® 100 mg m−2 docetaxel and FEC 75 cyclophosphamide 500 mg m−2, fluorouracil 500 mg m−2 and epirubicin 75 mg m−2, in alternating and sequential schedules for the first-line treatment of metastatic breast cancer. One hundred and thirty-six women were randomly allocated, to one of three treatment regimens: DTX 100 plus FEC 75, alternated for eight courses (ALT); four courses of DTX 100 followed by four courses of FEC 75 (SEQ T); or four courses of FEC 75 followed by four courses of DTX 100 (SEQ F). One hundred and thirty-one women were evaluable for tumour response. Although the treatment outcome was equivalent in the two sequential arms and the alternating regimen (P=0.110, not significant), the response rate was less encouraging in the SEQ F arm (52.3%) than in the other two arms (71.1% for ALT and 70.5% for SEQ T), in which docetaxel was administered first. Time to progression was similar in the ALT, SEQ T and SEQ F arms (9.5, 9.3 and 10.4 months respectively). Grade 3–4 neutropenia was observed in nearly all patients; febrile neutropenia occurred in 9% (ALT), 16% (SEQ T) and 2% (SEQ F) of patients. Few patients (⩽9%) developed grade 3–4 non-haematological toxicities. Relative dose intensity was 97–99% for all regimens. All treatment regimens were active and well tolerated.
British Journal of Cancer (2002) 86, 692–697. DOI: 10.1038/sj/bjc/6600165
© 2002 Cancer Research UK
PMCID: PMC2375306  PMID: 11875727
metastatic breast cancer; sequential therapy; alternating therapy; docetaxel; FEC

Results 1-8 (8)