The Influence of Meteorology on the Spread of Influenza: Survival Analysis of an Equine Influenza (A/H3N8) Outbreak

The influences of relative humidity and ambient temperature on the transmission of influenza A viruses have recently been established under controlled laboratory conditions. The interplay of meteorological factors during an actual influenza epidemic is less clear, and research into the contribution of wind to epidemic spread is scarce. By applying geostatistics and survival analysis to data from a large outbreak of equine influenza (A/H3N8), we quantified the association between hazard of infection and air temperature, relative humidity, rainfall, and wind velocity, whilst controlling for premises-level covariates. The pattern of disease spread in space and time was described using extraction mapping and instantaneous hazard curves. Meteorological conditions at each premises location were estimated by kriging daily meteorological data and analysed as time-lagged time-varying predictors using generalised Cox regression. Meteorological covariates time-lagged by three days were strongly associated with hazard of influenza infection, corresponding closely with the incubation period of equine influenza. Hazard of equine influenza infection was higher when relative humidity was <60% and lowest on days when daily maximum air temperature was 20–25°C. Wind speeds >30 km hour−1 from the direction of nearby infected premises were associated with increased hazard of infection. Through combining detailed influenza outbreak and meteorological data, we provide empirical evidence for the underlying environmental mechanisms that influenced the local spread of an outbreak of influenza A. Our analysis supports, and extends, the findings of studies into influenza A transmission conducted under laboratory conditions. The relationships described are of direct importance for managing disease risk during influenza outbreaks in horses, and more generally, advance our understanding of the transmission of influenza A viruses under field conditions

New high-Q discrete-time LC bandpass filter design with center frequency broadband tuning

Discrete-time switched-capacitor filters have been in wide-spread used for a few years, for the realization of stable, accurate and high quality filters. This paper describes the design of a new 8-path pseudo switched-capacitor LC bandpass filter and its command circuit made up by a ring voltage controlled oscillator (VCO) with 'XOR' gates. The proposed architecture presents the possibility of tuning over a frequency broadband allowing to sweep different channels with a high quality factor. This circuit is intended to replace the surface acoustic wave (SAW) filters in broadband wireless applications. Experimental results carried out on a prototype show quality factors up to 200, and a tunable center frequency range of 300 MHz [250-550 MHz]

Concurrent concentrated chemoradiation therapy in squamous cell carcinoma of the esophagus: long term results of a national multicenter phase II study in 122 inoperable patients (FFCD 8803)

International audienceObjectives-Concomitant radiochemotherapy improves survival from inoperable esophageal cancer compared to radiotherapy alone. Several regimens of radiotherapy (standard or concentrated split course radiotherapy) are used, however the optimum protocol remains to be determined The aim of this study was to analyze the efficacy and tolerance of concentrated concomitant split course radiochemotherapy. prognostic factors as well as those positively influencing complete response were also studied. Methods - This multicentric phase II trial looked at patients with histologically proven, inoperable, squamous cell esophageal carcinoma without metastases or invasion of the tracheobronchial mucosa. Treatment included 3 cycles of chemotherapy by 5-FU continuous infusion (800 mg/m(2).d D1-D5, D22-D26, D43-D47) cisplatin (70 mg/m(2) D2, D23, D44) and radiotherapy 15 Gy/5d (D1-D5, D22-26, D43-D47). Efficacy was analyzed by endoscopy, biopsy and computerized axial tomography during the 12(th) week of treatment. Results - The trial included 122 patients from 21 centers (110 M and 12 F, mean age 63.1 +/- 8.6 years, range 40 - 78). In accordance with the TNM-UICC classification (1978), 8 patients were classified stage I (T1 N0) 13 stage II (T2 N0), 100 stage III (T3 and/or N1) and stage was unknown in 1 patient. Median follow-vp was 63 months. Treatment was complete in half of the patients. 5 premature deaths (4.1%) were recorded over the treatment period, of which was directly linked to the toxicity of the the treatment. 16% of patients showed at least one severe side-effect. 117 patients received all 3 cycles of the treatment 88 of them without delay, and all were evaluated. 58 (47.5% of the patients included) showed a complete response with a negative biopsy, 36 (29.5%) showed a partial response, 13 (10.7%) were stable and 10 (8.2%) showed progressive disease. The median duration of complete responses wets 11.5 months. Symptomatically, dysphagia improved in 80% of the the cases, performance status in 40%, and weight gain was observed in 30% of the patients with weight loss. At evaluation, oral feeding was impossible in 4 patients only and possible in 113 patients; however, endoscopic treatment of the dysphagia remained necessary in 28 patients. Median survival in the 122 patients included was 13.0 +/- 1.6 months and survival rates were 52.9, 29.8 and 12.1% at 1, 2 and 5 years, respectively. Three pretherapeutic prognostic factors influenced survival in a multivariate analysis: initial severe dysphagia (risk of premature death increased 3-fold in the first year), circumferential extension and the differentiated nature of the tumor (risk of death doubled regardless of the time delay). Factors influencing a complete clinical response were on early tumor siege, a poorly differenciated tumor in patients older than 65, and no circumferential extension. The risk of recurrence was 54.8% at 1 year in the 58 Patients with complete remission. Complete circumferential extension and a well or moderately differentiated tumour influenced recurrence. Conclusion - This trial confirms the efficacy and good tolerance of concentrated split course radiochemotherapy in patients with inoperable esophageal cancer with a 5-year survival rate of 12%. This reinforces the need fbr a comparative trial (split course irradiation vs standard irradiation) such as the one currently being conducted in France

Concurrent concentrated chemoradiation therapy in squamous cell carcinoma of the esophagus: long term results of a national multicenter phase II study in 122 inoperable patients (FFCD 8803)

International audienceObjectives-Concomitant radiochemotherapy improves survival from inoperable esophageal cancer compared to radiotherapy alone. Several regimens of radiotherapy (standard or concentrated split course radiotherapy) are used, however the optimum protocol remains to be determined The aim of this study was to analyze the efficacy and tolerance of concentrated concomitant split course radiochemotherapy. prognostic factors as well as those positively influencing complete response were also studied. Methods - This multicentric phase II trial looked at patients with histologically proven, inoperable, squamous cell esophageal carcinoma without metastases or invasion of the tracheobronchial mucosa. Treatment included 3 cycles of chemotherapy by 5-FU continuous infusion (800 mg/m(2).d D1-D5, D22-D26, D43-D47) cisplatin (70 mg/m(2) D2, D23, D44) and radiotherapy 15 Gy/5d (D1-D5, D22-26, D43-D47). Efficacy was analyzed by endoscopy, biopsy and computerized axial tomography during the 12(th) week of treatment. Results - The trial included 122 patients from 21 centers (110 M and 12 F, mean age 63.1 +/- 8.6 years, range 40 - 78). In accordance with the TNM-UICC classification (1978), 8 patients were classified stage I (T1 N0) 13 stage II (T2 N0), 100 stage III (T3 and/or N1) and stage was unknown in 1 patient. Median follow-vp was 63 months. Treatment was complete in half of the patients. 5 premature deaths (4.1%) were recorded over the treatment period, of which was directly linked to the toxicity of the the treatment. 16% of patients showed at least one severe side-effect. 117 patients received all 3 cycles of the treatment 88 of them without delay, and all were evaluated. 58 (47.5% of the patients included) showed a complete response with a negative biopsy, 36 (29.5%) showed a partial response, 13 (10.7%) were stable and 10 (8.2%) showed progressive disease. The median duration of complete responses wets 11.5 months. Symptomatically, dysphagia improved in 80% of the the cases, performance status in 40%, and weight gain was observed in 30% of the patients with weight loss. At evaluation, oral feeding was impossible in 4 patients only and possible in 113 patients; however, endoscopic treatment of the dysphagia remained necessary in 28 patients. Median survival in the 122 patients included was 13.0 +/- 1.6 months and survival rates were 52.9, 29.8 and 12.1% at 1, 2 and 5 years, respectively. Three pretherapeutic prognostic factors influenced survival in a multivariate analysis: initial severe dysphagia (risk of premature death increased 3-fold in the first year), circumferential extension and the differentiated nature of the tumor (risk of death doubled regardless of the time delay). Factors influencing a complete clinical response were on early tumor siege, a poorly differenciated tumor in patients older than 65, and no circumferential extension. The risk of recurrence was 54.8% at 1 year in the 58 Patients with complete remission. Complete circumferential extension and a well or moderately differentiated tumour influenced recurrence. Conclusion - This trial confirms the efficacy and good tolerance of concentrated split course radiochemotherapy in patients with inoperable esophageal cancer with a 5-year survival rate of 12%. This reinforces the need fbr a comparative trial (split course irradiation vs standard irradiation) such as the one currently being conducted in France

Genomic evidence for the evolution of Streptococcus equi : host restriction, increased virulence, and genetic exchange with human pathogens

The continued evolution of bacterial pathogens has major implications for both human and animal disease, but the exchange of genetic material between host-restricted pathogens is rarely considered. Streptococcus equi subspecies equi (S. equi) is a host-restricted pathogen of horses that has evolved from the zoonotic pathogen Streptococcus equi subspecies zooepidemicus (S. zooepidemicus). These pathogens share approximately 80% genome sequence identity with the important human pathogen Streptococcus pyogenes. We sequenced and compared the genomes of S. equi 4047 and S. zooepidemicus H70 and screened S. equi and S. zooepidemicus strains from around the world to uncover evidence of the genetic events that have shaped the evolution of the S. equi genome and led to its emergence as a host-restricted pathogen. Our analysis provides evidence of functional loss due to mutation and deletion, coupled with pathogenic specialization through the acquisition of bacteriophage encoding a phospholipase A(2) toxin, and four superantigens, and an integrative conjugative element carrying a novel iron acquisition system with similarity to the high pathogenicity island of Yersinia pestis. We also highlight that S. equi, S. zooepidemicus, and S. pyogenes share a common phage pool that enhances cross-species pathogen evolution. We conclude that the complex interplay of functional loss, pathogenic specialization, and genetic exchange between S. equi, S. zooepidemicus, and S. pyogenes continues to influence the evolution of these important streptococci.Publisher PDFPeer reviewe