Towards the development of a DNA-sequence based approach to serotyping of Salmonella enterica

BACKGROUND: The fliC and fljB genes in Salmonella code for the phase 1 (H1) and phase 2 (H2) flagellin respectively, the rfb cluster encodes the majority of enzymes for polysaccharide (O) antigen biosynthesis, together they determine the antigenic profile by which Salmonella are identified. Sequencing and characterisation of fliC was performed in the development of a molecular serotyping technique. RESULTS: FliC sequencing of 106 strains revealed two groups; the g-complex included those exhibiting "g" or "m,t" antigenic factors, and the non-g strains which formed a second more diverse group. Variation in fliC was characterised and sero-specific motifs identified. Furthermore, it was possible to identify differences in certain H antigens that are not detected by traditional serotyping. A rapid short sequencing assay was developed to target serotype-specific sequence motifs in fliC. The assay was evaluated for identification of H1 antigens with a panel of 55 strains. CONCLUSION: FliC sequences were obtained for more than 100 strains comprising 29 different H1 alleles. Unique pyrosequencing profiles corresponding to the H1 component of the serotype were generated reproducibly for the 23 alleles represented in the evaluation panel. Short read sequence assays can now be used to identify fliC alleles in approximately 97% of the 50 medically most important Salmonella in England and Wales. Capability for high throughput testing and automation give these assays considerable advantages over traditional methods

Energy loss in a strongly coupled anisotropic plasma

We study the energy loss of a rotating infinitely massive quark moving, at constant velocity, through an anisotropic strongly-coupled N=4 plasma from holography. It is shown that, similar to the isotropic plasma, the energy loss of the rotating quark is due to either the drag force or radiation with a continuous crossover from drag-dominated regime to the radiation dominated regime. We find that the anisotropy has a significant effect on the energy loss of the heavy quark, specially in the crossover regime. We argue that the energy loss due to radiation in anisotropic media is less than the isotropic case. Interestingly this is similar to analogous calculations for the energy loss in weakly coupled anisotropic plasma.Comment: 26+1 pages, 10 figures, typos fixe

The forecasting of dynamical Ross River virus outbreaks: Victoria, Australia

Ross River virus (RRV) is Australia’s most epidemiologically important mosquito-borne disease.During RRV epidemics in the State of Victoria (such as 2010/11 and 2016/17) notifications canaccount for up to 30% of national RRV notifications. However, little is known about factors which canforecast RRV transmission in Victoria. We aimed to understand factors associated with RRVtransmission in epidemiologically important regions of Victoria and establish an early warningforecast system. We developed negative binomial regression models to forecast human RRVnotifications across 11 Local Government Areas (LGAs) using climatic, environmental, andoceanographic variables. Data were collected from July 2008 to June 2018. Data from July 2008 toJune 2012 were used as a training data set, while July 2012 to June 2018 were used as a testing dataset. Evapotranspiration and precipitation were found to be common factors for forecasting RRVnotifications across sites. Several site-specific factors were also important in forecasting RRVnotifications which varied between LGA. From the 11 LGAs examined, nine experienced an outbreakin 2011/12 of which the models for these sites were a good fit. All 11 LGAs experienced an outbreakin 2016/17, however only six LGAs could predict the outbreak using the same model. We documentsimilarities and differences in factors useful for forecasting RRV notifications across Victoria anddemonstrate that readily available and inexpensive climate and environmental data can be used to predict epidemic periods in some areas. Furthermore, we highlight in certain regions the complexityof RRV transmission where additional epidemiological information is needed to accurately predictRRV activity. Our findings have been applied to produce a Ross River virus Outbreak SurveillanceSystem (ROSS) to aid in public health decision making in Victoria

Vaccination against Foot-and-mouth disease : do initial conditions affect its benefit?

When facing incursion of a major livestock infectious disease, the decision to implement a vaccination programme is made at the national level. To make this decision, governments must consider whether the benefits of vaccination are sufficient to outweigh potential additional costs, including further trade restrictions that may be imposed due to the implementation of vaccination. However, little consensus exists on the factors triggering its implementation on the field. This work explores the effect of several triggers in the implementation of a reactive vaccination-to-live policy when facing epidemics of foot-and-mouth disease. In particular, we tested whether changes in the location of the incursion and the delay of implementation would affect the epidemiological benefit of such a policy in the context of Scotland. To reach this goal, we used a spatial, premises-based model that has been extensively used to investigate the effectiveness of mitigation procedures in Great Britain. The results show that the decision to vaccinate, or not, is not straightforward and strongly depends on the underlying local structure of the population-at-risk. With regards to disease incursion preparedness, simply identifying areas of highest population density may not capture all complexities that may influence the spread of disease as well as the benefit of implementing vaccination. However, if a decision to vaccinate is made, we show that delaying its implementation in the field may markedly reduce its benefit. This work provides guidelines to support policy makers in their decision to implement, or not, a vaccination-to-live policy when facing epidemics of infectious livestock disease

Atorvastatin reduces lipopolysaccharide-induced expression of cyclooxygenase-2 in human pulmonary epithelial cells

OBJECTIVE: To explore the effects of atorvastatin on expression of cyclooxygenase-2 (COX-2) in human pulmonary epithelial cells (A549). METHODS: A549 cells were incubated in DMEM medium containing lipopolysaccharide (LPS) in the presence or absence of atorvastatin. After incubation, the medium was collected and the amount of prostaglandin E(2 )(PGE(2)) was measured by enzyme-linked immunosorbent assay (ELISA). The cells were harvested, and COX-2 mRNA and protein were analyzed by RT-PCR and western-blot respectively. RESULTS: LPS increased the expression of COX-2 mRNA and production of PGE(2 )in a dose- and time-dependent manner in A549. Induction of COX-2 mRNA and protein by LPS were inhibited by atorvastatin in a dose-dependent manner. Atorvastatin also significantly decreased LPS-induced production of PGE(2). There was a positive correlation between reduced of COX-2 mRNA and decreased of PGE(2 )(r = 0.947, P < 0.05). CONCLUSION: Atorvastatin down-regulates LPS-induced expression of the COX-2 and consequently inhibits production of PGE(2 )in cultured A549 cells

Early-Time Energy Loss in a Strongly-Coupled SYM Plasma

We carry out an analytic study of the early-time motion of a quark in a strongly-coupled maximally-supersymmetric Yang-Mills plasma, using the AdS/CFT correspondence. Our approach extracts the first thermal effects as a small perturbation of the known quark dynamics in vacuum, using a double expansion that is valid for early times and for (moderately) ultrarelativistic quark velocities. The quark is found to lose energy at a rate that differs significantly from the previously derived stationary/late-time result: it scales like T^4 instead of T^2, and is associated with a friction coefficient that is not independent of the quark momentum. Under conditions representative of the quark-gluon plasma as obtained at RHIC, the early energy loss rate is a few times smaller than its late-time counterpart. Our analysis additionally leads to thermally-corrected expressions for the intrinsic energy and momentum of the quark, in which the previously discovered limiting velocity of the quark is found to appear naturally.Comment: 39 pages, no figures. v2: Minor corrections and clarifications. References added. Version to be published in JHE

Major depression, fibromyalgia and labour force participation: A population-based cross-sectional study

BACKGROUND: Previous studies have documented an elevated frequency of depressive symptoms and disorders in fibromyalgia, but have not examined the association between this comorbidity and occupational status. The purpose of this study was to describe these epidemiological associations using a national probability sample. METHODS: Data from iteration 1.1 of the Canadian Community Health Survey (CCHS) were used. The CCHS 1.1 was a large-scale national general health survey. The prevalence of major depression in subjects reporting that they had been diagnosed with fibromyalgia by a health professional was estimated, and then stratified by demographic variables. Logistic regression models predicting labour force participation were also examined. RESULTS: The annual prevalence of major depression was three times higher in subjects with fibromyalgia: 22.2% (95% CI 19.4 – 24.9), than in those without this condition: 7.2% (95% CI 7.0 – 7.4). The association persisted despite stratification for demographic variables. Logistic regression models predicting labour force participation indicated that both conditions had an independent (negative) effect on labour force participation. CONCLUSION: Fibromyalgia and major depression commonly co-occur and may be related to each other at a pathophysiological level. However, each syndrome is independently and negatively associated with labour force participation. A strength of this study is that it was conducted in a large probability sample from the general population. The main limitations are its cross-sectional nature, and its reliance on self-reported diagnoses of fibromyalgia

Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial

IMPORTANCE: Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. OBJECTIVE: To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. DESIGN, SETTING, AND PARTICIPANTS: The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. INTERVENTIONS: Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. RESULTS: In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. CONCLUSIONS AND RELEVANCE: Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00849615.info:eu-repo/semantics/publishedVersio