Determination of the Discriminating Concentration Towards Permethrin for Surveying Resistance in Amblyomma americanum.

Amblyomma americanum Linnaeus (Ixodida: Ixodidae) is ubiquitously present throughout the southeastern United States and is capable of vectoring several pathogens. White-tailed deer are the main host for adult A. americanum. However, this tick species is a generalist that will feed on most vertebrates, including humans, deer, livestock, and pets. Management of this species can be challenging due to a lack of cost-effective strategies. Acaricides are often utilized, however, this may lead to pesticide resistance. The Food and Agriculture Organization of the United Nations (FAO) larval packet test (LPT) was performed on susceptible A. americanum to determine the lethal concentration (LC) and discriminating concentration (DC) values for permethrin. The FAO LPT was used at these pre-established values to compare levels of resistance in ticks collected from a captive deer farm and wild areas representing high and low permethrin exposure settings, respectively. Resistance ratios (RR) calculated from the LC values for the ticks collected from farmed and wild deer ranged between 1 and 2. A. americanum collected from farmed and wild deer were not found to be resistant, however, some samples had slightly elevated RRs as compared to the susceptible laboratory strain, which may suggest tolerance development. Although the A. americanum sampled in this study were not resistant to permethrin, the DC calculated in this study will allow for rapid evaluation of resistance in a permethrin resistance monitoring program such that alternate management strategies can be adopted if resistance is detected.

Assessment of human baroreflex function using carotid ultrasonography: what have we learnt?

The arterial baroreflex is critical to both short- and long-term regulation of blood pressure. However, human baroreflex research has been largely limited to the association between blood pressure and cardiac period (or heart rate) or indices of vascular sympathetic function. Over the past decade, emerging techniques based on carotid ultrasound imaging have allowed new means of understanding and measuring the baroreflex. In this review, we describe the assessment of the mechanical and neural components of the baroreflex through the use of carotid ultrasound imaging. The mechanical component refers to the change in carotid artery diameter in response to changes in arterial pressure, and the neural component refers to the change in R-R interval (cardiac baroreflex) or muscle sympathetic nerve activity (sympathetic baroreflex) in response to this barosensory vessel stretch. The key analytical concepts and techniques are discussed, with a focus on the assessment of baroreflex sensitivity via the modified Oxford method. We illustrate how the application of carotid ultrasound imaging has contributed to a greater understanding of baroreflex physiology in humans, covering topics such as ageing and diurnal variation, and physiological challenges including exercise, postural changes and mental stress.

Postural influences on the mechanical and neural components of the cardiovagal baroreflex.

AIM: The ability to maintain arterial blood pressure when faced with a postural challenge has implications for the occurrence of syncope and falls. It has been suggested that posture-induced declines in the mechanical component of the baroreflex response drive reductions in cardiovagal baroreflex sensitivity associated with postural stress. However, these conclusions are largely based upon spontaneous methods of baroreflex assessment, the accuracy of which has been questioned. Therefore, the aim was to engage a partially open-loop approach to explore the influence of posture on the mechanical and neural components of the baroreflex. METHODS: In nine healthy participants, we measured continuous blood pressure, heart rate, RR interval and carotid artery diameter during supine and standing postures. The modified Oxford method was used to quantify baroreflex sensitivity. RESULTS: In response to falling pressures, baroreflex sensitivity was similar between postures (P = 0.798). In response to rising pressures, there was an attenuated (P = 0.042) baroreflex sensitivity (mean ± SE) in the standing position (-0.70 ± 0.11 beats min(-1) mmHg(-1)) compared with supine (-0.83 ± 0.06 beats min(-1) mmHg(-1)). This was explained by a diminished (P = 0.016) neural component whilst standing (-30.17 ± 4.16 beats min(-1) mm(-1)) compared with supine (-38.23 ± 3.31 beats min(-1) mm(-1)). These effects were consistent when baroreflex sensitivity was determined using RR interval. CONCLUSION: Cardiovagal baroreflex sensitivity in response to rising pressures is reduced in young individuals during postural stress. Our data suggest that the mechanical component is unaffected by standing, and the reduction in baroreflex sensitivity is driven by the neural component.

The effectiveness of local child weight management programmes: an audit study.

BACKGROUND: Many different child weight management programmes exist, with varying degrees of evaluation to provide evidence of their success. The purpose of this research was to use a standardized approach to audit the effectiveness of weight management intervention programmes in the West Midlands region of the UK, specifically to assess the benefits to participating children in terms of health improvement and behaviour change. METHODS: An audit of seven family-based intervention programmes currently in place in the West Midlands. Programmes were audited against the Standard Evaluation Framework. RESULTS: The programmes provided a partial data set relating to a change in weight from the baseline to the end of the programme; none of the programmes provided all of the measures indicated by the Standard Evaluation Form as being essential for evaluation. Weight change ranged from an increase in group mean of 0.4 kg to a decrease of 0.9 kg. Body Mass Index SD decreased by 0.1-0.2 points in four programmes and remained unchanged in two programmes. Four programmes collected long-term follow-up data at 6 months. This was often limited because of participant dropout. Improvement in diet and exercise were reported by participants in all programmes which measured these behaviours. CONCLUSIONS: Ongoing evaluation of all programmes, using a standard approach, is essential in order to improve the evidence base and support future commissioning.

Pre-race dietary carbohydrate intake can independently influence sub-elite marathon running performance.

We examined whether selected anthropometric and nutritional factors influenced field-based marathon running performance. An internet-based data collection tool allowed competitors in the 2009 London Marathon (n=257, mean ± SD age: 39 ± 8 years, finish time: 273.8 ± 59.5 min) to record a range of anthropometric, training and nutritional predictors. Multivariate statistical methods were used to quantify the change in running speed mediated by a unit change in each predictor via the 95% confidence interval for each covariate-controlled regression slope ( B). Gender ( B=1.22 to 1.95 km/h), body mass index ( B=-0.14 to -0.27 km/h), training distance ( B=0.01 to 0.04 km/h) and the amount of carbohydrate consumed the day before the race ( B=0.08 to 0.26 km/h) were significant predictors, collectively accounting for 56% of the inter-individual variability in running speed (P<0.0005). Further covariate-adjusted analysis revealed that those competitors who consumed carbohydrate the day before the race at a quantity of >7 g/kg body mass had significantly faster overall race speeds (P=0.01) and maintained their running speed during the race to a greater extent than with those who consumed <7 g/kg body mass (P=0.02). We conclude that, in addition to gender, body size and training, pre-race day carbohydrate intake can significantly and independently influence marathon running performance.

Neurovascular coupling and distribution of cerebral blood flow during exercise.

We examined how cerebral blood flow velocity (CBV) and neurovascular coupling is influenced by exercise. Blood velocities in the posterior and middle cerebral arteries (PCAv and MCAv) during rest and cycling exercise at 60% estimated maximal oxygen consumption were measured. Neurovascular coupling was quantified as the ΔPCAv with visual stimulation. During exercise, despite a 15.2±13.6% and 26.1±22.5% increase from rest in the MCAv and PCAv, respectively, neurovascular coupling was unaltered. Thus, despite regionally heterogeneous elevations in CBV during exercise, neurometabolic coupling is maintained.

Blood pressure status and post-exercise hypotension: an example of a spurious correlation in hypertension research?

A single bout of exercise lowers blood pressure (BP) for up to 24 h afterwards. The magnitude of this post-exercise hypotension (PEH) has been reported to be correlated most strongly to pre-exercise BP, and this apparent relationship has influenced position statements about the value of exercise in arterial hypertension. Nevertheless, this correlation could be adversely affected by mathematical coupling and regression-to-the-mean artefacts. Therefore, we aimed to examine the degree to which BP status moderates PEH while, for the first time, controlling for these statistical artefacts. A total of 32 participants, with pre-exercise mean arterial pressures of 65-110 mm Hg, cycled for 30 min at 70% peak oxygen uptake. Systolic BP and diastolic BP were measured (Portapres) before exercise and for 20 min after exercise. Changes in BP were regressed against pre-exercise values, and against the mean of pre- and post-exercise BP, among other indices that are also known not to be prone to artefacts. Correlations between pre-exercise BP and the exercise-mediated reductions were typical of those previously reported (r=0.37-0.62, P<0.05), but not large enough to rule out spuriousness (P>0.05). Artefact-free indices of BP status (pre- and post-exercise mean as well as an earlier independent measurement) did not correlate with reductions in BP (P>0.05), which were moderated more by peak oxygen uptake and time of day (P<0.05). These data indicate that, if statistical artefacts are not controlled for, the influence of BP status on the degree of PEH can be spuriously exaggerated to the extent that other more important moderators of BP change are masked.

Carbohydrate Moieties as Vaccine Candidates: meeting summary.

In September 2007, a meeting entitled 'Carbohydrate Moieties as Vaccine Candidates' was held at the National Institutes of Health (Bethesda, MD). This meeting brought together scientists from a number of disciplines to address issues concerning carbohydrate moieties as targets for vaccines for a variety of pathogens and tumors. In addition, the meeting participants addressed fundamental topics of glycoimmunology including the recognition of glycotopes by B and T lymphocytes, the ontogeny of anti-carbohydrate immune responses, peptide mimicry, carbohydrate antigen processing pathways and adjuvants. One session reported progress in the development of new tools such as computational algorithms, glycan arrays and oligosaccharide synthesis and their application to carbohydrate vaccine research. The session titles were: (1) immune response to bacterial carbohydrate antigens; (2) immune response to glycolipids; (3) immune response to carbohydrate antigens on other microbes and on tumors; (4) novel vaccine approaches; (5) novel tools in carbohydrate vaccine research; (6) bench to bedside: carbohydrate moieties as vaccine immunopotentiators.

Diagnosis of human metapneumovirus by immunofluorescence staining with monoclonal antibodies in the North-East of England.

BACKGROUND: Since its discovery in 2001 human metapneumovirus (hMPV) has been shown to be a significant cause of human respiratory disease, responsible for 5-8% of respiratory infections in hospitalised children. Diagnosis hitherto has been largely carried out by reverse tanscriptase polymerase chain reaction (RT-PCR) but immunofluorescence staining of cells from nasopharyngeal secretions (IF) offers advantages for some laboratories and may produce a more rapid result in urgent cases. We have recently demonstrated that IF with a rabbit antiserum gave sensitivity equal to that of RT-PCR. However, monoclonal antibodies offer a more plentiful, uniform IF reagent. OBJECTIVES: Here we have evaluated a pool of anti-hMPV monoclonal antibodies in the routine diagnosis of respiratory infections in hospitalised infants and children. STUDY DESIGN: Eight hundred and fifty-seven routine respiratory specimens were tested by IF with rabbit polyclonal antiserum and monoclonal antibody pool in parallel. A further 1003 specimens were tested with the monoclonal antibody pool alone. All specimens were also tested for a panel of other respiratory viruses by IF. RESULTS: Both rabbit polyclonal antiserum and monoclonal antibody pool gave positive results in 56 and negative results in 797 specimens. The rabbit polyclonal antibody detected virus in a further two specimens which were negative when tested with the monoclonal pool giving a concordance of 96.6% and a specificity of 100% for the monoclonal antibody pool. Overall hMPV was detected in 5% of specimens whilst 18.4% were positive for hRSV. CONCLUSIONS: The monoclonal antibody pool-based IF is a robust assay suitable for routine use with a sensitivity only slightly less than that of the other major diagnostic methodologies available.

Value of bronchoalveolar lavage before haematopoietic stem cell transplantation for primary immunodeficiency or autoimmune diseases.

Pulmonary infection, often insidious, is frequent in primary immunodeficiency (PID) and acquired immunodeficiency. Pulmonary complications are serious obstacles to success of haematopoietic SCT (HSCT) for these conditions. Bronchoalveolar lavage (BAL) permits identification of lower respiratory tract pathogens that may direct specific treatment and influence prognosis. There are no reports about the utility of pre-HSCT BAL for immunodeficient patients. We prospectively studied the value of 'routine' BAL before commencing transplantation in patients undergoing HSCT for severe immunological disease. Routine non-bronchoscopic BAL was performed under general anaesthetic, a few days before commencing pre-HSCT cytoreductive chemotherapy. Patients were categorized as symptomatic or asymptomatic with respect to pulmonary disease or infection. Samples were sent for microbiological processing. Complications arising from the procedure, pathogens isolated and treatments instituted were recorded. Results were available from 69/75 patients transplanted during the study period; 26 (38%) had pathogens identified (six asymptomatic patients), 10 (14.5%) developed complications post-procedure (two asymptomatic patients)-all recovered, 21 had management changes. There was no statistically significant difference in the number of positive isolates from severe combined or other immunodeficient patients, or of symptomatic or asymptomatic patients. Routine non-bronchoscopic BAL is safe in immunodeficient patients about to undergo HSCT, and leads to management changes.

Molecular dynamics simulations of methane hydrate using polarizable force fields.

Molecular dynamics simulations of methane hydrate have been carried out using the polarizable AMOEBA and COS/G2 force fields. Properties calculated include the temperature dependence of the lattice constant, the OC and OO radial distribution functions, and the vibrational spectra. Both the AMOEBA and COS/G2 force fields are found to successfully account for the available experimental data, with overall somewhat better agreement with experiment being found for the AMOEBA model. Comparison is made with previous results obtained using TIP4P and SPC/E effective two-body force fields and the polarizable TIP4P-FQ force field, which allows for in-plane polarization only. Significant differences are found between the properties calculated using the TIP4P-FQ model and those obtained using the other models, indicating an inadequacy of restricting explicit polarization to in-plane only.

Patterns of irrigated rice growth and malaria vector breeding in Mali using multi-temporal ERS-2 synthetic aperture radar.

We explored the use of the European Remote Sensing Satellite 2 Synthetic Aperture Radar (ERS-2 SAR) to trace the development of rice plants in an irrigated area near Niono, Mali and relate that to the density of anopheline mosquitoes, especially An. gambiae. This is important because such mosquitoes are the major vectors of malaria in sub-Saharan Africa, and their development is often coupled to the cycle of rice development. We collected larval samples, mapped rice fields using GPS and recorded rice growth stages simultaneously with eight ERS-2 SAR acquisitions. We were able to discriminate among rice growth stages using ERS-2 SAR backscatter data, especially among the early stages of rice growth, which produce the largest numbers of larvae. We could also distinguish between basins that produced high and low numbers of anophelines within the stage of peak production. After the peak, larval numbers dropped as rice plants grew taller and thicker, reducing the amount of light reaching the water surface. ERS-2 SAR backscatter increased concomitantly. Our data support the belief that ERS-2 SAR data may be helpful for mapping the spatial patterns of rice growth, distinguishing different agricultural practices, and monitoring the abundance of vectors in nearby villages.

Mapping rice field anopheline breeding habitats in Mali, West Africa, using Landsat ETM+ sensor data.

The aim of this study was to determine whether remotely sensed data could be used to identify rice-related malaria vector breeding habitats in an irrigated rice growing area near Niono, Mali. Early stages of rice growth show peak larval production, but Landsat sensor data are often obstructed by clouds during the early part of the cropping cycle (rainy season). In this study, we examined whether a classification based on two Landsat Enhanced Thematic Mapper (ETM)+ scenes acquired in the middle of the season and at harvesting times could be used to map different land uses and rice planted at different times (cohorts), and to infer which rice growth stages were present earlier in the season. We performed a maximum likelihood supervised classification and evaluated the robustness of the classifications with the transformed divergence separability index, the kappa coefficient and confusion matrices. Rice was distinguished from other land uses with 98% accuracy and rice cohorts were discriminated with 84% accuracy (three classes) or 94% (two classes). Our study showed that optical remote sensing can reliably identify potential malaria mosquito breeding habitats from space. In the future, these 'crop landscape maps' could be used to investigate the relationship between cultivation practices and malaria transmission.

Genetic differentiation of Anopheles gambiae s.s. populations in Mali, West Africa, using microsatellite loci.

Anopheles gambiae sensu stricto is a principal vector of malaria through much of sub-Saharan Africa, where this disease is a major cause of morbidity and mortality in human populations. Accordingly, population sizes and gene flow in this species have received special attention, as these parameters are important in attempts to control malaria by impacting its mosquito vector. Past measures of genetic differentiation have sometimes yielded conflicting results, in some cases suggesting that gene flow is extensive over vast distances (6000 km) and is disrupted only by major geological disturbances and/or barriers. Using microsatellite DNA loci from populations in Mali, West Africa, we measured genetic differentiation over uniform habitats favorable to the species across distances ranging from 62 to 536 km. Gene flow was strongly correlated with distance (r(2) = 0.77), with no major differences among chromosomes. We conclude that in this part of Africa, at least, genetic differentiation for microsatellite DNA loci is consistent with traditional models of isolation by distance.

Microstructure determination of AOT + phenol organogels utilizing small-angle X-ray scattering and atomic force microscopy.

Dry reverse micelles of the anionic twin-tailed surfactant bis(2-ethylhexyl) sulfosuccinate (AOT) dissolved in nonpolar solvents spontaneously form an organogel when p-chlorophenol is added in a 1:1 AOT:phenol molar ratio. The solvents used were benzene, toluene, m-xylene, 2,2,4-trimethylpentane (isooctane), decane, dodecane, tetradecane, hexadecane, and 2,6,10,14-tetramethylpentadecane (TMPD). The proposed microstructure of the gel is based on strands of stacked phenols linked to AOT through hydrogen bonding. Small-angle X-ray scattering (SAXS) spectra of the organogels suggest a characteristic length scale for these phenol-AOT strands that is independent of concentration but dependent on the chemical nature of the nonpolar solvent used. Correlation lengths determined from the SAXS spectra indicate that the strands self-assemble into fibers. Direct visualization of the gel in its native state is accomplished by using tapping mode atomic force microscopy (AFM). It is shown that these organogels consist of fiber bundle assemblies. The SAXS and AFM data reinforce the theory of a molecular architecture consisting of three length scales-AOT/phenolic strands (ca. 2 nm in diameter) that self-assemble into fibers (ca. 10 nm in diameter), which then aggregate into fiber bundles (ca. 20-100 nm in diameter) and form the organogel.

DNA analysis of transferred sperm reveals significant levels of gene flow between molecular forms of Anopheles gambiae.

Anopheles gambiae populations in west Africa are complex, being composed of multiple, sympatric subpopulations. Recent studies have failed to reveal significant genetic differences among subpopulations, stimulating a debate regarding the levels of gene flow among them. The observed homogeneity may be the consequence of substantial contemporary gene flow or it may be that reproductive isolation is complete, but too recent for the accumulation of significant levels of genic divergence. Here, we report the results of a study estimating contemporary levels of gene flow between An. gambiae subpopulations by analysing females and transferred sperm removed from their reproductive systems. A total of 251 female and associated sperm extracts was analysed from a single site in Mali. Two molecular forms of An. gambiae, the M- and S-forms, occurred in sympatry at this site. Overall, we found very strong positive assortative mating within forms, however, we did observe significant hybridization between forms. In the M subpopulation 2/195 females (1.03%) contained sperm from S-form males and in 55 S-form females we found one female containing M-form sperm (1.82%). We also identified a mated M xS hybrid adult female. From mating frequencies, we estimate the Nem between the M- and S-form at 16.8, and from the adult hybrid frequency at 5.6. These values are consistent with our earlier estimate, based on FST for 21 microsatellite loci in which Nem = 5.8. We conclude that the general lack of genetic divergence between the M and S subpopulations of An. gambiae can be explained entirely by contemporary gene flow.

Smoking cessation in China: findings from the 1996 national prevalence survey.

OBJECTIVES: To describe patterns of smoking and smoking cessation in China within the context of the stages of change model, using data from the 1996 national prevalence survey. DESIGN: A cross sectional survey was carried out using the 145 preselected disease surveillance points, which provide a representative sample for the entire country. A standardised questionnaire on smoking was interviewer administered. SETTING: The country of China. SUBJECTS: 122,220 people aged 15-69 years. MAINTENANCE MEASURES: Smoking cessation patterns, as defined by smoking status (current or former) and stage of change (precontemplation, contemplation, and action). RESULTS: The sample included 45,995 ever smokers of whom 4336 had quit. About 72% of current smokers reported not intending to give up their smoking behaviour, and about 16% of current smokers said they intended to do so, but have not taken any action. Of all ever smokers, the percentage of former smokers was 9.5%, and 12% of current smokers had quit at least once, but relapsed by the time of the survey. The patterns were similar in men and women with regard to the stated intent to quit. Among males, the percentage of former smokers increased with age but the percentage intending to quit was constant at about 15% across age strata. The most common reason for quitting was illness. Participants with a university education were more likely to have made an attempt to quit. CONCLUSIONS: The percentage of smokers contemplating quitting was low in China in 1996. The study shows that smokers in China must be mobilised to contemplate quitting and then to take action.

Respiratory viral infections in primary immune deficiencies: significance and relevance to clinical outcome in a single BMT unit.

Respiratory viral infections are major causes of morbidity and mortality in children with SCID and other primary immunodeficiencies who require BMT. Twenty-two of 73 (30%) such children were admitted with respiratory viral infections, of whom 13/22 (59%) died. All viruses were detected in nasopharyngeal aspirate (NPA). Virus was only found in BAL in those with LRTI. Eleven of 22 (50%) had paramyxovirus infections, all with severe viral pneumonitis which worsened post BMT. Five of 11 (45.5%) survived overall. All 11 received aerosolised ribavirin; five of 11 received additional inhaled immunoglobulin and corticosteroid. Three of 5 (60%) survived compared with two of six (33.3%) not thus treated. Three of 22 (13.6%) had adenoviruses; one died of disseminated disease, including pneumonia despite intravenous ribavirin. Eleven patients had rhinovirus detected; nine of 11 (82%) were asymptomatic or coryzal and survived. Two patients with additional severe lung pathologies had LRT rhinovirus and died. All patients received intravenous immunoglobulin. No treatments resulted in viral clearance without successful T cell engraftment. Respiratory viruses, particularly paramyxoviruses and adenoviruses are common, significant pathogens in these patients, significantly worsening outcome of BMT. NPA is an ideal specimen for diagnosis and monitoring of infection. Aggressive treatments may reduce viral replication and damage. Nebulised immunoglobulin and corticosteroid in LRTI may improve respiratory function and outcome.