Assessing the use of minimally invasive self-sampling at home for long-term monitoring of the microbiota within UK families.

Monitoring the presence of commensal and pathogenic respiratory microorganisms is of critical global importance. However, community-based surveillance is difficult because nasopharyngeal swabs are uncomfortable and painful for a wide age range of participants. We designed a methodology for minimally invasive self-sampling at home and assessed its use for longitudinal monitoring of the oral, nasal and hand microbiota of adults and children within families. Healthy families with two adults and up to three children, living in and near Liverpool, United Kingdom, self-collected saliva, nasal lining fluid using synthetic absorptive matrices and hand swabs at home every two weeks for six months. Questionnaires were used to collect demographic and epidemiological data and assess feasibility and acceptability. Participants were invited to take part in an exit interview. Thirty-three families completed the study. Sampling using our approach was acceptable to 25/33 (76%) families, as sampling was fast (76%), easy (76%) and painless (60%). Saliva and hand sampling was acceptable to all participants of any age, whereas nasal sampling was accepted mostly by adults and children older than 5 years. Multi-niche self-sampling at home can be used by adults and children for longitudinal surveillance of respiratory microorganisms, providing key data for design of future studies.

Ease and comfort of pre-oxygenation with high-flow nasal oxygen cannulae vs. facemask: a randomised controlled trial.

The Difficult Airway Society recommends that all patients should be pre-oxygenated before the induction of general anaesthesia, but this may not always be easy or comfortable and anaesthesia may often be induced without full pre-oxygenation. We tested the hypothesis that high-flow nasal oxygen cannulae would be easier and more comfortable than facemasks for pre-oxygenation. We randomly allocated 199 patients undergoing elective surgery aged ≥ 10 years to pre-oxygenation using either high-flow nasal oxygen or facemask. Ease and comfort were assessed by anaesthetists and patients on 10-cm visual analogue scale and six-point smiley face scale, respectively. Secondary endpoints included end-tidal oxygen fraction after securing a definitive airway and time to secure an airway. A mean difference (95%CI) between groups in ratings of -0.76 (-1.25 to -0.27) cm for ease of use (p = 0.003) and -0.45 (-0.75 to -0.13) points for comfort (p = 0.006), both favoured high-flow nasal oxygen. A mean difference (95%CI) between groups in end-tidal oxygen fraction of 3.89% (2.41-5.37%) after securing a definitive airway also favoured high-flow nasal oxygen (p < 0.001). There was no significant difference between groups in the number of patients with hypoxaemia (Sp O2 < 90%) or severe hypoxaemia (Sp O2 < 85%) lasting ≥ 1 min or ≥ 2 min; in the proportion of patients with an end-tidal oxygen fraction < 87% in the first 5 min after tracheal intubation (52.2% vs. 58.9% in facemask and high-flow nasal oxygen groups, respectively; p = 0.31); or in time taken to secure an airway (11.6 vs. 12.2 min in facemask and high-flow nasal oxygen groups, respectively; p = 0.65). In conclusion, we found pre-oxygenation with high-flow nasal oxygen to be easier for anaesthetists and more comfortable for patients than pre-oxygenation with a facemask, with no clinically relevant differences in end-tidal oxygen fraction after securing a definitive airway or time to secure an airway. The differences in ease and comfort were modest.

Surface acceleration transmission during drop landings in humans.

The purpose of this study was to quantify the magnitude and frequency content of surface-measured accelerations at each major human body segment from foot to head during impact landings. Twelve males performed two single leg drop landings from each of 0.15 m, 0.30 m, and 0.45 m. Triaxial accelerometers (2000 Hz) were positioned over the: first metatarsophalangeal joint; distal anteromedial tibia; superior to the medial femoral condyle; L5 vertebra; and C6 vertebra. Analysis of acceleration signal power spectral densities revealed two distinct components, 2-14 Hz and 14-58 Hz, which were assumed to correspond to time domain signal joint rotations and elastic wave tissue deformation, respectively. Between each accelerometer position from the metatarsophalangeal joint to the L5 vertebra, signals exhibited decreased peak acceleration, increased time to peak acceleration, and decreased power spectral density integral of both the 2-14 Hz and 14-58 Hz components, with no further attenuation beyond the L5 vertebra. This resulted in peak accelerations close to vital organs of less than 10% of those at the foot. Following landings from greater heights, peak accelerations measured distally were greater, as was attenuation prior to the L5 position. Active and passive mechanisms within the lower limb therefore contribute to progressive attenuation of accelerations, preventing excessive accelerations from reaching the torso and head, even when distal accelerations are large.

Tool use and social homophily among male bottlenose dolphins.

Homophilous behaviour plays a central role in the formation of human friendships. Individuals form social ties with others that show similar phenotypic traits, independently of relatedness. Evidence of such homophily can be found in bottlenose dolphins ( Tursiops aduncus) in Shark Bay, Western Australia, where females that use marine sponges as foraging tools often associate with other females that use sponges. 'Sponging' is a socially learned, time-consuming behaviour, transmitted from mother to calf. Previous research illustrated a strong female bias in adopting this technique. The lower propensity for males to engage in sponging may be due to its incompatibility with adult male-specific behaviours, particularly the formation of multi-level alliances. However, the link between sponging and male behaviour has never been formally tested. Here, we show that male spongers associated significantly more often with other male spongers irrespective of their level of relatedness. Male spongers spent significantly more time foraging, and less time resting and travelling, than did male non-spongers. Interestingly, we found no difference in time spent socializing. Our study provides novel insights into the relationship between tool use and activity budgets of male dolphins, and indicates social homophily in the second-order alliance composition of tool-using bottlenose dolphins.

Multi-modal sexual displays in Australian humpback dolphins.

Sexual displays enriched by object carrying serve to increase individual male fitness, yet are uncommon phenomena in the animal kingdom. While they have been documented in a variety of taxa, primarily birds, they are rare outside non-human mammals. Here, we document marine sponge presenting associated with visual and acoustic posturing found in several, geographically widespread populations of Australian humpback dolphins (Sousa sahulensis) over ten years of observation. Only adult males presented marine sponges, typically doing so in the presence of sexually mature females, although social groups predominantly consisted of mixed age and sex classes. Male humpback dolphins appear to be using sponges for signalling purposes in multi-modal sexual displays. Further, based on limited behavioural and genetic data, we hypothesise that pairs of adult male Sousa form at least temporary coalitions or alliances. The use of objects in sexual displays by non-human mammals is rare and, moreover, cooperation between males in the pursuit of an indivisible resource is an evolutionary hurdle relatively few species have overcome. These findings suggest a hitherto unrecognised level of social complexity in humpback dolphins.

Measurement of the sound intensity during suction of middle-ear fluid following myringotomy.

OBJECTIVE: To determine noise intensity during middle-ear aspiration in order to evaluate whether levels can be potentially harmful. METHODS: In this prospective, observational study, middle-ear effusion was aspirated following myringotomy using a suction instrument with a probe tube microphone. Sound pressure levels and duration were measured, and frequency domain analysis was performed. RESULTS: Forty-four ears were analysed, consisting of 20 with mucoid effusion, 11 with serous effusion and 13 with no effusion. Maximum peak sound intensity ranged from 84 to 157 dB. Half of the ears (50 per cent) were exposed to greater than 140 dB; of these, 82 per cent were exposed for longer than 0.2 ms (range, 0.05-14 ms). There was no significant difference in sound pressure level between ears with mucoid and serous effusion; however, ears with mucoid effusion required longer suction times (p < 0.0030). In addition, peak intensity was greater for ears with mucoid effusion versus those with serous or no effusion (p < 0.0001). CONCLUSION: Middle-ear aspiration during myringotomy caused noise levels within a potentially harmful range.

A high-dose preparation of lactobacilli and bifidobacteria in the prevention of antibiotic-associated and Clostridium difficile diarrhoea in older people admitted to hospital: a multicentre, randomised, double-blind, placebo-controlled, parallel arm trial (PLACIDE).

BACKGROUND: Antibiotic-associated diarrhoea (AAD) occurs most commonly in older people admitted to hospital and within 12 weeks of exposure to broad-spectrum antibiotics. Although usually a mild and self-limiting illness, the 15-39% of cases caused by Clostridium difficile infection [C. difficile diarrhoea (CDD)] may result in severe diarrhoea and death. Previous research has shown that probiotics, live microbial organisms that, when administered in adequate numbers, are beneficial to health, may be effective in preventing AAD and CDD. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of a high-dose, multistrain probiotic in the prevention of AAD and CDD in older people admitted to hospital. DESIGN: A multicentre, randomised, double-blind, placebo-controlled, parallel-arm trial. SETTING: Medical, surgical and elderly care inpatient wards in five NHS hospitals in the UK. PARTICIPANTS: Eligible patients were aged ≥ 65 years, were exposed to one or more oral or parenteral antibiotics and were without pre-existing diarrhoeal disorders, recent CDD or at risk of probiotic adverse effects. Out of 17,420 patients screened, 2981 (17.1%) were recruited. Participants were allocated sequentially according to a computer-generated random allocation sequence; 1493 (50.1%) were allocated to the probiotic and 1488 (49.9%) to the placebo arm. INTERVENTIONS: Vegetarian capsules containing two strains of lactobacilli and two strains of bifidobacteria (a total of 6 × 10(10) organisms per day) were taken daily for 21 days. The placebo was inert maltodextrin powder in identical capsules. MAIN OUTCOME MEASURES: The occurrence of AAD within 8 weeks and CDD within 12 weeks of recruitment was determined by participant follow-up and checking hospital laboratory records by research nurses who were blind to arm allocation. RESULTS: Analysis based on the treatment allocated included 2941 (98.7%) participants. Potential risk factors for AAD at baseline were similar in the two study arms. Frequency of AAD (including CDD) was similar in the probiotic (159/1470, 10.8%) and placebo arms [153/1471, 10.4%; relative risk (RR) 1.04; 95% confidence interval (CI) 0.84 to 1.28; p = 0.71]. CDD was an uncommon cause of AAD and occurred in 12/1470 (0.8%) participants in the probiotic and 17/1471 (1.2%) in the placebo arm (RR 0.71; 95% CI 0.34 to 1.47; p = 0.35). Duration and severity of diarrhoea, common gastrointestinal symptoms, serious adverse events and quality of life measures were also similar in the two arms. Total health-care costs per patient did not differ significantly between the probiotic (£8020; 95% CI £7620 to £8420) and placebo (£8010; 95% CI £7600 to £8420) arms. CONCLUSION: We found no evidence that probiotic administration was effective in preventing AAD. Although there was a trend towards reduced CDD in the probiotic arm, on balance, the administration of this probiotic seems unlikely to benefit older patients exposed to antibiotics. A better understanding of the pathogenesis of AAD and CDD and the strain-specific effects of probiotics is needed before further clinical trials of specific microbial preparations are undertaken. Evaluation of the effectiveness of other probiotics will be difficult where other measures, such as antibiotic stewardship, have reduced CDD rates. TRIAL REGISTRATION: This trial is registered as ISRCTN70017204. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 57. See the NIHR Journals Library website for further project information.

Inducing an incipient terahertz finite plasmonic crystal in coupled two dimensional plasmonic cavities.

We measured a change in the current transport of an antenna-coupled, multigate, GaAs/AlGaAs field-effect transistor when terahertz electromagnetic waves irradiated the transistor and attribute the change to bolometric heating of the electrons in the two dimensional electron channel. The observed terahertz absorption spectrum indicates coherence between plasmons excited under adjacent biased device gates. The experimental results agree quantitatively with a theoretical model we developed that is based on a generalized plasmonic transmission line formalism and describes an evolution of the plasmonic spectrum with increasing electron density modulation from homogeneous to the crystal limit. These results demonstrate an electronically induced and dynamically tunable plasmonic band structure.

Models incorporating pin joints are suitable for simulating performance but unsuitable for simulating internal loading.

Simulation models of human movement comprising pin-linked segments have a potential weakness for reproducing accurate ground reaction forces during high impact activities. While the human body contains many compliant structures such a model only has compliance in wobbling masses and in the foot-ground interface. In order to determine whether accurate GRFs can be produced by allowing additional compliance in the foot-ground interface, a subject-specific angle-driven computer simulation model of triple jumping with 13 pin-linked segments was developed, with wobbling masses included within the shank, thigh, and trunk segments. The foot-ground interface was represented by spring-dampers at three points on each foot: the toe, ball, and heel. The parameters of the spring-dampers were varied by a genetic algorithm in order to minimise the differences between simulated GRFs, and those measured from the three phases of a triple jump in three conditions: (a) foot spring compression limited to 20 mm; (b) this compression limited to 40 mm; (c) no restrictions. Differences of 47.9%, 15.7%, and 12.4% between simulation and recorded forces were obtained for the 20 mm, 40 mm, and unrestricted conditions, respectively. In the unrestricted condition maximum compressions of between 43 mm and 56 mm were obtained in the three phases and the mass centre position was within 4mm of the actual position at these times. It is concluded that the unrestricted model is appropriate for simulating performance whereas the accurate calculation of internal forces would require a model that incorporates compliance elsewhere in the link system.

Use of cytokine immunotherapy to block CNS demyelination induced by a recombinant HSV-1 expressing IL-2.

We previously have described a model of multiple sclerosis (MS) in which constitutive expression of murine interleukin (IL)-2 by herpes simplex virus type 1 (HSV-1) (HSV-IL-2) causes central nervous system (CNS) demyelination in different strains of mice. In the current study, we investigated whether this HSV-IL-2-induced demyelination can be blocked using recombinant viruses expressing different cytokines or by injection of plasmid DNA. We have found that coinfection of HSV-IL-2-infected mice with recombinant viruses expressing IL-12p35, IL-12p40 or IL-12p35+IL-12p40 did not block the CNS demyelination, and that coinfection with a recombinant virus expressing interferon (IFN)-γ exacerbated it. In contrast, coinfection with a recombinant virus expressing IL-4 reduced demyelination, whereas coinfection of HSV-IL-2-infected mice with a recombinant HSV-1 expressing the IL-12 heterodimer (HSV-IL-12p70) blocked the CNS demyelination in a dose-dependent manner. Similarly, injection of IL-12p70 DNA blocked HSV-IL-2-induced CNS demyelination in a dose-dependent manner and injection of IL-35 DNA significantly reduced CNS demyelination. Injection of mice with IL-12p35 DNA, IL-12p40 DNA, IL-12p35+IL-12p40 DNA or IL-23 DNA did not have any effect on HSV-IL-2-induced demyelination, whereas injection of IL-27 DNA increased the severity of the CNS demyelination in the HSV-IL-2-infected mice. This study demonstrates for the first time that IL-12p70 can block HSV-IL-2-induced CNS demyelination and that IL-35 can also reduce this demyelination, whereas IFN-γ and IL-27 exacerbated the demyelination in the CNS of the HSV-IL-2-infected mice. Our results suggest a potential role for IL-12p70 and IL-35 signaling in the inhibition of HSV-IL-2-induced immunopathology by preventing development of autoaggressive T cells.

The population genetics and dynamics of the thalassemias.

The inherited disorders of hemoglobin, including the thalassemias, are by far the commonest monogenic diseases. Although several factors are responsible for their very high frequency, the major mechanism seems to be natural selection mediated by heterozygote protection against severe forms of malaria. Recent work has highlighted the complexity of the interplay among the different hemoglobin variants themselves and among different levels of malaria resistance, and is helping to explain the extraordinary heterogeneity in the distribution of the hemoglobin disorders even within short geographical distances. Some progress has also been made toward understanding the cellular and immune mechanisms that may underlie heterozygote protection against malaria in these conditions. In addition to providing valuable information about human evolutionary biology, work in this field has an increasingly important influence on the development of programs for the better management of the hemoglobin disorders, particularly in the poorer countries of the tropical world.

Is a single or double arm technique more advantageous in triple jumping?

Triple jumpers employ either an asymmetrical 'single-arm' action or symmetrical 'double-arm' action in the takeoff of each phase of the jump. This study investigated which technique is more beneficial in each phase using computer simulation. Kinematic data were obtained from an entire triple jump using a Vicon automatic motion capture system. A planar 13-segment torque-driven subject-specific computer simulation model was evaluated by varying torque generator activation timings using a genetic algorithm in order to match performance data. The matching produced a close agreement between simulation and performance, with differences of 3.8%, 2.7%, and 3.1% for the hop, step, and jump phases, respectively. Each phase was optimised for jump distance and an increase in jump distance beyond the matched simulations of 3.3%, 11.1%, and 8.2% was obtained for the hop, step, and jump, respectively. The optimised technique used symmetrical shoulder flexion whereas the triple jumper had used an asymmetrical arm technique. This arm action put the leg extensors into slower concentric conditions allowing greater extensor torques to be produced. The main increases in work came at the joints of the stance leg but the largest increases in angular impulse came at the shoulder joints, indicating the importance of both measures when assessing the impact of individual joint actions on changes in technique. Possible benefits of the double-arm technique include: cushioning the stance leg during impact; raising the centre of mass of the body at takeoff; facilitating an increase in kinetic energy at takeoff; allowing a re-orientation of the body during flight.

Neuromuscular function in healthy occlusion.

This study aimed to measure neuromuscular function for the masticatory muscles under a range of occlusal conditions in healthy, dentate adults. Forty-one subjects conducted maximum voluntary clenches under nine different occlusal loading conditions encompassing bilateral posterior teeth contacts with the mandible in different positions, anterior teeth contacts and unilateral posterior teeth contacts. Surface electromyography was recorded bilaterally from the anterior temporalis, superficial masseter, sternocleidomastoid, anterior digastric and trapezius muscles. Clench condition had a significant effect on muscle function (P = 0.0000) with the maximum function obtained for occlusions with bilateral posterior contacts and the mandible in a stable centric position. The remaining contact points and moving the mandible to a protruded position, whilst keeping posterior contacts, resulted in significantly lower muscle activities. Clench condition also had a significant effect on the per cent overlap, anterior-posterior and torque coefficients (P = 0.0000-0.0024), which describe the degree of symmetry in these muscle activities. Bilateral posterior contact conditions had significantly greater symmetry in muscle activities than anterior contact conditions. Activity in the sternocleidomastoid, anterior digastric and trapezius was consistently low for all clench conditions, i.e. <20% of the maximum voluntary contraction level. In conclusion, during maximum voluntary clenches in a healthy population, maximum masticatory muscle activity requires bilateral posterior contacts and the mandible to be in a stable centric position, whilst with anterior teeth contacts, both the muscle activity and the degree of symmetry in muscle activity are significantly reduced.

Extracorporeal membrane oxygenation for cardiorespiratory failure in four patients with pandemic H1N1 2009 influenza virus and secondary bacterial infection.

We report four patients with pandemic H1N1 2009 influenza virus and secondary bacterial infection who were treated with extracorporeal membrane oxygenation (ECMO) for cardiorespiratory failure. Three of the four patients had profound shock, necessitating support with venoarterial ECMO. Two patients died during ECMO support. The two survivors had prolonged hospital stays, which were complicated by renal failure and limb ischaemia.

Interaction of malaria with a common form of severe thalassemia in an Asian population.

In many Asian populations, the commonest form of severe thalassemia results from the coinheritance of HbE and beta thalassemia. The management of this disease is particularly difficult because of its extreme clinical diversity; although some genetic and adaptive factors have been identified as phenotypic modifiers, the reasons remain unclear. Because the role of the environment in the course of severe thalassemia has been neglected completely and because malaria due to both Plasmodium falciparum and Plasmodium vivax has been prevalent in Sri Lanka, we carried out a pilot study of patients with HbE beta thalassemia that showed high frequencies of antibodies to both parasite species and that 28.6% of the children had DNA-based evidence of current infection with P. vivax. Malarial antibodies then were assessed in patients with HbE beta thalassemia compared with those in age-matched controls. There was a significant increase in the frequency of antibodies in the thalassemic patients, particularly against P. vivax and in young children. There was also a higher frequency in those who had been splenectomized compared with those with intact spleens, although in the latter it was still higher than that in the controls. The thalassemic patients showed significant correlations between malaria antibody status and phenotype. Patients with HbE beta thalassemia may be more prone to malaria, particularly P. vivax, which is reflected in their clinical severity. Because P. vivax malaria is widespread in Asia, further studies of its interaction with HbE beta thalassemia and related diseases are required urgently as a part of ongoing thalassemia control programs.

Adsorption characteristics of reactive dyes in columns of activated carbon.

Adsorption behaviour of reactive dyes in fixed-bed adsorber was evaluated in this work. The characteristics of mass transfer zone (MTZ), where adsorption in column occurs, were affected by carbon bed depth and influent dye concentration. The working lifetime (t(x)) of MTZ, the height of mass transfer zone (HMTZ), the rate of mass transfer zone (RMTZ), and the column capacity at exhaustion (q(column)) were estimated for the removal of remazol reactive yellow and remazol reactive black by carbon adsorber. The results showed that column capacity calculated at 90% of column exhaustion was lower than carbon capacity obtained from equilibrium studies. This indicated that the capacity of activated carbon was not fully utilized in the fixed-bed adsorber. The bed-depth service time model (BDST) was applied for analysis of reactive yellow adsorption in the column. The adsorption capacity of reactive yellow calculated at 50% breakthrough point (N(0)) was found to be 0.1 kg kg(-1) and this value is equivalent to about 14% of the available carbon capacity. The results of this study indicated the applicability of fixed-bed adsorber for removing remazol reactive yellow from solution.

A plasmonic terahertz detector with a monolithic hot electron bolometer.

A plasmonic terahertz detector that integrates a voltage-controlled planar barrier into a grating gated GaAs/AlGaAs high electron mobility transistor has been fabricated and experimentally characterized. The plasmonic response at fixed grating gate voltage has a full width at half-maximum of 40 GHz at ∼405 GHz. Substantially increased responsivity is achieved by introducing an independently biased narrow gate that produces a lateral potential barrier electrically in series with the resonant grating gated region. DC electrical characterization in conjunction with bias-dependent terahertz responsivity and time constant measurements indicate that a hot electron bolometric effect is the dominant response mechanism at 20 K.