Coaxial laser absorption and optical emission spectroscopy of high-pressure aluminum monoxide.

This work advances laser absorption spectroscopy with measurements of aluminum monoxide (AlO) temperature and column density in extreme pressure (P > 60 bar) and temperature (T > 4000 K) environments. Measurements of the AlO A2Πi-X2Σ+ transition are made using a microelectromechanical system, tunable vertical cavity surface emitting laser (MEMS-VCSEL). Simultaneous emission measurements of the AlO B2Σ+-X2Σ+ transition are made along a line of sight that is coaxial with the laser absorption. Absorption temperature fits agree with emission spectra for a T = 3200 K, P = 9 bar case. In cases with T > 4000 K, P > 60 bar, absorption fits match the ambient temperature while emission fits over-estimate it, owing to high optical depths. These data juxtapose passive and active spectroscopic methods and demonstrate the versatility of AlO laser absorption in high-pressure and high-temperature environments where experimental data remain scarce, and engineering models will benefit from refined measurements.

Surveillance optimisation to detect poliovirus in the pre-eradication era: a modelling study of England and Wales.

Surveillance for acute flaccid paralysis (AFP) cases are essential for polio eradication. However, as most poliovirus infections are asymptomatic and some regions of the world are inaccessible, additional surveillance tools require development. Within England and Wales, we demonstrate how inclusion of environmental sampling (ENV) improves the sensitivity of detecting both wild and vaccine-derived polioviruses (VDPVs) when compared to current surveillance. Statistical modelling was used to estimate the spatial risk of wild and VDPV importation and circulation in England and Wales. We estimate the sensitivity of each surveillance mode to detect poliovirus and the probability of being free from poliovirus, defined as being below a pre-specified prevalence of infection. Poliovirus risk was higher within local authorities in Manchester, Birmingham, Bradford and London. The sensitivity of detecting wild poliovirus within a given month using AFP and enterovirus surveillance was estimated to be 0.096 (95% CI 0.055-0.134). Inclusion of ENV in the three highest risk local authorities and a site in London increased surveillance sensitivity to 0.192 (95% CI 0.191-0.193). The sensitivity of ENV strategies can be compared using the framework by varying sites and the frequency of sampling. The probability of being free from poliovirus slowly increased from the date of the last case in 1993. ENV within areas thought to have the highest risk improves detection of poliovirus, and has the potential to improve confidence in the polio-free status of England and Wales and detect VDPVs.

An outbreak of norovirus GI-6 infection following a wedding in North West England.

In August 2015 a gastroenteritis outbreak occurred following a wedding. An outbreak investigation was undertaken and a cohort study was conducted using an online survey. Of 140 guests, 134 received the survey and 113 responded (84·3% response rate). Seventy respondents met the case definition of vomiting and/or diarrhoea within 72 h of the wedding (61·9% attack rate). Fifteen exposures were associated with illness; on stratification, all were confounded by the ham hock starter. Multivariable analysis showed a significant association with exposure to ham hock (risk ratio 6·62, 95% confidence interval 2·19-20·03). Eight guests and two catering staff submitted stool samples. All tested positive for norovirus GI-6 infection, including a food handler who had vomiting less than 48 h before the wedding. A single genotype was detected among all samples, suggesting a single source of contamination. The transmission pattern suggested point-source exposure. The most plausible cause of the outbreak was transmission from an infected food handler via contaminated food. This highlights the importance of appropriate exclusions for symptomatic food handlers. Additionally, the food handler's stool sample was submitted 7 days after symptom resolution. The potential for extended viral excretion, and the extremely low infective dose of norovirus, may mean that current exclusion guidelines are not of sufficient duration.

The emergence of enterovirus D68 in England in autumn 2014 and the necessity for reinforcing enterovirus respiratory screening.

In autumn 2014, enterovirus D68 (EV-D68) cases presenting with severe respiratory or neurological disease were described in countries worldwide. To describe the epidemiology and virological characteristics of EV-D68 in England, we collected clinical information on laboratory-confirmed EV-D68 cases detected in secondary care (hospitals), between September 2014 and January 2015. In primary care (general practitioners), respiratory swabs collected (September 2013-January 2015) from patients presenting with influenza-like illness were tested for EV-D68. In secondary care 55 EV-D68 cases were detected. Among those, 45 cases had clinical information available and 89% (40/45) presented with severe respiratory symptoms. Detection of EV-D68 among patients in primary care increased from 0.4% (4/1074; 95% CI 0.1-1.0) (September 2013-January 2014) to 0.8% (11/1359; 95% CI 0.4-1.5) (September 2014-January 2015). Characterization of EV-D68 strains circulating in England since 2012 and up to winter 2014/2015 indicated that those strains were genetically similar to those detected in 2014 in USA. We recommend reinforcing enterovirus surveillance through screening respiratory samples of suspected cases.

The development of Web-based surveillance provides new insights into the burden of norovirus outbreaks in hospitals in England.

A new surveillance system for outbreaks of norovirus in English hospitals, the hospital norovirus outbreak reporting system (HNORS), was launched in January 2009. On site investigators were enabled to enter data on outbreaks of norovirus directly onto a tailored system via an Internet-based front end. A standard dataset was designed to collect information describing the key epidemiological characteristics of each outbreak. In the period 1992-2008, 1817 suspected and confirmed outbreaks of norovirus in English hospitals were reported to national surveillance. After introduction of the new system there were 3980 reports of outbreaks of suspected and confirmed norovirus received in the years 2009-2011. Data from the new reporting system demonstrates that transmission of norovirus levies a heavy burden on English hospitals. On average, reported outbreaks are associated with 13,000 patients and 3400 staff becoming ill, 8900 days of ward closure and the loss of over 15,500 bed-days annually.

Transport and storage of serotonin by thrombin-treated platelets.

Repeated thrombin treatment of washed platelets prepared from rabbits can decrease the serotonin content of the platelets by about 80%. When these platelets are deaggregated they reaccumulate serotonin but their storage capacity for serotonin is reduced by about 60%. If thrombin-pretreated platelets are allowed to equilibrate with a high concentration of serotonin (123 mu M), they release a smaller percentage of their total serotonin upon further thrombin treatment, in comparison with the percentage of serotonin released from control platelets equilibrated with the same concentration of serotonin calculations indicate that in thrombin-treated platelets reequilibrated with serotonin, two-thirds of the serotonin is in the granule compartment and one-third is in the extragranular compartment, presumably the cytoplasm. Analysis of the exchange of serotonin between the suspending fluid and the platelets showed that thrombin treatment does not alter the transport rate of serotonin across the platelet membrane and does not cause increased diffusion of serotonin from the platelets into the suspending fluid. The primary reason for the reduced serotonin accumulation by the thrombin-treated platelets appears to be loss of amine storage granules or of the storage capacity within the granules.

Current approaches in haemophilic arthropathy of the hip.

The hip is considered to be one of the main load bearing joints of the body. In the haemophilic patient joint bleeds can be catastrophic, leading to long-term joint degeneration and accompanying arthritis. In this review we explore the mechanisms of joint destruction, with particular consideration of the anatomy of the hip and how it may influence disease progression. We also review current strategies for treatment including hip replacement in the haemophilic patient and describe our experiences as a unit. Finally we evaluate future prospects in the management of hip disease in haemophilia.

Evaluation of Parameterized Convective Transport of Trace Gases in Simulation of Storms Observed During the DC3 Field Campaign.

Deep convective transport of surface moisture and pollution from the planetary boundary layer to the upper troposphere and lower stratosphere affects the radiation budget and climate. This study uses cloud-parameterized Weather Research and Forecasting model coupled with Chemistry simulations to analyze the subgrid deep convective transport of CO at 12- and 36-km horizontal resolution in supercell and mesoscale convective systems observed during the 2012 Deep Convective Clouds and Chemistry field campaign and compares the simulation results with aircraft measurements and cloud-resolved simulations. The best Weather Research and Forecasting simulation of these storms was obtained with the use of the Grell-Freitas convective scheme. The default Weather Research and Forecasting model coupled with Chemistry subgrid convective transport scheme was replaced with a scheme to compute convective transport within the Grell-Freitas subgrid cumulus parameterization, which resulted in improved transport simulations. We examined the CO tendencies due to subgrid- and grid-scale convective transport. Results showed that the subgrid convective transport started earlier than the grid-scale convective transport. The subgrid-scale convective transport reached its maximum during the hour prior to the formation of the grid-scale constant-altitude detrainment layer. After that, both the subgrid- and grid-scale convective transport began to decrease. The subgrid-scale convective transport played a more significant role in the supercell case than the mesoscale convective system case. Subgrid contribution reached ~90% at the beginning of the storm and decreased to ~30% (17%) for the 36-km (12-km) domain 4 hr later.

Thrombin-triggered platelet apoptosis.

BACKGROUND: Thrombin is primarily known as a coagulation factor and as an inducer of platelet activation and aggregation. It has been reported that thrombin modulates apoptosis of nucleated cells. OBJECTIVES: The current study investigated whether thrombin can affect apoptosis in anucleated human platelets. METHODS: Using flow cytometry, we studied platelet apoptosis at the single-cell level, analyzing markers of mitochondrial and cytoplasmic apoptosis. Western blotting was also employed, in addition to flow cytometry, for determining the expression of Bcl-2 family proteins. RESULTS: We found that human alpha-thrombin induced four key manifestations of apoptosis in human platelets: (i) mitochondrial inner transmembrane potential (DeltaPsi m) depolarization; (ii) strong expression of pro-apoptotic Bax and Bak proteins but only weak expression of anti-apoptotic Bcl-2 protein; (iii) caspase-3 activation; and (iv) phosphatidylserine (PS) exposure. CONCLUSIONS: This study demonstrates that, aside from its 'classical' function as an inducer of platelet activation, thrombin can trigger platelet apoptosis, where it acts as a death ligand. These data indicate that thrombin triggers platelet apoptosis by impacting on several intracellular apoptotic targets, including shifting the balance between Bcl-2 regulatory proteins in a pro-apoptotic direction, depolarizing the inner mitochondrial membrane, activating the executioner caspase-3, and stimulating aberrant exposure of PS on the platelet surface.

Impacts of chilling temperatures on photosynthesis in warm-climate plants.

Photosynthesis in warm-climate plants is substantially reduced after chilling. Tropical and subtropical species offer the opportunity to study the effects of low temperature on photosynthetic processes undisguised by the myriad of protective responses observed in temperate species. In this article, we highlight the primary components of photosynthesis that are affected by a short chill, in both the dark and the light, and discuss what is known of the mechanisms involved. Recent work implicates impaired redox and circadian regulation among other processes.

Early impact of rotavirus vaccination in a large paediatric hospital in the UK.

The impact of routine rotavirus vaccination on community-acquired (CA) and healthcare-associated (HA) rotavirus gastroenteritis (RVGE) at a large paediatric hospital, UK, was investigated over a 13-year period. A total of 1644 hospitalized children aged 0-15 years tested positive for rotavirus between July 2002 and June 2015. Interrupted time-series analysis demonstrated that, post vaccine introduction (July 2013 to June 2015), CA- and HA-RVGE hospitalizations were 83% [95% confidence interval (CI): 72-90%) and 83% (95% CI: 66-92%] lower than expected, respectively. Rotavirus vaccination has rapidly reduced the hospital rotavirus disease burden among both CA- and HA-RVGE cases.

Expression of immunoglobulin heavy chain-ricin A chain fusions in mammalian cells.

Mammalian cell lines were transfected with antibody heavy (H) chain-ricin A chain gene fusions in attempts to assemble a recombinant immunotoxin. We found that a light chain-secreting mouse plasmacytoma cell line can be transfected stably with such a chimaeric gene, but only if the ricin A chain portion is disarmed by genetic means prior to transfection; if not, stable transfection appears to select for genetic inactivation of the transfected gene. Co-expression of an antibody heavy chain-ricin A chain fusion with light chain in non-lymphoid cells results in cell death. We conclude that the ricin A chain moiety retains biological activity precluding the expression of biologically active antibody-ricin A chain fusion proteins in mammalian cells.

Scanning electron microscopy of epiplexus macrophages (Kolmer cells) in the dog.

Young dogs (6-14 weeks) were perfused with buffered aldehydes by standard techniques. The inferior medullary velum and tela choroidea were removed intact from the fourth ventricle, post-osmicated, dehydrated, critical point dried, coated with palladium-gold and examined in a Cambridge Stereoscan S4 scanning electron microscope. Selected samples after thorough scanning were routinely prepared for transmission electron microscopy (TEM). This study depicts numerous epiplexus (Kolmer cell) macrophages that exhibit extreme polymorphism. Because of the pleomorphic nature of these cells and their processes, classification based on external morphology is not practical. TEM shows their internal structure to be that of a macrophage. Bleb-like structures and bulbous projections appear to emerge from certain ependymal cell surfaces which seem to be completely or partially devoid of cilia.

Scanning electron microscopy of the subarachnoid space in the dog. III. Cranial levels.

Young dogs were anesthetized by intrathoracic injection of sodium pentobarbital and perfused with buffered aldehydes. Lining tissue samples from the cranial subarachnoid space were prepared for scanning electron microscopy (SEM) by postfixing in buffered OSO4. Samples were then dehydrated, dried in a Critical Point Drying System, and coated with carbon and palladium-gold. Specimens were viewed in a Cambridge S4 scanning electron microscope. After thorough scanning, selected samples were routinely prepared for transmission electron microscopy (TEM) and viewed in a Philips EM-200 transmission electron microscope. This study depicts the surface morphology of the meningeal linings of the cranial subarachnoid space. The cranial pia mater possesses natural gaps or fenestrations between cells. SEM reveals a more complex morphology of arachnoid trabeculae than previously interpreted from light and transmission electron microscopy. Many free cells are observed on the meningeal linings of the subarachnoid space. The present study establishes that these free cells are macrophages by means of definitive TEM correlates. Microvillous-like processes extending between macrophages and the pial surface are present. The frequency and the nature of these thin processes suggest the possibility of a plasmalemma-mediated system of communication.

Mode of action of alpha-methylnoradrenaline on temperature and oxygen consumption in young chickens.

1. Temperature, oxygen consumption, electromyographic activity, plasma non-esterified fatty acids and blood sugar were estimated in conscious unrestrained young chickens under conditions of thermoneutrality (31 degrees C) and below thermoneutrality (16 degrees C). In some chickens carotid arterial pressure was also recorded.2. At thermoneutrality, alpha-methylnoradrenaline lowered temperature and oxygen consumption in intact or chronically vagotomized chicks. alpha-Methylnoradrenaline was ineffective on temperature in chicks with transection of the brain-stem posterior to the hypothalamus but anterior to the respiratory centre. Hypothermia due to alpha-methylnoradrenaline was associated with a significant reduction of plasma non-esterified fatty acids but blood sugar was not significantly altered. Lowering of temperature by alpha-methylnoradrenaline occurred despite vasoconstriction which would hinder heat loss.3. Temperature and oxygen consumption were reduced by alpha-methylnoradrenaline in chronically thyroidectomized chicks to the same extent as in intact chicks but recovery did not occur unless the chicks were taken from the metabolism chamber and warmed artificially. In contrast, chronically thyroidectomized chicks given replacement thyroxine were relatively resistant to alpha-methylnoradrenaline.4. Oxygen consumption of tissue slices from different parts of the chick's brain, including the diencephalon, was not altered by alpha-methylnoradrenaline over an extensive dose range. The effects of alpha-methylnoradrenaline on temperature and oxygen consumption in intact chickens were unlikely, therefore, to be due to depressed metabolism of neurones.5. In an environment below thermoneutrality (16 degrees C) temperature was considerably reduced and carotid arterial pressure fell 40-50 mmHg. In contrast, electromyographic activity, oxygen consumption and plasma non-esterified fatty acids were markedly raised whereas blood sugar was insignificantly elevated.6. In experiments at 16 degrees C, alpha-methylnoradrenaline markedly reduced oxygen consumption although values were still higher than those at thermoneutrality. Temperature fell further, but whereas the reductions in oxygen consumption and temperature were long-lasting, electromyographic activity (shivering) was only transiently diminished. Plasma non-esterified fatty acids were reduced after alpha-methylnoradrenaline but not significantly so; blood sugar was not significantly altered. The time-course for recovery of oxygen consumption following a-methylnoradrenaline paralleled recovery from its blood pressure effects but the effect on oxygen consumption was not a consequence of the blood pressure changes. The effects of a-methylnoradrenaline on temperature, oxygen consumption and electromyographic activity were similar to those of another central depressant, pentobarbitone.

Evidence of remodeling in dura mater cardiac valves.

Subcellular changes in 12 dura mater cardiac valves (in the mitral or aortic position) surgically removed after 23 to 108 months of implantation owing to calcification, rupture, or endocarditis show signs of a remodeling process. Significant morphologic changes in the connective tissue fiber matrices and cell populations were noted in the recovered valvular leaflets. Macrophages were found within electronlucent (cleared-out) areas, and they seemed to play an essential role in the remodeling process by ingesting and digesting selected connective tissue components. Fibroblasts found within these "rebuilding" areas in the dura mater tissue possessed small cytoplasmic vesicles (65 nm in diameter) being extruded from the cell. Evidence of early collagen formation was also found in association with both peripheral filaments and peripheral condensations, as well as within the connective tissue matrices surrounding the cellular elements, where electron dense amorphous material was observed. In conclusion, the long-term durability of dura mater bioprosthetic cardiac valves may be directly related to (1) glycerin stabilization and preservation of the collagen fibers, (2) the viability of the fibroblasts and macrophages within the implanted valves, and (3) the unique morphology and fine structure of the double-layered dura mater encephali. We hypothesize that the fibroblasts or myofibroblast-like cells found within the implanted leaflets, no matter what their origin, are capable of giving form and organization to the early developing connective tissue.

Microscopic study of normal parietal pericardium and unimplanted Puig-Zerbini pericardial valvular heterografts.

This investigation used light microscopy and transmission and scanning electron microscopy to study native human and bovine parietal pericardium, glutaraldehyde-fixed bovine pericardial patch-grafts, and bovine pericardial cusps of unimplanted Incor or Puig - Zerbini heart valves. The primary objective was to obtain a data base for the future evaluation of postimplantation structural alteration in this valve and in other cardiac valvular bioprostheses constructed of pericardium. The mesothelial cell layer in normal pericardium was best preserved in the bovine tissue. In both bovine patch-grafts and Puig - Zerbini valvular cusps, the serosal surface usually was completely devoid of mesothelial cells and revealed an underlying, finely fibrillar basal lamina. The fibrosa varied in thickness and organization, both within and between the two species, but similar nervous, vascular, and connective tissue components were observed in each. The epipericardial surface was smoother, had fewer elastic fibers, and possessed more surface cells in the human tissue than in the bovine tissue. No evidence of significant tissue degeneration or remodeling was noted in either the stored patch-grafts or heart valves when compared with control bovine and human pericardial tissue layers.

Scanning electron microscopy of Acanthamoeba culbertsoni as observed in the subarachnoid space.

Scanning electron microscopy was used to study the pathogenic protozoan, Acanthamoeba culbertsoni, in the leptomeningeal subarachnoid space surrounding the spinal cord of the experimentally inoculated dog. Know to inhabit such areas as moist soils, stagnant waters, and sewage around the world, these protozoans have been identified as etiologic agents in numerous cases of meningoencephalitis. Infection occurs via a nasopharyngeal inoculation, through penetration of the olfactory mucosal epithelium and cribriform plate, into the subarachnoid space, whence it gains access to the central nervous system. Stock preparations of these amebae extracted directly from their culture medium for scanning microscopic study provided an index for their identification within the subarachnoid space and also permitted a heretofore unobserved survey of their pleomorphic surface features. From the observations of others, it had appeared that the ultimate portal of entry into the central nervous system involved some type of cytolytic process; however, this study illustrates an action of simple diapedesis in which the organisms seek a pathway of least resistance; namely the naturally-occurring pial fenestrations.

In vivo evaluation of an electroenzymatic glucose sensor implanted in subcutaneous tissue.

Cleanroom processing techniques have been used to mass-produce flexible, electroenzymatic glucose sensors designed for implantation in subcutaneous tissue. In vitro characterization studies have shown the sensor's performance to be acceptable. Initial in vivo studies were conducted with the sensor implanted in the subcutaneous tissue of rabbits. Sensors implanted in the subcutaneous tissue of normal human subjects showed an excellent correlation between glucose concentrations measured by the sensor and capillary finger sticks measured with a commercial analyzer.