Molecular detection of Rickettsia infection in field-collected bed bugs.

Bed bugs are now one of the most prevalent human-associated, blood-feeding pests in the urban world, but few studies of their association with human pathogens have been conducted since their resurgence. Here, we used PCR to screen samples of field-collected bed bugs (Cimex spp.) for the presence of Rickettsia bacteria and we describe the first detection of an uncharacterized Rickettsia in Cimex lectularius in nature. Rickettsia was detected in 5/39 (12.8%) of the bed bug samples tested. In particular, three pools from the USA and two individual insects from the UK were positive for Rickettsia DNA. Sequencing and analysis of a fragment of the citrate synthase gene (gltA) from positive samples from each country revealed that the Rickettsia detected in both were identical and were closely related to a Rickettsia previously detected in the rat flea Nosopsyllus laeviceps. Additional experiments indicated that the Rickettsia localizes to multiple tissues in the bed bug and reaches high titres. Attempts were made to infect mammalian cells in culture but these efforts were inconclusive. Our findings suggest that Rickettsia are secondary endosymbionts of bed bugs and have potential implications for both bed bug control and public health. However, further investigation is required to determine the pathogenicity of this Rickettsia, its transmission mechanisms, and its contributions to bed bug physiology.

Valuing and understanding fish populations in the Anthropocene: key questions to address.

Research on the values of fish populations and fisheries has primarily focused on bio-economic aspects; a more nuanced and multidimensional perspective is mostly neglected. Although a range of social aspects is increasingly being considered in fisheries research, there is still no clear understanding as to how to include these additional values within management policies nor is there a cogent appreciation of the major knowledge gaps that should be tackled by future research. This paper results from a workshop held during the 50th anniversary symposium of the Fisheries Society of the British Isles at the University of Exeter, UK, in July 2017. Here, we aim to highlight the current knowledge gaps on the values of fish populations and fisheries thus directing future research. To this end, we present eight questions that are deeply relevant to understanding the values of fish populations and fisheries. These can be applied to all habitats and fisheries, including freshwater, estuarine and marine.

A rate-based transcutaneous CO2 sensor for noninvasive respiration monitoring.

The pain and risk of infection associated with invasive blood sampling for blood gas measurements necessitate the search for reliable noninvasive techniques. In this work we developed a novel rate-based noninvasive method for a safe and fast assessment of respiratory status. A small sampler was built to collect the gases diffusing out of the skin. It was connected to a CO2 sensor through gas-impermeable tubing. During a measurement, the CO2 initially present in the sampler was first removed by purging it with nitrogen. The gases in the system were then recirculated between the sampler and the CO2 sensor, and the CO2 diffusion rate into the sampler was measured. Because the measurement is based on the initial transcutaneous diffusion rate, reaching mass transfer equilibrium and heating the skin is no longer required, thus, making it much faster and safer than traditional method. A series of designed experiments were performed to analyze the effect of the measurement parameters such as sampler size, measurement location, subject positions, and movement. After the factor analysis tests, the prototype was sent to a level IV NICU for clinical trial. The results show that the measured initial rate of increase in CO2 partial pressure is linearly correlated with the corresponding arterial blood gas measurements. The new approach can be used as a trending tool, making frequent blood sampling unnecessary for respiratory status monitoring.

Living in warmer, more acidic oceans retards physiological recovery from tidal emersion in the velvet swimming crab, Necora puber.

The distribution patterns of many species in the intertidal zone are partly determined by their ability to survive and recover from tidal emersion. During emersion, most crustaceans experience gill collapse, impairing gas exchange. Such collapse generates a state of hypoxemia and a hypercapnia-induced respiratory acidosis, leading to hyperlactaemia and metabolic acidosis. However, how such physiological responses to emersion are modified by prior exposure to elevated CO2 and temperature combinations, indicative of future climate change scenarios, is not known. We therefore investigated key physiological responses of velvet swimming crabs, Necora puber, kept for 14 days at one of four pCO2/temperature treatments (400 µatm/10°C, 1000 µatm/10°C, 400 µatm/15°C or 1000 µatm/15°C) to experimental emersion and recovery. Pre-exposure to elevated pCO2 and temperature increased pre-emersion bicarbonate ion concentrations [HCO3(-)], increasing resistance to short periods of emersion (90 min). However, there was still a significant acidosis following 180 min emersion in all treatments. The recovery of extracellular acid-base via the removal of extracellular pCO2 and lactate after emersion was significantly retarded by exposure to both elevated temperature and pCO2. If elevated environmental pCO2 and temperature lead to slower recovery after emersion, then some predominantly subtidal species that also inhabit the low to mid shore, such as N. puber, may have a reduced physiological capacity to retain their presence in the low intertidal zone, ultimately affecting their bathymetric range of distribution, as well as the structure and diversity of intertidal assemblages.

Modification of anodised aluminium surfaces using a picosecond fibre laser for printing applications.

The use of an ultrafast fibre laser at a wavelength of 1064 nm has allowed the surface modification of anodised aluminium plates coated with a 2 micron thick anodised layer for potential industrial applications. The micro- and nano-scale structuring of the anodised aluminium using picosecond pulses of approximately 25 ps duration at 200 kHz repetition rate was investigated. The interaction of the laser with the substrate created a hydrophilic surface, giving a contact angle of less than 10 degrees. On examination under a Scanning Electron Microscope (SEM), a morphology created due to laser induced spallation was observed. It has been found that these laser processed hydrophilic surfaces revert to a hydrophobic state with time. This has potential for application in the printing industry and offers reusability and sustainability of the process materials. This has been confirmed in initial trials.

A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex® (nabiximols).

BACKGROUND: Open-label studies are not ideal for providing robust evidence for long-term maintenance of efficacy of medicines, especially where medicines provide symptom relief and where long-term use of a placebo may be problematic and not ethical. OBJECTIVE: To evaluate the maintenance of efficacy of Sativex in subjects who have gained long-term symptomatic relief of spasticity in multiple sclerosis (MS), and to assess the impact of sudden medicine withdrawal. METHODS: An enriched enrolment randomized withdrawal study design was used. Eligible subjects with ongoing benefit from Sativex for at least 12 weeks entered this 5-week placebo-controlled, parallel-group, randomized withdrawal study. Each subjects' previous effective and tolerated dose was continued. RESULTS: A total of 18 subjects per group were enrolled. Demographics showed a mean duration of MS of 16.4 years, spasticity 12.7 years, mean duration of Sativex use of 3.6 years (median 3.4 years) and a mean daily dose of 8.25 sprays. Primary outcome of time to treatment failure was significantly in favour of Sativex (p = 0.013). Secondary endpoints showed significant changes in the Carer and Subject's Global Impression of Change scales in favour of Sativex. CONCLUSIONS: Maintenance of Sativex efficacy in long-term symptomatic improvement of spasticity to a group of subjects with MS has been confirmed using this study design.

Surface modification of anodised aluminium using a femtosecond laser.

Femtosecond laser pulses at 775 nm, combined with a scanning galvonometer system, have allowed the micro scale structuring of an aluminium plate coated with a 2 micron thick anodised aluminium layer for potential industrial applications. The micro-scale structuring of aluminium was investigated using ultrafast pulses of 180 fs duration at a repetition rate of 1 kHz. Under suitably optimised conditions, the interaction of the laser pulses with the substrate created a hydrophilic surface with a contact angle of less than 10 degrees. These surfaces revealed a 'lotus-leaf' like morphology when examined under a Scanning Electron Microscope (SEM). It has been found that these laser processed hydrophilic surfaces revert with time and they undergo this cycle of alternate hydrophilic/hydrophobic behaviour several times upon exposure to the laser pulses. Their potential application in the printing industries is strong due to their reusability and sustainability; initial trials on printing confirm this. This technology would offer extra advantages as a non-chemical process without the need for developer, thereby reducing the overall cost and time of printing.

Early evidence of the genus Homo in East Asia.

The timing and route of the earliest dispersal from Africa to Eastern Asia are contentious topics in the study of early human evolution because Asian hominin fossil sites with precise age constraints are very limited. Here we report new high-resolution magnetostratigraphic results that place stringent age controls on excavated hominin incisors and stone tools from the Yuanmou Basin, southwest China. The hominin-bearing layer resides in a reverse polarity magnetozone just above the upper boundary of the Olduvai subchron, yielding an estimated age of 1.7Ma. The finding represents the age of the earliest documented presence of Homo, with affinities to Homo erectus, in mainland East Asia. This age estimate is roughly the same as for H. erectus in island Southeast Asia and immediately prior to the oldest archaeological evidence in northeast Asia. Mammalian fauna and pollen obtained directly from the hominin site indicate that the Yuanmou hominins lived in a varied habitat of open vegetation with patches of bushland and forest on an alluvial fan close to a lake or swamp. The age and location are consistent with a rapid southern migration route of initial hominin populations into Eastern Asia.

An investigation of the shielding characteristics of computed radiography cassettes.

Computed radiography (CR) systems are rapidly replacing film screen techniques. Previous estimates have been made of the degree of attenuation that occurs as a primary diagnostic X-ray beam passes through a film-screen cassette at different tube potentials. Cassette attenuation is commonly stated in terms of equivalent thickness of lead, which can be calculated using lead attenuation curves. These values can then be subtracted from the shielding requirements calculated for diagnostic X-ray rooms. Since the introduction of CR, no comparison has been made between the attenuation of the old film-screen and the new CR cassettes. In order to perform such a comparison, transmission factors for two CR cassettes and one film-screen cassette were measured, in addition to experimental lead attenuation curves. Lead equivalent thickness values were calculated for all three cassettes using both a semi-theoretical model and measured data. Although there was some discrepancy between the two methods, both found that the new cassettes provided a similar or greater degree of attenuation as the film screen cassette.

Assessment of dioxin and dioxin-like compounds in mainstream smoke from selected US cigarette brands and reference cigarettes.

Mainstream cigarette smoke (MSS) from 12 US cigarette brands and two reference cigarettes was evaluated to determine concentrations of dioxins (i.e., polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (PCBs)). The study included three 'tar' ranges based on Federal Trade Commission (FTC) determination: Low Yield (LY) < or = 5.5, Medium Yield (MY) 9.6-12.2, and High Yield (HY)> or = 14.5 mg/cig. Of the brands studied, the HY cigarettes yielded the greatest mean concentrations of 2005 World Health Organization Toxic Equivalents (WHO-TEQs) on a per cigarette basis. WHO-TEQ levels in LY cigarettes were significantly lower than for HY cigarettes (p=0.039) on a yield per cigarette basis and WHO-TEQ concentrations correlated with 'tar' yield (r=0.73, p=0.007), as did concentration on a WHO-TEQ per body mass per day basis (r=0.73, p=0.007). However, a statistically significant relationship was not observed between 'tar' yield levels and WHO-TEQ concentrations on a per mg Total Particulate Matter (TPM) basis. Concentrations for all brands tested ranged from 0.44 to 3.88 fg WHO-TEQ/mg TPM. Maximum daily exposure estimates calculated from this range (0.004-0.074 pg WHO-TEQ/kg bw/day) are below the current WHO Tolerable Daily Intake range of 1-5 pg/kg bw/day.

Molar enamel thickness and dentine horn height in Gigantopithecus blacki.

Absolutely thick molar enamel is consistent with large body size estimates and dietary inferences about Gigantopithecus blacki, which focus on tough or fibrous vegetation. In this study, 10 G. blacki molars demonstrating various stages of attrition were imaged using high-resolution microtomography. Three-dimensional average enamel thickness and relative enamel thickness measurements were recorded on the least worn molars within the sample (n = 2). Seven molars were also virtually sectioned through the mesial cusps and two-dimensional enamel thickness and dentine horn height measurements were recorded. Gigantopithecus has the thickest enamel of any fossil or extant primate in terms of absolute thickness. Relative (size-scaled) measures of enamel thickness, however, support a thick characterization (i.e., not "hyper-thick"); G. blacki relative enamel thickness overlaps slightly with Pongo and completely with Homo. Gigantopithecus blacki dentine horns are relatively short, similar to (but shorter than) those of Pongo, which in turn are shorter than those of humans and African apes. Gigantopithecus blacki molar enamel (and to a lesser extent, that of Pongo pygmaeus) is distributed relatively evenly across the occlusal surface compared with the more complex distribution of enamel thickness in Homo sapiens. The combination of evenly distributed occlusal enamel and relatively short dentine horns in G. blacki results in a flat and low-cusped occlusal surface suitable to grinding tough or fibrous food objects. This suite of molar morphologies is also found to varying degrees in Pongo and Sivapithecus, but not in African apes and humans, and may be diagnostic of subfamily Ponginae.

Thalamic dementia: an example of primary astroglial dystrophy of Seitelberger.

Pure thalamic dementia is highly uncommon and typically demonstrates widespread loss of neurons throughout the thalamus associated with reactive gliosis. This report describes an autopsy case in which there is widespread gliosis of subcortical white matter, focal hippocampal sclerosis and a unique proliferation of protoplasmic astrocytes in the thalamus, with limited bilateral focal loss of neurons. The alterations of the protoplasmic astrocytes consist of proliferation of perivascular feet surrounding blood vessels and velate sheets which surround individual neurons. It is proposed that the astrocytic alterations, or astrocytic dystrophy, constitute the primary and critical pathologic-change, sufficiently severe to produce dementia in the presence of a relatively intact neuronal population.

New evidence on the earliest human presence at high northern latitudes in northeast Asia.

The timing of early human dispersal to Asia is a central issue in the study of human evolution. Excavations in predominantly lacustrine sediments at Majuangou, Nihewan basin, north China, uncovered four layers of indisputable hominin stone tools. Here we report magnetostratigraphic results that constrain the age of the four artefact layers to an interval of nearly 340,000 yr between the Olduvai subchron and the Cobb Mountain event. The lowest layer, about 1.66 million years old (Myr), provides the oldest record of stone-tool processing of animal tissues in east Asia. The highest layer, at about 1.32 Myr, correlates with the stone tool layer at Xiaochangliang, previously considered the oldest archaeological site in this region. The findings at Majuangou indicate that the oldest known human presence in northeast Asia at 40 degrees N is only slightly younger than that in western Asia. This result implies that a long yet rapid migration from Africa, possibly initiated during a phase of warm climate, enabled early human populations to inhabit northern latitudes of east Asia over a prolonged period.

High-resolution vegetation and climate change associated with Pliocene Australopithecus afarensis.

Plio-Pleistocene global climate change is believed to have had an important influence on local habitats and early human evolution in Africa. Responses of hominin lineages to climate change have been difficult to test, however, because this procedure requires well documented evidence for connections between global climate and hominin environment. Through high-resolution pollen data from Hadar, Ethiopia, we show that the hominin Australopithecus afarensis accommodated to substantial environmental variability between 3.4 and 2.9 million years ago. A large biome shift, up to 5 degrees C cooling, and a 200- to 300-mm/yr rainfall increase occurred just before 3.3 million years ago, which is consistent with a global marine delta(18)O isotopic shift.

Mechanisms regulating the cadmium-mediated suppression of Sp1 transcription factor activity in alveolar epithelial cells.

This study demonstrates that in vitro exposure of adult rat alveolar epithelial cells to CdCl(2) decreases DNA binding activity of specificity protein 1 (Sp1), a zinc-finger transcription factor known to play a key role in eukaryotic gene expression, maintenance of homeostasis, cell cycle control, terminal differentiation, and apoptosis. Suppression of Sp1 function, as assessed by electrophoretic mobility shift assays (EMSAs), is dependent upon cadmium (Cd) dose and duration of exposure. A 45% decrease of Sp1 activity occurs as early as 30 min after Cd addition. By 2 h, Sp1 activity is reduced even further with no loss of cell viability, suggesting that Sp1 inactivation precedes cell death. If Cd is removed from cultures during these early periods of exposure, inhibition of Sp1 binding activity is reversed. Sp1 inactivation does not appear to be a generalized, non-selective response to Cd as other transcription factors are up-regulated under the same conditions. Phosphorylation is involved in Sp1 down-regulation, as evidenced by the finding that alkaline phosphatase treatment of nuclear extracts from cells exposed to Cd for 2 h helps restore Sp1 binding activity. A broad spectrum Protein Kinase C (PKC) inhibitor, GF109203X, substantially reduces the Cd-mediated effect on Sp1 suggesting that a member of the PKC family is required for Sp1 phosphorylation. More prolonged Cd exposure promotes Sp1 degradation with the appearance of cleavage products (40 and 50 kDa), as detected by Western blotting. Changes in the integrity of the Sp1 protein are accompanied by a corresponding decline in cell survival. Cd-induced cell death is substantially attenuated if cells are pretreated with antagonists of PKC activity which implies that a PKC isoform is also a participant in this process.

Clinical evaluation of the GlucoWatch biographer: a continual, non-invasive glucose monitor for patients with diabetes.

A device providing frequent, automatic, and non-invasive glucose measurements for persons with diabetes has been developed: the GlucoWatch biographer. This device extracts glucose through intact skin via reverse iontophoresis where it is detected by an amperometric biosensor. The biographer can provide glucose readings every 20 min for 12 h. The performance of this device was evaluated in two large clinical studies in a controlled clinical environment (n=231), and the home environment (n=124). Accuracy of the biographer was evaluated by comparing the automatic biographer readings to serial finger-stick blood glucose (BG) measurements. Biographer performance was comparable in both environments. Mean difference between biographer and finger-stick measurements was -0.01 and 0.26 mmol l(-1) for the clinical and home environments, respectively. The mean absolute value of the relative difference was 1.06 and 1.18 mmol l(-1) for the same studies. Correlation coefficient (r) between biographer and finger-stick measurements was 0.85 and 0.80 for the two studies. In both studies, over 94% of the biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low BG levels. Biographer accuracy is relatively constant over all rates of BG changes, except when BG decreases more than 10 mmol l(-1) h(-1), which occurred for only 0.2% of points in the home environment study. Biographer precision, as measured by CV%, is approx. 10%. Skin irritation, characterized by erythema and edema, was either non-existent or mild in >90% of subjects and resolved in virtually all subjects without treatment in several days.

Earliest presence of humans in northeast Asia.

The timing of the earliest habitation and oldest stone technologies in different regions of the world remains a contentious topic in the study of human evolution. Here we contribute to this debate with detailed magnetostratigraphic results on two exposed parallel sections of lacustrine sediments at Xiaochangliang in the Nihewan Basin, north China; these results place stringent controls on the age of Palaeolithic stone artifacts that were originally reported over two decades ago. Our palaeomagnetic findings indicate that the artifact layer resides in a reverse polarity magnetozone bounded by the Olduvai and Jaramillo subchrons. Coupled with an estimated rate of sedimentation, these findings constrain the layer's age to roughly 1.36 million years ago. This result represents the age of the oldest known stone assemblage comprising recognizable types of Palaeolithic tool in east Asia, and the earliest definite occupation in this region as far north as 40 degrees N.

Detection of hypoglycemia with the GlucoWatch biographer.

OBJECTIVE: Hypoglycemia is a common acute complication of diabetes therapy. The GlucoWatch biographer provides frequent and automatic glucose measurements with an adjustable low-glucose alarm. We have analyzed the performance of the biographer low-glucose alarm relative to hypoglycemia as defined by blood glucose < or = 3.9 mmol/l. RESEARCH DESIGN AND METHODS: The analysis was based on 1,091 biographer uses from four clinical trials. which generated 14,487 paired (biographer and blood glucose) readings. RESULTS: The results show that as the low-glucose alert level of the biographer is increased, the number of true positive alerts (alarm sounds and blood glucose < or = 3.9 mmol/l) and false positive alerts (alarm sounds but blood glucose >3.9 mmol/l) increased. When analyzed as a function of varying low-glucose alert levels, the results show receiver operator characteristic curves consistent with a highly useful diagnostic tool. Setting the alert level from 1.1 to 1.7 mmol/l above the level of concern is likely to optimize the trade-off between true positives and false positives for each user. When the same blood glucose data are analyzed for typical monitoring practices (two or four measurements per day), the results show that fewer hypoglycemic events are detected than those detected with the biographer.

Effect of combination therapy on immunologic progression of human immunodeficiency virus at a population level.

There is accumulating evidence from clinical trials and cohort studies that highly active antiretroviral combination therapy is effective at halting immunologic and clinical progression of human immunodeficiency virus (HIV). Its impact at a population level is less well known because the regimes may be difficult to tolerate and compliance poorer. The authors make use of population data for almost all of the HIV-infected people in Scotland in 1997 who were under clinical care and monitor their response to therapy during the first year when these effective treatments became widely available. More than two thirds of the HIV-positive patients were on some form of antiretroviral therapy during the year. The authors show that all treated groups, even those who were on changing regimes, showed net improvement in immunologic status during the year. For the group of patients on triple or quadruple therapy, there was an average increase of more than 100 CD4 cells/mm(3) over the year, with other treatment groups showing more modest, but significant, increases.

Inhibition of oxidative DNA repair in cadmium-adapted alveolar epithelial cells and the potential involvement of metallothionein.

This study evaluated the effects of cadmium (Cd) adaptation in cultured alveolar epithelial cells on oxidant-induced DNA damage and its subsequent repair. Using the comet assay, we determined that lower levels of DNA damage occurred in Cd-adapted cells compared with non-adapted cells following treatment of cells with hydrogen peroxide (H(2)O(2)). This may be a consequence of increased thiol-containing antioxidants that were observed in adapted cells, including metallothionein and glutathione. Cd-adapted cells were, however, less efficient at repairing total oxidative DNA damage compared with non-adapted cells. Subsequently, we investigated the effect of Cd adaptation on the repair of particular oxidized DNA lesions by employing lesion-specific enzymes in the comet assay, namely formamidopyrimidine DNA glycosylase (Fpg), an enzyme that predominantly repairs 8-oxoguanine (8-oxoG), and endonuclease III, that is capable of repairing oxidized pyrimidines. The data demonstrated that adaptation to Cd results in significantly impaired repair of both Fpg- and endonuclease III-sensitive lesions. In addition, in situ detection of 8-oxoG using a recombinant monoclonal antibody showed that Cd-adaptation reduces the repair of this oxidative lesion after exposure of cells to H(2)O(2). Activities of 8-oxoG-DNA glycosylase and endonuclease III were determined in whole cell extracts using 32P-labeled synthetic oligonucleotides containing 8-oxoG and dihydrouracil sites, respectively. Cd adaptation was associated with an inhibition of 8-oxoG-DNA glycosylase and endonuclease III enzyme activity compared with non-adapted cells. In summary, this study has shown that Cd adaptation: (1) reduces oxidant-induced DNA damage; (2) increases the levels of key intracellular antioxidants; (3) inhibits the repair of oxidative DNA damage.