Hybridized electromagnetic-triboelectric nanogenerator for scavenging air-flow energy to sustainably power temperature sensors.
We report a hybridized nanogenerator with dimensions of 6.7 cm × 4.5 cm × 2 cm and a weight of 42.3 g that consists of two triboelectric nanogenerators (TENGs) and two electromagnetic generators (EMGs) for scavenging air-flow energy. Under an air-flow speed of about 18 m/s, the hybridized nanogenerator can deliver largest output powers of 3.5 mW for one TENG (in correspondence of power per unit mass/volume: 8.8 mW/g and 14.6 kW/m(3)) at a loading resistance of 3 MΩ and 1.8 mW for one EMG (in correspondence of power per unit mass/volume: 0.3 mW/g and 0.4 kW/m(3)) at a loading resistance of 2 kΩ, respectively. The hybridized nanogenerator can be utilized to charge a capacitor of 3300 μF to sustainably power four temperature sensors for realizing self-powered temperature sensor networks. Moreover, a wireless temperature sensor driven by a hybridized nanogenerator charged Li-ion battery can work well to send the temperature data to a receiver/computer at a distance of 1.5 m. This work takes a significant step toward air-flow energy harvesting and its potential applications in self-powered wireless sensor networks.


Interaction of tRNA-derivatives and oligonucleotide primers with AZT-resistant mutants of HIV-1 reverse transcriptase.
While the molecular basis of HIV-1 AZT resistance has been widely studied, a biochemical explanation of this process is not well known. No significant changes in the binding affinity of reverse transcriptase (RT) mutants for AZT-triphosphate has been found. Here we analyzed the interaction of wild type and AZT-resistant mutant forms of HIV-1 RT with different primers. Site-directed mutagenesis was used to introduce point mutations on the retroviral enzyme. Primers were either synthetic oligonucleotides or tRNA(Lys3) derivatives containing d(pT)n or r(pU)n at the 3' end. In all cases, determination of kinetic parameters was done in the presence or absence of compounds known to modify protein conformation, such as dimethyl sulfoxide (DMSO), urea, and Triton X-100. Although we found similar K(m) values for all RTs, there was generally an increase in the affinity when enzymes were tested in the presence of DMSO, urea, and Triton X-100. Then, we analyzed the nucleation and elongation steps of the polymerization process. The efficiency of formation of the first base pair was determined by measuring K(m1), the affinity between RT and the 3' terminal nucleotide of the primer. An important difference was found: in the presence of DMSO, urea, and Triton X-100, the K(m1) values for mutated enzymes were higher than those of wild type RTs. Thus, the presence of compounds able to change protein conformation led to a marked destabilization of the interaction of mutated RTs with the 3' terminal nucleotide of the primer. From these results, it can be hypothesized that resistance to AZT is not due to the direct influence of mutations on RT, but rather to conformational changes of the mutated RT in complex with the template-primer altering the ability of the enzyme to select or reject an incoming dNTP.


Sonic hedgehog regulates Bmi1 in human medulloblastoma brain tumor-initiating cells.
Bmi1 is a key stem cell regulatory gene implicated in the pathogenesis of many aggressive cancers, including medulloblastoma. Overexpression of Bmi1 promotes cell proliferation and is required for hedgehog (Hh) pathway-driven tumorigenesis. This study aimed to determine if Sonic hedgehog (Shh) modulates the key stem cell regulatory gene Bmi1 in childhood medulloblastoma brain tumor-initiating cells (BTICs). Although current literature suggests that there is a correlation between Shh pathway genes and Bmi1 expression, it is unclear whether there is indeed a direct regulatory mechanism. To address whether Shh induces expression of Bmi1, stem cell-enriched populations from medulloblastoma cell lines and primary samples were treated with Shh ligand and KAAD-cyclopamine (Shh antagonist). Our data indicate that Bmi1 expression positively correlates with increasing Shh ligand concentrations. Chromatin immunoprecipitation reveals that Gli1 preferentially binds to the Bmi1 promoter, and Bmi1 transcript levels are increased and decreased by Gli1 overexpression and downregulation, respectively. Knockdown experiments of Bmi1 in vitro and in vivo demonstrate that Hh signaling not only drives Bmi1 expression, but a feedback mechanism exists wherein downstream effectors of Bmi1 may, in turn, activate Hh pathway genes. These findings implicate Bmi1 and Hh as mutually indispensable pathways in medulloblastoma BTIC maintenance. Recent molecular characterization of medulloblastoma also reveals that Bmi1 is overexpressed across all subgroups of medulloblastoma, particularly in the most aggressive subtypes. Lastly, despite recent identification of BTIC markers, the molecular characterization of these cell populations remains unclear. In this work, we propose that the BTIC marker CD133 may segregate a cell population with a Hh-receptor phenotype, thus demonstrating a cell-cell interaction between the CD133+ Hh receptor cells and the CD133- Hh-secreting cells.


Economic and public health consequences of delayed access to medical care for migrants living with HIV in France.
In 2013, migrants accounted for 46% of newly diagnosed cases of HIV (human immunodeficiency virus) infection in France. These populations meet with specific obstacles leading to late diagnosis and access to medical care. Delayed access to care (ATC) for HIV-infected migrants reduces their life expectancy and quality of life. Given the reduction of infectivity under antiretroviral (ARV) treatment, delayed ATC for HIV-infected migrants may also hinder the control of the HIV epidemic. The objective of this study is to measure the public health and economic consequences of delayed ATC for migrants living with HIV in France. Using a healthcare payer perspective, our model compares the lifetime averted infections and costs of early vs. late ATC for migrants living with HIV in France. Early and late ATC are defined by an entry into care with a CD4 cell count of 350 and 100/mm3, respectively. Our results show that an early ATC is dominant, even in the worst-case scenario. In the most favorable scenario, early ATC generates an average net saving of €198,000 per patient, and prevents 0.542 secondary infection. In the worst-case scenario, early ATC generates an average net saving of €32,000 per patient, and prevents 0.299 secondary infection. These results are robust to various adverse changes in key parameters and to a definition of late ATC as an access to care at a CD4 level of 200/mm3. In addition to individual health benefits, improving ATC for migrants living with HIV proves efficient in terms of public health and economics. These results stress the benefit of ensuring early ATC for all individuals living with HIV in France.


Detection of tick blood parasites in Egypt using PCR assay II- Borrelia burgdorferi sensu lato.
The prevalence of Borrelia burgdorferi sensu lato (s.l.), the etiologic agent of Lyme borrelosis (LB), was determined for the first time in Egypt by using polymerase chain reaction (PCR). Questing 5243 hard and soft ticks were collected from animal farms throughout Giza Governorate. DNA from 500 individual tick species was extracted and PCR was performed. Primers verified from the sequence of German strain Pko of Borrelia afzelii were used. Fragments of 642 bp were generated and sequenced. The prevalence of B. burgdorferi sensu lato (s.l.) was 28% of examined soft and hard ticks. High infection rate (66%) of B. burgdorferi s.l. was observed in both nymph and adult soft ticks Ornithodoros savignyi. Beside, the role of hard ticks as potential vectors of Lyme disease in Egypt, where the infection rate was between 0.0-50.0%. Sequence analysis of PCR product of Borrelia burgdorferi sensu lato shares high degree of similarity in sequence compared to similar species in GenBank.


Negative autoregulation of BMP dependent transcription by SIN3B splicing reveals a role for RBM39.
BMP signalling is negatively autoregulated by several genes including SMAD6, Noggin and Gremlin, and autoregulators are possible targets for enhancing BMP signalling in disorders such as fibrosis and pulmonary hypertension. To identify novel negative regulators of BMP signalling, we used siRNA screening in mouse C2C12 cells with a BMP-responsive luciferase reporter. Knockdown of several splicing factors increased BMP4-dependent transcription and target gene expression. Knockdown of RBM39 produced the greatest enhancement in BMP activity. Transcriptome-wide RNA sequencing identified a change in Sin3b exon usage after RBM39 knockdown. SIN3B targets histone deacetylases to chromatin to repress transcription. In mouse, Sin3b produces long and short isoforms, with the short isoform lacking the ability to recruit HDACs. BMP4 induced a shift in SIN3B expression to the long isoform, and this change in isoform ratio was prevented by RBM39 knockdown. Knockdown of long isoform SIN3B enhanced BMP4-dependent transcription, whereas knockdown of the short isoform did not. We propose that BMP4-dependent transcription is negatively autoregulated in part by SIN3B alternative splicing, and that RBM39 plays a role in this process.


Modified MacNeille cube polarizer for a wide angular field.
Well known relationships exist between thicknesses and indices of a stack of optical layers which permit the definition of very good polarizers of light. One of the most famous types of polarizer is the MacNeille cube. In this case the hypotenuse face of an isosceles right angled prism is coated with a polarizing deposit and then cemented to the hypotenuse face of an identical prism. This polarizer can be used over a large spectral range located in the s vibration stop band. Unfortunately, the insertion losses for thep vibration are large when the angular field is larger than +/-2 degrees . Using very simple optical considerations, we design suitable coating structures that allow the use of cube polarizers over a wide angular range, typically +/-10 degrees in air, when T(p)>0.97 and T(s) </= 10(-3). However, the spectral range is reduced. Diagrams are given to calculate the thickness of the layers according to the substrate and the indices of the evaporated materials. The prism angle is also determined to have a symmetric angular field in air. Such polarizers are suitable for semiconductor lasers because they can be used without a collimating lens in spite of their large divergence. Good optical characteristics up to T(p) approximately 0.95 and T(s) approximately 10(-4) over the range of +/-5 degrees have been measured for these polarizers manufactured in the Laboratoires de Marcoussis.


Beneath it all: bedrock geology of the Catskill Mountains and implications of its weathering.
The Devonian-age bedrock of the Catskill Mountains has been the focus of many studies. This paper reviews the character and composition of the rocks of the Catskills, and examines weathering (rock decay) processes and their implications in the Catskills. Rocks of the Catskills and closest foothills consist of siliciclastic rocks (sandstones, mudrocks, conglomerates) with minimal, locally dispersed carbonate rocks. The former are dominated by quartz, metamorphic and sedimentary rock fragments, and clay minerals. Other minor sediment components include cements, authigenic and heavy minerals, and fossil organic matter. Physical, chemical, and biological weathering of the Catskill bedrock since uplift of the Appalachian region, combined with glaciation, have dissected a plateau of nearly horizontally layered rocks into a series of ridges, valleys, and peaks. The varied weathering processes, in conjunction with many factors (natural and anthropogenic), fragment the rocks, forming sediment and releasing various elements and compounds. These may have positive, neutral, or negative implications for the region's soils, waters, ecology, and human usage. A new generation of studies and analyses of the Catskill bedrock is needed to help answer a broad set of questions and problems across various fields of interest.


The chloroplastic DEVH-box RNA helicase INCREASED SIZE EXCLUSION LIMIT 2 involved in plasmodesmata regulation is required for group II intron splicing.
INCREASED SIZE EXCLUSION LIMIT 2 (ISE2) encodes a putative DEVH-box RNA helicase originally identified through a genetic screening for Arabidopsis mutants altered in plasmodesmata (PD) aperture. Depletion of ISE2 also affects chloroplasts activity, decreases accumulation of photosynthetic pigments and alters expression of photosynthetic genes. In this work, we show the chloroplast localization of ISE2 and decipher its role in plastidic RNA processing and, consequently, PD function. Group II intron-containing RNAs from chloroplasts exhibit defective splicing in ise2 mutants and ISE2-silenced plants, compromising plastid viability. Furthermore, RNA immunoprecipitation suggests that ISE2 binds in vivo to several splicing-regulated RNAs. Finally, we show that the chloroplast clpr2 mutant (defective in a subunit of a plastidic Clp protease) also exhibits abnormal PD function during embryogenesis, supporting the idea that chloroplast RNA processing is required to regulate cell-cell communication in plants.


DPABI: Data Processing & Analysis for (Resting-State) Brain Imaging.
Brain imaging efforts are being increasingly devoted to decode the functioning of the human brain. Among neuroimaging techniques, resting-state fMRI (R-fMRI) is currently expanding exponentially. Beyond the general neuroimaging analysis packages (e.g., SPM, AFNI and FSL), REST and DPARSF were developed to meet the increasing need of user-friendly toolboxes for R-fMRI data processing. To address recently identified methodological challenges of R-fMRI, we introduce the newly developed toolbox, DPABI, which was evolved from REST and DPARSF. DPABI incorporates recent research advances on head motion control and measurement standardization, thus allowing users to evaluate results using stringent control strategies. DPABI also emphasizes test-retest reliability and quality control of data processing. Furthermore, DPABI provides a user-friendly pipeline analysis toolkit for rat/monkey R-fMRI data analysis to reflect the rapid advances in animal imaging. In addition, DPABI includes preprocessing modules for task-based fMRI, voxel-based morphometry analysis, statistical analysis and results viewing. DPABI is designed to make data analysis require fewer manual operations, be less time-consuming, have a lower skill requirement, a smaller risk of inadvertent mistakes, and be more comparable across studies. We anticipate this open-source toolbox will assist novices and expert users alike and continue to support advancing R-fMRI methodology and its application to clinical translational studies.


Substantial declines in urban tree habitat predicted under climate change.
Globally, local governments are increasing investment in urban greening projects. However, there is little consideration of whether the species being planted will be resilient to climate change. We assessed the distribution of climatically suitable habitat, now and in the future, for 176 tree species native to Australia, commonly planted across Australia's Significant Urban Areas (SUAs) and currently grown by commercial nurseries. Species' occurrence records were obtained from inventories and herbaria, globally and across Australia, and combined with baseline climate data (WorldClim, 1960-1990) and six climate scenarios for 2030 and 2070 using climatic suitability models (CSMs). CSMs for each species were calibrated and projected onto baseline and future scenarios. We calculated changes in the size of climatically suitable habitat for each species across each SUA, and identified urban areas that are likely to have suitable climate for either fewer or more of our study species under future climate. By 2070, climatically suitable habitat in SUAs is predicted to decline for 73% of species assessed. For 18% of these species, climatically suitable area is predicted to be more than halved, relative to their baseline extent. Generally, for urban areas in cooler regions, climatically suitable habitat is predicted to increase. By contrast, for urban areas in warmer regions, a greater proportion of tree species may lose climatically suitable habitat. Our results highlight changing patterns of urban climatic space for commonly planted species, suggesting that local governments and the horticultural industry should take a proactive approach to identify new climate-ready species for urban plantings.


Biomimicry at the nanoscale: current research and perspectives of two-photon polymerization.
Living systems such as cells and tissues are extremely sensitive to their surrounding physico-chemical microenvironment. In the field of regenerative medicine and tissue engineering, the maintenance of culture conditions suitable for the formation of proliferation niches, for the self-renewal maintenance of stem cells, or for the promotion of a particular differentiation fate is an important issue that has been addressed using different strategies. A number of investigations suggests that a particular cell behavior can be in vitro resembled by mimicking the corresponding in vivo conditions. In this context, several biomimetic environments have been designed in order to control cell phenotypes and functions. In this review, we will analyze the most recent examples of the control of the in vitro physical micro/nano-environment by exploiting an innovative technique of high resolution 3D photolithography, the two-photon polymerization (2pp). The biomedical applications of this versatile and disruptive computer assisted design/manufacturing technology are very wide, and range from the fabrication of biomimetic and nanostructured scaffolds for tissue engineering and regenerative medicine, to the microfabrication of biomedical devices, like ossicular replacement prosthesis and microneedles.


The behavior and social communication of honey bees (Apis mellifera carnica Poll.) under the influence of alcohol.
In this study, the effects of ethanol on honey bee social communication and behavior within the hive were studied to further investigate the usefulness of honey bees as an ethanol-abuse model. Control (1.5 M sucrose) and experimental (1.5 M sucrose, 2.5% w/v ethanol) solutions were directly administered to individual forager bees via proboscis contact with glass capillary tubes. The duration, frequency, and proportion of time spent performing social and nonsocial behaviors were the dependent variables of interest. No differences in the relative frequency or proportion of time spent performing the target behaviors were observed. However, ethanol consumption significantly decreased bouts of walking, resting, and the duration of trophallactic (i.e., food-exchange) encounters. The results of this study suggest that a low dose of ethanol is sufficient to disrupt both social and nonsocial behaviors in honey bees. In view of these results, future behavioral-genetic investigations of honey bee social behavior are encouraged.


The influence of bonus payments to doctors on hospital revenue: results of a quasi-experimental study.
There is wide consensus that the ways in which providers are reimbursed by third parties will affect their behaviour and, hence, the efficient use of limited resources and the performance of health systems. However, there seems to be little evidence on how payment to hospital-based doctors affects hospital performance. This paper reports a case study conducted in China on the effects of different types of bonus payment to doctors, with a focus on how bonus payment might have affected hospital revenue growth. This has been an increasingly important goal of public hospitals as they have gained increased autonomy. A set of longitudinal quasi-experimental data, and a set of cross-sectional data, both derived from 108 public hospitals, were used for the analysis. It was found that, when a bonus system was introduced, and when the bonus model switched from one with a weaker incentive to provide services to one with a stronger incentive, there was a consistent sudden increase in the rate of growth of hospital revenue. Bonus type was also associated with the size of hospital service revenue. The results highlight the potential risks of linking remuneration too closely with revenue generation, and the need to ensure adequate attention to mechanisms of control and accountability when hospitals are given greater autonomy.


Knowledge translation strategies to improve the use of evidence in public health decision making in local government: intervention design and implementation plan.
Knowledge translation strategies are an approach to increase the use of evidence within policy and practice decision-making contexts. In clinical and health service contexts, knowledge translation strategies have focused on individual behavior change, however the multi-system context of public health requires a multi-level, multi-strategy approach. This paper describes the design of and implementation plan for a knowledge translation intervention for public health decision making in local government. Four preliminary research studies contributed findings to the design of the intervention: a systematic review of knowledge translation intervention effectiveness research, a scoping study of knowledge translation perspectives and relevant theory literature, a survey of the local government public health workforce, and a study of the use of evidence-informed decision-making for public health in local government. A logic model was then developed to represent the putative pathways between intervention inputs, processes, and outcomes operating between individual-, organizational-, and system-level strategies. This formed the basis of the intervention plan. The systematic and scoping reviews identified that effective and promising strategies to increase access to research evidence require an integrated intervention of skill development, access to a knowledge broker, resources and tools for evidence-informed decision making, and networking for information sharing. Interviews and survey analysis suggested that the intervention needs to operate at individual and organizational levels, comprising workforce development, access to evidence, and regular contact with a knowledge broker to increase access to intervention evidence; develop skills in appraisal and integration of evidence; strengthen networks; and explore organizational factors to build organizational cultures receptive to embedding evidence in practice. The logic model incorporated these inputs and strategies with a set of outcomes to measure the intervention's effectiveness based on the theoretical frameworks, evaluation studies, and decision-maker experiences. Documenting the design of and implementation plan for this knowledge translation intervention provides a transparent, theoretical, and practical approach to a complex intervention. It provides significant insights into how practitioners might engage with evidence in public health decision making. While this intervention model was designed for the local government context, it is likely to be applicable and generalizable across sectors and settings. Australia New Zealand Clinical Trials Register ACTRN12609000953235.


Bendability optimization of flexible optical nanoelectronics via neutral axis engineering.
The enhancement of bendability of flexible nanoelectronics is critically important to realize future portable and wearable nanoelectronics for personal and military purposes. Because there is an enormous variety of materials and structures that are used for flexible nanoelectronic devices, a governing design rule for optimizing the bendability of these nanodevices is required. In this article, we suggest a design rule to optimize the bendability of flexible nanoelectronics through neutral axis (NA) engineering. In flexible optical nanoelectronics, transparent electrodes such as indium tin oxide (ITO) are usually the most fragile under an external load because of their brittleness. Therefore, we representatively focus on the bendability of ITO which has been widely used as transparent electrodes, and the NA is controlled by employing a buffer layer on the ITO layer. First, we independently investigate the effect of the thickness and elastic modulus of a buffer layer on the bendability of an ITO film. Then, we develop a design rule for the bendability optimization of flexible optical nanoelectronics. Because NA is determined by considering both the thickness and elastic modulus of a buffer layer, the design rule is conceived to be applicable regardless of the material and thickness that are used for the buffer layer. Finally, our design rule is applied to optimize the bendability of an organic solar cell, which allows the bending radius to reach about 1 mm. Our design rule is thus expected to provide a great strategy to enhance the bending performance of a variety of flexible nanoelectronics.


CA/TG sequence at the 5' end of oligo(A)-tracts strongly modulates DNA curvature.
An analysis of the base pair doublet geometries in available crystal structures indicates that the often reported intrinsic curvature of DNA containing oligo-(d(A).d(T)) tracts may also depend on the nature of the flanking sequences. The presence of CA/TG doublet in particular at the 5' end of these tracts is expected to enhance their intrinsic bending property. To test this proposition, three oligonucleotides, d(GAAAAAC-CCCCC), d(CCCCCCAAAAAG), d(GAAAAATTTTTC), and their complementary sequences were synthesized to study the effect of various flanking sequences, at the 5' and 3' ends of the A-tracts, on the curvature of DNA in solution. An analysis of the polyacrylamide gel electrophoretic mobilities of these sequences under different conditions of salts and temperatures (below their melting points) clearly showed that the oligomer with CA/TG sequence in the center was always more retarded than the oligomer with AC/GT sequence, as well as the oligomer with AT/AT sequence. Hydroxyl radical probing of the sequences with AC/GT and CA/TG doublet junctions gives a similar cutting pattern in the A-tracts, which is quite different from that in the C-tracts, indicating that the oligo(A)-tracts have similar structures in the two oligomers. KMnO4 probing shows that the oligomer with a CA/TG doublet junction forms a kink that is responsible for its inherent curvature and unusual electrophoretic mobility. UV melting shows a reduced thermal stability of the duplex with CA/TG doublet junction, and circular dichroism (CD) studies indicate that a premelting transition occurs in the oligomer with CA/TG doublet step before global melting but not in the oligomer with AC/GT doublet step, which may correspond to thermally induced unbending of the oligomer. These observations indicate that the CA/TG doublet junction at the 5' end of the oligo(A)-tract has a crucial role in modulating the overall curvature in DNA.


Efficacy and Safety of Augmenting the Preclose Technique with a Collagen-Based Closure Device for Percutaneous Endovascular Aneurysm Repair.
To report our experience of selectively augmenting the preclose technique for percutaneous endovascular aneurysm repair (p-EVAR) with an Angio-Seal device as a haemostatic adjunct in cases of significant bleeding after tensioning the sutures of the suture-mediated closure devices. Prospectively collected data for p-EVAR patients at our institute were analysed. Outcomes included technical success and access site complications. A logistic regression model was used to analyse the effects of sheath size, CFA features and stent graft type on primary failure of the preclose technique necessitating augmentation and also on the development of complications. p-EVAR was attempted via 122 CFA access sites with a median sheath size of 18-French (range 12- to 28-French). Primary success of the preclose technique was 75.4% (92/122). Angio-Seal augmentation was utilised as an adjunct to the preclose technique in 20.5% (25/122). The overall p-EVAR success rate was 95.1% (116/122). There was a statistically significant relationship (p = 0.0093) between depth of CFA and primary failure of preclose technique. CFA diameter, calcification, type of stent graft and sheath size did not have significant effects on primary preclose technique failure. Overall 4.9% (6/122) required surgical conversion but otherwise there were no major complications. Augmentation with an Angio-Seal device is a safe and effective adjunct to increase the success rate of the preclose technique in p-EVAR.


Profile reconstruction of periodic interface.
The reconstruction problem for periodic (arbitrary profiled within a period) boundary between two homogeneous media is considered. Our approach to the solution of the inverse problem is based on the Tikhonov regularization technique, which requires successive selection of the boundaries on the basis of multiple solutions of the direct problem of wave diffraction by the candidate boundaries. The analytical numerical C method has been chosen as a simple but rather efficient tool for the direct problem solving. The scheme for numerical tests of algorithms and criteria for reconstruction accuracy have been suggested and verified. Results of numerical experiments that prove the validity of the approach are presented.


The reconstruction algorithm used for [68Ga]PSMA-HBED-CC PET/CT reconstruction significantly influences the number of detected lymph node metastases and coeliac ganglia.
To investigate whether the numbers of lymph node metastases and coeliac ganglia delineated on [68Ga]PSMA-HBED-CC PET/CT scans differ among datasets generated using different reconstruction algorithms. Data were constructed using the BLOB-OS-TF, BLOB-OS and 3D-RAMLA algorithms. All reconstructions were assessed by two nuclear medicine physicians for the number of pelvic/paraaortal lymph node metastases as well the number of coeliac ganglia. Standardized uptake values (SUV) were also calculated in different regions. At least one [68Ga]PSMA-HBED-CC PET/CT-positive pelvic or paraaortal lymph node metastasis was found in 49 and 35 patients using the BLOB-OS-TF algorithm, in 42 and 33 patients using the BLOB-OS algorithm, and in 41 and 31 patients using the 3D-RAMLA algorithm, respectively, and a positive ganglion was found in 92, 59 and 24 of 100 patients using the three algorithms, respectively. Quantitatively, the SUVmean and SUVmax were significantly higher with the BLOB-OS algorithm than with either the BLOB-OS-TF or the 3D-RAMLA algorithm in all measured regions (p < 0.001 for all comparisons). The differences between the SUVs with the BLOB-OS-TF- and 3D-RAMLA algorithms were not significant in the aorta (SUVmean, p = 0.93; SUVmax, p = 0.97) but were significant in all other regions (p < 0.001 in all cases). The SUVmean ganglion/gluteus ratio was significantly higher with the BLOB-OS-TF algorithm than with either the BLOB-OS or the 3D-RAMLA algorithm and was significantly higher with the BLOB-OS than with the 3D-RAMLA algorithm (p < 0.001 in all cases). The results of [68Ga]PSMA-HBED-CC PET/CT are affected by the reconstruction algorithm used. The highest number of lesions and physiological structures will be visualized using a modern algorithm employing time-of-flight information.


Orthotopic, but reversed implantation of the liver allograft in situs inversus totalis-a simple new approach to a difficult problem.
Situs inversus totalis is a rare congenital anomaly in which the heart and abdominal organs are oriented in a mirror image of normal. It provides a unique challenge as there is no established technique for liver transplantation in these patients. Employing two major alterations from our standard technique, a liver was transplanted in the left subphrenic space of a patient with situs inversus totalis. First, the liver was flipped 180 degrees from right to left (facing backward). Second, a reversed cavaplasty (anterior, not posterior, donor suprahepatic caval incision) was performed. Otherwise, it was standard, with end-to-end anastomoses of the portal vein, hepatic artery and bile duct. Three years after the entirely uneventful transplant, the recipient continues to enjoy the benefits of a normally functioning liver. The described technique prevented torsion, kinking and tension on the anastomosed structures by allowing the liver to sit naturally in an anatomical position in the left hepatic fossa. As it required no special measurements or maneuvers, the technique was easy to execute and required no donor liver size restrictions. This novel technique, with a reversed cavaplasty and a 180 degrees right-to-left flip of the liver into a left-sided hepatic fossa, may be ideal for situs inversus totalis.


Molecular characterization of boscalid resistance in field isolates of Botrytis cinerea from apple.
Botrytis cinerea isolates obtained from apple orchards were screened for resistance to boscalid. Boscalid-resistant (BosR) isolates were classified into four phenotypes based on the levels of the concentration that inhibited fungal growth by 50% relative to control. Of the 220 isolates tested, 42 were resistant to boscalid, with resistant phenotypes ranging from low to very high resistance. There was cross resistance between boscalid and carboxin. Analysis of partial sequences of the iron-sulfur subunit of succinate dehydrogenase gene in B. cinerea (BcSdhB) from 13 BosR and 9 boscalid-sensitive (BosS) isolates showed that point mutations in BcSdhB leading to amino acid substitutions at the codon position 272 from histidine to either tyrosine (H272Y) or arginine (H272R) were correlated with boscalid resistance. Allele-specific polymerase chain reaction (PCR) analysis of 66 BosR isolates (including 24 additional isolates obtained from decayed apple fruit) showed that 19 carried the point mutation H272Y and 46 had the point mutation H272R, but 1 BosR isolate gave no amplification product. Analysis of the BcSdhB sequence of this isolate revealed a different point mutation at codon 225, resulting in a substitution of proline (P) by phenylalanine (F) (P225F). The results indicated that H272R/Y in BcSdhB were the dominant genotypes of mutants in field BosR isolates from apple. A multiplex allele-specific PCR assay was developed to detect point mutations H272R/Y in a single PCR amplification. Levels of boscalid resistance ranged from low to very high within isolates carrying either the H272R or H272Y mutation, indicating that, among BosR isolates, different BosR phenotypes (levels of resistance) were not associated with particular types of point mutations (H272R versus H272Y) in BcSdhB. Analysis of genetic relationships between 39 BosR and 56 BosS isolates based on three microsatellite markers showed that 39 BosR isolates and 30 BosS isolates were clustered into two groups, and the third group consisted of only BosS isolates, suggesting that the development of resistance to boscalid in B. cinerea likely is not totally random, and resistant populations may come from specific genetic groups.


Reduced myofibrillar connectivity and increased Z-disk width in nebulin-deficient skeletal muscle.
A prominent feature of striated muscle is the regular lateral alignment of adjacent sarcomeres. An important intermyofibrillar linking protein is the intermediate filament protein desmin, and based on biochemical and structural studies in primary cultures of myocytes it has been proposed that desmin interacts with the sarcomeric protein nebulin. Here we tested whether nebulin is part of a novel biomechanical linker complex, by using a recently developed nebulin knockout (KO) mouse model and measuring Z-disk displacement in adjacent myofibrils of both extensor digitorum longus (EDL) and soleus muscle. Z-disk displacement increased as sarcomere length (SL) was increased and the increase was significantly larger in KO fibers than in wild-type (WT) fibers; results in 3-day-old and 10-day-old mice were similar. Immunoelectron microscopy revealed reduced levels of desmin in intermyofibrillar spaces adjacent to Z-disks in KO fibers compared with WT fibers. We also performed siRNA knockdown of nebulin and expressed modules within the Z-disk portion of nebulin (M160-M170) in quail myotubes and found that this prevented the mature Z-disk localization of desmin filaments. Combined, these data suggest a model in which desmin attaches to the Z-disk through an interaction with nebulin. Finally, because nebulin has been proposed to play a role in specifying Z-disk width, we also measured Z-disk width in nebulin KO mice. Results show that most Z-disks of KO mice were modestly increased in width (approximately 80 nm in soleus and approximately 40 nm in EDL fibers) whereas a small subset had severely increased widths (up to approximately 1 microm) and resembled nemaline rod bodies. In summary, structural studies on a nebulin KO mouse show that in the absence of nebulin, Z-disks are significantly wider and that myofibrils are misaligned. Thus the functional roles of nebulin extend beyond thin filament length regulation and include roles in maintaining physiological Z-disk widths and myofibrillar connectivity.


Investigation of milk proteins binding to the oral mucosa.
High protein dairy beverages are considered to be mouth drying. The drying sensation may be due to the product protein content; however the mechanism of this mouth drying is uncertain. This study investigated the potential adhesion of milk proteins to porcine oral mucosa in vitro. Purified casein and β-lactoglobulin were fluorescently labelled, placed on porcine oral mucosal tissues and their resistance to wash out with simulated saliva was monitored using fluorescence microscopy. Casein was found to be more adhesive to porcine mucosa than β-lactoglobulin. Some investigation into the reason for this difference in mucoadhesion was conducted by thiol-content analysis, rheology and zeta-potential measurements. The higher viscosity of casein solution and smaller zeta-potential is believed to be responsible for its better retention on mucosal surfaces. These findings suggest that casein and whey protein are both capable of binding and eliciting mouth drying in high protein dairy beverages.


The effects of metal ion PCR inhibitors on results obtained with the Quantifiler(®) Human DNA Quantification Kit.
Forensic DNA samples may include the presence of PCR inhibitors, even after extraction and purification. Studies have demonstrated that metal ions, co-purified at specific concentrations, inhibit DNA amplifications. Metal ions are endogenous to sample types, such as bone, and can be introduced from environmental sources. In order to examine the effect of metal ions as PCR inhibitors during quantitative real-time PCR, 2800 M DNA was treated with 0.0025-18.750 mM concentrations of aluminum, calcium, copper, iron, nickel, and lead. DNA samples, both untreated and metal-treated, were quantified using the Quantifiler(®) Human DNA Quantification Kit. Quantification cycle (Cq) values for the Quantifiler(®) Human DNA and internal PCR control (IPC) assays were measured and the estimated concentrations of human DNA were obtained. Comparisons were conducted between metal-treated and control DNA samples to determine the accuracy of the quantification estimates and to test the efficacy of the IPC inhibition detection. This kit is most resistant to the presence of calcium as compared to all metals tested; the maximum concentration tested does not affect the amplification of the IPC or quantification of the sample. This kit is most sensitive to the presence of aluminum; concentrations greater than 0.0750 mM negatively affected the quantification, although the IPC assay accurately assessed the presence of PCR inhibition. The Quantifiler(®) Human DNA Quantification Kit accurately quantifies human DNA in the presence of 0.5000 mM copper, iron, nickel, and lead; however, the IPC does not indicate the presence of PCR inhibition at this concentration of these metals. Unexpectedly, estimates of DNA quantity in samples treated with 18.750 mM copper yielded values in excess of the actual concentration of DNA in the samples; fluorescence spectroscopy experiments indicated this increase was not a direct interaction between the copper metal and 6-FAM dye used to label the probe that targets human DNA in the Quantifiler(®) kit. Evidence of inhibition was observed for the human-specific assay at a lower metal concentration than detected by the IPC, for all metals examined except calcium. These results strongly suggest that determination of a "true negative" sample should not be based solely on the failure of the IPC to indicate the presence of a PCR inhibitor and indicate that amplification of all samples should be attempted, regardless of the quantification results.


Cigarette craving, smoking withdrawal, and clonidine.
Clonidine, an alpha-2-adrenergic agonist, significantly reduces opiate withdrawal. Fifteen heavy smokers abstained from cigarettes on three separate occasions and received instead clonidine, placebo, or the benzodiazepine alprazolam. Clonidine and alprazolam diminished withdrawal symptoms. The two drugs suppressed anxiety, tension, irritability, and restlessness equally but clonidine had a greater effect than alprazolam on cigarette craving. These observations suggest that noradrenergic activity is a common feature in the pathophysiology of withdrawal and that a special relationship exists between central noradrenergic activity and craving.


A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis.
Accurate patient stratification into prognostic categories and targeting Amyotrophic Lateral Sclerosis (ALS)-associated pathways may pave the way for promising trials. We evaluated blood-based prognostic indicators using an array of pathological markers. Plasma samples were collected as part of a large, phase III clinical trial (Mitotarget/TRO19622) at months 1, 6, 12 and 18. The ALSFRS-r score was used as a proxy of disease progression to assess the predictive value of candidate biological indicators. First, established clinical predictors were evaluated in all 512 patients. Subsequently, pathologic markers, such as proxies of neuronal integrity (Neurofilament light chain and phosphorylated heavy chain), DNA oxidation (8-oxo-2'-desoxyguanosine), lipid peroxidation (4-hydroxy-2-nonenal, isoprostane), inflammation (interleukin-6) and iron status (ferritin, hepcidin, transferrin) were assessed in a subset of 109 patients that represented the whole cohort. Markers of neuronal integrity, DNA and lipid oxidation, as well as iron status at baseline are accurate predictors of disability at 18-month follow-up. The composite scores of these markers in association with established clinical predictors enable the accurate forecasting of functional decline. The identified four biomarkers are all closely associated with 'ferroptosis', a recently discovered form of programmed cell death with promising therapeutic targets. The predictive potential of these pathophysiology-based indicators may offer superior patient stratification for future trials, individualised patient care and resource allocation.


Tonsillitis.
The definition of severe recurrent throat infections is arbitrary, but recent criteria have defined severe tonsillitis as: five or more episodes of true tonsillitis a year; symptoms for at least 1 year; and episodes that are disabling and prevent normal functioning. Diagnosis of acute tonsillitis is clinical, and it can be difficult to distinguish viral from bacterial infections. Rapid antigen testing has a very low sensitivity in the diagnosis of bacterial tonsillitis, but more accurate tests take longer to deliver results. Bacteria are cultured from few people with tonsillitis. Other causes include infectious mononucleosis from Epstein-Barr virus infection, cytomegalovirus, toxoplasmosis, HIV, hepatitis A, and rubella. We conducted a systematic review and aimed to answer the following clinical question: What are the effects of tonsillectomy in children and adults with acute recurrent or chronic throat infections? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 15 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review, we present information relating to the effectiveness and safety of the following interventions: cold-steel tonsillectomy and diathermy tonsillectomy.


The epidemiology of Legionella pneumophila infections.
The study of outbreaks of Legionella pneumophila has been essential in understanding the organism, the disease, and its pathogenesis. Early epidemics defined the clinical spectrum: Pontiac fever is an acute, self-limited, febrile illness with an attack rate of 95% to 100% and an incubation period of 36 hours. In contrast, legionnaires' disease is a life-threatening bronchopneumonia with an attack rate of 2% to 7% and an incubation period of two to ten days. Three times as many males as females are affected with legionnaires' disease, and age, cigarette smoking, and chronic medical disease (particularly immunosuppression) appear to be separate risk factors. Furthermore, L pneumophila is responsible for approximately 1% to 3% of community-acquired pneumonias, 13% of those acquired in the hospital and as many as 26% of atypical pneumonias. Diverse environmental reservoirs have been identified, including cooling systems, potable or domestic water systems, respiratory therapy devices, industrial coolants, and whirlpool spas. Hot water temperature, stagnant water, sediment, and the presence of other microorganisms are important factors in the amplification of the Legionellaceae. Although airborne transmission has been widely suggested, aspiration may be an important mode in certain patients. Regional and national surveillance may identify common sources and allow the introduction of early control measures. The latter have included primarily pulse and continuous hyperchlorination and super-heating hot water systems to 50 to 60 degrees C. Experimental data suggest that ozone and UV light may be useful in the future. Additionally, cooling towers and evaporative condensers have been decontaminated and maintained with a variety of biocides. The prevention of outbreaks requires thoughtful planning, redesign, and good engineering practices.


Long-Term Climatic and Anthropogenic Impacts on Streamwater Salinity in New York State: INCA Simulations Offer Cautious Optimism.
The long-term application of road salts has led to a rise in surface water chloride (Cl-) concentrations. While models have been used to assess the potential future impacts of continued deicing practices, prior approaches have not incorporated changes in climate that are projected to impact hydrogeology in the 21st century. We use an INtegrated CAtchment (INCA) model to simulate Cl- concentrations in the Tioughnioga River watershed. The model was run over a baseline period (1961-1990) and climate simulations from a range of GCMs run over three 30-year intervals (2010-2039; 2040-2069; 2070-2099). Model projections suggest that Cl- concentrations in the two river branches will continue to rise for several decades, before beginning to decline around 2040-2069, with all GCM scenarios indicating reductions in snowfall and associated salt applications over the 21st century. The delay in stream response is most likely attributed to climate change and continued contribution of Cl- from aquifers. By 2100, surface water Cl- concentrations will decrease to below 1960s values. Catchments dominated by urban lands will experience a decrease in average surface water Cl-, although moderate compared to more rural catchments.


Probing the Link among Genomic Cargo, Contact Mechanics, and Nanoindentation in Recombinant Adeno-Associated Virus 2.
Recombinant adeno-associated virus (AAV) is a promising gene therapy vector. To make progress in this direction, the relationship between the characteristics of the genomic cargo and the capsid stability must be understood in detail. The goal of this study is to determine the role of the packaged vector genome in the response of AAV particles to mechanical compression and adhesion to a substrate. Specifically, we used atomic force microscopy to compare the mechanical properties of empty AAV serotype 2 (AAV2) capsids and AAV2 vectors packaging single-stranded DNA or self-complementary DNA. We found that all species underwent partial deformation upon adsorption from buffer on an atomically flat graphite surface. Upon adsorption, a preferred orientation toward the twofold symmetry axis on the capsid, relative to the substrate, was observed. The magnitude of the bias depended on the cargo type, indicating that the interfacial properties may be influenced by cargo. All particles showed a significant relative strain before rupture. Different from interfacial interactions, which were clearly cargo-dependent, the elastic response to directional stress was largely dominated by the capsid properties. Nevertheless, small differences between particles laden with different cargo were measurable; scAAV vectors were the most resilient to external compression. We also show how elastic constant and rupture force data sets can be analyzed according a multivariate conditional probability approach to determine the genome content on the basis of a database of mechanical properties acquired from nanoindentation assays. Implications for understanding how recombinant AAV capsid-genome interactions can affect vector stability and effectiveness of gene therapy applications are discussed.


CD8+ T-cell senescence: no role for mTOR.
Aging is accompanied by immune decline leading to increased incidence of infections and malignancies, given the demographic shift of humans towards an older age the identification of strategies for the manipulation of immunity is an important goal. Evidence implicates mammalian target of rapamycin (mTOR) to be a key modulator of aging and the use of mTOR inhibitors has been shown to ameliorate much age-related pathology; however, recent data suggest that senescent CD8(+) T-cells function independently of mTOR. This review article will challenge the perceived dogma that mTOR universally controls CD8(+) T-cell function.


Inhibition of human alkaline phosphatases by vanadate.
Orthovanadate was shown to be a potent competitive inhibitor (Ki less than 1 microM) of purified alkaline phosphatase from human liver, intestine of kidney. Inhibition was reversed and full enzymic activity restored in the presence of 1mM-adrenaline. Phosphate and vanadate competed for the same binding site on the enzyme.


Target-in-the-loop beam control: basic considerations for analysis and wave-front sensing.
Target-in-the-loop (TIL) wave propagation geometry represents perhaps the most challenging case for adaptive optics applications that are related to maximization of irradiance power density on extended remotely located surfaces in the presence of dynamically changing refractive-index inhomogeneities in the propagation medium. We introduce a TIL propagation model that uses a combination of the parabolic equation describing coherent outgoing-wave propagation, and the equation describing evolution of the mutual correlation function (MCF) for the backscattered wave (return wave). The resulting evolution equation for the MCF is further simplified by use of the smooth-refractive-index approximation. This approximation permits derivation of the transport equation for the return-wave brightness function, analyzed here by the method of characteristics (brightness function trajectories). The equations for the brightness function trajectories (ray equations) can be efficiently integrated numerically. We also consider wave-front sensors that perform sensing of speckle-averaged characteristics of the wave-front phase (TIL sensors). Analysis of the wave-front phase reconstructed from Shack-Hartmann TIL sensor measurements shows that an extended target introduces a phase modulation (target-induced phase) that cannot be easily separated from the atmospheric-turbulence-related phase aberrations. We also show that wave-front sensing results depend on the extended target shape, surface roughness, and outgoing-beam intensity distribution on the target surface. For targets with smooth surfaces and nonflat shapes, the target-induced phase can contain aberrations. The presence of target-induced aberrations in the conjugated phase may result in a deterioration of adaptive system performance.


Cellular interactions of Candida albicans with human oral epithelial cells and enterocytes.
The human pathogenic fungus Candida albicans can cause systemic infections by invading epithelial barriers to gain access to the bloodstream. One of the main reservoirs of C. albicans is the gastrointestinal tract and systemic infections predominantly originate from this niche. In this study, we used scanning electron and fluorescence microscopy, adhesion, invasion and damage assays, fungal mutants and a set of fungal and host cell inhibitors to investigate the interactions of C. albicans with oral epithelial cells and enterocytes. Our data demonstrate that adhesion, invasion and damage by C. albicans depend not only on fungal morphology and activity, but also on the epithelial cell type and the differentiation stage of the epithelial cells, indicating that epithelial cells differ in their susceptibility to the fungus. C. albicans can invade epithelial cells by induced endocytosis and/or active penetration. However, depending on the host cell faced by the fungus, these routes are exploited to a different extent. While invasion into oral cells occurs via both routes, invasion into intestinal cells occurs only via active penetration.


Understanding the individual to implement the ecosystem approach to fisheries management.
Ecosystem-based approaches to fisheries management (EAFMs) have emerged as requisite for sustainable use of fisheries resources. At the same time, however, there is a growing recognition of the degree of variation among individuals within a population, as well as the ecological consequences of this variation. Managing resources at an ecosystem level calls on practitioners to consider evolutionary processes, and ample evidence from the realm of fisheries science indicates that anthropogenic disturbance can drive changes in predominant character traits (e.g. size at maturity). Eco-evolutionary theory suggests that human-induced trait change and the modification of selective regimens might contribute to ecosystem dynamics at a similar magnitude to species extirpation, extinction and ecological dysfunction. Given the dynamic interaction between fisheries and target species via harvest and subsequent ecosystem consequences, we argue that individual diversity in genetic, physiological and behavioural traits are important considerations under EAFMs. Here, we examine the role of individual variation in a number of contexts relevant to fisheries management, including the potential ecological effects of rapid trait change. Using select examples, we highlight the extent of phenotypic diversity of individuals, as well as the ecological constraints on such diversity. We conclude that individual phenotypic diversity is a complex phenomenon that needs to be considered in EAFMs, with the ultimate realization that maintaining or increasing individual trait diversity may afford not only species, but also entire ecosystems, with enhanced resilience to environmental perturbations. Put simply, individuals are the foundation from which population- and ecosystem-level traits emerge and are therefore of central importance for the ecosystem-based approaches to fisheries management.


Predicting changes of body weight, body fat, energy expenditure and metabolic fuel selection in C57BL/6 mice.
The mouse is an important model organism for investigating the molecular mechanisms of body weight regulation, but a quantitative understanding of mouse energy metabolism remains lacking. Therefore, we created a mathematical model of mouse energy metabolism to predict dynamic changes of body weight, body fat, energy expenditure, and metabolic fuel selection. Based on the principle of energy balance, we constructed ordinary differential equations representing the dynamics of body fat mass (FM) and fat-free mass (FFM) as a function of dietary intake and energy expenditure (EE). The EE model included the cost of tissue deposition, physical activity, diet-induced thermogenesis, and the influence of FM and FFM on metabolic rate. The model was calibrated using previously published data and validated by comparing its predictions to measurements in five groups of male C57/BL6 mice (N = 30) provided ad libitum access to either chow or high fat diets for varying time periods. The mathematical model accurately predicted the observed body weight and FM changes. Physical activity was predicted to decrease immediately upon switching from the chow to the high fat diet and the model coefficients relating EE to FM and FFM agreed with previous independent estimates. Metabolic fuel selection was predicted to depend on a complex interplay between diet composition, the degree of energy imbalance, and body composition. This is the first validated mathematical model of mouse energy metabolism and it provides a quantitative framework for investigating energy balance relationships in mouse models of obesity and diabetes.


Simultaneous quantum yield measurements of carbon uptake and oxygen evolution in microalgal cultures.
The photosynthetic quantum yield (Φ), defined as carbon fixed or oxygen evolved per unit of light absorbed, is a fundamental but rarely determined biophysical parameter. A method to estimate Φ for both net carbon uptake and net oxygen evolution simultaneously can provide important insights into energy and mass fluxes. Here we present details for a novel system that allows quantification of carbon fluxes using pH oscillation and simultaneous oxygen fluxes by integration with a membrane inlet mass spectrometer. The pHOS system was validated using Phaeodactylum tricornutum cultured with continuous illumination of 110 μmole quanta m-2 s-1 at 25°C. Furthermore, simultaneous measurements of carbon and oxygen flux using the pHOS-MIMS and photon flux based on spectral absorption were carried out to explore the kinetics of Φ in P. tricornutum during its acclimation from low to high light (110 to 750 μmole quanta m-2 s-1). Comparing results at 0 and 24 hours, we observed strong decreases in cellular chlorophyll a (0.58 to 0.21 pg cell-1), Fv/Fm (0.71 to 0.59) and maximum ΦCO2 (0.019 to 0.004) and ΦO2 (0.028 to 0.007), confirming the transition toward high light acclimation. The Φ time-series indicated a non-synchronized acclimation response between carbon uptake and oxygen evolution, which has been previously inferred based on transcriptomic changes for a similar experimental design with the same diatom that lacked physiological data. The integrated pHOS-MIMS system can provide simultaneous carbon and oxygen measurements accurately, and at the time-resolution required to resolve high-resolution carbon and oxygen physiological dynamics.


Effectiveness of computer-mediated interventions for informal carers of people with dementia-a systematic review.
Caring for a friend or relative with dementia can be burdensome and stressful, and puts carers at increased risk of physical and psychological problems. A number of psychosocial interventions, some delivered by computer, have been developed to support carers. This review evaluates the outcomes of computer-mediated interventions. PsychINFO, MEDLINE, and CINAHL Plus were searched for papers published between January 2000 and September 2012. Study quality was evaluated using a modified version of Downs and Black's (1998) checklist. Fourteen empirical studies, evaluating a range of complex, multifaceted interventions, met inclusion criteria. The most commonly measured variables were carer burden/stress and depression. In general, higher quality studies found that interventions did have an effect on these variables. Two higher quality studies also found that anxiety was reduced following intervention. Most studies found that positive aspects of caring were increased through these interventions, as was carer self-efficacy. There were mixed results in relation to social support, and physical aspects of caring did not seem to be affected. Program impact measures indicated general acceptability of these interventions. The findings support the provision of computer-mediated interventions for carers of people with dementia. Future studies would benefit from design improvements, such as articulating clearly defined aims, having a control group, having adequate statistical power, and measuring a greater range of factors important to carers themselves.


High-throughput proteomics using matrix-assisted laser desorption/ ionization mass spectrometry.
It has become evident that the mystery of life will not be deciphered just by decoding its blueprint, the genetic code. In the life and biomedical sciences, research efforts are now shifting from pure gene analysis to the analysis of all biomolecules involved in the machinery of life. One area of these postgenomic research fields is proteomics. Although proteomics, which basically encompasses the analysis of proteins, is not a new concept, it is far from being a research field that can rely on routine and large-scale analyses. At the time the term proteomics was coined, a gold-rush mentality was created, promising vast and quick riches (i.e., solutions to the immensely complex questions of life and disease). Predictably, the reality has been quite different. The complexity of proteomes and the wide variations in the abundances and chemical properties of their constituents has rendered the use of systematic analytical approaches only partially successful, and biologically meaningful results have been slow to arrive. However, to learn more about how cells and, hence, life works, it is essential to understand the proteins and their complex interactions in their native environment. This is why proteomics will be an important part of the biomedical sciences for the foreseeable future. Therefore, any advances in providing the tools that make protein analysis a more routine and large-scale business, ideally using automated and rapid analytical procedures, are highly sought after. This review will provide some basics, thoughts and ideas on the exploitation of matrix-assisted laser desorption/ ionization in biological mass spectrometry - one of the most commonly used analytical tools in proteomics - for high-throughput analyses.


IoT-based user-driven service modeling environment for a smart space management system.
The existing Internet environment has been extended to the Internet of Things (IoT) as an emerging new paradigm. The IoT connects various physical entities. These entities have communication capability and deploy the observed information to various service areas such as building management, energy-saving systems, surveillance services, and smart homes. These services are designed and developed by professional service providers. Moreover, users' needs have become more complicated and personalized with the spread of user-participation services such as social media and blogging. Therefore, some active users want to create their own services to satisfy their needs, but the existing IoT service-creation environment is difficult for the non-technical user because it requires a programming capability to create a service. To solve this problem, we propose the IoT-based user-driven service modeling environment to provide an easy way to create IoT services. Also, the proposed environment deploys the defined service to another user. Through the personalization and customization of the defined service, the value and dissemination of the service is increased. This environment also provides the ontology-based context-information processing that produces and describes the context information for the IoT-based user-driven service.


Differences in the metabolism of very-low-density lipoproteins by isolated beating-heart cells and the isolated perfused rat heart. Evidence for collagenase-released extracellular lipoprotein lipase.
1. The metabolism of VLD lipoproteins (very-low-density lipoproteins) was studied in intact isolated beating-heart cells and isolated perfused rat heart from starved animals by using [14C]triacylglycerol fatty acid-labelled VLD lipoprotein prepared from rats previously injected with [1-14C]palmitate. 2. 14C-labelled VLD lipoprotein was metabolized by the isolated perfused heart, but was only minimally metabolized by the heart cells unless an exogenous source of lipoprotein lipase was added. 3. Measurements of lipoprotein lipase at pH 7.4 with the natural substrate 14C-labelled VLD lipoprotein indicated that during collagenase perfusion of the heart the enzyme was released into the perfusate, the activity released being proportional to the concentration of collagenase used. Lipoprotein lipase activity in homogenates of hearts that had been perfused with collagenase showed a corresponding loss of activity. 4. At high perfusate concentrations of collagenase, inactivation of the released lipoprotein lipase occurred. 5. Lipoprotein lipase activity was largely undetectable in the homogenate of the isolated heart cells. 6. It is concluded that the lipoprotein lipase responsible for the hydrolysis of VLD lipoprotein triacylglycerol is predominantly located externally to the heart muscle cells and that its release can be facilitated by perfusion of the heart with bacterial collagenase.


Food insecurity, depression and the modifying role of social support among people living with HIV/AIDS in rural Uganda.
Depression is common among people living with HIV/AIDS and contributes to a wide range of worsened HIV-related outcomes, including AIDS-related mortality. Targeting modifiable causes of depression, either through primary or secondary prevention, may reduce suffering as well as improve HIV-related outcomes. Food insecurity is a pervasive source of uncertainty for those living in resource-limited settings, and cross-sectional studies have increasingly recognized it as a critical determinant of poor mental health. Using cohort data from 456 men and women living with HIV/AIDS initiating HIV antiretroviral therapy in rural Uganda, we sought to (a) estimate the association between food insecurity and depression symptom severity, (b) assess the extent to which social support may serve as a buffer against the adverse effects of food insecurity, and (c) determine whether the buffering effects are specific to certain types of social support. Quarterly data were collected by structured interviews and blood draws. The primary outcome was depression symptom severity, measured by a modified Hopkins Symptom Checklist for Depression. The primary explanatory variables were food insecurity, measured with the Household Food Insecurity Access Scale, and social support, measured with a modified version of the Functional Social Support Questionnaire. We found that food insecurity was associated with depression symptom severity among women but not men, and that social support buffered the impacts of food insecurity on depression. We also found that instrumental support had a greater buffering influence than emotional social support. Interventions aimed at improving food security and strengthening instrumental social support may have synergistic beneficial effects on both mental health and HIV outcomes among PLWHA in resource-limited settings.


Supporting crop pollinators with floral resources: network-based phenological matching.
The production of diverse and affordable agricultural crop species depends on pollination services provided by bees. Indeed, the proportion of pollinator-dependent crops is increasing globally. Agriculture relies heavily on the domesticated honeybee; the services provided by this single species are under threat and becoming increasingly costly. Importantly, the free pollination services provided by diverse wild bee communities have been shown to be sufficient for high agricultural yields in some systems. However, stable, functional wild bee communities require floral resources, such as pollen and nectar, throughout their active season, not just when crop species are in flower. To target floral provisioning efforts to conserve and support native and managed bee species, we apply network theoretical methods incorporating plant and pollinator phenologies. Using a two-year dataset comprising interactions between bees (superfamily Apoidea, Anthophila) and 25 native perennial plant species in floral provisioning habitat, we identify plant and bee species that provide a key and central role to the stability of the structure of this community. We also examine three specific case studies: how provisioning habitat can provide temporally continuous support for honeybees (Apis mellifera) and bumblebees (Bombus impatiens), and how resource supplementation strategies might be designed for a single genus of important orchard pollinators (Osmia). This framework could be used to provide native bee communities with additional, well-targeted floral resources to ensure that they not only survive, but also thrive.


Linking canonical microcircuits and neuronal activity: Dynamic causal modelling of laminar recordings.
Neural models describe brain activity at different scales, ranging from single cells to whole brain networks. Here, we attempt to reconcile models operating at the microscopic (compartmental) and mesoscopic (neural mass) scales to analyse data from microelectrode recordings of intralaminar neural activity. Although these two classes of models operate at different scales, it is relatively straightforward to create neural mass models of ensemble activity that are equipped with priors obtained after fitting data generated by detailed microscopic models. This provides generative (forward) models of measured neuronal responses that retain construct validity in relation to compartmental models. We illustrate our approach using cross spectral responses obtained from V1 during a visual perception paradigm that involved optogenetic manipulation of the basal forebrain. We find that the resulting neural mass model can distinguish between activity in distinct cortical layers - both with and without optogenetic activation - and that cholinergic input appears to enhance (disinhibit) superficial layer activity relative to deep layers. This is particularly interesting from the perspective of predictive coding, where neuromodulators are thought to boost prediction errors that ascend the cortical hierarchy.


Comparative Genomics of Marine Bacteria from a Historically Defined Plastic Biodegradation Consortium with the Capacity to Biodegrade Polyhydroxyalkanoates.
Biodegradable and compostable plastics are getting more attention as the environmental impacts of fossil-fuel-based plastics are revealed. Microbes can consume these plastics and biodegrade them within weeks to months under the proper conditions. The biobased polyhydroxyalkanoate (PHA) polymer family is an attractive alternative due to its physicochemical properties and biodegradability in soil, aquatic, and composting environments. Standard test methods are available for biodegradation that employ either natural inocula or defined communities, the latter being preferred for standardization and comparability. The original marine biodegradation standard test method ASTM D6691 employed such a defined consortium for testing PHA biodegradation. However, the taxonomic composition and metabolic potential of this consortium have never been confirmed using DNA sequencing technologies. To this end, we revived available members of this consortium and determined their phylogenetic placement, genomic sequence content, and metabolic potential. The revived members belonged to the Bacillaceae, Rhodobacteraceae, and Vibrionaceae families. Using a comparative genomics approach, we found all the necessary enzymes for both PHA production and utilization in most of the members. In a clearing-zone assay, three isolates also showed extracellular depolymerase activity. However, we did not find classical PHA depolymerases, but identified two potentially new extracellular depolymerases that resemble triacylglycerol lipases.


Betamethasone and the rhesus fetus: effect on lung morphometry and connective tissue.
Pregnant rhesus monkeys (Macaca mulatta) at 67 to 85% of term pregnancy were treated with betamethasone for 3 days and then delivered by cesarean section. These treated fetuses had larger lung volumes (32.6 +/- 1.8 ml/kg of body weight) compared to gestational age-matched controls (22.9 +/- 3.2 ml/kg of body weight; P less than 0.025) but no alterations in surfactant properties as measured by amniotic fluid L/S ratios, alveolar deflation stability, or lung phosphatidylcholine. These findings suggest that betamethasone effects an increase in fetal lung volume by some method other than alteration in alveolar surfactant concentrations. Results also demonstrated an 11% increase in the collagen to elastin concentration in the treated fetuses as compared to the control animals (P less than 0.01), suggesting alterations in lung connective tissue. Morphometric studies done on the air-fixed inflated lung demonstrated a decrease in the number of alveoli per unit volume of lung among the treated animals (0.95 +/- 0.07 x 10(6)) compared to the control animals (1.19 +/- 0.08 x 10(6); P less than 0.025) and a reduction in the mean surface area of the lungs of the treated animals (506 +/- 10 cm2 per cm3) compared to the control animals (561 +/- 9 cm2 per cm3; P less than 0.005). These findings suggest that at least part of the increased maximal lung volumes is related to increased alveolar distensibility. Together, these pressure volume findings, biochemical studies, and morphometric analyses indicate that a major effect of betamethasone on the rhesus fetal lung is to alter lung connective tissue characteristics. Alterations in lung surfactant appear to be of less functional significance in this rhesus fetal model. The disparity between these findings and other animal studies might be due to differences in species, the preparation, or the method of glucocorticoid administration.


First Pregnancy Characteristics, Postmenopausal Breast Density, and Salivary Sex Hormone Levels in a Population at High Risk for Breast Cancer.
It remains unknown if later life breast cancer risk as determined by reproductive history is mediated by postmenopausal breast density and/or sex steroid levels. Increased breast density is a strong surrogate for future breast cancer risk. A cross-sectional study with a longitudinal follow up for breast health outcomes evaluated women without breast cancer (n = 1,023; 682 = parous), drawn from a high risk postmenopausal population, with questionnaire reported reproductive histories. The questionnaire was linked to prospective screening mammogram breast density measurements, and saliva biospecimens that were used to assess sex steroid hormone levels. Expected age and postmenopause related declines in salivary estradiol (E), progesterone (P), dehydroepiandrosterone (DHEA) and testosterone (T) levels were observed. This was most pronounced for DHEA and T, which were also the only postmenopausal hormone levels significantly associated with any reproductive characteristics: parity and breast feeding for DHEA, age-at-first birth for T. Postmenopausal breast density was borderline significantly lower with parity and higher body mass index (BMI). After multivariate analysis, T was the only hormone level to retain any association (negative, p<0.05) with breast density. While reproductive characteristics, in particular parity, generally demonstrated independent associations with postmenopausal breast density and E, P and DHEA levels, T levels showed concordant inverse associations with age-at-first birth and breast density. These findings suggest that reproductive effects and later life salivary sex steroid hormone levels may have independent effects on later life breast density and cancer risk.


Intranasal corticosteroids in management of acute sinusitis: a systematic review and meta-analysis.
Acute sinusitis is a common condition in ambulatory care, where it is frequently treated with antibiotics, despite little evidence of their benefit. Intranasal corticosteroids might relieve symptoms; however, evidence for this benefit is currently unclear. We performed a systematic review and meta-analysis of the effects of intranasal corticosteroids on the symptoms of acute sinusitis. We searched MEDLINE, EMBASE, the Cochrane Central register of Controlled Trials (CENTRAL), and Centre for Reviews and Dissemination databases until February 2011 for studies comparing intranasal corticosteroids with placebo in children or adults having clinical symptoms and signs of acute sinusitis or rhinosinusitis in ambulatory settings. We excluded chronic/allergic sinusitis. Two authors independently extracted data and assessed the studies' methodologic quality. We included 6 studies having a total of 2,495 patients. In 5 studies, antibiotics were prescribed in addition to corticosteroids or placebo. Intranasal corticosteroids resulted in a significant, small increase in resolution of or improvement in symptoms at days 14 to 21 (risk difference [RD] = 0.08; 95% CI, 0.03-0.13). Analysis of individual symptom scores revealed most consistently significant benefits for facial pain and congestion. Subgroup analysis by time of reported outcomes showed a significant beneficial effect at 21 days (RD = 0.11; 95% CI, 0.06-0.17), but not at 14 to 15 days (RD = 0.05; 95% CI, -0.01 to 0.11). Meta-regression analysis of trials using different doses of mometasone furoate showed a significant dose-response relationship (P=.02). Intranasal corticosteroids offer a small therapeutic benefit in acute sinusitis, which may be greater with high doses and with courses of 21 days' duration. Further trials are needed in antibiotic-naïve patients.


An embedded subnetwork of highly active neurons in the neocortex.
Unbiased methods to assess the firing activity of individual neurons in the neocortex have revealed that a large proportion of cells fire at extremely low rates (<0.1 Hz), both in their spontaneous and evoked activity. Thus, firing in neocortical networks appears to be dominated by a small population of highly active neurons. Here, we use a fosGFP transgenic mouse to examine the properties of cells with a recent history of elevated activity. FosGFP-expressing layer 2/3 pyramidal cells fired at higher rates compared to fosGFP(-) neurons, both in vivo and in vitro. Elevated activity could be attributed to increased excitatory and decreased inhibitory drive to fosGFP(+) neurons. Paired-cell recordings indicated that fosGFP(+) neurons had a greater likelihood of being connected to each other. These findings indicate that highly active, interconnected neuronal ensembles are present in the neocortex and suggest these cells may play a role in the encoding of sensory information.


Variegated gene expression caused by cell-specific long-range DNA interactions.
Mammalian genomes contain numerous regulatory DNA sites with unknown target genes. We used mice with an extra β-globin locus control region (LCR) to investigate how a regulator searches the genome for target genes. We find that the LCR samples a restricted nuclear subvolume, wherein it preferentially contacts genes controlled by shared transcription factors. No contacted gene is detectably upregulated except for endogenous β-globin genes located on another chromosome. This demonstrates genetically that mammalian trans activation is possible, but suggests that it will be rare. Trans activation occurs not pan-cellularly, but in 'jackpot' cells enriched for the interchromosomal interaction. Therefore, cell-specific long-range DNA contacts can cause variegated expression.


Evolving systems biology approaches to understanding non-coding RNAs in pulmonary hypertension.
Our appreciation of the roles of non-coding RNAs, in particular microRNAs, in the manifestation of pulmonary hypertension (PH) has advanced considerably over the past decade. Comprised of small nucleotide sequences, microRNAs have demonstrated critical and broad regulatory roles in the pathogenesis of PH via the direct binding to messenger RNA transcripts for degradation or inhibition of translation, thereby exerting a profound influence on cellular activity. Yet, as inherently pleiotropic molecules, microRNAs have been difficult to study using traditional, reductionist approaches alone. With the advent of high-throughput -omics technologies and more advanced computational modelling, the study of microRNAs and their multi-faceted and complex functions in human disease serves as a fertile platform for the application of systems biology methodologies in combination with traditional experimental techniques. Here, we offer our viewpoint of past successes of systems biology in elucidating the otherwise hidden actions of microRNAs in PH, as well as areas for future development to integrate these strategies into the discovery of RNA pathobiology in this disease. We contend that such successful applications of systems biology in elucidating the functional architecture of microRNA regulation will further reveal the molecular mechanisms of disease, while simultaneously revealing potential diagnostic and therapeutic strategies in disease amelioration.


Investigation of the N-Glycosylation of the SARS-CoV-2 S Protein Contained in VLPs Produced in Nicotiana benthamiana.
The emergence of the SARS-CoV-2 coronavirus pandemic in China in late 2019 led to the fast development of efficient therapeutics. Of the major structural proteins encoded by the SARS-CoV-2 genome, the SPIKE (S) protein has attracted considerable research interest because of the central role it plays in virus entry into host cells. Therefore, to date, most immunization strategies aim at inducing neutralizing antibodies against the surface viral S protein. The SARS-CoV-2 S protein is heavily glycosylated with 22 predicted N-glycosylation consensus sites as well as numerous mucin-type O-glycosylation sites. As a consequence, O- and N-glycosylations of this viral protein have received particular attention. Glycans N-linked to the S protein are mainly exposed at the surface and form a shield-masking specific epitope to escape the virus antigenic recognition. In this work, the N-glycosylation status of the S protein within virus-like particles (VLPs) produced in Nicotiana benthamiana (N. benthamiana) was investigated using a glycoproteomic approach. We show that 20 among the 22 predicted N-glycosylation sites are dominated by complex plant N-glycans and one carries oligomannoses. This suggests that the SARS-CoV-2 S protein produced in N. benthamiana adopts an overall 3D structure similar to that of recombinant homologues produced in mammalian cells.


Can child safeguarding training be improved?: findings of a multidisciplinary audit.
Child protection has become a very poignant subject in the UK. The Laming report into the death of Victoria Climbié led to the implementation of multidisciplinary safeguarding policies and training for healthcare professionals, social services staff and police. However, many dental practitioners, as well as other healthcare professionals, have little confidence when reporting their concerns and reducing the 'gap' between suspicion and reporting (Laming in The victoria climbie inquiry: report of an inquiry by Lord Laming, 2003. https://www.gov.uk/government/publications/the-victoria-climbie-inquiry-report-of-an-inquiry-by-lord-laming ). Our audit aimed to identify and address the barriers of reporting safeguarding concerns amongst the hospital team. Questionnaires were distributed to staff at Surrey and Sussex Healthcare National Health Service Trust with a valid Safeguarding Children Level 3 certificate in order to assess their knowledge of safeguarding children. Changes to traditional safeguarding training (Group 1) were implemented to include a broader range of speakers, each speaking for shorter times with more personal and focused presentations (Groups 2 and 3). Three cohorts of participants were assessed including healthcare assistants, nurses, dentists, and doctors. Group 1 (n = 100) reported 64% experience of reporting compared with group 2 (n = 100) 43% and group 3 (n = 76) 51%. Confidence was higher in those with more experience in child protection. The most common barrier was the uncertainty of diagnosis. More barriers to reporting existed in the new style of training in groups 2 and 3. The scenarios were answered with appropriate concern and reporting by groups 1 and 2, however, less for group 3. Experienced and trained practitioners are more likely to refer children to child protection teams when they have concerns of abuse or neglect. Personalising training was shown to be less effective and the focus should be more on diagnosis and local protocols. Early training from undergraduate level was a unanimous request. Focused training on diagnosis and local protocols, accompanied by bespoke teaching for specific specialties would be the most constructive tool for safeguarding children. Exploring modern methods such as simulation-based training could be effective. Structured forms and local policies that are familiar to clinicians prevent omissions and encourage professional awareness.


To grow old in southern Italy: a comprehensive description of the old and oldest old in Calabria.
The unprecedented growth of the elderly population is posing important social and medical problems as management of this population is highly demanding in terms of assistance and care. Consequently, many studies are focusing on the elderly subjects in order to better understand their needs by identifying various environmental, social, psychological, and genetic factors determining the quality of ageing. Our aim was to carry out a survey of the elderly Calabrian population in order to highlight the social and medical conditions of this continuously growing population group. We have been monitoring the elderly population of Calabria for more than 10 years. For the present study, we collected data regarding 853 subjects by using two specific questionnaires, one for the subjects older than 90 years (400 subjects) and one for the subjects aged between 65 and 85 years (453 subjects). The survey allowed us to carry out an extensive description of the ageing Calabrian population regarding the sociodemographic characteristics, living conditions, cognitive functioning, level of independence in activities of daily living, former and current diseases and health disorders. We could notice that males were in a better condition than females. In fact, male subjects turned out to have better physical performance and lower comorbidity, although their life expectancy is lower. Ultranonagenarians had a lower incidence of serious diseases (such as diabetes, osteoporosis and gastric ulcer), but a higher incidence of non-fatal chronic, debilitating conditions (cataract and bronchitis among others). The data we collected and analyzed offer a portrait of elderly Calabrian subjects, on who they are, how they feel, which social and psychological resources they have, and what their health status is. Analysis of the data highlighted that they are characterized by a lower physical performance in comparison to other European populations. Finally, the data presented here may also serve as a valuable source of information to characterize the ageing Calabrian population and improve the care of these subjects.


Intradermal implantation of bovine collagen. Humoral immune responses associated with clinical reactions.
A special collagen implant (Zyderm) (ZCI) is a biomaterial used for the correction of dermal contour deformities. Although infrequent, reactions believed to be of an immunologic nature have followed treatment. To investigate whether humoral immunity is associated with these reactions, we studied 40 patients for the presence of anti-ZCI antibodies using an enzyme-linked immunosorbent assay. Ten patients who had had adverse treatment reactions uniformly exhibited circulating anti-ZCI antibodies. Twenty-nine of 30 control patients, including nine who had received ZCI without adverse reaction, failed to produce the high levels of antibodies found in all clinical reactors. This difference was statistically significant. Additional investigations confirmed that the antibodies studied were directed primarily against the bovine collagen component of the ZCI. These data suggest that the humoral immune system is capable of recognizing ZCI and that the presence of antibodies to the ZCI correlates with the occurrence of adverse reactions.


In vitro biological responses to nanofibrillated cellulose by human dermal, lung and immune cells: surface chemistry aspect.
Nanocellulose, and particularly nanofibrillated cellulose (NFC), has been proposed for a diversity of applications in industry and in the biomedical field. Its unique physicochemical and structural features distinguish nanocellulose from traditional materials and enable its use as an advance nanomaterial. However, its nanoscale features may induce unknown biological responses. Limited studies with NFC are available and the biological impacts of its use have not been thoroughly explored. This study assesses the in vitro biological responses elicited by wood-derived NFC gels, when human dermal fibroblasts, lung MRC-5 cells and THP-1 macrophage cells are exposed to the nanomaterial. Furthermore, whether the presence of surface charged groups (i.e. carboxymethyl and hydroxypropyltrimethylammonium groups) on NFC can induce distinct biological responses is investigated. The introduction of surface charged groups resulted in individual nanofibrils, while fibril aggregates predominated in the unmodified NFC gel suspensions as observed by transmission electron microscopy. In the presence of proteins, the surface modified NFCs formed compact agglomerates while the agglomeration pattern of the unmodified NFC was similar in the presence of proteins and in physiological buffer. Unmodified and modified NFC gels did not induce cytotoxicity in human dermal fibroblasts, lung and macrophage cells. No significant ROS production by THP-1 macrophages was found and no cellular uptake was observed. However, an inflammatory response was detected when THP-1 macrophages were treated with unmodified NFC as assessed by an increase in TNF-α and IL1-β levels, an effect that was absent when surface charged groups were introduced into NFC. Taken together, the data presented here show the absence of cytotoxic effects associated with the exposure to unmodified, carboxymethylated and hydroxypropyltrimethylammonium-modified NFCs. Unmodified NFC presented a pro-inflammatory effect which can be further moderated by introducing surface modifications such as carboxymethyl and hydroxypropyltrimethylammonium groups into the nanofibrils. The present findings suggest that the inflammatory response to NFC might be driven by the material surface chemistry, and thus open up for the possibility of designing safe nanocellulose materials.


Fixation of a trabecular metal knee arthroplasty component. A prospective randomized study.
Uncemented tibial components of total knee replacements have lower survival rates than cemented components. Radiostereometric analysis is a highly accurate, effective tool for investigating new implant designs. The purpose of this study was to compare an uncemented Trabecular Metal tibial component with a conventional cemented stemmed tibial component of the same design. Seventy subjects undergoing total knee replacement were randomized to receive either the Trabecular Metal or the cemented tibial component. Radiostereometric analysis of micromotion of the tibial components was performed postoperatively at six, twelve, and twenty-four months, and the maximum total point motion of the implant and three-dimensional translations and rotations were recorded. Follow-up was complete for twenty-eight subjects in the Trabecular Metal group and twenty-one subjects in the cemented group. A subset of the Trabecular Metal components migrated extensively in the postoperative period, but all stabilized by one year and the proportion considered to be at risk for early aseptic loosening was 0.0 (95% confidence interval, 0.0 to 0.12) in the group as a whole. Four cemented components were considered to be at risk for early aseptic loosening (proportion at risk, 0.19; 95% confidence interval, 0.08 to 0.4). This study suggests that the Trabecular Metal component may be an effective alternative to the standard cemented tibial component.


A survey of general dental practitioners in the North West of England concerning the dental care of patients following head and neck radiotherapy.
The aim of this survey was to investigate the views of general dental practitioners (GDPs) on their perceived roles and the barriers regarding dental care of patients following head and neck radio-therapy. From a total of 1163 GDPs on the Mersey Postgraduate Dental Deanery mailing list, 369 were selected at random. Questionnaires were sent out in February 2010 followed by reminders a month later. A study-specific questionnaire was piloted prior to the survey. One hundred and ninety-eight of the potential 336 respondents returned valid questionnaires, a response rate of 59%. They did not respond to all questions. Of those who responded, 99/188 (53%) were either 'not at all' or 'little' happy about managing these patients and 118/183 (64%) and 100/173 (58%), respectively, perceived that complex management and the new General Dental Services (nGDS) contract introduced in 2006 were 'quite a bit' or 'very much' barriers to treatment. The majority of the respondents felt that they were 'quite a bit' or 'very much' happy to carry out routine fillings (177/195; 90%), periodontal treatment (166/195; 85%), removable dentures (161/195; 83%), crown and bridge work (123/192; 64%), and root canal therapy (114/195; 58%) but only 53/191 (28%) to perform dental extractions. Over half of the respondents felt that they had 'quite a bit' or a 'main role' in managing radiotherapy caries, xerostomia, detecting recurrence and offering smoking-cessation advice. The majority of the GDPs who responded had been involved in the management of patients who had undergone radio-therapy to the head and neck. A substantial number perceived barriers to care, such as the complexity of the treatment and the nGDS contract. These findings need further investigation. Continuing professional development would be helpful to improve GDPs' confidence in dealing with this group of patients.


Fussy feeders: phyllosoma larvae of the Western Rocklobster (Panulirus cygnus) demonstrate prey preference.
The Western Rocklobster (Panulirus cygnus) is the most valuable single species fishery in Australia and the largest single country spiny lobster fishery in the world. In recent years a well-known relationship between oceanographic conditions and lobster recruitment has become uncoupled, with significantly lower recruitment than expected, generating interest in the factors influencing survival and development of the planktonic larval stages. The nutritional requirements and wild prey of the planktotrophic larval stage (phyllosoma) of P. cygnus were previously unknown, hampering both management and aquaculture efforts for this species. Ship-board feeding trials of wild-caught mid-late stage P. cygnus phyllosoma in the eastern Indian Ocean, off the coast of Western Australia, were conducted in July 2010 and August-September 2011. In a series of experiments, phyllosoma were fed single and mixed species diets of relatively abundant potential prey items (chaetognaths, salps, and krill). Chaetognaths were consumed in 2-8 times higher numbers than the other prey, and the rate of consumption of chaetognaths increased with increasing concentration of prey. The highly variable lipid content of the phyllosoma, and the fatty acid profiles of the phyllosoma and chaetognaths, indicated they were from an oligotrophic oceanic food chain where food resources for macrozooplankton were likely to be constrained. Phyllosoma fed chaetognaths over 6 days showed significant changes in some fatty acids and tended to accumulate lipid, indicating an improvement in overall nutritional condition. The discovery of a preferred prey for P. cygnus will provide a basis for future oceanographic, management and aquaculture research for this economically and ecologically valuable species.


A role for CD5 in TCR-mediated signal transduction and thymocyte selection.
CD5 is a transmembrane protein that is expressed on the surface of T cells and a subset of B cells. The absence of CD5 rendered thymocytes hyperresponsive to stimulation through the T cell antigen receptor (TCR) in vitro. Selection of T cells expressing three distinct transgenic TCRs was also abnormal in CD5-deficient mice. These observations indicate that CD5 can influence the fate of developing thymocytes by acting as a negative regulator of TCR-mediated signal transduction.