Practicality of wavelength selection to improve signal-to-noise ratio in near-infrared spectroscopy.
Near-infrared spectroscopy (NIRS), which can be used to detect changes in the concentration of oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) in tissue by using illumination at two different wavelengths, is often applied to noninvasive measurements of human brain functions. It is common to use two wavelengths that are on opposite sides of the point where the optical absorptions of oxy- and deoxy-Hb are equal (about 800 nm) but an optimal wavelength pair has not yet been determined. In this study, we conducted simultaneous recordings at five wavelengths (678, 692, 750, 782, and 830 nm) to determine the best wavelength for pairing with 830 nm. A theory suggests that pairing a shorter wavelength with 830 nm can provide more sensitivity because of the larger difference in absorption coefficients of hemoglobin between two wavelengths. The changes measured in four cortical areas (frontal, occipital, parietal, and temporal) showed that the noise level when the 678-, 692-, and 750-nm wavelengths were paired with 830 nm was usually lower than when the 782-nm wavelength was paired with 830 nm, which is consistent with theoretical prediction. Moreover, the signal-to-noise ratios (S/Ns) and wavelength dependencies of the power detected in all areas and subjects together suggest that the 692-nm pairing had the highest S/N. This suggests that the optimal wavelengths depend on not only the difference in the absorption coefficients of hemoglobin but also on the optical properties in the measurement area, which affect the strength of the attenuation data. The 692-nm wavelength is thus a more optimal choice than wavelengths around 780 nm for pairing with 830 nm to measure Hb changes induced by cortical activation. The improved S/N enables more sensitive statistical analysis, which is essential to functional mapping with NIRS.


The Italian Code of Medical Deontology: characterizing features of its 2014 edition.
The latest edition of the Italian Code of Medical Deontology has been released by the Italian Federation of the Registers of Physicians and Dentists in May 2014 (1). The previous edition of the Italian Code dated back to 2006 (2), and it has been integrated and updated by a multi-professional and inter-disciplinary panel involving, besides physicians, representatives of scientific societies and trade unions, jurisconsults and experts in bioethics....


Expression profiles of adult T-cell leukemia-lymphoma and associations with clinical responses to zidovudine and interferon alpha.
Adult T-cell leukemia-lymphoma (ATLL) is an HTLV-1-associated lymphoproliferative malignancy that is frequently fatal. We compared gene expression profiles (GEPs) of leukemic specimens from nine patients with ATLL at the time of diagnosis and immediately after combination therapy with zidovudine (AZT) and interferon alpha (IFNalpha). GEPs were also related to genetic aberrations determined by comparative genomic hybridization. We identified several genes anomalously over-expressed in the ATLL leukemic cells at the mRNA level, including LYN, CSPG2, and LMO2, and confirmed LMO2 expression in ATLL cells at the protein level. In vivo AZT-IFNalpha therapy evoked a marked induction of interferon-induced genes accompanied by repression of cell-cycle regulated genes, including those encoding ribosomal proteins. Remarkably, patients not responding to AZT-IFNalpha differed most from responding patients in lower expression of these same IFN-responsive genes, as well as components of the antigen processing and presentation apparatus. Demonstration of specific gene expression signatures associated with response to AZT-IFNalpha therapy may provide novel insights into the mechanisms of action in ATLL.


The use of reflective and reasoned portfolios by doctors.
Reflective portfolios have been widely trailed in vocational programmes for health sciences education. While not raised explicitly yet, there is recognition that an essential part of a portfolio may still be missing - that is the experience of theoretical and analytic questioning that should occur after reflection. In this paper, we argue that portfolios require both reflective and reasoned components to provide a more complete range of educational experiences for postgraduate doctors in the pursuit of higher qualifications. We describe the differentiating features between the two components and conclude with some suggestions on how both reflective and reasoned components of portfolios may work synergistically through a series of case studies. The reflective style of portfolio, which is in current use, has been widely accepted as a major advance in postgraduate medical education at all levels. It provides an effective vehicle for encouraging self-consideration and generalizability. It is an important adjunct where it functions as a personal development tool as well as a sophisticated log book. A reasoned or pedagogic element encourages more analytic activities: adding an additional component that can ground the portfolio in theory or research. The portfolio is then able to function in a range of academic spheres and provide a theoretical platform for the wide range of non-clinical empirical work undertaken in clinical settings. The addition of a reasoned component also increases the emphasis on the introduction of new concepts outside the sphere of the learner's experience. A portfolio containing both reflective and reasoned components is then able to function in a range of academic spheres and provide a theoretical platform for the wide range of non-clinical empirical work undertaken in clinical settings. In an iterative mode, such a portfolio element can support a forum for questioning established concepts within a pedagogical environment - the essence of evidence-based practice.


The specificity of allergic reactions. I. Delayed versus Arthus hypersensitivity.
Guinea pigs sensitized with either hen, duck, or goose egg albumin showed delayed hypersensitivity followed by Arthus reactions to the homologous antigen, but tended to have much weaker delayed responses and slower antibody formation to heterologous antigens. Guinea pigs with delayed hypersensitivity to one of the avian antigens had a slower antibody response to a secondary injection of heterologous antigen than to one of the homologous antigen. Sensitization with a protein conjugated with a hapten such as picryl chloride (Pi) or dinitrofluorobenzene (DFB) resulted in delayed hypersensitivity to the homologous conjugate, the homologous protein, and the homologous protein with a heterologous hapten. Circulating antibody and Arthus reactions occurred subsequently to the homologous conjugate, as well as to the homologous hapten attached to a heterologous protein. Delayed hypersensitivity thus seemed associated with the protein moiety, and Arthus responses with the hapten. Anamnestic responses followed injection of an antigen causing delayed hypersensitivity, but not of a hapten not causing delayed reactions. Thus, animals sensitized initially with Pi.HEA, DFB.HEA, or HEA produced antibodies sooner after a secondary injection of Pi.HEA than did unsensitized animals. No anamnestic response resulted when animals sensitized to Pi.BGG were injected with Pi.HEA. Thus, delayed hypersensitivity is indicated to be a preliminary and immature step in the immune process, with specificity directed against broad, more general features of the protein antigen. This intermediate step is followed by production of circulating antibody to any antigen having a similar basic structure, with the specificity of the antibody also directed against smaller immunologically active sites on the antigen molecule.


Electrochemical Polarization Dependence of the Elastic and Electrostatic Driving Forces to Aliovalent Dopant Segregation on LaMnO3.
Segregation of aliovalent dopant cations is a common degradation pathway on perovskite oxide surfaces in energy conversion and catalysis applications. Here we focus on resolving quantitatively how dopant segregation is affected by oxygen chemical potential, which varies over a wide range in electrochemical and thermochemical energy conversion reactions. We employ electrochemical polarization to tune the oxygen chemical potential over many orders of magnitude. Altering the effective oxygen chemical potential causes the oxygen nonstoichiometry to change in the electrode. This then influences the mechanisms underlying the segregation of aliovalent dopants. These mechanisms are (i) the formation of oxygen vacancies that couples to the electrostatic energy of the dopant in the perovskite lattice and (ii) the elastic energy of the dopant due to cation size mismatch, which also promotes the reaction of the dopant with O2 from the gas phase. The present study resolves these two contributions over a wide range of effective oxygen pressures. Ca-, Sr-, and Ba-doped LaMnO3 are selected as model systems, where the dopants have the same charge but different ionic sizes. We found that there is a transition between the electrostatically and elastically dominated segregation regimes, and the transition shifted to a lower oxygen pressure with increasing cation size. This behavior is consistent with the results of our ab initio thermodynamics calculations. The present study provides quantitative insights into how the elastic energy and the electrostatic energy determine the extent of segregation for a given overpotential and atmosphere relevant to the operating conditions of perovskite oxides in energy conversion applications.


Marine nucleosides: structure, bioactivity, synthesis and biosynthesis.
Nucleosides are glycosylamines that structurally form part of nucleotide molecules, the building block of DNA and RNA. Both nucleosides and nucleotides are vital components of all living cells and involved in several key biological processes. Some of these nucleosides have been obtained from a variety of marine resources. Because of the biological importance of these compounds, this review covers 68 marine originated nucleosides and their synthetic analogs published up to June 2014. The review will focus on the structures, bioactivities, synthesis and biosynthetic processes of these compounds.


Palladium nanoparticle formation processes in fluoropolymers by thermal decomposition of organometallic precursors.
Palladium nanoparticles were synthesized directly in solid fluoropolymer films by thermal decomposition of a palladium acetylacetonate precursor molecularly infused in the fluoropolymer matrix. This chemical infusion synthesis technique was studied using transmission electron microscopy along with selective area electron diffraction to gain insight into the nucleation and growth of palladium nanoparticles. Formation of palladium nanoparticles can be correlated with defects in the polymer matrix as well as their associated free volume such that a relationship between average particle size and mean free volume fraction can be constructed. At low processing temperatures, the average particle radius increases monotonically with the processing time but more complicated variations occur for longer times. The growth of nanoparticles was interpreted using a modified diffusion-limited growth model. While nearly monodisperse nanoparticles dispersed throughout the polymer volume were obtained at low processing temperatures, surface percolation of nanoparticles was observed at relatively high temperatures owing to high precursor decomposition and diffusion rates.


Hearing specific and generic measures of the psychosocial impact of hearing aids.
Hearing-specific and generic measures of hearing aid outcome were examined in order (a) to determine their relative sensitivity to hearing aid use and (b) to examine the relationship between pre-hearing aid use expectations and post-use outcomes. Ninety-two hearing-impaired individuals completed some combination of the Abbreviated Profile of Hearing Aid Benefit, Expected Consequences of Hearing Aid Ownership (ECHO), Satisfaction with Amplification in Daily Life (SADL), and Psychosocial Impact of Assistive Devices Scale, and provided reports of their daily and lifetime hearing aid use. In general, (a) the longer individuals wear hearing aids, the more positive the reported outcome, and (b) ECHO scores of non-hearing aid users are higher than SADL scores of new hearing aid users (six weeks to one year of use) but are similar to those obtained from experienced users (greater than one year of use). Between-questionnaire comparisons showed the generic measure to be as sensitive as the hearing aid specific measures. We suggest that generic measures have some advantages over hearing specific measures but that each has a place in the clinic.


Comments on potential health effects of MRI-induced DNA lesions: quality is more important to consider than quantity.
Magnetic resonance imaging (MRI) is increasingly being used in cardiology to detect heart disease and guide therapy. It is mooted to be a safer alternative to imaging techniques, such as computed tomography (CT) or coronary angiographic imaging. However, there has recently been an increased interest in the potential long-term health risks of MRI, especially in the light of the controversy resulting from a small number of research studies reporting an increase in DNA damage following exposure, with calls to limit its use and avoid unnecessary examination, according to the precautionary principle. Overall the published data are somewhat limited and inconsistent; the ability of MRI to produce DNA lesions has yet to be robustly demonstrated and future experiments should be carefully designed to optimize sensitivity and benchmarked to validate and assess reproducibility. The majority of the current studies have focussed on the initial induction of DNA damage, and this has led to comparisons between the reported induction of γH2AX and implied double-strand break (DSB) yields produced following MRI with induction by imaging techniques using ionizing radiation. However, γH2AX is not only a marker of classical double-ended DSB, but also a marker of stalled replication forks and in certain circumstances stalled DNA transcription. Additionally, ionizing radiation is efficient at producing complex DNA damage, unique to ionizing radiation, with an associated reduction in repairability. Even if the fields associated with MRI are capable of producing DNA damage, the lesions produced will in general be simple, similar to those produced by endogenous processes. It is therefore inappropriate to try and infer cancer risk by simply comparing the yields of γH2AX foci or DNA lesions potentially produced by MRI to those produced by a given exposure of ionizing radiation, which will generally be more biologically effective and have a greater probability of leading to long-term health effects. As a result, it is important to concentrate on more relevant downstream end points (e.g. chromosome aberration production), along with potential mechanisms by which MRI may lead to DNA lesions. This could potentially involve a perturbation in homeostasis of oxidative stress, modifying the background rate of endogenous DNA damage induction. In summary, what the field needs at the moment is more research and less fear mongering.


Influences on the water testing behaviors of private well owners.
Many private wells in the United States and Canada already are contaminated, or are at risk of contamination. Regular testing for pathogenic bacteria is one of the most concrete measures well owners can use to determine whether or not their drinking water quality is safe. This study explored the factors and causal relationships that influence well owner water quality testing behavior. In-depth, semi-structured interviews were used to evaluate the stewardship behavior of 22 well owners in Ontario, Canada. Causal networks were created for each interviewee. These were then aggregated to determine key factors and causal relationships. The research revealed that motivations for regular testing include peace of mind and reassurance. Barriers include complacency, inconvenience, and lack of a perceived problem. Knowledge and better information by themselves were found to provide a weak basis for changing behavior. Implications of this research for promoting water testing behavior are discussed.


Trends in selected chronic conditions and behavioral risk factors among women of reproductive age, behavioral risk factor surveillance system, 2001-2009.
Some potentially modifiable risk factors and chronic conditions cause significant disease and death during pregnancy and promote the development of chronic disease. This study describes recent trends of modifiable risk factors and controllable chronic conditions among reproductive-aged women. Data from the 2001 to 2009 Behavioral Risk Factor Surveillance System, a representative state-based telephone survey of health behavior in US adults, was analyzed for 327,917 women of reproductive age, 18 to 44 years. We calculated prevalence ratios over time to assess trends for 4 selected risk factors and 4 chronic conditions, accounting for age, race/ethnicity, education, health care coverage, and individual states. From 2001 to 2009, estimates of 2 risk factors improved: smoking declined from 25.9% to 18.8%, and physical inactivity declined from 25.0% to 23.0%. One risk factor, heavy drinking, did not change. From 2003 to 2009, the estimates for 1 risk factor and 4 chronic conditions worsened: obesity increased from 18.3% to 24.7%, diabetes increased from 2.1% to 2.9%, high cholesterol increased from 10.3% to 13.6%, asthma increased from 13.5% to 16.2%, and high blood pressure increased from 9.0% to 10.1%. All trends were significant after adjustment, except that for heavy drinking. Among women of reproductive age, prevalence of smoking and physical inactivity improved, but prevalence of obesity and all 4 chronic conditions worsened. Understanding reasons for the improvements in smoking and physical activity may support the development of targeted interventions to reverse the trends and help prevent chronic disease and adverse reproductive outcomes among women in this age group.


Method to determine snow albedo values in the ultraviolet for radiative transfer modeling.
For many cases modeled and measured UV global irradiances agree to within +/-5% for cloudless conditions, provided that all relevant parameters for describing the atmosphere and the surface are well known. However, for conditions with snow-covered surfaces this agreement is usually not achievable, because on the one hand the regional albedo, which has to be used in a model, is only rarely available and on the other hand UV irradiance alters with different snow cover of the surface by as much as 50%. Therefore a method is given to determine the regional albedo values for conditions with snow cover by use of a parameterization on the basis of snow depth and snow age, routinely monitored by the weather services. An algorithm is evolved by multiple linear regression between the snow data and snow-albedo values in the UV, which are determined from a best fit of modeled and measured UV irradiances for an alpine site in Europe. The resulting regional albedo values in the case of snow are in the 0.18-0.5 range. Since the constants of the regression depend on the area conditions, they have to be adapted if the method is applied for other sites. Using the algorithm for actual cases with different snow conditions improves the accuracy of modeled UV irradiances considerably. Compared with the use of an average, constant snow albedo, the use of actual albedo values, provided by the algorithm, halves the average deviations between measured and modeled UV global irradiances.


Exhaustive Multi-Parametric Assessment of the Behavioral Array of Daily Activities of Mice Using Cluster and Factor Analysis.
Using automated supervised behavioral assessment software, we recorded and analyzed 24 h non-interrupted recordings of mice for a duration of 11 days. With the assistance of free R programming, we used correlation matrix-based hierarchical clustering and factor analysis to separate the 33 activities into meaningful clusters and groups without losing the exhaustive nature of the findings. These groups represent novel meaningful behavioral patterns exhibited by mice in home cage. Thirty-three activities were separated into 5 clusters based on dissimilarity between activities and 6 factors based on statistical modeling. Using these two methods, we describe and compare behavioral arrays of two groups of animals: 1. Continuously recorded for 11 days in social isolation and 2. Intermittently socially isolated for recording on days 1, 3, 5, 8, and 10, while socializing on the other days. This is the first work to our knowledge that interprets mouse home cage activities throughout a 24 h period and proposes a base line of a daily routine of a healthy C57Bl/6J mouse that can be used for various experimental paradigms, including disease, neuroinflammation, or drug testing to trace behavioral changes that follow intervention. In this work, we defined the necessary acclimatization period for the 24 h recording paradigm of home cage behavior. We demonstrated the behavioral changes that are associated with the effect of social isolation, intermittent socialization, and re-introduction to a familiar home cage. We provide the full description of the codes used in R.


Yersinia enterocolitica type III secretion: evidence for the ability to transport proteins that are folded prior to secretion.
Pathogenic Yersinia species (Y. enterocolitica, Y. pestis, Y. pseudotuberculosis) share a type three secretion system (TTSS) which allows translocation of effector proteins (called Yops) into host cells. It is believed that proteins are delivered through a hollow needle with an inner diameter of 2-3 nm. Thus transport seems to require substrates which are essentially unfolded. Recent work from different groups suggests that the Yersinia TTSS cannot accommodate substrates which are folded prior to secretion. It was suggested that folding is prevented either by co-translational secretion or by the assistance of specific Yop chaperones (called Sycs). In this study we have fused YopE secretion signals of various length to the mouse dihydrofolate reductase (DHFR) in order to analyse the DHFR folding state prior to secretion. We could demonstrate that secretion-deficient as well as secretion-competent YopE-DHFR fusions complexed to SycE can be efficiently purified from Yersinia cytosol by affinity chromatography using methotrexate-agarose. This implies the folding of the DHFR fusion moiety despite SycE binding and contradicts the previously presented model of folding inhibition by chaperone binding. Secretion-deficient YopE-DHFR fusions caused severe jamming of the TTSS. This observation contradicts the co-translational secretion model. We present evidence that the Yersinia TTSS is familiar with the processing of transport substrates which are folded prior to secretion. We therefore predict that an unfoldase is involved in type III secretion.


Slow and steady wins the race: The behaviour and welfare of commercial faster growing broiler breeds compared to a commercial slower growing breed.
Broilers have been bred for fast growth which has led to welfare problems such as high mortality, lameness and skin lesions. Slower growing breeds are thought to have better welfare but are not as efficient in production. This study investigated welfare, behaviour, production and meat quality of faster growing broilers from three main commercial broiler companies (breeds FA, FB and FC) with a commercially available slower growing breed (Hubbard JA757, S). Four hundred birds of each breed (total 1600 birds) were reared in pens of 50 birds, 8 per breed (total 32 pens). Home pen behaviour was recorded once a week in hourly scan samples to get behavioural time budgets. Welfare Assessments (WA) were done when the average bird weight per breed was 2.2 and 2.5kg. Birds and feed supplied were regularly weighed by pen and Feed Conversion Ratio (FCR) and Average Daily Gain (ADG) were calculated at 2.2kg. Birds were then slaughtered and meat quality measures were taken. S and FC had lower mortality and culls due to lameness (P<0.05 for both). Breeds FA, FB and FC grew faster, ate less feed and had better FCR and ADG (P<0.05 for all). S had scores indicating higher welfare for the majority of WA measures and spent more time active and less time sitting, feeding and drinking than the other breeds (P<0.05 for all). Faster growing breeds had more breast meat and S had more leg meat; although S had better meat quality scores (P<0.05). Overall, S birds have improved welfare in terms of activity and welfare measure scores compared to the other breeds but take longer to reach slaughter weight and are not as efficient in production measures. However if lower mortality and improved meat quality are taken into account, as well as the premium price paid for these birds, slower growing broilers may be a viable commercial option.


Association between thermal environment and Salmonella in fecal samples from dairy cattle in midwestern United States.
The objective of this study was to describe the association between thermal measures in the barn environment (pen temperature and humidity) and fecal shedding of Salmonella in dairy cattle. A repeated cross-sectional study was conducted within a commercial dairy herd located in the midwestern United States. Five pooled fecal samples were collected monthly from each pen for 9 mo and submitted for microbiological culture. Negative binomial regression methods were used to test the association [incidence rate ratio (IRR)] between Salmonella pen status (the count of Salmonella-positive pools) and thermal environmental parameters [average temperature and temperature humidity index (THI)] for 3 time periods (48 h, 72 h, and 1 wk) before fecal sampling. Salmonella was cultured from 10.8% [39/360; 95% confidence interval (CI): 7.8% to 14.5%] of pooled samples. The highest proportion of positive pools occurred in August. The IRR ranged from 1.26 (95% CI: 1.15 to 1.39, THI 1 wk) to 4.5 (95% CI: 2.13 to 9.51, heat exposure 1 wk) across all thermal parameters and lag time periods measured. For example, the incidence rate of Salmonella-positive pools increased by 54% for every 5°C increment in average temperature (IRR = 1.54; 95% CI: 1.29 to 1.85) and 29% for every 5-unit increase in THI (IRR = 1.29; 95% CI: 1.16 to 1.42) during the 72 h before sampling. The incidence rate ratio for pens exposed to higher temperatures (> 25°C) was 4.5 times (95% CI: 2.13 to 9.51) the incidence rate ratio for pens exposed to temperatures < 25°C in the 72 h before sampling. Likewise, the incidence rate ratio for pens exposed to THI > 70 was 4.23 times greater (95% CI: 2.1 to 8.28) than when the THI was < 70 in the 72 h before sampling. An association was found between the thermal environment and Salmonella shedding in dairy cattle. Further research is warranted in order to fully understand the component risks associated with the summer season and increased Salmonella shedding.


Subunit vaccination of mice against new world cutaneous leishmaniasis: comparison of three proteins expressed in amastigotes and six adjuvants.
A mixture of well-defined recombinant antigens together with an adjuvant that preferentially stimulates specific gamma interferon (IFN-gamma)-secreting helper type 1 CD4(+) T cells (Th1 cells) presents a rational option for a vaccine against leishmaniasis. The potential of this approach was investigated in murine infections with Leishmania mexicana, which are characterized by the absence of a parasite-specific Th1 response and uncontrolled parasite proliferation. A mixture of three antigens (glycoprotein 63, cysteine proteinases, and a membrane-bound acid phosphatase), which are all expressed in amastigotes, the mammalian stage of the parasite, were used for the immunization of C57BL/6 mice in combination with six adjuvants (interleukin 12 [IL-12], Detox, 4'-monophosphoryl lipid A, QS-21, Mycobacterium bovis BCG, and Corynebacterium parvum). All six vaccine formulations containing the mixture of recombinant antigens were protective against challenge infections with promastigotes, the insect stage of the parasite, in that mice controlled and healed infections but developed transient and, in certain cases, accentuated disease. The most effective adjuvants were IL-12 followed by Detox. Further studies using these two adjuvants showed that a similar protective effect was observed with a mixture of the corresponding native proteins, and mice which had controlled the infection showed a preponderance of IFN-gamma-secreting CD4(+) T cells in the lymph nodes draining the lesion. Using the recombinant proteins individually, it is shown that the relatively abundant cysteine proteinases and glycoprotein 63, but not the acid phosphatase, are able to elicit a protective response. The results are discussed in comparison to previous studies with subunit vaccines and with respect to cell biological aspects of antigen presentation in Leishmania-infected macrophages.


Physical Activity Classification for Elderly People in Free-Living Conditions.
Physical activity is strongly linked with mental and physical health in the elderly population and accurate monitoring of activities of daily living (ADLs) can help improve quality of life and well-being. This study presents and validates an inertial sensors-based physical activity classification system developed with older adults as the target population. The dataset was collected in free-living conditions without placing constraints on the way and order of performing ADLs. Four sensor locations (chest, lower back, wrist, and thigh) were explored to obtain the optimal number and combination of sensors by finding the best tradeoff between the system's performance and wearability. Several feature selection techniques were implemented on the feature set obtained from acceleration and angular velocity signals to classify four major ADLs (sitting, standing, walking, and lying). A support vector machine was used for the classification of the ADLs. The findings show the potential of different solutions (single sensor or multisensor) to correctly classify the ADLs of older people in free-living conditions. Considering a minimal set-up of a single sensor, the sensor worn at the L5 achieved the best performance. A two-sensor solution (L5 + thigh) achieved a better performance with respect to a single-sensor solution. By contrast, considering more than two sensors did not provide further improvements. Finally, we evaluated the computational cost of different solutions and it was shown that a feature selection step can reduce the computational cost of the system and increase the system performance in most cases. This can be helpful for real-time applications.


Desmoplastic melanoma morphology on Thinprep: a report of two cases.
Desmoplastic melanoma is a variant of malignant melanoma that can range in appearance from sarcomatoid to scar-like. Cytomorphology of desmoplastic melanoma has been previously described on conventional smears; however, to our knowledge, detailed cytomorphology on ThinPrep has so far not been described. Herein, we describe the cytomorphology of two cases of desmoplastic melanoma on fine needle aspiration processed as ThinPrep slides and compare it to that seen on conventional smears. Pertinent immunocytochemical stains, performed on ThinPrep slides are also discussed. The first case is a woman with a history of desmoplastic melanoma of the scalp with previous local recurrences and lymph node metastasis with a new submandibular mass. The second case is a man with a previously resected desmoplastic melanoma with his first local recurrence. Conventional smears, including air-dried Diff-Quik-stained and alcohol-fixed Papanicolaou-stained smears, demonstrated aggregates of pleomorphic spindle cells admixed with fibrous stroma and single spindle cells. In both cases, nuclei were elongated and plump with irregular nuclear contours, deep grooves, and folds. Chromatin was dark and coarse with either inconspicuous or multiple prominent nucleoli. Cytoplasm was located at the nuclear poles and was fine, wispy, and delicate. The background was clean with no evidence of necrosis or melanin pigment. Papanicolaou-stained ThinPrep slides were prepared from needle rinses and demonstrated excellent correlation of nuclear and cytoplasmic detail of single spindle cells to that seen on conventional smears with the exception of only slight decrease in nuclear size; however, nuclear and cytoplasmic detail of spindle cells embedded in stroma was markedly attenuated. Confirmatory immunostain for S-100 protein in both cases was performed on ThinPrep slides demonstrating crisp cytoplasmic staining in the spindle cells. The cytomorphology of desmoplastic melanoma shows excellent correlation between cytomorphology of single spindle cells on conventional smears and on ThinPrep slides. The major difference noted on ThinPrep slides was attenuated nuclear and cytoplasmic detail of spindle cells embedded in fibrous stoma.


PEGylated Dendrimers as Drug Delivery Vehicles for the Photosensitizer Silicon Phthalocyanine Pc 4 for Candidal Infections.
Fungi account for billions of infections worldwide. The second most prominent causative agent for fungal infections is Candida albicans (C. albicans). As strains of fungi become resistant to antifungal medications, new treatment modalities must be investigated to combat these infections. One approach is to employ photodynamic therapy (PDT). PDT utilizes a photosensitizer, light, and cellular O2 to produce reactive oxygen species (ROS), which then induce oxidative stress resulting in apoptosis. Silicon phthalocyanine Pc 4 is a photosensitizer that has exhibited success in clinical trials for a myriad of skin diseases. The hydrophobic nature of Pc 4, however, poses significant formulation and delivery challenges in the use of this therapy. To mitigate these concerns, a drug delivery vehicle was synthesized to better formulate Pc 4 into a viable PDT agent for treating fungal infections. Utilizing poly(amidoamine) dendrimers as the framework for the vehicle, ∼13% of the amine chain ends were PEGylated to promote water solubility and deter nonspecific adsorption. In vitro studies with C. albicans demonstrate that the potency of Pc 4 was not hindered by the dendrimer vehicle. Encapsulated Pc 4 was able to effectively generate ROS and obliterate fungal pathogens upon photoactivation. The results presented within describe a nanoparticulate delivery vehicle for Pc 4 that readily kills drug-resistant C. albicans and eliminates solvent toxicity, thus, improving formulation characteristics for the hydrophobic photosensitizer.


HIV and hepatitis C prevalence, and related risk behaviours among people who inject drugs in three cities in Croatia: Findings from respondent-driven sampling surveys.
There are limited data on HIV and hepatitis C virus (HCV) epidemiology among people who inject drugs (PWID) in Croatia. This study aims to provide data on HIV and HCV prevalence and sexual and injecting risk behaviours among PWID in Zagreb, Split, and Rijeka. Using respondent-driven sampling (RDS) we recruited from November 2014 to February 2015 a total of 176 PWID in Zagreb, 255 in Rijeka and 399 in Split. Participants provided biological specimens for HIV and HCV testing and completed a behavioural questionnaire. The proportion of female PWID ranged from 19.5% in Zagreb to 26.0% in Split. In the month before the survey, 2.5% of PWID in Split, 5.6% in Rijeka and 8.0% in Zagreb reported sharing non-sterile needles and syringes. Many PWID injected opioid substitution therapy (OST) in the month before the survey (57.0% in Zagreb and 57.5% in Split and Rijeka, respectively). Among PWID who had a casual sexual partner in the past 12 months (ranging from 39.2% in Split to 44.4% in Rijeka) condom use was low. Although HIV prevalence was low (0.2% in Rijeka and Zagreb, 0.3% in Split), HCV antibody prevalence was considerable (29.1% in Zagreb, 31.5% in Rijeka, 38.3% in Split). HIV and HCV testing coverage in the past 12 months was insufficient (6.8% and 7.0% in Split; 13.2% and 13.5% in Zagreb; 20.2% and 21.5% in Rijeka, respectively). We found a low-level HIV epidemic and a sizable HCV epidemic among PWID in Zagreb, Split and Rijeka. Presence of high-risk injecting and sexual behaviours together with inadequate HIV and HCV testing coverage call for development of a comprehensive approach to harm reduction and introduction of needle and syringe exchange programmes in prisons, as well as strengthening sexual health interventions.


A Comparative Study of Serum Exosome Isolation Using Differential Ultracentrifugation and Three Commercial Reagents.
Exosomes play a role in cell-to-cell signaling and serve as possible biomarkers. Isolating exosomes with reliable quality and substantial concentration is a major challenge. Our purpose is to compare the exosomes extracted by three different exosome isolation kits (miRCURY, ExoQuick, and Invitrogen Total Exosome Isolation Reagent) and differential ultracentrifugation (UC) using six different volumes of a non-cancerous human serum (5 ml, 1 ml, 500 μl, 250 μl, 100 μl, and 50 μl) and three different volumes (1 ml, 500 μl and 100 μl) of six individual commercial serum samples collected from human donors. The smaller starting volumes (100 μl and 50 μl) are used to mimic conditions of limited availability of heterogeneous biological samples. The isolated exosomes were characterized based upon size, quantity, zeta potential, CD63 and CD9 protein expression, and exosomal RNA (exRNA) quality and quantity using several complementary methods: nanoparticle tracking analysis (NTA) with ZetaView, western blot, transmission electron microscopy (TEM), the Agilent Bioanalyzer system, and droplet digital PCR (ddPCR). Our NTA results showed that all isolation techniques produced exosomes within the expected size range (40-150 nm). The three kits, though, produced a significantly higher yield (80-300 fold) of exosomes as compared to UC for all serum volumes, except 5 mL. We also found that exosomes isolated by the different techniques and serum volumes had similar zeta potentials to previous studies. Western blot analysis and TEM immunogold labelling confirmed the expression of two common exosomal protein markers, CD63 and CD9, in samples isolated by all techniques. All exosome isolations yielded high quality exRNA, containing mostly small RNA with a peak between 25 and 200 nucleotides in size. ddPCR results indicated that exosomes isolated from similar serum volumes but different isolation techniques rendered similar concentrations of two selected exRNA: hsa-miR-16 and hsa-miR-451. In summary, the three commercial exosome isolation kits are viable alternatives to UC, even when limited amounts of biological samples are available.


Impact of donor infections on outcome of orthotopic liver transplantation.
Infection occurs when microbial agents enter the host, either through airborne transmission or by direct contact of a substance carrying the infectious agent with the host. Human body fluids, solid organs, or other tissues often are ideal vectors to support microbial agents and can transmit infections efficiently from donor to recipient. In the case of blood transfusion and tissue transplantation, the main consequence of such a transmission is infection of the recipient. However, in the case of solid-organ transplantation, and particularly for liver transplantation, donor infections are not only transmitted to the recipient, the donor infection also may affect the donated liver's preservability and subsequent function in the recipient irrespective of the systemic consequences of the infection. In addition, solid organ recipients of infected organs are less able to respond to the infectious agent because of their immunosuppressive treatment. Thus, transmission of infections from organ donor to liver recipient represents serious potential risks that must be weighed against a candidate's mortality risk without the transplant. However, the ever-increasing gap between the number of donors and those waiting for liver grafts makes consideration of every potential donor, regardless of the infection status, essential to minimize waiting list mortality. In this review, we will focus on assessing the risk of transmission of bacterial, fungal, viral, and parasitic infectious agents from cadaveric liver donors to recipients and the effect such a transmission has on liver function, morbidity, and mortality. We will also discuss risk-benefit deliberations for using organs from infected donors for certain types of recipients. These issues are critically important to maximize the use of donated organs but also minimize recipient morbidity and graft dysfunction.


Finger-powered microfluidic systems using multilayer soft lithography and injection molding processes.
Point-of-care (POC) and disposable biomedical applications demand low-power microfluidic systems with pumping components that provide controlled pressure sources. Unfortunately, external pumps have hindered the implementation of such microfluidic systems due to limitations associated with portability and power requirements. Here, we propose and demonstrate a 'finger-powered' integrated pumping system as a modular element to provide pressure head for a variety of advanced microfluidic applications, including finger-powered on-chip microdroplet generation. By utilizing a human finger for the actuation force, electrical power sources that are typically needed to generate pressure head were obviated. Passive fluidic diodes were designed and implemented to enable distinct fluids from multiple inlet ports to be pumped using a single actuation source. Both multilayer soft lithography and injection molding processes were investigated for device fabrication and performance. Experimental results revealed that the pressure head generated from a human finger could be tuned based on the geometric characteristics of the pumping system, with a maximum observed pressure of 7.6 ± 0.1 kPa. In addition to the delivery of multiple, distinct fluids into microfluidic channels, we also employed the finger-powered pumping system to achieve the rapid formation of both water-in-oil droplets (106.9 ± 4.3 μm in diameter) and oil-in-water droplets (75.3 ± 12.6 μm in diameter) as well as the encapsulation of endothelial cells in droplets without using any external or electrical controllers.


Fear of negative and positive evaluation and reactivity to social-evaluative videos in social anxiety disorder.
Social anxiety disorder (SAD) is marked by persistent fear of being scrutinized by others. This and most diagnostic symptoms relate to some form of fear of negative evaluation (FNE). More recent accounts of SAD, such as the Bivalent Fear of Evaluation Model, however, complement FNE with fear of positive evaluation (FPE), described as distress and avoidance of positive feedback. An explicit test of the incremental validity of FPE in discriminating SAD patients from controls - over and on top of the explanatory power of FPE - is currently missing and generally, well controlled laboratory experiments with positive and negative social stimuli in this patient group are rare. To fill this gap, we exposed 35 patients with SAD and healthy controls (HCs) to short social-evaluative video clips with actors expressing negative and positive as well as neutral statements while recording reactivity on experiential measures (valence, arousal, and approval ratings) as well as on facial electromyography and electrocardiography. In addition, participants completed questionnaire measures of FNE and FPE. Results revealed that FPE questionnaire scores as well as experiential (valence and appreciation) and electromyographical reactivity measures to positive videos improved prediction of group membership beyond the predictive power of FNE questionnaires scores and reactivity to negative videos. Results document the importance of FPE to more fully characterize and understand social anxiety and SAD. Implications include amendments to future diagnostic criteria, theoretical models, and treatment approaches for SAD.


Long-acting injectable antipsychotics for prevention and management of violent behaviour in psychotic patients.
It has been well established that long-term antipsychotic treatment prevents relapse, lowers number of rehospitalisations, and also effectively reduces violent behaviour. Although violent behaviour is not a typical manifestation of schizophrenia or other psychotic disorders, the diagnosis of psychosis increases the overall risk of violence. One of the few modifiable factors of violence risk is adherence with medication. In contrast, non-adherence with drug treatment and subsequent relapse increases risk of violent acts. Non-adherence can be addressed partially by long-acting injectable antipsychotics (LAI). The aim of our review was to examine the role of antipsychotic drugs, especially LAI, in prevention and management of violent behaviour in psychosis. This is a non-systematic, narrative review of the data from open, naturalistic, retrospective, and population studies, case series, and post hoc analyses of randomised controlled trials. Search of electronic databases (PubMed, Embase) was performed to identify relevant papers. Nine published papers (3 cross-sectional chart reviews, 4 retrospective studies, 2 prospective, randomised trials) were found. The results indicated positive clinical and antiaggressive effects of LAI in psychotic patients with high risk of violent behaviour. Reviewed evidence suggests that secured drug treatment with LAI may have clinical benefit in schizophrenia patients with high risk of violent behaviour. LAI significantly reduced the severity of hostility, aggressivity, number of violent incidents, and criminal offences. These findings are supported further by the empirical evidence from clinical practice, high rates of prescribed LAI to schizophrenia patients in high-security and forensic psychiatric facilities. Available data encourage the use of LAI in forensic psychiatry, especially during court-ordered commitment treatment.


Serial changes in focal hyperemia associated with hypertensive putaminal hemorrhage.
Seventeen separate xenon-enhanced computed tomographic images were performed in seven patients with hypertensive putaminal hemorrhage. Regional cerebral blood flow maps were then computed and assessed. All patients were categorized as being of good recovery potential, with moderate-sized hematomas, and all were treated conservatively. The regional cerebral blood flow assessments were scheduled within 4 days after, 2 weeks after, and less than 25 days after the ictus. The initial decrease in hemispheric blood flow ipsilateral to the side of the hematoma was calculated as the ratio of ipsilateral to contralateral hemispheric blood flow and was correlated with the size of the hematoma; that is, the larger the hematoma, the greater the decrease in the ratio of ipsilateral to contralateral hemispheric blood flow. The decrease persisted for 1 month. The mean of the ratio at 2 weeks after onset was 70%, the lowest during follow-up. All cases examined within 4 days after onset demonstrated perihematomatous focal hyperemia, or "luxury perfusion," which accounted for the delayed decrease. The same tissue that had previously shown hyperemia showed decreased regional cerebral blood flow 2 weeks after onset. Our results demonstrate that the luxury perfusion syndrome caused the secondary brain damage even in the cases that were in relatively good condition. The feasibility of treatment can be assessed by considering these results.


Developmental trajectories of boys' and girls' delinquency: sex differences and links to later adolescent outcomes.
This study examined gender differences in trajectories of delinquent behaviors over a 6-year period in adolescence and differential outcomes of these diverse developmental pathways. Participants were 754 children who were part of a longitudinal study of the development of early starting conduct problems. Four trajectory patterns were identified across grades 7-12: increasing, desisting, chronic, and nonproblem groups. Although the proportion of boys and girls varied across the pathways, both genders were represented on these trajectories. Boys were more represented on the chronic and desisting trajectories; girls were more represented in the nonproblem group. However, the proportion of boys and girls was similar in the increasing trajectory. Trajectory membership significantly predicted age 19 outcomes for partner violence, risky sexual behavior and depression, and the risk conferred on these negative adjustment outcomes did not vary by gender. The overall pattern was characterized by poor outcomes at age 19 for youth in both the chronic and the increasing trajectories. The major conclusion is that, other than base rate differences, developmental patterns and outcomes for girls mimic those previously found for boys.


Air pollution, environmental chemicals, and smoking may trigger vitamin D deficiency: Evidence and potential mechanisms.
Beyond vitamin D (VD) effect on bone homeostasis, numerous physiological functions in human health have been described for this versatile prohormone. In 2016, 95% of the world's population lived in areas where annual mean ambient particulate matter (<2.5 μm) levels exceeded the World Health Organization guideline value (Shaddick et al., 2018). On the other hand, industries disperse thousands of chemicals continually into the environment. Further, considerable fraction of populations are exposed to tobacco smoke. All of these may disrupt biochemical pathways and cause detrimental consequences, such as VD deficiency (VDD). In spite of the remarkable number of studies conducted on the role of some of the above mentioned exposures on VDD, the literature suffers from two main shortcomings: (1) an overview of the impacts of environmental exposures on the levels of main VD metabolites, and (2) credible engaged mechanisms in VDD because of those exposures. To summarize explanations for these unclear topics, we conducted the present review, using relevant keywords in the PubMed database, to investigate the adverse effects of exposure to air pollution, some environmental chemicals, and smoking on the VD metabolism, and incorporate relevant potential pathways disrupting VD endocrine system (VDES) leading to VDD. Air pollution may lead to the reduction of VD cutaneous production either directly by blocking ultraviolet B photons or indirectly by decreasing outdoor activity. Heavy metals may reduce VD serum levels by increasing renal tubular dysfunction, as well as downregulating the transcription of cytochrome P450 mixed-function oxidases (CYPs). Endocrine-disrupting chemicals (EDCs) may inhibit the activity and expression of CYPs, and indirectly cause VDD through weight gain and dysregulation of thyroid hormone, parathyroid hormone, and calcium homeostasis. Smoking through several pathways decreases serum 25(OH)D and 1,25(OH)2D levels, VD intake from diet, and the cutaneous production of VD through skin aging. In summary, disturbance in the cutaneous production of cholecalciferol, decreased intestinal intake of VD, the modulation of genes involved in VD homeostasis, and decreased local production of calcitriol in target tissues are the most likely mechanisms that involve in decreasing the serum VD levels.


Sulforaphane protects against ethanol-induced apoptosis in neural crest cells through restoring epithelial-mesenchymal transition by epigenetically modulating the expression of Snail1.
Ethanol-induced apoptosis in neural crest cells (NCCs), a multipotent progenitor cell population, is implicated in the Fetal Alcohol Spectrum Disorders (FASD). Studies have demonstrated that sulforaphane (SFN) can prevent ethanol-induced apoptosis in NCCs. The objective of this study is to investigate whether ethanol exposure can induce apoptosis in NCCs by inhibiting epithelial-mesenchymal transition (EMT) and whether SFN can prevent ethanol-induced apoptosis by epigenetically modulating the expression of Snail1, a key transcriptional factor that promotes EMT. We found that ethanol exposure resulted in a significant increase in apoptosis in NCCs. Co-treatment with SFN significantly reduced ethanol-induced apoptosis. Treatment with SFN also dramatically diminished ethanol-induced changes in the expression of E-cadherin and vimentin, and restored EMT in ethanol-exposed NCCs. In addition, ethanol exposure reduced the levels of trimethylation of histone H3 lysine 4 (H3K4me3) at the promoters of Snail1. SFN treatment diminished the ethanol-induced reduction of H3K4me3 at the promoter regions of the Snail1 gene, restored the expression of Snail1 and down-regulated Snail1 target gene E-cadherin. Knockdown of Snail1 significantly reduced the protective effects of SFN on ethanol-induced apoptosis. These results demonstrate that SFN can protect against ethanol-induced apoptosis by preventing ethanol-induced reduction in the levels of H3K4me3 at the promoters of Snail1, restoring the expression of Snail1 and EMT in ethanol-exposed NCCs.


Rapid hybridization kinetics of DNA attached to submicron latex particles.
We describe a novel method for attaching any DNA molecule to submicron latex beads and characterize the hybridization kinetic properties of these bead-DNA conjugates. The conjugates hybridize to DNA in solution with rates comparable to homogeneous hybridization reactions, are compatible with common hybridization conditions and are conveniently manipulated. They should thus serve as useful reagents for the fractionation and characterization of DNA and RNA.


Single-cell technologies for monitoring immune systems.
The complex heterogeneity of cells, and their interconnectedness with each other, are major challenges to identifying clinically relevant measurements that reflect the state and capability of the immune system. Highly multiplexed, single-cell technologies may be critical for identifying correlates of disease or immunological interventions as well as for elucidating the underlying mechanisms of immunity. Here we review limitations of bulk measurements and explore advances in single-cell technologies that overcome these problems by expanding the depth and breadth of functional and phenotypic analysis in space and time. The geometric increases in complexity of data make formidable hurdles for exploring, analyzing and presenting results. We summarize recent approaches to making such computations tractable and discuss challenges for integrating heterogeneous data obtained using these single-cell technologies.


Glucokinase MODY and implications for treatment goals of common forms of diabetes.
Treatment goals in diabetes concentrate on reducing the risk of vascular complications, largely through setting targets for glycated haemoglobin (HbA1c). These targets are based on epidemiological studies of complication development, but so far have not adequately addressed the adverse effects associated with lowering HbA1c towards the normal range. Glucokinase (GCK) mutations cause a monogenic form of hyperglycaemia (GCK-MODY) characterised by fasting hyperglycaemia with low postprandial glucose excursions and a marginally elevated HbA1c. Minimal levels of vascular complications (comparable with nondiabetic individuals) are observed in GCK-MODY, leading to the hypothesis that GCK-MODY may represent a useful paradigm for assessing treatment goals in all forms of diabetes. In this review, we discuss the evidence behind this concept, suggest ways of translating this hypothesis into clinical practice and address some of the caveats of such an approach.


Feasibility of incorporating self-collected rectal swabs into a community venue-based survey to measure the prevalence of HPV infection in men who have sex with men.
Inclusion of self-collected rectal swabs (SCRS) into existing community venue-based HIV surveillance systems for men who have sex with men (MSM) may provide a feasible method for monitoring human papillomavirus (HPV) vaccine-related outcomes in this population. We measured the prevalence of HPV and anal dysplasia through incorporating SCRS into ManCount, the Vancouver site of the M-Track HIV surveillance system. Participating MSM were provided with a self-collection kit for collection on-site or at a follow-up venue. Swabs were subject to polymerase chain reaction amplification for HPV detection, and cytology slides were reviewed for anal dysplasia. Factors associated with participation were identified through multivariate logistic regression. Of 766 men completing ManCount, 268 (35%) agreed to participate, self-collecting 252 specimens (247 on-site). Of 239 complete specimens, 33.5% did not have detectable β-globin; in the remainder (159 specimens) the prevalence of HPV infection was 62.3% (23.3% HPV type 16 or 18; 38.4% HPV type 6, 11, 16, or 18). In the 62.3% (149) of specimens adequate for cytology, the prevalence of anal dysplasia was 42.3% (HSIL 11.4%, LSIL 18.8%, ASC-US 6.7%, ASC-H 5.4%). Participation was associated with venue type, availability of on-site collection, and other characteristics. SCRS can be feasibly integrated within existing community venue-based HIV surveillance systems for MSM, and may be a suitable method for monitoring the impact of HPV vaccination in this population. However, participation may be influenced by venue type and availability of on-site collection, and adequacy of SCRS specimens may be lower in community venues as compared with clinical settings.


Medical termination for pregnancy in early first trimester (≤ 63 days) using combination of mifepristone and misoprostol or misoprostol alone: a systematic review.
A wide range of drugs have been studied for first trimester medical abortion. Studies evaluating different regimens, including combination mifepristone and misoprostol and misoprostol alone regimens, show varying results related to safety, efficacy and other outcomes. Thus, the objectives of this systematic review were to compare the safety, effectiveness and acceptability of medical abortion and to compare medical with surgical methods of abortion ≤63 days of gestation. Pubmed and EMBASE were systematically searched from database inception through January 2019 using a combination of MeSH, keywords and text words. Randomized controlled trials on induced abortion at ≤63 days that compared different regimens of medical abortion using mifepristone and/or misoprostol and trials that compared medical with surgical methods of abortion were included. We extracted data into a pre-designed form, calculated effect estimates, and performed meta-analyses where possible. The primary outcomes were ongoing pregnancy and successful abortion. Thirty-three studies composed of 22,275 participants were included in this review. Combined regimens using mifepristone and misoprostol had lower rates of ongoing pregnancy, higher rates of successful abortion and satisfaction compared to misoprostol only regimens. In combined regimens, misoprostol 800 μg was more effective than 400 μg. There was no significant difference in dosing intervals between mifepristone and misoprostol and routes of misoprostol administration in combination or misoprostol alone regimens. The rate of serious adverse events was generally low. In this systematic review, we find that medical methods of abortion utilizing combination mifepristone and misoprostol or misoprostol alone are effective, safe and acceptable. More robust studies evaluating both the different combination and misoprostol alone regimens are needed to strengthen existing evidence as well as assess patient perspectives towards a particular regimen.


Surface-mediated assembly, polymerization and degradation of thiophene-based monomers.
Ullmann coupling of halogenated aromatics is widely used in on-surface synthesis of two-dimensional (2D) polymers and graphene nanoribbons. It stands out among other reactions for regioselectively connecting aromatic monomers into 1D and 2D π-conjugated polymers, whose final structure and properties are determined by the initial building blocks. Thanks to their exceptional electronic properties, thiophene-containing monomers are frequently used for the synthesis of various conjugated materials. On the other hand, their use in on-surface polymerization is hampered by the possibility of ring opening when adsorbed on metal surfaces. In the present work, we mapped the temperature regime for these two competing reactions by investigating the adsorption of a thiophene-based prochiral molecule using scanning tunneling microscopy, X-ray photoelectron spectroscopy and density functional theory calculations. We followed the formation of organometallic (OM) networks, their evolution into covalent structures and the competition between C-C coupling and thiophene ring opening. The effect of surface reactivity was explored by comparing the adsorption on three (111) coinage metal substrates, namely Au, Ag and Cu. While outlining strategies to minimize the ring opening reaction, we found that the surface temperature during deposition is of paramount importance for the preparation of 2D OM networks, greatly enhancing the overall ordering of the product by depositing on hot Ag surface. Notably, the same protocol permits the creation of OM structures on the air-stable Au surface, thereby allowing the synthesis and application of 2D OM networks outside the ultra-high vacuum environment.


Lithium and 5-HT1A receptor sensitivity: a neuroendocrine study in healthy volunteers.
The effect of lithium administration (800 mg daily for 7 days) on the neuroendocrine and temperature responses to the 5-HT1A receptor agonist, gepirone, was studied in eight healthy male volunteers. Gepirone (20 mg orally) significantly increased plasma levels of prolactin, growth hormone, corticotropin and cortisol, and lowered oral temperature. None of these responses was significantly altered by lithium treatment. The results suggest that the ability of short-term lithium treatment to increase 5-HT-mediated neuroendocrine responses in humans is unlikely to be related to changes in the sensitivity of pre- or post-synaptic 5-HT1A receptors.


Financing institutional long-term care for the elderly in China: a policy evaluation of new models.
A rapid ageing population coupled with changes in family structure has brought about profound implications to social policy in China. Although the past decade has seen a steady increase in public funding to long-term care (LTC), the narrow financing base and vast population have created significant unmet demand, calling for reforms in financing. This paper focuses on the financing of institutional LTC care by examining new models that have emerged from local policy experiments against two policy goals: equity and efficiency. Three emerging models are explored: Social Health Insurance (SHI) in Shanghai, LTC Nursing Insurance (LTCNI) in Qingdao and a means-tested model in Nanjing. A focused systematic narrative review of academic and grey literature is conducted to identify and assess these models, supplemented with qualitative interviews with government officials from relevant departments, care home staff and service users. This paper argues that, although SHI appears to be a convenient solution to fund LTC, this model has led to systematic bias in affordable access among participants of different insurance schemes, and has created a powerful incentive for the over-provision of unnecessary services. The means-tested method has been remarkably constrained by narrow eligibility and insufficiency of funding resources. The LTCNI model is by far the most desirable policy option among the three studied here, but the narrow definition of eligibility has substantively excluded a large proportion of elders in need from access to care, which needs to be addressed in future reforms. This paper proposes three lines of LTC financing reforms for policy-makers: (1) the establishment of a prepaid financing mechanism pooled specifically for LTC costs; (2) the incorporation of more stringent eligibility rules and needs assessment; and (3) reforming the dominant fee-for-service methods in paying LTC service providers.


Improving survival: infection control and burns.
In the past, survival of the thermally injured patient was greatly hindered by invasive infection that originated in the burn wound. Current treatment modalities, including early excision of the burn wound and prompt wound closure, administration of systemic antibiotics and topical antimicrobial agents, and mechanical isolation, have improved survival. However, infection and the sequelae of infection continue to be the leading causes of morbidity and mortality for the thermally injured patient. In addition, the burn patient remains highly susceptible to other infectious processes. A thorough understanding of infection control and burns are essential to the successful treatment of burn injuries.


High performance thin layer chromatography qualitative densitometry as a sensitive method to assess shelf life of polyherbal formulations: A study on Hutabhugadi Churna.
Measuring chemical stability of polyherbal formulations is very challenging due to diversity in phytochemical composition. As there are no comprehensive guidelines for stability testing of herbal products, there is a need for a sensitive tool to detect how the quality of herbal products varies with time under the influence of environmental conditions. To validate the employability of high-performance thin layer chromatography (HPTLC) for real-time stability of Hutabhugadi Churna (HC). The chromatograms were developed using toluene/ethyl acetate/formic acid (10:5:1) and ethyl acetate/formic acid (10:1) as a mobile phase for chloroform and ethanolic extract, respectively. The plates were scanned under 254, 366, 540 (pre-derivatization) and 540 nm (post-derivatization). Samples were analyzed immediately after preparation and after 3(rd) and 6(th) months of storage. Alteration of fingerprint profiles from the initial pattern, in terms of number of peaks, was employed as diagnostic tools. Percentage variation in composition at given period was calculated. HC is found to be stable at room temperature up to 1.3 months using the method of calculation of 10% degradation period employing slope and intercept values for the initial, 3(rd) and 6(th) months' deviation in number of bands. The data obtained were subjected to regression analysis in context to number of bands obtained. The curve was found to be linear with R(2) value of 0.89-0.96 supported by their tolerance range of 0.04-0.11. The proposed model is a new logic with prospects to become working method for stability assessment of polyherbal formulations under controlled conditions.


A secreted Plasmodium falciparum kinase reveals a signature motif for classification of tyrosine kinase-like kinases.
Thorough bioinformatic and phylogenetic analyses of Plasmodium falciparum tyrosine kinase-like kinase (TKL) sequences revealed a clear evolutionary relationship of PF3D7_1121300 (thereafter called PfTKL2) to the IL-1 receptor-associated kinase (IRAK)/receptor-like kinase (RLK)/Pelle protein family. We identified a novel conserved motif that is unique to this family, as well as an insertion whose length allows distribution of its members into two distinct subfamilies, in a way that matches exactly the dichotomy between 'Tube/Tube-like kinases' (TTLKs) and 'Pelle-like kinases' (PLKs) distinguished previously on the basis of features in accessory domains. The PfTKL2 protein is expressed ubiquitously in asexual blood stages and in gametocytes, and the recombinant enzyme displays kinase activity in vitro. The protein is exported to the host erythrocyte; furthermore, in accordance with data from a previous study of the extracellular proteome of Plasmodium-infected erythrocytes, we show that PfTKL2 is secreted into the culture medium. Considering the functions of other members of the RLK/Pelle family in immunity, and its secretion to the extracellular medium, we speculate that PfTKL2 functions may include an immunomodulatory role promoting parasite survival in the human host.


Basin-scale seasonal changes in marine free-living bacterioplankton community in the Ofunato Bay.
The Ofunato Bay in the northeastern Pacific Ocean area of Japan possesses the highest biodiversity of marine organisms in the world and has attracted much attention due to its economic and environmental importance. We report here a shotgun metagenomic analysis of the year-round variation in free-living bacterioplankton collected across the entire length of the bay. Phylogenetic differences among spring, summer, autumn and winter bacterioplankton suggested that members of Proteobacteria tended to decrease at high water temperatures and increase at low temperatures. It was revealed that Candidatus Pelagibacter varied seasonally, reaching as much as 60% of all sequences at the genus level in the surface waters during winter. This increase was more evident in the deeper waters, where they reached up to 75%. The relative abundance of Planktomarina also rose during winter and fell during summer. A significant component of the winter bacterioplankton community was Archaea (mainly represented by Nitrosopumilus), as their relative abundance was very low during spring and summer but high during winter. In contrast, Actinobacteria and Cyanobacteria appeared to be higher in abundance during high-temperature periods. It was also revealed that Bacteroidetes constituted a significant component of the summer bacterioplankton community, being the second largest bacterial phylum detected in the Ofunato Bay. Its members, notably Polaribacter and Flavobacterium, were found to be high in abundance during spring and summer, particularly in the surface waters. Principal component analysis and hierarchal clustering analyses showed that the bacterial communities in the Ofunato Bay changed seasonally, likely caused by the levels of organic matter, which would be deeply mixed with surface runoff in the winter.


Stages of change in adults with acquired hearing impairment seeking help for the first time: application of the transtheoretical model in audiologic rehabilitation.
This study investigated the application of the transtheoretical (stages-of-change) model in audiologic rehabilitation. More specifically, it described the University of Rhode Island Change Assessment (URICA) scores of adults with acquired hearing impairment. It reported the psychometric properties (construct, concurrent, and predictive validity) of the stages-of-change model in this population. At baseline, 153 adults with acquired hearing impairment seeking help for the first time completed the URICA as well as measures of degree of hearing impairment, self-reported hearing disability, and years since hearing impairment onset. Participants were subsequently offered intervention options: hearing aids, communication programs, and no intervention. Their intervention uptake and adherence were assessed 6 months later and their intervention outcomes were assessed 3 months after intervention completion. First, the stages-of-change construct validity was evaluated by investigating the URICA factor structure (principal component analysis), internal consistency, and correlations between stage scores. The URICA scores were reported in terms of the scores for each stage of change, composite scores, stages with highest scores, and stage clusters (cluster analysis). Second, the concurrent validity was assessed by examining associations between stages of change and degree of hearing impairment, self-reported hearing disability, and years since hearing impairment onset. Third, the predictive validity was evaluated by investigating associations between stages of change and intervention uptake, adherence, and outcomes. First, in terms of construct validity, the principal component analysis identified four instead of three stages (precontemplation, contemplation, preparation, and action) for which the internal consistency was good. Most of the sample was in the action stage. Correlations between stage scores supported the model. Cluster analysis identified four stages-of-change clusters, which the authors named active change, initiation, disengagement, and ambivalence. In terms of concurrent validity, participants who reported a more advanced stage of change had a more severe hearing impairment, reported greater hearing disability, and had a hearing impairment for a longer period of time. In terms of predictive validity, participants who reported a more advanced stage of change were more likely to take up an intervention and to report successful intervention outcomes. However, stages of change did not predict intervention adherence. The majority of the sample was in the action stage. The construct, concurrent, and predictive validity of the stages-of-change model were good. The stages-of-change model has some validity in the rehabilitation of adults with hearing impairment. The data support that change might be better represented on a continuum rather than by movement from one step to the next. Of all the measures, the precontemplation stage score had the best concurrent and predictive validity. Therefore, further research should focus on addressing the precontemplation stage with a measure suitable for clinical use.


COSMOS: COmparing Standard Maternity care with one-to-one midwifery support: a randomised controlled trial.
In Australia and internationally, there is concern about the growing proportion of women giving birth by caesarean section. There is evidence of increased risk of placenta accreta and percreta in subsequent pregnancies as well as decreased fertility; and significant resource implications. Randomised controlled trials (RCTs) of continuity of midwifery care have reported reduced caesareans and other interventions in labour, as well as increased maternal satisfaction, with no statistically significant differences in perinatal morbidity or mortality. RCTs conducted in the UK and in Australia have largely measured the effect of teams of care providers (commonly 6-12 midwives) with very few testing caseload (one-to-one) midwifery care. This study aims to determine whether caseload (one-to-one) midwifery care for women at low risk of medical complications decreases the proportion of women delivering by caesarean section compared with women receiving 'standard' care. This paper presents the trial protocol in detail. A two-arm RCT design will be used. Women who are identified at low medical risk will be recruited from the antenatal booking clinics of a tertiary women's hospital in Melbourne, Australia. Baseline data will be collected, then women randomised to caseload midwifery or standard low risk care. Women allocated to the caseload intervention will receive antenatal, intrapartum and postpartum care from a designated primary midwife with one or two antenatal visits conducted by a 'back-up' midwife. The midwives will collaborate with obstetricians and other health professionals as necessary. If the woman has an extended labour, or if the primary midwife is unavailable, care will be provided by the back-up midwife. For women allocated to standard care, options include midwifery-led care with varying levels of continuity, junior obstetric care and community based general medical practitioner care. Data will be collected at recruitment (self administered survey) and at 2 and 6 months postpartum by postal survey. Medical/obstetric outcomes will be abstracted from the medical record. The sample size of 2008 was calculated to identify a decrease in caesarean birth from 19 to 14% and detect a range of other significant clinical differences. Comprehensive process and economic evaluations will be conducted. Australian New Zealand Clinical Trials Registry ACTRN012607000073404.


Ubiquitination of alpha-synuclein in Lewy bodies is a pathological event not associated with impairment of proteasome function.
Lewy bodies are intracellular fibrillar inclusions composed of alpha-synuclein. They constitute the pathological hallmark of Parkinson's disease, dementia with Lewy bodies, and other neurodegenerative diseases. Although the majority of Lewy bodies are stained for ubiquitin by immunohistochemistry, the substrate for this modification is poorly understood. Insoluble, urea-soluble alpha-synuclein was separated from soluble fractions and subjected to two-dimensional gel electrophoresis to further characterize pathogenic alpha-synuclein species from disease brains. By using this approach, we found that in sporadic Lewy body diseases a highly modified, disease-associated 22-24-kDa alpha-synuclein species is ubiquitinated. Conjugation of one, two, and, to a lesser extent, three ubiquitins was detected. This 22-24-kDa alpha-synuclein species represents partly phosphorylated protein. Furthermore, no generalized impairment of the proteolytic activity of the proteasome was detected in brain regions with Lewy body pathology. Because unmodified alpha-synuclein is degraded by the proteasome in a ubiquitin-independent manner, these data suggest that accumulation of modified 22-24-kDa alpha-synuclein is a disease-specific event which may overwhelm the proteolytic system, leading to aberrant ubiquitination. Accordingly, carboxyl-terminal-truncated alpha-synuclein, presumably the result of aberrant proteolysis, is found only in association with alpha-synuclein aggregates.


Isolation of infectious salmon anemia virus (ISAV) from Atlantic salmon in New Brunswick, Canada.
Infectious salmon anemia virus (ISAV) was isolated at a marine grow-out site in New Brunswick, Canada, from Atlantic salmon Salmo salar which experienced mortalities due to hemorrhagic kidney syndrome (HKS). Of 20 fish sampled in this study, 14 showed histologically various degrees of interstitial hemorrhaging, tubular epithelial degeneration and necrosis, and tubular casts in the posterior kidney, typical of HKS. Posterior kidney and spleen homogenates produced a cytopathic effect on chinook salmon embryo (CHSE-214) cells 10 to 14 d after inoculation. Pleomorphic virus particles in the size range 80 to 120 nm were seen by electron microscopy. The virus was confirmed as ISAV using reverse transcriptase-polymerase chain reaction (RT-PCR). This is a systematic diagnostic study of the isolation of ISAV on the North American continent and the first description of the growth of ISAV on the CHSE-214 cell line.


A spring-assisted hybrid triboelectric-electromagnetic nanogenerator for harvesting low-frequency vibration energy and creating a self-powered security system.
With the rapid development of portable electronics, exploring sustainable power sources is becoming more and more urgent. Utilizing a nanogenerator to harvest ambient mechanical energy could be an effective approach to solve this challenge. In this work, a novel spring-assisted hybrid nanogenerator (HG) consisting of a triboelectric nanogenerator (TENG) and an electromagnetic generator (EMG) was developed for harvesting low-frequency vibration energy. The results show that the TENG with a PTFE surface nanostructure has better output performance than that without the nanostructure. The effect of operating frequency on the open-circuit voltage and short-circuit current of the TENG and EMG is systematically investigated. Under a 2 Hz operating frequency, the EMG and TENG are able to produce a peak power of about 57.6 mW with a resistive load of 2000 Ω and 1682 μW with a resistive load of 50 MΩ, respectively. The impedance matching between the TENG and EMG can be realized by using a transformer to reduce the impedance of the TENG. The charging performance of the HG is much better than that of the individual EMG or TENG. The HG enabled us to develop a self-powered safety system and to power LEDs, and drive some electronic devices. The present work provides a superior solution to improve the output performance of the HG for harvesting low-frequency vibration energy.


Exploring the genome of the salt-marsh Spartina maritima (Poaceae, Chloridoideae) through BAC end sequence analysis.
Spartina species play an important ecological role on salt marshes. Spartina maritima is an Old-World species distributed along the European and North-African Atlantic coasts. This hexaploid species (2n = 6x = 60, 2C = 3,700 Mb) hybridized with different Spartina species introduced from the American coasts, which resulted in the formation of new invasive hybrids and allopolyploids. Thus, S. maritima raises evolutionary and ecological interests. However, genomic information is dramatically lacking in this genus. In an effort to develop genomic resources, we analysed 40,641 high-quality bacterial artificial chromosome-end sequences (BESs), representing 26.7 Mb of the S. maritima genome. BESs were searched for sequence homology against known databases. A fraction of 16.91% of the BESs represents known repeats including a majority of long terminal repeat (LTR) retrotransposons (13.67%). Non-LTR retrotransposons represent 0.75%, DNA transposons 0.99%, whereas small RNA, simple repeats and low-complexity sequences account for 1.38% of the analysed BESs. In addition, 4,285 simple sequence repeats were detected. Using the coding sequence database of Sorghum bicolor, 6,809 BESs found homology accounting for 17.1% of all BESs. Comparative genomics with related genera reveals that the microsynteny is better conserved with S. bicolor compared to other sequenced Poaceae, where 37.6% of the paired matching BESs are correctly orientated on the chromosomes. We did not observe large macrosyntenic rearrangements using the mapping strategy employed. However, some regions appeared to have experienced rearrangements when comparing Spartina to Sorghum and to Oryza. This work represents the first overview of S. maritima genome regarding the respective coding and repetitive components. The syntenic relationships with other grass genomes examined here help clarifying evolution in Poaceae, S. maritima being a part of the poorly-known Chloridoideae sub-family.


Zika virus epidemiology: from Uganda to world pandemic, an update.
Zika virus (ZIKV) infection is an emergent worldwide public health problem. Historically, 84 countries have reported vector-borne ZIKV transmission, 61 of which report on-going transmission. It is a Flavivirus transmitted through arthropods belonging to the Aedes genus. Since 2015, ZIKV infections have increased dramatically; with 1.3 million people infected during 2015 in Brazil alone. This paper's objective is to highlight the conjectural epidemiological points of the virus' dissemination. The digital archives Pubmed, MEDLINE, EMBASE and Cochrane were searched for papers that assessed aspects of ZIKV transmission and epidemiology. The first isolation occurred in Uganda in 1947. Since then, important outbreaks were documented globally. Consequently, an emergent public health problem arose from a rapidly increasing incidence and its association with the development of neurological diseases such as microcephaly and Guillain-Barré syndrome. Key factors in the successful containment of outbreaks include surveillance of mosquitos in the neighbourhood, an early mosquito control treatment, an assertive information campaign, and the involvement of the local population and healthcare workers. As such, while ZIKV seems to be spreading globally in a similar manner to other arboviruses, such as Dengue and Chikungunya viruses, it can also be rapidly contained due to the pre-existing availability of necessary resources and regulatory tools as control measures. This review aims to provide a description of those characteristics of ZIKV infection that may be useful in the construction of effective outbreak control strategies.


Context-aware stacked convolutional neural networks for classification of breast carcinomas in whole-slide histopathology images.
Currently, histopathological tissue examination by a pathologist represents the gold standard for breast lesion diagnostics. Automated classification of histopathological whole-slide images (WSIs) is challenging owing to the wide range of appearances of benign lesions and the visual similarity of ductal carcinoma in-situ (DCIS) to invasive lesions at the cellular level. Consequently, analysis of tissue at high resolutions with a large contextual area is necessary. We present context-aware stacked convolutional neural networks (CNN) for classification of breast WSIs into normal/benign, DCIS, and invasive ductal carcinoma (IDC). We first train a CNN using high pixel resolution to capture cellular level information. The feature responses generated by this model are then fed as input to a second CNN, stacked on top of the first. Training of this stacked architecture with large input patches enables learning of fine-grained (cellular) details and global tissue structures. Our system is trained and evaluated on a dataset containing 221 WSIs of hematoxylin and eosin stained breast tissue specimens. The system achieves an AUC of 0.962 for the binary classification of nonmalignant and malignant slides and obtains a three-class accuracy of 81.3% for classification of WSIs into normal/benign, DCIS, and IDC, demonstrating its potential for routine diagnostics.


A study of the referral patterns of obstetric clinics and the performance of receiving neonatal intensive care units in Taiwan.
To study the referral patterns of obstetric clinics, and the performance of receiving intensive care units measured by the survival of transported neonates, transport records were collected prospectively between July, 1991 and June, 1992. Two hundred and fifty-four transported neonates born in 51 obstetric clinics (level I units) in Tainan City and County, in southern Taiwan, were enrolled in this study. Nineteen percent of the transported neonates were very low birthweight infants (< 1500 g). Nearly equal numbers of them were transported to eight district hospitals (level II units) and to a tertiary center (level III unit), but these infants were 1.5 times more likely to die in a level II unit than a level III unit. In addition, equal numbers of infants assisted by mechanical ventilators were transported to level II and III units, but these infants were three times more likely to die in a level II unit than a level III unit (P = 0.006). Seventy-seven percent of the normal birthweight infants (> or = 2500 g) were transported to level II units, and the mortality in this group was 12.3% compared with 0% in those transported to the level III unit. Approximately 56% of these normal birthweight infants in level II units died of severe birth asphyxia. The referral patterns of level 1 units had an unfavorable effect on the survival of neonates requiring mechanical ventilation. Enhancing the skills of the staff in level I units to recognize and stabilize such infants, elevating the capability of level II units in treating some of these cases, and increasing the hospital beds for level III care are necessary to increase their chance of survival.


Cardiac differentiation of embryonic stem cells with point-source electrical stimulation.
The use of pluripotent stem cells as a means to repair damaged heart tissue has recently emerged as a promising, yet controversial therapy. Despite the different approaches and the variety of cell types used, many of these procedures have been met with mixed success. The lack of understanding of the differentiation and integration process, notably with respect to electrical signaling, significantly hampers the development of these therapies. A system was thus developed allowing the use of point source electrical stimulation on embryonic stem (ES) cells to study the effect of physiologically-relevant electrical stimulus. When modulating the amplitude of the stimulus over various differentiation stages of embryonic stem cells, differences in the proportions of cardiomyocytes to embryonic stem cells were observed through quantitative PCR. The use of this technique might have larger applications in understanding molecular pathways towards the regeneration process.


Impact of water quality on the bacterial populations and off-flavours in recirculating aquaculture systems.
A variety of factors affecting water quality in recirculating aquaculture systems (RAS) are associated with the occurrence of off-flavours. In this study, we report the impact of water quality on the bacterial diversity and the occurrence of the geosmin-synthesis gene (geoA) in two RAS units operated for 252 days. Unit 2 displayed a higher level of turbidity and phosphate, which affected the fresh water quality compared with unit 1. In the biofilter, nitrification is one of the major processes by which high water quality is maintained. The bacterial population observed in the unit 1 biofilter was more stable throughout the experiment, with a higher level of nitrifying bacteria compared with the unit 2 biofilter. Geosmin appeared in fish flesh after 84 days in unit 2, whereas it appeared in unit 1 after 168 days, but at a much lower level. The geoA gene was detected in both units, 28 days prior to the detection of geosmin in fish flesh. In addition, we detected sequences associated with Sorangium and Nannocystis (Myxococcales): members of these genera are known to produce geosmin. These sequences were observed at an earlier time in unit 2 and at a higher level than in unit 1. This study confirms the advantages of new molecular methods to understand the occurrence of geosmin production in RAS.


Five-year safety and immunogenicity of GlaxoSmithKline's candidate malaria vaccine RTS,S/AS02 following administration to semi-immune adult men living in a malaria-endemic region of The Gambia.
RTS,S is a pre-erythrocytic malaria vaccine candidate antigen based on the circumsporozoite surface protein of Plasmodium falciparum fused to HBsAg, incorporating a novel Adjuvant System (AS02). The first field efficacy of RTS,S/AS02 against infection was demonstrated in a trial initiated in The Gambia in 1998. This paper presents the five-year safety and immunogenicity follow up of the 306 men who were enrolled in the original trial. In the primary study men aged 18 to 45 years were randomized to receive either RTS,S/AS02 or rabies vaccine at 0, 1, 5 months followed by a booster dose at month 19. The subjects were observed for long term safety and immunogenicity continuously until month 58. Of the 153 subjects in each group at enrollment, 80 (52%) subjects in the RTS,S/AS02 group and 83 (54%) subjects in the rabies group returned for the final long-term follow-up visit at month 58. The main reason for non-attendance at month 58 was migration (76% of all drop-outs). Nine subjects in the RTS,S/AS02 group and seven in the rabies group experienced serious adverse events (SAEs) over the 58 month surveillance period, of which seven had a fatal outcome (five RTS,S/AS02 and two rabies group). None of the SAEs with fatal outcome were attributed to the study vaccine. Anti-CS antibody persistence compared to control was observed for five years, although titres had waned from post-booster levels; similar responses in anti-HBs antibody persistence were observed in initially HBsAg seronegative subjects. This study provides the first indication of the long-term safety and persistence of anti-CS and anti-HBs antibodies of the RTS,S vaccine candidate in combination with the novel AS02 Adjuvant System.


Comorbidity of oppositional defiant disorder and anxiety disorders in preschoolers.
The aim was to study the comorbidity of oppositional defiant disorder (ODD) and anxiety disorders (AD) among preschool children of the general population, and to assess the contribution of comorbidity to the child's functional impairment. 622 children were assessed at the ages of 3 and 5, through a diagnostic interview. They were clustered into three diagnostic groups: only ODD, only AD and comorbid ODD+AD. At age 3, ODD was associated with specific phobia, OR = 4.7, 95% CI [1.4, 14.1], and at age 5, with any anxiety disorder, OR=3.9; 95% CI [1.8, 8.4]. ODD at age 3 was predictive of separation anxiety at age 5, OR=4.1; 95% CI [1.2, 14.3]. Comorbid ODD+AD cases showed a higher risk of functional impairment at school and in behavior toward others. Sex and socioeconomic status were not related to the diagnostic group. ODD+AD comorbidity can be identified in preschool children. Early identification of this association is needed to adequately treat the affected children.


Accuracy of non-invasive continuous total hemoglobin measurement by Pulse CO-Oximetry in severe traumatized and surgical bleeding patients.
The Masimo Radical-7 Pulse CO-Oximeter (Masimo Corp., USA) non-invasively computes hemoglobin concentration (SpHb). SpHb was compared to Co-Oximeter readings (CoOxHb) of arterial samples in surgery patients of the emergency department. Forty-six patients were enrolled. The Masimo R1 25L (revision F and G) adult adhesive sensor was attached to the ring finger of the arterially cannulated hand. Before start, every 30 min during surgery and in the case of severe bleeding SpHb and CoOxHb values were documented. SpHb and post hoc adjusted SpHb (AdSpHb) values were analyzed. Linear regression analysis and Bland-Altman plot for agreement were performed. The detection failure rate of SpHb was 24.5 %. CoOxHb and SpHb showed a strong correlation (r = +0.81), but agreement was moderate [bias (LOA) of -0.6 (-3.0; +1.9)] g/dl. Positive and negative predicted value was 0.49 and 0.69. Exclusion of changes of CoOxHb values ≤1 g/dl resulted in a positive and negative predictive value of 0.66 and 1.00. Post hoc adjustment of the SpHb (AdSpHb) improved linear correlation of CoOxHb and AdSpHb [r = +0.90 (p < 0.001)] but less the agreement [bias (LOA) of CoOxHb and AdSpHb = -0.1 (-2.1/+1.9) g/dl]. SpHb agreed only moderately with CoOxHb values and predicted decreases of CoOxHb only if changes of SpHb ≤ 1.0 g/dl were excluded. The detection failure rate of SpHb was high. At present, additional refinements of the current technology are necessary to further improve performance of non-invasive hemoglobin measurement in the clinical setting.


A stochastic broadcast feedback approach to regulating cell population morphology for microfluidic angiogenesis platforms.
This paper presents a framework for controlling the development of a vascular system in an in vitro angiogenesis process. Based on online measurement of cell growth and a stochastic cell population model, a closed-loop control system is developed for regulating the process of cell migration and vascular system development. Angiogenesis is considered in a microfluidic environment, where chemical and mechanical stimuli can be applied to the cell population. A systems-level description of the angiogenesis process is formulated, and a control scheme that chooses an optimal sequence of control inputs to drive collective cell patterns toward a desired goal is presented in this paper. In response to control inputs, the k-step ahead prediction of morphologic pattern measures is evaluated, and the input that minimizes expected squared error between the future measure and its desired value is selected for the current control. Initial simulation experiments demonstrate that vascular development can be guided toward a desired morphologic pattern using this technique.


Are readmissions avoidable?
To examine the possible use of readmission rates as an outcome indicator of hospital inpatient care by investigating avoidability of unplanned readmissions within 28 days of discharge. Retrospective analysis of a stratified random sample of case notes of patients with an unplanned readmission between July 1987 and June 1988 by nine clinical assessors (263 assessments) and categorisation of the readmission as avoidable, unavoidable, or unclassifiable. District in North East Thames region. 481 General medical, geriatric, and general surgical inpatients with a readmission at 0-6 days or 21-27 days after the first (index) discharge between July 1987 and June 1988 from whom 100 case notes were selected randomly and of which 74 were available for study. Assessment of readmissions as avoidable, unavoidable, unclassifiable, variability of assessment within cases and variability among assessors according to specialty and duration to readmission. General medical and geriatric readmissions and surgical readmissions at 0-6 days after discharge were more likely to be assessed as avoidable than those at 21-27 days (medical readmissions 32 v 6%, surgical admissions 49 v 19%). General surgical readmissions were significantly more frequently assessed as avoidable than general medical and geriatric readmissions. The extent of agreement between doctors varied, with general medical and geriatric readmissions at 21-27 days after first discharge causing the greatest variability of judgment. Differences were apparent in the extent of avoidability of readmissions in different groups of admissions. However, assessors rated only 49.3% of the group with the highest proportion of avoidable admissions (surgical readmissions at 0-6 days) as avoidable. The remainder were thought to be unavoidable except for 2%, which could not be classified. The use of readmission rates as an outcome indicator of hospital inpatient care should be avoided.


Expression of proinflammatory cytokines in four regions of the brain in Macaque mulatta (rhesus) monkeys infected with Plasmodium coatneyi.
We have characterized brain cytokine expression profiles in the Plasmodium coatneyi/rhesus (Macaque mulatta) malaria model. Eight rhesus monkeys were included in the study; four were infected with P. coatneyi, and four were used as uninfected controls. All inoculated animals became infected. Eleven days after parasite inoculation, the rhesus monkeys were killed and tissue samples from 4 regions of the brain (cortex and white matter of the cerebrum, cerebellum, and midbrain) were collected for quantitation of mRNA expression of cytokines, adhesion molecules, and inducible nitric oxide synthetase (iNOS) by reverse transcriptase-polymerase chain reaction (RT-PCR). The expression levels of tumor necrosis actor-alpha (TNF-alpha), gamma interferon (IFN-gamma), interleukin-1-beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synethetase (iNOS) were highest in the cerebellum of infected animals, correlating well with pathologic observations of sequestration of parasitized erythrocytes in this region of the brain. Infected animals also had higher TNF-alpha expression levels in the cortex and IL-1beta expression levels in the cortex, white matter, and midbrain. Thus, the expression of pro-inflammatory and T helper-1 (TH-1) cytokines, adhesion molecules, and iNOS appears to predominate in the cerebellum of infected rhesus monkeys.