On-Chip Fluorescent Labeling using Reversed-phase Monoliths and Microchip Electrophoretic Separations of Selected Preterm Birth Biomarkers.
On-chip preconcentration, purification, and fluorescent labeling are desirable sample preparation steps to achieve complete automation in integrated microfluidic systems. In this work, we developed electrokinetically operated microfluidic devices for solid-phase extraction and fluorescent labeling of preterm birth (PTB) biomarkers. Reversed-phase monoliths based on different acrylate monomers were photopolymerized in cyclic olefin copolymer microdevices and studied for the selective retention and elution of a fluorescent dye and PTB biomarkers. Octyl methacrylate-based monoliths with desirable retention and elution characteristics were chosen and used for on-chip fluorescent labeling of three PTB biomarkers. Purification of on-chip labeled samples was done by selective elution of unreacted dye prior to sample. Automated and rapid on-chip fluorescent labeling was achieved with similar efficiency to that obtained for samples labeled off chip. Additionally, protocols for microchip electrophoresis of several off-chip-labeled PTB biomarkers were demonstrated in poly(methyl methacrylate) microfluidic devices. This study is an important step toward the development of integrated on-chip labeling and separation microfluidic devices for PTB biomarkers.


Zinc and liver disease.
Zinc is an essential trace element required for normal cell growth, development, and differentiation. It is involved in DNA synthesis, RNA transcription, and cell division and activation. It is a critical component in many zinc protein/enzymes, including critical zinc transcription factors. Zinc deficiency/altered metabolism is observed in many types of liver disease, including alcoholic liver disease (ALD) and viral liver disease. Some of the mechanisms for zinc deficiency/altered metabolism include decreased dietary intake, increased urinary excretion, activation of certain zinc transporters, and induction of hepatic metallothionein. Zinc deficiency may manifest itself in many ways in liver disease, including skin lesions, poor wound healing/liver regeneration, altered mental status, or altered immune function. Zinc supplementation has been documented to block/attenuate experimental ALD through multiple processes, including stabilization of gut-barrier function, decreasing endotoxemia, decreasing proinflammatory cytokine production, decreasing oxidative stress, and attenuating apoptotic hepatocyte death. Clinical trials in human liver disease are limited in size and quality, but it is clear that zinc supplementation reverses clinical signs of zinc deficiency in patients with liver disease. Some studies suggest improvement in liver function in both ALD and hepatitis C following zinc supplementation, and 1 study suggested improved fibrosis markers in hepatitis C patients. The dose of zinc used for treatment of liver disease is usually 50 mg of elemental zinc taken with a meal to decrease the potential side effect of nausea.


Urbanization effects on tree growth in the vicinity of New York City.
Plants in urban ecosystems are exposed to many pollutants and higher temperatures, CO2 and nitrogen deposition than plants in rural areas. Although each factor has a detrimental or beneficial influence on plant growth, the net effect of all factors and the key driving variables are unknown. We grew the same cottonwood clone in urban and rural sites and found that urban plant biomass was double that of rural sites. Using soil transplants, nutrient budgets, chamber experiments and multiple regression analyses, we show that soils, temperature, CO2, nutrient deposition, urban air pollutants and microclimatic variables could not account for increased growth in the city. Rather, higher rural ozone (O3) exposures reduced growth at rural sites. Urban precursors fuel the reactions of O3 formation, but NO(x) scavenging reactions resulted in lower cumulative urban O3 exposures compared to agricultural and forested sites throughout the northeastern USA. Our study shows the overriding effect of O3 despite a diversity of altered environmental factors, reveals 'footprints' of lower cumulative urban O3 exposures amidst a background of higher regional exposures, and shows a greater adverse effect of urban pollutant emissions beyond the urban core.


Laboratory investigation of thrombophilia: the good, the bad, and the ugly.
Thrombophilia can be broadly defined as an increased tendency toward hypercoagulability and venous thrombosis. There are several defined risk factors for thrombosis, and these are generally distinguished as either acquired or congenital, although sometimes this distinction is blurred because of interrelationships. Congenital risk factors include deficiencies or defects in natural anticoagulants, such as antithrombin, Protein C and Protein S, and genetic polymorphisms such as prothrombin G20210A and cleavage-resistant forms of factor V (in particular factor V Leiden), that lead to a condition commonly known as activated protein C resistance. Acquired risk factors include antiphospholipid antibodies, detected as lupus anticoagulants and/or anticardiolipin antibodies and/or anti-beta-2-glycoprotein-I antibodies. High levels of clotting factors, dysfibrinogenemia, hyperhomocysteinemia, prolonged immobilization, increasing age, surgery, trauma, cancer, obesity, poor nutrition, pregnancy, oral contraceptives, and hormone replacement therapy comprise just some of the other risk factors. Each of these elements constitutes a component of increased risk, which is compounded when concomitant. There is ongoing debate regarding relative and compound risks, the value of laboratory screening, whom and when to screen for these markers, which tests and methodologies to use, and the form and duration of therapeutic management. The current article explores several important issues primarily from a scientific perspective and predominantly related to laboratory testing. Many of these issues appear to be simply overlooked by some clinicians managing patients with thromboses. In brief, although there is potential significance in testing for various thrombophilia-associated markers, this value is limited and greatly diminishes when inappropriately applied. The application of excessive or inappropriate thrombophilia testing is of particular concern, and the net effect of current worldwide testing trends is likely to be more detrimental than beneficial. In short, it is likely that current generalized testing is simply doing more harm than good, and thus that ordering practice requires scrutiny.


Mixed azide and 5-(pyrimidyl)tetrazole bridged Co(II)/Mn(II) polymers: synthesis, crystal structures, ferroelectric and magnetic behavior.
The reaction of pyrimidine-2-carbonitrile, NaN(3) in the presence of Co(NO(3))(2)·6H(2)O or MnCl(2)·4H(2)O leads to the formation of complexes [Co(pmtz)(μ(1,3)-N(3))(H(2)O)](n) (1) and [Mn(pmtz)(μ(1,3)-N(3))(H(2)O)](n) (2) respectively, under hydrothermal condition [pmtz = 5-(pyrimidyl)tetrazolate]. These two complexes have been fully characterized by single crystal X-ray diffraction. Complex 1 crystallizes in a non-centrosymmetric space group Aba2 in the orthorhombic system and is found to exhibit ferroelectric behavior, whereas complex 2 crystallizes in the P2(1)/c space group in the monoclinic system. Variable temperature magnetic characterizations in the temperature range of 2-300 K indicate that complex 1 is a canted antiferromagnet (weak ferromagnet) with T(c) = 15.9 K. Complex 1 represents a unique example of a multiferroic coordination polymer containing tetrazole as a co-ligand. Complex 2 is a one-dimensional chain of Mn(II) bridged by a well-known antiferromagnetic coupler end-to-end azido ligand. In contrast to the role played by the end-to-end azido pathway in most of the transition metal complexes, complex 2 showed unusual ferromagnetic behavior below 40 K because of spin canting.


Differential segregation of human and hamster cathepsin D in transfected baby-hamster kidney cells.
The segregation of human cathepsin D, studied in baby-hamster kidney cells (BHK) transfected with human cathepsin D cDNA and compared with that of hamster cathepsin D in the same cells, showed that, in cells that expressed human cathepsin D at a low rate, most of the enzyme remained intracellular. In contrast, when the enzyme was expressed at a high rate, most was secreted. The segregation was examined with an anti-(human cathepsin D) antibody that reacted with the human enzyme exclusively and an anti-(rat cathepsin D) antibody that reacted with both enzymes. In one protocol the cells were metabolically labelled and the two antibodies were used in sequence to precipitate the enzymes from extracts of cells and medium. High expression of the human enzyme did not interfere with the segregation of hamster cathepsin D. In another protocol the activity of cathepsin D in cells and medium was measured before and after titration with anti-(human cathepsin D) antiserum. Human cathepsin D was found predominantly in the medium, and hamster cathepsin D mainly in the cells. In the presence of 10 mM-NH4Cl the intracellular segregation of hamster cathepsin D was strongly inhibited, while the segregation of human cathepsin D was only slightly diminished. In BHK cells, at least two systems participate in the sorting of the two cathepsins, one of them being rather insensitive to NH4Cl.


The elixir phase of chain molecules.
A phase of matter is a familiar notion for inanimate physical matter. The nature of a phase of matter transcends the microscopic material properties. For example, materials in the liquid phase have certain common properties independent of the chemistry of the constituents: liquids take the shape of the container; they flow; and they can be poured-alcohol, oil, and water as well as a Lennard-Jones computer model exhibit similar behavior when poised in the liquid phase. Here, we identify a hitherto unstudied "phase" of matter, the elixir phase, in a simple model of a polymeric chain whose backbone has the correct local cylindrical symmetry induced by the tangent to the chain. The elixir phase appears on breaking the cylindrical symmetry by adding side spheres along the negative normal direction, as in proteins. This phase, nestled between other phases, has multiple ground states made up of building blocks of helices and almost planar sheets akin to protein native folds. We discuss the similarities of this "phase" of a finite size system to the liquid crystal and spin glass phases. Our findings are relevant for understanding proteins; the creation of novel bioinspired nanomachines; and also may have implications for life elsewhere in the cosmos.


The dynamic duo: combining NMR and small angle scattering in structural biology.
Structural biology provides essential information for elucidating molecular mechanisms that underlie biological function. Advances in hardware, sample preparation, experimental methods, and computational approaches now enable structural analysis of protein complexes with increasing complexity that more closely represent biologically entities in the cellular environment. Integrated multidisciplinary approaches are required to overcome limitations of individual methods and take advantage of complementary aspects provided by different structural biology techniques. Although X-ray crystallography remains the method of choice for structural analysis of large complexes, crystallization of flexible systems is often difficult and does typically not provide insights into conformational dynamics present in solution. Nuclear magnetic resonance spectroscopy (NMR) is well-suited to study dynamics at picosecond to second time scales, and to map binding interfaces even of large systems at residue resolution but suffers from poor sensitivity with increasing molecular weight. Small angle scattering (SAS) methods provide low resolution information in solution and can characterize dynamics and conformational equilibria complementary to crystallography and NMR. The combination of NMR, crystallography, and SAS is, thus, very useful for analysis of the structure and conformational dynamics of (large) protein complexes in solution. In high molecular weight systems, where NMR data are often sparse, SAS provides additional structural information and can differentiate between NMR-derived models. Scattering data can also validate the solution conformation of a crystal structure and indicate the presence of conformational equilibria. Here, we review current state-of-the-art approaches for combining NMR, crystallography, and SAS data to characterize protein complexes in solution.


Independent evolution of transcriptional inactivation on sex chromosomes in birds and mammals.
X chromosome inactivation in eutherian mammals has been thought to be tightly controlled, as expected from a mechanism that compensates for the different dosage of X-borne genes in XX females and XY males. However, many X genes escape inactivation in humans, inactivation of the X in marsupials is partial, and the unrelated sex chromosomes of monotreme mammals have incomplete and gene-specific inactivation of X-linked genes. The bird ZW sex chromosome system represents a third independently evolved amniote sex chromosome system with dosage compensation, albeit partial and gene-specific, via an unknown mechanism (i.e. upregulation of the single Z in females, down regulation of one or both Zs in males, or a combination). We used RNA-fluorescent in situ hybridization (RNA-FISH) to demonstrate, on individual fibroblast cells, inactivation of 11 genes on the chicken Z and 28 genes on the X chromosomes of platypus. Each gene displayed a reproducible frequency of 1Z/1X-active and 2Z/2X-active cells in the homogametic sex. Our results indicate that the probability of inactivation is controlled on a gene-by-gene basis (or small domains) on the chicken Z and platypus X chromosomes. This regulatory mechanism must have been exapted independently to the non-homologous sex chromosomes in birds and mammals in response to an over-expressed Z or X in the homogametic sex, highlighting the universal importance that (at least partial) silencing plays in the evolution on amniote dosage compensation and, therefore, the differentiation of sex chromosomes.


A Comprehensive Analysis of Cell Type-Specific Nuclear RNA From Neurons and Glia of the Brain.
Studies in psychiatric genetics have identified >100 loci associated with disease risk, yet many of these loci are distant from protein coding genes. Recent characterization of the transcriptional landscape of cell lines and whole tissues has suggested widespread transcription in both coding and noncoding regions of the genome, including differential expression from loci that produce regulatory noncoding RNAs that function within the nucleus; however, the nuclear transcriptome of specific cell types in the brain has not been previously investigated. We defined the nuclear transcriptional landscape of the three major cellular divisions of the nervous system using flow sorting of genetically labeled nuclei from bacTRAP mouse lines. Next, we characterized the unique expression of coding, noncoding, and intergenic RNAs in the mature mouse brain with RNA-Seq and validation with independent methods. We found diverse expression across the cell types of all classes of RNAs, including long noncoding RNAs, several of which were confirmed as highly enriched in the nuclei of specific cell types using anatomic methods. We also discovered several examples of cell type-specific expression of tandem gene fusions, and we report the first cell type-specific expression of circular RNAs-a neuron-specific and nuclear-enriched RNA arising from the gene Hnrnpu. These data provide an important resource for studies evaluating the function of various noncoding RNAs in the brain, including noncoding RNAs that may play a role in psychiatric disease.


Thermophysiological, haematological, biochemical and behavioural stress responses of sheep transported on road.
The study was conducted to evaluate the thermophysiological, haematological, biochemical and behavioural stress responses of sheep transported on road. A total of 44 Chamarita breed adult ewes were randomly allotted to one of two groups, one control group (untransported) and transported group (journey of 4 h), and blood stress indicators were measured 1 day before transport and at four time points post-transport (0, 4 and 24 h). Thermophysiological profiles of ewes were measured by temperature buttons (iButton Thermochron® ) and placed in intravaginal sponges. Direct observations, with a combination of scan and behaviour sampling, were carried out to collect information on individual behaviour and the time it took the ewes to drink water, eat and rest after returning to their pen respectively. Transported ewes lost approximately 1 kg live weight compared to controls and had higher body temperatures until 12 h post-transport. Cortisol, glucose, non-esterified fatty acid (NEFA) concentrations as well as the neutrophil-lymphocyte ratio (N/L) and other physiological indicators were higher immediately after unloading in transported ewes but mostly returned to normal after 4 h, with complete recovery after 24 h. Behavioural analysis post-transport demonstrated that transported ewes chose to eat before drinking and spent less time resting than controls in the first 3 h after unloading. The study demonstrates that transportation even under short-journey conditions induced behavioural, physiological and thermophysiological responses indicative of the induction of significant stress, leading to live weight shrinkage that may jeopardize farmer's incomes. Finally, results of this study validated the use of iButton Thermochron® data loggers for monitoring the stress response during transport.


A microfluidic ExoSearch chip for multiplexed exosome detection towards blood-based ovarian cancer diagnosis.
Tumor-derived circulating exosomes, enriched with a group of tumor antigens, have been recognized as a promising biomarker source for cancer diagnosis via a less invasive procedure. Quantitatively pinpointing exosome tumor markers is appealing, yet challenging. In this study, we developed a simple microfluidic approach (ExoSearch) which provides enriched preparation of blood plasma exosomes for in situ, multiplexed detection using immunomagnetic beads. The ExoSearch chip offers a robust, continuous-flow design for quantitative isolation and release of blood plasma exosomes in a wide range of preparation volumes (10 μL to 10 mL). We employed the ExoSearch chip for blood-based diagnosis of ovarian cancer by multiplexed measurement of three exosomal tumor markers (CA-125, EpCAM, CD24) using a training set of ovarian cancer patient plasma, which showed significant diagnostic power (a.u.c. = 1.0, p = 0.001) and was comparable with the standard Bradford assay. This work provides an essentially needed platform for utilization of exosomes in clinical cancer diagnosis, as well as fundamental exosome research.


Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase.
A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE -/-) versus wild type (AChE +/+) mice indicated that while these OPs inhibited axonal growth in AChE+/+ DRG neurons, they had no effect on axonal growth in AChE -/- DRG neurons. However, transfection of AChE -/- DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs.


Is fenofibrate a cost-saving treatment for middle-aged individuals with type II diabetes? An economic analysis of the FIELD Study.
The aim of this study was to determine the impact of fenofibrate therapy on health care costs in middle-aged patients with type II diabetes at high risk of future cardiovascular events. We undertook an economic analysis of the FIELD study conducted from the perspective of the third party payer (direct costs) with all "within trial" health care costs derived from reported clinical outcomes using pooled data from all 9795 study participants. All analyses were performed on an intention-to-treat-basis and items of expenditure were derived from 2001/2002 health economic data: comparing Diagnostic Related Groupings (DRG) costs of major morbid events from an average of unit costs derived from three European countries (UK, France and Germany). Despite the additional cost of applying fenofibrate therapy, that was off-set slightly by a reduced need for supplementary lipid-lowering therapy (a net cost increase of 20,495 Euros per 1000 person years to apply combined lipid-lowering therapy), fenofibrate was associated with a net saving of 23,607 Euros in health care costs per 1000 person years of follow-up. This represents an approximate 10% net saving in health care costs (total of 227,111 versus 203,415 Euros for the placebo and treatment groups, respectively). As such, based on the 95% CI calculated for observed event rates per 1000 person years at risk, the cost impact of fenofibrate therapy ranged from a 24% net saving to a 4% net increase in health care costs relative to treatment with placebo. When the highest compared to lowest DRG unit costs were applied to observed event rates, the cost impact of fenofibrate therapy varied from a 5% to 12% net saving (low versus high cost health care models) in health care costs relative to usual care. The robust nature of these analyses suggest potential cost advantages in the longer-term by applying fenofibrate in this type of patient cohort (quite possibly in combination with statin therapy) via a marked reduction in costly cardiac events and procedures.


A New Approach to Pathogen Containment in the Operating Room: Sheathing the Laryngoscope After Intubation.
Anesthesiologists may contribute to postoperative infections by means of the transmission of blood and pathogens to the patient and the environment in the operating room (OR). Our primary aims were to determine whether contamination of the IV hub, the anesthesia work area, and the patient could be reduced after induction of anesthesia by removing the risk associated with contaminants on the laryngoscope handle and blade. Therefore, we conducted a study in a simulated OR where some of the participants sheathed the laryngoscope handle and blade in a glove immediately after it was used to perform an endotracheal intubation. Forty-five anesthesiology residents (postgraduate year 2-4) were enrolled in a study consisting of identical simulation sessions. On entry to the simulated OR, the residents were asked to perform an anesthetic, including induction and endotracheal intubation timed to approximately 6 minutes. Of the 45 simulation sessions, 15 were with a control group conducted with the intubating resident wearing single gloves, 15 with the intubating resident using double gloves with the outer pair removed and discarded after verified intubation, and 15 wearing double gloves and sheathing the laryngoscope in one of the outer gloves after intubation. Before the start of the scenario, the lips and inside of the mouth of the mannequin were coated with a fluorescent marking gel. After each of the 45 simulations, an observer examined the OR using an ultraviolet light to determine the presence of fluorescence on 25 sites: 7 on the patient and 18 in the anesthesia environment. Of the 7 sites on the patient, ultraviolet light detected contamination on an average of 5.7 (95% confidence interval, 4.4-7.2) sites under the single-glove condition, 2.1 (1.5-3.1) sites with double gloves, and 0.4 (0.2-1.0) sites with double gloves with sheathing. All 3 conditions were significantly different from one another at P < 0.001. Of the 18 environmental sites, ultraviolet light detected fluorescence on an average of 13.2 (95% confidence interval, 11.3-15.6) sites under the single-glove condition, 3.5 (2.6-4.7) with double gloves, and 0.5 (0.2-1.0) with double gloves with sheathing. Again, all 3 conditions were significantly different from one another at P < 0.001. The results of this study suggest that when an anesthesiologist in a simulated OR sheaths the laryngoscope immediately after endotracheal intubation, contamination of the IV hub, patient, and intraoperative environment is significantly reduced.


Imaging, image processing and pattern analysis of skin capillary ensembles.
BACKGROUND/AIMS: The capillary bed is recognized as the site where metabolic and nutrient processes occur for living tissues at all levels. The evaluation of this vital process is a major concern in microcirculation. Unlike traditional approaches that concentrated on the extreme local properties of this process, a more global analysis toward capillary ensembles is employed here, since capillaries work as a cooperative entirety. As a first step toward ensemble analysis, the static and planar geometric parameters are investigated. Parameters such as the capillary adjacency and size information are very important in predicting and analysing certain malfunctions in the microvascular bed. METHODS/RESULTS: In order to achieve an objective and accurate analysis of these vital parameters, a computerized imaging system is proposed. Not only the number of capillaries and the capillary cross-sectional areas are important in describing the microvascular bed but the planar distribution pattern of the capillaries also carries valid information. This information, unique to the ensemble analysis, can be used to reveal, visualise and quantify the clustering of capillaries; and this information, according to the Krogh model, is fundamental in estimating the tissue oxygen supply. Two spatial models, the closest neighbor and triangulation methods, have been applied to the captured images of capillary ensembles. The closest neighbor technique generates a minimal distance map or displays a distribution, which depicts the local clustering of capillaries. The triangulation technique, on the other hand, generates a mutual distance map, which is a global description of the capillary positions. Triangulation methods have been evaluated but all except the Greedy triangulation method have been rejected due to lack of robustness and model weakness. Therefore, the capillaries are triangulated by the Greedy triangulation method, and the capillary distribution uniformity is defined as one minus the coefficient of variance of the edge lengths of the mutual distance map. CONCLUSIONS: A series of advanced image processing methods have been developed that efficiently extract the capillary position, size and distribution information from the images. These results facilitate the automatic counting of capillaries and the capillary size-related pathological analysis.


COVID-19 Prognosis via Self-Supervised Representation Learning and Multi-Image Prediction.
The rapid spread of COVID-19 cases in recent months has strained hospital resources, making rapid and accurate triage of patients presenting to emergency departments a necessity. Machine learning techniques using clinical data such as chest X-rays have been used to predict which patients are most at risk of deterioration. We consider the task of predicting two types of patient deterioration based on chest X-rays: adverse event deterioration (i.e., transfer to the intensive care unit, intubation, or mortality) and increased oxygen requirements beyond 6 L per day. Due to the relative scarcity of COVID-19 patient data, existing solutions leverage supervised pretraining on related non-COVID images, but this is limited by the differences between the pretraining data and the target COVID-19 patient data. In this paper, we use self-supervised learning based on the momentum contrast (MoCo) method in the pretraining phase to learn more general image representations to use for downstream tasks. We present three results. The first is deterioration prediction from a single image, where our model achieves an area under receiver operating characteristic curve (AUC) of 0.742 for predicting an adverse event within 96 hours (compared to 0.703 with supervised pretraining) and an AUC of 0.765 for predicting oxygen requirements greater than 6 L a day at 24 hours (compared to 0.749 with supervised pretraining). We then propose a new transformer-based architecture that can process sequences of multiple images for prediction and show that this model can achieve an improved AUC of 0.786 for predicting an adverse event at 96 hours and an AUC of 0.848 for predicting mortalities at 96 hours. A small pilot clinical study suggested that the prediction accuracy of our model is comparable to that of experienced radiologists analyzing the same information.


Effect of magnesium supplementation on blood pressure: a meta-analysis.
To date, there has been inconclusive evidence regarding the effect of magnesium supplements on blood pressure (BP). This meta-analysis was conducted to assess the effect of magnesium supplementation on BP and to establish the characteristics of trials showing the largest effect size. Primary outcome measures were systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the end of the follow-up period. One hundred and forty-one papers were identified, of which 22 trials with 23 sets of data (n=1173), with 3 to 24 weeks of follow-up met the inclusion criteria, with a supplemented elemental magnesium range of 120-973 mg (mean dose 410 mg). 95% confidence intervals (CI) were calculated using DerSimonian and Laird's random-effects model, with effect size calculated using Hedges G. Combining all data, an overall effect of 0.36 and 0.32 for DBP and SBP, respectively, was observed (95% CI 0.27-0.44 for DBP and 0.23-0.41 for SBP), with a greater effect being seen for the intervention in crossover trials (DBP 0.47, SBP 0.51). Effect size increased in line with increased dosage. Although not all individual trials showed significance in BP reduction, combining all trials did show a decrease in SBP of 3-4 mm Hg and DBP of 2-3 mm Hg, which further increased with crossover designed trials and intake >370 mg/day. To conclude, magnesium supplementation appears to achieve a small but clinically significant reduction in BP, an effect worthy of future prospective large randomised trials using solid methodology.


Mono- and di-nuclear Re(i) complexes and the role of protonable nitrogen atoms in quenching emission by hydroquinone.
Mono-nuclear fac-[Re(CO)3(ph2phen)(4,4'-bpy)]+ and di-nuclear [(ph2phen)(CO)3Re(4,4'-bpy)Re(ph2phen)(CO)3]2+ complexes, ph2phen = 4,7-diphenyl-1,10-phenanthroline and 4,4'-bpy = 4,4'-bipyridine, were synthesized and characterized by 1H NMR, UV-visible and FT-IR spectroscopy. Also, their photophysical properties were investigated using steady-state and time-resolved emission spectroscopy. Both complexes showed UV absorption assigned to intraligand, 1ILph2phen, and metal-to-ligand charge transfer, 1MLCTRe→ph2phen, transitions, and typical 3MLCTRe→ph2phen emission (ϕ = 0.360 and τ = 3.81 μs; ϕ = 0.177 and τ = 1.90 μs for mono- and di-nuclear, respectively). Additionally, the luminescence of these complexes is quenched by hydroquinone with approximately 4 × 109 L mol-1 s-1 rate constant for the bimolecular excited state, kq. The Stern-Volmer constants, KSV, determined by the emission intensity and lifetime showed excellent correlation, which is indicative of the dynamic quenching. The similarity of the bimolecular rate constants between the two complexes implies that the photoinduced electron transfer is the main pathway with a very small (or no) influence of the proton transfer step. The results provide additional insight into the role of the protonable nitrogen atom in the photophysical properties of rhenium(i) complexes, using a dyad architecture.


Assessing phytochemical intake in a group of Mexican women.
Identify the content of selected phytochemicals (PHYs) in Mexican foods and evaluate the reliability of a food frequency questionnaire (FFQ) in assessing PHYs intake among Mexican women. Values for PHYs content were obtained from four different data sets. PHYs intake was assessed in 50 women of reproductive age enrolled in a longitudinal cohort study. Values were obtained from a FFQ administered twice, one year apart in order to evaluate its reliability. Selected PHYs included flavonol (FOL), flavones (FES), flavanol (FAL), secoisolariciresinol (SE), matairesinol (MA), lariciresinol (LA), pinoresinol (PI), cynamic acid (CA) and coumestrol (CU). Daily PHYs intake ranged from 1.3 microg +/- 0.9 for MA to 116.3 +/- 43.8 mg for CA. The adjusted correlation coefficients ranged from 0.17 for FAL to 0.47 for LA. Pinto beans, oranges, hot sauce, broccoli, apples and onions were the main sources of the selected PHYs daily intake. The results of this study contribute to our understanding of the consumption of PHYs in the Mexican diet, and would help evaluate their potential health impact.


The human N-alpha-acetyltransferase 40 (hNaa40p/hNatD) is conserved from yeast and N-terminally acetylates histones H2A and H4.
Protein N(α)-terminal acetylation (Nt-acetylation) is considered one of the most common protein modification in eukaryotes, and 80-90% of all soluble human proteins are modified in this way, with functional implications ranging from altered protein function and stability to translocation potency amongst others. Nt-acetylation is catalyzed by N-terminal acetyltransferases (NATs), and in yeast five NAT types are identified and denoted NatA-NatE. Higher eukaryotes additionally express NatF. Except for NatD, human orthologues for all yeast NATs are identified. yNatD is defined as the catalytic unit Naa40p (Nat4) which co-translationally Nt-acetylates histones H2A and H4. In this study we identified and characterized hNaa40p/hNatD, the human orthologue of the yeast Naa40p. An in vitro proteome-derived peptide library Nt-acetylation assay indicated that recombinant hNaa40p acetylates N-termini starting with the consensus sequence Ser-Gly-Gly-Gly-Lys-, strongly resembling the N-termini of the human histones H2A and H4. This was confirmed as recombinant hNaa40p Nt-acetylated the oligopeptides derived from the N-termini of both histones. In contrast, a synthetically Nt-acetylated H4 N-terminal peptide with all lysines being non-acetylated, was not significantly acetylated by hNaa40p, indicating that hNaa40p catalyzed H4 N(α)-acetylation and not H4 lysine N(ε)-acetylation. Also, immunoprecipitated hNaa40p specifically Nt-acetylated H4 in vitro. Heterologous expression of hNaa40p in a yeast naa40-Δ strain restored Nt-acetylation of yeast histone H4, but not H2A in vivo, probably reflecting the fact that the N-terminal sequences of human H2A and H4 are highly similar to each other and to yeast H4 while the N-terminal sequence of yeast H2A differs. Thus, Naa40p seems to have co-evolved with the human H2A sequence. Finally, a partial co-sedimentation with ribosomes indicates that hNaa40p co-translationally acetylates H2A and H4. Combined, our results strongly suggest that human Naa40p/NatD is conserved from yeast. Thus, the NATs of all classes of N-terminally acetylated proteins in humans now appear to be accounted for.


Streamlined digital bioassays with a 3D printed sample changer.
Droplet-based microfluidics has permeated many areas of life sciences including biochemistry, biology and medicine. Water-in-oil droplets act as independent femto- to nano-liter reservoirs, enabling the parallelization of (bio)chemical reactions with a minimum sample input. Among the range of applications spanned by droplet microfluidics, digital detection of biomolecules, using Poissonian isolation of single molecules in compartments, has gained considerable attention due to the high accuracy, sensitivity and robustness of these methods. However, while the droplet throughput can be very high, the sample throughput of these methods is poor in comparison to well plate-based assays. This limitation comes from the necessity to convert independently each sample into a monodisperse emulsion. In this paper, we report a versatile device that performs the quick sequential partitioning of up to 15 samples using a single microfluidic chip. A 3D printed sample rotor is loaded with all samples and connected to a pressure source. Simple magnetic actuation is then used to inject the samples in the microfluidic chip without pressure disruption. This procedure generates monodisperse droplets with high sample-to-sample consistency. We also describe a fluorescent barcoding strategy that allows all samples to be collected, incubated, imaged and analyzed simultaneously, thus decreasing significantly the time of the assay. As an example of application, we perform a droplet digital PCR assay for the quantification of a DNA amplicon from 8 samples in less than 2 hours. We further validate our approach demonstrating the parallel quantification of 11 microRNAs from a human sample using an isothermal nucleic acid amplification chemistry. As an off-chip device, the sample changer can be connected to a variety of microfluidic geometries and therefore, used for a wide range of applications.


Analysis of a 1600-kilobase Rhizobium meliloti megaplasmid using defined deletions generated in vivo.
A series of 120-600 kilobase deletions with defined endpoints were made in the 1600-kilobase Rhizobium meliloti megaplasmid pRmeSU47b, by homologous recombination between the IS50 elements of transposon insertions. Utilizing IS 50-mediated homologous recombination we also made defined reductions in deletion size and combined adjacent deletions. Deletion structure was confirmed by phage transduction and Southern hybridization analysis. Collectively these deletions span 1400 kilobases of pRmeSU47b, indicating that the majority of the plasmid is not essential for cell viability. This was further confirmed by the construction of a strain SU47 derivative which carries only 450 kilobases of the pRmeSU47b megaplasmid. Examination of the deletion mutants for phenotype revealed novel loci required for dulcitol, melibiose, raffinose, beta-hydroxybutyrate, acetoacetate, protocatechuate and quinate utilization. Previously unidentified loci required for effective root nodule development and exopolysaccharide synthesis were also found. Various deletion mutants were deficient in dicarboxylate transport, lactose utilization, and thiamine and exopolysaccharide biosynthesis, as predicted from earlier studies of this megaplasmid.


A Software Tool for Heart AVJ Motion Tracking Using Cine Cardiovascular Magnetic Resonance Images.
One important index to assess left ventricular diastolic function is the quantitative measurement of atrioventricular junction (AVJ) motion in one cardiac cycle including systole and diastole. The best way to perform the measurement is to use a software tool that can conduct AVJ motion tracking from cine cardiovascular magnetic resonance (CMR) images. In this paper, a software tool for this purpose is presented by using the insight segmentation and registration toolkit (ITK), the visualization toolkit (VTK), and Qt. We propose a surface area-based tracking approach in the software tool. In the tracking approach to obtain the surface area swept by six points being tracked, we manually select six points from four-, three- and two-chamber views of CMR images. After that, we reconstruct the 3-D coordinates of the six points from image acquisition parameters extracted from DICOM files. We perform interpolation by using parametric cubic curve fitting techniques. From the curve fitting results, we finally obtain the surface areas for all time points in one cardiac cycle. The software tool has been successfully implemented. The functionality include single point-based tracking, surface area-based tracking by using 6 tracked points, generation of displacement, sweep surface area and velocity, and generation of tracking movies. From the software engineering practice, it is concluded that ITK, VTK, and Qt are very handy software systems to implement automatic image analysis functions for CMR images, such as quantitative measure of motion by visual tracking. The software tool provides a convenient and efficient way to measure AVJ motion and extends the scope of methods for ventricular function assessment.


Patient characteristics and patterns of intoxication: one-time and repeated use of emergency ambulance services.
The aim of this study was to investigate the utilization of ambulance services that resulted from alcohol and drug intoxication over a period of 1 year in a metropolitan area, with an emphasis on characteristic differences between patients with one-time versus repeated use. All ambulance-service report forms filed in 2010 were systematically screened for utilizations in which alcohol intoxication or intoxication resulting from consumption of illicit or legal drugs other than alcohol was the chief complaint (N = 2,341 patients; 65% male). Repeat users differed from persons with one-time use in their characteristics and patterns of intoxication. On average, patients with repeated ambulance use were almost 8 years older and had a different pattern of ambulance use over the course of the week with no clear peak on any specific day. The mean number of ambulance services in patients with repeated use was 2.8 (SD = 1.517) in the 1-year study period. Repeat users were less likely to be injured than patients with one-time ambulance-service use and more often showed aggression or uncooperative behavior toward paramedics. All cases of death associated with intoxication involved patients with one-time ambulance use. The ambulance-service users' generally slight impairment of consciousness and the high proportion of intoxicated patients without any injuries raise the question of how many of these patients could be adequately cared for in a sobering center. Sobering centers might relieve hospital emergency departments of patients not requiring acute emergency care and, in addition, could provide intervention services to prevent relapses.


Competing conceptions of diagnostic reasoning--is there a way out?
Diagnostic errors are more frequently a result of the clinician's failure to combine medical knowledge adequately than of data inaccuracy. Diagnostic reasoning studies are valuable to understand and improve diagnostic reasoning. However, most diagnostic reasoning studies are characterized by some limitations which make these studies seem more simple than diagnostic reasoning in real life situations actually is. These limitations are connected both to the failure to acknowledge components of knowledge used in clinical practice as well as to acknowledge the physician-patient relationship's influence on clinical knowledge and on the reasoning process itself. In addition the modes of reasoning described in these studies frequently is oversimplified. In this paper three simplistic and competing models of diagnostic reasoning are analyzed and criticized, followed by an evaluation of two alternative models proposing a combined view.


Investigation of medical effect of multiple ketamine infusions on patients with major depressive disorder.
Single-dose intravenous ketamine has rapid but time-limited antidepressant effects. We aimed to examine the sustained effects of six consecutive ketamine infusions in Chinese patients with major depressive disorder. Seventy-seven patients with major depressive disorder were eligible to receive augmentation with six ketamine infusions (0.5 mg/kg over 40 min) administered over the course of 12 days (Monday-Wednesday-Friday). The coprimary outcome measures were the rates of response and remission as measured on the 10-item Montgomery-Asberg Depression Rating Scale. Psychotomimetic and dissociative symptoms were measured with the Brief Psychiatric Rating Scale-positive symptoms and the Clinician Administered Dissociative States Scale, respectively. After the first ketamine infusion, only 10 (13.0%) and 6 (7.8%) patients responded and remitted, respectively; after six ketamine infusions, 52 (67.5%) patients responded and 37 (48.1%) remitted. There was a significant mean decrease in Montgomery-Asberg Depression Rating Scale score at four hours after the first ketamine infusion (7.0±7.5, p<0.001), and this decrease was maintained for the duration of the infusion period. The response to ketamine treatment was positively associated with no history of psychiatric hospitalization (odds ratio=3.56, p=0.009). Suicidal ideation rapidly decreased across the entire study sample, even among the nonresponder group. No significant differences were found regarding Brief Psychiatric Rating Scale and Clinician Administered Dissociative States Scale scores from the first infusion at baseline to four hours post-infusion. Six ketamine infusions increased rates of response and remission when compared to a single-dose ketamine infusion in patients with major depressive disorder. Future controlled studies are warranted to confirm and expand these findings.


The Infant Feeding Genogram: a tool for exploring family infant feeding history and identifying support needs.
Family culture and beliefs are passed through the generations within families and influence what constitutes appropriate infant care. This includes infant feeding decisions where a family history and support network congruent with women's infant feeding intentions has been shown to be important to women's breastfeeding experience. This is reflected in breastfeeding rates where women who were not breastfed themselves are less likely to initiate and continue with breastfeeding. Given the importance of family infant feeding history in the initiation and duration of breastfeeding, and the limited ability of some families to provide support; it is unclear why infant feeding family history and support networks are not explored during pregnancy. The Infant Feeding Genogram was adapted from a simple pictorial device that is widely used in psychotherapy and genetic counselling. This tool was developed as part of a study investigating the experience of women when they were the first to breastfeed in their family. Fourteen Scottish participants completed their Infant Feeding Genogram as part of a semi-structured interview. The tool was adapted alongside their narratives to give a visual representation of each participant's family infant feeding history. The utility of the genogram is illustrated through two contrasting case examples with very different family feeding histories. The genogram showed family structures, patterns of infant feeding over time, and supportive or conflicting relationships. In the research setting it assisted women to explore their infant feeding history, identify challenges and sources of support and build rapport with the interviewer. The infant feeding genogram is proposed as a time efficient tool that could assist health professionals and other breastfeeding workers to support women and their families and by stimulating discussion around breastfeeding, Bby identifying strengths or possible deficits in social support for each individual, the tool could inform tailored support and care interventions. The effectiveness and acceptability of the Infant Feeding Genogram requires testing in the clinical environment. However, its successful application in other clinical contexts, combined with the interest in genealogy in popular culture, mean this is likely to be an acceptable, family friendly way to develop more effective breastfeeding conversations.


The seco-iridoid pathway from Catharanthus roseus.
The (seco)iridoids and their derivatives, the monoterpenoid indole alkaloids (MIAs), form two large families of plant-derived bioactive compounds with a wide spectrum of high-value pharmacological and insect-repellent activities. Vinblastine and vincristine, MIAs used as anticancer drugs, are produced by Catharanthus roseus in extremely low levels, leading to high market prices and poor availability. Their biotechnological production is hampered by the fragmentary knowledge of their biosynthesis. Here we report the discovery of the last four missing steps of the (seco)iridoid biosynthesis pathway. Expression of the eight genes encoding this pathway, together with two genes boosting precursor formation and two downstream alkaloid biosynthesis genes, in an alternative plant host, allows the heterologous production of the complex MIA strictosidine. This confirms the functionality of all enzymes of the pathway and highlights their utility for synthetic biology programmes towards a sustainable biotechnological production of valuable (seco)iridoids and alkaloids with pharmaceutical and agricultural applications.


Performance of the LACE index to predict 30-day hospital readmissions in patients with chronic obstructive pulmonary disease.
Patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease (COPD) have a high 30-day hospital readmission rate, which has a large impact on the health care system and patients' quality of life. The use of a prediction model to quantify a patient's risk of readmission may assist in directing interventions to patients who will benefit most. The objective of this study was to calculate the rate of 30-day readmissions and evaluate the accuracy of the LACE index (length of stay, acuity of admission, co-morbidities, and emergency department visits within the last 6 months) for 30-day readmissions in a general hospital population of COPD patients. All patients admitted with a principal diagnosis of COPD to Liverpool Hospital, a tertiary hospital in Sydney, Australia, between 2006 and 2016 were included in the study. A LACE index score was calculated for each patient and assessed using receiver operator characteristic curves. During the study period, 2,662 patients had 5,979 hospitalizations for COPD. Four percent of patients died in hospital and 25% were readmitted within 30 days; 56% of all 30-day readmissions were again due to COPD. The most common reasons for readmission, following COPD, were heart failure, pneumonia, and chest pain. The LACE index had moderate discriminative ability to predict 30-day readmission (C-statistic =0.63). The 30-day hospital readmission rate was 25% following hospitalization for COPD in an Australian tertiary hospital and as such comparable to international published rates. The LACE index only had moderate discriminative ability to predict 30-day readmission in patients hospitalized for COPD.


Radiographic validation of a self-report instrument for hallux valgus.
Hallux valgus (HV) is a common condition causing substantial morbidity. Radiographic assessment is the gold standard for grading severity but is not always feasible in clinical/research settings. HV line-drawings, consisting of five drawings for each foot depicting a sequential increase in HV angle of 15°, have been clinically validated for self-reporting severity. We aimed to undertake radiographic validation of this self-report instrument. Adults aged ≥50 from four GP practices were sent a health survey. Responders self-reported HV severity for each foot using the line-drawing instrument. Those reporting foot pain in the last year had radiographs taken at a research clinic from which intermetatarsal, hallux abductus and hallux interphalangeal abductus angles were calculated. Ten feet were randomly selected for each HV line-drawing grade for both feet. Associations between self-reported HV line drawings and radiographic measurements were assessed using Spearman's ρ correlation coefficients, mean radiographic angle measurement (95% confidence interval) and one-way analysis of variance. Increasing HV line-drawing grade was positively correlated with radiographic measurements for intermetatarsal and hallux abductus angles (Spearman's ρ = 0.602, p < 0.001; 0.821, p < 0.001, respectively). Hallux interphalangeal abductus angle showed an inverse correlation with increasing line-drawing grade (-0.204, p = 0.053). Differences in radiographic measures between HV line drawing grades were significant for intermetatarsal (F = 13.98, p < 0.001) hallux abductus (F = 38.90, p < 0.001) but not hallux interphalangeal abductus angle (F = 2.21, p = 0.075). Grading HV severity by self-reported HV line-drawings provides a valid representation of deformity determined from radiographic measurements and is a useful screening/self-reporting tool.


Fishery consequences of marine reserves: short-term pain for longer-term gain.
Marine reserves are often established in areas that support fisheries. Larval export from reserves is argued to help compensate for the loss of fishable habitat; however, previous modeling studies have focused on long-term equilibrium outcomes. We examined the transient consequences of reserve establishment for fished metapopulations, considering both a well-mixed larval pool and a spatially explicit model based on a coral trout (Plectropomus spp.) metapopulation. When fishing pressure was reallocated relative to the area protected, yields decreased initially, then recovered, and ultimately exceeded pre-reserve levels. However, recovery time was on the order of several years to decades. If fishing pressure intensified to maintain pre-reserve yields, reserves were sometimes unable to support the increased mortality and the metapopulation collapsed. This was more likely when reserves were small, or located peripherally within the metapopulation. Overall, reserves can achieve positive conservation and fishery benefits, but fisheries management complementary to reserve implementation is essential.


Parkinson's disease is associated with hippocampal atrophy.
Patients with Parkinson's disease (PD) may have hippocampal atrophy compared with controls. We compared hippocampal, and extra-hippocampal volumes between PD, PDD (patients with PD who have mild cognitive impairment or dementia), Alzheimer's disease (AD) and controls using volumetric magnetic resonance imaging (MRI). Participants (10 patients with PD, 10 with PDD, 11 with AD, and 12 control subjects) had an informant interview, neurological examination, and psychometric testing. Established, reliable methods were used to measure the hippocampus, parahippocampal gyrus, temporal, frontal, and parieto-occipital lobes. Correction for intracranial volume was carried out before comparison. There was no age difference between groups (mean age, 74 years). On the Clinical Dementia Rating scale (CDR) cognitive impairment was mild (CDR = 0.5) in the majority of PDD and AD patients. Hippocampal (P < 0.0004) volumes were smaller in the patient groups. Effect sizes compared with the control group were: PD, 0.66; PDD, 1.22; and AD, 1.81. The other volumes did not differ significantly. Among PD and PDD patients, recognition memory (r = 0.54, P = 0.015) and Mini-Mental State Examination scores (r = 0.56, P = 0.01) correlated with left, but not right hippocampal volume. In conclusion, hippocampal volume showed a pattern (Control > PD > PDD > AD) suggesting progressive hippocampal volume loss in PD. Volumetric MRI imaging might provide an early marker for dementia in PD.


Antitumor effects of ZD6474 on head and neck squamous cell carcinoma.
Angiogenesis is required for tumor growth and metastasis and, therefore, represents a target for cancer treatment. While many factors have been implicated in promoting angiogenesis, vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. ZD6474 is a potent VEGF receptor-2 (VEGFR-2) tyrosine kinase inhibitor which also has activity against the epidermal growth factor receptor (EGFR) tyrosine kinase. The purpose of this study was to investigate the sensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines to ZD6474, and to evaluate its antitumor efficacy on HNSCC xenografts. This is the first demonstration of antitumor effects of ZD6474 on HNSCC. In vitro ZD6474 displayed antiproliferative effects on HNSCC cells and inhibition of VEGFR-2 and EGFR pathways. In vivo ZD6474 displayed antitumor activity, induced apoptosis and antiangiogenic activity on nude mice bearing an established xenograft of YCU-H891 cells. These results suggest that ZD6474 has the potential to inhibit two key pathways in tumor growth via inhibition of VEGF-dependent tumor angiogenesis and via inhibition of EGFR-dependent tumor cell proliferation.


LOINC® - A Universal Catalog of Individual Clinical Observations and Uniform Representation of Enumerated Collections.
In many areas of practice and research, clinical observations are recorded on data collection forms by asking and answering questions, yet without being represented in accepted terminology standards these results cannot be easily shared among clinical care and research systems. LOINC contains a well-developed model for representing variables, answer lists, and the collections that contain them. We have successfully added many assessments and other collections of variables to LOINC in this model. By creating a uniform representation and distributing it worldwide at no cost, LOINC aims to lower the barriers to interoperability among systems and make this valuable data available across settings when and where it is needed.


The heavy vehicle study: a case-control study investigating risk factors for crash in long distance heavy vehicle drivers in Australia.
Heavy vehicle transportation continues to grow internationally; yet crash rates are high, and the risk of injury and death extends to all road users. The work environment for the heavy vehicle driver poses many challenges; conditions such as scheduling and payment are proposed risk factors for crash, yet the precise measure of these needs quantifying. Other risk factors such as sleep disorders including obstructive sleep apnoea have been shown to increase crash risk in motor vehicle drivers however the risk of heavy vehicle crash from this and related health conditions needs detailed investigation. The proposed case control study will recruit 1034 long distance heavy vehicle drivers: 517 who have crashed and 517 who have not. All participants will be interviewed at length, regarding their driving and crash history, typical workloads, scheduling and payment, trip history over several days, sleep patterns, health, and substance use. All participants will have administered a nasal flow monitor for the detection of obstructive sleep apnoea. Significant attention has been paid to the enforcement of legislation aiming to deter problems such as excess loading, speeding and substance use; however, there is inconclusive evidence as to the direction and strength of associations of many other postulated risk factors for heavy vehicle crashes. The influence of factors such as remuneration and scheduling on crash risk is unclear; so too the association between sleep apnoea and the risk of heavy vehicle driver crash. Contributory factors such as sleep quality and quantity, body mass and health status will be investigated. Quantifying the measure of effect of these factors on the heavy vehicle driver will inform policy development that aims toward safer driving practices and reduction in heavy vehicle crash; protecting the lives of many on the road network.


Patient-Provider Communication About Prostate Cancer Screening and Treatment: New Evidence From the Health Information National Trends Survey.
The American Urological Association, American Cancer Society, and American College of Physicians recommend that patients and providers make a shared decision with respect to prostate-specific antigen (PSA) testing for prostate cancer (PCa). The goal of this study is to determine the extent of patient-provider communication for PSA testing and treatment of PCa and to examine the patient specific factors associated with this communication. Using recent data from the Health Information National Trends Survey, this study examined the association of patient characteristics with four domains of patient-provider communication regarding PSA test and PCa treatment: (1) expert opinion of PSA test, (2) accuracy of PSA test, (3) side effects of PCa treatment, and (4) treatment need of PCa. The current results suggested low level of communication for PSA testing and treatment of PCa across four domains. Less than 10% of the respondents report having communication about all four domains. Patient characteristics like recent medical check-up, regular healthcare provider, global health status, age group, marital status, race, annual household income, and already having undergone a PSA test are associated with patient-provider communication. There are few discussions about PSA testing and PCa treatment options between healthcare providers and their patients, which limits the shared decision-making process for PCa screening and treatment as recommended by the current best practice guidelines. This study helps identify implications for changes in physician practice to adhere with the PSA screening guidelines.


Physical activity in the mass media: an audience perspective.
Physical activity's role in promoting health is highlighted in public health campaigns, news and current affairs, reality television and other programs. An investigation of audience exposure, beliefs and reactions to media portrayals of physical activity offers insights into the salience and influence of this communication. An audience reception study was conducted involving in-depth interviews with 46 adults in New South Wales, Australia. The sample was stratified by gender, age group, area of residence and body mass index. Most respondents could only recall media coverage of physical activity with prompting. Television was the primary channel of exposure, with reality television the dominant source, followed by news programs and sports coverage. The messages most readily recalled were the health risks of inactivity, especially obesity, and the necessity of keeping active. Physical activity was regarded as a matter of personal volition, or for children, parental responsibility. Respondents believed that the media had given physical activity inadequate attention, focused too heavily on risks and not provided practical advice. In Australia, there is a need to counter the framing of physical activity by reality television, and engage the media to generate understanding of the socioecological determinants of inactivity. Physical activity campaigns should deliver positive and practical messages.


A supervised hidden markov model framework for efficiently segmenting tiling array data in transcriptional and chIP-chip experiments: systematically incorporating validated biological knowledge.
Large-scale tiling array experiments are becoming increasingly common in genomics. In particular, the ENCODE project requires the consistent segmentation of many different tiling array datasets into 'active regions' (e.g. finding transfrags from transcriptional data and putative binding sites from ChIP-chip experiments). Previously, such segmentation was done in an unsupervised fashion mainly based on characteristics of the signal distribution in the tiling array data itself. Here we propose a supervised framework for doing this. It has the advantage of explicitly incorporating validated biological knowledge into the model and allowing for formal training and testing. In particular, we use a hidden Markov model (HMM) framework, which is capable of explicitly modeling the dependency between neighboring probes and whose extended version (the generalized HMM) also allows explicit description of state duration density. We introduce a formal definition of the tiling-array analysis problem, and explain how we can use this to describe sampling small genomic regions for experimental validation to build up a gold-standard set for training and testing. We then describe various ideal and practical sampling strategies (e.g. maximizing signal entropy within a selected region versus using gene annotation or known promoters as positives for transcription or ChIP-chip data, respectively). For the practical sampling and training strategies, we show how the size and noise in the validated training data affects the performance of an HMM applied to the ENCODE transcriptional and ChIP-chip experiments. In particular, we show that the HMM framework is able to efficiently process tiling array data as well as or better than previous approaches. For the idealized sampling strategies, we show how we can assess their performance in a simulation framework and how a maximum entropy approach, which samples sub-regions with very different signal intensities, gives the maximally performing gold-standard. This latter result has strong implications for the optimum way medium-scale validation experiments should be carried out to verify the results of the genome-scale tiling array experiments.