Treatment with pegylated interferon alpha-2b and ribavirin in patients unresponsive to previous treatments with standard interferon as monotherapy or combined with ribavirin.
Little information is available on the effect of pegylated interferon (PEG) and ribavirin (RBV) in patients with chronic hepatitis due to virus C (CHC) who were non-responders to previous treatment. To evaluate response to treatment in patients who were non-responders to previous treatment. One hundred and twenty-four patients who were non-responders to previous treatment were included. All patients were treated with PEG alpha 2b interferon (dose: 1.5 mg/kg body weight) and RBV (weight-dependent dosage). A qualitative PCR of virus C after six months was evaluated. In those in whom this was positive, treatment was discontinued; in those who were negative treatment was continued to the end of the year. Response following treatment (RFT) was 35.4% (44 patients), and sustained viral response (SVR) 29.8% (37 patients). No relation was observed between RFT, SVR and any previous treatment. RFT was dependent on low initial viremia and SVR was significantly and independently related to low serum hepatitis C RNA and a non-1 genotype. In general, treatment was well tolerated. Medication was discontinued in 5 patients, and doses reduced in 18. On retreatment with PEG and RBV a SVR of 29.8% was achieved in patients who had not responded to previous treatment, so its use in this group of patients is indicated.


Regulatory non-coding RNAs in pluripotent stem cells.
The most part of our genome encodes for RNA transcripts are never translated into proteins. These include families of RNA molecules with a regulatory function, which can be arbitrarily subdivided in short (less than 200 nucleotides) and long non-coding RNAs (ncRNAs). MicroRNAs, which act post-transcriptionally to repress the function of target mRNAs, belong to the first group. Included in the second group are multi-exonic and polyadenylated long ncRNAs (lncRNAs), localized either in the nucleus, where they can associate with chromatin remodeling complexes to regulate transcription, or in the cytoplasm, acting as post-transcriptional regulators. Pluripotent stem cells, such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), represent useful systems for modeling normal development and human diseases, as well as promising tools for regenerative medicine. To fully explore their potential, however, a deep understanding of the molecular basis of stemness is crucial. In recent years, increasing evidence of the importance of regulation by ncRNAs in pluripotent cells is accumulating. In this review, we will discuss recent findings pointing to multiple roles played by regulatory ncRNAs in ESC and iPSCs, where they act in concert with signaling pathways, transcriptional regulatory circuitries and epigenetic factors to modulate the balance between pluripotency and differentiation.


Interactions between Ambient Air Particles and Greenness on Cause-specific Mortality in Seven Korean Metropolitan Cities, 2008-2016.
This study aims to investigate the association of particulate matter with an aerodynamic diameter smaller than 10 μm (PM10) and greenness with cause-specific mortality and their interactions in seven Korean metropolitan cities. We obtained the annual standardized cause-specific mortality rates, annual mean concentration of PM10, and annual Normalized Difference Vegetation Index (NDVI) for 73 districts for the period 2008-2016. We used negative binomial regression with city-specific random effects to estimate the association of PM10 and greenness with mortality. The models were adjusted for potential confounders and spatial autocorrelation. We also conducted stratified analyses to investigate whether the association between PM10 and mortality differs by the level of greenness. Our findings suggest an increased risk of all causes examined, except respiratory disease mortality, with high levels of PM10 and decreased risk of cardiovascular-related mortality with a high level of greenness. In the stratified analyses, we found interactions between PM10 and greenness, but these interactions in the opposite direction depend on the cause of death. The effects of PM10 on cardiovascular-related mortality were attenuated in greener areas, whereas the effects of PM10 on non-accidental mortality were attenuated in less green areas. Further studies are needed to explore the underlying mechanisms.


[Comparison of diagnostic methods for Clostridium difficile-associated diarrhea].
In order to compare different methods for the diagnosis of Clostridium difficile-associated diarrhea, fecal filtrates from patients presenting symptoms compatible with this condition, were analyzed. Biological activity on Vero cells (biological assay), dot blot with antibodies anti-TcdA and anti-TcdB, and a PCR assay for the tcdB gene, were evaluated. Titles of biological assays were > or =64 for 44 out of 177 samples. Nineteen samples were positive in both biological and PCR assays. The analysis by dot blot using anti-TcdA and anti-TcdB antibodies showed that 46 samples out of 149 were positive for both toxins whereas 12 samples were only positive for TcdB, and 5 samples only positive for TcdA. Discrepancies in the different methods could be related to truncated genes, low number of microorganisms in the samples and toxin degradation. The results herein presented show the need for developing diagnostic approaches compatible with the complex epidemiological situation of this clinically relevant intestinal pathogen.


Assessment of nutritional profiles: a novel system based on a comprehensive approach.
The prevalence of non-communicable diseases (for example, cardiovascular disorders, type 2 diabetes and cancer) is rampant in Western societies, accounting for approximately 60 % of all causes of death. A large proportion of non-communicable diseases can be prevented through appropriate diets and lifestyles. Accordingly, several health authorities and regulatory bodies are assessing the nutritional profiles of food items and whole diets, to implement guidelines aimed at improving the diet of the general population. While a global approach is desirable, the need of individuals to maintain their distinct dietary habits must also be taken into account. The portion sizes of food as well as pattern of food consumption, for example during or between the main meals, are very important in determining the nutritional profile of a diet. A novel method to assess the nutritional profile of foods is being proposed and made available on-line. Its main innovative aspects are (1) the comprehensive manner with which the system analyses and computes a great range of features of individual food items and (2) the distinction among eating occasions, namely during or in-between the main meals. Moreover, this approach allows for rapid modification and great flexibility to suit individual needs and gastronomic habits.


Identification and characterization of insulin receptors on foetal-mouse brain-cortical cells.
The occurrence of insulin receptors was investigated in freshly dissociated brain-cortical cells from mouse embryos. By analogy with classical insulin-binding cell types, binding of 125I-insulin to foetal brain-cortical cells was time- and pH-dependent, only partially reversible, and competed for by unlabelled insulin and closely related peptides. Desalanine-desasparagine-insulin, pig proinsulin, hagfish insulin and turkey insulin were respectively 2%, 4%, 2% and 200% as potent as bovine insulin in inhibiting 125I-insulin binding to brain-cortical cells, which corresponds to their relative biological potencies in classical insulin-target cells; no competition was observed with glucagon and nerve growth factor, even at high concentrations. Scatchard analysis of competitive-binding data resulted in curvilinear plots with a high-affinity binding of Ka = 3.6 X 10(8) M-1. Insulin binding to foetal brain-cortical cells differed, however, in two distinct aspects from that to classical insulin-binding cell types. Firstly, dilution of 125I-insulin-bound cells in the presence of unlabelled insulin did not accelerate dissociation of the labelled hormone. Secondly, exposure of brain-cortical cells to insulin before the binding assay enhanced insulin binding, suggesting up-regulation of insulin receptors in response to insulin. In conclusion, foetal-mouse brain-cortical cells bear specific binding sites for insulin. Their insulin receptor shows a marked specificity and affinity for insulin, but differs in at least two properties from most classical insulin receptors. These differences in hormone-receptor interaction could reflect structural differences between insulin receptors on embryonic and differentiated cells.


Mitochondrial DNA and Y chromosome variation provides evidence for a recent common ancestry between Native Americans and Indigenous Altaians.
The Altai region of southern Siberia has played a critical role in the peopling of northern Asia as an entry point into Siberia and a possible homeland for ancestral Native Americans. It has an old and rich history because humans have inhabited this area since the Paleolithic. Today, the Altai region is home to numerous Turkic-speaking ethnic groups, which have been divided into northern and southern clusters based on linguistic, cultural, and anthropological traits. To untangle Altaian genetic histories, we analyzed mtDNA and Y chromosome variation in northern and southern Altaian populations. All mtDNAs were assayed by PCR-RFLP analysis and control region sequencing, and the nonrecombining portion of the Y chromosome was scored for more than 100 biallelic markers and 17 Y-STRs. Based on these data, we noted differences in the origin and population history of Altaian ethnic groups, with northern Altaians appearing more like Yeniseian, Ugric, and Samoyedic speakers to the north, and southern Altaians having greater affinities to other Turkic speaking populations of southern Siberia and Central Asia. Moreover, high-resolution analysis of Y chromosome haplogroup Q has allowed us to reshape the phylogeny of this branch, making connections between populations of the New World and Old World more apparent and demonstrating that southern Altaians and Native Americans share a recent common ancestor. These results greatly enhance our understanding of the peopling of Siberia and the Americas.


Short-term mechanical circulatory support by veno-arterial extracorporeal membrane oxygenation in the management of cardiogenic shock and end-stage heart failure.
Despite modern treatment modalities, cardiogenic shock is associated with a very high risk of mortality and morbidity. The short- and long-term survival in patients with cardiogenic shock or end-stage heart failure has improved considerably by recent technological advances in short and long-term mechanical circulatory support devices. For short-term mechanical support, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used as bridge-to-decision and bridge-to-recovery in cardiogenic shock patients. Long-term mechanical circulatory support devices such as left ventricular assist devices (LVADs) are widely available and play a central role in bridge-to-transplantation in those eligible for heart transplantation (HTX) and as destination therapy (DT) in those not eligible for heart transplantation. Nevertheless, patients with critical cardiogenic shock show a deleterious outcome after LVAD-implantation or HTX with higher mortality, more complications and higher burden on financial resources. These considerations underscore the importance of optimal timing and appropriate patient selection for eventual LVAD therapy. The current report will focus on the immediate management of patients with cardiogenic shock with inotropes, discuss the use of IABP and focus mainly on pivotal choices to be made in the period spanned by short term mechanical circulatory support in patients with refractory cardiogenic shock.


Synthesis of a poly-pendant 1-D chain based on 'trans-vanadium' bicapped, Keggin-type vanadtungstate and its photocatalytic properties.
A vanadtungstate cluster-based organic-inorganic hybrid material [NiL4V(IV)W(VI)10W(V)2O40(V(IV)O)2] (1, L = 1,4-bis(imidazol-1-ylmethyl)benzene) was synthesized and characterized by elemental analysis, IR spectra, thermal gravimetric analysis, and single crystal X-ray diffraction analysis. Structural analysis reveals that compound 1 contains a transition metal-centered, bicapped Keggin-type {VW12O40(VO)2} core, connected by nickel linkers into a 1-D chain. These 1D chains interdigitated with each other, achieving an interdigitated 3D supermolecular architecture. Photocatalytic studies indicate that compound 1 exhibits not only active photocatalytic degradation of dye molecules, but also selective photocatalytic activity for degradation of cationic dyes in aqueous solution. Further, this photocatalyst is stable and easily separated from the photocatalytic system for reuse as well.


Optical classification of algae species with a glass lab-on-a-chip.
The identification of submillimetre phytoplankton is important for monitoring environmental and climate changes, as well as evaluating water for health reasons. Current standard methods for phytoplankton species identification require sample collection and ex situ analysis, an expensive procedure which prevents the rapid identification of phytoplankton outbreaks. To address this, we use a glass-based microchip with a microchannel and waveguide included on a monolithic substrate, and demonstrate its use for identifying phytoplankton species. The microchannel and the specimens inside it are illuminated by laser light from the curved waveguide as algae-laden water is passed through the channel. The intensity distribution of the light collected from the biochip is monitored with an external photodetector. Here, we demonstrate that the characteristics of the photodiode signal from this simple and robust system can provide significant and useful information as to the contents of the channel. Specifically, we show first that the signals are correlated to the size of algae cells. Using a pattern-matching neural network, we demonstrate the successful classification of five algae species with an average 78% positive identification rate. Furthermore, as a proof-of-concept for field-operation, we show that the chip can be used to distinguish between detritus in field-collected water and the toxin-producing cyanobacterium Cyanothece.


Liking compared with wanting for high- and low-calorie foods in anorexia nervosa: aberrant food reward even after weight restoration.
Recent frameworks for understanding food rewards recognize the role of separable affective and motivational processes (liking and wanting) in driving human eating behavior. Separate assessments of liking and wanting may aid in understanding the complex eating-related behaviors seen in anorexia nervosa (AN). The aim of this study was to examine separately liking and wanting for foods of different energy densities in women at different stages of AN and in healthy volunteers at both an implicit and an explicit level. Explicit liking and wanting responses to high- and low-calorie foods were derived from analog ratings, whereas an implicit "wanting" measure was identified by using reaction time in a forced-choice procedure. Explicit and implicit processes were compared across 3 groups of AN participants (current AN, weight-restored AN, and recovered AN) and healthy volunteers. Currently underweight AN participants explicitly wanted high-calorie foods less than did the other groups. Both current and weight-restored AN groups demonstrated significantly less implicit "wanting" for high-calorie foods and more implicit "wanting" for low-calorie foods-an inverted pattern to never-ill participants. The aberrant responses to food that characterize AN may be driven more by altered motivational salience ("wanting") than by explicit liking responses. This pattern of aberrant food reward appears to be independent of weight status. Examining the processes that motivate approach or avoidance of low- and high-calorie foods in AN may aid the development of targeted strategies to augment existing interventions.


Cryopreservation of specialized chicken lines using cultured primordial germ cells.
Biosecurity and sustainability in poultry production requires reliable germplasm conservation. Germplasm conservation in poultry is more challenging in comparison to other livestock species. Embryo cryopreservation is not feasible for egg-laying animals, and chicken semen conservation has variable success for different chicken breeds. A potential solution is the cryopreservation of the committed diploid stem cell precursors to the gametes, the primordial germ cells ( PGCS: ). Primordial germ cells are the lineage-restricted cells found at early embryonic stages in birds and form the sperm and eggs. We demonstrate here, using flocks of partially inbred, lower-fertility, major histocompatibility complex- ( MHC-: ) restricted lines of chicken, that we can easily derive and cryopreserve a sufficient number of independent lines of male and female PGCs that would be sufficient to reconstitute a poultry breed. We demonstrate that germ-line transmission can be attained from these PGCs using a commercial layer line of chickens as a surrogate host. This research is a major step in developing and demonstrating that cryopreserved PGCs could be used for the biobanking of specialized flocks of birds used in research settings. The prospective application of this technology to poultry production will further increase sustainability to meet current and future production needs.


Filling the Void: Introducing Aromatic Interactions into Solvent Tunnels To Enhance Lipase Stability in Methanol.
An enhanced stability of enzymes in organic solvents is desirable under industrial conditions. The potential of lipases as biocatalysts is mainly limited by their denaturation in polar alcohols. In this study, we focused on selected solvent tunnels in lipase from Geobacillus stearothermophilus T6 to improve its stability in methanol during biodiesel synthesis. Using rational mutagenesis, bulky aromatic residues were incorporated to occupy solvent channels and induce aromatic interactions leading to a better inner core packing. The chemical and structural characteristics of each solvent tunnel were systematically analyzed. Selected residues were replaced with Phe, Tyr, or Trp. Overall, 16 mutants were generated and screened in 60% methanol, from which 3 variants showed an enhanced stability up to 81-fold compared with that of the wild type. All stabilizing mutations were found in the longest tunnel detected in the "closed-lid" X-ray structure. The combination of Phe substitutions in an A187F/L360F double mutant resulted in an increase in unfolding temperature (Tm ) of 7°C in methanol and a 3-fold increase in biodiesel synthesis yield from waste chicken oil. A kinetic analysis with p-nitrophenyl laurate revealed that all mutants displayed lower hydrolysis rates (kcat), though their stability properties mostly determined the transesterification capability. Seven crystal structures of different variants were solved, disclosing new π-π or CH/π intramolecular interactions and emphasizing the significance of aromatic interactions for improved solvent stability. This rational approach could be implemented for the stabilization of other enzymes in organic solvents.IMPORTANCE Enzymatic synthesis in organic solvents holds increasing industrial opportunities in many fields; however, one major obstacle is the limited stability of biocatalysts in such a denaturing environment. Aromatic interactions play a major role in protein folding and stability, and we were inspired by this to redesign enzyme voids. The rational protein engineering of solvent tunnels of lipase from Geobacillus stearothermophilus is presented here, offering a promising approach to introduce new aromatic interactions within the enzyme core. We discovered that longer tunnels leading from the surface to the enzyme active site were more beneficial targets for mutagenesis for improving lipase stability in methanol during biodiesel biosynthesis. A structural analysis of the variants confirmed the generation of new interactions involving aromatic residues. This work provides insights into stability-driven enzyme design by targeting the solvent channel void.


An analysis of optical effects caused by thermally induced mirror deformations.
This paper analyzes thermally induced mirror deformations and their resulting wavefront distortions which occur under the conditions of radially nonuniform mirror heating. The analysis is adaptable to heating produced by any radially nonuniform incident radiation. Specific examples of radiation distributions which are considered are the cosine squared and the gaussian and TEM(0, 1) laser distributions. Deformation effects are examined from two aspects, the first of which is the reflected wavefront radial phase distortion profile caused by the thermally induced surface irregularities at the mirror face. These phase distortion effects appear as aberrations in noncoherent optical applications and as the loss of spatial coherence in coherent applications. The second aspect is the gross wavefront bending due to mirror curvature effects. The analysis considers substrate material, geometry, and cooling in order to determine potential deformation controlling factors. Substrate materials are compared, and performance indicators are suggested to aid in selecting an optimum material for a given heating condition. Deformation examples are given for materials of interest and specific absorbed power levels.


Comorbid PTSD and Social Anxiety Disorder: Associations With Quality of Life and Suicide Attempts.
Posttraumatic stress disorder (PTSD) and social anxiety disorder (SAD) frequently co-occur. Preliminary data from treatment-seeking and veteran samples suggest that the impact of PTSD-SAD comorbidity may be additive, conferring distress and impairment beyond that of either disorder alone. The current study sought to clarify and extend existent research using wave 2 of the National Epidemiologic Survey of Alcohol and Related Conditions, an epidemiological sample of American adults. Individuals who met criteria for comorbid PTSD-SAD were compared to those with either disorder alone on measures of lifetime suicide attempts or quality of life as measured by the Medical Outcomes Study Questionnaire. Relative to those with either PTSD or SAD, individuals with comorbid PTSD-SAD demonstrated an elevated risk of lifetime suicide attempts and substantially lower levels of physical and mental quality of life. The psychosocial consequences of PTSD-SAD comorbidity are substantial. Patients may benefit from early interventions to remediate social distress and improve support networks before more intensive psychotherapeutic interventions.


Quantification of human sebum on skin and human meibum on the eye lid margin using Sebutape®, spectroscopy and chemical analysis.
The purpose of this study was to determine if the variability in the amount of lid margin meibum is from donor-to-donor or from day-to-day variations and to determine if meibum from donors with meibomian gland dysfunction (MGD) had altered levels of casual eyelid meibum or skin sebum. Lipid absorbent Sebutape(®) was used to collect sebum or meibum. Samples were collected from six donors without dry eye and 21 donors with MGD. Lipid absorbed to Sebutape(®) was quantified using infrared and visible absorbance spectroscopy. The amount of sebum from donors with MGD and donors without MGD was not significantly different. The amount of casual meibum from normal donors was 50% lower than that for donors with MGD using the spectroscopic assay, but was not significantly different using the chemical assay. The frequency and bandwidth of the infrared carbonyl band from sebum samples was significantly higher than that for meibum samples which indicates the carbonyls are in a different "dielectric" environment. The average relative standard deviation for the casual level of meibum and the level of sebum suggests that the 49% relative standard deviation of casual meibum measured once for each subject using a meibometer may have been due to day-to-day variations and not necessarily due to variations between individuals. The values measured using two different assays were correlated and therefore reliable. The idea that tear film instability is associated with the quantity of lid margin lipid is not supported by this study because the quantity did not change with MGD. The amount of forehead sebum was not a bio-marker for MGD. Sebutape(®) is an excellent vehicle to remove tenths of a milligram of meibum from the eyelid and sebum from skin for experimental analysis.


Full length TrkB potentiates estrogen receptor alpha mediated transcription suggesting convergence of susceptibility pathways in schizophrenia.
In this study, we determined if estrogen receptor alpha (ERα) can interact with the full length tropomyosin receptor kinase B (TrkB-TK+), both of which are implicated in schizophrenia pathogenesis. Using neuronal (SHSY5Y) and non-neuronal (CHOK1) cell-lines, we showed that TrkB-TK+ can increase transcription at estrogen response elements (EREs) with and without exogenous estrogen treatment. In the presence of estrogen, TrkB-TK+ further potentiated the effect of estrogen stimulation on ERα-mediated transcription. This synergistic effect of TrkB-TK+ on ERα-mediated transcription was not due to direct effects of TrkB-TK+ in the nucleus, but occurred through cytoplasmic signaling of TrkB-TK+ via the MAPK/ERK pathway to phosphorylate ERα, leading to an induction in ERα-mediated transcription. When we examined the PI3K/AKT pathway, we found that PI3K/AKT activity constitutively inhibited baseline transcription at EREs. Furthermore, we showed that signaling via PI3K/AKT inhibited TrkB-TK+-dependent transcriptional potentiation at EREs. Our findings suggest that TrkB-TK+-linked second messenger signaling pathways can reciprocally regulate ERα-mediated transcription at EREs. Considering that both ERα and TrkB-TK+ expression are reduced in schizophrenia, our findings suggest that dysfunction in TrkB-TK+ signaling may occur upstream of, or in conjunction with a dysfunction in ERα, and that transcriptional regulation by ERα may be decreased by reductions in TrkB-TK+.


Novel Risk Score Efficiently Prevents Tolvaptan-Induced Hypernatremic Events in Patients With Heart Failure.
It has been 7 years since tolvaptan was approved in Japan for the indication of heart failure in patients with volume overload; the drug can be used in patients with normonatremia. Hypernatremia was identified as a significant adverse event to be prevented.Methods and Results:We compiled and analyzed data from 3,349 patients over 5 years to identify patients at high risk of hypernatremia with tolvaptan treatment. The incidence of hypernatremia, defined as serum sodium ≥150 mEq/L, was 3.65%. Baseline serum sodium concentrations, serum potassium concentrations, blood urea nitrogen : creatinine ratio, initial tolvaptan dose, and age were identified as risk factors for hypernatremia. A hypernatremia risk score was developed using the odds ratios for these factors. The high-risk population was defined as patients with a risk score ≥17.80. To prevent the occurrence of hypernatremic events in patients taking tolvaptan, we recommend a very low starting dose (i.e., 3.75 mg/day) in patients identified as being at high risk of hypernatremia using our new scoring process.


Petrography, stable isotope compositions, microRaman spectroscopy, and presolar components of Roberts Massif 04133: A reduced CV3 carbonaceous chondrite.
Here, we report the mineralogy, petrography, C-N-O-stable isotope compositions, degree of disorder of organic matter, and abundances of presolar components of the chondrite Roberts Massif (RBT) 04133 using a coordinated, multitechnique approach. The results of this study are inconsistent with its initial classification as a Renazzo-like carbonaceous chondrite, and strongly support RBT 04133 being a brecciated, reduced petrologic type >3.3 Vigarano-like carbonaceous (CV) chondrite. RBT 04133 shows no evidence for aqueous alteration. However, it is mildly thermally altered (up to approximately 440 °C); which is apparent in its whole-rock C and N isotopic compositions, the degree of disorder of C in insoluble organic matter, low presolar grain abundances, minor element compositions of Fe,Ni metal, chromite compositions and morphologies, and the presence of unequilibrated silicates. Sulfides within type I chondrules from RBT 04133 appear to be pre-accretionary (i.e., did not form via aqueous alteration), providing further evidence that some sulfide minerals formed prior to accretion of the CV chondrite parent body. The thin section studied contains two reduced CV3 lithologies, one of which appears to be more thermally metamorphosed, indicating that RBT 04133, like several other CV chondrites, is a breccia and thus experienced impact processing. Linear foliation of chondrules was not observed implying that RBT 04133 did not experience high velocity impacts that could lead to extensive thermal metamorphism. Presolar silicates are still present in RBT 04133, although presolar SiC grain abundances are very low, indicating that the progressive destruction or modification of presolar SiC grains begins before presolar silicate grains are completely unidentifiable.


Effect of Bhramari pranayama and OM chanting on pulmonary function in healthy individuals: A prospective randomized control trial.
Yoga is an ancient Indian science as well as the way of life. Pranayama is a part of yoga, which improves pulmonary function in combination of many pranayama, but the aim of our study is to evaluate the effect of only Bhramari pranayama and OM chanting on pulmonary function in healthy individuals. A total of 82 subjects were randomized into the study group (SG) (n = 41) and control group (CG) (n = 41). Baseline assessment was performed before intervention for both groups. SG practiced Bhramari pranayama and OM chanting for the duration of 10 min (5 min for each practice)/day for the period of 6 days/week for 2 weeks and CG did not practice so. After intervention post-assessment was performed for SG (n = 40) and CG (n = 39). Statistical analysis was performed by Independent samples t-test and Student's paired t-test with the use of Statistical Package for the Social Sciences version 16 (2007, USA). The result showed a significant improvement in peak expiratory flow (PEF), forced expiratory flow (FEF)25% and maximal voluntary ventilation (MVV) along with a significant reduction in weight in SG compared with CG in independent samples t-test. Significant improvement in slow vital capacity (SVC), forced expired volume in 1 s (FEV1) along with PEF, FEF25% and MVV; Significant reduction in weight and body mass index were observed in SG unlike in CG in Student's paired t-test. No significant changes were found in forced vital capacity, FEV1 /SVC and FEF50% , between and within the group analysis of SG and CG. Bhramari pranayama and OM chanting are effective in improving pulmonary function in healthy individuals.


Birefringence imaging of human skin by polarization-sensitive spectral interferometric optical coherence tomography.
We have developed a spectral interferometric optical coherence tomography (OCT) system with polarization sensitivity that is able to measure a two-dimensional tomographic image by means of one-dimensional mechanical scanning. Our system, which has an axial resolution of 32 mum , calculates the distribution of each element of the Müller matrix of a measured object from 16 OCT images. The OCT system successfully reveals the birefringent nature of human skin tissue.


A comprehensive analysis of common IGF1, IGFBP1 and IGFBP3 genetic variation with prospective IGF-I and IGFBP-3 blood levels and prostate cancer risk among Caucasians.
The insulin-like growth factor (IGF) pathway has been implicated in prostate development and carcinogenesis. We conducted a comprehensive analysis, utilizing a resequencing and tagging single-nucleotide polymorphism (SNP) approach, between common genetic variation in the IGF1, IGF binding protein (BP) 1, and IGFBP3 genes with IGF-I and IGFBP-3 blood levels, and prostate cancer (PCa) risk, among Caucasians in the NCI Breast and Prostate Cancer Cohort Consortium. We genotyped 14 IGF1 SNPs and 16 IGFBP1/IGFBP3 SNPs to capture common [minor allele frequency (MAF) >or= 5%] variation among Caucasians. For each SNP, we assessed the geometric mean difference in IGF blood levels (N = 5684) across genotypes and the association with PCa risk (6012 PCa cases/6641 controls). We present two-sided statistical tests and correct for multiple comparisons. A non-synonymous IGFBP3 SNP in exon 1, rs2854746 (Gly32Ala), was associated with IGFBP-3 blood levels (P(adj) = 8.8 x 10(-43)) after adjusting for the previously established IGFBP3 promoter polymorphism A-202C (rs2854744); IGFBP-3 blood levels were 6.3% higher for each minor allele. For IGF1 SNP rs4764695, the risk estimates among heterozygotes was 1.01 (99% CI: 0.90-1.14) and 1.20 (99% CI: 1.06-1.37) for variant homozygotes with overall PCa risk. The corrected allelic P-value was 8.7 x 10(-3). IGF-I levels were significantly associated with PCa risk (P(trend) = 0.02) with a 21% increase of PCa risk when compared with the highest quartile to the lowest quartile. We have identified SNPs significantly associated with IGFBP-3 blood levels, but none of these alter PCa risk; however, a novel IGF1 SNP, not associated with IGF-I blood levels, shows preliminary evidence for association with PCa risk among Caucasians.


Lifetime risks of specific breast cancer subtypes among women in four racial/ethnic groups.
Breast cancer comprises clinically distinct subtypes, but most risk statistics consider breast cancer only as a single entity. To estimate subtype-specific lifetime breast cancer risks, we took advantage of population-based data for which information regarding tumor expression of estrogen receptor (ER), progesterone receptor (PR) and HER2/neu (HER2) was newly available. We included women whose breast cancer was diagnosed in the state of California from 2006 to 2007 and was reported to the National Cancer Institute's Surveillance, Epidemiology and End Results Program (N = 40,936). We calculated absolute lifetime and age-specific probabilities (percent, 95% confidence interval) of developing breast cancer subtypes defined by ER, PR, and HER2 status - luminal (ER and/or PR-positive, HER2-negative), HER2-positive (ER and PR-positive or negative, HER2-positive), and triple-negative (ER-negative, PR-negative, and HER2-negative) - separately for white, black, Hispanic, and Asian women. The luminal breast cancer subtype predominates across racial/ethnic groups, with lifetime risk lowest in Hispanic women (4.60%, 4.41-4.80%) and highest in white women (8.10%, 7.94-8.20%). HER2-positive breast cancer varies less by race (1.56-1.91%). Lifetime risk of triple-negative breast cancer is highest in black women (1.98%, 1.80-2.17%), compared to 0.77% (0.67-0.88%) for Asians, 1.04% (0.96-1.13%) for Hispanics and 1.25% (1.20-1.30%) for whites. Across racial/ethnic groups, nearly half of all luminal breast cancers occur after age 70. These absolute risk estimates may inform health policy and resource planning across diverse populations, and can help patients and physicians weigh the probabilities of developing specific breast cancer subtypes against competing health risks.


Identifying Novel Clinical Surrogates to Assess Human Bone Fracture Toughness.
Fracture risk does not solely depend on strength but also on fracture toughness; ie, the ability of bone material to resist crack initiation and propagation. Because resistance to crack growth largely depends on bone properties at the tissue level, including collagen characteristics, current X-ray based assessment tools may not be suitable to identify age-related, disease-related, or treatment-related changes in fracture toughness. To identify useful clinical surrogates that could improve the assessment of fracture resistance, we investigated the potential of (1)H nuclear magnetic resonance spectroscopy (NMR) and reference point indentation (RPI) to explain age-related variance in fracture toughness. Harvested from cadaveric femurs (62 human donors), single-edge notched beam (SENB) specimens of cortical bone underwent fracture toughness testing (R-curve method). NMR-derived bound water showed the strongest correlation with fracture toughness properties (r = 0.63 for crack initiation, r = 0.35 for crack growth, and r = 0.45 for overall fracture toughness; p < 0.01). Multivariate analyses indicated that the age-related decrease in different fracture toughness properties were best explained by a combination of NMR properties including pore water and RPI-derived tissue stiffness with age as a significant covariate (adjusted R(2) = 53.3%, 23.9%, and 35.2% for crack initiation, crack growth, and overall toughness, respectively; p < 0.001). These findings reflect the existence of many contributors to fracture toughness and emphasize the utility of a multimodal assessment of fracture resistance. Exploring the mechanistic origin of fracture toughness, glycation-mediated nonenzymatic collagen crosslinks and intracortical porosity are possible determinants of bone fracture toughness and could explain the sensitivity of NMR to changes in fracture toughness. Assuming fracture toughness is clinically important to the ability of bone to resist fracture, our results suggest that improvements in fracture risk assessment could potentially be achieved by accounting for water distribution (quantitative ultrashort echo time magnetic resonance imaging) and by a local measure of tissue resistance to indentation, RPI.


Effects of permethrin-treated bed nets on immunity to malaria in western Kenya I. Antibody responses in pregnant women and cord blood in an area of intense malaria transmission.
As part of a community-based group-randomized trial on the impact of permethrin-treated bed nets (ITNs) on malaria in pregnancy in a holoendemic area of western Kenya, we assessed their effects on antibody responses to Plasmodium falciparum pre-erythrocytic antigens (recombinant circumsporozoite protein [CSP] and peptides complimentary to the repeat region of the liver stage antigen-1 [LSA-1]) and blood stage antigen (recombinant C-terminal domain of the merozoite surface protein-1 [MSP-1(19) kD]) in paired maternal/cord plasma samples obtained from 296 deliveries (157 from ITN villages and 139 control villages). Levels of total IgG and IgG subclasses 1-3 to LSA-1 and total IgG and IgG3 to MSP-1 were lower, whereas those of total IgG to CSP were significantly higher in women from ITN villages than those from control villages. In cord plasma, levels of total IgG and IgG2 to LSA-1 and IgG3 to MSP-1 were lower in ITN villages than in control villages, but antibody responses to CSP were similar. Our results suggest that the use of ITNs decreases antibody responses to LSA-1 and MSP-1 antigens in pregnant women with associated reductions in levels of the same antibodies in cord blood. In contrast, ITN use was found to be associated with increased antibody responses to CSP in pregnant women, but had no effect on antibody levels to CSP in cord blood.


Pancreatic cancer biomarkers discovery by surface-enhanced laser desorption and ionization time-of-flight mass spectrometry.
Surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF/MS), a laboratory-friendly technique, is used to identify biomarkers for cancer. The aim of the present study was to explore the application of SELDI proteomic patterns in serum for distinguishing between cases of pancreatic cancer, chronic pancreatitis, type 2 diabetes mellitus and healthy controls. Sera from 12 healthy controls, 24 patients with type 2 diabetes mellitus, 126 with pancreatic cancer, including 84 with diabetes, and 61 with chronic pancreatitis, 32 of which were diabetics, were analyzed using SELDI-TOF/MS. Spectra (IMAC-30) were clustered and classified using Biomarker Wizard and Biomarker Pattern software. Two decision tree classification algorithms, one with and one without CA 19-9, were constructed. In the absence of CA 19-9, the splitting protein peaks were: m/z 1526, 1211, and 3519; when CA 19-9 was used in the analysis, it replaced the m/z 3519 splitter. The two algorithms performed equally for classifying patients. A classification tree that considered diabetic patients only was constructed; the main splitters were: 1211, CA 19-9, 7903, 3359, 1802. With this algorithm, 100% of patients with type 2 diabetes mellitus, 97% with chronic pancreatitis and 77% of patients with pancreatic cancer were correctly classified. SELDI-TOF/MS features improved the diagnostic accuracy of CA 19-9 (AUC = 0.883 for CA 19-9; AUC = 0.935 for CA 19-9 and SELDI-TOF/MS features combined). SELDI-TOF/MS allows identification of new peptides which, in addition to CA 19-9, enable the correct classification of the vast majority of patients with pancreatic cancer, which can be distinguished from patients with chronic pancreatitis or type 2 diabetes mellitus.


Non-uniform distribution of islet amyloid in the pancreas of 'maturity-onset' diabetic patients.
Quantitative morphometry of the pancreases of five 'maturity-onset' diabetic subjects has demonstrated more amyloid in islets of the head, body and tail (where it was found in a mean 29% of the islets occupying a mean 11% islet area) than in islets of the 'pancreatic-polypeptide-rich' lobule of the head (where amyloid was found in a mean of 3% of the islets occupying a mean of 0.7% islet area, both p less than 0.005). The non-uniform amyloid distribution may relate to the hormone content of the islet; the head and tail contained significantly more A, B and D-cells than the pancreatic-polypeptide-rich lobule in both non-diabetic subjects (n = 8) and diabetic patients (n = 5; p less than 0.005). This result is compatible with the previous suggestion that amyloid may be derived from insulin or its precursors.


Photoluminescent characterization of atomic diffusion in core-shell nanoparticles.
Eu3+ doped LaF3 nanoparticles with core/shell morphologies were synthesized and selected spectroscopic properties were measured as a function of heat treatment times and temperatures. More specifically, the relative intensity of photoluminescence spectra, both through direct excitation of the lanthanide as well as phonon sideband spectra were evaluated with increasing amounts of time held at specific temperatures. A one dimensional approximation was used to compute an effective diffusion coefficient for the rare earth dopants in LaF3. Despite the simplicity of the model employed, the calculated diffusion coefficients based on the spectroscopic results are accurate within an order of magnitude in comparison to other fluoride crystals yielding a simplified approach to estimating kinetic and diffusion effects in optical materials.


Whole genome sequencing and analysis of plant growth promoting bacteria isolated from the rhizosphere of plantation crops coconut, cocoa and arecanut.
Coconut, cocoa and arecanut are commercial plantation crops that play a vital role in the Indian economy while sustaining the livelihood of more than 10 million Indians. According to 2012 Food and Agricultural organization's report, India is the third largest producer of coconut and it dominates the production of arecanut worldwide. In this study, three Plant Growth Promoting Rhizobacteria (PGPR) from coconut (CPCRI-1), cocoa (CPCRI-2) and arecanut (CPCRI-3) characterized for the PGP activities have been sequenced. The draft genome sizes were 4.7 Mb (56% GC), 5.9 Mb (63.6% GC) and 5.1 Mb (54.8% GB) for CPCRI-1, CPCRI-2, CPCRI-3, respectively. These genomes encoded 4056 (CPCRI-1), 4637 (CPCRI-2) and 4286 (CPCRI-3) protein-coding genes. Phylogenetic analysis revealed that both CPCRI-1 and CPCRI-3 belonged to Enterobacteriaceae family, while, CPCRI-2 was a Pseudomonadaceae family member. Functional annotation of the genes predicted that all three bacteria encoded genes needed for mineral phosphate solubilization, siderophores, acetoin, butanediol, 1-aminocyclopropane-1-carboxylate (ACC) deaminase, chitinase, phenazine, 4-hydroxybenzoate, trehalose and quorum sensing molecules supportive of the plant growth promoting traits observed in the course of their isolation and characterization. Additionally, in all the three CPCRI PGPRs, we identified genes involved in synthesis of hydrogen sulfide (H2S), which recently has been proposed to aid plant growth. The PGPRs also carried genes for central carbohydrate metabolism indicating that the bacteria can efficiently utilize the root exudates and other organic materials as energy source. Genes for production of peroxidases, catalases and superoxide dismutases that confer resistance to oxidative stresses in plants were identified. Besides these, genes for heat shock tolerance, cold shock tolerance and glycine-betaine production that enable bacteria to survive abiotic stress were also identified.


Despite Boosting Children's Coverage Rates To Historic Levels, Medicaid And CHIP Face An Uncertain Future.
The Children's Health Insurance Program (CHIP), which was enacted twenty years ago, covers uninsured children who do not qualify for Medicaid but lack access to affordable coverage. Together these safety-net programs have boosted the health insurance coverage rate among US children to historic levels, exceeding 95 percent of children in 2015. However, the future of both CHIP and Medicaid is uncertain. In the current congressional debate over the Affordable Care Act, Medicaid has become a target for potential funding reductions and other changes that would undermine the scope of children's coverage. Congress has yet to act to extend CHIP funding beyond September 30, 2017, when the current appropriation expires. State and federal policy makers should act now to preserve the foundation of coverage currently in place while striving to ensure that every child in the United States has health coverage.


Organ-specific defects in insulin-like growth factor and insulin receptor signaling in late gestational asymmetric intrauterine growth restriction in Cited1 mutant mice.
Late gestational placental insufficiency resulting in asymmetric intrauterine organ growth restriction (IUGR) is associated with an increased incidence of diabetes, cardiovascular and renal disease in adults. The molecular mechanisms mediating these defects are poorly understood. To explore this, we investigated the mechanisms leading to IUGR in Cited1 knockout mice, a genetic model of late gestational placental insufficiency. We show that loss of placental Cited1 leads to asymmetric IUGR with decreased liver, lung, and kidney sizes and preservation of fetal brain weight. IGF and insulin signaling regulate embryonic organ growth. IGF-I and IGF-II protein and mRNA expression are reduced in livers, lungs, and kidneys of embryonic d 18.5 embryos with IUGR. Decreased IGF-I is associated with reduced activating phosphorylation of the type 1 IGF receptor (pIGF-IR) in the kidney, whereas reduced IGF-II is associated with decreased phosphorylation of the insulin receptor (pIR) in the lung. In contrast, decreased pIR is associated with reduced IGF-I but not IGF-II in the liver. However, pancreatic β-cell mass and serum insulin levels are also decreased in mice with IUGR, suggesting that hepatic IR signaling may be regulated by alterations in fetal insulin production. These findings contrast with observations in IUGR fetal brains in which there is no change in IGF-IR/IR phosphorylation, and IGF-I and IGF-II expression is actually increased. In conclusion, IUGR disrupts normal fetal IGF and insulin production and is associated with organ-specific defects in IGF-IR and IR signaling that may regulate asymmetric IUGR in late gestational placental insufficiency.


Glucocorticoid-induced leucine zipper (GILZ) inhibits B cell activation in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a serious multisystem autoimmune disease, mediated by disrupted B cell quiescence and typically treated with glucocorticoids. We studied whether B cells in SLE are regulated by the glucocorticoid-induced leucine zipper (GILZ) protein, an endogenous mediator of anti-inflammatory effects of glucocorticoids. We conducted a study of GILZ expression in blood mononuclear cells of patients with SLE, performed in vitro analyses of GILZ function in mouse and human B cells, assessed the contributions of GILZ to autoimmunity in mice, and used the nitrophenol coupled to keyhole limpet haemocyanin model of immunisation in mice. Reduced B cell GILZ was observed in patients with SLE and lupus-prone mice, and impaired induction of GILZ in patients with SLE receiving glucocorticoids was associated with increased disease activity. GILZ was downregulated in naïve B cells upon stimulation in vitro and in germinal centre B cells, which contained less enrichment of H3K4me3 at the GILZ promoter compared with naïve and memory B cells. Mice lacking GILZ spontaneously developed lupus-like autoimmunity, and GILZ deficiency resulted in excessive B cell responses to T-dependent stimulation. Accordingly, loss of GILZ in naïve B cells allowed upregulation of multiple genes that promote the germinal centre B cell phenotype, including lupus susceptibility genes and genes involved in cell survival and proliferation. Finally, treatment of human B cells with a cell-permeable GILZ fusion protein potently suppressed their responsiveness to T-dependent stimuli. Our findings demonstrated that GILZ is a non-redundant regulator of B cell activity, with important potential clinical implications in SLE.


Newborn care training of midwives and neonatal and perinatal mortality rates in a developing country.
This study was designed to test the hypothesis that 2 training programs would reduce incrementally 7-day neonatal mortality rates for low-risk institutional deliveries. Using a train-the-trainer model, certified research midwives sequentially trained the midwives who performed deliveries in low-risk, first-level, urban, community health clinics in 2 cities in Zambia in the protocol and data collection, in the World Health Organization Essential Newborn Care (ENC) course (universal precautions and cleanliness, routine neonatal care, resuscitation, thermoregulation, breastfeeding, kangaroo care, care of small infants, and common illnesses), and in the American Academy of Pediatrics Neonatal Resuscitation Program (in-depth basic resuscitation). Data were collected during 3 periods, after implementation of each training course. A total of 71 689 neonates were enrolled in the 3 study periods. All-cause, 7-day neonatal mortality rates decreased from 11.5 deaths per 1000 live births to 6.8 deaths per 1000 live births after ENC training (relative risk: 0.59 [95% confidence interval: 0.48-0.77]; P < .001), because of decreases in rates of deaths attributable to birth asphyxia and infection. Perinatal mortality rates but not stillbirth rates decreased. The 7-day neonatal mortality rate was decreased further after Neonatal Resuscitation Program training, after correction for loss to follow-up monitoring. ENC training for midwives reduced 7-day neonatal mortality rates in low-risk clinics. Additional in-depth basic training in neonatal resuscitation may reduce mortality rates further.


High-quality multimodal volume rendering for preoperative planning of neurosurgical interventions.
Surgical approaches tailored to an individual patient's anatomy and pathology have become standard in neurosurgery. Precise preoperative planning of these procedures, however, is necessary to achieve an optimal therapeutic effect. Therefore, multiple radiological imaging modalities are used prior to surgery to delineate the patient's anatomy, neurological function, and metabolic processes. Developing a three-dimensional perception of the surgical approach, however, is traditionally still done by mentally fusing multiple modalities. Concurrent 3D visualization of these datasets can, therefore, improve the planning process significantly. In this paper we introduce an application for planning of individual neurosurgical approaches with high-quality interactive multimodal volume rendering. The application consists of three main modules which allow to (1) plan the optimal skin incision and opening of the skull tailored to the underlying pathology; (2) visualize superficial brain anatomy, function and metabolism; and (3) plan the patient-specific approach for surgery of deep-seated lesions. The visualization is based on direct multi-volume raycasting on graphics hardware, where multiple volumes from different modalities can be displayed concurrently at interactive frame rates. Graphics memory limitations are avoided by performing raycasting on bricked volumes. For preprocessing tasks such as registration or segmentation, the visualization modules are integrated into a larger framework, thus supporting the entire workflow of preoperative planning.


The verdict is not in yet. Analysis of the randomized trials of high-dose chemotherapy for breast cancer.
The relative efficacy of high-dose chemotherapy (HDC) compared to standard treatment for high-risk primary (HRPBC) or metastatic breast cancer (MBC) constitutes an area of intense controversy among the medical oncology community. A number of randomized trials have been conducted to address this issue. In most cases, the results of these trials are premature and contradictory. Furthermore, they have often been interpreted, incorrectly in this author's judgment, as proof of lack of benefit of HDC. The results of studies published in peer-reviewed medical journals or presented in scientific meetings are discussed. In some cases, the status of the studies was determined through direct communication with the trial's principal investigator. The encouraging results of phase II trials suggested a benefit for HDC in important categories of patients with breast cancer. It has been argued that selection of patients might have been a critical factor in those studies. The results, in most cases preliminary, of numerous randomized trials in metastatic and high-risk primary disease cannot offer a definitive answer to this crucial question as of yet. Important concepts in the interpretation of these studies, such as size and statistical power, length of follow-up, magnitude of clinical benefit, and broad applicability of the results, are discussed in this review. The role of HDC for HRPBC or MBC patients remains undefined. Longer follow-up and mature analyses of the randomized trials are necessary before definitive conclusions are drawn. In the meantime, it is imperative that research continues, to enhance the efficacy of the procedure through innovative strategies.


The spectrum kernel: a string kernel for SVM protein classification.
We introduce a new sequence-similarity kernel, the spectrum kernel, for use with support vector machines (SVMs) in a discriminative approach to the protein classification problem. Our kernel is conceptually simple and efficient to compute and, in experiments on the SCOP database, performs well in comparison with state-of-the-art methods for homology detection. Moreover, our method produces an SVM classifier that allows linear time classification of test sequences. Our experiments provide evidence that string-based kernels, in conjunction with SVMs, could offer a viable and computationally efficient alternative to other methods of protein classification and homology detection.


A new and improved population-based Canadian reference for birth weight for gestational age.
Existing fetal growth references all suffer from 1 or more major methodologic problems, including errors in reported gestational age, biologically implausible birth weight for gestational age, insufficient sample sizes at low gestational age, single-hospital or other non-population-based samples, and inadequate statistical modeling techniques. We used the newly developed Canadian national linked file of singleton births and infant deaths for births between 1994 and 1996, for which gestational age is largely based on early ultrasound estimates. Assuming a normal distribution for birth weight at each gestational age, we used the expectation-maximization algorithm to exclude infants with gestational ages that were more consistent with 40-week births than with the observed gestational age. Distributions of birth weight at the corrected gestational ages were then statistically smoothed. The resulting male and female curves provide smooth and biologically plausible means, standard deviations, and percentile cutoffs for defining small- and large-for-gestational-age births. Large-for-gestational age cutoffs (90th percentile) at low gestational ages are considerably lower than those of existing references, whereas small-for-gestational-age cutoffs (10th percentile) postterm are higher. For example, compared with the current World Health Organization reference from California (Williams et al, 1982) and a recently proposed US national reference (Alexander et al, 1996), the 90th percentiles for singleton males at 30 weeks are 1837 versus 2159 and 2710 g. The corresponding 10th percentiles at 42 weeks are 3233 versus 3086 and 2998 g. This new sex-specific, population-based reference should improve clinical assessment of growth in individual newborns, population-based surveillance of geographic and temporal trends in birth weight for gestational age, and evaluation of clinical or public health interventions to enhance fetal growth. fetal growth, birth weight, gestational age, preterm birth, postterm birth.


Depressed children with asthma evidence increased airway resistance: "vagal bias" as a mechanism?
Depression is prevalent in pediatric asthma, and implicated in asthma morbidity and mortality. Pathways linking stress, depression, and asthma are unknown. To examine, under controlled laboratory conditions, pathways by which depressive states affect airway function via autonomic dysregulation. Participants were 171 children with asthma, age 7 to 17 years, presenting to an emergency department for asthma exacerbation. Forty-five children with asthma and high depressive symptoms (D) were contrasted with 45 with low/no depressive symptoms (ND). Depressive symptoms, asthma disease severity, vagal and sympathetic reactivity to film stressors, airflow (FEV1), and airway resistance were compared between the groups. A subgroup with greater airway reactivity (nonmedicated FEV1<80% predicted) was also studied. Correlations among variables were examined for the entire sample. Groups did not differ in demographics, disease severity, medications, or adherence. The D group with FEV1<80% predicted showed greater airway resistance throughout all conditions (P = .03), and vagal bias in the film stressors. The D group's vagal response was significant for the sad stimuli: family distress/loss (P = .03), dying (P = .003), and death (P = .03). The ND group showed sympathetic activation to sad stimuli: lonely (P = .04) and dying (P = .04). Depressive symptoms were correlated with respiratory resistance (r = .43; P = .001) and vagal bias in scene 3 (r = .24; P = .03), and vagal bias (scene 3) was correlated with postmovie airway resistance (r = 0.39; P = .004). Children with asthma and depressive symptoms manifest vagal bias when emotionally stressed. Those with depressive symptoms and FEV1<80% manifest greater airway resistance. Depression, vagal bias, and airway resistance were intercorrelated for the full sample.


A discussion of potential exposure metrics for use in epidemiological studies on human exposure to radiowaves from mobile phone base stations.
There is currently a high level of concern in many countries that exposure to radiowaves from mobile phone base stations may be hazardous to health. When investigating such suggested risks, epidemiologists need to define an exposure metric that can reliably discriminate between exposed and unexposed groups of people. We conducted a feasibility study to investigate if either short-term measurements of electric field strength, calculations of electric field strength, or distance from nearby mobile phone base stations could be used to develop a metric reflecting an individual's exposure to radiowaves. With electric field strengths in the range of 0.012-0.343 V/m, radiowaves from mobile phone base stations were found to give a material contribution to total exposure; however, stronger signals were frequently measured from other sources such as broadcast radio and television transmitters. Theoretical considerations and the measurements made during this work demonstrated that studies at the population level on suggested adverse effects of radiowaves from mobile phone base stations are not feasible since no valid metric for estimating historical exposures is currently available. The pace of radio infrastructure development is also such that today's measurements are unlikely to be good proxies for either past or future exposures. The complex propagation characteristics affecting the beams from base station antennas include shielding effects and multiple reflections from house walls and other buildings. These factors, combined with the presence of other environmental sources of radiowaves, cause distance from a base station to be a poor proxy for exposure to radiowaves indoors. It may be possible to adapt computer models developed by network providers to predict network coverage for epidemiological purposes; however, this has yet to be investigated. Furthermore, there is little evidence that presently justifies epidemiological studies being restricted to adverse effects of radiowaves from mobile phone base stations while neglecting radiowaves at other frequencies produced by different transmitters.


Prevention of Group B Streptococcal Early-Onset Disease in Newborns: ACOG Committee Opinion, Number 797.
Group B streptococcus (GBS) is the leading cause of newborn infection. The primary risk factor for neonatal GBS early-onset disease (EOD) is maternal colonization of the genitourinary and gastrointestinal tracts. Approximately 50% of women who are colonized with GBS will transmit the bacteria to their newborns. Vertical transmission usually occurs during labor or after rupture of membranes. In the absence of intrapartum antibiotic prophylaxis, 1-2% of those newborns will develop GBS EOD. Other risk factors include gestational age of less than 37 weeks, very low birth weight, prolonged rupture of membranes, intraamniotic infection, young maternal age, and maternal black race. The key obstetric measures necessary for effective prevention of GBS EOD continue to include universal prenatal screening by vaginal-rectal culture, correct specimen collection and processing, appropriate implementation of intrapartum antibiotic prophylaxis, and coordination with pediatric care providers. The American College of Obstetricians and Gynecologists now recommends performing universal GBS screening between 36 0/7 and 37 6/7 weeks of gestation. All women whose vaginal-rectal cultures at 36 0/7-37 6/7 weeks of gestation are positive for GBS should receive appropriate intrapartum antibiotic prophylaxis unless a prelabor cesarean birth is performed in the setting of intact membranes. Although a shorter duration of recommended intrapartum antibiotics is less effective than 4 or more hours of prophylaxis, 2 hours of antibiotic exposure has been shown to reduce GBS vaginal colony counts and decrease the frequency of a clinical neonatal sepsis diagnosis. Obstetric interventions, when necessary, should not be delayed solely to provide 4 hours of antibiotic administration before birth. This Committee Opinion, including , , and , updates and replaces the obstetric components of the CDC 2010 guidelines, "Prevention of Perinatal Group B Streptococcal Disease: Revised Guidelines From CDC, 2010."


SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.
The magnitude of effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on specific cardiovascular and renal outcomes and whether heterogeneity is based on key baseline characteristics remains undefined. We did a systematic review and meta-analysis of randomised, placebo-controlled, cardiovascular outcome trials of SGLT2i in patients with type 2 diabetes. We searched PubMed and Embase for trials published up to Sept 24, 2018. Data search and extraction were completed with a standardised data form and any discrepancies were resolved by consensus. Efficacy outcomes included major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), the composite of cardiovascular death or hospitalisation for heart failure, and progression of renal disease. Hazard ratios (HRs) with 95% CIs were pooled across trials, and efficacy outcomes were stratified by baseline presence of atherosclerotic cardiovascular disease, heart failure, and degree of renal function. We included data from three identified trials and 34 322 patients (60·2% with established atherosclerotic cardiovascular disease), with 3342 major adverse cardiovascular events, 2028 cardiovascular deaths or hospitalisation sfor heart failure events, and 766 renal composite outcomes. SGLT2i reduced major adverse cardiovascular events by 11% (HR 0·89 [95% CI 0·83-0·96], p=0·0014), with benefit only seen in patients with atherosclerotic cardiovascular disease (0·86 [0·80-0·93]) and not in those without (1·00 [0·87-1·16], p for interaction=0·0501). SGLT2i reduced the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77 [0·71-0·84], p<0·0001), with a similar benefit in patients with and without atherosclerotic cardiovascular disease and with and without a history of heart failure. SGLT2i reduced the risk of progression of renal disease by 45% (0·55 [0·48-0·64], p<0·0001), with a similar benefit in those with and without atherosclerotic cardiovascular disease. The magnitude of benefit of SGLT2i varied with baseline renal function, with greater reductions in hospitalisations for heart failure (p for interaction=0·0073) and lesser reductions in progression of renal disease (p for interaction=0·0258) in patients with more severe kidney disease at baseline. SGLT2i have moderate benefits on atherosclerotic major adverse cardiovascular events that seem confined to patients with established atherosclerotic cardiovascular disease. However, they have robust benefits on reducing hospitalisation for heart failure and progression of renal disease regardless of existing atherosclerotic cardiovascular disease or a history of heart failure. None.


Positive outcome expectancy mediates the relationship between social influence and Internet addiction among senior high-school students.
Background and aims Based on the foundations of Bandura's social cognitive theory and theory of triadic influence (TTI) theoretical framework, this study was designed to examine the mediating role of positive outcome expectancy of Internet use in the relationship between social influence and Internet addiction (IA) in a large representative sample of senior high-school students in Taiwan. Methods Using a cross-sectional design, 1,922 participants were recruited from senior high schools throughout Taiwan using both stratified and cluster sampling, and a comprehensive survey was administered. Results Structural equation modeling and bootstrap analyses results showed that IA severity was significantly and positively predicted by social influence, and fully mediated through positive outcome expectancy of Internet use. Discussion and conclusions The results not only support Bandura's social cognitive theory and TTI framework, but can also serve as a reference to help educational agencies and mental health organizations design programs and create policies that will help in the prevention of IA among adolescents.


Cerebral ischemia and neuroregeneration.
Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke (a form of cerebral ischemia)-related costs are expected to reach 240.67 billion dollars by 2030, options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics (i.e., tissue plasminogen activator) and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies against stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism(s) underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies (i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells) as it relates to cerebral ischemia.


Next-generation DNA sequencing.
DNA sequence represents a single format onto which a broad range of biological phenomena can be projected for high-throughput data collection. Over the past three years, massively parallel DNA sequencing platforms have become widely available, reducing the cost of DNA sequencing by over two orders of magnitude, and democratizing the field by putting the sequencing capacity of a major genome center in the hands of individual investigators. These new technologies are rapidly evolving, and near-term challenges include the development of robust protocols for generating sequencing libraries, building effective new approaches to data-analysis, and often a rethinking of experimental design. Next-generation DNA sequencing has the potential to dramatically accelerate biological and biomedical research, by enabling the comprehensive analysis of genomes, transcriptomes and interactomes to become inexpensive, routine and widespread, rather than requiring significant production-scale efforts.


CpG inclusion in feed reduces sea lice, Lepeophtheirus salmonis, numbers following re-infection.
Lepeophtheirus salmonis infections in Atlantic salmon, Salmo salar, have been characterized by little to no hyperplastic response and a biphasic immune response that results in chronic inflammation with tissue repair as the infection progresses. We hypothesized that CpG administration with prior lice exposure would enhance epithelial inflammatory mechanisms and boost the Atlantic salmon immune response to L. salmonis, leading to greater protection against infection. We administered multiple exposures of L. salmonis to two groups of Atlantic salmon and compared responses against first-time exposed Atlantic salmon. Following re-exposure, CpG fed fish exhibited increased skin expression of interleukin (IL)-1β and IL-12 β compared to control previously exposed (CPE) and control first-time exposed (CFE) animals, respectively. This inflammatory enhancement occurred with significantly lower expression of matrix metalloproteinase-9 (MMP 9), both systemically (spleen) and locally (skin). Reduced MMP 9 expression was a hallmark of the re-infected fish (occurred in both tissues at both times). When significant differences were present in the skin or spleen, the two re-exposed groups showed greater similarity than with the first exposure group. Lice numbers on CpG fed fish were significantly lower than CFE fish at 7 days post-re-infection (dpri), and although they were not significantly different at 17 dpri, the trend of lower lice levels remained. CpG fed fish also showed nearly twofold greater protection than CPE when compared to the CFE group (48.5% vs. 27.0% reductions at 7 dpri and 27.2% vs. 13.1% reductions at 17 dpri, respectively). The enhanced protection of CpG oligodeoxynucleotide administration to previous exposure was consistent across all body surfaces and suggests that CpG can not only enhance innate responses to L. salmonis in Atlantic salmon, but also further stimulate adaptive responses.


[On possible role of endothelial dysfunction in development of acute venous thrombosis].
The study included a total of 18 patients (12 women and 6 men, aged from 22 to 51 years, mean age 34 years) with newly onset unilateral acute thrombosis of deep veins in the system of inferior vena cava, confirmed by the findings of ultrasound duplex scanning. The patients had no apparent risk factors for venous thromboembolic complications, they had not used antiplatelet drugs during the last month and were characterized by a low level of risk for cardiovascular complications. Along with general clinical examination the patients were subjected to measuring the quantitative level of the von Willebrand factor (vWF), resistance to activated C-protein conditioned by V factor mutation, D-dimer, qualitative assessment of the level of C-reactive protein by a highly sensitive method, as well as integral assessment of the links of blood coagulation and fibrinolysis by means of thromboelastography. Eighteen (100%) patients had the vWF level above the norm, four (22.2%) patients were found to have resistance to activated C protein conditioned by factor V mutation, these patients had non-O (I) blood group. In twelve (66.7%) patients the quantitative level of D-dimer remained within the normal limits, and in 6 patients the D-dimer level was above the norm. The findings of thromboelastography demonstrated decreased activity of blood platelets. Fibrinolysis (LY30 and LY60) in the absolute majority of the examined patients was lowered. Six (33.3%) patients when comparing the LY30 and LY60 levels had no significant elevation of the index (<1%), four (22.2%) patients when comparing LY30 and LY60 showed an elevation of the index (>3.8%). The mean level of C-reactive protein (4.93 mg/l) exceeded the median of the reference values (2.5 mg/l) and in five (27.8%) out of 18 patients the value was two times higher than the reference ones. The obtained experimental data suggest that acute venous thrombosis is accompanied by alterations in the work of the coagulation and fibrinolytic systems, associated with endothelial dysfunction.


Blood eosinophils to direct corticosteroid treatment of exacerbations of chronic obstructive pulmonary disease: a randomized placebo-controlled trial.
Exacerbations of chronic obstructive pulmonary disease (COPD) and responses to treatment are heterogeneous. Investigate the usefulness of blood eosinophils to direct corticosteroid therapy during exacerbations. Subjects with COPD exacerbations were entered into a randomized biomarker-directed double-blind corticosteroid versus standard therapy study. Subjects in the standard arm received prednisolone for 2 weeks, whereas in the biomarker-directed arm, prednisolone or matching placebo was given according to the blood eosinophil count biomarker. Both study groups received antibiotics. Blood eosinophils were measured in the biomarker-directed and standard therapy arms to define biomarker-positive and -negative exacerbations (blood eosinophil count > and ≤ 2%, respectively). The primary outcome was to determine noninferiority in health status using the chronic respiratory questionnaire (CRQ) and in the proportion of exacerbations associated with a treatment failure between subjects allocated to the biomarker-directed and standard therapy arms. There were 86 and 80 exacerbations in the biomarker-directed and standard treatment groups, respectively. In the biomarker-directed group, 49% of the exacerbations were not treated with prednisolone. CRQ improvement after treatment in the standard and biomarker-directed therapy groups was similar (0.8 vs. 1.1; mean difference, 0.3; 95% confidence interval, 0.0-0.6; P = 0.05). There was a greater improvement in CRQ in biomarker-negative exacerbations given placebo compared with those given prednisolone (mean difference, 0.45; 95% confidence interval, 0.01-0.90; P = 0.04). In biomarker-negative exacerbations, treatment failures occurred in 15% given prednisolone and 2% of those given placebo (P = 0.04). The peripheral blood eosinophil count is a promising biomarker to direct corticosteroid therapy during COPD exacerbations, but larger studies are required.


The quantification of single cell adhesion on functionalized surfaces for cell sheet engineering.
The use of force spectroscopy to measure and quantify the forces involved in the adhesion of 3T3 fibroblasts to different chemically functionalized surfaces has been investigated. Cells were grown on glass surfaces as well as on surfaces used for cell sheet engineering: surfaces coated with polyelectrolyte multilayers (poly-L-lysine and hyaluronic acid) and thermally-responsive poly(N-isopropylacrylamide) (PNIPAM) brushes. Individual adherent cells were detached from their culture substrate using an AFM cantilever coated with fibronectin. The maximum forces of detachment of each cell were measured and taken as characteristic of the cellular adhesion. Large differences in cellular adhesion were observed on polyelectrolyte coatings depending on the number of polyelectrolyte layers. On PNIPAM-grafted surfaces, changes of more than an order of magnitude were observed in cell adhesion above and below the lower critical solution temperature. Glass surfaces patterned with periodic PNIPAM microdomains were also investigated, and it was shown that cellular adhesion could be reduced while keeping cellular morphology unchanged.


Negative Regulation of Semaphorin-3A Expression in Peripheral Blood Mononuclear Cells Using MicroRNA-497-5p.
Semaphorin-3A (Sema3A), as a secreted semaphorin, is an immune modulator molecule participating in the pathogenesis of autoimmune diseases. MicroRNAs (miRNAs) modulate the target-gene expression at the post-transcriptional level. It has been proposed that miRNAs may be crucial to the modulation of the function of semaphorins. Previous findings have proven that miR-497-5p is upregulated and Sema3A is downregulated in some autoimmune disorders. Thus, we aimed to examine the presence of any correlation between Sema3A and miR-497-5p in peripheral blood mononuclear cells (PBMCs). PBMCs were cultured and transfected with miR-497-5p mimic using the X-tremeGENE™ reagent. The expression level of Sema3A was assessed after 48 hours in supernatants and cells via the enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction, respectively. Cell viability was evaluated using the methylthiazol tetrazolium assay. All the experiments were done in triplicate, and the statistical analyses were performed with SPSS, version 20. P values equal to or less than 0.05 were considered significant. We observed downregulation of the Sema3A gene (P=0.0001) and its secretion (P=0.032) in the PBMCs through miR-497-5p transfection. Moreover, transfection with miR-497-5p mimic and downregulation of Sema3A did not affect the viability of the PBMCs (P=0.061). Based on the obtained results, we suggest that miR-497-5p has a high suppressive effect on Sema3A expression and both Sema3A and miR-497-5p can be considered critical targets for further studies on future therapeutic attempts for the treatment of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis.


Studying the Effects of Nonindicated Medications on Cancer: Etiologic versus Action-Focused Analysis of Epidemiologic Data.
The study of nonindicated medications on cancer outcomes is challenged by potential time-related biases. The literature has strongly advocated for treating the exposure as time-varying and summarizing the outcomes through a dose-response model (an etiologic-focused analysis). An alternative is to refashion the data to resemble a hypothetical randomized trial of drug use (an action-focused analysis). To our knowledge, their relative treatment of time-related bias and aspects of interpretation have not been compared. In this commentary, using the study of metformin use on colorectal cancer risk by Bradley and colleagues (2018) as motivation, we compare the etiologic versus action-focused analysis of epidemiologic data. We examine their treatment of immortal person-time, time-varying confounding, selection bias, and the biological and clinical relevance of their results. In doing so, we aim to establish areas of common ground and points of departure that can guide future observational studies of medications on cancer risk, recurrence, and survival. Cancer Epidemiol Biomarkers Prev; 27(5); 520-4. ©2018 AACRSee related article by Bradley et al., p. 525.


Validation of a human angiopoietin-2 ELISA for measurement of angiopoietin-2 concentrations in canine plasma samples and supernatant of primary canine aortic endothelial cell cultures.
OBJECTIVE To assess 2 human ELISA kits for measurement of angiopoietin-1 and -2 concentrations in canine plasma samples, determine whether plasma angiopoeitin-2 concentration differed between septic and healthy dogs, and determine the effect of tumor necrosis factor-α (TNF-α) stimulation on angiopoeitin-2 release from primary canine aortic endothelial cells (pCAECs) in vitro. ANIMALS 10 healthy dogs and 10 septic dogs. PROCEDURES Human angiopoietin-1 and -2 ELISAs were used to detect recombinant canine angiopoietins-1 and -2 in canine plasma samples. The angiopoietin-2 ELISA was further validated by use of plasma samples from healthy and septic dogs and supernatants of pCAEC cultures. Associations between plasma angiopoeitin-2 and C-reactive protein (CRP) concentrations were examined. RESULTS Angiopoeitin-2 but not angiopoeitin-1 was detected in canine plasma samples by the respective ELISAs. The angiopoeitin-2 ELISA had excellent dilutional linearity, parallelism, accuracy, precision, and reproducibility for measurements in canine plasma samples and pCAEC supernatants. Plasma angiopoeitin-2 concentration was significantly higher in septic dogs (median, 25.5 ng/mL) than in healthy dogs (median, 6.7 ng/mL) and was positively correlated with plasma CRP concentration (R2 = 0.60). Stimulation of pCAECs with TNF-α resulted in a significant increase in supernatant angiopoietin-2 concentration. CONCLUSIONS AND CLINICAL RELEVANCE The tested human angiopoietin-2 ELISA kit was useful for measuring angiopoietin-2 concentrations in canine plasma samples and pCAEC supernatants. Sepsis appeared to increase angiopoietin-2 concentration in dogs in vivo, whereas TNF-α stimulation caused release of angiopoietin-2 from pCAECs in vitro. These findings support the use of angiopoietin-2 as a marker of endothelial cell activation and inflammation in dogs.


Assessment of the applicability of the Hertzian contact theory to edge-loaded prosthetic hip bearings.
The components of prosthetic hip bearings may experience in-vivo subluxation and edge loading on the acetabular socket as a result of joint laxity, causing abnormally high, damaging contact stresses. In this research, edge-loaded contact of prosthetic hips is examined analytically and experimentally in the most commonly used categories of material pairs. In edge-loaded ceramic-on-ceramic hips, the Hertzian contact theory yields accurate (conservatively, <10% error) predictions of the contact dimensions. Moreover, the Hertzian theory successfully captures slope and curvature trends in the dependence of contact patch geometry on the applied load. In an edge-loaded ceramic-on-metal pair, a similar degree of accuracy is observed in the contact patch length; however, the contact width is less accurately predicted due to the onset of subsurface plasticity, which is predicted for loads >400N. The Hertzian contact theory is shown to be ill-suited to edge-loaded ceramic-on-polyethylene pairs due to polyethylene's nonlinear material behavior. This work elucidates the methods and the accuracy of applying classical contact theory to edge-loaded hip bearings. The results help to define the applicability of the Hertzian theory to the design of new components and materials to better resist severe edge loading contact stresses.


Correlates of Sexual Risky Behaviours, HIV Testing, and HIV Testing Intention among Sexually Active Youths in Northern Tanzania.
HIV testing services are important entry-point into the HIV cascade to care and treatment in order to slow down the spread of HIV infection. Over half of all new HIV infections in Sub-Saharan Africa occur among young people under the age of 25, particularly women. The study aimed to determine factors influencing young people's decision to undergo HIV testing services in Northern Tanzania. A total of 536 sexually active participants aged 15 to 24 years old completed a semi-structured questionnaire based on the Health Belief Model (HBM) and the Theory of Planned Behaviour (TPB). Males compared to femaleparticipants were significantly younger at first age of sexual intercourse (15.4 vs. 16.7 years; p = .001). Out of 536 participants, 418(78%) reported inconsistent condom use, and 203/303(67%) were those practicing casual sex. Only, 189/536(35.3%) of the participants reported to have had an HIV-test. Age, socioeconomic status, perceived HIV severity, attitudes and social approval regarding testing and beliefs about testing procedures and perceived barriers to testing were significant predictors of HIV testing (R2 =.22). Age, unsafe casual sex, perceived severity, HIV-testing attitudes, self-efficacy, social approval, cues for actions and perceived quality of testing procedures were significant and positively related to HIV-testing intentions, while perceived barriers to testing were negatively related (R2 = .36). The integrated constructs of HBM and TPB provides a framework for identifying correlates of HIV testing behaviours and HIV testing intentions among sexually active youths. Future behaviour change interventions should focus on reduction of sexually risky behaviours, increasing perceived HIV severity, enhance positive attitudes and social approvals on testing, reduce misconceptions about testing procedures, alleviation of perceived barriers to testing and improve testing self-efficacy among sexually active youths in this setting.


Tonotopic gradients in human primary auditory cortex: concurring evidence from high-resolution 7 T and 3 T fMRI.
The tonotopic representations within the primary auditory cortex (PAC) have been successfully mapped with ultra-high field fMRI. Here, we compared the reliability of this tonotopic mapping paradigm at 7 T with 1.5 mm spatial resolution with maps acquired at 3 T with the same stimulation paradigm, but with spatial resolutions of 1.8 and 2.4 mm. For all subjects, the mirror-symmetric gradients within PAC were highly similar at 7 T and 3 T and across renderings at different spatial resolutions; albeit with lower percent signal changes at 3 T. In contrast, the frequency maps outside PAC tended to suffer from a reduced BOLD contrast-to-noise ratio at 3 T for a 1.8 mm voxel size, while robust at 2.4 mm and at 1.5 mm at 7 T. Overall, our results showed the robustness of the phase-encoding paradigm used here to map tonotopic representations across scanners.


The Lancet Countdown on health benefits from the UK Climate Change Act: a modelling study for Great Britain.
Climate change poses a dangerous and immediate threat to the health of populations in the UK and worldwide. We aimed to model different scenarios to assess the health co-benefits that result from mitigation actions. In this modelling study, we combined a detailed techno-economic energy systems model (UK TIMES), air pollutant emission inventories, a sophisticated air pollution model (Community Multi-scale Air Quality), and previously published associations between concentrations and health outcomes. We used four scenarios and focused on the air pollution implications from fine particulate matter (PM2·5), nitrogen dioxide (NO2) and ozone. The four scenarios were baseline, which assumed no further climate actions beyond those already achieved and did not meet the UK's Climate Change Act (at least an 80% reduction in carbon dioxide equivalent emissions by 2050 compared with 1990) target; nuclear power, which met the Climate Change Act target with a limited increase in nuclear power; low-greenhouse gas, which met the Climate Change Act target without any policy constraint on nuclear build; and a constant scenario that held 2011 air pollutant concentrations constant until 2050. We predicted the health and economic impacts from air pollution for the scenarios until 2050, and the inequalities in exposure across different socioeconomic groups. NO2 concentrations declined leading to 4 892 000 life-years saved for the nuclear power scenario and 7 178 000 life-years saved for the low-greenhouse gas scenario from 2011 to 2154. However, the associations that we used might overestimate the effects of NO2 itself. PM2·5 concentrations in Great Britain are predicted to decrease between 42% and 44% by 2050 compared with 2011 in the scenarios that met the Climate Change Act targets, especially those from road traffic and off-road machinery. These reductions in PM2·5 are tempered by a 2035 peak (and subsequent decline) in biomass (wood burning), and by a large, projected increase in future demand for transport leading to potential increases in non-exhaust particulate matter emissions. The potential use of biomass in poorly controlled technologies to meet the Climate Change Act commitments would represent an important missed opportunity (resulting in 472 000 more life-years lost from PM2·5 in the low-greenhouse gas scenario and 1 122 000 more life-years lost in the nuclear power scenario from PM2·5 than the baseline scenario). Although substantial overall improvements in absolute amounts of exposure are seen compared with 2011, these outcomes mask the fact that health inequalities seen (in which socioeconomically disadvantaged populations are among the most exposed) are projected to be maintained up to 2050. The modelling infrastructure created will help future researchers explore a wider range of climate policy scenarios, including local, European, and global scenarios. The need to strengthen the links between climate change policy objectives and public health imperatives, and the benefits to societal wellbeing that might result is urgent. National Institute for Health Research.


Blending theory with practice: implementing kindergarten transition using the interactive systems framework.
The Interactive Systems Framework (ISF; Wandersman et al. in Am J Commu Psychol 41(3-4):171-181, 2008) was used to implement a kindergarten transition demonstration project collaboratively developed by elementary and early education providers, community-based family and housing services, parents, and a University intermediary and technical assistance group. First person accounts from stakeholders at all levels provide a complementary and broad perspective on the project's implementation. The practice model blended existing research on kindergarten transition and parent involvement with feedback from stakeholders to create a community-specific program designed to help all children make a smooth entry into kindergarten. During implementation, evidence-based approaches needed to be adjusted to fit the specific needs of each community. Using the ISF as a guide, next steps and lessons learned include increasing leadership through a district-wide plan that is still flexible within each school community, increasing information and supports to individual schools, and improving data collection for continuous program improvement.


Inhibition of atherosclerotic lesion development in the ApoE-/- mouse by a novel β-oxa polyunsaturated fatty acid.
Recent findings that a novel polyunsaturated fatty acid, β-oxa 23:4n-6, inhibits adhesion molecule expression on vascular endothelial cells and leukocyte adhesion led us to examine its ability to inhibit the development of atherosclerosis in the apoE-deficient (apoE) mouse. The mice were kept on normal chow or a high-fat/high-cholesterol diet for various periods and treated with either vehicle or β-oxa 23:4n-6 by the intraperitoneal route. The hearts and aortae were isolated and lesion development at the aortic root was determined. Morphometric assessment revealed that lesion development was a function of compensatory aortic enlargement, suggesting that measurement of plaque size per se is the appropriate assessment of lesion size. Using this criterion, we found that atherosclerosis development was reduced in response to β-oxa 23:4n-6, plaque size by 74% and aortic cross-sectional area by 62%, under an optimized regime. The number of foam cells per unit tissue area in the lesions of β-oxa 23:4n-6-treated mice was significantly reduced by 37.5%. The blood levels of β-oxa23:4n-6 in these mice exceeded the concentrations previously found to inhibit adhesion molecule expression in cultured endothelial cells. These data show that β-oxa23:4n-6 protects against experimental atherosclerosis, most likely by reducing the number of infiltrating monocytes.


Diversity, Virulence, and Antimicrobial Resistance in Isolates From the Newly Emerging Klebsiella pneumoniae ST101 Lineage.
The global dissemination of Klebsiella pneumoniae and Klebsiella pneumoniae carbapenemase (KPC) has been largely attributed to a few high-risk sequence types (STs) (ST258, ST11, ST512) associated with human disease. ST101 is an emerging clone that has been identified in different parts of the world with the potential to become a global, persistent public health threat. Recent research suggests the ST101 lineage is associated with an 11% increase in mortality rate in comparison to non-ST101 infections. In this study, we generated a high-quality, near-finished genome assembly of a multidrug-resistant (MDR) isolate from Italy (isolate 4743) that is a single locus variant of ST101 (ST1685). We demonstrate that the 4743 genome contains virulence features such as an integrative conjugative element carrying the yersiniabactin siderophore (ICEKp3), the mannose-resistant Klebsiella-like (type III) fimbriae cluster (mrkABCDFHIJ), the ferric uptake system (kfuABC), the yersiniabactin receptor gene fyuA, a capsular K type K17, and an O antigen type of O1. K. pneumoniae 4743 carries the blaKPC-2 carbapenemase gene along with genes conferring resistance to aminoglycosides, beta-lactams, fluoroquinolones, fosfomycin, macrolides, lincosamides, and streptogramin B. A comparative genomics analysis of 44 ST101 genomes as well as newly sequenced isolate 4743 identified variable antimicrobial resistance (AMR) resistance profiles and incompatibility plasmid types, but similar virulence factor profiles. Using Bayesian methodologies, we estimate the common ancestor for the ST101 lineage emerged in 1990 (95% HPD: 1965 to 2007) and isolates within the lineage acquired bla KPC after the divergence from its parental clonal group and dissemination. The identification of virulence factors and antibiotic resistance genes acquired by this newly emerging clone provides insight into the reported increased mortality rates and highlights its potential success as a persistent nosocomial pathogen. With a combination of both colistin resistance, carbapenem resistance, and several known virulence factors, the ST101 genetic repertoire may be a "perfect storm" allowing for a newly emerging, high-risk, extensively antibiotic resistant clone. This high-risk clone appears adept at acquiring resistance and may perpetuate the dissemination of extensive antimicrobial resistance. Greater focus on the acquisition of virulence factors and antibiotic resistance genes is crucial for understanding the spread of antibiotic resistance.


Diffraction of volume Bragg gratings under high flux laser irradiation.
Diffraction property of transmitting volume Bragg gratings (VBGs) recorded in photo-thermo-refractive glass (PTR) is studied under the irradiation of a continuous-wave fiber laser with flux of 1274 W/cm2. Dependence of temperature characteristics of VBGs prepared by different crystallization temperatures is presented. When temperature of VBGs rises up to 33°C, there are a 2.7% reduction and 1.59% ripple of diffraction efficiency for VBGs. The period variation caused by the thermal expansion of VBGs is used to explain the reduction of diffraction efficiency, and experimental results are in agreement with theoretical analysis.


Doppler optical micro-angiography for volumetric imaging of vascular perfusion in vivo.
We propose a Doppler optical micro-angiography (DOMAG) method to image flow velocities of the blood flowing in functional vessels within microcirculatory tissue beds in vivo. The method takes the advantages of recently developed optical micro-angiography (OMAG) technology, in which the endogenous optical signals backscattered from the moving blood cells are isolated from those originated from the tissue background, i.e., the tissue microstructures. The phase difference between adjacent A scans of OMAG flow signals is used to evaluate the flow velocity, similar to phase-resolved Doppler optical coherence tomography (PRDOCT). To meet the requirement of correlation between adjacent A scans in using the phase resolved technique to evaluate flow velocity, an ideal tissue-sample background (i.e., optically homogeneous tissue sample) is digitally reconstructed to replace the signals that represent the heterogeneous features of the static sample that are rejected in the OMAG flow images. Because of the ideal optical-homogeneous sample, DOMAG is free from the characteristic texture pattern noise due to the heterogeneous property of sample, leading to dramatic improvement of the imaging performance. A series of phantom flow experiments are performed to evaluate quantitatively the improved imaging performance. We then conduct in vivo experiments on a mouse brain to demonstrate that DOMAG is capable of quantifying the flow velocities within cerebrovascular network, down to capillary level resolution. Finally, we compare the in vivo imaging performance of DOMAG with that of PRDOCT, and show that DOMAG delivers at least 15-fold increase over the PRDOCT method in terms of the lower limit of flow velocity that can be detected.