[Vegetation stress spectra and their relations with the contents of metal elements within the plant leaves in metal mines in Heilongjiang].
In this paper, Duobao Mt. and Tong Mt. were taken as examples. The spectra of the crown or leaf of the vegetation were collected. Fourteen metal elements in the rock, soil (A, B, C) and vegetation (root, trunk, leaf), and biological chemical parameters were measured. It was indicated that different metal elements were selected and enriched in different vegetation. The red edge position (REP) and the absorbing depth are related to biological chemical parameters. A multivariable regression equation was built between the absorption depths and the contents of metal elements. The relative coefficients between the absorbing depths and chemical elements, including Co, Cu, N, Mo, Ag, Sb, W, Pb and As, are greater than 0.75. Thus, it is important to analyze and measure the contents of metal elements by hyper-spectral remote sensing of vegetation stress spectrum.


Calibration of the PlusOptix PowerRef 3 with change in viewing distance, adult age and refractive error.
The PowerRef 3 is frequently used in studying the near triad of accommodation, vergence and pupil responses in normal and clinical populations. Within a range, the defocus measurement of the PowerRef 3 is linearly related to the eye's defocus. While the default factory-calibrated slope of this relation (calibration factor) is 1, it has been shown that the slope can vary across individuals. Here, we addressed the impact of changes in viewing distance, age and defocus of the eye on the calibration factor. We manipulated viewing distance (40 cm, 1 m and 6 m) and recruited participants with a range of accommodative capabilities: participants in their 20s, 40s and over 60 years old. To test whether any effect was larger than the range of measurement reliability of the instrument, we collected data for each condition four times: two in the same session, another on the same day, and one on a different day. The results demonstrated that viewing distance did not affect the calibration factor over the linear range, regardless of age or uncorrected refractive error. The largest proportion of the variance was explained by between-subject differences. Calibration data for the PowerRef 3 were not sensitive to changes in viewing distance. Nevertheless, our results re-emphasise the relevance of calibration for studies of individual participants.


Current models of care for disorders of sex development - results from an International survey of specialist centres.
To explore the current models of practice in centres delivering specialist care for children with disorders of sex development (DSD), an international survey of 124 clinicians, identified through DSDnet and the I-DSD Registry, was performed in the last quarter of 2014. A total of 78 (63 %) clinicians, in 75 centres, from 38 countries responded to the survey. A formal national network for managing DSD was reported to exist in 12 (32 %) countries. The paediatric specialists routinely involved in the initial evaluation of a newborn included: endocrinologist (99 %), surgeon/urologist (95 %), radiologist (93 %), neonatologist (91 %), clinical geneticist (81 %) and clinical psychologist (69 %). A team consisting of paediatric specialists in endocrinology, surgery/urology, clinical psychology, and nursing was only possible in 31 (41 %) centres. Of the 75 centres, 26 (35 %) kept only a local DSD registry and 40 (53 %) shared their data in a multicentre DSD registry. Attendance in local, national and international DSD-related educational programs was reported by 69, 78 and 84 % clinicians, respectively. Participation in audits/quality improvement exercises in DSD care was reported by 14 (19 %) centres. In addition to complex biochemistry and molecular genetic investigations, 40 clinicians (51 %) also had access to next generation sequencing. A genetic test was reported to be more preferable than biochemical tests for diagnosing 5-alpha reductase deficiency and 17-beta hydroxysteroid dehydrogenase 3 deficiency by 50 and 55 % clinicians, respectively. DSD centres report a high level of interaction at an international level, have access to specialist staff and are increasingly relying on molecular genetics for routine diagnostics. The quality of care provided by these centres locally requires further exploration.


A facile room temperature chemical transformation approach for binder-free thin film formation of Ag2Te and lithiation/delithiation chemistry of the film.
The present work demonstrates a highly controllable, facile and environmentally friendly aqueous solution based synthetic method for oxide contamination-free Ag2Te thin films on desired substrates at room temperature using ion exchange induced chemical transformation of Ag/AgxO thin films. The films before and after chemical transformation reaction are characterized using an energy dispersive X-ray analyzer, field emission scanning electron microscopy, X-ray photoelectron spectroscopy, thin film X-ray diffraction technique, high resolution transmission electron microscopy, and the selected area electron diffraction analysis technique. The as-deposited Ag2Te films show a highly crystalline nature even without thermal treatment. Furthermore, the electrochemistry for lithiation/delithiation of the Ag2Te film is studied for exploring its feasibility in the application as an anode material in a Li-ion battery. The experimentally estimated capacity of the Ag2Te electrode for Li storage is found to be about two and half fold larger than the theoretical capacity of the Ag2Te material. This implies that the binder-free Ag2Te film prepared by the current method could find a potential application in the Li-ion or other similar charge storing devices.


Molecular dynamics simulations of urea-water binary droplets on flat and pillared hydrophobic surfaces.
We performed molecular dynamics (MD) simulations to investigate equilibrium behavior of urea-water binary droplets on flat (graphitic) and pillared surfaces. The contact angles as a function of urea concentration on the flat surface are computed. It is found that the contact angle decreases as the urea concentration increases. At the equilibrium state, the urea molecules in the droplet tend to be located near the hydrophobic graphite surface. This behavior is consistent with the denaturing effects of urea in protein solutions. We also performed MD simulations of collision between a urea-water droplet and the pillared surface to examine the tendency for the droplet being in the Cassie state (droplet staying on top of the pillared surface) or in the Wenzel state (droplet staying at the bottom of the pillared surface), at various urea concentrations.


Genome-wide RNAi screen reveals disease-associated genes that are common to Hedgehog and Wnt signaling.
The Hedgehog (Hh) and Wnt signal transduction pathways are master regulators of embryogenesis and tissue renewal and represent anticancer therapeutic targets. Using genome-wide RNA interference screening in murine cultured cells, we established previously unknown associations between these signaling pathways and genes linked to developmental malformations, diseases of premature tissue degeneration, and cancer. We identified functions in both pathways for the multitasking kinase Stk11 (also known as Lkb1), a tumor suppressor implicated in lung and cervical cancers. We found that Stk11 loss resulted in disassembly of the primary cilium, a cellular organizing center for Hh pathway components, thus dampening Hh signaling. Loss of Stk11 also induced aberrant signaling through the Wnt pathway. Chemicals that targeted the Wnt acyltransferase Porcupine or that restored primary cilia length by inhibiting the tubulin deacetylase HDAC6 (histone deacetylase 6) countered deviant pathway activities driven by Stk11 loss. Our study demonstrates that Stk11 is a critical mediator in both the Hh and the Wnt pathways, and our approach provides a platform to support the development of targeted therapeutic strategies.


A method for pooling alleles from different genotyping experiments.
Single tandem repeat (STR) polymorphisms are widely used in linkage and association studies. One of the drawbacks of using these markers is that genetic data coming from different experiments cannot be easily pooled together, because both allele length and binning distance may change. As large studies with multiple series of subjects sequentially included become more and more common, there is an increasing interest in pooling the genetic data obtained in different experiments. Correct reconstruction of allelic correspondences between genotyping experiments is particularly crucial for association-oriented studies, such as candidate gene studies and genome-wide association studies in isolated populations. Here, we suggest a maximum-likelihood framework to find the best correspondence between alleles typed in different genotyping experiments. We also address the issue of goodness-of-fit and robustness. We perform a study simulating results obtained in a genome scan using 787 STR markers. The simulations show that the suggested method yields good results with respect to the error rate, even if the sizes of the samples to be pooled are as low as 10 subjects (3% errors), though only 9% of alleles pass our tests. As sample sizes increase to 250 subjects the proportion of alleles pooled reaches 96% with an error rate of <0.1%.


Pneumococcal pneumonia prevalence among adults with severe acute respiratory illness in Thailand - comparison of Bayesian latent class modeling and conventional analysis.
Determining the etiology of pneumonia is essential to guide public health interventions. Diagnostic test results, including from polymerase chain reaction (PCR) assays of upper respiratory tract specimens, have been used to estimate prevalence of pneumococcal pneumonia. However limitations in test sensitivity and specificity and the specimen types available make establishing a definitive diagnosis challenging. Prevalence estimates for pneumococcal pneumonia could be biased in the absence of a true gold standard reference test for detecting Streptococcus pneumoniae. We conducted a case control study to identify etiologies of community acquired pneumonia (CAP) from April 2014 through August 2015 in Thailand. We estimated the prevalence of pneumococcal pneumonia among adults hospitalized for CAP using Bayesian latent class models (BLCMs) incorporating results of real-time polymerase chain reaction (qPCR) testing of upper respiratory tract specimens and a urine antigen test (UAT) from cases and controls. We compared the prevalence estimate to conventional analyses using only UAT as a reference test. The estimated prevalence of pneumococcal pneumonia was 8% (95% CI: 5-11%) by conventional analyses. By BLCM, we estimated the prevalence to be 10% (95% CrI: 7-16%) using binary qPCR and UAT results, and 11% (95% CrI: 7-17%) using binary UAT results and qPCR cycle threshold (Ct) values. BLCM suggests a > 25% higher prevalence of pneumococcal pneumonia than estimated by a conventional approach assuming UAT as a gold standard reference test. Higher quantities of pneumococcal DNA in the upper respiratory tract were associated with pneumococcal pneumonia in adults but the addition of a second specific pneumococcal test was required to accurately estimate disease status and prevalence. By incorporating the inherent uncertainty of diagnostic tests, BLCM can obtain more reliable estimates of disease status and improve understanding of underlying etiology.


Positive Relations Between Vision and Posture in the Fixation Task Performed Upright.
In an upright stance, individuals sway in unpredictable ways. Their eyes also move in unpredictable ways in fixation tasks. The objective of this study was to analyze visual functions, postural control, and cognitive involvement in stationary gaze. A total of 14 healthy young adults performed a fixation task and a free-viewing task (three trials per task, 45 s per trial). As expected, the results showed many (n = 32) significant positive Pearson correlation coefficients between the eye and center of pressure/body (head, neck, and lower back) movements in the fixation task. In the free-viewing task, the correlations were nonsignificant. Only 3 of the 32 significant correlations (9.4%) were significantly related to cognitive involvement (measured with a subjective questionnaire). These results indirectly strengthened the validity of the synergistic model of postural control.


Non-neurogenic electrically evoked relaxation in canine airway muscle involves action of free radicals on K+ channels.
Cyclopiazonic acid (selective blocker of the internal Ca+2 pump) evoked tonic contraction in canine bronchial smooth muscle (BSM) and tracheal smooth muscle. This contraction was biphasic, including an initial component that was relatively insensitive to blockade of Ca+2 influx (e.g., removal of external Ca+2; nifedipine; hyperpolarization using lemakalim) followed by a component that was sensitive to all such interventions. In BSM, but not in tracheal smooth muscle, electrical field stimulation (EFS) evoked relaxations that were not affected by interventions designed to prevent release of autacoids from nerve endings or the epithelium, Na+/Ca+2 exchange or Ca(+2)-ATPase activities (internal or plasmalemmal). EFS evoked little or no relaxant response in carbachol-precontracted BSM in the presence of propranolol. After Ca+2 was replaced with Sr+2, however, carbachol evoked comparable contraction after which EFS evoked non-neurogenic relaxations. We found that the EFS-evoked relaxations were abolished by TEA or high KCI, were reduced significantly by charydotoxin or quinine, were reduced partially by ouabain and were unaffected by removal of external K+, by apamin or by glybenclamide. In addition, the relaxations were reduced significantly by the free radical scavenger N-acetylcysteine, were mimicked by H2O2 but were unaffected by superoxide dismutase or catalase. These observations suggest that the cyclopiazonic acid-evoked contraction involves pharmacomechanical coupling mechanisms (i.e., Ca(+2)-release) initially, followed by electromechanical coupling (i.e., voltage-dependent Ca+2 influx). After depletion of the internal Ca+2 store (e.g., by cyclopiazonic acid or Sr+2), EFS is able to evoke in BSM (but not in tracheal smooth muscle) relaxations that seem to involve opening of K+ channels (including those of the large-conductance Ca(+2)-dependent type) by EFS-liberated free radicals.


Sphingomonas alaskensis strain AFO1, an abundant oligotrophic ultramicrobacterium from the North Pacific.
Numerous studies have established the importance of picoplankton (microorganisms of < or =2 microm in length) in energy flow and nutrient cycling in marine oligotrophic environments, and significant effort has been directed at identifying and isolating heterotrophic picoplankton from the world's oceans. Using a method of diluting natural seawater to extinction followed by monthly subculturing for 12 months, a bacterium was isolated that was able to form colonies on solid medium. The strain was isolated from a 10(5) dilution of seawater where the standing bacterial count was 3.1 x 10(5) cells ml(-1). This indicated that the isolate was representative of the most abundant bacteria at the sampling site, 1.5 km from Cape Muroto, Japan. The bacterium was characterized and found to be ultramicrosized (less than 0.1 microm(3)), and the size varied to only a small degree when the cells were starved or grown in rich media. A detailed molecular (16S rRNA sequence, DNA-DNA hybridization, G+C mol%, genome size), chemotaxonomic (lipid analysis, morphology), and physiological (resistance to hydrogen peroxide, heat, and ethanol) characterization of the bacterium revealed that it was a strain of Sphingomonas alaskensis. The type strain, RB2256, was previously isolated from Resurrection Bay, Alaska, and similar isolates have been obtained from the North Sea. The isolation of this species over an extended period, its high abundance at the time of sampling, and its geographical distribution indicate that it has the capacity to proliferate in ocean waters and is therefore likely to be an important contributor in terms of biomass and nutrient cycling in marine environments.


One-stage Soave pull-through for Hirschsprung's disease: a comparison of the transanal and open approaches.
The authors reviewed their experience using the transanal Soave technique, to determine (1) if it offers any advantages over the standard open approach and (2) whether routine laparoscopic visualization is necessary. The case reports of 37 consecutive children less than 3 years old undergoing Soave pull-through were reviewed. Patients were excluded from analysis if they had total colon disease or had a previous colostomy. The patients were divided into 3 groups: open Soave (OS, n = 13), transanal Soave with routine laparoscopic visualization (LVS, n = 9), and transanal Soave with selective laparoscopy or minilaparotomy (TAS, n = 15). Cost was calculated based on hospital stay, operating room time, and use of laparoscopic equipment. In the TAS group, suspicion of a longer segment led to the selective use of laparoscopy with or without biopsy in 2 children, and the use of a small umbilical incision for mobilization of the splenic flexure in 2. There were no differences among groups with respect to age, weight, gender, transition zone, operating time, blood loss, intraoperative complications, enterocolitis, or stricture or cuff narrowing. Hospital stay was significantly longer in the OS group (median, 7 days; range, 3 to 47) than the LVS (median, 1; range 1 to 6) or TAS (median, 1, range, 1 to 3) groups. Cost (in thousands of dollars) was also higher in the OS group (median, 6.9; range, 3.9-25.7) than the LVS (median, 3.9; range, 3.6 to 6.4) or TAS (median, 3.4; range, 2.2 to 9.4) groups. Repeat surgery was necessary for 4 OS patients: 2 adhesive small bowel obstructions (1 of whom died), 1 twisted pull-through, and 1 recurrent aganglionosis. Three TAS patients required repeat surgery: 1 twisted pull-through, 1 anastomotic leak, and 1 cuff narrowing. These data suggest that the transanal pull-through is associated with a significantly shorter hospital stay and lower cost than the open approach, without an increased risk of complications. Because there is no intraabdominal dissection, there probably is a lower incidence of adhesive bowel obstruction. Routine laparoscopic visualization or minilaparotomy is not necessary but should be used in children who are at higher risk for long segment disease.


Individual Differences in Premotor Brain Systems Underlie Behavioral Apathy.
Lack of physical engagement, productivity, and initiative-so-called "behavioral apathy"--is a common problem with significant impact, both personal and economic. Here, we investigate whether there might be a biological basis to such lack of motivation using a new effort and reward-based decision-making paradigm, combined with functional and diffusion-weighted imaging. We hypothesized that behavioral apathy in otherwise healthy people might be associated with differences in brain systems underlying either motivation to act (specifically in effort and reward-based decision-making) or in action processing (transformation of an intention into action). The results demonstrate that behavioral apathy is associated with increased effort sensitivity as well as greater recruitment of neural systems involved in action anticipation: supplementary motor area (SMA) and cingulate motor zones. In addition, decreased structural and functional connectivity between anterior cingulate cortex (ACC) and SMA were associated with increased behavioral apathy. These findings reveal that effort sensitivity and translation of intentions into actions might make a critical contribution to behavioral apathy. We propose a mechanism whereby inefficient communication between ACC and SMA might lead to increased physiological cost--and greater effort sensitivity--for action initiation in more apathetic people.


Seven Dictyostelium discoideum phosphodiesterases degrade three pools of cAMP and cGMP.
The Dictyostelium discoideum genome uncovers seven cyclic nucleotide PDEs (phosphodiesterases), of which six have been characterized previously and the seventh is characterized in the present paper. Three enzymes belong to the ubiquitous class I PDEs, common in all eukaryotes, whereas four enzymes belong to the rare class II PDEs that are present in bacteria and lower eukaryotes. Since all D. discoideum PDEs are now characterized we have calculated the contribution of each enzyme in the degradation of the three important pools of cyclic nucleotides: (i) extracellular cAMP that induces chemotaxis during aggregation and differentiation in slugs; (ii) intracellular cAMP that mediates development; and (iii) intracellular cGMP that mediates chemotaxis. It appears that each cyclic nucleotide pool is degraded by a combination of enzymes that have different affinities, allowing a broad range of substrate concentrations to be degraded with first-order kinetics. Extracellular cAMP is degraded predominantly by the class II high-affinity enzyme DdPDE1 and its close homologue DdPDE7, and in the multicellular stage also by the low-affinity transmembrane class I enzyme DdPDE4. Intracellular cAMP is degraded by the DdPDE2, a class I enzyme regulated by histidine kinase/phospho-relay, and by the cAMP-/cGMP-stimulated class II DdPDE6. Finally, basal intracellular cGMP is degraded predominantly by the high-affinity class I DdPDE3, while the elevated cGMP levels that arise after receptor stimulation are degraded predominantly by a cGMP-stimulated cGMP-specific class II DdPDE5. The analysis shows that the combination of enzymes is tuned to keep the concentration and lifetime of the substrate within a functional range.


Higher-order lloyd interferometer.
The Lloyd moiré interferometer was introduced in Appl. Opt. 6, 1707 (1967), as a means of testing interferometrically a path across very large surfaces in oblique to grazing incidence. The width of the path is determined by the optics in use. For any sensible angle of incidence, the Lloyd interference fringes will be very narrowly spaced, but they are transformed into conveniently visible fringes by a moiré grating. The precision of the Lloyd moiré interferometer is limited by the very large angle of incidence and by the relatively poor definition of the moiré fringes. The objective of the present paper is to show an improved Lloyd interferometer technique, which with equally simple instrumentation permits one to vary and increase the sensitivity in testing large surfaces in oblique incidence by decreasing the angle of incidence.


Assessing the value of transgenic crops.
In the current controversy about the value of transgenic crops, matters open to empirical inquiry are centrally at issue. One such matter is a key premise in a common argument (that I summarize) that transgenic crops should be considered to have universal value. The premise is that there are no alternative forms of agriculture available to enable the production of sufficient food to feed the world. The proponents of agroecology challenge it, claiming that agroecology provides an alternative, and they deny the claim that it is well founded on empirical evidence. It is, therefore, a matter of both social and scientific importance that this premise and the criticisms of it be investigated rigorously and empirically, so that the benefits and disadvantages of transgenic-intensive agriculture and agroecology can be compared in a reliable way. Conducting adequate investigation about the potential contribution of agroecology requires that the cultural conditions of its practice (and, thus, of the practices and movements of small-scale farmers in the "third world") be strengthened--and this puts the interests of investigation into tension with the socio-economic interests driving the development of transgenics. General issues about relationship between ethical argument and empirical (scientific) investigation are raised throughout the article.


Patch testing experience with 1000 patients.
Patch testing is a definitive tool for diagnosing allergic contact dermatitis (ACD). It reveals the prevalence and trends of contact sensitization in the community, thereby paving the way for better standard series. There is paucity of large series of patch-tested patients from India. To report the 9-year patch-test data from a single general dermatology centre in North India. Consecutive patients presenting with signs/symptoms of suspected ACD were patch tested from May 1997 to April 2006. The Indian Standard Series was used. Parthenium was tested only in selected patients and cetrimide and chloroxylenol were added to the series. In total, records of 1000 patients (566 male, 434 female) were analyzed, yielding 1155 positive reactions in 590 (59%) patients. Footwear dermatitis was the commonest suspected diagnosis, followed by ACD to medicaments, cosmetic dermatitis and plant dermatitis. Out of the allergens that were tested in all the patients, positivity to nickel was the commonest (12.9%), followed by potassium dichromate (11.1%) neomycin (7%), mercaptobenzthiazole (6.6%), nitrofurazone (6%), colophony (5.7%), fragrance mix (5.5%) and cobalt chloride (5.4%). However, parthenium was the commonest allergen based on the proportion of patients tested with it (14.5%). In men, potassium dichromate (30%) was the commonest sensitizer and in women, nickel (43%) was the commonest to show patch-test positivity. Our study revealed higher prevalence of footwear and medicament dermatitis in comparison to existing data. Allergy to antiseptics is significant in our patients. Further collaborative studies involving patients from other parts of India are required to have an overall view of ACD in India.


Physiological, biochemical and psychological markers of strenuous training-induced fatigue.
The purpose of the study was to investigate whether severe fatigue, possibly leading to overreaching, could be diagnosed at an early stage by a combination of parameters. Seven well-trained male subjects (age [mean +/- SD]: 25.3 +/- 4.7 yr; body mass: 76 +/- 6.6 kg; VO2max: 61.1 +/- 7 ml.kg(-1).min(-1)) increased their training load by doubling their training volume and increasing the intensity by 15 % over a period of two weeks. Before and after this intensified training period subjects underwent a series of tests including a maximal incremental cycle ergometer test (Wmax) with continuous ventilatory measurements and blood lactate values, time trial, basal blood parameter tests (red and white blood profile), hormones [growth hormone (GH), insulin-like growth factor 1(IGF-1), adreno-corticotropic hormone (ACTH), cortisol], neuro-endocrine stress test [short insulin tolerance test (SITT), combined anterior pituitary test (CAPT) and exercise], a shortened Profile of Mood State (POMS), the estimated rate of perceived exertion (RPE) and a cognitive reaction time test. The intensified training period resulted in a significant increase of the training load (p <0.01), training monotony (p <0.01) and training strain (p <0.01). The RPE during training increased significantly (p <0.01) during the intensified training period. Total mood score obtained from the POMS tended to increase (p=0.06), reflecting an increase in worse mood state. A novel finding was that reaction times increased significantly, indicating that overreaching might adversely affect speed of information processing by the brain, especially for the most difficult conditions. After the intensified training period, neither changes in exercise-induced plasma hormone values, nor SITT values were observed. During the CAPT only cortisol showed a significant decrease after the intensified training period. Hemoglobin showed a significant decrease after the intensified training period whereas hematocrit, red blood cell count (RBC) and MCV tended to decrease. The intensified training had no effect on physical performance (Wmax or time trial), maximal blood lactate, maximal heart rate and white blood cell profile. The most sensitive parameters for detecting overreaching are reaction time performance (indicative for cognitive brain functioning), RPE and to a lesser extend the shortened POMS. This strongly suggests, that central fatigue precedes peripheral fatigue. All other systems,including the neuro-endocrine, are more robust and react most likely at a later stage in exhaustive training periods.


Long-term hyperglucagonaemia induces early metabolic and renal phenotypes of Type 2 diabetes in mice.
Clinical studies have shown that patients with early Type 2 diabetes often have elevated serum glucagon rather than insulin deficiency. Imbalance of insulin and glucagon in favouring the latter may contribute to impaired glucose tolerance, persistent hyperglycaemia, microalbuminuria and glomerular injury. In the present study, we tested the hypothesis that long-term glucagon infusion induces early metabolic and renal phenotypes of Type 2 diabetes in mice by activating glucagon receptors. Five groups of adult male C57BL/6J mice were treated with vehicle, glucagon alone (1 microg/h via an osmotic minipump, intraperitoneally), glucagon plus the glucagon receptor antagonist [Des-His(1)-Glu(9)]glucagon (5 microg/h via an osmotic minipump), [Des-His(1)-Glu(9)]glucagon alone or a high glucose load alone (2% glucose in the drinking water) for 4 weeks. Glucagon infusion increased serum glucagon by 129% (P<0.05), raised systolic BP (blood pressure) by 21 mmHg (P<0.01), elevated fasting blood glucose by 42% (P<0.01), impaired glucose tolerance (P<0.01), increased the kidney weight/body weight ratio (P<0.05) and 24 h urinary albumin excretion by 108% (P<0.01) and induced glomerular mesangial expansion and extracellular matrix deposition. These responses were associated with marked increases in phosphorylated ERK1/2 (extracellular-signal-regulated kinase 1/2) and Akt signalling proteins in the liver and kidney (P<0.01). Serum insulin did not increase proportionally. Concurrent administration of [Des-His(1)-Glu(9)]glucagon with glucagon significantly attenuated glucagon-increased BP, fasting blood glucose, kidney weight/body weight ratio and 24 h urinary albumin excretion. [Des-His(1)-Glu(9)]glucagon also improved glucagon-inpaired glucose tolerance, increased serum insulin by 56% (P<0.05) and attenuated glomerular injury. However, [Des-His(1)-Glu(9)]glucagon or high glucose administration alone did not elevate fasting blood glucose levels, impair glucose tolerance or induce renal injury. These results demonstrate for the first time that long-term hyperglucagonaemia in mice induces early metabolic and renal phenotypes of Type 2 diabetes by activating glucagon receptors. This supports the idea that glucagon receptor blockade may be beneficial in treating insulin resistance and Type 2 diabetic renal complications.


Functional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN.
CIRE/mDC-SIGN is a C-type lectin we originally identified as a molecule differentially expressed by mouse dendritic cell (DC) populations. Immunostaining with a CIRE/mDC-SIGN-specific mAb revealed that CIRE/mDC-SIGN is indeed on the surface of some CD4+, CD4- 8- DCs and plasmacytoid pre-DCs, but not on CD8+ DCs. It has been proposed that CIRE/mDC-SIGN is the functional orthologue of human DC-SIGN (hDC-SIGN), a molecule that both enhances T cell responses and facilitates antigen uptake. We assessed if CIRE/mDC-SIGN and hDC-SIGN exhibit functional similarities. CIRE/mDC-SIGN is down-regulated upon activation, but unlike hDC-SIGN, incubation with IL-4 and IL-13 did not enhance CIRE/mDC-SIGN expression, indicating differences in gene regulation. Like hDC-SIGN, CIRE/mDC-SIGN bound mannosylated residues. However, we could detect no role for CIRE/mDC-SIGN in T cell-DC interactions and the protein did not bind to pathogens known to interact with hDC-SIGN, including Leishmania mexicana, cytomegalovirus, HIV and lentiviral particles bearing the Ebolavirus glycoprotein. The binding of CIRE/mDC-SIGN to hDC-SIGN ligands was not rescued when CIRE/mDC-SIGN was engineered to express the stalk region of hDC-SIGN. We conclude that there are significant differences in the fine specificity of the C-type lectin domains of hDC-SIGN and CIRE/mDC-SIGN and that these two molecules may not be functional orthologues.


The increase in global HIV epidemics in MSM.
Epidemics of HIV in MSM continue to expand in most low, middle, and upper income countries in 2013 and rates of new infection have been consistently high among young MSM. Current prevention and treatment strategies are insufficient for this next wave of HIV spread. We conducted a series of comprehensive reviews of HIV prevalence and incidence, risks for HIV, prevention and care, stigma and discrimination, and policy and advocacy options. The high per act transmission probability of receptive anal intercourse, sex role versatility among MSM, network level effects, and social and structural determinants play central roles in disproportionate disease burdens. HIV can be transmitted through large MSM networks at great speed. Molecular epidemiologic data show marked clustering of HIV in MSM networks, and high proportions of infections due to transmission from recent infections. Prevention strategies that lower biological risks, including those using antiretrovirals, offer promise for epidemic control, but are limited by structural factors including, discrimination, criminalization, and barriers to healthcare. Subepidemics, including among racial and ethnic minority MSM in the United States and UK, are particularly severe and will require culturally tailored efforts. For the promise of new and combined bio-behavioral interventions to be realized, clinically competent healthcare is necessary and community leadership, engagement, and empowerment are likely to be key. Addressing the expanding epidemics of HIV in MSM will require continued research, increased resources, political will, policy change, structural reform, community engagement, and strategic planning and programming, but it can and must be done.


Mobile devices in medicine: a survey of how medical students, residents, and faculty use smartphones and other mobile devices to find information.
The research investigated the extent to which students, residents, and faculty members in Canadian medical faculties use mobile devices, such as smartphones (e.g., iPhone, Android, Blackberry) and tablet computers (e.g., iPad), to answer clinical questions and find medical information. The results of this study will inform how health libraries can effectively support mobile technology and collections. An electronic survey was distributed by medical librarians at four Canadian universities to medical students, residents, and faculty members via departmental email discussion lists, personal contacts, and relevant websites. It investigated the types of information sought, facilitators to mobile device use in medical information seeking, barriers to access, support needs, familiarity with institutionally licensed resources, and most frequently used resources. The survey of 1,210 respondents indicated widespread use of smartphones and tablets in clinical settings in 4 Canadian universities. Third- and fourth-year undergraduate students (i.e., those in their clinical clerkships) and medical residents, compared to other graduate students and faculty, used their mobile devices more often, used them for a broader range of activities, and purchased more resources for their devices. Technological and intellectual barriers do not seem to prevent medical trainees and faculty from regularly using mobile devices for their medical information searches; however, barriers to access and lack of awareness might keep them from using reliable, library-licensed resources. Libraries should focus on providing access to a smaller number of highly used mobile resources instead of a huge collection until library-licensed mobile resources have streamlined authentication processes.


Corticofugal control of vibrissa-sensitive neurons in the interpolaris nucleus of the trigeminal complex.
Trigeminal sensory nuclei that give rise to ascending pathways of vibrissal information are heavily linked by intersubnuclear connections. This is the case, for instance, of the principal trigeminal nucleus, which receives strong inhibitory input from the caudal sector of the interpolaris subnucleus. Because this inhibitory input can gate the relay of sensory messages through the lemniscal pathway, a central issue in vibrissal physiology is how brain regions that project to the interpolaris control the activity of inhibitory cells. In the present study, we examined how corticotrigeminal neurons of the primary and second somatosensory cortical areas control the excitability of interpolaris cells. Results show that these two cortical areas exert a differential control over the excitability of projection cells and intersubnuclear interneurons, and that this control also involves the recruitment of inhibitory cells in the caudalis subnucleus. These results provide a basic circuitry for a mechanism of disinhibition through which the cerebral cortex can control the relay of sensory messages in the lemniscal pathway. It is proposed that top-down control of brainstem circuits is prompted by motor strategies, expectations, and motivational states of the animal.


Isolation of an efficient actin promoter for use in rice transformation.
We have characterized the 5' region of the rice actin 1 gene (Act1) and show that it is an efficient promoter for regulating the constitutive expression of a foreign gene in transgenic rice. By constructing plasmids with 5' regions from the rice Act1 gene fused to the coding sequence of a gene encoding bacterial beta-glucuronidase, we demonstrate that a region 1.3 kilobases upstream of the Act1 translation initiation codon contains all of the 5'-regulatory elements necessary for high-level beta-glucuronidase (GUS) expression in transient assays of transformed rice protoplasts. The rice Act1 primary transcript has a noncoding exon separated by a 5' intron from the first coding exon. Fusions that lack this Act1 intron showed no detectable GUS activity in transient assays of transformed rice protoplasts. Deletion analysis of the Act1 5' intron suggests that the intron-mediated stimulation of GUS expression is associated, in part, with an in vivo requirement for efficient intron splicing.


Tumor recognition in wireless capsule endoscopy images using textural features and SVM-based feature selection.
Tumor in digestive tract is a common disease and wireless capsule endoscopy (WCE) is a relatively new technology to examine diseases for digestive tract especially for small intestine. This paper addresses the problem of automatic recognition of tumor for WCE images. Candidate color texture feature that integrates uniform local binary pattern and wavelet is proposed to characterize WCE images. The proposed features are invariant to illumination change and describe multiresolution characteristics of WCE images. Two feature selection approaches based on support vector machine, sequential forward floating selection and recursive feature elimination, are further employed to refine the proposed features for improving the detection accuracy. Extensive experiments validate that the proposed computer-aided diagnosis system achieves a promising tumor recognition accuracy of 92.4% in WCE images on our collected data.


Interdependent action of KH domain proteins Krr1 and Dim2 drive the 40S platform assembly.
Ribosome biogenesis begins in the nucleolus with the formation of 90S pre-ribosomes, from which pre-40S and pre-60S particles arise that subsequently follow separate maturation pathways. Here, we show how structurally related assembly factors, the KH domain proteins Krr1 and Dim2, participate in ribosome assembly. Initially, Dim2 (Pno1) orchestrates an early step in small subunit biogenesis through its binding to a distinct region of the 90S pre-ribosome. This involves Utp1 of the UTP-B module, and Utp14, an activator of the DEAH-box helicase Dhr1 that catalyzes the removal of U3 snoRNP from the 90S. Following this dismantling reaction, the pre-40S subunit emerges, but Dim2 relocates to the pre-40S platform domain, previously occupied in the 90S by the other KH factor Krr1 through its interaction with Rps14 and the UTP-C module. Our findings show how the structurally related Krr1 and Dim2 can control stepwise ribosome assembly during the 90S-to-pre-40S subunit transition.


Randomised controlled trial of stand-alone tailored emails for smoking cessation.
Digital technology has created opportunities for delivering smoking cessation assistance at the population level. However, the efficacy of sending multiple, automated, tailored emails providing motivation, support and information for quitting is unknown. Smokers planning to quit (n=1070) were randomly assigned to (1) 27 tailored cessation emails (deluxe email group (DEG)), (2) 3 to 4 tailored emails with links to downloadable booklets (basic email group (BEG)) or (3) a single non-tailored email (single email group (SEG)). All emails included links to quitting resources. Self-reported 7-day point-prevalence abstinence was assessed at 1 month, 3 months and 6 months postenrolment. Across follow-ups, abstinence was significantly greater for smokers in the DEG (34%) compared with the SEG (25.8%; OR=1.47, 95% CI 1.07 to 2.02, p=0.02) but there was no difference between the BEG (30.8%) and the SEG (p=0.13). Results were independent of baseline cigarettes per day, interest in quitting, smoker in household, use of nicotine replacement therapy (NRT) or varenicline and gender, themselves associated with abstinence (ps<0.05). Missing=smoking and multiple imputation analyses based on 25 data sets corroborated results. Participants in the DEG were also more likely to use non-medication aids (eg, quit smoking website, cessation class/clinic) compared with the SEG (OR=1.34, p=0.02, CI 1.06 to 1.71), but use of these or NRT by the 4-week follow-up (vs no use) increased abstinence across follow-ups primarily for those in the SEG. Stand-alone tailored, multiple emails providing support, motivation and information during a quit attempt are an easily deployable, inexpensive mode of providing effective cessation assistance to large numbers of smokers planning to quit.


A 35-gene signature discriminates between rapidly- and slowly-progressing glioblastoma multiforme and predicts survival in known subtypes of the cancer.
Gene expression can be employed for the discovery of prognostic gene or multigene signatures cancer. In this study, we assessed the prognostic value of a 35-gene expression signature selected by pathway and machine learning based methods in adjuvant therapy-linked glioblastoma multiforme (GBM) patients from the Cancer Genome Atlas. Genes with high expression variance was subjected to pathway enrichment analysis and those having roles in chemoradioresistance pathways were used in expression-based feature selection. A modified Support Vector Machine Recursive Feature Elimination algorithm was employed to select a subset of these genes that discriminated between rapidly-progressing and slowly-progressing patients. Survival analysis on TCGA samples not used in feature selection and samples from four GBM subclasses, as well as from an entirely independent study, showed that the 35-gene signature discriminated between the survival groups in all cases (p<0.05) and could accurately predict survival irrespective of the subtype. In a multivariate analysis, the signature predicted progression-free and overall survival independently of other factors considered. We propose that the performance of the signature makes it an attractive candidate for further studies to assess its utility as a clinical prognostic and predictive biomarker in GBM patients. Additionally, the signature genes may also be useful therapeutic targets to improve both progression-free and overall survival in GBM patients.


High Photoluminescence Quantum Yields in Organic Semiconductor-Perovskite Composite Thin Films.
One of the obstacles towards efficient radiative recombination in hybrid perovskites is a low exciton binding energy, typically in the orders of tens of meV. It has been shown that the use of electron-donor additives can lead to a substantial reduction of the non-radiative recombination in perovskite films. Herein, the approach using small molecules with semiconducting properties, which are candidates to be implemented in future optoelectronic devices, is presented. In particular, highly luminescent perovskite-organic semiconductor composite thin films have been developed, which can be processed from solution in a simple coating step. By tuning the relative concentration of methylammonium lead bromide (MAPbBr3 ) and 9,9spirobifluoren-2-yl-diphenyl-phosphine oxide (SPPO1), it is possible to achieve photoluminescent quantum yields (PLQYs) as high as 85 %. This is attributed to the dual functions of SPPO1 that limit the grain growth while passivating the perovskite surface. The electroluminescence of these materials was investigated by fabricating multilayer LEDs, where charge injection and transport was found to be severely hindered for the perovskite/SPPO1 material. This was alleviated by partially substituting SPPO1 with a hole-transporting material, 1,3-bis(N-carbazolyl)benzene (mCP), leading to bright electroluminescence. The potential of combining perovskite and organic semiconductors to prepare materials with improved properties opens new avenues for the preparation of simple lightemitting devices using perovskites as the emitter.


Prediction of electron energies in metal oxides.
The ability to predict energy levels in metal oxides is paramount to developinguseful materials, such as in the development of water photolysis catalysts and efficient photovoltaic cells. The binding energy of electrons in materials encompasses a wealth of information concerning their physicochemistry. The energies control the optical and electrical properties, dictating for which kinds of chemistry and physics a particular material is useful. Scientists have developed theories and models for electron energies in a variety of chemical systems over the past century. However, the prediction of quantitative energy levels in new materials remains a major challenge. This issue is of particular importance in metal oxide research, where novel chemistries have opened the possibility of a wide range of tailored systems with applications in important fields including light-emitting diodes, energy efficient glasses, and solar cells. In this Account, we discuss the application of atomistic modeling techniques, covering the spectrum from classical to quantum descriptions, to explore the alignment of electron energies between materials. We present a number of paradigmatic examples, including a series of oxides (ZnO, In2O3, and Cu2O). Such calculations allow the determination of a "band alignment diagram" between different materials and can facilitate the prediction of the optimal chemical composition of an oxide for use in a given application. Throughout this Account, we consider direct computational solutions in the context of heuristic models, which are used to relate the fundamental theory to experimental observations. We review a number of techniques that have been commonly applied in the study of electron energies in solids. These models have arisen from different answers to the same basic question, coming from solid-state chemistry and physics perspectives. We highlight common factors, as well as providing a critical appraisal of the strengths and weaknesses of each, emphasizing the difficulties in translating concepts from molecular to solid-state systems. Finally, we stress the need for a universal description of the alignment of band energies for materials design from first-principles. By demonstrating the applicability and challenges of using theory to calculate the relevant quantities, as well as impressing the necessity of a clarification and unification of the descriptions, we hope to provide a stimulus for the continued development of this field.


Organization of Mitochondrial Gene Expression in Two Distinct Ribosome-Containing Assemblies.
Mitochondria contain their own genetic system that provides subunits of the complexes driving oxidative phosphorylation. A quarter of the mitochondrial proteome participates in gene expression, but how all these factors are orchestrated and spatially organized is currently unknown. Here, we established a method to purify and analyze native and intact complexes of mitochondrial ribosomes. Quantitative mass spectrometry revealed extensive interactions of ribosomes with factors involved in all the steps of posttranscriptional gene expression. These interactions result in large expressosome-like assemblies that we termed mitochondrial organization of gene expression (MIOREX) complexes. Superresolution microscopy revealed that most MIOREX complexes are evenly distributed throughout the mitochondrial network, whereas a subset is present as nucleoid-MIOREX complexes that unite the whole spectrum of organellar gene expression. Our work therefore provides a conceptual framework for the spatial organization of mitochondrial protein synthesis that likely developed to facilitate gene expression in the organelle.


Robust Point Set Registration Using Gaussian Mixture Models.
In this paper, we present a unified framework for the rigid and nonrigid point set registration problem in the presence of significant amounts of noise and outliers. The key idea of this registration framework is to represent the input point sets using Gaussian mixture models. Then, the problem of point set registration is reformulated as the problem of aligning two Gaussian mixtures such that a statistical discrepancy measure between the two corresponding mixtures is minimized. We show that the popular iterative closest point (ICP) method [1] and several existing point set registration methods [2], [3], [4], [5], [6], [7] in the field are closely related and can be reinterpreted meaningfully in our general framework. Our instantiation of this general framework is based on the the L2 distance between two Gaussian mixtures, which has the closed-form expression and in turn leads to a computationally efficient registration algorithm. The resulting registration algorithm exhibits inherent statistical robustness, has an intuitive interpretation, and is simple to implement. We also provide theoretical and experimental comparisons with other robust methods for point set registration.


Tracking hospital costs in the last year of life - The Shanghai experience.
One aim of the current study was to track end-of-life care using individual data in Shanghai, China to profile hospital costs for decedents and those for the entire population. A second aim of this study was to clarify the effect of proximity to death. Data from the Information Center of the Shanghai Municipal Commission of Health and Family Planning (SMCHFP) were examined. For decedents who died in medical facilities in 2015, inpatient care was tracked for 1 year before death. A total of 43,765 decedents were included in the study, accounting for 35% of total deaths in 2015 in Shanghai. Hospital costs were higher for people who died before the age of 45 (14,228.62 USD) than for those aged 90 or older (8,696.34 USD). The ratio of costs for decedents to the entire population declined significantly with age. Women received less care than men in the last year of life (t = -15.1244, p < 0.05). Average tertiary hospital costs per decedent declined significantly with age, whereas average secondary hospital costs increased slightly with age. Among the top 14 causes of death classified using the ICD-10, rectal cancer incurred the greatest costs (13,973 USD per decedent). Over 43% of hospital costs were incurred during the month before death. Declining costs in the last year of life with age as well as with distance to death demonstrate the existence of a proximity to death phenomenon in health care expenses. Disease-specific studies should be conducted and attention should be paid to gender equity when examining end-of-life medical costs in the future.


The autoimmune disease-associated PTPN22 variant promotes calpain-mediated Lyp/Pep degradation associated with lymphocyte and dendritic cell hyperresponsiveness.
A variant of the PTPN22-encoded Lyp phosphatase (Lyp620W) confers risk for autoimmune disease, but the mechanisms underlying this association remain unclear. We show here that mice expressing the Lyp variant homolog Pep619W manifest thymic and splenic enlargement accompanied by increases in T-cell number, activation and positive selection and in dendritic- and B-cell activation. Although Ptpn22 (Pep) transcript levels were comparable in Pep619W and wild-type Pep619R mice, Pep protein levels were dramatically reduced in the mutant mice, with Pep619W protein being more rapidly degraded and showing greater association with and in vitro cleavage by calpain 1 than Pep619R. Similarly, levels of the Lyp620W variant were decreased in human T and B cells, and its calpain binding and cleavage were increased relative to wild-type Lyp620R. Thus, calpain-mediated degradation with consequently reduced Lyp/Pep expression and lymphocyte and dendritic cell hyperresponsiveness represents a mechanism whereby Lyp620W may increase risk for autoimmune disease.


Faecal pyruvate kinase isoenzyme type M2 for colorectal cancer screening: a meta-analysis.
To present a critical discussion of the efficacy of the faecal pyruvate kinase isoenzyme type M2 (faecal M2-PK) test for colorectal cancer (CRC) screening based on the currently available studies. A literature search in PubMed and Embase was conducted using the following search terms: fecal Tumor M2-PK, faecal Tumour M2-PK, fecal M2-PK, faecal M2-PK, fecal pyruvate kinase, faecal pyruvate kinase, pyruvate kinase stool and M2-PK stool. Stool samples from 704 patients with CRC and from 11 412 healthy subjects have been investigated for faecal M2-PK concentrations in seventeen independent studies. The mean faecal M2-PK sensitivity was 80.3%; the specificity was 95.2%. Four studies compared faecal M2-PK head-to-head with guaiac-based faecal occult blood test (gFOBT). Faecal M2-PK demonstrated a sensitivity of 81.1%, whereas the gFOBT detected only 36.9% of the CRCs. Eight independent studies investigated the sensitivity of faecal M2-PK for adenoma (n = 554), with the following sensitivities: adenoma < 1 cm in diameter: 25%; adenoma > 1 cm: 44%; adenoma of unspecified diameter: 51%. In a direct comparison with gFOBT of adenoma > 1 cm in diameter, 47% tested positive with the faecal M2-PK test, whereas the gFOBT detected only 27%. We recommend faecal M2-PK as a routine test for CRC screening. Faecal M2-PK closes a gap in clinical practice because it detects bleeding and non-bleeding tumors and adenoma with high sensitivity and specificity.


In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis.
Adipose tissue-derived stromal cells (ASCs) natively reside in a relatively low-oxygen tension (i.e., hypoxic) microenvironment in human body. Low oxygen tension (i.e., in situ normoxia), has been known to enhance the growth and survival rate of ASCs, which, however, may lead to the risk of tumourigenesis. Here, we investigated the tumourigenic potential of ASCs under their physiological condition to ensure their safe use in regenerative therapy. Human ASCs isolated from subcutaneous fat were cultured in atmospheric O2 concentration (21% O2) or in situ normoxia (2% O2). We found that ASCs retained their surface markers, tri-lineage differentiation potential, and self-renewal properties under in situ normoxia without altering their morphology. In situ normoxia displayed a higher proliferation and viability of ASCs with less DNA damage as compared to atmospheric O2 concentration. Moreover, low oxygen tension significantly up-regulated VEGF and bFGF mRNA expression and protein secretion while reducing the expression level of tumour suppressor genes p16, p21, p53, and pRb. However, there were no significant differences in ASCs telomere length and their relative telomerase activity when cultured at different oxygen concentrations. Collectively, even with high proliferation and survival rate, ASCs have a low tendency of developing tumour under in situ normoxia. These results suggest 2% O2 as an ideal culture condition for expanding ASCs efficiently while maintaining their characteristics.


Further development of a model of chronic bone marrow aplasia in the busulphan-treated mouse.
Aplastic anaemia (AA) in man is an often fatal disease characterized by pancytopenia of the peripheral blood and aplasia of the bone marrow. AA is a toxic effect of many drugs and chemicals (e.g. chloramphenicol, azathioprine, phenylbutazone, gold salts, penicillamine and benzene). However, there are no widely used or convenient animal models of drug-induced AA. Recently, we reported a new model of chronic bone marrow aplasia (CBMA = AA) in the busulphan (BU)-treated mouse: eight doses of BU (10.50 mg/kg) were administered to female BALB/c mice over a period of 23 days; CBMA was evident at day 91/112 post-dosing with significantly reduced erythrocytes, platelets, leucocytes and nucleated bone marrow cell counts. However, mortality was high (49.3%). We have now carried out a study to modify the BU-dosing regime to induce CBMA without high mortality, and investigated the patterns of cellular responses in the blood and marrow in the post-dosing period. Mice (n = 64/65) were dosed 10 times with BU at 0 (vehicle control), 8.25, 9.0 and 9.75 mg/kg over 21 days and autopsied at day 1, 23, 42, 71, 84, 106 and 127 post-dosing (n = 7-15); blood and marrow samples were examined. BU induced a predictable bone marrow depression at day 1 post-dosing; at day 23/42 post-dosing, parameters were returning towards normal during a period of recovery. At day 71, 84, 106 and 127 post-dosing, a stabilized, late-stage, nondose-related CBMA was evident in BU-treated mice, with decreased erythrocytes, platelets and marrow cell counts, and increased MCV. At day 127 post-dosing, five BU-treated mice showed evidence of lymphoma. In this study, mortality was low, ranging from 3.1% (8.25 mg/kg BU) to 12.3% (9.75 mg/kg BU). It is concluded that BU at 9.0 mg/kg (or 9.25 mg/kg) is an appropriate dose level to administer (10 times over 21 days) to induce CBMA at approximately day 50-120 post-dosing.


Expression of alpha-smooth muscle (alpha-SM) actin during corneal stromal wound healing.
The purpose of this study was to correlate the temporal expression of alpha-smooth muscle specific actin (alpha-SM actin), a molecular marker for myofibroblast transformation, with corneal wound contraction. After full-thickness, central corneal injury in rabbit eyes, the anterior width of the wound (wound gape) was measured in the same animals using in vivo confocal microscopy. In addition, animals were sacrificed at various times after injury for the determination of alpha-SM actin expression by immunofluorescent microscopy using a mouse monoclonal antibody specific for human alpha-actin. Antibody specificity was confirmed by Western blot analysis of normal and wound fibroblasts. Expression of alpha-SM actin also was related spatially to f-actin and the wound margin by co-localization with phalloidin and DTAF (5([4,6-dichlorotriazin-2yl]amino)fluorescein), a fluorescent marker bound to the wound margin. Wound contraction was most evident from days 7 to 42, when wound gape progressively decreased from 574 +/- 120 microns to 250 +/- 61 microns. Thereafter, the wound remained stable to day 84 (304 +/- 58 microns). Expression of alpha-SM actin directly correlated with wound contraction--appearing across the wound at day 7, the full thickness of the wound at day 14, and the posterior wound at day 28. alpha-SM actin was localized exclusively to phalloidin-stained, f-actin microfilament bundles or stress fibers within wound healing fibroblasts, and the disappearance of alpha-SM actin correlated with the concomitant disappearance of stress fibers at days 28 to 42. Staining of the wound margin with DTAF confirmed that the expression of alpha-SM actin was limited to fibroblasts within the wound. The expression of alpha-SM actin was directly correlated to corneal wound contraction, appearing at the initiation of and disappearing at the completion of the contraction process. Furthermore, the exclusive expression of alpha-SM actin by fibroblasts present only within the wound suggests that local environmental factors unique to the wound may play an important role in myofibroblast transformation.


Mother's social capital and child health in Indonesia.
Social capital has been shown to be positively associated with a range of health outcomes, yet few studies have explored the association between mother's social capital and children's health. This study examines the relation between mothers' access to social capital (via participation in community activities) and child health. Instrumental variable estimation was applied to cross sectional data of the Indonesian Family Life Survey (IFLS) 2007 which consist of face-to-face interviews among the adult population in Indonesia (N(mothers) = 3450, N(children) = 4612, N(communities) = 309, and participation rate at 92%). The findings show strong evidence for the causal flow running from a mother's social capital to her children's health. All instruments are highly correlated with mothers' social capital but uncorrelated with child health. The findings are also robust to individual and community characteristics associated with child health, and suggest that enlarging mothers' social capital through various community activities is a particularly relevant intervention for reducing child health disparities in Indonesia.


Applications of fluorescence spectroscopy for predicting percent wastewater in an urban stream.
Dissolved organic carbon (DOC) is a significant organic carbon reservoir in many ecosystems, and its characteristics and sources determine many aspects of ecosystem health and water quality. Fluorescence spectroscopy methods can quantify and characterize the subset of the DOC pool that can absorb and re-emit electromagnetic energy as fluorescence and thus provide a rapid technique for environmental monitoring of DOC in lakes and rivers. Using high resolution fluorescence techniques, we characterized DOC in the Tualatin River watershed near Portland, Oregon, and identified fluorescence parameters associated with effluent from two wastewater treatment plants and samples from sites within and outside the urban region. Using a variety of statistical approaches, we developed and validated a multivariate linear regression model to predict the amount of wastewater in the river as a function of the relative abundance of specific fluorescence excitation/emission pairs. The model was tested with independent data and predicts the percentage of wastewater in a sample within 80% confidence. Model results can be used to develop in situ instrumentation, inform monitoring programs, and develop additional water quality indicators for aquatic systems.


Ultraviolet exposure and mortality among women in Sweden.
Ecological studies have reported possible effects of sunlight on the risk of several diseases. Little evidence is available on the association between mortality and solar and artificial UV exposure by individual level from prospective studies. The Swedish Women's Lifestyle and Health cohort study included women aged 30 to 49 years in 1991-1992. Participants completed a questionnaire and were followed-up through linkages to national registries until the end of 2006. Cox models were used to estimate adjusted HRs and 95% CIs for all-cause mortality and for cancer and cardiovascular disease (CVD) mortality. During 15 years of follow-up, among the 38,472 women included in the present study, 754 deaths occurred: 457 due to cancer and 100 due to CVD. When combining the information on sun exposure from age 10 to 39 years, women who got sunburned twice or more per year during adolescence had a reduced all-cause mortality, compared with women who had been sunburned once or less. A reduced risk for all-cause and CVD mortality was observed in women who went on sunbathing vacations more than once a year over three decades. Solarium use once or more per month for at least one decade increased the risk of all-cause mortality, when compared with women who never used a solarium. Solar UV exposure was associated with reduced overall and CVD mortality, whereas artificial UV exposure was associated with increased overall and cancer mortality among Swedish women. Moderate sun exposure may protect against cause-specific mortality.


Management of chyle fistulization in association with neck dissection.
Chylous fistula after neck dissection is a relatively rare but potentially lethal complication. Sequelae range from severe fluid, electrolyte, and protein loss to fistula formation, skin-flap necrosis, and carotid blowout. A thorough knowledge of the anatomy is essential to avoid injury to the thoracic duct or right lymph duct. After surgery, drainage of large amounts of fluid, particularly if milky, may alert the surgeon to the danger of chylous leakage. Certain diagnosis, however, is not so easy. Once the diagnosis is made, the management has to address the immediate and late effects of the loss of chyle into an operative site. This article seeks to examine these factors through review of the literature and personal experience with the problem. Total parenteral nutrition allows for control of the fluid and protein loss while avoiding flow of chyle, and in most cases it results in resolution. In those cases that do not resolve, fibrin glue with some type of mesh and muscle flaps usually succeed in closure.


A randomized, crossover comparison of herbal medicine and bromocriptine against risperidone-induced hyperprolactinemia in patients with schizophrenia.
Hyperprolactinemia is a common adverse effect that occurs as a result of antipsychotic therapies, which often results in discontinuation. Empirical evidence has shown that some herbal medicines have suppressive effects on prolactin (PRL) hyperactivities. This study was designed to compare the herbal preparation called Peony-Glycyrrhiza Decoction (PGD) with bromocriptine (BMT), a dopamine agonist widely used for PRL-secreting disorders, in the treatment of risperidone-induced hyperprolactinemia. Twenty schizophrenic women who were under risperidone maintenance treatment, diagnosed with hyperprolactinemia (serum PRL levels >50 mug/L), and currently experiencing oligomenorrhea or amenorrhea were selected for the study. Subjects were randomized to additional treatment with PGD (45 g/d) followed by BMT (5 mg/d) or BMT followed by PGD at the same doses for 4 weeks each, with an interval of 4-week washout period between 2 treatment sessions. The severity of psychotic symptoms, adverse events, serum PRL, estradiol, testosterone, and progesterone levels were examined at baseline and end point. Peony-Glycyrrhiza Decoction treatment produced a significant baseline-end point decrease in serum PRL levels, without exacerbating psychosis and changing other hormones, and the decreased amplitudes were similar to those of BMT (24% vs 21%-38%). Moreover, there was a significantly greater proportion of patients during PGD treatment than BMT treatment showing improvements on adverse effects associated with hyperprolactinemia (56% vs 17%, P = 0.037). These results suggest that the herbal therapy can yield additional benefits while having comparable efficacy in treating antipsychotic-induced hyperprolactinemia in individuals with schizophrenia.


Multidomain interventions: state-of-the-art and future directions for protocols to implement precision dementia risk reduction. A user manual for Brain Health Services-part 4 of 6.
Although prevention of dementia and late-life cognitive decline is a major public health priority, there are currently no generally established prevention strategies or operational models for implementing such strategies into practice. This article is a narrative review of available evidence from multidomain dementia prevention trials targeting several risk factors and disease mechanisms simultaneously, in individuals without dementia at baseline. Based on the findings, we formulate recommendations for implementing precision risk reduction strategies into new services called Brain Health Services. A literature search was conducted using medical databases (MEDLINE via PubMed and SCOPUS) to select relevant studies: non-pharmacological multidomain interventions (i.e., combining two or more intervention domains), target population including individuals without dementia, and primary outcomes including cognitive/functional performance changes and/or incident cognitive impairment or dementia. Further literature searches covered the following topics: sub-group analyses assessing potential modifiers for the intervention effect on cognition in the multidomain prevention trials, dementia risk scores used as surrogate outcomes in multidomain prevention trials, dementia risk scores in relation to brain pathology markers, and cardiovascular risk scores in relation to dementia. Multidomain intervention studies conducted so far appear to have mixed results and substantial variability in target populations, format and intensity of interventions, choice of control conditions, and outcome measures. Most trials were conducted in high-income countries. The differences in design between the larger, longer-term trials that met vs. did not meet their primary outcomes suggest that multidomain intervention effectiveness may be dependent on a precision prevention approach, i.e., successfully identifying the at-risk groups who are most likely to benefit. One such successful trial has already developed an operational model for implementing the intervention into practice. Evidence on the efficacy of risk reduction interventions is promising, but not yet conclusive. More long-term multidomain randomized controlled trials are needed to fill the current evidence gaps, especially concerning low- and middle-income countries and integration of dementia prevention with existing cerebrovascular prevention programs. A precision risk reduction approach may be most effective for dementia prevention. Such an approach could be implemented in Brain Health Services.


Exploring the links between peptoid antibacterial activity and toxicity.
Peptoids are a promising class of antimicrobial agents with reported activities against a range of both Gram-positive and Gram-negative bacteria, fungi and most recently parasites. However, at present the available toxicity data is somewhat limited and as such rationally designing effective antimicrobial peptoids can be challenging. Herein, we present the toxicity profiling of a series of linear peptoids against mammalian cell lines (HaCaT and HepG2). The cytotoxicity of the peptoid library has then been correlated with their antibacterial properties against Gram-positive and Gram-negative bacteria and also to the hydrophobicity of the peptoid sequences. The work presented provides valuable data to aid in the future rational design of antimicrobial peptoids.


Carbohydrate and domain architecture of an immature antibody glycoform exhibiting enhanced effector functions.
Antibodies contain a conserved glycosylation site that has emerged as a target for the modulation of antibody effector functions. The crystal structure of a biosynthetic intermediate of human IgG1, bearing immature oligomannose-type glycans and reported to display increased antibody-dependent cellular cytotoxicity, demonstrates that glycan engineering can bias the Fc to an open conformation primed for receptor binding.


Effects of singlet oxygen on human lens crystallins in vitro.
We have recently demonstrated that singlet oxygen-mediated photooxidation can cause an increase in blue fluorescence and covalent cross-linking in bovine lens crystallins in vitro. Because these changes closely parallel modifications known to occur in human crystallins during aging and cataractogenesis, it was suggested that singlet oxygen may play an important role in these processes in vivo. to confirm these results, obtained with photosensitizers free in solution, we now report results from experiments with a polymer-bound photosensitizer and with photophysically generated singlet oxygen. Singlet oxygen photodynamically generated by polymer-immobilized rose bengal produced the following modifications to human lens crystallins in vitro: covalent cross-linking, increased blue fluorescence, yellow pigmentation, and formation of heavy-molecular-weight aggregates. Singlet oxygen generated photophysically was shown to cause an increase in blue fluorescence and covalent cross-linking in human crystallins. These findings substantiate the hypothesis that singlet oxygen may play an important role in the changes seen in human lens proteins during aging and cataractogenesis.


Genetic algorithms for protein threading.
Despite many years of efforts, a direct prediction of protein structure from sequence is still not possible. As a result, in the last few years researchers have started to address the "inverse folding problem": Identifying and aligning a sequence to the fold with which it is most compatible, a process known as "threading". In two meetings in which protein folding predictions were objectively evaluated, it became clear that threading as a concept promises a real breakthrough, but that much improvement is still needed in the technique itself. Threading is a NP-hard problem, and thus no general polynomial solution can be expected. Still a practical approach with demonstrated ability to find optimal solutions in many cases, and acceptable solutions in other cases, is needed. We applied the technique of Genetic Algorithms in order to significantly improve the ability of threading algorithms to find the optimal alignment of a sequence to a structure, i.e. the alignment with the minimum free energy. A major progress reported here is the design of a representation of the threading alignment as a string of fixed length. With this representation validation of alignments and genetic operators are effectively implemented. Appropriate data structure and parameters have been selected. It is shown that Genetic Algorithm threading is effective and is able to find the optimal alignment in a few test cases. Furthermore, the described algorithm is shown to perform well even without pre-definition of core elements. Existing threading methods are dependent on such constraints to make their calculations feasible. But the concept of core elements is inherently arbitrary and should be avoided if possible. While a rigorous proof is hard to submit yet an, we present indications that indeed Genetic Algorithm threading is capable of finding consistently good solutions of full alignments in search spaces of size up to 10(70).


Genotypic and phenotypic relationships among methicillin-resistant Staphylococcus aureus from three multicentre bacteraemia studies.
At a time when the molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) was changing, we sought to characterize several genotypic markers and glycopeptide susceptibility features of clinical isolates from patients with bacteraemia. One hundred and sixty-eight MRSA bloodstream isolates obtained from three multicentre clinical trials were microbiologically and genotypically characterized. All isolates were susceptible to vancomycin (MIC < or = 2 mg/L); 38% belonged to accessory gene regulator (agr) group I, 52% belonged to group II and 10% belonged to group III. Typing of the staphylococcal cassette chromosome mec (SCCmec) showed that 67% were type II and 33% were type IV. The agr group II polymorphism was associated with SCCmec II (P < 0.001). Fifty-three percent of SCCmec II and 27% of SCCmec IV isolates had vancomycin MICs > or =1 mg/L (P = 0.001). One hundred percent of agr II strains were predicted to be members of clonal complex 5. SCCmec II was the genetic marker most predictive of vancomycin MICs of > or =1 mg/L. SCCmec IV isolates were more likely to have vancomycin MICs < or =0.5 mg/L. Given that SCCmec IV is a marker for a community-based organism for which less prior vancomycin exposure is predicted, we conclude that prior antibiotic exposure in agr group II organisms may account for their increased vancomycin MICs.


Snacks, nudges and asymmetric peer influence: Evidence from food choice experiments with children in Indonesia.
Many children in low- and middle-income countries are growing up during a rapid nutrition transition. Experimental evidence on food choice in developing countries is scarce, while it is unclear to what extent evidence from high-income countries can be generalized. Children participated in a snack choice experiment. We expose some children to emoji labels encouraging healthy snacks, while others observe healthy or unhealthy snacking by peers. While emoji labels moderately promote healthy snacking, the adverse effect of observing a peer eating the unhealthy snack is very large. The effect associated with observing a healthy peer is insignificant. Additionally, cross-randomized blocks of children watched a nutrition video to study the interaction of information provision and nudging. The video independently improves healthy choices but does not aid the emoji nudge and cannot counter the strong negative peer effect. We compare our findings to studies conducted in developed countries and discuss policy implications.


Structural Gray Matter Changes in the Hippocampus and the Primary Motor Cortex on An-Hour-to-One- Day Scale Can Predict Arm-Reaching Performance Improvement.
Recent studies have revealed rapid (e.g., hours to days) training-induced cortical structural changes using magnetic resonance imaging (MRI). Currently, there is great interest in studying how such a rapid brain structural change affects behavioral improvement. Structural reorganization contributes to memory or enhanced information processing in the brain and may increase its capability of skill learning. If the gray matter (GM) is capable of such rapid structural reorganization upon training, the extent of volume increase may characterize the learning process. To shed light on this issue, we conducted a case series study of 5-day visuomotor learning using neuroanatomical imaging, and analyzed the effect of rapid brain structural change on motor performance improvement via regression analysis. Participants performed an upper-arm reaching task under left-right mirror-reversal for five consecutive days; T1-weighted MR imaging was performed before training, after the first and fifth days, and 1 week and 1 month after training. We detected increase in GM volume on the first day (i.e., a few hours after the first training session) in the primary motor cortex (M1), primary sensory cortex (S1), and in the hippocampal areas. Notably, regression analysis revealed that individual differences in such short-term increases were associated with the learning levels after 5 days of training. These results suggest that GM structural changes are not simply a footprint of previous motor learning but have some relationship with future motor learning. In conclusion, the present study provides new insight into the role of structural changes in causing functional changes during motor learning.


Loss of Jak2 selectively suppresses DC-mediated innate immune response and protects mice from lethal dose of LPS-induced septic shock.
Given the importance of Jak2 in cell signaling, a critical role for Jak2 in immune cells especially dendritic cells (DCs) has long been proposed. The exact function for Jak2 in DCs, however, remained poorly understood as Jak2 deficiency leads to embryonic lethality. Here we established Jak2 deficiency in adult Cre(+/+)Jak2(fl/fl) mice by tamoxifen induction. Loss of Jak2 significantly impaired DC development as manifested by reduced BMDC yield, smaller spleen size and reduced percentage of DCs in total splenocytes. Jak2 was also crucial for the capacity of DCs to mediate innate immune response. Jak2(-/-) DCs were less potent in response to inflammatory stimuli and showed reduced capacity to secrete proinflammatory cytokines such as TNFalpha and IL-12. As a result, Jak2(-/-) mice were defective for the early clearance of Listeria after infection. However, their potency to mediate adaptive immune response was not affected. Unlike DCs, Jak2(-/-) macrophages showed similar capacity secretion of proinflammatory cytokines, suggesting that Jak2 selectively modulates innate immune response in a DC-dependent manner. Consistent with these results, Jak2(-/-) mice were remarkably resistant to lethal dose of LPS-induced septic shock, a deadly sepsis characterized by the excessive innate immune response, and adoptive transfer of normal DCs restored their susceptibility to LPS-induced septic shock. Mechanistic studies revealed that Jak2/SATA5 signaling is pivotal for DC development and maturation, while the capacity for DCs secretion of proinflammatory cytokines is regulated by both Jak2/STAT5 and Jak2/STAT6 signaling.


Distribution of renin mRNA and its protein in the developing kidney.
The intrarenal distribution of renin changes markedly during maturation. To determine whether renin gene expression changes along the developing renal vasculature, renin mRNA distribution was assessed using in situ hybridization histochemistry. Fetal, newborn, and adult kidney tissue sections from Wistar-Kyoto rats were hybridized with an oligonucleotide complementary to rat renin mRNA. In fetal kidneys, renin mRNA was found in the vascular pole of juxtamedullary glomeruli and along afferent, interlobular, and arcuate arteries. In kidneys from newborn rats, renin mRNA localized throughout the whole length of afferent arterioles, but was not detected in interlobular or arcuate arteries. In adult kidneys, hybridization signals were less intense and confined to the juxtaglomerular apparatus. Immunolocalization of renin with a polyclonal anti-rat renin antibody paralleled closely the mRNA distribution. Northern blot analyses demonstrated that renin mRNA levels were higher in fetal and newborn (20- and 10-fold, respectively) than in adult kidneys. We conclude the following. 1) The fetal kidney expresses the renin gene. 2) Expression of the renin gene is subjected to developmental changes. 3) As maturation progresses, localization of renin synthesis and storage shifts from large intrarenal arteries to a restricted, classical juxtaglomerular site in the afferent arteriole.


Intraerythrocytic development and antigenicity of Plasmodium falciparum and comparison with simian and rodent malaria parasites.
Using sorbitol-synchronised cultures and metabolic labelling with [35S]methionine, the stage specificity of polypeptides synthesised by the intraerythrocytic stages of Plasmodium falciparum was studied. We confirmed that the synthesis of many polypeptides is restricted to defined morphological stages of parasite development, while other polypeptides are synthesised more or less throughout the cycle. The synthesis of at least 6 polypeptides was confined to the period of differentiation of mature trophozoites to schizonts and merozoites. Polypeptides synthesised by a cloned long-term passage isolate were very similar to those of a recently cultured uncloned isolate. Comparison of polypeptides synthesized during differentiation of mature trophozoites to schizonts and merozoites by P. falciparum with those of P. chabaudi and P. knowlesi showed that while P. chabaudi and P. knowlesi synthesised a 250 000 molecular weight polypeptide at this stage the apparently equivalent polypeptide of P. falciparum was of significantly lower molecular weight being 200 000. Using a surface immunoprecipitation technique, it was shown that this 200 000 mol. wt. polypeptide was accessible to antibodies on the surface of erythrocytes infected with mature trophozoites and schizonts. A 150 000 mol. wt. polypeptide was also accessible to antibodies. By comparing polypeptides synthesised during the differentiation of mature trophozoites to schizonts and merozoites with those recovered in the ring stage parasites after schizogony and erythrocyte invasion, it was shown that this 200 000 mol. wt. polypeptide and 140 000 and 120 000 mol. wt. polypeptides were not taken into the erythrocyte by the invading merozoite. The importance of these polypeptides in terms of the parasite biology and in the induction and expression of immunity to malaria is discussed.


Stable localized modes in asymmetric waveguides with gain and loss.
It is shown that asymmetric waveguides with gain and loss can support a stable propagation of optical beams. This means that the propagation constants of modes of the corresponding complex optical potential are real. A class of such waveguides is found from a relation between two spectral problems. A particular example of an asymmetric waveguide, described by the hyperbolic functions, is analyzed. The existence and stability of linear modes and of continuous families of nonlinear modes are demonstrated.


Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression.
Synchronization of spiking activity in neuronal networks is a fundamental process that enables the precise transmission of information to drive behavioural responses. In cortical areas, synchronization of principal-neuron spiking activity is an effective mechanism for information coding that is regulated by GABA (γ-aminobutyric acid)-ergic interneurons through the generation of neuronal oscillations. Although neuronal synchrony has been demonstrated to be crucial for sensory, motor and cognitive processing, it has not been investigated at the level of defined circuits involved in the control of emotional behaviour. Converging evidence indicates that fear behaviour is regulated by the dorsomedial prefrontal cortex (dmPFC). This control over fear behaviour relies on the activation of specific prefrontal projections to the basolateral complex of the amygdala (BLA), a structure that encodes associative fear memories. However, it remains to be established how the precise temporal control of fear behaviour is achieved at the level of prefrontal circuits. Here we use single-unit recordings and optogenetic manipulations in behaving mice to show that fear expression is causally related to the phasic inhibition of prefrontal parvalbumin interneurons (PVINs). Inhibition of PVIN activity disinhibits prefrontal projection neurons and synchronizes their firing by resetting local theta oscillations, leading to fear expression. Our results identify two complementary neuronal mechanisms mediated by PVINs that precisely coordinate and enhance the neuronal activity of prefrontal projection neurons to drive fear expression.


Blue-emitting acridine-tagged silver(i)-bis-N-heterocyclic carbene.
Herein, the photophysical properties of an acridine derivative of a bis-N-heterocyclic carbene silver complex were investigated. The HOMO and LUMO energy differences between 9-[(N-methyl imidazol-2-ylidene)]acridine and 4,5-bis[(N-methyl-imidazol-2-ylidene)methyl]acridine were theoretically compared. Based on the calculation, the 4,5-bis N-heterocyclic carbene-tethered acridine type of ligand was found to be a potential source for tuning the fluorescent nature of the resultant metal derivatives. Thus, a 4,5-bis N-heterocyclic carbene (NHC)-tethered acridine silver(i) salt was synthesized, and its photophysical properties were investigated. The 4,5-bis[(N-isopropylimidazol-2-ylidene)methyl]acridine silver(i) hexafluorophosphate complex was obtained from the reaction between [4,5-bis{(N-isopropylimidazolium)methyl}acridine] hexafluorophosphate and Ag2O in very good yield; this molecule was characterized by elemental analysis and FTIR, multinuclear (1H and 13C) NMR, UV-Vis, and fluorescence spectroscopic techniques. The molecular structure has been confirmed by single-crystal X-ray diffraction analysis, which has revealed that the complex is a homoleptic mononuclear silver(i) cationic solid. The charge of the Ag(i)-NHC cation is balanced by the hexafluorophosphate anion. The cationic moieties are closely packed in the chair and inverted chair forms where silver(i) possesses a quasi-linear geometry. Moreover, the silver complex provided blue emission from all the three excitations with good fluorescence quantum yield. The fluorescence lifetime of the silver(i) complex has been determined using the time-correlated single photon counting technique. Interestingly, the fluorescence decay pattern and the fluorescence lifetimes of the silver complex are largely different from those of the parent ligand acridine imidazolium salt. Moreover, the theoretical predictions have been found to be in good agreement with the experimental results.


Six years' experience in ovum donation using vitrified oocytes: report of cumulative outcomes, impact of storage time, and development of a predictive model for oocyte survival rate.
To describe the clinical outcomes achieved after 6 years' experience in ovum donation conducted with vitrified oocytes; to attempt to find predictors of survival; and to provide information about the probability of having a baby according to the number of oocytes consumed. Retrospective, observational study. Private university-affiliated in vitro fertilization center. Recipients of vitrified oocytes (January 2007-March 2013), including all the warming procedures (n = 3,610) and all the donations made during the same period (n = 3,467). None. Survival rate per warming procedure, cumulative delivery rates (CDR) per single donation cycle, oocyte-to-baby rate, and cumulative live birth rate (CLBR) per oocyte consumed. Oocyte survival rate was 90.4%. It was not possible to develop a predictive model for survival owing to the lack of prognostic value of the studied variables. Implantation, clinical, and ongoing pregnancy rates per donation cycle were 39.0% (95% confidence interval [CI], 37.8-40.5), 48.4% (95% CI, 46.7-50.1), and 39.9% (95% CI, 38.3-41.5), respectively. Statistical differences were found when comparing blastocysts versus day 3 ETs (42.5%; 95% CI, 40.4-45.2 vs. 37.5%; 95% CI, 35.3-39.7 ongoing pregnancy rate). The CDR/donation cycle, including cryotransfers, was 78.8% (95% CI, 73.5-84.1). The oocyte-to-baby rate was 6.5%. CLBR increased progressively according to the number of oocytes consumed. We provide detailed information about the high efficiency of using vitrified/warmed oocytes. There is currently no way of estimating donors' oocytes survival when considering baseline characteristics, storage time, or controlled ovarian stimulation parameters. The probability of achieving a baby using vitrified oocytes increases progressively with the number of oocytes consumed.


Effect of short chain fatty acids infused intraileally on interdigestive exocrine pancreatic secretions in growing pigs.
The effect of intraileally infused short chain fatty acids (SCFA) and saline as control on the exocrine pancreatic secretions during the interdigestive phase was studied using three 8-weeks-old piglets. Pigs were surgically fitted with a pancreatic duct catheter, re-entrant duodenal T-cannula for collection and subsequent return of pancreatic juice, and with an infusion T-cannula at the distal ileum. Saline as control, 5.0 and 10.0 mm butyrate, 7.5 and 15.0 mm propionate and 85.0 and 170.0 mm acetate were infused at 2 ml/kg body weight (BW) for 30 min into the ileum of overnight fasted piglets via ileal T-cannula. The calculated volume of infusates was administrated in five equal bolus at 6 min intervals over a period of 30 min. The pancreatic juice was collected 60 and 30 min before and 30, 60, 90 and 120 min after the start of infusion. The trypsin (p = 0.07, p > 0.15 respectively) and protein (p > 0.15, p = 0.05 respectively) outputs immediately decreased after the infusion of acetate at the dose of 85.0 and 170.0 mm, respectively, whereas pancreatic juice outflow (p > 0.15) was not significantly affected when compared with levels 30 min before infusion. After the infusion of butyrate at the dose of 5.0 mm, trypsin (p = 0.01) and protein (p = 0.12) outputs increased immediately whereas pancreatic juice outflow was not affected (p > 0.15) in comparison with levels 30 min before infusion. No significant differences were observed after infusion of butyrate at the dose of 10 mm for the pancreatic juice outflow, trypsin and protein outputs when compared with the level before infusion, although these values were numerically lower immediately after the infusion. The pancreatic juice outflow increased (p = 0.03) after the infusion of propionate at the dose of 7.5 mm and decreased (p = 0.005) immediately after the infusion of propionate at the dose of 15.0 mm when compared with the levels 30 min before the infusions. After the infusion of propionate at the dose of 7.5 or 15.0 mm for the output of protein and trypsin, no significant differences (p > 0.15) were observed when compared with levels 30 min before infusion. In summary, the intraileal infusion of SCFA at different doses exerts a short-term and moderate effect on the interdigestive exocrine pancreatic secretions in pigs.


Older adult participation in cancer clinical trials: A systematic review of barriers and interventions.
Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.


Sex difference in clinical outcomes of Chinese patients with atrial fibrillation and coronary stenting according to age.
Sex differences in the clinical outcomes of patients with atrial fibrillation (AF) and coronary stenting should be assessed according to age. We analyzed the clinical data of all patients with nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. A total of 2,146 patients (71.8% men and 28.2% women) were included in the study. The mean age of the patients was 66.6±9.4 years. Women in this study were older and had higher prevalence of hypertension, diabetes, chronic kidney disease (CKD), and anemia. Smoking history was found to be higher in men, and women were less likely to be current smokers. The mean follow-up duration was 39.7 months. Women younger than 65 years had a remarkably higher mortality (11.2% vs. 5.3%, p=0.012) and a significantly lower rate of repeat revascularization (1.6% vs. 6.3%, p=0.034) than men. Female gender remained an independent predictor for all-cause mortality [hazard ratio (HR)=2.03, 95% confidence interval (CI): 1.09-3.79, p=0.025], along with heart failure (HR=3.64, 95% CI: 2.02-6.57, p<0.001) and CKD (HR=2.46, 95% CI: 1.09-5.57, p=0.031) after multivariate regression analysis. No significant difference was noted between men and women with regard to mortality, ischemic events, and major bleeding in elderly patients. In Chinese patients younger than 65 years with AF and coronary stenting, female gender was independently associated with increased mortality; men were more likely to receive repeat revascularization possibly due to the current smoking. Whether it was a biological difference or a recognition disparity of the disease between men and women warrants further investigation.


Unbound Plasma, Total Plasma, and Whole-Blood Tacrolimus Pharmacokinetics Early After Thoracic Organ Transplantation.
Therapeutic drug monitoring of tacrolimus whole-blood concentrations is standard care in thoracic organ transplantation. Nevertheless, toxicity may appear with alleged therapeutic concentrations possibly related to variability in unbound concentrations. However, pharmacokinetic data on unbound concentrations are not available. The objective of this study was to quantify the pharmacokinetics of whole-blood, total, and unbound plasma tacrolimus in patients early after heart and lung transplantation. Twelve-hour tacrolimus whole-blood, total, and unbound plasma concentrations of 30 thoracic organ recipients were analyzed with high-performance liquid chromatography-tandem mass spectrometry directly after transplantation. Pharmacokinetic modeling was performed using non-linear mixed-effects modeling. Plasma concentration was < 1% of the whole-blood concentration. Maximum binding capacity of erythrocytes was directly proportional to hematocrit and estimated at 2700 pg/mL (95% confidence interval 1750-3835) with a dissociation constant of 0.142 pg/mL (95% confidence interval 0.087-0.195). The inter-individual variability in the binding constants was considerable (27% maximum binding capacity, and 29% for the linear binding constant of plasma). Tacrolimus association with erythrocytes was high and suggested a non-linear distribution at high concentrations. Monitoring hematocrit-corrected whole-blood tacrolimus concentrations might improve clinical outcomes in clinically unstable thoracic organ transplants. NTR 3912/EudraCT 2012-001909-24.